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Articles by Brian Peterson in JoVE

Other articles by Brian Peterson on PubMed

Adherence with Hand Hygiene: Does Number of Sinks Matter?

Infection Control and Hospital Epidemiology. Mar, 2003  |  Pubmed ID: 12683516

We observed adherence with hand hygiene in 14 units at 4 hospitals with varying sink-to-bed ratios (range, 1:1 to 1:6). Adherence was less than 50% in all units and there was no significant trend toward improved hand hygiene with increased sink-to-bed ratios.

Impact of Ring Wearing on Hand Contamination and Comparison of Hand Hygiene Agents in a Hospital

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Jun, 2003  |  Pubmed ID: 12766832

We determined risk factors for hand contamination and compared the efficacy of 3 randomly allocated hand hygiene agents in a group of surgical intensive care unit nurses. We cultured samples of one of the subjects' hands before and samples of the other hand after hand hygiene was performed. Ring wearing was associated with 10-fold higher median skin organism counts; contamination with Staphylococcus aureus, gram-negative bacilli, or Candida species; and a stepwise increased risk of contamination with any transient organism as the number of rings worn increased (odds ratio [OR] for 1 ring worn, 2.6; OR for >1 ring worn, 4.6). Compared with use of plain soap and water, hand contamination with any transient organism was significantly less likely after use of an alcohol-based hand rub (OR, 0.3; 95% confidence interval [CI], 0.1-0.8) but not after use of a medicated hand wipe (OR, 0.9; 95% CI, 0.5-1.6). Ring wearing increased the frequency of hand contamination with potential nosocomial pathogens. Use of an alcohol-based hand rub resulted in significantly less frequent hand contamination.

Coil Embolization of an Inferior Pancreaticoduodenal Artery Aneurysm Associated with Celiac Artery Occlusion

Cardiovascular Surgery (London, England). Dec, 2003  |  Pubmed ID: 14627975

Pancreaticoduodenal arcade aneurysms are rare. Untreated, these lesions enlarge progressively and have the potential for spontaneous rupture. Aneurysmal degeneration of pancreaticoduodenal arcade vessels is known to be associated with celiac artery occlusion, vasculitis, and certain connective tissue disorders. Given their precarious location, surgical expiration is a challenging endeavor. Innovations in endovascular techniques offer a possible alternative. We report a case of a 55-year-old gentleman with a 2.2x2.1-cm aneurysm of one of the inferior pancreaticoduodenal arteries and a concomitant finding of occlusion of the celiac artery trunk. Percutaneous coil embolization of the aneurysm was employed as the treatment in this case with the successful exclusion of the aneurysm sac, while maintaining continuity of the native circulation. This case report demonstrates that, due to the success rate of aneurysm exclusion and the relatively low morbidity and mortality rates seen with endovascular repair as compared to surgical intervention, endovascular treatment has become the treatment of choice for pancreaticoduodenal artery aneurysms.

Electronic Interpretation of Chest Radiograph Reports to Detect Central Venous Catheters

Infection Control and Hospital Epidemiology. Dec, 2003  |  Pubmed ID: 14700412

To evaluate whether a natural language processing system, SymText, was comparable to human interpretation of chest radiograph reports for identifying the mention of a central venous catheter (CVC), and whether use of SymText could detect patients who had a CVC.

Effects of Fasting on Circulating IGF-binding Proteins, Glucose, and Cortisol in Channel Catfish (Ictalurus Punctatus)

Domestic Animal Endocrinology. Apr, 2004  |  Pubmed ID: 15036377

The effects of fasting on IGF-binding proteins (IGFBPs), glucose, and cortisol in channel catfish were examined. Fed fish (controls) were compared to 14-, 30-, and 45-day fasted fish and 45-day fasted fish refed for 15 additional days. Body length and weight changes, condition factor (CF), hepatosomatic index (HSI), and plasma glucose and cortisol were assessed to determine growth and metabolic status. Body length and growth rates were inhibited (P<0.05) after 14, 30, and 45 days of fasting. The 14-, 30-, and 45-day fasted fish exhibited hypoglycemia and reduced CF and HSI. Cortisol levels were increased (22.8 +/- 15.2 ng/ml versus 4.7 +/- 3.9 ng/ml) in 30-day fasted fish compared to fed controls (P<0.05). Associated with the increase in cortisol in fasted fish was a concomitant increase in plasma levels of a 20-kDa IGFBP through day 45. A 35- and a 45-kDa IGFBP were also identified but were similar between fed and unfed fish throughout the experiment. At the end of 15 days of refeeding, 20-kDa IGFBP, glucose, and cortisol levels were similar to fed controls. Refeeding also caused an increase in growth rates. These results suggest the existence of a catfish counter part to mammalian IGFBP-1, similar to lower molecular mass IGFBPs reported in other species of fish. These results also suggest that a 20-kDa IGFBP is upregulated during fasting-induced growth inhibition of channel catfish and provide additional evidence of the conserved nature of the IGF-IGFBP-growth axis in fish.

Xenopus U8 SnoRNA Binding Protein is a Conserved Nuclear Decapping Enzyme

Molecular Cell. Mar, 2004  |  Pubmed ID: 15053875

U8 snoRNP is required for accumulation of mature 5.8S and 28S rRNA in vertebrates. We are identifying proteins that bind U8 RNA with high specificity to understand how U8 functions in ribosome biogenesis. Here, we characterize a Xenopus 29 kDa protein (X29), which we previously showed binds U8 RNA with high affinity. X29 and putative homologs in other vertebrates contain a NUDIX domain found in MutT and other nucleotide diphosphatases. Recombinant X29 protein has diphosphatase activity that removes m(7)G and m(227)G caps from U8 and other RNAs in vitro; the putative 29 kDa human homolog also displays this decapping activity. X29 is primarily nucleolar in Xenopus tissue culture cells. We propose that X29 is a member of a conserved family of nuclear decapping proteins that function in regulating the level of U8 snoRNA and other nuclear RNAs with methylated caps.

Human Microvascular Endothelial Cell Prostaglandin E1 Synthesis During in Vitro Ischemia-reperfusion

Journal of Cellular Biochemistry. Jun, 2004  |  Pubmed ID: 15156559

Ischemia-reperfusion injury is a microvascular event documented in numerous in vivo animal models. In animal models, prostaglandin and prostaglandin analogues have been found to ameliorate reperfusion injury. These studies were undertaken to evaluate human microvascular endothelial PGE(1) synthesis during in vitro ischemia followed by reperfusion. Human (neonatal) microvascular endothelial cell (MEC) cultures (n = 6) were subjected to sequential 2 h periods of normoxia (20% O(2)), ischemia (1.5% O(2)), and reperfusion (20% O(2)). Prostaglandin E(2) synthesis in conditioned media was determined by ELISA. Steady state levels of MEC prostaglandin H synthase (PGHS)-1 and -2 mRNA were assessed at the end of each 2-h period using RT-PCR and a quantitative mRNA ELISA. MEC PGHS protein levels were analyzed using an ELISA. PGE(1) release increased significantly during the initial 30 min of ischemia, but rapidly fell below normoxic levels by 90 and 120 min. During reperfusion, PGE(1) release returned to normoxic levels at 30, 60, and 90 min, and exceeded normoxic levels at 120 min. PGHS-1 mRNA levels were undetectable during all experimental conditions. PGHS-2 mRNA levels were unchanged by ischemia, but were decreased by reperfusion. In contrast, PGHS-2 protein levels increased 3-fold during ischemia, and remained elevated during reperfusion. Human MEC do not express PGHS-1 mRNA in vitro. Prolonged ischemia decreases MEC PGE(1) synthesis, and stimulates increased PGHS-2 protein levels without altering the steady state levels of COX-2 mRNA. During reperfusion, increased PGHS-2 protein levels persist and are associated with stimulated PGE(2) secretion, despite relative decreases in PGHS-2 mRNA.

IGF-I and IGF-II MRNA Expression in Slow and Fast Growing Families of USDA103 Channel Catfish (Ictalurus Punctatus)

Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology. Nov, 2004  |  Pubmed ID: 15556387

The objective of this study was to examine insulin-like growth factor (IGF)-I and IGF-II mRNA levels in fast and slow growing families of catfish. Relative levels of IGF-I and IGF-II mRNA were determined by real-time PCR. Family A exhibited a specific growth rate (SGR) of 3.6 and was designated as fast growing, while family H exhibited a SGR of 3.1 and was designated as slow growing (P=0.017). Levels of IGF-II mRNA were 3.3-fold greater (P=0.006) in muscle for the fast growing family compared to the slow growing family. Levels of IGF-II mRNA were 1.8-fold greater (P=0.049) in liver for the fast growing family compared to the slow growing family. Levels of IGF-II mRNA from both fast and slow families were 12.2-fold greater (P<0.001) in muscle and 5.8-fold greater (P=0.021) in liver, respectively, compared to levels of IGF-I mRNA. Muscle and liver levels of IGF-I mRNA were similar between families. Elevated levels of IGF-II mRNA in muscle and liver compared to IGF-I mRNA, as well as differences in levels of IGF-II mRNA between fast and slow growing families of fish suggests a role of IGF-II in growth of channel catfish.

Locally Administered Ketorolac and Bupivacaine for Control of Postoperative Pain in Breast Augmentation Patients

Plastic and Reconstructive Surgery. Dec, 2004  |  Pubmed ID: 15577367

With recent developments in the field of analgesia, the question arises whether there is a role for placing local anesthetics, nonsteroidal anti-inflammatory drugs, or both into the breast implant pocket. The objective of this study was to test the effectiveness of locally administered intraoperative ketorolac and bupivacaine with epinephrine at reducing pain in the postoperative period. The study was a prospective, randomized, double-blind clinical trial. One hundred consecutive retropectoral breast augmentation patients were enrolled, and informed consent was obtained. A standard anesthetic protocol and surgical procedure were followed. Normal saline, ketorolac alone (30 mg), bupivacaine alone (150 mg), or ketorolac and bupivacaine (30 mg and 150 mg respectively) were placed into the implant pocket before implant insertion. All patients completed the study. The power of this study to detect a 20 percent difference with respect to the primary outcome was 0.90 and confidence intervals of 95 percent were used to determine significance. The primary outcome was pain as measured by the visual analogue pain scale. The secondary outcome was time spent in the recovery room. Intraoperative placement of ketorolac combined with bupivacaine reduced pain in the postoperative period. It did not appear that anesthesiologist, anesthesia time, surgeon, operating room time, difficulty of dissection, breast incision, or implant size had a significant effect on postoperative pain. There was a trend that the ketorolac and bupivacaine patients spent less time in the recovery room and used fewer analgesics postoperatively than the other patients. There were no hematomas requiring reoperation and no complications. Locally administered intraoperative ketorolac and bupivacaine with epinephrine significantly reduced pain in the postoperative period.

Establishment of a Time-resolved Fluoroimmunoassay for Measuring Plasma Insulin-like Growth Factor I (IGF-I) in Fish: Effect of Fasting on Plasma Concentrations and Tissue MRNA Expression of IGF-I and Growth Hormone (GH) in Channel Catfish (Ictalurus Punctatus)

Domestic Animal Endocrinology. Feb, 2005  |  Pubmed ID: 15713367

A time-resolved fluoroimmunoassay (TR-FIA) was established and validated that allows for the determination of plasma concentrations of insulin-like growth factor I (IGF-I) in three domestically cultured fishes: channel catfish (Ictalurus punctatus), hybrid striped bass (Morone chrysopsxM. saxatilis), and rainbow trout (Oncorhynchus mykiss). Sensitivity of the assay was 0.20 ng/ml. Intra- and inter-assay coefficients of variation (CV) were <7 and <12%, respectively. Serial dilutions of plasma from each species were parallel to the standard curve. Recovery of IGF-I from spiked plasma samples was >90% for all three species of fishes. The IGF-I TR-FIA was biologically validated via its use to determine the effect of fasting on circulating IGF-I levels in channel catfish. Fasting-induced changes in plasma growth hormone (GH), hepatic IGF-I mRNA expression, and pituitary GH mRNA expression were also determined. Fasted channel catfish lost 5.6 and 15.6% body mass after 2 and 4 weeks of fasting, respectively. Plasma IGF-I concentrations were depressed (P<0.05) relative to fed controls following 2 and 4 weeks of fasting. Plasma GH concentrations were not different (P>0.05) in fasted fish after 2 weeks, but significantly increased (P<0.05) by 4 weeks of fasting. Hepatic IGF-I mRNA expression after 2 and 4 weeks of fasting was reduced (P<0.05) relative to fed controls. Pituitary GH mRNA expression was similar (P>0.05) between 2-week-fasted catfish and fed controls, but was increased (P<0.05) in 4-week-fasted catfish. The IGF-I TR-FIA was sensitive, accurate, and precise for all three species of fishes, and provided a low-cost, and non-radioisotopic method for quantifying plasma IGF-I levels in fed and fasted channel catfish.

Effects of Exogenous Cortisol on the GH/IGF-I/IGFBP Network in Channel Catfish

Domestic Animal Endocrinology. May, 2005  |  Pubmed ID: 15826774

Glucocorticoids are known to hinder somatic growth in a number of vertebrate species. In order to better understand the mechanisms through which they may act in channel catfish, we examined the effects of feeding cortisol on the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein (IGFBP) network. Fish (30.6+/-3.0 g) were fed once daily for 4 weeks and treatments included: (1) High-cortisol (dietary cortisol provided at 400 mg/kg feed), (2) Low-cortisol (dietary cortisol provided at 200 mg/kg feed), and (3) Control (commercial catfish feed). Fish fed diets with cortisol weighed approximately 50% less than Controls. Feed intake was reduced by approximately 30% in both treatments of cortisol fed fish compared to Controls. A approximately 20-kDa IGFBP was observed in plasma from High- and Low-treated fish while it was not detected in Control fish plasma. High-cortisol treatment increased pituitary GH mRNA expression approximately 10-fold while liver IGF-I mRNA expression was not different between cortisol-treated fish and Controls. Cortisol treatments decreased plasma levels of IGF-I. These data indicate that feeding cortisol for 4 weeks reduces weight gain, feed intake, and plasma levels of IGF-I and induces a approximately 20-kDa IGFBP. One mechanism through which cortisol may impede growth of catfish is through an increase in a low molecular weight IGFBP which may lead to inhibitory effects on the action of IGF-I.

Differential Gene Expression of IGF-I, IGF-II, and Toll-like Receptors 3 and 5 During Embryogenesis in Hybrid (channel X Blue) and Channel Catfish

Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology. May, 2005  |  Pubmed ID: 15882955

Insulin-like growth factors-I and-II (IGF-I and IGF-II) play important roles in growth and development of mammals. Toll-like receptors (TLRs) are pattern recognition molecules that orchestrate the induction of early innate immune response by recognition of specific sequences. Evidence is growing that suggests a relationship between growth and immune function. The objective of the study was to examine changes in gene expression of IGF-I, IGF-II, TLR3, and TLR5 during embryogenesis and early larval development in hybrid (channel catfishxblue catfish) and channel catfish. Egg samples were taken pre- and post-fertilization; embryos were collected at two stages of embryogenesis, at hatch, and at swim-up. All genes were detected in unfertilized catfish eggs. Expression levels of TLR5 and IGF-I mRNA in channel catfish and expression levels of TLR3, IGF-I, and IGF-II mRNA in hybrids increased over time (P<0.01). Effect of time was not significant for expression of IGF-II or TLR3 mRNA in channel catfish and for TLR5 mRNA in hybrid catfish. Results of this study suggest growth (IGF-I and IGF-II) and immune (TLR3 and TLR5) associated genes could be functional and play important roles during embryogenesis and early development of hybrid and channel catfish.

Trauma Clip-art: Early Experience with an Improved Radiopaque Marker System for Delineating the Path of Penetrating Injuries

The Journal of Trauma. May, 2005  |  Pubmed ID: 15920430

Duplex Ultrasound Remains a Reliable Test Even After Carotid Stenting

Annals of Vascular Surgery. Nov, 2005  |  Pubmed ID: 16228805

Transluminal arterial stenting reduces vessel compliance and may alter accurate interpretation of flow velocities. We reviewed duplex ultrasonography (DUS) following carotid stenting to identify criteria indicative of severe recurrent stenosis. This is a single-center retrospective review of 158 carotid stenoses treated with carotid angioplasty and stenting (CAS) from April 2001 to December 2004. DUS was obtained preoperatively, postoperatively, and at 3-month intervals thereafter. Peak systolic velocity (PSV) and end diastolic velocity (EDV) were analyzed. Mean follow-up was 12 months (range 1-40). Mean age was 71 +/- 9 years (range 51-91; 74% men, 26% women). Three patients (1.9%) developed restenosis and one (0.6%) developed an asymptomatic occlusion during follow-up. Average preoperative PSV was 373 +/- 123 cm/sec (mean +/- SD) and EDV was 148 +/- 63 cm/sec. Immediate postoperative PSV and EDV decreased by an average of 70% (average 118 +/- 45 cm/sec) and 72% (average 32 +/- 15 cm/sec), respectively. In patients free from restenosis or occlusion, these reductions (range 65-80%) were maintained throughout follow-up and remained within 1-25% of immediate postoperative values. In patients suffering restenosis or occlusion, follow-up PSV and EDV increased 34% and 28%, respectively, compared to preoperative values. PSV and EDV increased by an average of 287% and 500%, respectively, compared to immediate postoperative values. Using criteria of PSV >170 cm/sec and a 50% increase of PSV over immediate postoperative values, restenosis or occlusion was detected with 100% sensitivity and specificity in our patients. Additionally, EDV >120 cm/sec and a 50% increase in EDV over immediate postoperative values detected restenosis and occlusion with 100% sensitivity and specificity. Presumed restenosis and occlusion detected by DUS were confirmed in all cases with angiography. Restenosis or occlusion after CAS at our institution can reliably be detected by carotid duplex using cut-off values of 170 cm/sec PSV, 120 cm/sec EDV, and >50% increase over immediate postoperative values. While these criteria are applied to patients undergoing CAS at our institution, they serve only as suggested guidelines for patient populations at other centers and must be customized to each Intersocietal Commission for the Accreditation of Vascular Laboratories-accredited vascular laboratory.

Endovascular Repair of Descending Aortic Dissections

Seminars in Thoracic and Cardiovascular Surgery. 2005  |  Pubmed ID: 16253832

Endoluminal aortic stent-grafts have revolutionized the contemporary management of abdominal aortic aneurysms. The application of this treatment option for aortic dissections has been hampered by the difficult anatomic constraints frequently encountered with both acute and chronic forms of the disease. Although the data are sparse, it is rapidly growing as technologic advances are made in the design and delivery of various stent-grafts. Reviewed is our current understanding of the pathophysiology of descending thoracic aortic dissections, available stent-graft designs, techniques of implantation, and alternatives for complex anatomy. The section concludes with an overview of published data on stent-graft repair of both acute and chronic aortic dissections.

Endovascular Repair of Thoracic Aortic Pathology with Custom-made Devices

Surgery. Oct, 2005  |  Pubmed ID: 16269287

Open repair of thoracic aortic aneurysms (TAAs) is fraught with high morbidity and mortality rates. The availability of endoprostheses for treating thoracic aortic pathology has not kept pace with those for treating abdominal aneurysms. Technical feasibility, durability, and safety of custom-made stent-grafts for the treatment of TAAs and dissections are evaluated.

Molecular Characterization of the Insulin-like Growth Factor-I (IGF-I) Gene in Channel Catfish (Ictalurus Punctatus)

Biochimica Et Biophysica Acta. Dec, 2005  |  Pubmed ID: 16298440

The insulin-like growth factor I (IGF-I) gene was characterized in channel catfish. Partial cDNA sequence, missing exon 1 and part of exon 2, was obtained in 5'- and 3'-RACE experiments. Direct sequencing of two bacterial artificial chromosome clones revealed gene structure and provided sequence from 640 bp upstream of the initiator methionine to 136 bp beyond the polyadenylation site. Genomic sequence contained a putative TATA box 506 bp upstream of the initiator methionine. The 477-bp reading frame within five exons encoded a 159-amino acid (aa) pre-propeptide highly similar to IGF-I in higher vertebrates. The sequence encoding the signal peptide was unique in catfish and contained 70% G+C content with the potential for a stable stem-loop structure. Full-length cDNA was only maintained in recombination-deficient (DH10B) strain E. coli. Levels of IGF-I mRNA were highest in liver, followed by brain and muscle, then heart and kidney (P<0.05). A CT/GA dinucleotide microsatellite in intron 1 was highly polymorphic in commercial channel catfish, and permitted placement of the IGF-I gene on the catfish genetic map. However, specific IGF-I alleles were not correlated with differences in growth rate from 100 to 130 days post-hatch in USDA103 line catfish.

Percutaneous Endovascular Repair of Blunt Thoracic Aortic Transection

The Journal of Trauma. Nov, 2005  |  Pubmed ID: 16385279

Untreated traumatic aortic transection carries a mortality rate higher than 85%. Standard therapy has been open repair via a left thoracotomy with systemic heparin and is associated with a high risk of paralysis. We reviewed our experience of endoluminal stent-graft repair for treatment of acute traumatic thoracic aortic transection.

Response of Toll-like Receptors, Lysozyme, and IGF-I in Back-cross Hybrid (F1 Male (blue X Channel) X Female Channel) Catfish Challenged with Virulent Edwardsiella Ictaluri

Fish & Shellfish Immunology. Jan, 2006  |  Pubmed ID: 15905103

Responses of toll-like receptors (TLR3 and TLR5), lysozyme, and insulin-like growth factor-I (IGF-I) to experimental challenge with virulent Edwardsiella ictaluri were measured in back-cross hybrid (F1 male (blue x channel) x female channel) catfish. The resistance levels to E. ictaluri and host response mechanisms of back-cross hybrids are unknown. Fish were challenged with virulent E. ictaluri and sampled pre-challenge, 2 h and 2, 5, 8, 14, and 21 days post-challenge. Levels of mRNA expression of two toll-like receptors (TLR3 and TLR5) in liver, kidney, spleen, and stomach, plasma lysozyme activity, and circulating IGF-I levels were measured at each timepoint. Throughout challenge, TLR3 was expressed at higher levels than TLR5 in liver (P=0.0011) and kidney (P=0.0007) whereas TLR5 was more highly expressed than TLR3 in stomach (P=0.0032). TLR3 was upregulated in comparison to non-exposed controls in liver (P=0.0015) and stomach (P<0.0001) on day 14 and TLR5 was upregulated in liver (P=0.0175) on days 2 through 8. Plasma lysozyme activity peaked on day 5 (P<0.001) and IGF-I levels significantly decreased on days 2 through 14 (P<0.0001). TLR expression patterns suggest that both TLR3 and TLR5 may play a role in host response to bacterial challenge. Plasma lysozyme activity also increased and circulating IGF-I decreased in response to the presence of the pathogen.

Reduction in Channel Catfish Hepatic Growth Hormone Receptor Expression in Response to Food Deprivation and Exogenous Cortisol

Domestic Animal Endocrinology. Nov, 2006  |  Pubmed ID: 16423501

The objective of this study was to assess the effects of food deprivation and exogenous cortisol administration on somatic growth of channel catfish, Ictalurus punctatus, and examine the resultant changes in circulating insulin-like growth factor-I (IGF-I) concentrations and growth hormone receptor (GHR) gene expression. Integral to this objective, we report the isolation, sequence, and characterization of channel catfish GHR. Sequence analysis and characterization results indicate sequence identity and tissue distribution similar to GHRs in other teleost fish and several functional characteristics conserved in known vertebrate GHRs. The effects of food deprivation and dietary exogenous cortisol administration were assessed as part of a 4-week study. Growth was significantly reduced after 4 weeks in cortisol-fed fish compared to fed-control fish, and fasting resulted in weight loss. At the end of the 4-week study, both IGF-I plasma concentrations and hepatic GHR mRNA abundance were significantly reduced in fasted and cortisol-fed catfish. Levels of hepatic GHR mRNA were positively correlated to circulating IGF-I levels. These results suggest that a reduction in hepatic GHR gene expression might serve as a mechanism for the reduction of circulating IGF-I and growth in channel catfish during periods of food deprivation and stress.

Subclavian Artery Transposition and Bypass Techniques for Use with Endoluminal Repair of Acute and Chronic Thoracic Aortic Pathology

Journal of Vascular Surgery. Feb, 2006  |  Pubmed ID: 16473175

The Malpractice Surcharge. A Simple Answer to Rising Malpractice Rates or a Greater Threat to Quality Patient Care?

The Journal of Legal Medicine. Mar, 2006  |  Pubmed ID: 16510367

Utility of Left Subclavian Artery Revascularization in Association with Endoluminal Repair of Acute and Chronic Thoracic Aortic Pathology

Journal of Vascular Surgery. Mar, 2006  |  Pubmed ID: 16520151

A rapidly increasing number of thoracic aortic lesions are now treated by endoluminal exclusion by using stent grafts. Many of these lesions abut the great vessels and limit the length of the proximal landing zone. Various methods have been used to address this issue. We report our experience with subclavian artery revascularization in association with endoluminal repair of acute and chronic thoracic aortic pathology.

Aortic Arch Vessel Stenting: a Single-center Experience Using Cerebral Protection

Archives of Surgery (Chicago, Ill. : 1960). Jun, 2006  |  Pubmed ID: 16785356

Endovascular interventions have revolutionized the contemporary treatment of peripheral vascular occlusive disease. Traditional management of supra-aortic trunk disease has employed surgical extra-anatomic bypass via a cervical approach or median sternotomy. Endoluminal therapy may be a less morbid alternative.

The Effect of Temperature, Stress, and Cortisol on Plasma IGF-I and IGFBPs in Sunshine Bass

General and Comparative Endocrinology. Dec, 2006  |  Pubmed ID: 16854418

The mechanisms through which stress and cortisol regulate insulin like growth factor-I (IGF-I) and insulin like growth factor binding proteins (IGFBPs) were studied in sunshine bass, by measuring plasma IGF-I and IGFBPs in fish maintained at 5, 10, 15, 20, 25, or 30 degrees C, fish subjected to an acute 15 min confinement stress at 25 and 30 degrees C, and fish fed 100 mg cortisol/kg feed. Plasma IGF-I concentrations were higher at 25 and 30 degrees C than at 20 degrees C and below. A 15 min confinement stress resulted in a decrease in IGF-I 2h post-confinement. Plasma concentrations of IGFBP with molecular weights of 24, 28, and 33 kDa were similar for fish acclimated to different temperatures, except for 5 degrees C where a 33-kDa IGFBP was significantly reduced. After a 15 min low-water stress at 25 degrees C, a 33-kDa IGFBP was reduced and IGFBPs with molecular weights of 24 and 28 kDa were increased at 2 and 6h, respectively. A 15 min low-water stress at 30 degrees C, resulted in no change in levels of a 33-kDa IGFBP over the 6-h recovery period. However, levels of a 24- and 28-kDa IGFBP were significantly increased at 2 and 6h, respectively. A single feeding with 100 mg cortisol/kg feed increased plasma cortisol but did affect plasma concentrations of IGF-I or any of the three IGFBPs. Acute stress appears to result in a decrease in IGF-I, but the mechanism of the decrease does not appear to be caused by cortisol released during the stress.

Endovascular Repair of Thoracic Aortic Tears

The Annals of Thoracic Surgery. Sep, 2006  |  Pubmed ID: 16928500

Standard treatment of traumatic thoracic aortic transection (TTAT) is open repair by left thoracotomy with or without the use of partial cardiopulmonary bypass. However, open repair is associated with high rates of morbidity and mortality, particularly in multiply injured trauma patients. We reviewed our experiences of endovascular repair of acute TTAT.

Stent-graft Treatment of Thoracoabdominal Aortic Aneurysms After Complete Visceral Debranching

Journal of Vascular and Interventional Radiology : JVIR. Sep, 2006  |  Pubmed ID: 16990473

Complex thoracoabdominal aortic aneurysm repair remains a difficult problem from both open and endoluminal approaches. The reduced morbidity and mortality rates reported to be associated with aortic stent-graft procedures makes this option more attractive, but it is hampered by the need for adequate proximal and distal seal zones. While branched and fenestrated aortic stent-grafts are being refined, an alternative is a two-stage surgical and endoluminal approach that is particularly useful for aneurysms involving the aortic visceral segment. The present report describes stent-graft repair in two patients after complete visceral artery revascularization or "debranching."

Human Microvascular Endothelial Synthesis of Interleukin-8 During in Vitro Ischemia and Reperfusion

Journal of Cellular Biochemistry. Feb, 2007  |  Pubmed ID: 16927373

These studies were undertaken to evaluate human microvascular endothelial cell (MEC) synthesis of interleukin-8 (IL-8), a potent neutrophil chemoattractant, under in vitro conditions of ischemia and reperfusion. IL-8 and other related CXC chemokines are believed to mediate tissue injury in a variety of pathologic conditions in humans. MEC grown on microcarrier beads were exposed to 3 or 6 h of in vitro ischemia followed by 2 h of reperfusion. Conditioned medium, MEC protein, and total RNA extracts were assayed for IL-8 using an ELISA. During ischemia alone, MEC increased intracellular, but not extracellular levels of IL-8 secretion. In contrast, reperfusion markedly stimulated both intracellular and extracellular IL-8 secretion. Neither 3 h of ischemia alone or followed by reperfusion altered steady-state levels of IL-8 mRNA when compared to pre-ischemic levels. In contrast, after 6 h of ischemia alone and ischemia followed by reperfusion, IL-8 mRNA was increased eight- and sixfold, respectively, when compared to pre-ischemic levels. These studies demonstrate an inverse relationship between the rate of IL-8 protein secretion and the steady-state levels of IL-8 mRNA during ischemia and reperfusion. During ischemia and reperfusion both the increase in cell-associated IL-8 protein and the release of IL-8 into the medium is dependent on de novo protein synthesis rather than the intracellular accumulation of IL-8. These experiments indicate that post-ischemic modulation of IL-8 release and synthesis following ischemia reperfusion will require strategies directed towards inhibition of IL-8 transcription and in depth knowledge of the mechanisms regulating IL-8 secretion.

Effects of GH on Immune and Endocrine Responses of Channel Catfish Challenged with Edwardsiella Ictaluri

Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology. Jan, 2007  |  Pubmed ID: 17030140

The effects of GH on immune and endocrine responses to channel catfish challenged with the bacterium Edwardsiella ictaluri were examined. Catfish (11.7+/-1.0 g) treated with recombinant bovine growth hormone (rbGH) and challenged with E. ictaluri experienced similar mortality as control-exposed fish. Plasma activity of lysozyme was higher (P<0.01) in rbGH-exposed fish. Compared to day 0 controls (non-exposed fish), IGF-I levels decreased (P<0.05) in challenged fish while levels were similar (P>0.10) between treatments. Abundance of GH receptor (GHR) mRNA tended to decrease (P=0.055) in liver of challenged fish while toll like receptor 5 (TLR5) mRNA increased (P<0.05) in liver compared to d 0 controls. An increase in lysozyme may suggest GH enhances a nonspecific immune response. A decrease in GHR mRNA and plasma IGF-I suggests a downregulation of the somatotropic axis in response to disease. The increase in TLR5 mRNA suggests that TLR5 may play a role in host response to bacterial challenge. While exogenous rbGH may play a stimulatory role to increase lysozyme levels, there was no apparent effect of rbGH on mortality to E. ictaluri.

Five-year Report of a Multicenter Controlled Clinical Trial of Open Versus Endovascular Treatment of Abdominal Aortic Aneurysms

Journal of Vascular Surgery. May, 2007  |  Pubmed ID: 17398057

Compare long-term results of endovascular treatment and standard open repair of abdominal aortic aneurysms in a multicenter, concurrent-controlled trial.

Bare Metal Stent Infections: Case Report and Review of the Literature

Journal of Vascular Surgery. Oct, 2007  |  Pubmed ID: 17903662

Infection of bare metal stents in the vasculature is rare, but associated with significant morbidity and mortality. We report two cases of bare metal stent infections and review the literature regarding infected bare metal stents with respect to risk factors, pathophysiology, diagnosis, treatment, and prevention. Overall, this article highlights the need to have a high index of suspicion of bare metal stent infection, since prompt diagnosis and treatment can ultimately decrease the morbidity and mortality associated with this devastating problem.

Competitive Inhibition at the Glycine Site of the N-methyl-D-aspartate Receptor by the Anesthetics Xenon and Isoflurane: Evidence from Molecular Modeling and Electrophysiology

Anesthesiology. Nov, 2007  |  Pubmed ID: 18073551

Inhibition of N-methyl-D-aspartate (NMDA) receptors by anesthetic gases and vapors may play an important role in anesthesia and neuroprotection. However, the site of action of these agents on the NMDA receptor is unknown. The authors show that xenon and isoflurane compete for the binding of the coagonist glycine on the NMDA receptor NR1 subunit.

Bedside Vena Cava Filter Placement with Intravascular Ultrasound: a Simple, Accurate, Single Venous Access Method

Journal of Vascular Surgery. Dec, 2007  |  Pubmed ID: 18155009

Two techniques of vena cava filter placement with intravascular ultrasound (IVUS) guidance have been described previously. Placement with real-time IVUS imaging requires two venous access sites, one for the filter delivery system and one for the IVUS catheter, which makes the procedure more invasive. Alternatively, a single-access technique of IVUS imaging of the vena cava requires measuring the distance from the access site to the desired location for filter placement and then delivering the filter to that distance blindly, risking filter misplacement. We describe in this article a single puncture technique that allows for real-time imaging to position the filter delivery sheath using IVUS and reduces the uncertainty of the blind positioning of the filter delivery system.

Differences in Mortality, Growth, Lysozyme, and Toll-like Receptor Gene Expression Among Genetic Groups of Catfish Exposed to Virulent Edwardsiella Ictaluri

Fish & Shellfish Immunology. Jan, 2008  |  Pubmed ID: 18023209

Survivorship to ESC (enteric septicemia of catfish) varies among and within strains of commercially raised catfish, however the immunological basis for differences in susceptibility is not well-understood. We assessed the effect of pathogen challenge with Edwardsiella ictaluri on five genetic groups of catfish by measuring both phenotypic response (mortality, pathogen levels, specific growth rate), and three measures of immune response, including lysozyme activity and mRNA expression of two toll-like receptors (TLR3 and TLR5). Both mortality and pathogen loads, in addition to non-specific immune response, consistently ranged from the least susceptible Blue catfish (24%, 3.4 x 10(2)+/-9.3 x 10(1)cell-equivalents/mg, 13.2+/-3.2U/mL tissue, respectively) to the most susceptible 103 channel catfish (65%, 1.1x10(4)+/-6.4 x 10(3)cell-equivalents/mg tissue, 67.3+/-28.7U/mL, respectively). Similarly, specific growth rate was reduced in exposed fish, compared to non-exposed controls, only in the most susceptible genetic groups (P=0.0051). Trends in mRNA expression levels were apparent in each tissue type for both genes. In kidney, differences were evident in expression of both TLR3 and TLR5 mRNA between strains early and late in challenge (P<0.01). TLR5 mRNA showed significant downregulation in all strains on days 1 and 4 (P=0.0001). In spleen, all strains had elevated levels of TLR3 (P=0.0050) and TLR5 mRNA (P<0.0001) only 1day post-exposure. In stomach, only one strain (103 x RR) showed upregulation (P=0.0063) throughout challenge. The relationship of phenotypic (mortality and growth) and immune responses measured here, suggests that variation in susceptibility to ESC is a function of differences in innate immune response. Understanding these differences will be crucial for enhancing the immune system through selective breeding and in developing disease management protocols for channel catfish.

Internal Endoconduit: an Innovative Technique to Address Unfavorable Iliac Artery Anatomy Encountered During Thoracic Endovascular Aortic Repair

Journal of Vascular Surgery. Feb, 2008  |  Pubmed ID: 18241768

Various strategies have been used to combat arterial access limitations encountered during thoracic endovascular aortic repair (TEVAR). Most require retroperitoneal dissection or aggressive angioplasty techniques that can lead to devastating complications. We describe a novel technique using an "internal endoconduit." Deployment of an iliac stent graft across the prohibitively stenotic area, followed by angioplasty and controlled rupture of the iliac artery, allows for safe passage of the delivery sheath. Adverse events associated with decreased pelvic perfusion or hemorrhage from iliac artery rupture are theoretically possible but have not been observed. Faced with unfavorable iliac anatomy, we use internal endoconduits rather than retroperitoneal access procedures and believe their use will increase the number of procedures that will be able to be performed through femoral access and substantially reduce the frequency of access-related complications.

Locally Administered Ketorolac and Bupivacaine for Control of Postoperative Pain in Breast Augmentation Patients: Part II. 10-day Follow-up

Plastic and Reconstructive Surgery. Feb, 2008  |  Pubmed ID: 18300985

Previously, it was shown that locally applied intraoperative ketorolac and bupivacaine significantly reduced pain in the recovery room. The objective of this study was to test the effectiveness of the same solution over the first 10 days.

Embolic Protection in Infrainguinal Interventions

Perspectives in Vascular Surgery and Endovascular Therapy. Mar, 2008  |  Pubmed ID: 18388018

The benefits of the use of embolic protection devices (EPDs) in saphenous vein coronary artery bypass grafts and carotid arteries have been shown, but the utility of their application during infrainguinal endovascular interventions is somewhat unclear. Patients with specific anatomical features or lesion characteristics, or patients undergoing specific types of endovascular interventions may benefit from the off-label use of EPDs, but this has yet to be determined. This report will examine the current literature related to the use of EPDs in infrainguinal endovascular interventions and attempt to identify the patients who would most likely benefit from their use. In addition, the setting in which EPDs have been used at one institution is briefly described. This discussion will serve as a general guideline for the use of EPDs and act as an impetus for the development of future clinical trials to help elucidate the patients who will truly benefit from EPDs use when undergoing lower extremity endovascular revascularization procedures.

Creative Options for Large Sheath Access During Aortic Endografting

Journal of Vascular and Interventional Radiology : JVIR. Jun, 2008  |  Pubmed ID: 18502383

Access-related limitations, namely small-caliber vessels and tortuous or calcified stenotic vessels, are often encountered during endovascular aneurysm repair (EVAR) and thoracic EVAR (TEVAR). Overcoming these limitations often requires the creation of a conduit through which the endovascular devices can be delivered. If these limitations are not recognized and respected preoperatively, significant morbidity and mortality may ensue because access-related complications are often addressed in emergent and chaotic situations. There are a variety of conduits described in the literature, each with their own advantages and disadvantages. The present report explores the use of conduits during EVAR and TEVAR by discussing the current literature, and the authors also describe a preferred method to address unfavorable iliac anatomy through the use of endoconduits.

Association of Cocaine- and Amphetamine-regulated Transcript (CART) Messenger RNA Level, Food Intake, and Growth in Channel Catfish

Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology. Oct, 2008  |  Pubmed ID: 18644459

Cocaine-and Amphetamine-Regulated Transcript (CART) is a potent hypothalamic anorectic peptide in mammals and fish. We hypothesized that increased food intake is associated with changes in expression of CART mRNA within the brain of channel catfish. Objectives were to clone the CART gene, examine tissue CART mRNA distribution, and changes in the amount of CART mRNA in relation to changes in food intake in channel catfish. Our results showed that channel catfish CART was highly similar to those of other fish species, particularly in the biologically active portion of the peptide. Expression of CART mRNA was detected in the brain and testis but not in other somatic tissues. Thirty days of fasting decreased (P<0.05) the amount of CART mRNA within the brain of channel catfish, while refeeding for 15 days restored its amount to a level similar to the fed control. In a separate 7 week feeding study, CART mRNA expression was lower in fish that consumed more food and gained more weight (P<0.05). These results suggest that CART is involved in regulation of food intake in channel catfish, similarly as it has been reported in other fish and mammals.

Stability of Reference Genes for Real-time PCR Analyses in Channel Catfish (Ictalurus Punctatus) Tissues Under Varying Physiological Conditions

Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology. Nov, 2008  |  Pubmed ID: 18692590

Real-time PCR is a highly sensitive, relatively easy to perform assay for quantifying mRNA abundance. However, there are several complexities built into the assay that can affect data interpretation. Most notably, the selection of an appropriate internal control for normalization is essential for expression data interpretation. In this study we investigated the suitability of seven commonly used genes [18S ribosomal RNA (18S), alpha tubulin (TUBA), beta actin (ACTB), beta-2 microglobulin (B2M), embryonic elongation factor-1 alpha (EEF1A), glyceraldehyde phosphate dehydrogenase (GAPDH), and RNA polymerase II polypeptide B (POLR2B)] as potential quantitative references for normalizing real-time PCR data generated in the study of channel catfish physiology. Gene expression and stability were evaluated among 15 channel catfish tissues and within physiologically-relevant tissues in response to experimental manipulation (i.e. LHRH injection, fasting, and acute stress). Expression of the seven candidate reference genes varied across all tissue types tested, indicating that none of the genes could suitably serve as reference genes for cross tissue comparisons. Experimentally altering the physiological state of the fish differentially affected expression of the various reference genes depending on experimental design and tissue type, with 18S unaffected by the experimental treatment in all tissues examined. For example, the selection of a differentially expressed gene, GAPDH, as opposed to 18S, to normalize hepatic growth hormone receptor during fasting resulted in misinterpretation of the data. These results reveal the importance of providing comprehensive details of reference gene validation when publishing real-time PCR results, with this manuscript serving as a basic guideline for reference gene selection in channel catfish research.

Tips and Tricks for Avoiding Access Problems when Using Large Sheath Endografts

Journal of Vascular Surgery. Feb, 2009  |  Pubmed ID: 19216972

Commentary on "femoral Arterial Access Management for Endovascular Aortic Aneurysm Repair: Evolution and Outcome"

Perspectives in Vascular Surgery and Endovascular Therapy. Mar, 2009  |  Pubmed ID: 19380390

Efficient Synthesis of Trisubstituted Pyrazoles and Isoxazoles Using a Traceless "catch and Release" Solid-phase Strategy

Journal of Combinatorial Chemistry. Jul-Aug, 2009  |  Pubmed ID: 19459688

An efficient three-component, two-step "catch and release" solid-phase synthesis of 3,4,5-trisubstituted pyrazoles and isoxazoles has been developed. The first step involves a base-promoted condensation of a 2-sulfonyl- or a 2-carbonyl-acetonitrile derivative (1 or 7) with an isothiocyanate 2 and in situ immobilization of the resulting thiolate anion on Merrifield resin. Reaction of the resin-bound sulfonyl intermediate 4 with hydrazine or hydroxylamine, followed by release from the resin and intramolecular cyclization, affords 3,5-diamino-4-(arylsulfonyl)-1H-pyrazoles 5 or isoxazoles 6, respectively. Reaction of the resin-bound carbonyl intermediate 9 with hydrazine, on the other hand, leads to 3-(arylamino)-5-aryl-1H-pyrazole-4-carbonitriles 10.

Validation of a Whole-body Cortisol Extraction Procedure for Channel Catfish (Ictalurus Punctatus) Fry

Fish Physiology and Biochemistry. Sep, 2010  |  Pubmed ID: 19680767

We validated a whole-body cortisol extraction technique for channel catfish, Ictalurus punctatus, fry. Three volume enhancement methods were tested: CAL method (zero calibrator A diluent added to lipid extract), PBS method (phosphate buffered saline added to lipid extract), and VO method (food grade vegetable oil added to lipid extract). The volume enhancement extracts were evaluated using a commercial radioimmunoassay kit. Sensitivity, accuracy, precision, reproducibility, and parallelism could not be determined for the PBS method as cortisol levels were not detected in any of the extracted samples. Intra-assay coefficient of variation (CV) for the CAL and VO methods were 7.3 and 8.3%, respectively, while inter-assay CV were 9.6 and 10.6%, respectively. Based on the sensitivity, accuracy, precision, reproducibility, and parallelism results, we conclude that the CAL method is the most appropriate method for volume enhancement of catfish fry lipid extract. Using the CAL method to detect cortisol in catfish fry, fish were stressed daily for 2 weeks. Fry weights were similar throughout the study while whole-body cortisol levels were higher (P < 0.01) in stressed fish after 1 day of stress. These data show the CAL method can effectively measure whole-body cortisol in catfish fry.

Characterization of Gene-activated Human Acid-beta-glucosidase: Crystal Structure, Glycan Composition, and Internalization into Macrophages

Glycobiology. Jan, 2010  |  Pubmed ID: 19741058

Gaucher disease, the most common lysosomal storage disease, can be treated with enzyme replacement therapy (ERT), in which defective acid-beta-glucosidase (GlcCerase) is supplemented by a recombinant, active enzyme. The X-ray structures of recombinant GlcCerase produced in Chinese hamster ovary cells (imiglucerase, Cerezyme) and in transgenic carrot cells (prGCD) have been previously solved. We now describe the structure and characteristics of a novel form of GlcCerase under investigation for the treatment of Gaucher disease, Gene-Activated human GlcCerase (velaglucerase alfa). In contrast to imiglucerase and prGCD, velaglucerase alfa contains the native human enzyme sequence. All three GlcCerases consist of three domains, with the active site located in domain III. The distances between the carboxylic oxygens of the catalytic residues, E340 and E235, are consistent with distances proposed for acid-base hydrolysis. Kinetic parameters (K(m) and V(max)) of velaglucerase alfa and imiglucerase, as well as their specific activities, are similar. However, analysis of glycosylation patterns shows that velaglucerase alfa displays distinctly different structures from imiglucerase and prGCD. The predominant glycan on velaglucerase alfa is a high-mannose type, with nine mannose units, while imiglucerase contains a chitobiose tri-mannosyl core glycan with fucosylation. These differences in glycosylation affect cellular internalization; the rate of velaglucerase alfa internalization into human macrophages is at least 2-fold greater than that of imiglucerase.

A Granulomatous Mass Surrounding a Maverick Total Disc Replacement Causing Iliac Vein Occlusion and Spinal Stenosis: a Case Report

The Journal of Bone and Joint Surgery. American Volume. May, 2010  |  Pubmed ID: 20439671

Conduits and Endoconduits, Percutaneous Access

Journal of Vascular Surgery. Oct, 2010  |  Pubmed ID: 20709484

Design of an Orally Efficacious Hydroxyethylamine (HEA) BACE-1 Inhibitor in a Preclinical Animal Model

Bioorganic & Medicinal Chemistry Letters. Nov, 2010  |  Pubmed ID: 20833041

In this Letter, we describe our efforts to design HEA BACE-1 inhibitors that are highly permeable coupled with negligible levels of permeability-glycoprotein activity. These efforts culminate in producing 16 which lowers Αβ by 28% and 32% in the cortex and CSF, respectively, in the preclinical wild type Hartley guinea pig animal model when dosed orally at 30mpk BID for 2.5days.

KneePR--Substantial Injuries Caused by Unorthodox Resuscitation Technique

The American Journal of Forensic Medicine and Pathology. Sep, 2011  |  Pubmed ID: 20177364

We report a case of cardiopulmonary resuscitation involving chest compressions performed with the rescuer's knee. The substantial injuries caused by this unorthodox technique could have been mistaken for the cause of death were it not for careful scene investigation and documentation.

Design and Synthesis of a Novel, Orally Active, Brain Penetrant, Tri-substituted Thiophene Based JNK Inhibitor

Bioorganic & Medicinal Chemistry Letters. Mar, 2011  |  Pubmed ID: 21316234

The SAR of a series of tri-substituted thiophene JNK3 inhibitors is described. By optimizing both the N-aryl acetamide region of the inhibitor and the 4-position of the thiophene we obtained single digit nanomolar compounds, such as 47, which demonstrated an in vivo effect on JNK activity when dosed orally in our kainic acid mouse model as measured by phospho-c-jun reduction.

Discovery, Optimization, and Pharmacological Characterization of Novel Heteroaroylphenylureas Antagonists of C-C Chemokine Ligand 2 Function

Journal of Medicinal Chemistry. Mar, 2011  |  Pubmed ID: 21341682

Through the application of TRAP (target-related affinity profiling), we identified a novel class of heteroaroylphenylureas that inhibit human CCL2-induced chemotaxis of monocytes/macrophages both in vitro and in vivo. This inhibition was concentration-dependent and selective with regard to other chemokines. The compounds, however, did not antagonize the binding of (125)I-labeled CCL2 to the CCR2 receptor nor did they block CCR2-mediated signal transduction responses such as calcium mobilization. Optimization of early leads for potency and pharmacokinetic parameters resulted in the identification of 17, a potent inhibitor of chemotaxis (IC(50) = 80 nM) with excellent oral bioavailability in rats (F = 60%). Compound 17 reduced swelling and joint destruction in two rat models of rheumatoid arthritis and delayed disease onset and produced near complete resolution of symptoms in a mouse model of multiple sclerosis.

Ophthalmoplegic Migraine

Headache. Jul-Aug, 2011  |  Pubmed ID: 21649657

Expression of Leptin-like Peptide (LLP) MRNA in Channel Catfish (Ictalurus Punctatus) is Induced by Exposure to Edwardsiella Ictaluri but is Independent of Energy Status

General and Comparative Endocrinology. Sep, 2011  |  Pubmed ID: 21741381

Leptin is a key pleiotropic cytokine involved in regulation of energy homeostasis and immunity in mammals. In channel catfish, the presence of a partial messenger RNA sequence that encodes a leptin-like peptide (LLP) has been identified and investigated. The objectives of the present studies were to clone and characterize full-length catfish LLP gene, examine tissue expression of LLP mRNA, and determine effects of prolonged fasting and exposure to Edwardsiella ictaluri (E. ictaluri), the bacteria that causes enteric septicemia in catfish, on LLP mRNA expression. Full-length catfish LLP gene was sequenced by genome walking and by 5'- and 3'-RACE. Catfish LLP gene contained three exons with the coding region located in exons 2 and 3. The amino acid sequence of the channel catfish LLP shared very low sequence similarities with leptin of other fish species or the mammalian leptin (24-49%). Using real-time polymerase chain reaction, LLP mRNA expression was detected in various tissues including brain, stomach, spleen, heart, liver, and trunk kidney and was especially high in the liver and trunk kidney. Expression of LLP mRNA in liver and brain was similar between fish that were fasted for 30days and those that received feed daily for 30days (P>0.10). Expression of LLP mRNA was increased in liver, spleen, and trunk kidney within 48h post-exposure to E. ictaluri compared to unexposed fish (P<0.05). Based on the results of the current studies, amino acid sequence of catfish LLP is highly dissimilar to mammalian and fish leptin. Unlike in most mammals, catfish LLP expression is independent of energy status. However, the expression of catfish LLP is increased after exposure to pathogenic bacteria, which is similar to mammals. Further investigations are required to clearly define the biological function and regulation of catfish LLP.

Design and Synthesis of Brain Penetrant Selective JNK Inhibitors with Improved Pharmacokinetic Properties for the Prevention of Neurodegeneration

Bioorganic & Medicinal Chemistry Letters. Sep, 2011  |  Pubmed ID: 21813278

The SAR of a series of brain penetrant, trisubstituted thiophene based JNK inhibitors with improved pharmacokinetic properties is described. These compounds were designed based on information derived from metabolite identification studies which led to compounds such as 42 with lower clearance, greater brain exposure and longer half life compared to earlier analogs.

Two Cases of Firearm Grip Impressions on the Hands of Suicide Victims

The American Journal of Forensic Medicine and Pathology. Mar, 2012  |  Pubmed ID: 20661121

Many factors are used to help distinguish firearm suicides from homicides and accidents, including range of fire, location of entrance defects, wound path trajectory, backspatter (blowback), and gunshot residue. Specifically, authors have discussed examination of the hands for backspatter, gunshot residue, cylinder gap effects, iron staining, and trauma as means of supporting a person having held a firearm while committing suicide. Here, we discuss 2 cases where suicidal gunshot wounds were accompanied by unique firearm grip impressions on the hands of the decedents. In 1 case, a "negative"[ impression of a grip pattern was left in a decedent's hand and in another case a grip pattern was left on the decedent's hand in dried blood. Such impressions can be used to provide support for establishing suicide as the manner of death.

Pre- and Postprandial Changes in Orexigenic and Anorexigenic Factors in Channel Catfish (Ictalurus Punctatus)

General and Comparative Endocrinology. Apr, 2012  |  Pubmed ID: 22366470

Ghrelin (GRLN), cocaine and amphetamine regulated transcript (CART), neuropeptide Y (NPY), and cholecystokinin (CCK) are neuropeptides involved in the regulation of appetite and feeding in vertebrates. We examined pre- and postprandial changes in the expression of plasma GHRL and mRNAs encoding GRLN, CART, NPY, and CCK in channel catfish. Fish were entrained to eat at 0900 h for 2 weeks. Fish were then sampled at 0700, 0800, and 0900 h. Remaining fish were either offered feed at 0900 h (Fed) or fasted (Unfed). Fish sampling continued at 0.5, 1, 2, and 4 h post feeding. Feeding increased abundance of whole brain CART mRNA out to 4 h with no effect observed in unfed fish. Whole brain NPY expression peaked at 0.5 h in both treatments. NPY expression then declined in fed fish but remained elevated in unfed fish. No differences in plasma or stomach GRLN expression were observed. Two separate cDNAs for CCK were identified. Brain CCKa and CCKb expression increased after feeding. These results suggest CART, NPY, and CCK play roles in the regulation of channel catfish feeding. Taken together, these results provide new insights into the neural and gastroenteric mechanisms regulating appetite in channel catfish.

Genetic Variation in Feed Consumption, Growth, Nutrient Utilization Efficiency and Mitochondrial Function Within a Farmed Population of Channel Catfish (Ictalurus Punctatus)

Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology. Oct, 2012  |  Pubmed ID: 22691874

We evaluated the effects of diets (32/4 or 36/6 percent protein/fat) and six channel catfish families for growth performance characteristics. Two families with fast- (C) and slow- (D) growth rate and with low and high feed efficiency (FE) were selected for analyses of mitochondrial complex enzymatic activities (I, II, III, and IV) and gene expression (ND1, CYTB, COX1, COX2, ATP6) levels in liver, muscle, and intestine. There were significant differences in growth rate and nutrient retention among the families. Mitochondrial enzymatic complex activities (I-V) in the tissues were all lower in family C. Four of the five genes were down-regulated in the liver and up-regulated in the muscle for the fast growing family C. There were significant differences between diets for some mitochondrial respiratory chain enzyme activities and gene expression levels. Significant diet×family interactions were observed for some enzyme activities and gene expression levels. Changes in mitochondrial respiratory chain enzyme activities and gene expression levels provide insight into the cellular mechanisms of fish with differences in growth rate and feed efficiency. Results also suggest that genotype×diet interactions should be accounted for when considering strategies for using mitochondrial function as a criteria in channel catfish selection programs for improved growth performance characteristics.

Spleen Index and Mannose-binding Lectin Levels in Four Channel Catfish Families Exhibiting Different Susceptibilities to Flavobacterium Columnare and Edwardsiella Ictaluri

Journal of Aquatic Animal Health. Sep, 2012  |  Pubmed ID: 22870893

Edwardsiella ictaluri and Flavobacterium columnare are two bacterial pathogens that affect channel catfish Ictalurus punctatus aquaculture. At the Catfish Genetics Research Unit (U.S. Department of Agriculture, Agricultural Research Service), some progress has been made in selectively breeding for resistance to E. ictaluri; however, the susceptibility of these families to F. columnare is not known. Our objectives were to obtain baseline information on the susceptibility of channel catfish families (maintained as part of the selective breeding program) to E. ictaluri and F. columnare and to determine whether the spleen index and plasma levels of mannose-binding lectin (MBL) are predictive indicators of susceptibility to these pathogens. Four channel catfish families were used: family A was randomly chosen from spawns of fish that were not selectively bred for resistance; families B, C, and D were obtained after selection for resistance to E. ictaluri. All four families were immersion challenged with both bacterial pathogens; the spleen index and plasma MBL levels of unchallenged fish from each family were determined. Mean cumulative percent mortality (CPM) after E. ictaluri challenge ranged from 4% to 33% among families. Families A and B were more susceptible to F. columnare (mean CPM of three independent challenges = 95% and 93%) than families C and D (45% and 48%), demonstrating that there is genetic variation in resistance to F. columnare. Spleen index values and MBL levels were not significantly different, indicating that these metrics are not predictive indicators of F. columnare or E. ictaluri susceptibility in the four tested families. Interestingly, the two families that exhibited the highest CPM after F. columnare challenges had the lowest CPM after E. ictaluri challenge. Further research on larger numbers of families is needed to determine whether there is any genetic correlation between resistance to E. ictaluri and resistance to F. columnare.

Short-term Outcomes of the C3 Excluder for Patients with Abdominal Aortic Aneurysms and Unfavorable Proximal Aortic Seal Zones

Annals of Vascular Surgery. Jan, 2013  |  Pubmed ID: 22981019

Endovascular abdominal aortic aneurysm repair (EVAR) in patients with unfavorable proximal seal zones remains challenging. The purpose of this study was to identify the incidence of proximal extension cuff usage for type I endoleaks in patients with abdominal aortic aneurysms and unfavorable necks treated with the C3 Excluder repositionable endoprosthesis compared with the traditional Excluder stent-graft.

Endovascular Repair of a Para-anastomotic Pseudoaneurysm After Renal Autotransplantation: an Alternative to Open Reconstruction

Annals of Vascular Surgery. Jan, 2013  |  Pubmed ID: 23079504

Renal artery anastomotic pseudoaneurysms are rare after renal transplantation. The etiology tends to be technical, infectious, or degenerative, and repair is difficult with a high postsurgical complication rate. We report the first case of a complex autotransplant renal artery pseudoaneurysm repaired with kissing covered stents. A 52-year-old woman presented with severe left lower quadrant abdominal pain 6 years after a renal autotransplant for ureteral stenosis and recurrent pyelonephritis. A computed tomographic angiography (CTA) scan revealed a bilobed aneurysm arising at the anastomosis between the renal and common iliac arteries. Kissing covered stents were placed within the common iliac artery proximally and extending into the transplant renal artery and external iliac artery. Postdeployment angiography confirmed complete exclusion of the pseudoaneurysm and excellent flow into the transplant kidney and left lower extremity. A follow-up CTA scan at 1 month revealed continued stent-graft patency and complete exclusion of the pseudoaneurysm. An endovascular approach to transplant anastomotic pseduoaneurysms using kissing covered stents is a viable option to exclude aneurysmal changes and preserve flow to the transplanted organ in carefully selected patients.

Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007): Metabolically Stable γ-secretase Inhibitors That Selectively Inhibit the Production of Amyloid-β over Notch

Journal of Medicinal Chemistry. Jul, 2013  |  Pubmed ID: 23713656

Herein, we describe our strategy to design metabolically stable γ-secretase inhibitors which are selective for inhibition of Aβ generation over Notch. We highlight our synthetic strategy to incorporate diversity and chirality. Compounds 30 (ELND006) and 34 (ELND007) both entered human clinical trials. The in vitro and in vivo characteristics for these two compounds are described. A comparison of inhibition of Aβ generation in vivo between 30, 34, Semagacestat 41, Begacestat 42, and Avagacestat 43 in mice is made. 30 lowered Aβ in the CSF of healthy human volunteers.

Basal Polarization of the Mucosal Compartment in Flavobacterium Columnare Susceptible and Resistant Channel Catfish (Ictalurus Punctatus)

Molecular Immunology. Dec, 2013  |  Pubmed ID: 23895942

The freshwater bacterial pathogen, Flavobacterium columnare, infects a variety of ornamental and farmed fish species worldwide through mucosal attachment points on the gill and skin. While previous studies have demonstrated a chemotactic response of F. columnare to fish mucus, little is known about how host gill mucosal molecular and cellular constituents may impact rates of adhesion, tissue invasion, and ultimately, mortality. Here, we describe the use of RNA-seq to profile gill expression differences between channel catfish (Ictalurus punctatus) differing in their susceptibility to F. columnare both basally (before infection) and at three early timepoints post-infection (1 h, 2 h, and 8 h). After sequencing and de novo assembly of over 350 million 100 base-pair transcript reads, between group comparisons revealed 1714 unique genes differentially expressed greater than 1.5-fold at one or more timepoints. In the large dataset, we focused our analysis on basal differential expression between resistant and susceptible catfish as these genes could potentially reveal genetic and/or environmental factors linked with differential rates of infection. A number of critical innate immune components including iNOS2b, lysozyme C, IL-8, and TNF-alpha were constitutively higher in resistant catfish gill, while susceptible fish showed high expression levels of secreted mucin forms, a rhamnose-binding lectin previously linked to susceptibility, and mucosal immune factors such as CD103 and IL-17. Taken together, the immune and mucin profiles obtained by RNA-seq suggest a basal polarization in the gill mucosa, with susceptible fish possessing a putative mucosecretory, toleragenic phenotype which may predispose them to F. columnare infection.

Oxidation of Primary and Secondary Benzylic Alcohols with Hydrogen Peroxide and Tert-butyl Hydroperoxide Catalyzed by a "helmet" Phthalocyaninato Iron Complex in the Absence of Added Organic Solvent

Dalton Transactions (Cambridge, England : 2003). Dec, 2014  |  Pubmed ID: 25351994

The oxidation of four benzylic alcohols employing hydrogen peroxide and TBHP as oxidants, catalyzed by an iron(III) complex bearing a 14,28-[1,3-diiminoisoindolinato]phthalocyaninato (diiPc) ligand has been studied and found to proceed with good selectivity, high turnover numbers, and high turnover frequencies in the absence of organic solvents other than the substrates themselves.

Effects of a Phytogenic Feed Additive on Growth Performance, Susceptibility of Channel Catfish to Edwardsiella Ictaluri and Levels of Mannose Binding Lectin

Fish & Shellfish Immunology. May, 2015  |  Pubmed ID: 25659231

A study was conducted to investigate the effect of a phytogenic feed additive (Digestarom® P.E.P. MGE; containing the essential oils carvacrol, thymol, anethol, and limonene) on growth performance and disease susceptibility to Edwardsiella ictaluri. Two hundred and fifty juvenile channel catfish, Ictalurus punctatus (7.2 ± 0.1 g) were allotted into the following treatments: Control (floating diet) and EO (floating diet supplemented with essential oils). The fish were fed their respective diets for 6 weeks. At the end of the study, all fish were exposed to virulent E. ictaluri by bath immersion (1.9 × 10(7) cfu/mL; final concentration). Plasma and tissue samples were taken to quantify protein and mRNA expression levels of mannose binding lectin (MBL). Weight gain and food conversion ratio were similar between treatments. After exposing fish to virulent E. ictaluri and monitoring mortality for 21 days, survival was 43% higher (69.5 vs 48.4%) in fish fed EO compared to fish not treated with EO (P < 0.05). One day after challenge, plasma MBL levels were down-regulated in the non-treated fish compared to non-challenged fish. In the EO fish, MBL levels were similar to non-challenged fish but significantly higher than non-treated fed fish (P < 0.001). By d 7, plasma MBL levels increased in non-treated fed fish to levels observed in the EO and non-challenged fish. On d 14, MBL mRNA levels were upregulated 15-fold in fish fed EO compared to non-treated fed fish and non-challenged fish (P < 0.001). The results demonstrate that essential oils improved survival of channel catfish challenged with E. ictaluri. Mechanisms through which essential oils improve survival may involve MBL.

Injuries to Post Mortem Human Surrogates in Oblique Aircraft Seat Environment

Biomedical Sciences Instrumentation. 2015  |  Pubmed ID: 25996749

Increased interest in the airline industry to enhance occupant comfort and maximize seating density has prompted the design and installation of obliquely mounted seats in aircraft. The potential for injury and their mechanism in this seating environment is unknown. Epidemiology-based field injury data do not exist for airplane crashes, however, typical impact scenarios have been determined and safety standards addressing fore, aft, and side-facing seats have been levied by the FAA. The impact scenarios defined in these standards can be used to study likely injuries and injury mechanisms using Post Mortem Human Surrogates (PMHS) in a controlled laboratory environment. Four PMHS were seated upright with Frankfurt plane horizontal in a custom designed seat configured to simulate potential aircraft environments and candidate restraint geometries. A scaled Part 25.562 Emergency Landing condition for horizontal impact was used as the dynamic test input. High speed video recorded occupant kinematics. Pre and posttest x-rays and CT’s were obtained and autopsies were conducted. Severe injuries to the cervical, thoracic, and lumbar spine were observed in three of the four specimens and attributed to torso flail. Pelvis injuries likely caused by the seat belt were found in two tests. Multiple rib fractures were also seen, caused by contact with arm rest or other body regions. The fourth test was run at a lower severity and did not produce injury. This suggests a conservative threshold for human tolerance to this loading environment. Although the study is of a limited sample size, it suggests the need for further testing to develop standards that provide similar levels of safety for obliquely mounted seats as forward/aft facing seats in aircraft.

Identification of Differentially Abundant Proteins of Edwardsiella Ictaluri During Iron Restriction

PloS One. 2015  |  Pubmed ID: 26168192

Edwardsiella ictaluri is a Gram-negative facultative anaerobe intracellular bacterium that causes enteric septicemia in channel catfish. Iron is an essential inorganic nutrient of bacteria and is crucial for bacterial invasion. Reduced availability of iron by the host may cause significant stress for bacterial pathogens and is considered a signal that leads to significant alteration in virulence gene expression. However, the precise effect of iron-restriction on E. ictaluri protein abundance is unknown. The purpose of this study was to identify differentially abundant proteins of E. ictaluri during in vitro iron-restricted conditions. We applied two-dimensional difference in gel electrophoresis (2D-DIGE) for determining differentially abundant proteins and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF/TOF MS) for protein identification. Gene ontology and pathway-based functional modeling of differentially abundant proteins was also conducted. A total of 50 unique differentially abundant proteins at a minimum of 2-fold (p ≤ 0.05) difference in abundance due to iron-restriction were detected. The numbers of up- and down-regulated proteins were 37 and 13, respectively. We noted several proteins, including EsrB, LamB, MalM, MalE, FdaA, and TonB-dependent heme/hemoglobin receptor family proteins responded to iron restriction in E. ictaluri.

Water Solubility of Selected C9-C18 Alkanes Using a Slow-stir Technique: Comparison to Structure - Property Models

Chemosphere. May, 2016  |  Pubmed ID: 26924078

Aqueous solubility is a fundamental physical-chemical substance property that strongly influences the distribution, fate and effects of chemicals upon release into the environment. Experimental water solubility was determined for 18 selected C9-C18 normal, branched and cyclic alkanes. A slow-stir technique was applied to obviate emulsion formation, which historically has resulted in significant overestimation of the aqueous solubility of such hydrophobic liquid compounds. Sensitive GC-MS based methods coupled with contemporary sample extraction techniques were employed to enable reproducible analysis of low parts-per billion aqueous concentrations. Water solubility measurements for most of the compounds investigated, are reported for the first time expanding available data for branched and cyclic alkanes. Measured water solubilities spanned four orders of magnitude ranging from 0.3 μg/L to 250 μg/L. Good agreement was observed for selected alkanes tested in this work and reported in earlier literature demonstrating the robustness of the slow-stir water solubility technique. Comparisons of measured alkane water solubilities were also made with those predicted by commonly used quantitative structure-property relationship models (e.g. SPARC, EPIWIN, ACD/Labs). Correlations are also presented between alkane measured water solubilities and molecular size parameters (e.g. molar volume, solvent accessible molar volume) affirming a mechanistic description of empirical aqueous solubility results and prediction previously reported for a more limited set of alkanes.

Ontogenetic Characterization of the Intestinal Microbiota of Channel Catfish Through 16S RRNA Gene Sequencing Reveals Insights on Temporal Shifts and the Influence of Environmental Microbes

PloS One. 2016  |  Pubmed ID: 27846300

Aquaculture recently overtook capture fisheries as the largest producer of food fish, but to continue increasing fish production the industry is in search of better methods of improving fish health and growth. Pre- and probiotic supplementation has gained attention as a means of solving these issues, however, for such approaches to be successful, we must first gain a more holistic understanding of the factors influencing the microbial communities present in the intestines of fish. In this study, we characterize the bacterial communities associated with the digestive tract of a highly valuable U.S. aquaculture species, channel catfish Ictalurus punctatus, over the first 193 days of life to evaluate temporal changes that may occur throughout ontogenetic development of the host. Intestinal microbiota were surveyed with high-throughput DNA sequencing of 16S rRNA V4 gene amplicons derived from fish at 3, 65, 125, and 193 days post hatch (dph), while also characterizing the environmental microbes derived from the water supply and the administered diets. Microbial communities inhabiting the intestines of catfish early in life were dynamic, with significant shifts occurring up to 125 dph when the microbiota somewhat stabilized, as shifts were less apparent between 125 to 193 dph. Bacterial phyla present in the gut of catfish throughout ontogeny include Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria; with the species Cetobacterium somerae and Plesiomonas shigelloides showing the highest abundance in the catfish microbiota after 3 dph. Comparisons of the gut microbiota to the environmental microbes reveals that the fish gut is maintained as a niche habitat, separate from the overall microbial communities present in diets and water-supply. Although, there is also evidence that the environmental microbiota serves as an inoculum to the fish gut. Our results have implications for future research related to channel catfish biology and culture, and increase our understanding of ontogenetic effects on the microbiota of teleost fish.

Responses and Injuries to PMHS in Side-Facing and Oblique Seats in Horizontal Longitudinal Sled Tests Per FAA Emergency Landing Conditions

Stapp Car Crash Journal. Nov, 2016  |  Pubmed ID: 27871096

The objective of the present exploratory study is to understand occupant responses in oblique and side-facing seats in the aviation environment, which are increasingly installed in modern aircrafts. Sled tests were conducted using intact Post Mortem Human Surrogates (PMHS) seated in custom seats approximating standard aircraft geometry. End conditions were selected to represent candidate aviation seat and restraint configurations. Three-dimensional head center-of-gravity linear accelerations, head angular velocities, and linear accelerations of the T1, T6, and T12 spinous processes, and sacrum were obtained. Three-dimensional kinematics relative to the seat were obtained from retroreflective targets attached to the head, T1, T6, T12, and sacrum. All specimens sustained spinal injuries, although variations existed by vertebral level. While the tension mechanism was associated with cervical spine injuries, complex distraction-coupled with bending and tension was attributed to thoracolumbar spine injuries. Skeletal fractures to the ribcage were attributed to compression induced by the restraint from the seatbelt, the presence of the armrest, and/or severe motions of the unconstrained torso. Pelvic injuries were also attributed to restraint offered by the lap belt on the accelerating torso-pelvis complex in the absence of the armrest. Lower extremity injuries occurred due to the unconstrained motion (flailing mechanism). These results serve as an initial dataset to understand the kinematics of different body regions, injuries and patterns, and potential injury mechanisms describing PMHS responses in the aviation environment.

High-content Screening of Clinically Tested Anticancer Drugs Identifies Novel Inhibitors of Human MRP1 (ABCC1)

Pharmacological Research. Feb, 2017  |  Pubmed ID: 28258008

Multidrug resistance protein 1 (MRP1/ABCC1), an integral transmembrane efflux transporter, belongs to the ATP-binding cassette (ABC) protein superfamily. MRP1 governs the absorption and disposition of a wide variety of endogenous and xenobiotic substrates including various drugs across organs and physiological barriers. Additionally, its overexpression has been implicated in multidrug resistance in chemotherapy of multiple cancers. Here, we describe the development of a high content imaging-based screening assay for MRP1 activity. This live cell-based automated microscopy assay is very robust and allows simultaneous detection of cell permeable, non-toxic and potent inhibitors. The validity of the assay was demonstrated by profiling a library of 386 anti-cancer compounds, which are under clinical trials, for interactions with MRP1. The assay identified 12 potent inhibitors including two known MRP1 inhibitors, cyclosporine A and rapamycin. On the other hand, MRP1-inhibitory activity of tipifarnib, AZD1208, deforolimus, everolimus, temsirolimus, HS-173, YM201636, ESI-09, TAK-733, and CX-6258 has not been previously reported. Inhibition of MRP1 activity was further validated using flow cytometry and confocal microscopy for the respective detection of calcein and doxorubicin in MRP1-overexpressing cells. Among the identified compounds, tipifarnib, AZD1208, rapamycin, deforolimus, everolimus, TAK-733, and temsirolimus resensitized MRP1-overexpressing H69AR cells towards vincristine, a cytotoxic chemotherapeutic agent, by 2-6-fold. Using purified HEK293 membrane vesicles overexpressing MRP1, MRP2, MRP3, and MRP4, we also demonstrated that the identified compounds exert differential and selective response on the uptake of estradiol glucuronide, an endogenous MRP substrate. In summary, we demonstrated the effectiveness of the high content imaging-based high-throughput assay for profiling compound interaction with MRP1.

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