Circadianicity of Hemostatic Function and Coronary Vasomotion

Cardiologia (Rome, Italy). Dec, 1999  |  Pubmed ID: 12497916

Acute myocardial infarction, sudden cardiac death and ischemic stroke show a circadian periodicity, occurring more frequently in the morning. Because arterial thrombosis is common to these disorders, a circadianicity of prothrombotic and antithrombotic processes may contribute to explain the 24 h rhythms of these acute events. Available data indeed indicate that coronary vasomotor tone, platelet aggregability, plasma inhibition of fibrinolysis, coagulant activity and blood viscosity are all greater in the morning than at other times of day, producting a relative prothrombotic state in the early morning.

Safety of Colonic Anastomosis Following Portal Triad Occlusion in Rats

International Journal of Surgical Investigation. , 2000  |  Pubmed ID: 12678527

Traumatic colon injuries frequently coexist with liver injury. Stopping the bleeding from hepatic pool may require complete portal triad occlusion. The possible effects of portal venous occlusion on healing of colonic anastomosis were examined using a rat model. A colo-colonic anastomosis following resection of a 1 cm segment of the transverse colon was done with just a simple manipulation on the liver and portal triad in the group A. In the group B the portal triad was clamped for 15 minutes. Then, the clamp was released for a thirty minutes reperfusion time. Subsequently, the same technique in the control group for colonic resection and anastomosis was applied. Ischemia/reperfusion resulted in histologically proven alterations in the large bowel in the group B. However, colonic tissue superoxide dismutase values showed no significant differences between the groups. On day 7, no differences were recorded in bursting pressures of the anastomoses and the hydroxyprolene levels of the anastomotic tissues of the two groups. These findings suggest that colonic anastomosis after portal triad occlusion is safe in the absence of peritonitis.

Immunohistochemical Localization of Amylin in Rat Brainstem

Peptides. Nov, 2000  |  Pubmed ID: 11090930

Immunohistochemical studies were conducted on rat brainstem using a specific polyclonal antiserum against the COOH-terminal (25-37) of human amylin. Amylin-immunoreactive cell bodies were observed in the vestibular, cochlear, trapezoid, and inner cerebellar nuclei and in the mesencephalic nucleus of trigeminal nerve. Positive cell bodies were also found in lateral, gigantocellular and magnocellular reticular nuclei. Numerous amylin-immunoreactive nerve fibers were shown in the trigeminal spinal tract, in the solitary area and in the area postrema. Amylin-immunoreactive cell bodies were often surrounded by a network of tyrosine hydroxylase-immunoreactive nerve fibers. These results provide morphologic evidence that amylin may play a role in some discrete sensory functions.

Mental Retardation with Rare Fragile Site Expressed at 2q11

Brain & Development. Dec, 2000  |  Pubmed ID: 11111064

Several rare autosomal folate sensitive fragile sites were reported in individuals with mental retardation, neurological abnormalities, and multiple congenital malformations. Only three of them: fra(11)(q22.3), fra(X)(q27.3) and fra(X)(q28), are known to be associated with mental retardation and phenotypic abnormalities. A possible association of the other rare fragile sites with idiopathic mental retardation is still being discussed. Here, a girl who has a fragile site at 2q11 with minor congenital anomalies and mental retardation is presented. This case has recalled the question of idiopathic mental retardation that might be the clinical expression of rare FSFS. Fragility was observed at 2q11 with a frequency of 3% in her cells along with a partial endoreduplication at 2 q11-->qter.

Glutathione S-transferase, Similar to Sigma Class, from Skin Secretions of Xenopus Laevis

IUBMB Life. Sep, 2000  |  Pubmed ID: 11142348

Using glutathione affinity chromatography followed by isoelectrofocusing, we purified from the skin secretion of Xenopus laevis an isoenzyme of glutathione S-transferase with an apparent subunit molecular mass of 22.5 kDa and an isoelectric point at pH 5.1. Its N-terminal amino acid sequence was highly similar to that of the sigma class glutathione S-transferase, which previously was demonstrated to have a glutathione-dependent prostaglandin D2 synthase activity. Immunohistochemistry analysis revealed that the isoenzyme was located in the cytoplasm of granular gland cells.

Ontogeny of Galanin-immunoreactive Elements in Chicken Embryo Autonomic Nervous System

The Anatomical Record. Mar, 2001  |  Pubmed ID: 11241195

To elucidate the main ontogenetic steps of galanin immunoreactivity within the extrinsic nerve supply of the alimentary tract, we undertook an immunohistochemical study of chicken embryo specimens. Fluorescence and streptavidin-biotin-peroxidase protocols were combined, using a galanin polyclonal antiserum, on transverse serial sections obtained from chicken embryos from embryonic Day 3 (E3) to hatching, and from 9-day-old newborn chicks. Galanin-immunoreactive cells were first detected at E3.5 within the pharyngeal pouch region, the nodose ganglion, the primary sympathetic chain, primitive splanchnic branches and the caudal portion of the Remak ganglion. At E5.5 galanin-immunoreactive cells and fibers appeared in the secondary (paravertebral) sympathetic chain, splanchnic nerves, peri- and preaortic plexuses, adrenal gland anlage and visceral nerves. Galanin-immunoreactive cells also lay scattered along the vagus nerve, and in the intermediate zone of the thoracolumbar spinal cord. At E18, galanin-immunoreactive cells and fibers were found along the entire Remak ganglion and around the gastrointestinal blood vessels. In post-hatching-9-day old chicks, the para- and prevertebral ganglia, but not the intermediate zone of the spinal cord, contained galanin-immunoreactive cells. Data indicate the presence of a consistent "galaninergic" nerve system supplying the chick embryonal gut wall. Whether this system has growth or differentiating role remains to be demonstrated. Its presence and distribution pattern in the later stages clearly support its well known role as a visceral neuromodulator of gut function.

Prevalence of Biliary Lithiasis in a Sicilian Population of Hemodialysis Patients

Clinical Nephrology. Feb, 2001  |  Pubmed ID: 11269676

Studies performed to date on the prevalence of biliary lithiasis (BL) in chronic renal failure patients on hemodialysis (HD) have given contradictory results. The aims of the present study were to evaluate the prevalence of BL and its main associated risk factors in a population of hemodialysis patients, and to compare the results with those we had obtained previously in an overt population of the same zone. The study included 171 patients (83 M, 88 F), mean age 62.5 years and mean duration of dialysis 66.7 months. The screening protocol also included body mass index (BMI), a number of biochemical parameters and an ultrasound scan of the gallbladder and biliary tract. The general prevalence of BL was 33.3% (30.1% in men and 36.4% in women), and this figure was significantly higher than that found in our previous study. Prevalence increased with age in both sexes (Mantel-Haenszel Chi-squared = 5.4, p < 0.03), but not with duration of dialysis. The main risk factors, evaluated with multiple logisstic regression, were the presence of diabetes mellitus and high serum phosphorus levels. Specific symptoms were also significantly associated in BL patients. No association was found with parity, BMI or serum lipid alterations. In conclusion, the prevalence of BL in a Sicilian population of HD patients was higher than that found in an overt population of the same area and the associated main risk factors were not coincident. Further studies are needed to establish the role played by the phase of end-stage renal disease before HD and to correct the metabolic disturbances to limit a high percentage of morbidity in a disease already in itself sufficiently disabling.

Clinical and Hematological Responses to Hydroxyurea in Sicilian Patients with Hb S/beta-thalassemia

Hemoglobin. Feb, 2001  |  Pubmed ID: 11300353

Although, several reports have detailed that hydroxyurea can ameliorate the clinical course of adult and pediatric patients with sickle cell anemia (Hb S or beta(S)), few clinical studies have been carried out in patients with beta(S)/beta-thalassemia. In a two-year clinical study, we evaluated the efficacy of hydroxyurea in a group of 22 adult Sicilian patients with beta(S)/beta-thalassemia with severe phenotypes. Among the 20 patients evaluated during 2 years of treatment, we observed a very good clinical response with a 93% reduction of the annual number of crises (median 7 versus 0.5 crises per year; P < 0.001) and of days in hospital (mean 22+/- 21.9 versus 1.2 +/- 2.3; P < 0.001), a significant increase in Hb F (7.5 +/- 5.3% versus 25.2 +/- 5.2%; P < 0.001) and in MCV (73.1 +/- 4.8 fL versus 96.4 +/- 7.2 fL; P < 0.001), and no significant modifications in Hb (9.6 +/- 1.3 g/dL versus 10.0 +/- 1.5 g/dL; P > 0.05) and in WBC (11.4 +/- 3.9 x 10(9)/L versus 10.2 +/- 3.9 x 10(9)/L; P > 0.05). Twelve patients had no crises from the first month of treatment; 16 patients showed a 2-3-fold increase over baseline in Hb F. During the study no severe complications and no important side effects of hydroxyurea were observed. Our data suggest that hydroxyurea efficacy in patients with beta(S)/beta-thalassemial may be greater than that described in patients with sickle cell disease. This pattern and durability of response will need to be confirmed in a larger, randomized, clinical trial.

Oral Supplements of Vitamin E Improve Measures of Oxidative Stress in Plasma and Reduce Oxidative Damage to LDL and Erythrocytes in Beta-thalassemia Intermedia Patients

Free Radical Research. May, 2001  |  Pubmed ID: 11378535

Fifteen beta-thalassemia intermedia patients, not requiring chronic transfusional therapy, were monitored in order to check their antioxidant status, and the lipid oxidation products in plasma, LDL, and erythrocytes before and during a 9-month oral treatment with 600 mg/day vitamin E. The low level of vitamin E, and high level of malondialdehyde in plasma clearly tended to normalize after three months (P < .001), and were quite similar to control after six months. The abnormally low level of vitamin E in LDL and the four times higher than control basal level of conjugated dienes (LDL-CD), were not modified after three months of treatment. Significant changes of LDL-VE (P < .05) and of the basal LDL-CD (P < .001) were evident after six months. LDL-VE was within the normal range after nine months, whereas LDL-CD still appeared twice as higher than control. Plasma vitamin A, ascorbate, beta-carotene, and lycopene increased markedly at the end of the trial (P < .005). The level of vitamin E in red blood cells was normalized after six months of supplementation. A decrease of the baseline value of conjugated dienes was observed after nine months, although it remained 1.4-fold higher than control. The RBC count and hematocrit appeared higher at the end of the trial (P < .05 and P < .001, respectively). The hemoglobin value did not show variations. A shift to normal of the resistance of erythrocytes to osmotic lysis was observed. Our findings provide evidence that an oral treatment with vitamin E improves the antioxidant/oxidant balance in plasma, LDL particles, and red blood cells, and counteracts lipid peroxidation processes in beta-thalassemia intermedia patients.

The Synthesis of Antimicrobial Peptides in the Skin of Rana Esculenta is Stimulated by Microorganisms

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. Jun, 2001  |  Pubmed ID: 11387247

Defective Lentiviral Vectors Are Efficiently Trafficked by HIV-1 and Inhibit Its Replication

Molecular Therapy : the Journal of the American Society of Gene Therapy. Jun, 2001  |  Pubmed ID: 11407907

Gene therapy against HIV infection should involve vector-mediated delivery of anti-HIV therapeutic genes into T-lymphocytes and macrophages or, alternatively, hematopoietic progenitors. Transduction of mature cells with defective vectors would have limited success because the vector would disappear with cell turnover. However, if a vector could be trafficked by wild-type HIV, initial transduction of a majority of the population would not be required, as the vector would be able to spread. We describe HIV-1-based lentiviral vectors that are efficiently packaged and trafficked by HIV-1, allowing a small number of cells initially transduced to spread the vector within a nontransduced cell population. We examined whether the presence or absence of the rev gene and the Rev-responsive element (RRE) would have a noticeable effect on the ability of lentiviral vectors to be trafficked and to inhibit HIV-1 replication. We found that replacement of rev/RRE with a constitutive transport element from Mason-Pfizer monkey virus had no apparent effect on trafficking and did not change the intrinsic inhibitory abilities of the vectors. We also constructed a rev/RRE-independent HIV-1-derived vector carrying a trans-dominant negative mutant of HIV-1 Rev, RevM10. This vector was less efficiently trafficked by HIV-1 and, despite the presence of an anti-HIV-1 gene, RevM10, was less efficient at inhibiting HIV-1 replication when introduced into a target T-cell population.

Guanylin and Uroguanylin in the Parotid and Submandibular Glands: Potential Intrinsic Regulators of Electrolyte Secretion in Salivary Glands

Histochemistry and Cell Biology. Jun, 2001  |  Pubmed ID: 11455453

The intestinal peptides guanylin and uroguanylin regulate the electrolyte/water transport in the gastrointestinal epithelium via activation of cystic fibrosis transmembrane conductance regulator (CFTR), the cystic fibrosis gene product. Because a major but incompletely understood function of the salivary glands is the CFTR-mediated secretion of an electrolyte-rich fluid, we investigated the rat and guinea pig parotid and submandibular glands for expression, cellular distribution, and subcellular localization of guanylin and uroguanylin. RT-PCR analyses with guanylin and uroguanylin-specific primers revealed that both peptides are highly expressed in the parotid and submandibular glands. At the translational level, western blotting analyses with peptide-specific guanylin and uroguanylin antibodies identified the expected 12.5-kDa immunoreactive peptides in these organs. At the cellular level, guanylin and uroguanylin were exclusively confined to epithelial cells of the intralobular and interlobular ducts. At the subcellular level, the immunoreactivities were localized by preembedding immunoelectron microscopy to small vesicles which were concentrated at the apical part of the secretory epithelial cells. The expression and cell-specific localization of guanylin and uroguanylin in the salivary glands indicate that these peptides may be specifically involved in the regulation of CFTR-mediated electrolyte/water secretion in the salivary gland ductal system.

Comparison of Electromagnetic Field Stimulation on the Healing of Small and Large Intestinal Anastomoses

Diseases of the Colon and Rectum. Aug, 2001  |  Pubmed ID: 11535860

Magnetic fields have been shown to affect biologic processes. Accordingly, an experimental study was designed to investigate the effect of electromagnetic field stimulation on intestinal healing and to compare small and large intestinal anastomoses.

[Familial Colonic Polyposis: Effect of Molecular Analysis on the Diagnostic-therapeutic Approach]

Annali Italiani Di Chirurgia. Mar-Apr, 2001  |  Pubmed ID: 11552476

Germline mutations of the Adenomatous polyposis gene (APC) are responsible for Familial Adenomatous Polyposis (FAP), an inherited condition that predisposes to the development of hundreds to thousands benign adenomas in the colo-rectum. If not surgically removed, they inevitably progress into malignant adenocarcinoma. To date more than 450 germline mutations have been described allowing the establishment of genotype/phenotype correlation between the site and type of molecular defects and their morbid consequences. Authors reviewed their experience concerning 22 FAP affected patients and their 26 first degree relatives, in whom the mutational analysis of the APC gene had been carried out. Site and type of mutations were associated with clinical parameters (age of onset, rectal involvement, extracolonic manifestations, presence of colorectal cancer) and treatments. The impact of mutational analyses on the clinical approach could be very interesting in the future, modifying both surveillance programs and therapeutical choices.

Mutation of the Methylated TRNA(Lys)(3) Residue A58 Disrupts Reverse Transcription and Inhibits Replication of Human Immunodeficiency Virus Type 1

Journal of Virology. Oct, 2001  |  Pubmed ID: 11559799

Cellular tRNA(Lys)(3) serves as the primer for reverse transcription of human immunodeficiency virus type 1 (HIV-1). tRNA(Lys)(3) interacts directly with HIV-1 reverse transcriptase (RT), is packaged into viral particles, and anneals to the primer-binding site (PBS) of the HIV-1 genome in order to initiate reverse transcription. Residue A58 of tRNA(Lys)(3), which lies outside the PBS-complementary region, is posttranscriptionally methylated to form 1-methyladenosine 58 (M(1)A58). This methylation is thought to serve as a pause signal for plus-strand strong-stop DNA synthesis during reverse transcription. However, formal proof that the methylation is necessary for the pausing of RT has not been obtained in vivo. In the present study, we investigated the role of tRNA(Lys)(3) residue A58 in the replication cycle of HIV-1 in living cells. We have developed a mutant tRNA(Lys)(3) derivative, tRNA(Lys)(3)A58U, in which A58 was replaced by U. This mutant tRNA was expressed in CEM cells. We demonstrate that the presence of M(1)A58 is necessary for the appropriate termination of plus-strand strong-stop DNA synthesis and that the absence of M(1)A58 allows RT to read the tRNA sequences beyond residue 58. In addition, we show that replacement of M(1)A58 with U inhibits the replication of HIV-1 in vivo. These results highlight the importance of tRNA primer residue A58 in the reverse transcription process. Inhibition of reverse transcription with mutant tRNA primers constitutes a novel approach for therapeutic intervention against HIV-1.

Distribution of Amylin-immunoreactive Neurons in the Monkey Hypothalamus and Their Relationships with the Histaminergic System

Archives of Histology and Cytology. Aug, 2001  |  Pubmed ID: 11575425

Amylin (AMY) is a 37 amino acid peptide of pancreatic origin that has been localized in peripheral and central nervous structures. Both peripheral and central injection of the peptide causes various effects, including anorectic behavior in rats. Prompted by previous reports showing that the anorectic effect of AMY is mediated by histamine release, we immunohistochemically investigated possible relationships between these two systems at the light microscopical level. Monkey (Macaca fuscata japonica) hypothalamus specimens were submitted to immunohistochemical double staining procedures using AMY and histidine decarboxylase (HDC) antisera. AMY-immunoreactive neurons were found widely distributed in several nuclei of the monkey hypothalamus including the supraoptic, paraventricular, perifornical, periventricular, ventromedial, arcuate, and tuberomammillary nuclei. We detected AMY-immunoreactive nerve fibers throughout the hypothalamus, the median eminence and hypothalamus-neurohypophysial tract. Although AMY- and HDC-immunoreactive neuronal cell bodies occupied distinct hypothalamic zones, many HDC-immunoreactive cell bodies and dendrites, particularly those in the periventricular, arcuate, and rostral tuberomammillary regions, were surrounded by numerous AMY-immunoreactive nerve fiber varicosities. These findings demonstrate for the first time the presence of a discrete number of AMY-immunoreactive neurons in the monkey hypothalamus and add morphological support to the experimental data demonstrating that AMY probably exerts its influence on food intake via the histaminergic system.

Fetal Alveolar Epithelial Cells Contain [D-Ala(2)]-deltorphin I-like Immunoreactivity: Delta- and Mu-opiate Receptors Mediate Opposite Effects in Developing Lung

American Journal of Respiratory Cell and Molecular Biology. Oct, 2001  |  Pubmed ID: 11694450

Opiate-like peptides can regulate many cellular functions. We now map [D-Ala(2)]deltorphin I (DADTI)-like immunoreactivity (DADTI-LI) in developing mouse lung and analyze potential functional roles. Most DADTI-LI-positive cells were alveolar cells negative for prosurfactant protein (proSP)-C immunoreactivity. Peak numbers of DADTI-LI-positive cells occurred on embryonic Day 18, decreasing postnatally. To analyze developmental effects of DADTI, e17-18 lung explants were treated with [D-Ala(2)]deltorphin II (DADTII, soluble DADTI analogue, delta-receptor-specific) versus dermorphin (mu-receptor-specific). Type II pneumocyte differentiation, assessed by [(3)H]choline incorporation into saturated phosphatidylcholine and proSP-C immunostaining, was inhibited by DADTII but stimulated by dermorphin. Cell proliferation, measured as [(3)H]-thymidine incorporation and proliferating cell nuclear antigen immunostaining, was stimulated by DADTII and inhibited by dermorphin. All effects were dose-dependent. DADTII-inhibited choline incorporation was reversed by the delta-blocker, naltrindole. Unexpectedly, DADTII-stimulated thymidine incorporation was augmented by naltrindole and reversed by naloxone (mu-blocker). Although dermorphin-stimulated choline incorporation was appropriately blocked by binaltorphimine, dermorphin-inhibited thymidine incorporation was reversed by delta, kappa-, or mu-blockers. The delta- and mu-receptor messenger RNAs occurred pre- and postnatally, whereas kappa-receptor transcripts occurred mainly prenatally. All three receptor proteins were present in epithelial and mesenchymal cells in e18 lung. Thus, DADTI-LI from proSP-C-immunonegative alveolar cells could regulate development via both direct and indirect effects involving multiple opiate receptors.

"Sentiments of a Private Nature": a Comment on Ann Laura Stoler's "Tense and Tender Ties."

Journal of American History (Bloomington, Ind.). , 2001  |  Pubmed ID: 18225375

Heroin Sensitization As Mapped by C-Fos Immunoreactivity in the Rat Striatum

Brain Research. Apr, 2002  |  Pubmed ID: 11931859

Immunohistochemistry was used to map the induction of c-Fos protein in the forebrain of rats treated with heroin. Acute injection of heroin to drug-naive rats caused significant induction of c-Fos protein in the nucleus accumbens shell, whereas the same dose of heroin given to drug-sensitized rats significantly increased c-Fos immunoreactivity in the dorsomedial caudate-putamen. These results show that the heroin-induced pattern of c-Fos protein in the rat striatum differs according to the rat's drug history. These findings may represent a neural correlate of the motor components of heroin sensitization.

Pinealectomy Does Not Affect the Healing of Experimental Colonic Anastomoses

Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research. Mar-Apr, 2002  |  Pubmed ID: 12028616

Gastrointestinal system anastomoses, especially colonic anastomoses, have significant morbidity and mortality despite recent technical improvements. Besides regulating the circadian rhythm, the pineal gland and its main neurohormone product melatonin have widespread actions in the organism. The purpose of this study was to investigate the effects of pinealectomy on the healing of colonic anastomoses. One hundred male albino Wistar rats were used in this study. The rats were separated into three groups: control, pinealectomy, and sham groups. In the control group, only colonic resection and anastomoses were performed. Following pinealectomy, colonic anastomosis was performed 2 weeks later on one half and 2 months later on the other half of the pinealectomy group. Only craniotomy was performed on the sham group, and the rats were separated and evaluated like the pinealectomy group. Colonic anastomoses were evaluated on postanastomotic day 3 and 7 by measuring the bursting pressure and the hydroxyproline levels in the anastomotic segments. There was no difference in the bursting pressure measurements between the groups on both postoperative day 3 and 7. Although hydroxyproline levels were different between groups on both postanastomotic days 3 and 7, it has been observed that neither normal nor anastomotic hydroxyproline levels influenced the anastomotic bursting pressure measurements. The percent deviation from the normal values was compared in the anastomotic segments, and no differences were found regarding the bursting pressure and hydroxyproline levels. It was concluded that pinealectomy has no effect on the healing of colonic anastomoses.

The Effects of Corticosteroids on the Healing of Tracheal Anastomoses in a Rat Model

Pharmacological Research : the Official Journal of the Italian Pharmacological Society. Apr, 2002  |  Pubmed ID: 12030793

The deleterious effects of corticosteroids on anastomotic healing have been widely demonstrated in various tissues. This study is designed to investigate the effects of corticosteroids on the healing of tracheal anastomoses. Forty-two adult female Wistar rats, randomly divided into five groups, underwent tracheal transection and primary anastomoses. The groups were assigned as follows: Group I, sham, ( N= 6); Group II, control, ( N= 6); Group III, dexamethasone, 0.1 mg kg (-1) per day, intramuscularly for a week ( N= 10); Group IV, dexamethasone, 1 mg kg (-1) per day, intramuscularly for a week (N= 10); Group V, dexamethasone, 6 mg kg (-1) intramuscularly as a single dose ( N= 10). After 7 days, anastomotic healing was assessed by measurement of bursting pressure and hydroxyproline content. Histological examination was performed according to the modified Ehrlich/Hunt scale. The bursting pressure was significantly decreased in Group III and Group IV when compared to the control group (P< 0.0001 for both groups). There was also significance between the bursting pressures of Group III and Group IV (P< 0.01). However, the difference failed to reach significance between Group V and the control group. The reduction of bursting pressure was not reflected in diminished hydroxyproline content. The hydroxyproline content of the study groups (GIII, GIV and GV) were not statistically different compared with the control group. Except for inflammatory cell infiltration, histological parameters including epithelial regeneration, fibroblast proliferation, collagen content, and angiogenesis also demonstrated significant differences among the groups (P< 0.05). The present study demonstrates that daily administration of dexamethasone for a week significantly impairs the healing of tracheal anastomoses in a dose-dependent manner while a single-dose postoperatively does not affect the healing process.

Short Bowel Syndrome Impairs Healing of Intestinal Anastomosis in Rats

Transplantation Proceedings. May, 2002  |  Pubmed ID: 12034293

Dissociation in the Effects of the D2/D3 Dopaminergic Agonist Quinpirole on Drinking and on Vasopressin Levels in the Rat

Neuroscience Letters. Jun, 2002  |  Pubmed ID: 12044626

In the present study, we investigated the role of vasopressin in the development of quinpirole-induced hyperdipsia in the rat. We report that: (1), an acute intraperitoneal (i.p.) injection of 0.56 mg/kg of quinpirole increased plasma vasopressin (radioimmunoassay) at 15 min but not at 30 or 120 min; (2), nine daily injections of quinpirole (0.56 mg/kg, i.p.) progressively increased water intake and diuresis for a period of several hours after each treatment; (3), quinpirole hyperdipsia was associated with apparently normal levels of vasopressin (which might be considered inappropriately high in the presence of excessive drinking); (4), quinpirole reduced vasopressin and oxytocin, but not angiotensin, immunoreactivity in the supraoptic nucleus. These findings suggest that quinpirole hyperdipsia is a sound animal model of psychotic polydipsia.

Effect of Topically Applied Charged Particles on Healing of Colonic Anastomoses

Archives of Surgery (Chicago, Ill. : 1960). Jul, 2002  |  Pubmed ID: 12093338

Various forms of electrical stimulation can improve wound healing in different tissues, but their application to gastrointestinal tract healing has not been investigated. We assumed that positively charged diethylaminoethyl cross-linked dextran bead (diethylaminoethyl Sephadex [DEAE-S]) particles would have a beneficial effect on the healing of colonic anastomoses.

[Polyembrioma of the Testis: Case Report Following Chemotherapy for Non-Hodgkin's Lymphoma]

Il Giornale Di Chirurgia. Mar, 2002  |  Pubmed ID: 12109226

Testicular tumours represent 2% of all male malignancies, mostly concerning young men (20-40 years old). The polyembryoma is one of the uncommonest lesions and just recently it has been identified as autonomous nosographic entity. The reported case is peculiar because the patient was older than the most ones described in the literature and the tumour arose after polychemotherapy for non Hodgkins' disease. The Authors analyse some aspects concerning etiology, pathology and clinical approach to such rare neoplasm.

Effects of Portal Triad Occlusion on Left-sided Colonic Anastomosis

International Surgery. Jan-Mar, 2002  |  Pubmed ID: 12144186

Anastomotic healing can deteriorate because of different local and systemic effects in cases of concomitant left colon and liver injuries. We evaluated the effects of portal triad occlusion (PTO) on bowel anastomosis after concomitant segmental left colonic resections achieved in rats. There were three separate groups of animals; each consisted of 20 Sprague-Dawley male rats weighing 250 +/- 20 g. In group I, left colonic segmental resection 1 cm in diameter and anastomosis were performed as controls. In group II, the same surgical procedure was done after 15 minutes of PTO followed by 30 minutes of reperfusion. In group III, PTO time was held at 30 minutes. The rats were killed at days 4 and 7 to evaluate anastomotic healing, histological changes, bursting pressures, and serum levels of malondialdehyde (MDA) and hydroxyproline. In group II, the bursting pressures of anastomosis on days 4 and 7 were similar to group I; these pressures were significantly lower in group III (P < 0.001), whereas the hydroxyproline levels in group II were lower than group I and group III levels (P < 0.002). There were histopathological changes that support the data found in groups II and III. Serum MDA levels in groups II and III were significantly higher than in group I (P < 0.001). We observed that serum MDA levels peaked at day 4 and gradually decreased with a statistically significant difference at day 7. In conclusion, there were no negative effects of PTO on colonic anastomosis in group II. But in group III, with longer occlusion times, anastomotic healing was impaired and the mortality rate was higher.

[Expression of Lewis Carbohydrate Antigen in Human Tumors]

Chirurgia Italiana. May-Jun, 2002  |  Pubmed ID: 12192932

In this study we show, by immunoblotting, that Mab B3, a newly isolated monoclonal antibody, reacts with a variety of glycoproteins with different molecular weights expressed in gastric, pancreatic and colorectal cancers. The reactivity pattern differed in cancers arising in different tissues, though no correlation was observed with the histopathological characteristics of the lesions analysed. MAb B3 does not react with liver, brain or kidney cancers and has a limited reactivity with lung cancers but reacts very strongly with metastatic lesions. Because of the limited reactivity of this antibody with normal tissues, MAb B3 genetically fused with toxin in the form of a recombinant immunotoxin may be useful in treating certain kinds of cancer such as metastatic lesions. However, until current trials are completed, we will not know whether this immunotoxin will be helpful in cancer treatment.

Locally Applied Granulocyte-macrophage Colony-stimulating Factor Improves the Impaired Bowel Anastomoses in Rats with Long-term Corticosteroid Treatment

World Journal of Surgery. Oct, 2002  |  Pubmed ID: 12205560

Inflammation is an essential component of the first phase of anastomotic wound healing, and it is suppressed by corticosteroids. The anti-inflammatory effect of corticosteroids is largely responsible for the impairment of wound healing in bowel anastomosis. It has been reported that local application of granulocyte-macrophage colony-stimulating factor (GM-CSF) improves the healing process in dermal wounds. In the present study, we investigated the effects of locally injected GM-CSF on anastomotic wound healing in long-term corticosteroid treated rats. Eighty male Sprague-Dawley rats were randomized into four groups. (1) control, (2) steroid, (3) steroid + local GM-CSF, (4) steroid + systemic GM-CSF. In groups 2, 3, and 4, methylprednisolone (5 mg/kg) was injected IM daily for 14 days. After 14 days, following anesthesia and laparotomy, colonic anastomosis was performed 3 cm away from the peritoneal reflection. In group 3, 50 mg GM-CSF was injected into the perianastomotic area. In group 4, 50 mg GM-CSF was applied subcutaneously. On postoperative day 3, repeat laparotomies were performed and bursting pressures, hydroxyproline levels, and histopathology examinations were studied. The mean values of bursting pressures and hydroxyproline levels in group 3, treated with steroid + local GM-CSF, were significantly higher than that of the group 2 and group 4 values. In the histopathology examination, the mean score of group 3 was significantly higher than that of groups 2 and 4. Our study indicates that local application of GM-CSF significantly improves the impaired anastomotic wound healing in rats treated with long-term corticosteroid.

Immunoreactive Neurons in the Brain of Two Mouse Strains After Incubation with an Antiserum Recognizing Asp-Val-Val-Gly.NH2 (DVVG), the C-terminal Fragment of (D-Ala2)-deltorphin I

Journal of Chemical Neuroanatomy. Sep, 2002  |  Pubmed ID: 12297265

D-Ala(2)-deltorphin I (DADTI) is a heptapeptide amide first extracted from frog skin that displays a high selectivity and affinity for delta opioid receptors. Previous studies using a polyclonal antiserum specific for its C-terminal tetrapeptide-amide (DVVG) have already described in rat and mouse brain the presence of immunoreactive neurons, most of them belonging to the mesencephalic dopaminergic neurons. C57BL/6J (C57) and DBA/2J (DBA) are two inbred strains of mice well known for showing marked genotype-dependent differences for phenotypes related to differential brain dopamine functioning. Brain specimens of both inbred mouse strains were frozen, cut and immunostained using the same antiserum. Some sections were also double immunostained with monoclonal anti-tyrosine hydroxylase (TH). DVVG-immunoreactive neurons were observed among both dopaminergic and non-dopaminergic neurons. DVVG- and TH-immunoreactive neurons were observed among the dopaminergic A8, A9 and A10 mesencephalic nuclei. They were on average 21.9% more numerous in DBA than in C57 mice. DVVG-immunoreactive nerve fibres could be seen in limbic, striatal, cortical and thalamic areas. The distribution patterns of DVVG-IR and TH-IR nerve fibres differed most conspicuously within the infralimbic, prelimbic and cingulate cortices, forming a dense network in DBA but rare in C57 mice. Non-dopaminergic DVVG-immunoreactive neurons did not differ significantly in the two strains. Our finding that the number and distribution pattern of this dopaminergic neuronal subpopulation differed in the two mouse strains could provide morphological support for the known behavioural differences between the DBA and C57 strains under normal and experimental conditions.

Intraoperative Radiochromoguided Mapping of Sentinel Lymph Node in Colon Cancer

Tumori. Jul-Aug, 2002  |  Pubmed ID: 12400991

The aim of our study was to assess the feasibility of sentinel lymph node (SLN) detection in colon cancer using a radiochromoguided technique. The regional lymph node status is crucial for colorectal cancer staging and the stage of disease at the time of diagnosis is the main factor influencing therapeutic decision-making and patient survival.

Citrus Limonoids and Their Semisynthetic Derivatives As Antifeedant Agents Against Spodoptera Frugiperda Larvae. A Structure-activity Relationship Study

Journal of Agricultural and Food Chemistry. Nov, 2002  |  Pubmed ID: 12405773

The antifeedant activity of Citrus-derived limonoids limonin (1), nomilin (2), and obacunone (3) and their semisynthetic derivatives 4-26 was evaluated against a commercially important pest, Spodoptera frugiperda. Simple chemical conversions were carried out on the natural limonoids obtained from seeds of Citrus limon. These conversions focused on functional groups considered to be important for the biological activity, namely the C-7 carbonyl and the furan ring. In particular, reduction at C-7 afforded the related alcohols, and from these their acetates, oximes, and methoximes were prepared. Hydrogenation of the furan ring was also performed on limonin and obacunone. The known antifeedant properties of the Citrus limonoids are confirmed. Comparison with previously reported data shows that insect species vary in their behavioral responses to these structural modifications. Highly significant antifeedant activity (P < 0.01) for two natural (1 and 3) and three semisynthetic limonoids (4, 8, and 10) was observed against S. frugiperda.

Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy: Report of New Cases and Review of the Literature

Neuropediatrics. Dec, 2002  |  Pubmed ID: 12571787

Spinal muscular atrophy (SMA) is a clinically and genetically heterogeneous disease characterised by loss of motor function and muscle atrophy due to anterior horn cell degeneration. The most common variant is chromosome 5-linked proximal SMA, ranging in severity from congenital onset and infantile death to onset in adult life. Genetically separate variants with different distribution of weakness and/or additional features such as central nervous system involvement have been described. A rare variant with associated myoclonic epilepsy and lower motor neuron disease had been previously described in three families before the SMN gene, responsible for the common form of SMA, was isolated. We report four patients from two additional families affected by a syndrome characterised by severe and progressive myoclonic epilepsy and proximal weakness, tremor and lower motor neuron disease proven by electrophysiologic and muscle biopsy findings. Extensive metabolic investigations were normal and genetic analysis excluded the SMN gene. This study confirms that the association of myoclonic epilepsy and motor neuron disease represents a separate clinical and genetic entity from chromosome 5-linked SMA, the primary defect of which remains unknown.

The Effect of Recombinant Growth Hormone on Intestinal Anastomotic Wound Healing in Rats with Obstructive Jaundice

The Turkish Journal of Gastroenterology : the Official Journal of Turkish Society of Gastroenterology. Mar, 2002  |  Pubmed ID: 16378269

Several clinical and experimental studies have shown that obstructive jaundice delays wound healing. Growth hormone may prevent delayed wound healing, since it has effects on the release of mediators in jaundice, as well as increasing the protein synthesis.

The Effect of Methylene Blue on Peritoneal Adhesion Formation

The Turkish Journal of Gastroenterology : the Official Journal of Turkish Society of Gastroenterology. Jun, 2002  |  Pubmed ID: 16378287

Postoperative adhesions following abdominopelvic surgery may cause significant morbidity. In this study, the effect of different doses of methylene blue in the formation of adhesions and the role of allopurinol in revealing the possible mechanism of action was evaluated.

In Vitro Evaluation of Different Techniques of Enamel Preparation for Pit and Fissure Sealing

The Journal of Adhesive Dentistry. , 2003  |  Pubmed ID: 15008338

To compare the penetration and the imperviousness of two pit and fissure sealants according to surface treatments involving different cleaning procedures with or without subsequent acid etching.

Cardiac Complications in Thalassemia: Noninvasive Detection Methods and New Directions in the Clinical Management

Expert Review of Cardiovascular Therapy. Sep, 2003  |  Pubmed ID: 15030271

The natural history of thalassemia has shown substantial change during these years. This applies for each aspect of the pathology (for example, endocrinological, hepatological and psychological) and also for the pathology that has presented and still presents the main cause of death: myocardial dysfunction. In this review, the pathophysiology of cardiac complications, possible role of myocarditis, new knowledge on pathogenesis, and noninvasive detection methods for iron overload in the heart are pointed out. Prophylaxis of cardiomyopathy and new therapy strategies of myocardial dysfunction, including the impact of the new chelation treatment, are discussed.

[Preparation of a Manual Treatment of Pressure Ulcers Which Draws Attention to Moisture of the Affected Part]

Gan to Kagaku Ryoho. Cancer & Chemotherapy. Dec, 2003  |  Pubmed ID: 15311773

As for pressure ulcers care, prevention is the most important approach. However, pressure ulcers, might develop despite enough care, depending on each person's physical condition. As for the treatment of pressure ulcers, maintenance of a moderately moist environment (60-70%) is quite important. We propose the use of ointment to control the moisture of a pressure ulcer environment. One ointment base absorbs moisture, while another provides moisture. We have prepared a manual that allows the user to select the medicine according to the degree of moisture of the affected part. When the moisture cannot be regulated with one ointment, it can be adjusted by mixing two or more ointments. In choosing a drug for external use, it is important to pay attention not only to the effect of the main ingredient but also to the physicochemical properties of the ointment base that serves as vehicle for that active component.

Effect of Fibrinogen Concentration and Platelet Count on the Inhibitory Effect of Abciximab and Tirofiban

Thrombosis and Haemostasis. Feb, 2003  |  Pubmed ID: 12574816

Glycoprotein (Gp) IIb/IIIa blockers are powerful antithrombotic agents, but display a wide variability of their effect using weight adjusted dosing. We investigated whether some hemostatic variables affected in vitro platelet inhibition exerted by the antibody abciximab and the peptidomimetic tirofiban. High fibrinogen concentrations reduced platelet inhibition by tirofiban, assessed in whole blood (r = -0.85, n = 10, p <0.01) and in platelet rich plasma (r = -0.89, n = 10, p <0.01) through PFA 100 and Born's aggregometry assay, respectively. Both drugs were unaffected by von Willebrand factor levels, while platelet count was inversely related to their inhibitory effect (tirofiban: r = -0.9, n = 7, p <0.01; abciximab: r = -0.81, n = 9, p <0.01). Analysis of GpIIb-IIIa blockade showed that receptor occupancy at a fixed abciximab dose was inversely related to platelet counts. These experimental data were in agreement with the classical model of receptor saturation by a tight binding inhibitor. A role for fibrinogen and/or platelet count in influencing the antithrombotic properties of platelet GpIIb-IIIa antagonists can be hypothesized.

Stapled and Open Hemorrhoidectomy: Randomized Controlled Trial of Early Results

World Journal of Surgery. Feb, 2003  |  Pubmed ID: 12616437

The aim of the study was to compare the early results in 52 patients randomly allocated to undergo either stapled or open hemorrhoidectomy. Seventy-four patients with grade III and IV hemorrhoids were randomly allocated to undergo either stapled (37 patients) or open (37 patients) hemorrhoidectomy. Stapled hemorrhoidectomy was performed with the use of a circular stapling device. Open hemorrhoidectomy was accomplished according to the Milligan-Morgan technique. Postoperative pain was assessed by means of a visual analogue scale (V.A.S.). Recovery evaluation included return to pain-free defecation and normal activities. A 6-month clinical follow-up and a 17.5 (10 to 27)-month median telephone follow-up was obtained in all patients. Operation time for stapled hemorrhoidectomy was shorter (median 25 [range 15 to 49] minutes versus 30 [range 20 to 44] minutes, p = 0.041). Median (range) V.A.S. scores in the stapled group were significantly lower (V.A.S. score after 4 hours: 4 [2 to 6] versus 5 [2 to 8], p = 0.001; V.A.S. score after 24 hours: 3 [1 to 6] versus 5 [3 to 7], p = 0.000; V.A.S. score after first defecation: 5 [3 to 8] versus 7 [3 to 9], p = 0.000). Resumption of pain-free defecation was significantly faster in the stapled group (10 [6 to 14] days vs 12 [9 to 19] days, p = 0.001). At follow-up 4 weeks and 6 months postoperatively the median (range) symptom severity score was similar in both groups (1 [0 to 2] versus 0 [0 to 3], p = 0.150 and 0 [0 to 2] versus 0 [0 to 2], p = 0.731). At long-term follow-up occasional pain was present in 6/37 (16.2) patients in the stapled group and 7/37 (18.9%) in the Milligan-Morgan group (p = 1.000); episodes of bleeding were reported by 8/37 (21.6%) patients in the stapled group and 5/37 (13.5%) patients in the Milligan-Morgan group (p = 0.542). No problems related to continence and defecation were reported in either group. Patients were satisfied with the operation in 33/37 (89.2%) cases in the stapled group and 31/37 (83.8%) cases in the Milligan-Morgan group (p = 0.735). Hemorrhoidectomy with a circular staple device is easy to perform and achieves better results than the Milligan-Morgan technique in terms of postoperative pain and recovery. Comparable results are obtained at long-term follow-up.

The Effects of Corticosteroids and Vitamin A on the Healing of Tracheal Anastomoses

International Journal of Pediatric Otorhinolaryngology. Feb, 2003  |  Pubmed ID: 12623145

This study investigates the deleterious effects of corticosteroids on tracheal anastomotic healing and the ability of vitamin A to reverse these effects in a rat model.

Principles and Advantages of Robotics in Urologic Surgery

Current Urology Reports. Apr, 2003  |  Pubmed ID: 12648427

Although the available minimally invasive surgical techniques (ie, laparoscopy) have clear advantages, these procedures continue to cause problems for patients. Surgical tools are limited by set axes of movement, restricting the degree of freedom available to the surgeon. In addition, depth perception is lost with the use of two-dimensional viewing systems. As surgeons view a "virtual" target on a television screen, they are hampered by decreased sensory input and a concurrent loss of dexterity. The development of robotic assistance systems in recent years could be the key to overcoming these difficulties. Using robotic systems, surgeons can experience a more natural and ergonomic surgical "feel." Surgical assistance, dexterity and precision enhancement, systems networking, and image-guided therapy are among the benefits offered by surgical robots. In return, the surgeon gains a shorter learning curve, reduced fatigue, and the opportunity to perform complex procedures that would be difficult using conventional laparoscopy. With the development of image-guided technology, robotic systems will become useful tools for surgical training and simulation. Remote surgery is not a routine procedure, but several teams are working on this and experiencing good results. However, economic concerns are the major drawbacks of these systems; before remote surgery becomes routinely feasible, the clinical benefits must be balanced with high investment and running costs.

Lipid Peroxidation and Extracellular Matrix in Normal and Cirrhotic Rat Livers Following 70% Hepatectomy

Hepato-gastroenterology. May-Jun, 2003  |  Pubmed ID: 12828089

The aim was to measure the deposition of collagens and proteoglycans and the underlying mechanism leading to lipid peroxidation due to oxidative stress in partially hepatectomized normal and cirrhotic rats.

The Role of the Spleen on Colonic Anastomotic Healing

Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research. Jul-Aug, 2003  |  Pubmed ID: 12893499

The role of the spleen on wound healing remains unclear. This study investigates the effect of splenectomy on the healing of colonic anastomoses. Twenty-six Wistar rats were assigned into four groups: sham, splenectomy, anastomoses, and splenectomy and anastomoses. The rats underwent a standardized left colonic resection and primary anastomoses, and/or splenectomy. Bursting pressure and hydroxyproline content were used to evaluate anastomotic healing, five days postoperatively. No differences were found in the bursting pressure and hydroxyproline content between the groups. The present results indicate that splenectomy has no negative effect on the healing of colonic anastomoses in rats.

Supportive Care in Patients with Advanced Non-small-cell Lung Cancer

British Journal of Cancer. Sep, 2003  |  Pubmed ID: 12966418

The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.

Norepinephrine-gamma-aminobutyric Acid (GABA) Interaction in Limbic Stress Circuits: Effects of Reboxetine on GABAergic Neurons

Biological Psychiatry. Jan, 2003  |  Pubmed ID: 12547473

Reboxetine is a selective norepinephrine (NE) reuptake inhibitor that exerts significant antidepressant action. The current study assessed norepinephrine-gamma-aminobutyric acid (GABA)-ergic mechanisms in reboxetine action, examining glutamic acid decarboxylase (GAD) mRNA expression in limbic neurocircuits following reboxetine within the context of chronic stress.

Effect of Electromagnetic Fields and Early Postoperative 5-fluorouracil on the Healing of Colonic Anastomoses

International Journal of Colorectal Disease. Mar, 2003  |  Pubmed ID: 12548416

Studies have indicated a deleterious effect of perioperative 5-fluorouracil (5-FU) administration on the healing of intestinal anastomoses. This study examined the effect of early postoperative 5-FU on the healing of colonic anastomoses and investigated the effect of electromagnetic fields (EMF) on colonic anastomotic repair under normal physiological conditions and in the presence of 5-FU therapy in a rat model.

Images in Cardiovascular Medicine. Membrane-type Subaortic Stenosis in the Adult

Italian Heart Journal : Official Journal of the Italian Federation of Cardiology. Sep, 2003  |  Pubmed ID: 14635386

[Preparation of a Manual Treatment of Pressure Ulcers Which Draws Attention to Moisture of the Affected Part]

Gan to Kagaku Ryoho. Cancer & Chemotherapy. Dec, 2003  |  Pubmed ID: 14708306

As for pressure ulcers care, prevention is the most important approach. However, pressure ulcers, might develop despite enough care, depending on each person's physical condition. As for the treatment of pressure ulcers, maintenance of a moderately moist environment (60-70%) is quite important. We propose the use of ointment to control the moisture of a pressure ulcer environment. One ointment base absorbs moisture, while another provides moisture. We have prepared a manual that allows the user to select the medicine according to the degree of moisture of the affected part. When the moisture cannot be regulated with one ointment, it can be adjusted by mixing two or more ointments. In choosing a drug for external use, it is important to pay attention not only to the effect of the main ingredient but also to the physicochemical properties of the ointment base that serves as vehicle for that active component.

ARS Component B: Structural Characterization, Tissue Expression and Regulation of the Gene and Protein (SLURP-1) Associated with Mal De Meleda

European Journal of Dermatology : EJD. Nov-Dec, 2003  |  Pubmed ID: 14721776

The ARS Component B gene (EMBL ID: HSARS81S, AC: X99977) encodes a 9 kD non-glycosylated polypeptide (also known as SLURP-1, SwissProt/TrEMBL: P55000), a soluble member of the human Ly6/uPAR superfamily. ARS Component B gene mutations have been implicated in Mal de Meleda. In this study we show by immunohistochemistry that SLURP-1 (secreted Ly-6/uPAR related protein, the protein product of the ARS Component B gene) is localized to human skin, exocervix, gums, stomach and esophagus. In the epidermis, keratinocytes underlying the stratum corneum are highly positive for SLURP1 immunostaining and cultured keratinocytes secrete the expected 9 kD protein. Circulating SLURP1 is detected in human plasma and urine. In the mouse, expression is evident in skin, eye, whole lung, trachea, esophagus and stomach. Human ARS Component B mRNA expression is regulated by retinoic acid, epidermal growth factor and interferon-gamma. The tissue localization and the association with Mal de Meleda suggest that ARS Component B and its protein product SLURP1 are implicated in maintaining the physiological and structural integrity of the keratinocyte layers of the skin.

The Mutation Spectrum of the APC Gene in FAP Patients from Southern Italy: Detection of Known and Four Novel Mutations

Human Mutation. Jun, 2003  |  Pubmed ID: 14961559

Familial adenomatous polyposis (FAP), an autosomal dominantly inherited condition accounting for about 1% of all colorectal cancers, results from mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. The clinical spectrum and severity of FAP varies greatly with the mutation site, and both between and within families. Using the protein truncation test, single strand conformation polymorphism analysis and DNA sequencing, we identified 30 (75%) mutant alleles in 40 unrelated FAP families, for a total of 22 different APC mutations. Of these, 18 are known and 4 are novel: c.1797C>A (C599X), c.893_894delAC, (c.3225T>A; c.3226C>A) and c.4526_4527insT. Of the 30 APC gene mutations, 5 (approximately 17%) are nonsense mutations, 17 (approximately 57%) are small deletions, 5 (approximately 17%) are small insertions and 3 (approximately 10%) are complete deletions. All mutations occurred in single pedigrees, except those at codons 1061 and 1062, each found in two unrelated families, and the mutation at codon 1309 in exon 15, found in five unrelated families. About 40% of mutations, mostly small deletions and insertions, are located at repeated sequences; they promote misalignment-mediated errors in DNA replication and could represent a hot spot mutation region. This study enlarges the spectrum of APC gene mutations and sheds light on the correlation between the site of APC germline mutations and clinical manifestations of FAP.

Ontogeny of Guanylin-immunoreactive Cells in Rat Salivary Glands

Anatomy and Embryology. Apr, 2004  |  Pubmed ID: 14986129

Guanylin-like peptides regulate electrolyte/water transport through the epithelia. Moreover, these peptides possess antiproliferative activity and regulate the turnover of epithelial cells. In an earlier study we localized guanylin immunoreactivity in secretory ducts of adult rodent salivary glands. In this study we investigated the appearance and distribution pattern of this peptide during the development of rat salivary glands. Guanylin immunoreactivity appeared at the beginning of cell differentiation from solid bud, on embryonic day 17 in the submandibular and sublingual glands and after day 18 in the parotid gland. Guanylin immunoreactivity appeared first in ductal and acinar anlage: its cell distribution pattern and fate differed in these two compartments. In the duct cells guanylin immunoreactivity spread after the duct system developed, whereas in acinar cells it disappeared after cell differentiation. The guanylin immunoreactivity we detected in adult salivary duct cells accords with guanylin's role in regulating electrolyte and water transport through the various epithelia. It does so by activating guanylate cyclase-C receptor, increasing intracellular cGMP concentration, and phosphorylating the cystic fibrosis transmembrane conductance regulator (CFTR) protein by the cGMP-dependent protein kinase II. This signaling cascade couples to the ductal electrolyte/water secretion and modulates finally the electrolyte composition of the saliva. On the other hand, CFTR is also involved in mechanisms of cell growth, by regulating apoptosis, and promoting cell differentiation. The early diffuse guanylin immunoreactivity we observed in ducts and acinar anlage, before the secretory set is operative, suggests guanylin has a role in cell differentiation.

Hepatocellular Carcinoma in the Thalassaemia Syndromes

British Journal of Haematology. Jan, 2004  |  Pubmed ID: 14675416

Hepatocellular carcinoma (HCC) frequently complicates hepatic cirrhosis secondary to viral infection or iron overload. Therefore, patients affected by thalassaemia syndromes have a theoretically high risk of developing the tumour. We collected data on patients attending Italian centres for the treatment of thalassaemia. Twenty-two cases of HCC were identified; 15 were male. At diagnosis, the mean age was 45 +/- 11 years and the mean serum ferritin was 1764 +/- 1448 microg/l. Eighty-six percent had been infected by hepatitis C virus. Nineteen of 22 cases were diagnosed after 1993, suggesting that this problem is becoming more frequent with the aging population of thalassaemia patients.

Hypogonadism and Hormone Replacement Therapy on Bone Mass of Adult Women with Thalassemia Major

Calcified Tissue International. Jan, 2004  |  Pubmed ID: 14523599

We studied bone mass and metabolism in 30 adult women (age 28.5 +/- 1.3) with thalassemia major (TM) and evaluated whether prolonged hormone replacement therapy (HRT) was able to optimize bone accrual. TM patients had reduced bone mass, increased bone turnover and lower serum gonadotropin and estradiol levels compared with 10 normal women of similar age. A significant correlation was found between bone mass and sex hormone levels. Six TM patients with normal ovarian function had normal bone turnover markers and modestly low bone mass (lumbar spine -1.29 +/- 0.31; femoral neck -0.60+/-0.21; Z-score). The other 24 TM women were hypogonadic and had significantly lower bone mass for age (lumbar spine -2.35 +/- 0.2, femoral neck -1.83 +/- 0.2) and increased bone turnover relative to eugonadal women. Of the hypogonadal patients, 13 had taken HRT since age 15 +/- 1 years, but their bone mass and turnover markers were not different than untreated hypogonadal patients. In conclusion, while hypogonadism negatively affects bone mass acquisition in adult TM women, HRT at the standard replacement doses is not sufficient to secure optimal bone accrual.

Conserved Structural and Sequence Elements Implicated in the Processing of Gene-encoded Circular Proteins

The Journal of Biological Chemistry. Nov, 2004  |  Pubmed ID: 15328347

The cyclotides are the largest family of naturally occurring circular proteins. The mechanism by which the termini of these gene-encoded proteins are linked seamlessly with a peptide bond to form a circular backbone is unknown. Here we report cyclotide-encoding cDNA sequences from the plant Viola odorata and compare them with those from an evolutionarily distinct species, Oldenlandia affinis. Individual members of this multigene family encode one to three mature cyclotide domains. These domains are preceded by N-terminal repeat regions (NTRs) that are conserved within a plant species but not between species. We have structurally characterized peptides corresponding to these NTRs and show that, despite them having no sequence homology, they form a structurally conserved alpha-helical motif. This structural conservation suggests a vital role for the NTR in the in vivo folding, processing, or detoxification of cyclotide domains from the precursor protein.

Late Coronary Thrombosis After Drug-eluting Stent: Stent Vs Patient-driven Prescription of Aspirin-clopidogrel Combination

Thrombosis and Haemostasis. Sep, 2004  |  Pubmed ID: 15457605

The Incidence of Thyroid Carcinoma in Multinodular Goiter: Retrospective Analysis

Acta Bio-medica : Atenei Parmensis. Aug, 2004  |  Pubmed ID: 15481700

Thyroid carcinoma (TC) is a relatively rare tumour, but it represents the most frequent form of cancer of the endocrine glands. Epidemiologically ascertained risk factors are ionising radiation, the presence of thyroid adenoma and multinodular goiter (MNG). Multinodularity of goiter should no longer be considered an indicator of probable benign disease. A retrospective analysis was performed on patients operated of MNG at the Unit of Otolaryngology, Sanremo Hospital (Italy) from January 1st 1995 to December 31st 2002, in order to establish the incidence of carcinoma. The results of this retrospective study, demonstrate that in 13.7% of the patients operated for goiter, the presence of a carcinoma was noticed in the definitive histopathologic examination. Such incidence percentage of MNG is in accordance with the data reported in published reports. Thus, the authors conclude that the risk of malignancy in MNG has not to be underestimated, and that a dominant nodule in MNG should be valued as if it were a solitary nodule in an otherwise normal gland.

Nervous System Development in Normal and Atresic Chick Embryo Intestine: an Immunohistochemical Study

Anatomy and Embryology. Dec, 2004  |  Pubmed ID: 15597193

Intestinal motility disorders are a common complication after surgery for neonatal intestinal atresia. Although intestinal atresia causes alterations in the enteric nervous system, especially in its inner structures (nervous fibers in the mucosa, submucous and deep muscular plexuses), how these alterations develop is unclear. The chick model is a useful research tool for investigating the ontogenesis of the enteric nervous system and the pathogenesis of congenital bowel diseases. More information is needed on the overlap between the developing enteric nervous system and intestinal atresia. Because vasoactive intestinal polypeptide and substance P are typical intestinal neuropeptides, and vasoactive intestinal polypeptide acts as a modulator in neurodevelopment and an inhibitor of smooth muscle cell proliferation, our aim in this study was to investigate the distribution of their immunoreactivity in the developing enteric nervous system of normal and experimental chick models. We studied gut specimens excised from normal chick embryos (aged 12-20 days) and experimental chick embryos (aged 15-20 days) that underwent surgical intervention on day 12 to induce intestinal atresia (atresic embryos) or simply to grasp the bowel loop (sham-operated embryos). In normal chick embryos we showed vasoactive intestinal polypeptide and substance P immunoreactivity from day 12 in the submucous and myenteric plexuses. The distribution of peptide immunoreactivity differed markedly in atresic and normal or sham-operated gut embryos. These differences especially affected the inner structures of the enteric nervous system of specimens proximal to atresia and were related to the severity of dilation. Because nerve structures in the gut wall mucosa and submucous and deep muscular plexuses play a role in motility control and stretch sensation in the intestinal wall, our findings in the chick embryo may help to explain how gut motility disorders develop after surgery for neonatal intestinal atresia.

[Having Trouble with Pressure Ulcers Care?]

Gan to Kagaku Ryoho. Cancer & Chemotherapy. Dec, 2004  |  Pubmed ID: 15645764

Since 1997, we, the community pharmacists, have established this society, Aichi Prefecture Society for the Study of Pressure Ulcers Care, in order to furnish drug information about pressure ulcers care. Moist atmosphere is required for the healing of pressure ulcers. The moist environment that could be regulated depends on the physicochemical property of ointment bases. Therefore, ointment should reasonably be chosen to adjust the moisture. Since 2000, we have been committed to providing pharmacists, who work on home care, with a booklet to instruct how to choose ointments for pressure ulcers treatment. In 2002, when the Aichi pharmaceutical association held a training conference held at various hospitals using the booklet as a teaching material, hospital pharmacists cooperated by making a field study trip to observe pressure ulcers treatments. Nowadays researchers at pharmaceutical colleges have also cooperated in studying the efficacy and economical effect of the method of blending different ointments to improve the healing process of pressure ulcers.

Inhibition of HIV Type 1 Replication Using Lentiviral-mediated Delivery of Mutant TRNA(Lys3)A58U

AIDS Research and Human Retroviruses. Dec, 2004  |  Pubmed ID: 15650425

In previous studies, we showed that residue A58 of cellular tRNALys3 is necessary for appropriate termination of viral plus-strand strong-stop DNA (+SS DNA), and therefore plays a critical role in the life cycle of HIV-1. We also performed proof-of-principle studies that established that a mutant form of this tRNA primer (tRNA(Lys3)A58U, which lacks the M1A58 residue necessary for +SS DNA termination) could inhibit HIV-1 replication. In the present work, we examined whether a third generation lentiviral vector (SIN) could be used to deliver tRNA(Lys3)A58U to CEM cells. Using both viral kinetic studies and limiting dilution assays (LDA), we observed significant impairment of HIV-1 replication, up to 3 logs in the LDA, in CEM sublines expressing mutant tRNA(Lys3)A58U. No inhibition occurred in cells that either expressed wild-type tRNA(Lys3) or were transduced with empty SIN vector. Further, we observed impairment of viral replication using primary isolates of both HIV-1 and HIV-2 in sublines containing tRNA(Lys3)A58U. We also detected "breakthrough" HIV-1 replication in some tRNA(Lys3)A58U-expressing cultures. Interestingly, analyzed breakthrough viruses appeared to be both genetically and phenotypically wild type. One possible explanation for virological breakthrough is that it reflects the gradual accumulation of HIV-1 within the infected cell culture, to a level that ultimately exceeds the containment "threshold" conferred by tRNA(Lys3)A58U. The fact that HIV-1 does not appear to acquire heritable resistance to tRNA(Lys3)A58U-mediated blockade differentiates this antiviral modality from other therapeutic interventions. It also suggests that tRNA-mediated inhibition of viral replication might be a valuable adjunct to other antiviral approaches.

Cigarette Smoking and Appendectomy Are Risk Factors for Extraintestinal Manifestations in Ulcerative Colitis

The American Journal of Gastroenterology. Feb, 2004  |  Pubmed ID: 15046225

Two common factors, cigarette smoking and appendectomy, have been found to play a role in ulcerative colitis (UC). Data on their role in the development of extraintestinal manifestations (EIM) are scarce.

Sustained Local Application of Low-dose Epidermal Growth Factor on Steroid-inhibited Colonic Wound Healing

Journal of Pediatric Surgery. Apr, 2004  |  Pubmed ID: 15065034

The effects of locally administered low-dose epidermal growth factor in a steroid-inhibited wound healing were investigated in a rat model.

A Novel Approach for Preventing Esophageal Stricture Formation: Sphingosylphosphorylcholine-enhanced Tissue Remodeling

Pediatric Surgery International. Oct, 2004  |  Pubmed ID: 15185106

Using a new class of intracellular 2nd messengers to prevent stricture formation after caustic ingestion, sphingosylphosphorylcholine (SPC) has a wide spectrum of activity in cell growth regulation and signal transduction. Caustic esophageal burns were created with 15% NaOH in an experimental rat model. Control group animals (n = 10) had esophageal burns with no treatment, whereas the SPC group (n = 10) had esophageal burns gavaged with SPC for 7 days. Efficacy of treatment was assessed in 28 days by contrast esophagograms, histopathologic evaluation, and biochemically by tissue hydroxyproline (OHP) content. Contrast esophagograms demonstrated that SPC significantly prevented stricture formation. Obvious collagen deposition was present in submucosa, muscularis mucosa, and muscular layers in the control group compared with the SPC group. The damage to the esophageal wall on histopathologic examination was significantly lower in the SPC group (p < 0.05). Tissue OHP contents were significantly lower in the SPC-treated group (3.0 +/- 0.1 microg/mg) compared with the control group (4.3 +/- 0.2 microg/mg) (p < 0.05). We conclude that SPC improves healing following caustic esophageal burns. Furthermore, SPC is effective in preventing caustic esophageal strictures. These effects of SPC occur through its proliferative and specifically its remodeling effects on wound healing.

Fate of (D-Ala2)-deltorphin-I-like Immunoreactive Neurons in 6-hydroxydopamine Lesioned Rat Brain

European Journal of Histochemistry : EJH. Apr-Jun, 2004  |  Pubmed ID: 15208081

The use of a polyclonal antiserum specific to C-terminal tetrapeptide amide of (D-Ala2)deltorphin-I, a naturally occurring amphibian skin opioid peptide, has already demonstrated the presence of immunoreactive neurons in rat midbrain. Double immunostaining identified these neurons as a subpopulation of the mesencephalic dopaminergic neurons that were also tyrosine hydroxylase-immunopositive and calbindin-D28kD- negative, namely, the neurons predominantly affected in Parkinson disease. We followed the fate of these neurons after a monolateral injection of 6-hydroxy-dopamine into rat brain. Almost all the immunopositive neurons and their nigrostriatal, mesolimbic and mesocortical projections on the side ipsilateral to the lesion disappeared. Only a few scattered immunopositive neurons within the substantia nigra, pars compacta, and those of supramammillary nucleus remained unaffected. The consistent overlap of dopamine and this new molecule provides a further key to identifying the mammalian counterpart of these amphibian skin opioid peptides.

[Does Sepsis Impair the Healing of Colonic Anastomosis in Splenectomized Rats?]

Ulusal Travma Dergisi = Turkish Journal of Trauma & Emergency Surgery : TJTES. Oct, 2005  |  Pubmed ID: 16341965

BACKGROUND: To investigate the effect of splenectomy on the healing of colonic anastomoses under normal and septic conditions. METHODS: Forty Wistar rats were assigned into six groups: group 1: sham, group 2: colonic anastomose, group 3: splenectomy, group 4: colonic anastomose plus sepsis, group 5: colonic anastomose plus splenectomy, group 6: colonic anastomose plus splenectomy plus sepsis. The rats underwent a standardized left colonic resection and primary anastomosis and/or splenectomy. Sepsis was produced by cecal ligation and puncture. Wound healing was evaluated by bursting pressure and hydroxiproline estimates. RESULTS: Bursting pressures were as follows: group 1: 173 +/- 14 mmHg, group 2: 186 +/- 7 mmHg, group 3: 168 +/- 6 mmHg, group 4: 113 +/- 14 mmHg, group 5: 167 +/- 10 mmHg, and group 6: 183 +/- 3 mmHg. Hidroksiprolin contents were: group 1: 3.5 +/- 0.2 microg/mg, group 2: 3.2 +/- 0.3 microg/mg, group 3: 3.4 +/- 0.2 microg/mg, group 4: 2.3 +/- 0.2 microg/mg, group 5: 3.0 +/- 0.2 microg/mg, grup 6 3.2 +/- 0.1 microg/mg. Statistical significance was found between group 4 and the other groups (p<0.05). CONCLUSION: Sepsis impairs the healing of colonic anastomoses. However, sepsis does not impair the intestinal wound healing in splenectomized rats.

Intestinal Permeability and Genetic Determinants in Patients, First-degree Relatives, and Controls in a High-incidence Area of Crohn's Disease in Southern Italy

The American Journal of Gastroenterology. Dec, 2005  |  Pubmed ID: 16393227

A defect of gastrointestinal barrier function is considered to represent an important step in the pathogenesis of Crohn's disease (CD) but the mechanisms leading to an increased intestinal permeability (IP) are poorly understood. Since IP is influenced by pro-inflammatory mediators, it seems likely that a genetically determined abnormal immune response may lead to a loss of barrier function.

Hepatocellular Carcinoma on Cirrhosis-free Liver in a HCV-infected Thalassemic

American Journal of Hematology. Feb, 2005  |  Pubmed ID: 15682406

Analysis of Superoxide Dismutase Activity Levels in Gingiva and Gingival Crevicular Fluid in Patients with Chronic Periodontitis and Periodontally Healthy Controls

Journal of Clinical Periodontology. Mar, 2005  |  Pubmed ID: 15766365

Superoxide dismutase (SOD) is an antioxidant enzyme that acts against superoxide, an oxygen radical, released in inflammatory pathways and causes connective tissue breakdown. In this study, SOD activities in gingiva and gingival crevicular fluid (GCF) from patients with chronic periodontitis (CP) and periodontally healthy controls were compared.

Guanylin-immunoreactive Cells in the Female and Male Rat Adenohypophysis and Their Changes Under Various Physiological and Experimental Conditions

Histochemistry and Cell Biology. Mar, 2005  |  Pubmed ID: 15812648

The peptide guanylin, first isolated from rat small intestine, is involved in the regulation of water-electrolyte transport between the intracellular and extracellular compartments of the epithelia. The main sites of guanylin expression are the intestinal, airway, or exocrine gland ductal epithelia where guanylin acts in a paracrine/luminocrine fashion. Because guanylin also circulates in the blood, sources of this peptide were sought in endocrine glands. Our group has already demonstrated the presence of guanylin-immunoreactive cells in the pars tuberalis of male rat adenohypophysis. In this study, we investigated whether guanylin-immunoreactive cells exist also in the adenohypophysial pars distalis and whether their appearance or distribution correlates with various physiological conditions in female rats or alters after gonadectomy in both sexes. These studies revealed that the rat pars distalis contains two guanylin-immunoreactive cell types, gonadotrophic cells, whose number varied notably during the estrous cycle, reached a peak in the proestrous phase, and increased consistently during pregnancy, in lactating animals, and after gonadectomy, and folliculo-stellate cells, a discrete number of which were found only in female rats at the estrous phase. These findings suggest that guanylin is involved in regulating gonadotrophic cell function. They also add important information on the controversially discussed functions of folliculo-stellate cells.

Granulocyte Macrophage-colony Stimulating Factor Improves Impaired Anastomotic Wound Healing in Rats Treated with Intraperitoneal Mitomycin-C

Surgery Today. , 2005  |  Pubmed ID: 15815844

Intraperitoneal chemotherapy (IPCT) delivers higher local concentrations of cytotoxic drugs than intravenous (i.v.) chemotherapy, but it can adversely affect the healing of intestinal anastomoses if given in the early postoperative period. Intestinal anastomotic leakage is a serious surgical complication. Experimental and clinical studies have shown that the local administration of granulocyte macrophage-colony stimulating factor (GM-CSF) improves would healing. Therefore, we evaluated the effects of locally applied GM-CSF on anastomotic wound healing in rats treated with intraperitoneal mitomycin-C immediately after surgery.

Optimal Duration of Antiplatelet Therapy in Recipients of Coronary Drug-eluting Stents

Drugs. , 2005  |  Pubmed ID: 15819586

Four weeks' therapy with clopidogrel, in addition to aspirin (acetylsalicylic acid), is currently standard care after percutaneous coronary intervention (PCI) with stent implantation. The recent availability of drug-eluting stents (DES), which dramatically reduce restenosis at the site of PCI, has again raised the issue of stent thrombosis. In clinical trials, the risk of stent thrombosis appeared unrelated to the presence of the drug eluting from the stent and was documented within the usual range of < or =1% at 9 months after DES implantation. However, these devices feature delayed strut endothelialisation and there are reports describing late DES thrombosis up to 18 months after PCI, in most cases after clopidogrel has been discontinued. Although infrequent after bare-metal stenting (0.4-2.8%), stent thrombosis is a catastrophic event. Before DES availability, adjunctive intravascular brachytherapy significantly reduced in-stent neointimal proliferation, at the price of a higher-than-expected rate of late stent occlusion (6-8%). In such setting, a 12-month aspirin plus clopidogrel regimen showed a beneficial effect on long-term adverse events. An additional consideration is that, among patients undergoing bare-metal stent PCI, combined antithrombotic therapy with aspirin and clopidogrel has been recently associated with favourable effects on cardiovascular outcome beyond stent thrombosis in two large-scale clinical trials. Therefore, we propose that prolonged combination therapy with aspirin and clopidogrel be mandatory up to 1 year after PCI in all patients receiving DES.

Pharmacodynamic Interaction of Naproxen with Low-dose Aspirin in Healthy Subjects

Journal of the American College of Cardiology. Apr, 2005  |  Pubmed ID: 15837265

We investigated the occurrence of pharmacodynamic interaction between low-dose aspirin and naproxen.

Anorectal Atresia Treated with Non-continent Pull Through and Artificial Bowel Sphincter: a Case Report

Techniques in Coloproctology. Apr, 2005  |  Pubmed ID: 15868499

Anorectal atresia, which is classified as a low anorectal malformation, is characterised by the absence of the anal verge and by variable rectal atresia. In some cases, which have been classified as rectal agenesis, the atresia is associated with the absence of the internal sphincter. The therapeutic options are definitely surgical, aiming to relieve the bowel occlusion and to restore faecal continence by lowering the cul-de-sac to the perineum. We present the case of an adult patient with congenital rectal agenesis, double fistula (cul-de-sac-urethra and cul-de-sac-perineum) and caecostomy since birth. The patient was treated with a resection of sigmoid-rectum for the presence of a 20-cm faecaloma in the cul-de-sac, with a non-continent pull-through, and with implantation of an artificial bowel sphincter. Despite some difficulties in managing the device and a slight symptomatic mucosal prolapse, the results after 30 months have so far satisfied both the patient and the medical staff, especially in consideration of the limited number of alternative therapies.

Latent Chlamydial Infections: the Probable Cause of a Wide Spectrum of Human Diseases

Medical Hypotheses. , 2005  |  Pubmed ID: 15993547

In the decade from 1980 to 1990, anamnestic data were amassed from 746 animal breeders on 31 farms, suffering from similar health problems and at the same time, 146 people from various professions outside agriculture were chosen as a control sample. A randomly selected group of 20 people from the 746 animal breeders were serologically tested for a wide range of infectious diseases (mycoplasmosis, tularaemia, leptospirosis, boreliosis, toxoplasmosis, listeriosis, and others). The analyses of these tests showed comparable figures in the majority of the tested people only in their serological response to chlamydial infection. Then, another randomly selected group of 157 people were serologically tested specifically for chlamydial infection. In 96% of these people a serological chlamydial response to a general chlamydial antigen and Chlamydia trachomatis antigen were diagnosed. Over the following eight years, these people were under medical observation and from one to four times a year they were serologically tested for various chlamydial antigens. After 12 years of intensive research, analyses and consultations with experts in both human and veterinary medicine, the findings of the research showed that the cause of a number of health problems and diseases could be identified in latent chlamydial infection. These findings were published in veterinary journals in the Czech Republic and Germany in 1992 [Von Bazala E, Renda J. Latente Chlamydieninfektionen als Ursache von Gesundheitsstörungen bei Schweine-, Rinder- und Schafzüchtern in der CSFR. Berl. Münch. Tierärztl. Wschr. 1992;105(145-149) 105. Heft 5. 1. Mai 1992]. Due to persistent and deteriorating health problems in a majority of the examined people, the research efforts were continued and similar symptoms were consequently discovered in people from urban, non-animal breeding communities, of whom most of the long-term afflicted were also in many cases tested Chlamydia seropositive.

The Effect of Exogenous Melatonin on Experimental Colonic Anastomosis

Acta Chirurgica Belgica. May-Jun, 2005  |  Pubmed ID: 16018525

In this study we investigated the role of exogenous melatonin administration on the healing of colonic anastomoses.

Heroin Sensitization Induces Circumventricular Organ Activation in the Rat Brain

Italian Journal of Anatomy and Embryology = Archivio Italiano Di Anatomia Ed Embriologia. , 2005  |  Pubmed ID: 16101018

Using c-Fos protein immunohistochemistry we previously demonstrated various sites of activation in the rat forebrain according to the animal's drug history. This study originates from a more detailed evaluation ex-post of the same specimens. A discrete number of c-Fos protein immunoreactive nuclei could be observed in some circumventricular organs, including the vascular organ of terminal lamina (OVLT) and subfornical organ (SFO) and in the nucleus of solitary tract near the area postrema, but only in specimens from sensitized rats. We therefore suggest that repeated drug injections activate the normally low drug metabolizing enzyme activity in the circumventricular organs thus implicating these organs in the complex mechanisms underlying behavioral sensitization.

Quantitative Evaluation of Oxidative Stress Status on Peripheral Blood in Beta-thalassaemic Patients by Means of Electron Paramagnetic Resonance Spectroscopy

British Journal of Haematology. Oct, 2005  |  Pubmed ID: 16173974

High oxidative stress status (OSS) is known to be one of the most important factors determining cell injury and consequent organ damage in thalassaemic patients with secondary iron overload. Using an innovative hydroxylamine 'radical probe' capable of efficiently trapping majority of oxygen-radicals including superoxide we measured, by electron paramagnetic resonance (EPR) spectroscopy, OSS in peripheral blood of 38 thalassaemic patients compared with sex-/age-matched healthy controls. Thalassaemic patients showed sixfold higher EPR values of OSS than controls. Significantly higher EPR values of OSS were observed in those with a severe phenotype (thalassaemia major, transfusion-dependent) with respect to mild phenotype (sickle-cell/beta-thalassaemia, not transfusion-dependent) or thalassaemia intermedia. In patients with thalassaemia major, EPR values of OSS were positively correlated with serum ferritin and with alanine aminotransferase levels. In patients with sickle cell/beta-thalassaemia, there was no correlation between EPR value of OSS and all parameters considered. The type of chelating therapy (desferrioxamine or deferiprone) did not have an effect on EPR value of OSS. In conclusion, EPR 'radical probe' seems to be a valid innovative method to determine total OSS in patients affected by thalassaemia and might be used for evaluating new strategies of chelation, new chelators, or the efficacy of antioxidant formula.

Pretreatment Quality of Life and Functional Status Assessment Significantly Predict Survival of Elderly Patients with Advanced Non-small-cell Lung Cancer Receiving Chemotherapy: a Prognostic Analysis of the Multicenter Italian Lung Cancer in the Elderly Study

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. Oct, 2005  |  Pubmed ID: 16192578

To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy.

Effect of Povidone-iodine Liposome Hydrogel on Colonic Anastomosis

European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes. Jul-Aug, 2005  |  Pubmed ID: 16260875

To evaluate the effect of povidone-iodine liposome hydrogel on colonic anastomosis.

The Role of Basal Insulin in Type 2 Diabetes Management

The Journal of Family Practice. Oct, 2005  |  Pubmed ID: 16271258

Respiratory Infections and Asthma

Respiratory Medicine. May, 2006  |  Pubmed ID: 16289785

Respiratory tract infections caused by both viruses and/or atypical bacteria are involved in the pathogenesis of asthma. In particular, several viruses such as respiratory syncytial virus, rhinovirus and influenza/parainfluenza viruses may favour the expression of the asthmatic phenotype, being also implicated in the induction of disease exacerbations. Within this pathological context, a significant role can also be played by airway bacterial colonizations and infections due to Chlamydiae and Mycoplasms. All these microbial agents probably interfere with complex immunological pathways, thus contributing to induce and exacerbate asthma in genetically predisposed individuals.

Stapled Vs Open Hemorrhoidectomy: Long-term Outcome of a Randomized Controlled Trial

International Journal of Colorectal Disease. Oct, 2006  |  Pubmed ID: 16479368

Stapled hemorrhoidectomy is a relatively new procedure, and studies on long-term outcomes are few. We present the results of a 5-year follow-up on patients recruited to a randomized controlled trial comparing stapled and Milligan-Morgan hemorrhoidectomy.

Treatment with Hydroxycarbamide for Intermedia Thalassaemia: Decrease of Efficacy in Some Patients During Long-term Follow Up

British Journal of Haematology. Apr, 2006  |  Pubmed ID: 16512837

Changes in Neuropeptide FF and NPY Immunohistochemical Patterns in Rat Brain Under Heroin Treatment

Brain Research. Apr, 2006  |  Pubmed ID: 16529722

Immunohistochemical distribution patterns of neuropeptide FF (NPFF) and neuropeptide tyrosine (NPY) were studied in the brain of rats submitted to two different protocols of heroin treatment. In drug-naive rats, acutely injected heroin significantly depleted NPFF-immunoreactive material within the neurons of the nucleus of solitary tract (NTS), significantly decreased the density of NPFF-immunoreactive nerve fibers within the median eminence, pituitary stalk, and neurohypophysis, and markedly increased NPY-immunoreactive neurons and nerve fibers in the thalamic paraventricular nucleus and bed nucleus of stria terminalis. In drug-sensitized rats, heroin significantly increased the number and immunostaining intensity of the NPFF-immunoreactive neurons within the NTS and induced minor changes in the NPFF-immunoreactive nerve fiber network of the median eminence, pituitary stalk, and neurohypophysis and a relatively minor increase in NPY neurons in the thalamic paraventricular nucleus and bed nucleus of stria terminalis. These heroin-induced changes suggest that NPFF is involved in regulating the effects of the heroin injection and in the mechanisms underlying behavioral sensitization. They also add further support to the key role of NPY in any conditions tending to change the animal homeostasis.

A Prospective Study of Hepatocellular Carcinoma Incidence in Thalassemia

Hemoglobin. , 2006  |  Pubmed ID: 16540424

Hepatocellular carcinoma (HCC) is a complication of cirrhosis. Due to blood transfusions, patients with beta-thalassemia (thal) are often infected with either hepatitis C virus (HCV) or hepatitis B virus (HBV). In the past, many patients did not survive long enough to develop HCC. The recent improvements in prognosis have helped in the diagnosis of HCC that has developed. The aim of this study was to evaluate HCC incidence in beta-thal. We performed liver ultrasound (US) on all adults without a previous diagnosis of HCC. Risk factors (iron overload, HCV infection, HBV infection, cirrhosis) were evaluated. One hundred and eight thalassemia patients have been evaluated; of whom three were excluded (two patients as they were under the age of 18 years and one patient because he had a previous history of HCC). Seventy-two patients [31 had thalassemia major (TM), 41 had thalassemia intermedia (TI)] with risk factors (iron overload in 72, HCV infection in 46, HBV infection in two, cirrhosis in 10) and 33 (four with TM and 29 with TI) without risk factors underwent liver US. Overall, two patients were found to have a newly developed HCC. Of these two patients, one was treated with surgery and the other with percutaneous radiofrequency. Further follow-up did not show any evidence of recurrence after 23 and 15 months, respectively. Ultrasound screening can allow early detection and treatment of HCC in thalassemia patients.

Effects of Beta-D-glucan on Steroid-induced Impairment of Colonic Anastomotic Healing

Acta Chirurgica Belgica. Jan-Feb, 2006  |  Pubmed ID: 16612917

Inflammation during the early phase of anastomotic wound healing is an essential cellular response and is suppressed by corticosteroids. The anti-inflammatory effect of corticosteroids is largely responsible for its impairment of wound healing in bowel anastomosis. Beta-D-glucan, a commonly used macrophage activator, has been shown to improve anastomotic wound healing under normal conditions. In the present study, we have investigated the effects of beta-D-glucan on anastomotic wound healing in rats treated with long-term corticosteroid.

Local Granulocyte-macrophage Colony-stimulating Factor Improves Incisional Wound Healing in Adriamycin-treated Rats

Surgery Today. , 2006  |  Pubmed ID: 16378193

Neoadjuvant treatment is often given for locally advanced malignancies; however, clinical and experimental studies have shown that some chemotherapeutic agents impair wound healing. It has been reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) applied locally improves dermal wound healing. Thus, we investigated the effects of locally injected GM-CSF on abdominal wounds impaired by adriamycin, a widely used chemotherapeutic agent.

Incidence of Crohn's Disease and CARD15 Mutation in a Small Township in Sicily

European Journal of Epidemiology. , 2006  |  Pubmed ID: 17160430

The incidence of Crohn's disease (CD) has been shown to be lower in Southern than in Northern Europe. Data on the frequency of the NOD2/CARD15 mutations for Mediterranean area are very scant.

Pica Presenting As Metabolic Alkalosis and Seizure in a Dialysis Patient

Clinical Nephrology. Jul, 2006  |  Pubmed ID: 16878440

Biological Targets for Therapeutic Interventions in COPD: Clinical Potential

International Journal of Chronic Obstructive Pulmonary Disease. , 2006  |  Pubmed ID: 18046869

COPD is a widespread inflammatory respiratory disorder characterized by a progressive, poorly reversible airflow limitation. Currently available therapies are mostly based on those used to treat asthma. However, such compounds are not able to effectively reduce the gradual functional deterioration, as well as the ongoing airway and lung inflammation occurring in COPD patients. Therefore, there is an urgent need to improve the efficacy of the existing drug classes and to develop new treatments, targeting the main cellular and molecular mechanisms underlying disease pathogenesis. These therapeutic strategies will be highlighted in the present review.

Psychological Insulin Resistance: Overcoming Barriers to Starting Insulin Therapy

The Diabetes Educator. Jun, 2006  |  Pubmed ID: 16831818

Treating to Target in Type 2 Diabetes: a Case Presentation

The Diabetes Educator. Jun, 2006  |  Pubmed ID: 16831817

Rapid Decline of Collateral Circulation Increases Susceptibility to Myocardial Ischemia: the Trade-off of Successful Percutaneous Recanalization of Chronic Total Occlusions

Journal of the American College of Cardiology. Jul, 2006  |  Pubmed ID: 16814649

We evaluated the time-behavior of changes in collateral circulation after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in chronic (>1 month) total occlusions (CTO), and assessed their relationship with myocardial ischemia.

Early Intervention to Achieve Optimal Outcomes in Type 2 Diabetes: a Case Presentation

Clinical Cornerstone. , 2006  |  Pubmed ID: 16939876

Type 2 diabetes mellitus (DM) is a progressive disease characterized by insulin resistance and impaired insulin secretion. To compensate for these metabolic dysfunctions, pancreatic beta-cells begin to overproduce insulin; however, it is this compensatory mechanism that eventually results in beta-cell exhaustion, impaired insulin secretion, and relative insulin deficiency. The metabolic abnormalities associated with diabetes also contribute to vascular dysfunction and an increased risk of coronary heart disease. Among patients with type 2 DM, cardiovascular disease, particularly macrovascular disease, is the primary cause of mortality, accounting for 55% of deaths. Management of the disease, therefore, must address all of the contributing factors, including a sedentary lifestyle and diet that contribute to overweight/obesity, and comorbidities such as hypertension and dyslipidemia. In this paper, we present a case study based on actual clinical experience to illustrate an evidence-based rationale for early and aggressive intervention for patients with type 2 DM, including lifestyle modification, oral antidiabetic agents, and insulin.

Celecoxib, Ibuprofen, and the Antiplatelet Effect of Aspirin in Patients with Osteoarthritis and Ischemic Heart Disease

Clinical Pharmacology and Therapeutics. Sep, 2006  |  Pubmed ID: 16952493

We performed a placebo-controlled, randomized study to address whether celecoxib or ibuprofen undermines the functional range of inhibition of platelet cyclooxygenase (COX)-1 activity by aspirin in patients with osteoarthritis and stable ischemic heart disease.

Heterogeneity in the Suppression of Platelet Cyclooxygenase-1 Activity by Aspirin in Coronary Heart Disease

Clinical Pharmacology and Therapeutics. Aug, 2006  |  Pubmed ID: 16890573

Complete and persistent suppression of platelet thromboxane (TX) A(2) biosynthesis by aspirin is mandatory to fulfill its cardioprotection. We explored the determinants of heterogeneity of TXB2 generation in clotting whole blood, a capacity index of platelet cyclooxygenase (COX) activity, in patients with coronary heart disease (CHD) versus healthy subjects treated with low-dose aspirin on a long-term basis.

Overcoming Psychological Barriers to Insulin Use in Type 2 Diabetes

Clinical Cornerstone. , 2006  |  Pubmed ID: 16939874

Type 2 diabetes mellitus (DM) is characterized by a gradual decrease in insulin sensitivity in peripheral tissues and the liver (insulin resistance), followed by a gradual decline in beta-cell function and insulin secretion. Given this decline, many patients with type 2 DM will require insulin therapy to achieve the glycemic target recommended by the American Diabetes Association of glycosylated hemoglobin (A1C) <7%. The combination of insulin plus oral antidiabetic drugs (OADs) has been shown to improve A1C values in patients who were not adequately controlled with OADs alone. Despite its established benefits, however, insulin therapy continues to be underused. The reluctance to initiate insulin therapy is often related to both provider and patient misperceptions about insulin's efficacy and side effects, as well as the perceived complexity of the treatment regimen. In addition, insulin therapy may be viewed as a "last resort" treatment option for severe disease or as "punishment" for patients' failure to manage their disease. However, patients should be made aware from the time of diagnosis that diabetes is a progressive disease and that it is likely that insulin therapy will be required at some point during the course of the disease. The subject of insulin therapy, therefore, should be approached positively and should be presented as an effective and flexible way to achieve glycemic goals for any patient at any time during therapy.

Early Development of Chick Embryo Respiratory Nervous System: an Immunohistochemical Study

Anatomy and Embryology. Oct, 2006  |  Pubmed ID: 16633821

The extrinsic and intrinsic respiratory nervous systems receive specific contributions from the vagal and sympathetic components. Using specific markers for vagal and sympathetic structures, we studied the distribution patterns of immunoreactivity to galanin (GAL), pituitary adenylate cyclase-activating polypeptide-27 (PACAP) and the tachykinin substance P in extrinsic and intrinsic nerve of chick embryo respiratory system, during development from the very early age to hatching. All peptides studied appeared in the intrinsic and extrinsic nervous systems early. We found substance P in both the vagal and sympathetic systems, PACAP in vagal components alone and GAL mainly in the sympathetic system. The intrinsic nervous system showed high immunoreactivity for all peptides studied. These data accord with the well known early trophic functions that peptides have on the development of nervous networks and modulatory activity on the intrinsic nervous system. The GAL again proves to be the main peptide in chick embryo sympathetic respiratory system.

[Prognostic Value of Splenectomy and Lymph-node Dissection During Gastric Cancer Resection]

Chirurgia Italiana. Mar-Apr, 2006  |  Pubmed ID: 16734164

Gastric carcinoma is the second most common cause of digestive tumour-related death in Europe, North America and Asia. Today, the gold standard of treatment is still surgery, but outcomes to date are unsatisfactory. The Japanese Society for Research in Gastric Cancer (JSRGC) recommends the routine execution of splenectomy during gastrectomy. This recommendation is contested by western Authors because of increased morbidity and mortality without any real advantage in terms of survival. Patients treated for gastric cancer in our department between 1993 and 2002 were selected for this study. The 132 patients recruited were divided into two groups: a) those treated for gastric cancer without splenectomy; and b) those in whom splenectomy was performed in conjunction with gastrectomy. We analysed: the extent of lymph node dissection, the execution of the splenectomy, and the prognostic importance of factors relating to the patient, tumour and surgeon. Splenectomy was not associated with any increase in morbidity. Complications, especially of the septic type, and perioperative mortality were similar in both groups, and the same was true of survival at both 3 and 5 years. In our opinion, splenectomy should not be routinely combined with surgery for gastric cancer but could be considered for T3-T4 neoplasms or those localized in the upper two thirds of the stomach.

Healing of Surgical Incision in Kidney Transplantation: a Single Transplant Center's Experience

Transplantation Proceedings. May, 2006  |  Pubmed ID: 16757258

Impaired healing of the surgical incision represents a common complication after kidney transplantation. We led a retrospective study seeking to understand the factors linked to these complications and reasons for their reduction during the last year.

Transplantation and Young Surgeons in Italy

Transplantation Proceedings. May, 2006  |  Pubmed ID: 16757306

The relation between young surgeons and transplantation has always been a "love and hate" one. Until a few years ago this branch of surgery was seen as pioneering, with extreme and and extensive training, and was reserved to few elected members. Nowadays things are different. In this article we try to understand the true reasons that young Italian surgeons avoid transplantation surgery.

Analysis of Delta-globin Gene Alleles in the Sicilian Population: Identification of Five New Mutations

Haematologica. Dec, 2006  |  Pubmed ID: 17145605

Although delta-globin gene (HBD MIM#142000) mutations have no clinical implications, co-inheritance of beta- and delta-thalassemia may lead to misdiagnosis. Among 7,153 samples studied for beta-thalassemia, 205 samples with lower than expected HbA2 levels were selected for our analysis and 183 samples (2.5%) were positive for delta-globin gene mutations. Twelve different mutations were detected, and among these five have not been not previously described (HbA2-Catania HBD c.8A-->T, HbA2-Corleone HBD c.41C-->A, HbA2-Ventimiglia HBD c.212C-->G, HbA2-Montechiaro HBD c.260C-->A, and HbA2-Bagheria HBD c.422C-->T). This study suggests that delta-globin gene defects are very common in Sicily. Thus, these mutations need to be considered during beta-thalassemia screening to avoid false negative results in the detection of at-risk couples.

Methylene Blue Prevents Surgery-induced Peritoneal Adhesions but Impairs the Early Phase of Anastomotic Wound Healing

Canadian Journal of Surgery. Journal Canadien De Chirurgie. Oct, 2006  |  Pubmed ID: 17152569

Adhesion formation continues to be an important problem in gastrointestinal surgery. In recent years, methylene blue (MB) has been reported to be an effective agent for preventing peritoneal adhesions. However, its effects on the wound healing process are unknown. In the present study, we investigated the effects of MB on the early and late phases of anastomotic wound healing and on adhesion formation.

Comparative Immunohistochemical Study of the Dopaminergic Systems in Two Inbred Mouse Strains (C57BL/6J and DBA/2J)

Journal of Chemical Neuroanatomy. Mar, 2007  |  Pubmed ID: 17276033

This study investigated possible neurochemical differences in the brain of two inbred mouse strains, C57BL/6J (C57) and DBA/2J (DBA) that in behavioral, memorization and learning tasks under normal and experimental conditions perform differently or often in an opposite manner. The immunohistochemical study, designed to investigate the dopaminergic system, identified many differences within the midbrain A10 area and less marked differences in areas A9 and A8. The number of dopamine transporter (DAT), vesicular monoamine transporter of type 2 (VMT) and tyrosine hydroxylase (TH) immunoreactive cell bodies was significantly higher in the midbrain of DBA mice than in C57 mice (on average +21.5%, P<0.001 in A10: +9.4% in A9, P<0.05: and +5.9% in A8, P<0.1). The distribution patterns of nerve fibres immunoreactive for same antisera also differed significantly in the two strains, especially at prelimbic, infralimbic and anterior cingulate cortical levels. In C57 mice these fibres were scanty whereas in DBA mice they were well represented. In the nucleus accumbens, also the territorial distribution of DAT immunoreactive nerve fibres differed in the two strains. In the midbrain, the galanin immunoreactive axons were more densely distributed in DBA than in C57 mice whereas neurotensin immunoreactive axons were more densely distributed in C57 than in DBA. These distinct immunohistochemical patterns could help to explain why performance differs in the two mouse strains.

Effects of TGF-beta and Glucocorticoids on Map Kinase Phosphorylation, IL-6/IL-11 Secretion and Cell Proliferation in Primary Cultures of Human Lung Fibroblasts

Journal of Cellular Physiology. Feb, 2007  |  Pubmed ID: 17044077

Transforming growth factor-beta1 (TGF-beta1) is crucially involved in the fibrotic events characterizing interstitial lung diseases (ILDs), as well as in the airway remodeling process typical of asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal and fibrotic human lung fibroblasts (HLFs), the effects of TGF-beta1 on mitogen-activated protein kinase (MAPK) phosphorylation, cell proliferation, and production of interleukins 6 (IL-6) and 11 (IL-11), in the presence or absence of a pretreatment with budesonide (BUD). MAPK phosphorylation was detected by Western blotting, cell viability and proliferation were evaluated using Trypan blue staining and [(3)H]-thymidine incorporation assay, respectively, and the release of IL-6 and IL-11 into cell culture supernatants was assessed by ELISA. TGF-beta1 (10 ng/ml) significantly stimulated MAPK phosphorylation (P < 0.01), and also enhanced cell proliferation as well as the secretion of both IL-6 and IL-11, which reached the highest increases at the 72nd h of cell exposure to this growth factor. All such effects were prevented by BUD (10(-8) M) and, with the exception of IL-6 release, also by a mixture of MAPK inhibitors. Therefore, our findings suggest that the fibrotic action exerted by TGF-beta1 in the lung is mediated at least in part by MAPK activation and by an increased synthesis of the profibrogenic cytokines IL-6 and IL-11; all these effects appear to be prevented by corticosteroids via inhibition of MAPK phosphorylation.

The Finding of Vascular and Urinary Anomalies in the Harvested Kidney for Transplantation

Transplantation Proceedings. Jul-Aug, 2007  |  Pubmed ID: 17692616

In kidney transplantation, anatomical vascular and excretory anomalies may represent causes of failure. Today's surgical techniques have made the most of the organs with anatomic anomalies and iatrogenic injury successfully used for transplantation.

Older Kidneys Donor Transplantation: Five Years' Experience Without Biopsy and Using Clinical Laboratory and Macroscopic Anatomy Evaluation

Transplantation Proceedings. Jul-Aug, 2007  |  Pubmed ID: 17692626

The exponential increase in organ demand is not associated with a similar increase of available kidneys. This emergency led to expanded criteria to consider a kidney transplantable. The aim of this retrospective study was to explain our use of older donor kidneys without biopsy.

Typing of the Immunological System in Human Embryos by Coelocentesis

European Journal of Haematology. Nov, 2007  |  Pubmed ID: 17714505

Coelocentesis offers a new opportunity for gaining access to the human embryos from 28 d postfertilization. However, while some studies about its biochemical composition have been reported, our knowledge about immunological pattern of this compartment is still limited. For this reason, we studied the human coelomic fluids sampled from 6.6 to 10 wk of gestation. The majority of cellular population consisted in mesenchymal/epithelial cells. In fluids sampled before 10 wk we found only a preT Cell Receptor expression and an absence or a very low frequency of B lymphocytes, T lymphocytes and NK (natural killer) antigens. These preliminary data suggest that the immunological system in human embryos could be in the ideal conditions to start a process of tolerance induction.

Critical DNA Binding Interactions of the Insulator Protein CTCF: a Small Number of Zinc Fingers Mediate Strong Binding, and a Single Finger-DNA Interaction Controls Binding at Imprinted Loci

The Journal of Biological Chemistry. Nov, 2007  |  Pubmed ID: 17827499

The DNA-binding protein CTCF (CCCTC binding factor) mediates enhancer blocking insulation at sites throughout the genome and plays an important role in regulating allele-specific expression at the Igf2/H19 locus and at other imprinted loci. Evidence is also accumulating that CTCF is involved in large scale organization of genomic chromatin. Although CTCF has 11 zinc fingers, we show here that only 4 of these are essential to strong binding and that they recognize a core 12-bp DNA sequence common to most CTCF sites. By deleting individual fingers and mutating individual sites, we determined the orientation of binding. Furthermore, we were able to identify the specific finger and its point of DNA interaction that are responsible for the loss of CTCF binding when CpG residues are methylated in the imprinted Igf2/H19 locus. This single interaction appears to be critical for allele-specific binding and insulation by CTCF.

[Physical Exercise and Sport Activities in Patients with and Without Coronary Heart Disease]

Monaldi Archives for Chest Disease = Archivio Monaldi Per Le Malattie Del Torace / Fondazione Clinica Del Lavoro, IRCCS [and] Istituto Di Clinica Tisiologica E Malattie Apparato Respiratorio, Università Di Napoli, Secondo Ateneo. Jun, 2007  |  Pubmed ID: 17886769

The quantity and intensity of physical activity required for the primary prevention of coronary heart disease remain unclear. Therefore, we examined the association between physical activity and coronary risk.

Surgical Bleeding After Pre-operative Unfractionated Heparin and Low Molecular Weight Heparin for Coronary Bypass Surgery

Haematologica. Mar, 2007  |  Pubmed ID: 17339186

Since the impairment of platelet function may cause excess peri-operative bleeding, pre-operative discontinuation of aspirin and heparin bridging are common for cardiac surgery. We evaluated the impact of pre-operative administration of enoxaparin and unfractionated heparin (UFH) on coagulation parameters and peri-operative bleeding in patients undergoing elective coronary artery bypass grafting (CABG) surgery after discontinuation of aspirin.

A Practical Approach for Implementation of a Basal-prandial Insulin Therapy Regimen in Patients with Type 2 Diabetes

Osteopathic Medicine and Primary Care. , 2007  |  Pubmed ID: 17448241

Basal-prandial insulin therapy is a physiologic approach to insulin delivery that utilizes multiple daily injections to cover both basal (ie, overnight fasting and between-meal) and prandial (ie, glucose excursions above basal at mealtime) insulin needs. While basal-prandial therapy with multiple daily injections is an important therapeutic option for patients with type 2 diabetes, there is a common perception that this therapy is difficult to initiate in the primary care setting. To address this issue, a panel of clinical experts convened to develop practical recommendations on how to initiate basal-prandial therapy in patients with type 2 diabetes, focusing on patient selection, simple dosing and titration, and monitoring. Patients with type 2 diabetes who are appropriate candidates for basal-prandial insulin therapy include those who: 1) are unable to achieve glycemic control on oral antidiabetic drugs, 2) are unable to achieve glycemic control on split-mixed/premixed insulin regimens, 3) are newly diagnosed but unlikely to respond to oral antidiabetic drugs alone (ie, the patient has severe hyperglycemia or a markedly elevated glycosylated hemoglobin A1C level for which oral antidiabetic drug therapy alone is unlikely to achieve goals), and 4) prefer this therapy due to socioeconomic or other individual considerations. Basal-prandial insulin can be initiated in a simple stepwise manner, starting first with the addition of basal insulin to the existing oral antidiabetic drug regimen, followed by the introduction of 1 prandial insulin injection to the basal insulin plus oral antidiabetic drug regimen (after basal insulin has been optimized). Subsequently, other injections of prandial insulin may be added when needed. Based on home glucose monitoring data, patients may be converted from split-mixed or premixed insulin regimens to basal-prandial regimens with similar ease. Basal-prandial therapy using newer insulin formulations, such as long- and rapid-acting insulin analogs, can be relatively simple to use in patients with type 2 diabetes and is an appropriate methodology for application by primary care clinicians.

The Effect of Erythropoietin on Healing of Obstructive Vs Nonobstructive Left Colonic Anastomosis: an Experimental Study

World Journal of Emergency Surgery : WJES. , 2007  |  Pubmed ID: 17502005

Anastomotic leakage is an important problem following primary resection in the left colon and is even more prominent when obstruction is present. We aimed to evaluate the possible effects of erythropoietin on the healing of anastomosis under both obstructive and non-obstructive states.

A Novel Plant Protein-disulfide Isomerase Involved in the Oxidative Folding of Cystine Knot Defense Proteins

The Journal of Biological Chemistry. Jul, 2007  |  Pubmed ID: 17522051

We have isolated a protein-disulfide isomerase (PDI) from Oldenlandia affinis (OaPDI), a coffee family (Rubiaceae) plant that accumulates knotted circular proteins called cyclotides. The novel plant PDI appears to be involved in the biosynthesis of cyclotides, since it co-expresses and interacts with the cyclotide precursor protein Oak1. OaPDI exhibits similar isomerase activity but greater chaperone activity than human PDI. Since domain c of OaPDI is predicted to have a neutral pI, we conclude that this domain does not have to be acidic in nature for PDI to be a functional chaperone. Its redox potential of -157 +/- 4 mV supports a role as a functional oxidoreductase in the plant. The mechanism of enzyme-assisted folding of plant cyclotides was investigated by comparing the folding of kalata B1 derivatives in the presence and absence of OaPDI. OaPDI dramatically enhanced the correct oxidative folding of kalata B1 at physiological pH. A detailed investigation of folding intermediates suggested that disulfide isomerization is an important role of the new plant PDI and is an essential step in the production of insecticidal cyclotides. The nucleotide sequence(s) reported in this paper have been submitted to the GenBank/EBI Data Bank with accession number(s) 911777.

Awake Systolic Blood Pressure Variability Correlates with Target-organ Damage in Hypertensive Subjects

Hypertension. Aug, 2007  |  Pubmed ID: 17562971

Growing evidence associates blood pressure (BP) variability with cardiovascular events in hypertensive patients. Here we tested the existence of a relationship between awake BP variability and target-organ damage in subjects referred for suspected hypertension. Systolic and diastolic BP variability were assessed as the standard deviation of the mean out of 24-hour, awake and asleep BP recordings in 180 untreated subjects, referred for suspected hypertension. Measurements were done at 15-minute intervals during daytime and 30-minute intervals during nighttime. Left ventricular mass index (by echo), intima-media thickness (by carotid ultrasonography), and microalbuminuria were assessed as indices of cardiac, vascular and renal damage, respectively. Intima-media thickness and left ventricular mass index progressively increased across tertiles of awake systolic BP variability (P for trend=0.001 and 0.003, respectively). Conversely, microalbuminuria was similar in the 3 tertiles (P=NS). Multivariable analysis identified age (P=0.0001), awake systolic BP (P=0.001), awake systolic BP variability (P=0.015) and diastolic BP load (P=0.01) as independent predictors of intima-media thickness; age (P=0.0001), male sex (P=0.012), awake systolic (P=0.0001) and diastolic BP (P=0.035), and awake systolic BP variability (P=0.028) as independent predictors of left ventricular mass index; awake systolic BP variability (P=0.01) and diastolic BP load (P=0.01) as independent predictors of microalbuminuria. Therefore, awake systolic BP variability by non-invasive ambulatory BP monitoring correlates with sub-clinical target-organ damage, independent of mean BP levels. Such relationship, found in subjects referred for recently suspected hypertension, likely appears early in the natural history of hypertension.

A Tensor Based Morphometry Study of Longitudinal Gray Matter Contraction in FTD

NeuroImage. Apr, 2007  |  Pubmed ID: 17350290

Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by progressive behavioural abnormalities and frontotemporal atrophy. Here we used tensor based morphometry (TBM) to identify regions of longitudinal progression of gray matter atrophy in FTD compared to controls. T1-weighted MRI images were acquired at presentation and 1-year follow-up from 12 patients with mild to moderate FTD and 12 healthy controls. Using TBM as implemented in SPM2, a voxel-wise estimation of regional tissue volume change was derived from the deformation field required to warp a subject's late to early anatomical images. A whole brain analysis was performed, in which a level of significance of p<0.05 corrected for multiple comparisons (family wise error-FWE) was accepted. Based on prior studies, a region of interest (ROI) analysis was also performed, including in the search area bilateral medial and orbital frontal regions, anterior cingulate gyrus, insula, amygdala and hippocampus. Within this ROI a level of significance of p<0.001 uncorrected was accepted. In the whole brain analysis, the anterior cingulate/paracingulate gyri were the only regions that showed significant atrophy change over 1 year. In the ROI analysis, the left ventro-medial frontal cortex, right medial superior frontal gyrus, anterior insulae and left amygdala/hippocampus showed significant longitudinal changes. In conclusion, limbic and paralimbic regions showed detectable gray matter contraction over 1 year in FTD, confirming the susceptibility of these regions to the disease and the consistency with their putative role in causing typical presenting behaviours. These results suggest that TBM might be useful in tracking progression of regional atrophy in FTD.

Rbm15 Modulates Notch-induced Transcriptional Activation and Affects Myeloid Differentiation

Molecular and Cellular Biology. Apr, 2007  |  Pubmed ID: 17283045

RBM15 is the fusion partner with MKL in the t(1;22) translocation of acute megakaryoblastic leukemia. To understand the role of the RBM15-MKL1 fusion protein in leukemia, we must understand the normal functions of RBM15 and MKL. Here, we show a role for Rbm15 in myelopoiesis. Rbm15 is expressed at highest levels in hematopoietic stem cells and at more moderate levels during myelopoiesis of murine cell lines and primary murine cells. Decreasing Rbm15 levels with RNA interference enhances differentiation of the 32DWT18 myeloid precursor cell line. Conversely, enforced expression of Rbm15 inhibits 32DWT18 differentiation. We show that Rbm15 alters Notch-induced HES1 promoter activity in a cell type-specific manner. Rbm15 inhibits Notch-induced HES1 transcription in nonhematopoietic cells but stimulates this activity in hematopoietic cell lines, including 32DWT18 and human erythroleukemia cells. Moreover, the N terminus of Rbm15 coimmunoprecipitates with RBPJkappa, a critical factor in Notch signaling, and the Rbm15 N terminus has a dominant negative effect, impairing activation of HES1 promoter activity by full-length-Rbm15. Thus, Rbm15 is differentially expressed during hematopoiesis and may act to inhibit myeloid differentiation in hematopoietic cells via a mechanism that is mediated by stimulation of Notch signaling via RBPJkappa.

Cod Liver Oil Supplementation Improves Cardiovascular and Metabolic Abnormalities in Streptozotocin Diabetic Rats

The Journal of Pharmacy and Pharmacology. Dec, 2007  |  Pubmed ID: 18053324

Abnormalities in the metabolism of essential fatty acids and the results of increased oxidative stress have been implicated in cardiovascular disorders observed in diabetes mellitus. This study, therefore, aimed to investigate the effects of cod liver oil (CLO, Lysi Ltd, Iceland), which comprises mainly an antioxidant vitamin A, n:3 polyunsaturated fatty acids (n:3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cardiovascular abnormalities in streptozotocin (STZ)-diabetic rats. Two days after single STZ (55 mg kg(-1), i.p.) or vehicle injection, diabetes was verified by increased blood glucose, and non-diabetic and diabetic rats were left untreated or treated with CLO (0.5 mL kg(-1) daily, by intragastric probing) for 12 weeks. Plasma glucose, triacylglycerol and cholesterol concentrations were significantly elevated in 12-week untreated-diabetic rats; CLO provided better weight gain, entirely prevented the plasma lipid abnormalities, but partially controlled the glycaemia in diabetic rats. In isolated aorta rings, diabetes resulted in increased phenylephrine-induced vasoconstriction and isoprenaline-induced vasorelaxation, impaired endothelium-dependent vasodilatation and unchanged responsiveness to sodium nitroprusside. CLO treatment completely prevented endothelial deficiency, partly corrected the phenylephrine-induced vasoconstriction and did not affect the responses to isoprenaline and sodium nitroprusside in diabetic aorta. Diabetes also produced a marked decrease in the rate of spontaneously beating right atria and a significant increase in basal contractile force of left ventricular papillary muscle. The responsiveness of right atria to the positive chronotropic effect of isoprenaline was significantly decreased in diabetic rats, and was increased in CLO-treated diabetic rats. The positive chronotropic effect of noradrenaline was markedly increased in diabetic atria, but prevented by CLO treatment. Diabetes also resulted in an increased positive inotropic response of papillary muscle to both noradrenaline and isoprenaline, which were prevented by CLO treatment. CLO treatment also resulted in lower tissue sensitivity (pD(2)) to these agonists in diabetic papillary muscle. Ventricular hydroxyproline content was found to be unchanged among the experimental groups. The ultrastructure of diabetic myocardium displayed various degenerations (i.e. intracellular oedema, myofibrillar fragmentation, condensed pleomorphic mitochondria, thick capillary irregular basement membrane, swollen endothelial cells), which were partially prevented by CLO treatment. We conclude that the supplementation with CLO is effective in preventing cardiovascular disorders observed in experimental diabetes.

Consequences of Missed Opportunities

Journal of Hospital Medicine : an Official Publication of the Society of Hospital Medicine. Jul, 2007  |  Pubmed ID: 17705210

Triple Antithrombotic Therapy with Aspirin, Clopidogrel and Warfarin--a Persisting Dilemma

Internal and Emergency Medicine. Oct, 2007  |  Pubmed ID: 17909706

Polyphenols Distribution in Juices from Citrus Allotetraploid Somatic Hybrids and Their Sexual Hybrids

Journal of Agricultural and Food Chemistry. Oct, 2007  |  Pubmed ID: 17914878

The polyphenol profile of an interspecific allotetraploid somatic hybrid, achieved by protoplast fusion, the 'Valencia' sweet orange ( Citrus sinensis L. Osbeck) + 'Femminello' lemon ( Citrus limon L. Burm), and three sexual hybrids obtained by backcrosses between Femminello lemon and the allotetraploid somatic hybrid ('Valencia' + 'Femminello') was studied by liquid chromatography-ultraviolet-diode array detector-mass spectrometry (LC-UV-DAD-MS). The aim of the work was to evaluate whether superior traits and improved performance can be observed in these new genotypes. Ten flavonoids (TF), comprising seven flavanones and three flavones, and four hydroxycinnamic acids (HCA) have been characterized and quantified in all hybrids and compared with those of the respective parents. The 'Valencia' + 'Femminello' somatic hybrid shows an intermediate polyphenol composition with respect to those of the parents, with a slight prevalence of lemon influence. The three sexual hybrids show, instead, different and more complex chromatographic profiles.

Facilitated PCI: Rationale, Current Evidence, Open Questions, and Future Directions

Journal of Cardiovascular Pharmacology. Jan, 2008  |  Pubmed ID: 18209562

Both thrombolysis and primary percutaneous coronary intervention (PCI) are validated therapies in the treatment of ST-elevation acute myocardial infarction (STEMI). Primary PCI appears now to be more effective, provided the vessel patency is restored within 120 minutes. An approach combining the possibility of quickly starting a clot-dissolving medication with a subsequent PCI of the culprit lesion has therefore recently gained considerable interest. Facilitated percutaneous coronary intervention (PCI) refers to a pretreatment with any pharmacological agent allowing the achievement of some recanalization and possibly myocardial reperfusion, which might translate into an improved clinical outcome. Many drugs reduce the thrombus burden; however, the term "facilitated" is currently operatively restricted to glycoprotein GP-IIb-IIIa inhibitors, thrombolytic drugs, and their combination. Several earlier clinical trials tested the hypothesis that facilitated PCI in the setting of STEMI allows the achievement of a better myocardial reperfusion compared with primary PCI and that this benefit translates into an improved clinical outcome. However, after the first promising results, the recent ASSENT-4 trial has been prematurely interrupted because of higher in-hospital mortality in the group of patients who underwent full-dose tenecteplase followed by PCI compared with subjects undergoing primary PCI alone. After a critical review of the current knowledge, and pending the completion of ongoing trials, no clear evidence currently exists on the benefit of any systemic pharmacological facilitation of PCI beyond the upfront administration of dual oral antiplatelet therapy with aspirin and clopidogrel. While awaiting the results of a few other currently ongoing trials, facilitated PCI should now probably be restricted to the administration of glycoprotein IIb-IIIa inhibitors for patients at high risk of cardiovascular events and at low risk of bleeding when a more than 60-minute delay to primary PCI is anticipated. In patients having first medical contact within 3 hours, with an anticipated absolute delay to PCI of more than 90 minutes, thrombolysis can be safely recommended.

Acute Aortic Syndromes: Role of Multi-detector Row CT

European Journal of Radiology. Mar, 2008  |  Pubmed ID: 17997067

Acute thoracic aortic syndromes encompass a spectrum of emergencies including aortic dissection, intramural haematoma, penetrating atherosclerotic ulcer and aneurysm rupture. All these life-threatening conditions require prompt diagnosis and appropriate management. To date multi-detector row Computed Tomography represents a valuable diagnostic tool especially in the emergency setting. This paper focus on the use of multi-detector row Computed Tomography in the evaluation of acute thoracic aortic syndromes and illustrates the key imaging findings related to each disease.

Increased Activation of P38 MAPK in COPD

The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. Jan, 2008  |  Pubmed ID: 17959643

Inflammation, oxidative stress and apoptosis, which are involved in chronic obstructive pulmonary disease (COPD) pathogenesis, may activate the p38 subgroup of mitogen-activated protein kinases (MAPKs). Therefore, the aim of the present study was to evaluate the expression of the phosphorylated, active form of p38 MAPK (phospho-p38) in the lungs of COPD patients. Surgical specimens were obtained from 18 smokers with COPD at different stages of disease severity, plus nine smoking and eight nonsmoking subjects with normal lung function. Phospho-p38+ cells were quantified by immunohistochemistry in both alveolar spaces and alveolar walls. Moreover, a Western blot analysis of phospho-p38 and total p38alpha isoform expressed by alveolar macrophages was performed. Phospho-p38+ alveolar macrophages and phospho-p38+ cells in alveolar walls were increased in patients with severe and mild/moderate COPD, compared with smoking and nonsmoking controls. Moreover, they were inversely correlated to values of forced expiratory volume in one second (FEV(1)) and FEV(1)/forced vital capacity. Western blot analysis showed that phosphorylated p38, but not the total p38alpha isoform, was specifically increased in alveolar macrophages from COPD patients. Activation of the p38 mitogen-activated protein kinase pathway appears to be involved in the pathogenesis of chronic obstructive pulmonary disease. The present findings suggest that this protein may be a suitable pharmacological target for therapeutic intervention.

Prevalence of CARD15/NOD2 Mutations in the Sicilian Population

The American Journal of Gastroenterology. Jan, 2008  |  Pubmed ID: 18184136

The Effects of Local and Sustained Release of Fibroblast Growth Factor on Wound Healing in Esophageal Anastomoses

Journal of Pediatric Surgery. Feb, 2008  |  Pubmed ID: 18280276

Postsurgical complications, such as anastomotic leaks in patients with esophageal atresia, have remained unchanged during the last 3 decades. Growth factors enhance healing in several wound-healing models. Therefore, an experimental study was used to evaluate the effects of local and sustained release of basic fibroblast growth factor (FGF) on wound healing in esophageal anastomoses.

Familial Mediterranean Fever Gene (MEVF) Mutations in Crohn's Disease in a Mediterranean Area

Inflammatory Bowel Diseases. Sep, 2008  |  Pubmed ID: 18340637

The Role of CARD15 Mutations and Smoking in the Course of Crohn's Disease in a Mediterranean Area

The American Journal of Gastroenterology. Mar, 2008  |  Pubmed ID: 18341489

To evaluate the role of CARD15 mutations and smoking in the main events of Crohn's disease (CD).

Breastfeeding in Northern Italy

Acta Paediatrica (Oslo, Norway : 1992). May, 2008  |  Pubmed ID: 18373720

To describe the duration and type, as classified by World Health Organization (WHO) criteria, of breastfeeding in Ligurian newborns up to 1 year of age, and to identify possible related factors.

Interleukin-6 Receptor Superantagonist Sant7 Inhibits TGF-beta-induced Proliferation of Human Lung Fibroblasts

Cell Proliferation. Jun, 2008  |  Pubmed ID: 18435790

Both interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) are crucially involved in fibrotic events that characterize interstitial lung diseases (ILD). Therefore, the aim of this study was to investigate in primary cultures of normal and fibrotic human lung fibroblasts (HLF), exposed to either IL-6 or TGF-beta1, the effects on phosphorylation of mitogen-activated protein kinases (MAPK) and cell growth of IL-6 signalling inhibition, performed by the IL-6 receptor superantagonist Sant7.

AMIC@: All MIcroarray Clusterings @ Once

Nucleic Acids Research. Jul, 2008  |  Pubmed ID: 18477631

The AMIC@ Web Server offers a light-weight multi-method clustering engine for microarray gene-expression data. AMIC@ is a highly interactive tool that stresses user-friendliness and robustness by adopting AJAX technology, thus allowing an effective interleaved execution of different clustering algorithms and inspection of results. Among the salient features AMIC@ offers, there are: (i) automatic file format detection, (ii) suggestions on the number of clusters using a variant of the stability-based method of Tibshirani et al. (iii) intuitive visual inspection of the data via heatmaps and (iv) measurements of the clustering quality using cluster homogeneity. Large data sets can be processed efficiently by selecting algorithms (such as FPF-SB and k-Boost), specifically designed for this purpose. In case of very large data sets, the user can opt for a batch-mode use of the system by means of the Clustering wizard that runs all algorithms at once and delivers the results via email. AMIC@ is freely available and open to all users with no login requirement at the following URL http://bioalgo.iit.cnr.it/amica.

First Visualization of Cholinergic Cells and Fibers by Immunohistochemistry for Choline Acetyltransferase of the Common Type in the Optic Lobe and Peduncle Complex of Octopus Vulgaris

The Journal of Comparative Neurology. Aug, 2008  |  Pubmed ID: 18543295

This study provides the first immunohistochemical evidence visualizing cholinergic octopus neurons containing choline acetyltransferase (ChAT), the synthetic enzyme of acetylcholine. Because the antiserum applied here was raised against a recombinant protein encoded by exons 7 and 8 of the rat gene for ChAT, and initially used for studies in mammals, to validate antibody specificity for the octopus counterpart enzyme we therefore used three methods. Immunoprecipitation using Pansorbin indicated that immunoreactive octopus brain molecules were capable of synthesizing acetylcholine. Western blot analysis after denatured gel electrophoresis of octopus brain extracts revealed a single band at approximately 81 kDa. A gel slice containing the 81-kDa protein after native (nondenatured) gel electrophoresis exhibited high ChAT activity. All findings obtained with these three methods clearly indicated that the antiserum effectively recognizes octopus ChAT. The immunohistochemical use of the antiserum in the retina, optic lobe, and its neighboring peduncle complex detected enzyme-containing neuronal cell bodies in only two regions, the cell islands of the optic lobe medulla and the cortical layer of the posterior olfactory lobule. Immunoreactive fibers and probable nerve terminals were also found in the plexiform layer of the deep retina, within the stroma of the optic gland, and the neuropils of the optic lobe, peduncle lobe, and olfactory lobe. These results provide information on the morphology and distribution patterns of cholinergic neurons in the octopus visual system, a useful invertebrate model for learning and memory where the cholinergic system, as in higher vertebrates including mammals, plays an important role.

Molecular Mechanisms Underlying Airway Smooth Muscle Contraction and Proliferation: Implications for Asthma

Respiratory Medicine. Aug, 2008  |  Pubmed ID: 18579364

Airway smooth muscle (ASM) plays a key role in bronchomotor tone, as well as in structural remodeling of the bronchial wall. Therefore, ASM contraction and proliferation significantly participate in the development and progression of asthma. Many contractile agonists also behave as mitogenic stimuli, thus contributing to frame a hyperresponsive and hyperplastic ASM phenotype. In this review, the molecular mechanisms and signaling pathways involved in excitation-contraction coupling and ASM cell growth will be outlined. Indeed, the recent advances in understanding the basic aspects of ASM biology are disclosing important cellular targets, currently explored for the implementation of new, more effective anti-asthma therapies.

Significance of Borderline Hemoglobin A2 Values in an Italian Population with a High Prevalence of Beta-thalassemia

Haematologica. Sep, 2008  |  Pubmed ID: 18603555

We report a retrospective analysis carried out on 23,485 subjects submitted to a screening program from 2000 to 2006. Of these subjects, 3,934 had borderline HbA(2) values from 3.1 to 3.9%; 410 samples, analyzed previously using PCR methods and sequencing because all of these were partners of a carrier of classical beta-thalassemia, were selected for statistical analysis. Of 410 subjects, 94 (22.9%) were positive for a molecular defect in the beta-, delta- or alpha-globin genes. The most prevalent molecular defects were beta IVS1 nt 6 (HBB c.92+6T C), co-inheritance of severe beta thalassemia and delta mutations, beta-promoter mutations and triplication of alpha genes were detected; alpha-thalassemia and Hb-variants were also evident. Borderline HbA(2) is not a rare event in a population with a high prevalence of beta-thalassemia carriers. These data support the necessity to investigate these cases at a molecular level, particularly if the partner is a carrier of beta-thalassemia.

The Role of Pharmacogenetics in Treating Central Nervous System Disorders

Experimental Biology and Medicine (Maywood, N.J.). Dec, 2008  |  Pubmed ID: 18849543

Symptoms of central nervous system (CNS) disorders include abnormalities in both physical and psychological domains. Many drugs indicated for the treatment of CNS disorders are fraught with side effects and/or poor efficacy which impact patients' quality of life and drives non-compliance. Moreover, for many CNS drugs such as antidepressants and antipsychotics, it takes time to determine whether a particular drug is efficacious in an individual patient. To optimize drug treatment for each patient, prescribing physicians often need to raise or lower doses, switch drug classes, or prescribe additional drugs to mitigate side effects, often in a "trial and error" fashion. Pharmacogenetic (PGx) testing, particularly in the realm of CNS therapy, can reduce the unpredictability of this process. By determining a patient's genetic profile, individual therapy parameters may be predicted pre-treatment for drug efficacy, optimal drug dose, and the risk of adverse drug reactions (ADRs). The intent of this review is to highlight the power of PGx testing to predict the likelihood of ADRs and efficacy during the treatment of the following CNS disorders: epilepsy, bipolar disorder, schizophrenia and depression.

Omalizumab in the Treatment of Severe Asthma: Efficacy and Current Problems

Therapeutic Advances in Respiratory Disease. Dec, 2008  |  Pubmed ID: 19124386

Omalizumab is a humanized monoclonal anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing their interactions with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high-affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include relevant improvements in respiratory symptoms and quality of life, paralleled by a marked reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma, inadequately controlled by high doses of standard inhaled treatments.

Awake Blood Pressure Variability, Inflammatory Markers and Target Organ Damage in Newly Diagnosed Hypertension

Hypertension Research : Official Journal of the Japanese Society of Hypertension. Dec, 2008  |  Pubmed ID: 19139603

Increased blood pressure (BP) may stimulate vascular inflammation, which may itself induce pathological arterial changes. BP variability has been associated with target-organ damage and future cardiovascular complications. We hypothesized that BP variability, as derived from ambulatory BP monitoring, is related to inflammatory markers in newly diagnosed hypertension. Systolic (S) and diastolic (D) BP variabilities were assessed as the SD of 24-h pressure recordings in a cohort of 190 recently (<6 months) diagnosed, untreated hypertensive subjects. Target organ damage, assessed by measuring the carotid artery intima-media thickness, left ventricular mass index, and microalbuminuria, was related to plasma high-sensitivity C-reactive protein (hsCRP) and soluble (s) E-selectin, an endothelium-specific molecule. The patients' age (mean+/-SD) was 53.0+/-8.5 years, and 59% were male. Multivariable analysis identified awake SBP variability (95% confidence interval [CI]: 0.002-0.042, p=0.034) as an independent correlate of hsCRP and awake SBP (95% CI: 0.003-0.014, p=0.003), awake SBP variability (95% CI: 0.003-0.035, p=0.018), and microalbuminuria (95% CI: 0.075-0.280, p=0.001) as independent correlates of sE-selectin. When patients were divided into low and high awake SBP variability groups, age (p=0.001), hsCRP (p=0.0001), and sE-selectin (p=0.005) were significantly different in the two groups. After adjusting for age, these differences remained significant (p=0.022 and p=0.001 for hsCRP and sE-selectin, respectively). In recently diagnosed hypertensive subjects, hsCRP and sE-selectin levels are related to awake SBP variability. High SBP variability is likely associated with vascular inflammation in newly diagnosed hypertension, independent of SBP. (Hypertens Res 2008; 31: 2137-2146).

In Situ Elongation Patch in Right Kidney Transplantation

Transplantation Proceedings. Jul-Aug, 2008  |  Pubmed ID: 18675075

A short right renal vein complicates transplantation causing traction and difficulties during anastomosis. When we perform a kidney transplantation from a cadaveric donor, this problem may be resolved by using the vena cava to create a venous duct. This elongation technique is proposed to be performed during bench surgery. We propose a small change in the technique: execution of an "elongation patch" during harvesting and under cold perfusion.

The MILES-2G Phase 2 Study of Single-agent Gemcitabine with Prolonged Constant Infusion in Advanced Non-small Cell Lung Cancer Elderly Patients

Lung Cancer (Amsterdam, Netherlands). Jul, 2008  |  Pubmed ID: 18683299

Gemcitabine has been widely studied in elderly patients affected by advanced non-small cell lung cancer (NSCLC). A prolonged constant infusion (10 mg/m2/min) has been proposed as a way to improve its efficacy. Aim of this study is to describe activity and toxicity of single-agent gemcitabine given as prolonged infusion in the treatment of elderly patients with advanced NSCLC.

Hb Southern Italy: Coexistence of Two Missence Mutations (the Hb Sun Prairie Alpha2 130 Ala --> Pro and Hb Caserta Alpha2 26 Ala --> Thr) in a Single HBA2 Gene

British Journal of Haematology. Oct, 2008  |  Pubmed ID: 18691171

This study describes a new molecular condition in the alpha(2)-globin gene (HBA2) found in six unrelated families from Southern Italy (Campania and Sicily). This new double mutant form of haemoglobin is called Hb Southern Italy and originated from the coexistence of two known mutations occurring in the same globin gene, HBA2 26 G-->A (Hb Caserta) and HBA2 130 G-->C (Hb Sun Prairie). Hb Sun Prairie was originally observed in Indian patients in either the homozygous state, with severe hemolytic anemia, and in the heterozygous state with microcytosis, or in asymptomatic cases as an alpha-thalassemia carrier phenotype. Hb Caserta was observed for the first time in a Casertian family (South Italy) that displayed a slowmigrating haemoglobin upon investigation. We report the clinical phenotype and molecular study of this new double mutant form of haemoglobin in heterozygous and homozygous subjects, as well as in association with alpha degrees delectional thalassemia.

Volatile Components of Grape Pomaces from Different Cultivars of Sicilian Vitis Vinifera L

Bioresource Technology. Jan, 2008  |  Pubmed ID: 17321134

The volatile components of grape pomace coming from the processing of some of the most important varieties of grape (Vitis vinifera L.) cultivated in Sicily, namely Nero d'Avola, Nerello Mascalese, Frappato and Cabernet Sauvignon, have been determined by gas-chromatography (GC) and gas-chromatography-mass spectrometry (GC-MS). According to the winemaking procedure that entails the removal of stalks before fermentation, two kinds of grape pomace are obtained. The first consists of skins, pulp residues and seeds, the proper grape pomace, which is partially used for grappa, a typical Italian spirit, and alcohol production, the second consists almost exclusively of stalks. On the whole, 38 components have been characterized in the samples of grape pomaces, with Frappato cv. showing the richest composition; instead, 88 components have been detected in the stalks of Frappato, Nero d'Avola, Nerello Mascalese and Cabernet Sauvignon varieties. In order to make a comparison between the grape varieties easier, the volatile components detected in the two sets of samples (grape pomaces and stalks) have been grouped in different classes. Significant differences among varieties have been detected and statistical treatment of data is also reported. This study is part of a wider project aimed at the possible exploitation of the main agro-industrial by-products. At the same time it is one of the first reports on the volatile components of this waste material.

Superoxide Dismutase Activity in Gingiva in Type-2 Diabetes Mellitus Patients with Chronic Periodontitis

Archives of Oral Biology. Jan, 2008  |  Pubmed ID: 17880913

Antioxidant defence reduces in diabetes mellitus (DM) and periodontitis. This study investigates antioxidant enzyme; superoxide dismutase (SOD) activity in gingiva and blood glucose and lipid levels in type-2 DM patients and systemically healthy individuals with chronic periodontitis (CP).

Influence of Climatic Variables on Acute Myocardial Infarction Hospital Admissions

International Journal of Cardiology. Oct, 2009  |  Pubmed ID: 18694607

Seasonal peaks in acute myocardial infarction (AMI) incidence have been widely reported. Weather has been postulated to be one of the elements at the basis of this association. The aim of our study was to determine the influence of seasonal variations and weather on AMI hospital admissions.

Immunolocalization of Alpha-synuclein in the Rat Spinal Cord by Two Novel Monoclonal Antibodies

Neuroscience. Feb, 2009  |  Pubmed ID: 19118601

This study provides the first immunohistochemical evidence of the presence and distribution patterns in the rat spinal cord of alpha-synuclein (alpha-Syn), a soluble acidic protein, widely expressed in the CNS and closely associated to the pathogenesis of neurodegenerative conditions such as Parkinson's and Alzheimer's diseases. We used two novel homemade monoclonal antibodies (2E3 and 3D5) recognizing two different epitopes of alpha-Syn. Both antibodies localized alpha-Syn within the nerve terminals, whereas 3D5 alone also localized it within the neuronal nuclei. alpha-Syn-immunoreactive nervous elements were widely recognized throughout rat spinal cord and in almost all the gray matter laminae. However, they appeared particularly concentrated within laminae I, II, VII and X and more scattered in the others. Double immunofluorescent labeling showed that alpha-Syn colocalized with synaptophysin in the presynaptic nerve terminals, with neuropeptide Y (NPY) in lamina I, II, IX and X, and had close relationships with tyrosine hydroxylase (TH) immunoreactive neurons in laminae VII and X. Interestingly, the alpha-Syn-immunoreactive nerve elements, in lamina X, contained little of calbindin-28KD and calretinin-31KD. Our findings could help in understanding the genesis of some early clinical symptoms of Parkinson's disease (PD), such as pain and dysautonomic disorders, and indicate the spinal cord as their probable starting point, according to the ascending theory of PD, proposed by Braak.

Role for MKL1 in Megakaryocytic Maturation

Blood. Mar, 2009  |  Pubmed ID: 19136660

Megakaryoblastic leukemia 1 (MKL1), identified as part of the t(1;22) translocation specific to acute megakaryoblastic leukemia, is highly expressed in differentiated muscle cells and promotes muscle differentiation by activating serum response factor (SRF). Here we show that Mkl1 expression is up-regulated during murine megakaryocytic differentiation and that enforced overexpression of MKL1 enhances megakaryocytic differentiation. When the human erythroleukemia (HEL) cell line is induced to differentiate with 12-O-tetradecanoylphorbol 13-acetate, overexpression of MKL1 results in an increased number of megakaryocytes with a concurrent increase in ploidy. MKL1 overexpression also promotes megakaryocytic differentiation of primary human CD34(+) cells cultured in the presence of thrombopoietin. The effect of MKL1 is abrogated when SRF is knocked down, suggesting that MKL1 acts through SRF. Consistent with these findings in human cells, knockout of Mkl1 in mice leads to reduced platelet counts in peripheral blood, and reduced ploidy in bone marrow megakaryocytes. In conclusion, MKL1 promotes physiologic maturation of human and murine megakaryocytes.

Predation Impact of Ciliated and Flagellated Protozoa During a Summer Bloom of Brown Sulfur Bacteria in a Meromictic Coastal Lake

FEMS Microbiology Ecology. Oct, 2009  |  Pubmed ID: 19622068

Anaerobic phagotrophic protozoa may play an important role in the carbon flux of chemically stratified environments, especially when phototrophic sulfur bacteria account for a high proportion of the primary production. To test this assumption, we investigated the vertical and temporal distribution of microbial heterotrophs and of autotrophic picoplankton throughout the water column of the meromictic coastal lake Faro (Sicily, Italy), in the summer of 2004, coinciding with a bloom of brown-colored green sulfur bacteria. We also assessed the grazing impact of ciliated and flagellated protozoa within the sulfur bacteria plate using a modification of the fluorescently labeled bacteria uptake approach, attempting to minimize the biases intrinsic to the technique and to preserve the in situ anoxic conditions. Significant correlations were observed between ciliate biomass and bacteriochlorophyll e concentration, and between heterotrophic nanoflagellate biomass and chlorophyll a concentration in the water column. The major predators of anaerobic picoplankton were pleuronematine ciliates and cryptomonad flagellates, with clearances of 26.6 and 9.5 nL per cell h(-1), respectively, and a cumulative impact on the picoplankton gross growth rate ranging between 36% and 72%. We concluded that protozoan grazing channels a large proportion of anaerobic picoplankton production to higher trophic levels without restraining photosynthetic bacteria productivity.

Neuron Protection As a Therapeutic Target in Acute Ischemic Stroke

Current Topics in Medicinal Chemistry. , 2009  |  Pubmed ID: 19849659

Involvement of various neurotransmitters and neuromodulators have been shown to contribute to the ischemic injury and neuronal death associated with stroke Role of excitatory amino acid receptor activation, calcium overload, nitric oxide, and oxidative stress in the pathogenesis of ischemic brain damage is well established. Several new strategies are currently emerging, based on recent advances in our understanding of molecular pathways that could be considered as potential therapeutic targets. For example reactive oxygen species (ROS) are important contributors to the secondary injury cascade following traumatic brain injury (TBI), and ROS inhibition has consistently been shown to be neuroprotective following experimental TBI and brain ischemia. Furthermore, more recently, some authors concluded that nonanticoagulant 3K3A-APC exhibits greater neuroprotective efficacy with no risk for bleeding compared with drotrecogin-alfa activated, a hyperanticoagulant form of APC. Excessive calcium entry into depolarized neurons contributes significantly to cerebral tissue damage after ischemia. Included in the sequence of events leading to neuronal death in ischemic tissue following stroke is an excessive and toxic rise in the intracellular Ca(2+)-concentration, predominantly due to an influx of Ca2+ through nonselective cation-channels as well as Ca(2+)-channels.. Some authros conducted a study to investigate whether the enhancement of GABA receptor activity could inhibit NMDA receptor-mediated nitric oxide (NO) production by neuronal NO synthase (nNOS) in brain ischemic injury. The results showed that both the GABA(A) receptor agonist muscimol and the GABA(B) receptor agonist baclofen had neuroprotective effect, and the combination of two agonists could significantly protect neurons against death induced by ischemia/reperfusion. On this basis we conclude that neuroprotection for ischemic stroke refers to strategies, applied singly or in combination, that antagonize the injurious biochemical and molecular events that eventuate in irreversible ischemic injury. There has been a recent explosion of interest in this field, with over 1000 experimental papers and over 400 clinical articles appearing within the past 6 years. These studies, in turn, are the outgrowth of three decades of investigative work to define the multiple mechanisms and mediators of ischemic brain injury, which constitute potential targets of neuroprotection.

K-Boost: a Scalable Algorithm for High-quality Clustering of Microarray Gene Expression Data

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology. Jun, 2009  |  Pubmed ID: 19522668

Microarray technology for profiling gene expression levels is a popular tool in modern biological research. Applications range from tissue classification to the detection of metabolic networks, from drug discovery to time-critical personalized medicine. Given the increase in size and complexity of the data sets produced, their analysis is becoming problematic in terms of time/quality trade-offs. Clustering genes with similar expression profiles is a key initial step for subsequent manipulations and the increasing volumes of data to be analyzed requires methods that are at the same time efficient (completing an analysis in minutes rather than hours) and effective (identifying significant clusters with high biological correlations). In this paper, we propose K-Boost, a clustering algorithm based on a combination of the furthest-point-first (FPF) heuristic for solving the metric k-center problem, a stability-based method for determining the number of clusters, and a k-means-like cluster refinement. K-Boost runs in O (|N| x k) time, where N is the input matrix and k is the number of proposed clusters. Experiments show that this low complexity is usually coupled with a very good quality of the computed clusterings, which we measure using both internal and external criteria. Supporting data can be found as online Supplementary Material at www.liebertonline.com.

New Anticoagulants for Atrial Fibrillation

Journal of Cardiovascular Medicine (Hagerstown, Md.). Jun, 2009  |  Pubmed ID: 19365276

Although warfarin and other vitamin K antagonists have clearly the greatest efficacy among treatments commonly available in preventing stroke in atrial fibrillation, their use is associated with a substantial risk of major bleedings and are unpractical and difficult to use because of their narrow therapeutic window, their interaction with drugs and foods, and the need of frequent coagulation monitoring. Several new anticoagulants are now undergoing phase III clinical trials in atrial fibrillation with the aim of demonstrating noninferiority compared with vitamin K antagonists or superiority compared with aspirin in patients in whom vitamin K antagonists are contraindicated or not tolerated. These drugs fall in different pharmacological categories of oral direct thrombin inhibitors, parenteral long-lived indirect factor Xa inhibitors, and oral direct factor Xa inhibitors. Cardiologists need to be aware of the explosive pharmacological literature being accrued with these new drugs, as most of these will likely enter the clinical arena in the near future.

The Structural Role of the Zinc Ion Can Be Dispensable in Prokaryotic Zinc-finger Domains

Proceedings of the National Academy of Sciences of the United States of America. Apr, 2009  |  Pubmed ID: 19369210

The recent characterization of the prokaryotic Cys(2)His(2) zinc-finger domain, identified in Ros protein from Agrobacterium tumefaciens, has demonstrated that, although possessing a similar zinc coordination sphere, this domain is structurally very different from its eukaryotic counterpart. A search in the databases has identified approximately 300 homologues with a high sequence identity to the Ros protein, including the amino acids that form the extensive hydrophobic core in Ros. Surprisingly, the Cys(2)His(2) zinc coordination sphere is generally poorly conserved in the Ros homologues, raising the question of whether the zinc ion is always preserved in these proteins. Here, we present a functional and structural study of a point mutant of Ros protein, Ros(56-142)C82D, in which the second coordinating cysteine is replaced by an aspartate, 5 previously-uncharacterized representative Ros homologues from Mesorhizobium loti, and 2 mutants of the homologues. Our results indicate that the prokaryotic zinc-finger domain, which in Ros protein tetrahedrally coordinates Zn(II) through the typical Cys(2)His(2) coordination, in Ros homologues can either exploit a CysAspHis(2) coordination sphere, previously never described in DNA binding zinc finger domains to our knowledge, or lose the metal, while still preserving the DNA-binding activity. We demonstrate that this class of prokaryotic zinc-finger domains is structurally very adaptable, and surprisingly single mutations can transform a zinc-binding domain into a nonzinc-binding domain and vice versa, without affecting the DNA-binding ability. In light of our findings an evolutionary link between the prokaryotic and eukaryotic zinc-finger domains, based on bacteria-to-eukaryota horizontal gene transfer, is discussed.

Inflammation As a Therapeutic Target in Acute Ischemic Stroke Treatment

Current Topics in Medicinal Chemistry. , 2009  |  Pubmed ID: 19849665

Animal models of focal ischaemia induced by middle cerebral artery occlusion (MCAO) provide most evidence for cellular inflammatory responses in stroke. Permanent MCAO results in a modest neutrophil infiltration at 24 h after ischaemia, predominantly around arterial vessels at the margins of infarction, whereas MCAO with subsequent reperfusion is associated with substantial infiltration by neutrophils throughout the entire infarct. Several studies show that C-reactive protein (CRP), an inflammatory marker, is associated with stroke outcomes and future vascular events. Several drugs, especially hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), have been demonstrated to reduce hsCRP levels independently of their effects on plasma cholesterol. Various cytokines were shown to be expressed in the injured brain. Recent investigations demonstrated that mRNAs of above cytokines were induced in the ischemic rat brain. TNF-alpha is a pleiotropic cytokine that mediates key roles in many physiological and pathological cellular processes including acute and chronic inflammation, programmed cell death or apoptosis, anti-tumor responses, and infection. Pharmaceutical industry to search a small molecule TNF inhibitor have taken multiple strategies. Significant protection after in vivo oral use of SB-239063 from brain injury and neurological deficits was observed in one study. In the same study significant protection from brain injury and neurological deficits was also demonstrated due to i.v post-stroke treatment with the same compound. Leukocyte-endothelial adhesion process consists of several steps, beginning with rolling of the leukocyte on the endothelial surface until it has slowed down to such a degree that it sticks to the endothelium. Treatment with a murine anti-ICAM-1 antibody (enlimomab) has been investigated in patients with acute ischemic stroke in the Enlimomab Acute Stroke Trial (EAST). Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group. Furthermore, experimental data have shown that focal cerebral ischemia induces a time-dependent activation of granulocytes, lymphocytes, and macrophages. Dissipation of ATP by CD39 reduced P2X7 receptor stimulation and thereby suppressed baseline leukocyte alphaMbeta2-integrin expression. As alphaMbeta2-integrin blockade reversed the postischemic, inflammatory phenotype of Cd39-/- mice, these data suggest that phosphohydrolytic activity on the leukocyte surface suppresses cell-cell interactions that would otherwise promote thrombosis or inflammation.

Endocrine Cells in Atresic Chick Embryo Intestine: Histochemical and Immunohistochemical Study

European Journal of Histochemistry : EJH. Jul-Sep, 2009  |  Pubmed ID: 19864208

Intestinal motility disorders are an important problem in the postoperative management of patients with intestinal atresia. Intestinal motility could be initiated by luminal factors that activate intrinsic and extrinsic primary afferent nerves involved in the peristaltic reflex. Endocrine cells act as a key point, because they transfer information regarding the intestinal contents and intraluminal pressure to nerve fibers lying in close proximity to the basolateral surface of the epithelium. In chick embryo, experimental intestinal atresia is associated with disorders in the development of the enteric nervous system, related to the severity of intestinal dilation. Our aim was to investigate the distribution pattern of endocrine cells in the developing endocrine system of chick embryo small intestine with experimentally-induced atresia on day 12 and on day 16. Changes in enteroendocrine population were examined in gut specimens (excised proximal and distal to the atresia) from experimental embryos 19 days old and in control sham-operated chick embryos at the same age. Sections from proximal and distal bowel and control bowel were stained with Grimelius silver stain, a valuable histochemical method for detecting the argyrophil and argentophilic cells, and with an immunohistochemical procedure for detecting serotonin and neurotensin immunoreactive cells. In chick embryo proximal bowel, intestinal dilation differed in the various embryos. We found significantly higher enteroendocrine cell counts in proximal bowel than in distal and control bowel. The differences depended on the precociousness of surgery and the severity of dilation. Considering the major contribution of enteroendocrine cells to the peristaltic reflex, our data may help to explain the pathogenesis of motility disorders related to intestinal atresia.

In Utero Haematopoietic Stem Cell Transplantation (IUHSCT)

Mediterranean Journal of Hematology and Infectious Diseases. , 2009  |  Pubmed ID: 21415998

In utero haematopoietic stem cell transplantation (IUHSCT) is a non-myeloablative approach for the prenatal treatment of genetic disorders. However, in target disorders, where there is not a selective advantage for donor cells, a useful donor-cell chimerism has not been achieved. There are three possible barriers to engraftment following IUHSCT: limited space in the fetus due to host-cell competition; the large number of donor cells needed, and the immunological asset of recipient.

Acute Cardiac Injury After Subarachnoid Haemorrhage: Two Case Reports

Cases Journal. , 2009  |  Pubmed ID: 20062617

It is well known that cardiopulmonary complications are often associated to subarachnoid haemorrhage. For appropriate therapeutic managing it is very important to distinguish acute coronary syndrome from neurogenic myocardial injury, which is a reversible condition. Furthermore, because the hearts of brain dead patients may be utilized for therapeutic purpose, it has became of importance to rule out erroneous diagnosis of cardiac ischemia in order to avoid rejection of hearts potential suitable for transplantation.We present a report of two female patients affected by cardiac complications caused by aneurismal subarachnoid haemorrhage admitted to our neurosurgical intensive care department.

IL-23R Determines Susceptibility in Crohn's Disease in a Mediterranean Area

Inflammatory Bowel Diseases. Feb, 2009  |  Pubmed ID: 18626976

Cytomegalovirus Disappearance After Treatment for Refractory Ulcerative Colitis in 2 Patients Treated with Infliximab and 1 Patient with Leukapheresis

Inflammatory Bowel Diseases. Jun, 2009  |  Pubmed ID: 18839422

Vegetarian Diets in Children and Adolescents

Pediatrics in Review / American Academy of Pediatrics. Jan, 2009  |  Pubmed ID: 19118135

Epidermal Growth Factor-containing Wound Closure Enhances Wound Healing in Non-diabetic and Diabetic Rats

International Wound Journal. Apr, 2009  |  Pubmed ID: 19432660

This study was designed to elucidate the in vivo efficacy of epidermal growth factor (EGF) on wound healing in non diabetic and diabetic rats.

[Intestinal Reconstruction After Dehiscence of a Jejunal Suture in a Patient Submitted to Aorto-enteric Fistula Repair: a Case Report]

Chirurgia Italiana. Mar-Apr, 2009  |  Pubmed ID: 19537002

Aorto-enteric fistulas are serious complications of aortic surgery that require swift, effective surgical intervention. We report a case of a secondary aortoenteric fistula treated with prosthesis replacement and an intestinal suture subsequently complicated by the dehiscence of the previously constructed anastomosis. We opted for reconstruction re-intervention, closing the intestinal lesion by means of a mechanical suture above the jejunal dehiscence, making a side-to-end jejuno-jejunal Roux anastomosis and an end-to-side anastomosis at the base of the loop. The operation was completed by performing a gastrostomy and transforming the fistula into a jejunostomy. This intervention enabled us to discharge the patient in good general condition after 30 days.

The Significance of the Hemoglobin A(2) Value in Screening for Hemoglobinopathies

Clinical Biochemistry. Dec, 2009  |  Pubmed ID: 19591816

The inherited hemoglobinopathies are a large group of disorders that include thalassemias and hemoglobin variants. Accurate determination of the carrier phenotype is essential for detecting couples at risk for producing offspring with hemoglobinopathy. Heterozygous beta-thalassemia is usually silent at the clinical level. His phenotype is characterized by microcytosis and hypochromia with increased hemoglobin A(2) (HbA(2)) value. Therefore, HbA(2) determination plays a key role in screening programs for hemoglobinopathy. The aim of this review is to address and suggest an approach for reducing or abolishing hemoglobinopathy screening mistakes.

Effects of Voriconazole on Tacrolimus Metabolism in a Kidney Transplant Recipient

Journal of Clinical Pharmacy and Therapeutics. Feb, 2010  |  Pubmed ID: 20175821

Infection occurs frequently in the organ transplant recipients during the post-transplant period because of immunosuppression. Therefore, prophylactic antimicrobial agents are often used. The azole antifungals, widely prescribed prophylactically, are known to have many drug-drug interactions. This report presents a case of drug-drug interaction between voriconazole and tacrolimus in a kidney transplant recipient. Voriconazole treatment led to a dramatic increase in tacrolimus concentration that required its discontinuation in spite of the manufacturer's guidelines that recommend a reduction of tacrolimus dosage by one-third. The present drug-drug interaction can be attributed to a strong inhibitory effect on cytochrome P450-3A4 activity by voriconazole. When voriconazole and tacrolimus are coadministered, close monitoring of tacrolimus blood levels is recommended as the rule-of-thumb reduction of tacrolimus dose by one-third may not be satisfactory.

Adjuvant Chemoradiotherapy in Patients with Stage III or IV Radically Resected Gastric Cancer: a Pilot Study

Archives of Surgery (Chicago, Ill. : 1960). Mar, 2010  |  Pubmed ID: 20231623

Adjuvant chemoradiotherapy does not represent the standard of care in patients with resected high-risk gastric cancer; however, results from phase 2 and randomized trials suggest improvement in overall survival. We assessed the feasibility and toxic effects of chemoradiotherapy as adjuvant treatment in locally advanced gastric cancer.

Design and Methodologies of the POSTconditioning During Coronary Angioplasty in Acute Myocardial Infarction (POST-AMI) Trial

Cardiology. Jul, 2010  |  Pubmed ID: 20588019

Reperfusion remains the definitive treatment for acute myocardial infarction (AMI), but restoring blood flow carries the potential to exacerbate the ischemia-related injury. Postconditioning might modify reperfusion-induced adverse events.

Effects of Budesonide on P38 MAPK Activation, Apoptosis and IL-8 Secretion, Induced by TNF-alpha and Haemophilus Influenzae in Human Bronchial Epithelial Cells

International Journal of Immunopathology and Pharmacology. Apr-Jun, 2010  |  Pubmed ID: 20646342

Non-typeable Haemophilus influenzae (NTHi) is one of the most frequently involved pathogens in bacterial exacerbations of chronic obstructive pulmonary disease (COPD). In the airways, the main tissue target of NTHi is bronchial epithelium, where this pathogen can further amplify the inflammatory and structural changes induced by proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha). Therefore, the aim of this study is to investigate, in primary cultures of human bronchial epithelial cells, the effects of NTHi on signal transduction pathways, apoptotic events and chemokine production activated by TNF-alpha. Moreover, we also evaluated the effects exerted on such cellular and molecular phenomena by a corticosteroid drug. p38 mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by Western blotting, using an anti-phospho-p38 MAPK monoclonal antibody. Apoptosis was assayed by active caspase-3 expression. Interleukin-8 (IL-8/CXCL8) was detected in cell-free culture supernatants by ELISA. TNF-alpha induced a significant increase in p38 MAPK phosphorylation. NTHi was able to potentiate the stimulatory actions of TNF-alpha on caspase-3 expression and, to a lesser extent, on IL-8 secretion. These effects were significantly (P less than 0.01) inhibited by a pharmacological pre-treatment with budesonide. These results suggest that TNF-alpha is able to stimulate, via activation of p38 MAPK signalling pathway, IL-8 release and airway epithelial cell apoptosis; the latter effect can be markedly potentiated by NTHi. Furthermore, budesonide can be very effective in preventing, through inhibition of p38 MAPK phosphorylation, both structural and proinflammatory changes elicited in bronchial epithelium by TNF-alpha and NTHi.

Mortality Predictors and Effects of Antithrombotic Therapies in Atrial Fibrillation: Insights from ACTIVE-W

European Heart Journal. Sep, 2010  |  Pubmed ID: 20685676

To assess the risk of death after the occurrence of different types of non-fatal events in patients with atrial fibrillation (AF). Antithrombotic therapies in AF have primarily focused on stroke prevention and bleeding. However, strokes and bleeds differ in severity, and the level of severity may differently impact mortality.

Training Program for Community Health Workers in Remote Areas in Senegal. First Experience

Acta Bio-medica : Atenei Parmensis. Dec, 2010  |  Pubmed ID: 20857853

In some countries, community health workers (CHWs) act as a bridge between the health care delivery system and the community, and ensure primary health care. It is essential to improve health worker education and training; however, in remote areas such as rural Senegal villages, these CHWs are often unable to leave their home community for training and education. We set out to perform a training program in a village in Senegal and to evaluate its effectiveness in that village.

The Immunostimulant OM-85 BV Prevents Wheezing Attacks in Preschool Children

The Journal of Allergy and Clinical Immunology. Oct, 2010  |  Pubmed ID: 20920766

No reagents have been shown to be effective in preventing wheezing attacks provoked by acute respiratory tract illnesses (ARTIs) in preschool children. New therapeutic agents and preventive strategies are needed.

Desensitization to Hydroxycarbamide Following Long-term Treatment of Thalassaemia Intermedia As Observed in Vivo and in Primary Erythroid Cultures from Treated Patients

British Journal of Haematology. Dec, 2010  |  Pubmed ID: 20955403

Hydroxycarbamide (HC) is a pharmacological agent capable of stimulating fetal haemoglobin (HbF) production during adult life. High levels of HbF may ameliorate the clinical course of β-thalassaemia and sickle cell disease. The efficacy of HC for the treatment of thalassaemia major and thalassaemia intermedia is variable. Although an increase of HbF has been observed in most patients, only some patients experience significant improvement in total haemoglobin levels. This study aimed to determine the effectiveness and safety of short- (1 year) and long-term (mean follow-up 68 months) HC treatment in 24 thalassaemia intermedia patients. Additionally, we evaluated if primary erythroid progenitor cells cultured from treated patients responded to HC treatment in a manner similar to that observed in vivo. Our results confirm a good response to HC after a short-term follow-up in 70% of thalassaemia intermedia patients and a reduction of clinical response in patients with a long follow-up. Erythroid cultures obtained from patients during treatment reproduced the observed in vivo response. Interestingly, haematopoietic stem cells from long-term treated patients showed reduced ability to develop into primary erythroid cultures some months before the reduction of the 'in vivo' response. The mechanism of this loss of response to HC remains to be determined.

Aspirin-triggered Lipoxin in Patients Treated with Aspirin and Selective Vs. Nonselective COX-2 Inhibitors

British Journal of Clinical Pharmacology. Mar, 2010  |  Pubmed ID: 20233202

Cyclooxygenase (COX)-2 inhibition has been reported to suppress the biosynthesis of the gastroprotective lipoxygenase metabolite 15(R)-epi-lipoxin A(4), also termed 'aspirin-triggered lipoxin' (ATL). We tested the hypothesis that the co-administration of aspirin with either the selective COX-2 inhibitor celecoxib or the nonselective COX inhibitor ibuprofen reduces ATL biosynthesis.

Effectiveness of Topical Zinc Oxide Application on Hypertrophic Scar Development in Rabbits

Burns : Journal of the International Society for Burn Injuries. Nov, 2010  |  Pubmed ID: 20381965

The etiology, biology, prevention and effective treatment of hypertrophic scars have not exactly been defined. Topical zinc oxide application was shown to be effective in the treatment of proliferative scars. We studied the effectiveness of topical zinc oxide ointment in the prevention of hypertrophic scar development by using the rabbit ear hypertrophic scar model.

SENP1-mediated GATA1 DeSUMOylation is Critical for Definitive Erythropoiesis

The Journal of Experimental Medicine. Jun, 2010  |  Pubmed ID: 20457756

Small ubiquitin-like modifier (SUMO) modification of proteins (SUMOylation) and deSUMOylation have emerged as important regulatory mechanisms for protein function. SENP1 (SUMO-specific protease) deconjugates SUMOs from modified proteins. We have created SENP1 knockout (KO) mice based on a Cre-loxP system. Global deletion of SENP1 (SENP1 KO) causes anemia and embryonic lethality between embryonic day 13.5 and postnatal day 1, correlating with erythropoiesis defects in the fetal liver. Bone marrow transplantation of SENP1 KO fetal liver cells to irradiated adult recipients confers erythropoiesis defects. Protein analyses show that the GATA1 and GATA1-dependent genes are down-regulated in fetal liver of SENP1 KO mice. This down-regulation correlates with accumulation of a SUMOylated form of GATA1. We further show that SENP1 can directly deSUMOylate GATA1, regulating GATA1-dependent gene expression and erythropoiesis by in vitro assays. Moreover, we demonstrate that GATA1 SUMOylation alters its DNA binding, reducing its recruitment to the GATA1-responsive gene promoter. Collectively, we conclude that SENP1 promotes GATA1 activation and subsequent erythropoiesis by deSUMOylating GATA1.

Long-term Oxygen Therapy in COPD: Evidences and Open Questions of Current Indications

Monaldi Archives for Chest Disease = Archivio Monaldi Per Le Malattie Del Torace / Fondazione Clinica Del Lavoro, IRCCS [and] Istituto Di Clinica Tisiologica E Malattie Apparato Respiratorio, Università Di Napoli, Secondo Ateneo. Mar, 2010  |  Pubmed ID: 20499792

Long term oxygen therapy (LTOT) has been shown to improve the survival rate in Chronic Obstructive Pulmonary Disease (COPD) patients with severe resting hypoxemia by NOTT and MRC studies, published more than 25 years ago. The improved survival was found in patients who received oxygen for more than 15 hours/day. The effectiveness of LTOT has been documented only in stable COPD patients with severe chronic hypoxemia at rest (PaO2 < 55 mmHg (7.3 kPa) or PaO2 ranging from 56 to 59 mmHg (7.4-7.8 kPa) in presence of signs of Cor Pulmonale, hematocrit > 55%. In fact no evidence supports the use of LTOT in COPD patients with moderate hypoxemia (55 < PaO2 < 65 mmHg), and in those with decreased oxygen saturation (SO 2 <90%) during exercise or sleep. Furthermore, it is generally accepted without evidence that LTOT in clinical practice is warranted in other forms of chronic respiratory failure not due to COPD when a-terial blood gas criteria match those established for COPD patients. The prescription of oxygen in these circumstances, as for unstable patients, increases the number of patients receiving supplemental oxygen and the related costs. Comorbidities are likely to affect both prognosis and health outcomes in COPD patients, but at the moment we do not know if LTOT in these patients with complex chronic diseases and mild-moderate hypoxemia could be of any use. For these reasons a critical revision of the actual guide lines indications for LTOT in order to optimise effectiveness and costs, and future research in the areas that have not previously been addressed by NOTT and MRC studies, are mandatory.

TRStalker: an Efficient Heuristic for Finding Fuzzy Tandem Repeats

Bioinformatics (Oxford, England). Jun, 2010  |  Pubmed ID: 20529928

Genomes in higher eukaryotic organisms contain a substantial amount of repeated sequences. Tandem Repeats (TRs) constitute a large class of repetitive sequences that are originated via phenomena such as replication slippage and are characterized by close spatial contiguity. They play an important role in several molecular regulatory mechanisms, and also in several diseases (e.g. in the group of trinucleotide repeat disorders). While for TRs with a low or medium level of divergence the current methods are rather effective, the problem of detecting TRs with higher divergence (fuzzy TRs) is still open. The detection of fuzzy TRs is propaedeutic to enriching our view of their role in regulatory mechanisms and diseases. Fuzzy TRs are also important as tools to shed light on the evolutionary history of the genome, where higher divergence correlates with more remote duplication events.

Embryo-fetal Erythroid Megaloblasts in the Human Coelomic Cavity

Journal of Cellular Physiology. Nov, 2010  |  Pubmed ID: 20533375

The coelomic cavity is part of the extraembryonic mesoderm, surrounding amniotic cavity, embryo, and yolk sac in the early gestation. It is now believed to represent an important transfer interface and a reservoir of nutrients for the embryo. Coelocentesis by ultrasound-guided transvaginal puncture offers an easier access to the early human embryo, from 28 days post-fertilization. However, despite some studies about its biochemical composition being reported, our knowledge about the presence of cellular elements and their quality in this compartment are still limited. Here we studied human coelomic fluids sampled from 6.6 (48 days) to 10 weeks of gestation, demonstrating the presence of functional embryonic erythroid precursors, that is, megaloblasts in the coelomic cavity. The ease of access of the coelomic cavity could allow the development of novel strategies for diagnostic or therapeutic purposes by ultrasound imaging and ultrasound-guided puncture.

PNA Zipper As a Dimerization Tool: Development of a BZip Mimic

Biopolymers. May, 2010  |  Pubmed ID: 19938072

The article describes the use of a PNA duplex (PNA zipper) as a tool to dimerize or bring in close proximity two polypeptides or protein domains. The amino acid sequence to be dimerized is covalently bound to complementary PNA sequences. Annealing of the PNA strands results in dimer formation. To test the ability of the "PNA-zipper" as a dimerization tool, we designed a GCN4 mimetic, where the leucine-zipper dimerization domain was replaced by the PNA zipper, whereas the basic DNA-binding domain was covalently attached to the PNA. The molecule was assembled by chemical ligation of the peptide corresponding to the DNA-binding domain of GCN4 modified with a succinyl thioester with two complementary PNAs harboring a cysteine residue. Electromobility-shift experiments show the ability of the PNA zipper-GCN4 to bind selected DNA duplexes. The PNA zipper-GCN4 binds both the TRE and CRE DNA sites, but it does not bind TRE and CRE mutants containing even a single base mutation, as the native GCN4. The ability to fold upon complexation with DNA was investigated by CD. A good correlation between the ability of the PNA zipper-GCN4 to fold into alpha helices and the ability to bind DNA was found.

Are Physical Activity and Nutrition Indicators of the Checklist of Health Promotion Environments at Worksites (CHEW) Associated with Employee Obesity Among Hotel Workers?

Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. Jan, 2010  |  Pubmed ID: 20061886

Worksites provide opportunities to reach more than 60% of adults in the United States, including populations diverse in race, ethnicity, gender, age, occupation, income, and health status. Employers that provide worksite weight management interventions have the potential to reduce sick leave, health care costs, and workers compensation costs, and increase employee morale and worker efficiency. Hotels specifically, represent a broad cross-section of job categories, and most hotels are staffed and operated similarly around the world. However, from our literature review, there have been no investigations of the association between the hotel environment and employees' obesity.

Intravascular Lipoma from Iliofemoral Tract

Updates in Surgery. Dec, 2010  |  Pubmed ID: 21069587

Lipoma is a benign tumour composed of well-differentiated adipocytes and is the most common soft tissue mass. We present a case of an intraluminal lipoma of the iliofemoral axis presenting as lower limb venous obstruction. In our case, definite diagnosis is impossible as there is aspecific symptomatology and radiologic imaging methods are not able to provide diriment data, considering rarity of the disease. Therefore, we could make correct diagnosis only intraoperatively. We preferred a direct reconstruction of the wall of vein. At 12-month follow-up, we have had complete disappearance of symptoms and functional diseases.

Facilitating the Development of a County Health Coverage Plan with Data from a Community-based Health Survey

Journal of Public Health Policy. Jul, 2010  |  Pubmed ID: 20535102

Community-Based Participatory Research (CBPR) has the twin goals of generating data and shaping policy decisions, yet examples that combine these goals are scarce in the literature. We describe how a community-based survey was created and used to help develop a county health plan. The Genesee Health Plan (GHP), a community-initiated non-profit organization, provides primary care, prescription drugs, and specialty care to uninsured, low-income adults through a network of independent physicians, clinics, and hospital systems. As part of an advocacy effort, GHP supporters used results from the Speak to Your Health! Community Survey to gain financial and political support for GHP. Our study, which used CBPR principles, was created by the community, local health department, and university partners. As a result, Genesee County became one of the first counties in the United States to make basic health care available to nearly all of its uninsured, low-income adults.

Inconsistency of Different Methods for Assessing Ex Vivo Platelet Function: Relevance for the Detection of Aspirin Resistance

Haematologica. Dec, 2010  |  Pubmed ID: 21123440

Assays to evaluate platelet function are often interchangeably used to assess "resistance" to aspirin. We compared different platelet function assays in patients treated or untreated with aspirin.

Gender, Sexuality, Health and Human Rights in Latin America and the Caribbean

Global Public Health. Apr, 2010  |  Pubmed ID: 20397083

Hepatocellular Carcinoma in Patients with Thalassaemia Syndromes: Clinical Characteristics and Outcome in a Long Term Single Centre Experience

British Journal of Haematology. Jul, 2010  |  Pubmed ID: 20433678

Low-dose Naproxen Interferes with the Antiplatelet Effects of Aspirin in Healthy Subjects: Recommendations to Minimize the Functional Consequences

Arthritis and Rheumatism. Mar, 2011  |  Pubmed ID: 21360514

To investigate whether low-dose naproxen sodium (220 mg twice a day) interferes with aspirin's antiplatelet effect in healthy subjects.

Choline Acetyltransferase of the Common Type Immunoreactivity in the Rat Brain Following Different Heroin Treatments: a Pilot Study

Journal of Chemical Neuroanatomy. Mar, 2011  |  Pubmed ID: 21184823

Previous studies suggest that behavioral consequences of heroin treatment depend on the drug history of the animals and that cholinergic neurotransmission is involved in both behavioral and motor sensitization induced by heroin and other drugs of abuse. Immunohistochemistry, using a recently developed antiserum, specific for choline acetyl-transferase of the common type (cChAT), was applied to four different groups of rats, differing in drug regimens. Two groups of rats were submitted to the same schedule of heroin sensitization and then challenged for vehicle or heroin before sacrifice, obtaining two distinct groups, namely heroin-vehicle (HV) and heroin-heroin (HH). The same challenge was applied to another group of rats, previously submitted to a treatment with vehicle, obtaining other two groups, vehicle-vehicle (VV) and vehicle-heroin (VH), respectively. The number of cChAT-positive neurons is significantly increased (p<0.05) in the diagonal band nuclei (with a consequent increase of cChAT positive fibers in the dentate gyrus) and notably, even not significantly (p>0.05), increased in the nucleus accumbens core of heroin-sensitized rats (HV, HH). Instead, acute heroin treatment significantly increase (p<0.05) the number of cChAT-positive cells in the nucleus accumbens shell of both heroin-naïve (VH) and heroin-sensitized (HH) rats. In heroin-sensitized rats (HV, HH), moreover, staining intensity of cChAT-positive fibers is significantly increased in the dorsal striatum, and basolateral amygdala (p<0.05). Unlikely, cChAT positive fibers in the central amygdala are significantly increased (p<0.05) by acute heroin treatments (VH, HH). The increase of cholinergic fibers in the dentate gyrus of the heroin sensitized rats (HV, HH) seems accompanied by a evident reduction in calretinin immunoreactive neurons in the same area. Our results, in a small group of animals, support the view that cholinergic mechanisms are intimately associated with the development of addictive phenotype. Furthermore, they suggest that cholinergic system is differentially engaged, following different heroin treatments.

Serum Heavy Metal and Antioxidant Element Levels of Children with Recurrent Wheezing

Allergologia Et Immunopathologia. Mar-Apr, 2011  |  Pubmed ID: 21236553

The aim of the study is to investigate the levels of toxic heavy metals related with environmental pollution and trace elements involved in antioxidant system in children suffering from recurrent wheezing.

Immunohistochemical Demonstration of Cholinergic Structures in Central Ganglia of the Slug (Limax Maximus, Limax Valentianus)

Neurochemistry International. Apr, 2011  |  Pubmed ID: 21315127

Immunohistochemical techniques were used to study the distribution of cholinergic neurons containing choline acetyltransferase of the common type (cChAT), the synthetic enzyme of acetylcholine, in the central nervous system of the slug Limax maximus and Limax valentianus. Because the antiserum applied here was raised against a recombinant protein encoded by exons 7 and 8 of the rat gene for ChAT, three methods were used in order to validate antibody specificity for the Limax counterpart enzyme. Western blot combined with ChAT activity assay following native gel electrophoresis and immunoprecipitation analysis both indicated that immunoreactive Limax brain molecules were capable of synthesizing acetylcholine. Western blot after denatured gel electrophoresis of Limax brain extracts revealed a single band of about 67kDa. All findings obtained with these three methods clearly indicated that the antiserum effectively recognized Limax cChAT. 1400 neuronal cell bodies positive for cChAT, mainly small to medium-sized, were found in various brain regions in the buccal, cerebral, pleural, parietal, visceral and pedal ganglia. cChAT immunoreactive nerve fibers were distributed extensively in the neuropil, connectives and commissures of these central ganglia. The map of cChAT-positive cells provided here are valuable for understanding the cholinergic mechanism in the slug brain, as well as giving an important hint to clarifying the mechanisms of learning and memory in higher vertebrates including humans.

Do Immunosupressive Patients Really Have a Severe Outcome with H1N1 Virus Infection?

Journal of Tropical Pediatrics. Apr, 2011  |  Pubmed ID: 20587734

Influenza virus is a common human pathogen that has the potential to cause widespread pandemics. The last pandemic began in April 2009 in CA, USA and killed about 14,000 people since then. The virus affects people at all ages, and school-aged children have the highest rates of infection. Chronic lung disease, immunosuppression and pregnancy are risk factors for seasonal influenza and pandemic influenza as well. Here, we report five immunosuppressive patients due to various diseases infected with H1N1 influenza and who were completely revealed after promptly treatment with oseltamivir.

Omalizumab Decreases Exacerbation Frequency, Oral Intake of Corticosteroids and Peripheral Blood Eosinophils in Atopic Patients with Uncontrolled Asthma

International Journal of Clinical Pharmacology and Therapeutics. Dec, 2011  |  Pubmed ID: 22122813

Omalizumab is a humanized monoclonal anti-IgE antibody approved in 2005 by the European Medicine Agency (EMA) for the treatment of severe persistent allergic asthma, which remains inadequately controlled despite optimal therapy with high doses of inhaled corticosteroids and long-acting β₂-adrenergic agonists. Within this context, the present observational study refers to 16 patients currently treated with omalizumab at the Respiratory Unit of "Magna Græcia" University Hospital located in Catanzaro, Italy, whose anti- IgE therapy was started in the period included between March 2007 and February 2010, thus lasting at least 10 months. After 40 weeks of add-on treatment with omalizumab, very relevant decreases were detected, in comparison with pre-treatment mean (± standard deviation) values, in monthly exacerbation numbers (from 1.1 ± 0.6 to 0.2 ± 0.4; p < 0.01) and oral corticosteroid consumption (from 22.6 ± 5.0 to 1.2 ± 2.9 mg/day of prednisone; p < 0.01). These changes were associated with stable improvements in lung function, expressed as increases of both FEV1 (from 53.6 ± 14.6% to 77.0 ± 14.9% of predicted values; p < 0.01) and FEV1/FVC ratio (from 56.3 ± 9.5% to 65.8 ± 9.2%; p < 0.01). Moreover, in 5 patients who persistently had increased numbers of eosinophils (mean ± SD: 15.9 ± 8.0% of total WBC count; absolute number: 1,588.0 ± 956.9/μl) despite a long-lasting therapy with inhaled and systemic corticosteroids, the peripheral counts of these cells decreased down to near normal levels (mean ± SD: 6.3 ± 2.3% of total WBC count; absolute number: 462.0 ± 262.3/μl) after 16 weeks of treatment with omalizumab. Therefore, this descriptive evaluation confirms the efficacy of add-on omalizumab therapy in selected patients with exacerbation-prone, chronic allergic uncontrolled asthma, requiring a continuous intake of oral corticosteroids.

IL28B Polymorphisms Influence Stage of the Liver Fibrosis and Spontaneousor Interferon-induced Viral Clearance in Thalassemia Patients with Hepatitis C Virus Infection

Haematologica. Dec, 2011  |  Pubmed ID: 22180419

Background. Polymorphisms in the interleukin-28B are important determinants in the spontaneous and drug-induced control of hepatitis C virus infection. Design and Methods. We assessed the association of rs8099917 and rs12979860 polymorphisms with spontaneous viral clearance, severity of liver fibrosis, and response to interferon-monotherapy in 245 Thalassemia Major patients with Hepatitis C Virus infection.Results. Ninety-eight patients (40%) had a spontaneous viral clearance, while 147 patients (60%) developed a chronic infection. Spontaneous viral clearance was more frequent among patients with the T/T genotype of rs8099917 polymorphism (OR 2.130; p=0.008) or C/C genotype of rs12979860 polymorphism (OR 2.425; p=0.001). During observation, 131 patients with chronic infection underwent a liver biopsy, age (OR 1.058; p=0.01) G/T or G/G genotypes of rs8099917 polymorphism (OR 3.962; p=0.001) and C/T or T/T genotypes of rs12979860 polymorphism (OR 3.494; p=0.005) were associated with severe liver fibrosis, independent of liver iron concentration. Finally, T/T genotype of rs8099917 polymorphism (OR 3.014; p=0.03) or C/C genotype of rs12979860 polymorphism (OR 3.285; p=0.01), age (OR 0.902; p=0.001), female gender (OR 3.418; p=0.01) and 2 or 3 virus C genotypes (OR 4.700; p=0.007 ) were independently associated with sustained virological response in 114 patients treated with alpha- interferon .Conclusions. Polymorphisms in the interleukin-28B are associated with the control of hepatitis C virus infection in Thalassemia Major patients, and the knowledge of allelic patterns has a relevant role in determining the prognosis and therapeutic management.

An Unusual Pediatric Case with Neurofibromatosis and Systemic Lupus Erythematosus

Rheumatology International. Jun, 2011  |  Pubmed ID: 21644043

Neurofibromatosis type 1 (NF1) is a relatively common autosomal dominant disorder affecting mainly ectodermal and mesodermal tissues. It is well known that patients with NF1 have an increased risk of developing benign and malignant tumors, but its association with autoimmune diseases has been rarely reported. Systemic lupus erythematosus is an autoimmune chronic inflammatory disease that has the potential to affect various organ systems. There are four cases with NF1 and SLE reported in the literature up to date. Here, we report a 9-year-old girl presenting with NF1 and SLE, and to our knowledge, this is the first childhood case in the literature.

Feasibility of DNA Diagnosis of Haemoglobinopathies on Coelocentesis

British Journal of Haematology. Mar, 2011  |  Pubmed ID: 21385172

At 5-12 weeks of gestation the amniotic sac is surrounded by celomic fluid, which contains cells of fetal origin. This fluid can be sampled by celocentesis, which involves the ultrasound-guided insertion of a needle through the vagina. The aim of this study was to examine the feasibility of prenatal diagnosis of haemoglobinopathies from the celomic fluid using a specific protocol. Celocentesis was performed at 7-9 weeks gestation in 26 singleton pregnancies at risk for haemoglobinopathies. In 25 cases more than 30 fetal cells were recovered from the celomic fluid and in all these cases molecular analysis for haemoglobinopathies was possible and the results were confirmed by subsequent chorionic villus sampling or amniocentesis. The results of this study suggest that reliable diagnosis of thalassemia syndromes can be performed from 7 weeks gestation by celocentesis. Further work is necessary to demonstrate the safety of celocentesis before widespread use.

The Genetic Heterogeneity of β-globin Gene Defects in Sicily Reflects the Historic Population Migrations of the Island

Blood Cells, Molecules & Diseases. Apr, 2011  |  Pubmed ID: 21353607

The aim of this study is to update the incidence and the distribution of the globin gene defects causing β-thalassemia and abnormal hemoglobins in Sicily. The data derived from a total of 8875 beta-thalassemia alleles and 1330 variant hemoglobin chromosomes studied in Sicily from 1990 during a hemoglobinopathy control program. Fifty-four beta-globin gene defects were characterized, involving 30 different beta-thalassemia mutations and 24 variant hemoglobins. Eight of 30 β-thalassemia defects accounted for 95.11% of examined alleles while other beta-globin gene defects were found at lower frequencies (<1%). A consistent number (24) of variant hemoglobins were identified of whom Hb S was the most represented (72.1%). Our data underline the heterogeneity of the beta-globin gene defects in the Sicily. The enormous progress in the technique for β-globin gene analysis permitted to characterize 99.93% of mutated alleles and it has made a first trimester prenatal diagnosis program possible in our region in all cases with a great improvement in thalassemia management. The origin of the large spectrum of mutations is discussed taking in consideration the history of the island.

Bullying in Early Adolescence and Its Association with Anti-social Behaviour, Criminality and Violence 6 and 10 Years Later

Criminal Behaviour and Mental Health : CBMH. Apr, 2011  |  Pubmed ID: 21370297

Few longitudinal studies have examined the links between engagement in bullying and later anti-social behaviour for both males and females.

Iron Deficiency Do Not Compromise the Diagnosis of High HbA2 Beta Thalassemia Trait

Haematologica. Nov, 2011  |  Pubmed ID: 22102712

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Marked Impact of IL28B Genotype in the Natural Clearance of Hepatitis C Virus in Patients with Haemoglobinopathies

British Journal of Haematology. Sep, 2011  |  Pubmed ID: 21615377

A Comparative Analysis of the Osteogenic Effects of BMP-2, FGF-2 and VEGFA in a Calvarial Defect Model

Tissue Engineering. Part A. Dec, 2011  |  Pubmed ID: 22195699

The utilization of growth factors for bone regeneration is a widely studied field. Since the approval of BMP-2 for therapeutic use in humans, the concept of utilizing growth factors for bone regeneration in translational medicine has become even more attractive. Despite many studies published on individual growth factors in various bone models, comparative analysis are largely lacking. The aim of our study was to compare three different pro-osteogenic factors under identical in vivo conditions. Thus, we tested the bone regeneration capacity of three different growth factors: BMP-2, FGF-2, VEGFA in a calvarial defect model. We demonstrated that BMP-2 and VEGFA had similar bone healing capacities, resulting in complete calvarial healing as early as week 3. FGF-2 also showed a significantly higher bone regeneration capacity, however the healing rate was lower than with BMP-2 and VEGFA. Interestingly, these findings were paralleled by an increased angiogenic response upon healing in BMP-2 and VEGFA treated calvarial defects as compared to FGF-2. Immunohistochemistry for proliferating and osteoprogenitors cells revealed activity at different points after surgery among the groups. In conclusion, we demonstrated an efficient bone regeneration capacity of both BMP-2 and VEGFA, which was superior to FGF-2. Moreover, this study highlights the efficient bone regeneration of VEGFA, which was comparable to BMP-2. These data provide a valuable comparative analysis, which can be used to further optimize growth factor based strategies in skeletal tissue engineering.

Update on Optimal Use of Omalizumab in Management of Asthma

Journal of Asthma and Allergy. , 2011  |  Pubmed ID: 21792319

Omalizumab is a humanized monoclonal anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing interaction with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include improvements in respiratory symptoms and quality of life, paralleled by a reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well-tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma inadequately controlled by high doses of standard inhaled treatments.

Surveillance of Suspected Adverse Reactions to Herbal Products Used As Laxatives

European Journal of Clinical Pharmacology. Mar, 2012  |  Pubmed ID: 21964980

To describe and evaluate spontaneous reports of suspected adverse reactions (ARs) associated with herbal laxatives received by the Italian Medicines Agency and the Italian National Institute of Health between April 2002 and January 2011.

Genetic Determinants of Blood Pressure Responses to Caffeine Drinking

The American Journal of Clinical Nutrition. Jan, 2012  |  Pubmed ID: 22170367

The widely observed between-subject variability in cardiovascular responses to coffee may have a genetic basis.

Adrenocortical Carcinoma: Effect of Hospital Volume on Patient Outcome

Langenbeck's Archives of Surgery / Deutsche Gesellschaft Für Chirurgie. Feb, 2012  |  Pubmed ID: 22069043

Optimal management of adrenocortical carcinoma (ACC) involves a detailed diagnostic workup, radical surgery, and appropriate adjuvant therapy. However, due to the rarity of this disease, adequate expertise is necessary to ensure optimal patient care. We evaluated if the experience of a treating center influences the outcome of ACC.

Relationship Between Hair Cadmium Levels, Indoor ETS Exposure and Wheezing Frequency in Children

Allergologia Et Immunopathologia. Jan, 2012  |  Pubmed ID: 21414712

Cadmium (Cd) is a toxic heavy metal and the components of tobacco and scalp hair effectively reflect a long-term environmental exposure.

Complete Response to Preoperative Chemoradiation and Survival in Esophageal Cancer: a Pooled Analysis of Three Single-institution Phase II Trials

Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. Feb, 2012  |  Pubmed ID: 21762278

This pooled analysis was performed using individual patient data from three phase II trials that included on the whole 113 esophageal cancer treated preoperatively with chemoradiotherapy (CRT), in order to analyze the efficacy and survival outcomes according to the achievement of the pathologic complete response (pCR). Thirty-nine patients were treated with 5-fluorouracil/cisplatin and RT (40 Gy), 33 patients received paclitaxel/cisplatin weekly during weeks 1-6 with and RT (46 Gy), 41 patients were treated with induction bio-chemotherapy with cetuximab and FOLFOX-4 followed by concomitant cetuximab and RT of 50.4 Gy. One hundred and two out of 113 resected patients were included in the survival analysis. The median overall survival (OS) time for the whole population was 21.5 months. The 12, 24, and 36 months OS rates were 85.4, 45.2, and 33%, respectively. The difference in survival probability between patients with pCR and patients with partial response or stable disease after treatment was significant (P= 0.0002, hazard ratios = 0.21, 95% CI 0.18-0.60). On multivariate analysis, the pathologic response and histology were the only covariates independently associated with OS (P= 0.0157 and P= 0.0212, respectively). In our series, complete responder patients had a significant longer survival probability after treatment when compared to patients with partial response or stable disease.