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Find video protocols related to scientific articles indexed in Pubmed.
Anatomic characteristics of bileaflet mitral valve prolapse--Barlow disease--in patients undergoing mitral valve repair.
Ital J Anat Embryol
PUBLISHED: 10-28-2014
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Barlow disease is a still challenging pathology for the surgeon. Aim of the present study is to report anatomic abnormalities of mitral valve in patients undergoing mitral valve repair.
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Successful Treatment of Refractory Seizures With Rufinamide in Children With Schizencephaly: Report of 3 Cases.
J. Child Neurol.
PUBLISHED: 07-24-2014
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Schizencephaly is an uncommon malformation of cortical development. Patients with schizencephaly present with a broad range of severe neurologic symptoms including pharmacoresistant epilepsy. Rufinamide is a new antiepileptic drug approved for use as adjunctive therapy of seizures associated with Lennox-Gastaut syndrome and it is also effective for refractory partial seizures. We report 3 cases of pediatric patients aged 7.2, 8.1, and 10.1 years, respectively, with intractable epilepsy associated with bilateral open-lip schizencephaly and septo-optic dysplasia. The follow-up ranged from 3.8 to 4.1 years. In our patients, the introduction of rufinamide as adjunctive drug led to a dramatic decline in the number of seizures and an improvement in EEG epileptic activity without side effects. Rufinamide seems to be efficacious and safe in patients with epileptic encephalopathies associated with pharmacoresistant epilepsy; further and larger clinical reports and controlled studies could confirm the usefulness of this anticonvulsant drug.
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Synergic effects of ultrasound and laser on the pain relief in women with hand osteoarthritis.
Lasers Med Sci
PUBLISHED: 06-08-2014
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Patients with pain avoid movements, leading to a gradual impairment of their physical condition and functionality. In this context, the use of ultrasound (US) and low-level laser therapy (LLLT) show promising results for nonpharmacological and noninvasive treatment. The aim of this study was evaluated the synergistic effects of the US and the LLLT (new prototype) with or without therapeutic exercises (TE) on pain and grip strength in women with hand osteoarthritis. Forty-five women with hand osteoarthritis, aged 60 to 80 years, were randomly assigned to one of three groups, but 43 women successfully completed the full study. The three groups were as follows: (i) the placebo group which did not perform TE, but the prototype without emitting electromagnetic or mechanical waves was applied (n?=?11); (ii) the US + LLLT group which carried out only the prototype (n?=?13); and (iii) the TE + US + LLLT group which performed TE before the prototype is applied (n?=?13). The parameters of US were frequency 1 MHz; 1.0 W/cm(2) intensity, pulsed mode 1:1 (duty cycle 50 %). Regarding laser, the output power of the each laser was fixed at 100 mW leading to an energy value of 18 J per laser. Five points were irradiated per hand, during 3 min per point and 15 min per session. The prototype was applied after therapeutic exercises. The treatments are done once a week for 3 months. Grip strength and pressure pain thresholds (PPT) were measured. Grip strength did not differ significantly for any of the groups (p???0.05). The average PPT between baseline and 3 months shows significant decrease of the pain sensitivity for both the US + LLLT group (??=?30?±?19 N, p?0.001) and the TE + US + LLLT group (??=?32?±?13 N, p?
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Activation of Bax in three models of retinitis pigmentosa.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 05-15-2014
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The process of photoreceptor cell death in retinitis pigmentosa is still not well characterized, and identification of common mechanisms will be instrumental for development of therapeutic strategies. Here we investigated activation of Bax in rd1, P23H transgenic, and Rho knockout retinas.
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Spray dried amikacin powder for inhalation in cystic fibrosis patients: a quality by design approach for product construction.
Int J Pharm
PUBLISHED: 05-14-2014
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An amikacin product for convenient and compliant inhalation in cystic fibrosis patients was constructed by spray-drying in order to produce powders of pure drug having high respirability and flowability. An experimental design was applied as a statistical tool for the characterization of amikacin spray drying process, through the establishment of mathematical relationships between six Critical Quality Attributes (CQAs) of the finished product and five Critical Process Parameters (CPPs). The surface-active excipient, PEG-32 stearate, studied for particle engineering, in general did not benefit the CQAs of the spray dried powders for inhalation. The spray drying feed solution required the inclusion of 10% (v/v) ethanol in order to reach the desired aerodynamic performance of powders. All desirable function solutions indicated that the favourable concentration of amikacin in the feed solution had to be kept at 1% w/v level. It was found that when the feed rate of the sprayed solution was raised, an increase in the drying temperature to the maximum value (160 °C) was required to maintain good powder respirability. Finally, the increase in drying temperature always led to an evident increase in emitted dose (ED) without affecting the desirable fine particle dose (FPD) values. The application of the experimental design enabled us to obtain amikacin powders with both ED and FPD, well above the regulatory and scientific references. The finished product contained only the active ingredient, which keeps low the mass to inhale for dose requirement.
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Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication.
Nat Commun
PUBLISHED: 01-27-2014
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The ability of PRC1 and PRC2 to promote proliferation is a main feature that links polycomb (PcG) activity to cancer. PcGs silence the expression of the tumour suppressor locus Ink4a/Arf, whose products positively regulate pRb and p53 functions. Enhanced PcG activity is a frequent feature of human tumours, and PcG inhibition has been proposed as a strategy for cancer treatment. However, the recurrent inactivation of pRb/p53 responses in human cancers raises a question regarding the ability of PcG proteins to affect cellular proliferation independently from this checkpoint. Here we demonstrate that PRCs regulate cellular proliferation and transformation independently of the Ink4a/Arf-pRb-p53 pathway. We provide evidence that PRCs localize at replication forks, and that loss of their function directly affects the progression and symmetry of DNA replication forks. Thus, we have identified a novel activity by which PcGs can regulate cell proliferation independently of major cell cycle restriction checkpoints.
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Early classification of childhood focal idiopathic epilepsies: is it possible at the first seizure?
Eur. J. Paediatr. Neurol.
PUBLISHED: 01-09-2014
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To evaluate the possibility of early syndrome classification of idiopathic partial epilepsies in children at the first seizure.
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Optimization of mucosal responses after intramuscular immunization with integrase defective lentiviral vector.
PLoS ONE
PUBLISHED: 01-01-2014
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Many infectious agents infiltrate the host at the mucosal surfaces and then spread systemically. This implies that an ideal vaccine should induce protective immune responses both at systemic and mucosal sites to counteract invasive mucosal pathogens. We evaluated the in vivo systemic and mucosal antigen-specific immune response induced in mice by intramuscular administration of an integrase defective lentiviral vector (IDLV) carrying the ovalbumin (OVA) transgene as a model antigen (IDLV-OVA), either alone or in combination with sublingual adjuvanted OVA protein. Mice immunized intramuscularly with OVA and adjuvant were compared with IDLV-OVA immunization. Mice sublingually immunized only with OVA and adjuvant were used as a positive control of mucosal responses. A single intramuscular dose of IDLV-OVA induced functional antigen-specific CD8+ T cell responses in spleen, draining and distal lymph nodes and, importantly, in the lamina propria of the large intestine. These results were similar to those obtained in a prime-boost regimen including one IDLV immunization and two mucosal boosts with adjuvanted OVA or vice versa. Remarkably, only in groups vaccinated with IDLV-OVA, either alone or in prime-boost regimens, the mucosal CD8+ T cell response persisted up to several months from immunization. Importantly, following IDLV-OVA immunization, the mucosal boost with protein greatly increased the plasma IgG response and induced mucosal antigen-specific IgA in saliva and vaginal washes. Overall, intramuscular administration of IDLV followed by protein boosts using the sublingual route induced strong, persistent and complementary systemic and mucosal immune responses, and represents an appealing prime-boost strategy for immunization including IDLV as a delivery system.
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Aberrant Proliferation of Differentiating Alveolar Cells Induces Hyperplasia in Resting Mammary Glands of SV40-TAg Transgenic Mice.
Front Oncol
PUBLISHED: 01-01-2014
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WAP-T1 transgenic mice express SV40-TAg under control of the whey acidic protein (WAP) promoter, which directs activity of this strong viral oncogene to luminal cells of the mammary gland. Resting uniparous WAP-T1 glands develop hyperplasia composed of TAg positive cells prior to appearance of advanced tumor stages. We show that cells in hyperplasia display markers of alveolar differentiation, suggesting that TAg targets differentiating cells of the alveolar compartment. The glands show significant expression of Elf5 and milk genes (Lalba, Csn2, and Wap). TAg expressing cells largely co-stain with antibodies to Elf5, lack the epithelial marker Sca1, and are hormone receptor negative. High expression levels of Elf5 but not of milk genes are also seen in resting glands of normal BALB/c mice. This indicates that expression of Elf5 in resting WAP-T1 glands is not specifically induced by TAg. CK6a positive luminal cells lack TAg. These cells co-express the markers prominin-1, CK6a, and Sca1, and are positive for hormone receptors. These hormone sensitive cells localize to ducts and seem not to be targeted by TAg. Despite reaching an advanced stage in alveolar differentiation, the cells in hyperplasia do not exit the cell cycle. Thus, expression of TAg in conjunction with regular morphogenetic processes of alveologenesis seem to provide the basis for a hormone independent, unscheduled proliferation of differentiating cells in resting glands of WAP-T1 transgenic mice, leading to the formation of hyperplastic lesions.
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A multidisciplinary approach to study the effects of balneotherapy and mud-bath therapy treatments on fibromyalgia.
Clin. Exp. Rheumatol.
PUBLISHED: 11-18-2013
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To study the effects of both balneotherapy and mud-bath therapy treatments in patients affected by primary fibromyalgia (FM) using rheumatological, psychiatric, biochemical and proteomic approaches.
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Adiponectin inhibits neutrophil apoptosis via activation of AMP kinase, PKB and ERK 1/2 MAP kinase.
Apoptosis
PUBLISHED: 08-29-2013
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Neutrophils are abundant, short-lived leukocytes that play a key role in the immune defense against microbial infections. These cells die by apoptosis following activation and uptake of microbes and will also enter apoptosis spontaneously at the end of their lifespan if they do not encounter a pathogen. Adiponectin exerts anti-inflammatory effects on neutrophil antimicrobial functions, but whether this abundant adipokine influences neutrophil apoptosis is unknown. Here we report that adiponectin in the physiological range (1-10 ?g/ml) reduced apoptosis in resting neutrophils, decreasing caspase-3 cleavage and maintaining Mcl-1 expression by stabilizing this anti-apoptotic protein. We show that adiponectin induced phosphorylation of AMP-activated kinase (AMPK), protein kinase B (PKB), extracellular signal-regulated kinase (ERK 1/2) and p38 mitogen activated protein kinase (MAPK). Pharmacological inhibition of AMPK, PKB and ERK 1/2 ablated the pro-survival effects of adiponectin and treatment of neutrophils with an AMPK specific activator (AICAR) and AMPK inhibitor (compound C) respectively decreased and increased apoptosis. Finally, activation of AMPK by AICAR or adiponectin also decreased ceramide accumulation in the neutrophil cell membrane, a process involved in the early stages of spontaneous apoptosis, giving another possible mechanism downstream of AMPK activation for the inhibition of neutrophil apoptosis.
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The influence of psychiatric comorbidity on sexual satisfaction in fibromyalgia patients.
Clin. Exp. Rheumatol.
PUBLISHED: 05-29-2013
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To investigate the influence of psychiatric comorbidity on sexual satisfaction in premenopausal and postmenopausal female affected by fibro-myalgia (FM).
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Pure insulin highly respirable powders for inhalation.
Eur J Pharm Sci
PUBLISHED: 04-17-2013
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The aim of the present research was to investigate the possibility to obtain by spray drying an insulin pulmonary powder respirable and stable at room temperature without the use of excipients. Several insulin spray-dried powders were prepared with or without the addition of excipients (mannitol, bovine serum albumin, aspartic acid) from water dispersions or from acidic aqueous solutions. Each formulation was characterized using laser diffraction, scanning electron microscopy and in vitro aerosol performance with a Turbospin DPI device. Stability was assessed by the quantification of impurities with a molecular mass greater than that of insulin (HMWP) and related proteins (A21+ORP). Insulin powders prepared without excipients from an acid solution showed a shrivelled, raisin-like shape of non-aggregated microparticles and a high respirability (FPF>65%). The optimal result with respect to respirability and stability was reached when the pH of the insulin acetic acid solution to spray dry was adjusted at pH 3.6 with ammonium hydroxide. The median volume diameter of the obtained powder was 4.04 ?m, insulin content 95%, emitted dose of 89.5%, MMAD 1.79 ?m and fine particle fraction of 83.6%. This powder was stable at room temperature over a period of eighteen months with respect to the content of A21+ORP. As far as the HMWP content was concerned, the powder complied with the specification limits for a period of five months. The insulin acetic powder opens up the possibility of a more effective pulmonary therapy less dependent on refrigerated storage.
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Eslicarbazepine acetate: An update on efficacy and safety in epilepsy.
Epilepsy Res.
PUBLISHED: 04-11-2013
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Epilepsy is a common neurological disorder. Despite a broad range of commonly used antiepileptic drugs, approximately 30% of patients with epilepsy have drug resistance or encounter significant adverse effects. Eslicarbazepine acetate is a new central nervous system-active compound with anticonvulsant activity whose mechanism of action is by blocking the voltage-gated sodium channel. Eslicarbazepine acetate was approved by the European Medicines Agency and launched onto the European market in 2009 for adjunctive treatment in adult subjects of partial-onset seizures, with or without secondary generalization. This article provides an overview on the recent studies on eslicarbazepine acetate in the treatment of drug-resistant partial epilepsy. Efficacy and safety of this drug for partial-onset seizures were assessed in four randomized clinical trials with responder rates ranged between 17% and 43%. Adverse events were usually mild to moderate in intensity and the most common were dizziness, somnolence, nausea, diplopia, headache, vomiting, abnormal coordination, blurred vision, vertigo and fatigue. Eslicarbazepine acetate is not recommended below 18 years, but a published phase II trial had the main goal to evaluate the pharmacokinetics, efficacy and safety of this drug in pediatric population. Eslicarbazepine acetate appears to be a safe and effective drug with a linear pharmacokinetics, very low potential for drug-drug interactions and therefore it can offer a valid alternative to current antiepileptic drugs. Additionally, it is undergoing investigation for monotherapy in subjects with partial epilepsy, and other neurological and psychiatric disorders.
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Innovative technologies for oral drug delivery.
Curr Drug Deliv
PUBLISHED: 03-14-2013
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Oral dosage forms have always been considered the preferred route of delivery, due to lower unit dose cost and improved patient compliance. The great increase in the duration and quality of human life was made possible by the availability of effective and well tolerated drugs, able to deal adequately with serious and widespread diseases. Now, the pharmaceutical challenge is shifted to drugs and preparations more specifically and focused on the needs of patient or groups of patients. Personalization of medicines or formulations can occur on the basis of dose adjustment, drug combination or different delivery kinetics. Innovative drug delivery systems have the potential to make treatments safer and more effective, or more convenient or acceptable to patients. Drug delivery systems are complex formulations in which the elements can concur to determine the delivery rate and kinetics. This paper is focused on the description of two technologies, such as powder agglomeration and module assembling, as approaches to obtain personalized dosage forms, dosing flexibility and/or combination products, as a function of patients needs and his therapeutic treatment.
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Complex product composition generates risks for generic substitution also with dosage forms for intravenous administration.
Int J Pharm
PUBLISHED: 02-08-2013
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Teicoplanin is an antibiotic made by fermentation in which a glycopeptide core is substituted by different fatty acids. The chemical structure and proportion of the various components are strictly dependent on the production process (Actinoplanes sp. strain, cell culture conditions and downstream process). Thus, a relevant variability can be introduced from different manufacturers. Interchangeability or substitution among the originator and the generic products of teicoplanin for injection is under debate with respect to pharmaceutical similarity. In fact, depending on the manufacturer, the six major components of teicoplanin show different quantitative distributions compared to that of the originator. The European Pharmacopoeia fixed an undifferentiated upper limit for the component content. A statistical approach is required for comparing complex products. In this paper the use of principal component analysis (PCA) as a tool for identifying the pharmaceutical equivalence among teicoplanin products from different sources was explored. The results obtained show that PCA can distinguish the differing origin of this biological drug.
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Lecithin/chitosan controlled release nanopreparations of tamoxifen citrate: loading, enzyme-trigger release and cell uptake.
J Control Release
PUBLISHED: 02-01-2013
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Tamoxifen citrate (TAM), an anticancer drug with amphiphilic properties, was loaded in lecithin/chitosan nanoparticles (LCN) with a view to oral administration. The influence of tamoxifen loading on the physico-chemical properties of nanoparticles was studied. Size, surface charge and morphological properties of tamoxifen-loaded nanoparticles (LCN-TAM) were assessed. The increase in the tamoxifen amount in the LCN-TAM preparation up to 60 mg/100 ml maintained the positive zeta potential value of about +45 mV. A statistically significant decrease in particle size was observed for TAM amounts between 5 and 20mg. A strong influence of loaded tamoxifen on the structure of lecithin/chitosan nanoparticles was observed, supported by the quantification of free chitosan and morphological analysis. A loading of tamoxifen in nanoparticles of around 19% was obtained. The release of the drug from the LCN-TAM colloidal dispersion was measured, showing that tamoxifen citrate was released very slowly in simulated gastro-intestinal fluids without enzymes. When enzymes able to dismantle the nanoparticle structure were added to the dissolution medium, drug release was triggered and continued in a prolonged manner. Tamoxifen-loaded nanoparticles showed cytotoxicity towards MCF-7 cells comparable to that obtained with tamoxifen citrate solution, but the rate of this toxic effect was dependent on drug release. Caco-2 cells, used as a model of the intestinal epithelium, were shown to take up the TAM loaded nanoparticles extensively.
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Blood pressure control and treatment adherence in hypertensive patients with metabolic syndrome: protocol of a randomized controlled study based on home blood pressure telemonitoring vs. conventional management and assessment of psychological determinants
Trials
PUBLISHED: 01-23-2013
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Inadequate blood pressure control and poor adherence to treatment remain among the major limitations in the management of hypertensive patients, particularly of those at high risk of cardiovascular events. Preliminary evidence suggests that home blood pressure telemonitoring (HBPT) might help increasing the chance of achieving blood pressure targets and improve patients therapeutic adherence. However, all these potential advantages of HBPT have not yet been fully investigated.
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Agglomerated oral dosage forms of artemisinin/?-cyclodextrin spray-dried primary microparticles showing increased dissolution rate and bioavailability.
AAPS PharmSciTech
PUBLISHED: 01-03-2013
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Artemisinin, a poorly water-soluble antimalarial drug, presents a low and erratic bioavailability upon oral administration. The aim of this work was to study an agglomerated powder dosage form for oral administration of artemisinin based on the artemisinin/?-cyclodextrin primary microparticles. These primary microparticles were prepared by spray-drying a water-methanol solution of artemisinin/?-cyclodextrin. ?-Cyclodextrin in spray-dried microparticles increased artemisinin water apparent solubility approximately sixfold. The thermal analysis evidenced a reduction in the enthalpy value associated with drug melting, due to the decrease in drug crystallinity. The latter was also evidenced by powder X-ray diffraction analysis, while (13)C-NMR analysis indicated the partial complexation with ?-cyclodextrin. Agglomerates obtained by sieve vibration of spray-dried artemisinin/?-cyclodextrin primary microparticles exhibited free flowing and close packing properties compared with the non-flowing microparticulate powder. The in vitro dissolution rate determination of artemisinin from the agglomerates showed that in 10 min about 70% of drug was released from the agglomerates, whereas less than 10% of artemisinin was dissolved from raw material powder. Oral administration of agglomerates in rats yielded higher artemisinin plasma levels compared to those of pure drug. In the case of the agglomerated powder, a 3.2-fold increase in drug fraction absorbed was obtained.
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Adiponectin inhibits neutrophil phagocytosis of Escherichia coli by inhibition of PKB and ERK 1/2 MAPK signalling and Mac-1 activation.
PLoS ONE
PUBLISHED: 01-01-2013
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Full length adiponectin is a potent immune modulatory adipokine, impacting upon the actions of several immune cells. Neutrophil oxidative burst has been shown to decrease in response to adiponectin, and we speculated that it could have other effects on neutrophil function. Here we report that adiponectin reduces the phagocytic ability of human neutrophils, decreasing significantly the ingestion of opsonised E. coli by these cells in whole blood (p<0.05) and as isolated neutrophils (p<0.05). We then determined the mechanisms involved. We observed that the activation of Mac-1, the receptor engaged in complement-mediated phagocytosis, was decreased by adiponectin in response to E. coli stimulation. Moreover, treatment of neutrophils with adiponectin prior to incubation with E. coli significantly inhibited signalling through the PI3K/PKB and ERK 1/2 pathways, with a parallel reduction of F-actin content. Studies with pharmacological inhibitors showed that inhibition of PI3K/PKB, but not ERK 1/2 signalling was able to prevent the activation of Mac-1. In conclusion, we propose that adiponectin negatively affects neutrophil phagocytosis, reducing the uptake of E. coli and inhibiting Mac-1 activation, the latter by blockade of the PI3K/PKB signal pathway.
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Layered lipid microcapsules for mesalazine delayed-release in children.
Int J Pharm
PUBLISHED: 07-22-2011
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The goal was to make available a delayed-release dosage form of mesalazine to be dispersed in water to facilitate swallowing in adults and children. Mesalazine microparticles containing carnauba wax were prepared by spray-congealing technique. A second step of spray-congealing of carnauba microparticles dispersed in liquefied stearic acid gave rise to mesalazine lipid microcapsules in which several carnauba microparticles remained embedded as cores in a reservoir structure. In order to favor their water dispersion, the lipid microcapsules were dry coated by tumbling them with different ratios of mannitol/lecithin microparticles prepared by spray-drying. Release rate measurements showed a delayed-release behavior, in particular a pH-dependence with less than 10% of drug released in acidic medium and complete release in phosphate buffer pH 7.4 in 4-5h. The layering with hydrophilic excipient microparticles allowed manufacturing of a pH-dependent dosage form suitable for extemporaneous oral use in adults and children.
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Integrase-defective lentiviral-vector-based vaccine: a new vector for induction of T cell immunity.
Expert Opin Biol Ther
PUBLISHED: 03-25-2011
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The development of new strategies for the induction of potent and broad immune responses is of high priority in the vaccine field. In this setting, integrase-defective lentiviral vectors (IDLV) represent a new and promising delivery system for immunization purposes.
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Surgical treatment in active infective endocarditis: results of a four-year experience.
ISRN Cardiol
PUBLISHED: 02-13-2011
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Background. Aim of present investigation was to analyze survival and recurrence rate in patients with active endocarditis referred to our centre for surgical treatment. Methods. 80 consecutive patients with active infective endocarditis (52 males, 28 females, mean age 59.2 years) were referred to our institution for surgical treatment. 78 patients underwent surgery, and 2 patients died before intervention. Results. Fifty patients had native valve endocarditis, 30 prosthetic valve involvement. Hospital mortality has been 10.2%. Three discharged patients (4.9%) died at an average 18-month followup. Endocarditis recurred in 4 (2 being S. aureus prosthetic tricuspid endocarditis in drug addicts). All patients who underwent valve repair or homograft implant were alive and free of recurrence. Conclusions. Our results suggest that with proper surgical treatment patients with active endocarditis discharged alive from hospital have a survival >90% at 18 months with a low recurrence rate.
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Structural surface changes and inflammatory responses against alginate-based microcapsules after exposure to human peritoneal fluid.
J Biomed Mater Res A
PUBLISHED: 02-09-2011
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Microencapsulation of cells is a promising approach to prevent rejection in the absence of immunosuppression. Clinical application, however, is hampered by insufficient insight in factors influencing biocompatibility of the capsules in humans. In the present study we exposed alginate-based capsules prepared of different types of alginate to human peritoneal fluid. Subsequently we studied the physicochemical changes of the capsules surface by applying micro-Fourier Transform Infrared Spectroscopy. We did test alginate-beads and alginate-poly-L-lysine capsules prepared of different types of alginate. In all tested capsule formulations we found adsorption of components from human peritoneal fluid and clear physicochemical changes of the surface. These changes were alginate-dependent. The adsorption had no significant effects on the permselective properties of the capsule but we found a strong increase of TNF? production by human peripheral blood mononuclear cells when exposed to alginate-beads treated with human peritoneal fluid. This elevated responsiveness was not observed with alginate-PLL capsules. The results show that alginate-based capsule surfaces always undergo physicochemical changes of the surface when exposed to human peritoneal fluid. This adsorption may lead to enhancement of the inflammatory responses against the microcapsules. Our result implicate that biocompatibility measurements should not only been done with freshly prepared capsules but also with capsules that have been exposed to fluid from the implantation site in order to predict the in vivo responses.
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Aromatase and 5-alpha reductase gene expression: modulation by pain and morphine treatment in male rats.
Mol Pain
PUBLISHED: 07-12-2010
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The steroid hormone testosterone has been found to be greatly reduced by opioids in different experimental and clinical conditions. The purpose of this study on male rats was to determine the effects of a single injection of morphine (5 mg/Kg) on persistent pain (formalin test) and the single or combined effects on p450-aromatase and 5-alpha reductase type 1 mRNA expression in the brain, liver and testis. Testosterone was determined in the plasma and in the brain, morphine was assayed in the plasma.
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Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination.
Vasc Health Risk Manag
PUBLISHED: 06-26-2010
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The renin-angiotensin-aldosterone system (RAAS), an important regulator of blood pressure and mediator of hypertension-related complications, is a prime target for cardiovascular drug therapy. Angiotensin-converting enzyme inhibitors (ACEIs) were the first drugs to be used to block the RAAS. Angiotensin II receptor blockers (ARBs) have also been shown to be equally effective for treatment. Although these drugs are highly effective and are widely used in the management of hypertension, current treatment regimens with ACEIs and ARBs are unable to completely suppress the RAAS. Combinations of ACEIs and ARBs have been shown to be superior than to either agent alone for some, but certainly not all, composite cardiovascular and kidney outcomes, but dual RAAS blockade with the combination of an ACEI and an ARB is sometimes associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The recent introduction of the direct renin inhibitor, aliskiren, has made available new combination strategies to obtain a more complete blockade of the RAAS with fewer adverse events. Renin system blockade with aliskiren and another RAAS agent has been, and still is, the subject of many large-scale clinical trials and furthermore, is already available in some countries as a fixed combination.
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Atrial fibrillation after cardiac surgery: incidence, risk factors, and economic burden.
J. Cardiothorac. Vasc. Anesth.
PUBLISHED: 05-31-2010
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To evaluate the incidence of postoperative atrial fibrillation (POAF), the predisposing factors, the results of treatment before discharge, and the impact on duration and costs of hospitalization.
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A proposal of simple calculation (ERI calculator) to predict the early response to TNF-? blockers therapy in rheumatoid arthritis.
Rheumatol. Int.
PUBLISHED: 05-19-2010
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Increasing evidence has been accumulated for treating rheumatoid arthritis (RA) with TNF-? blocking agents. The formulation and definition of an early indicator of patients reactivity during therapy may be extremely simplified by a mathematical model of clinical response. We analyzed the most significant clinical and laboratory parameters of response of 35 homogeneous patients (30 women, 5 men mean age ± SD: 52.31 ± 12.30 years) treated with adalimumab 40 mg every 2 weeks associated with methotrexate (MTX) 10-15 mg/week and with a stable dosage of steroids for 30 weeks. The over time trend of the studied parameters showed a linear response, which has allowed the realization of a simple mathematical model. The formula derived from this mathematical model was then applied and therefore validated in a group of 121 patients previously treated with several anti-TNF-alpha agents for at least 6 months. We drafted a mathematical model (early response indicator, ERI) that, by using a simple calculation, allows us to identify a high percentage of responder patients after only 2 weeks of treatment. ERI identified a high percentage (88%) of patients responding after only 2 weeks, as was confirmed at weeks 30; the use of ERI calculation after 6 weeks increases the proportion of responding patients to 92% with a percentage of false negatives of only 12%. ERI could be a useful tool to early differentiate the responder from the non-responder patients.
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Effects of chronic atrial fibrillation on active and passive force generation in human atrial myofibrils.
Circ. Res.
PUBLISHED: 05-13-2010
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Chronic atrial fibrillation (cAF) is associated with atrial contractile dysfunction. Sarcomere remodeling may contribute to this contractile disorder.
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Role of valsartan, amlodipine and hydrochlorothiazide fixed combination in blood pressure control: an update.
Vasc Health Risk Manag
PUBLISHED: 04-13-2010
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The treatment of moderate or severe hypertension in most cases requires the contemporaneous use of multiple antihypertensive agents. The most available two-drug combinations have an agent that addresses renin secretion and another one that is statistically more effective in renin-independent hypertension. The practice of combining agents that counteract different mechanisms is the most likely explanation for the fact that most available two-drug combinations have an agent that addresses renin secretion (beta-blocker, angiotensin converting enzyme inhibitor, angiotensin II receptor blocker or direct renin inhibitor) and another one that is more effective in renin-independent hypertension (diuretic, dihydropyridine or non-dihydropyridine calcium channel blocker). Based on these considerations, addition of hydrochlorothiazide to the combination of an antagonist of the renin-angiotensin system with a calcium channel blocker would constitute a logical approach. Inclusion of a diuretic in the triple combination is based on the evidence that these agents are effective and cheap, enhance the effect of other antihypertensive agents, and add a specific effect to individuals with salt-sensitivity of blood pressure. The benefit of triple combination therapy with amlodipine, valsartan and hydrochlorothiazide over its dual component therapies has been demonstrated, and the use of a single pill will simplify therapy resulting in better blood pressure control.
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New pyrazolo-[3,4-d]-pyrimidine derivative Src kinase inhibitors lead to cell cycle arrest and tumor growth reduction of human medulloblastoma cells.
FASEB J.
PUBLISHED: 03-30-2010
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Medulloblastoma is the most common malignant brain tumor in children, and despite improvements in the overall survival rate, it still lacks an effective treatment. Src plays an important role in cancer, and recently high Src activity was documented in medulloblastoma. In this report, we examined the effects of novel pyrazolo-[3,4-d]-pyrimidine derivative Src inhibitors in medulloblastoma. By MTS assay, we showed that the pyrimidine derivatives indicated as S7, S29, and SI163 greatly reduce the growth rate of medulloblastoma cells by inhibiting Src phosphorylation, compared with HT22 non-neoplastic nerve cells. These compounds also halt cells in the G(2)/M phase, and this effect likely occurs through the regulation of cdc2 and CDC25C phosphorylation, as shown by Western blot. Moreover, the exposure to pyrimidine derivatives induces apoptosis, assayed by the supravital propidium iodide assay, through modulation of the apoptotic proteins Bax and Bcl2, and inhibits tumor growth in vivo in a mouse model. Notably, S7, S29, and SI163 show major inhibitory effects on medulloblastoma cell growth compared with the chemotherapeutic agents cisplatin and etoposide. In conclusion, our results suggest that S7, S29, and SI163 could be novel attractive candidates for the treatment of medulloblastoma or tumors characterized by high Src activity.
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Persistence of mucosal and systemic immune responses following sublingual immunization.
Vaccine
PUBLISHED: 03-16-2010
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The development of mucosal vaccines for prevention of infectious diseases caused by pathogens entering through the mucosal surfaces is an important and challenging objective. To this purpose, we evaluated the efficacy and durability of immune response induced by sublingual immunization with tetanus toxoid (TT) as an antigen in the presence of mucosal adjuvants, such as E. coli Heat-Labile enterotoxin (LT) or the mutant of LT lacking ADP ribosyltransferase activity (LTK63). Both serum anti-TT IgG and mucosal anti-TT IgA antibodies reached a peak after four immunizations and decreased over time, maintaining detectable titers up to 4 months after the last immunization. Similarly, antigen-specific antibody secreting cells in bone marrow and TT-specific CD4+ and CD8+ T cells in draining lymph nodes and spleen were present up to 4 months from the last immunization. Overall, LT-treated mice showed significantly higher responses compared to LTK63 immunized mice. The efficacy and persistence of the immune response induced by sublingual immunization with different adjuvants strongly suggest that this route represents an appealing and promising alternative to the other mucosal routes of vaccine delivery.
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Prevalence and clinical significance of acquired left coronary artery fistulas after surgical myectomy in patients with hypertrophic cardiomyopathy.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 01-14-2010
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The relevance of iatrogenic left coronary artery fistulas complicating surgical myectomy in patients with hypertrophic cardiomyopathy is not known. We prospectively defined the echocardiographic features, prevalence, and clinical significance of left coronary artery fistulas in 40 consecutive patients with hypertrophic cardiomyopathy undergoing extended septal myectomy.
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The left ventricular outflow in hypertrophic cardiomyopathy: from structure to function.
J Cardiovasc Transl Res
PUBLISHED: 09-24-2009
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Left ventricular outflow tract obstruction (LVOTO) is one of the defining features of hypertrophic cardiomyopathy (HCM) and one of the main determinants of prognosis. Although the importance of obstruction was recognized since the original description by Teare and Brock, its exact cause and methods for its relief are still being hotly debated. We believe that a rational approach to solving these issues depends on thorough understanding of the specific structure and functions of the left ventricular outflow tract (LVOT) in health and disease. There is now compelling evidence that the LVOT performs a series of vital sophisticated functions which are mediated by the design characteristics, structure, and biological properties of its component parts and that dysregulation of one or more of these functions results in obstruction and other abnormalities. We here review the integrated functions of the LVOT, its structural and functional relationships, with particular reference to its component parts (the major players) and their role in HCM. This knowledge is essential to evolve tailored restorative techniques for treating HCM.
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The many faces of hypertrophic cardiomyopathy: from developmental biology to clinical practice.
J Cardiovasc Transl Res
PUBLISHED: 09-03-2009
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Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, characterized by complex pathophysiology, heterogeneous morphology, and variable clinical manifestations over time. Besides cardiac hypertrophy, the HCM phenotype is characterized by a host of manifestations, including mitral valve and subvalvar abnormalities, subaortic and mid-ventricular left ventricular (LV) obstruction, microvascular dysfunction, myocardial fibrosis, disarray, atrial remodeling, myocardial bridging of epicardial coronary arteries, LV apical aneurysms, and autonomic nervous system abnormalities. Such heterogeneous phenotype still lacks a comprehensive explanation, which cannot be accounted solely by genetic heterogeneity, despite the large number of genes and mutations involved. It is likely that pre-natal and acquired features deriving from the primary genetic defect interact with the environment to produce the final result evident in each patient. Based on novel insights provided by cardiac developmental biology, a common lineage ancestry of several HCM manifestations might be traced back to the pluripotent epicardium-derived cells, which early during heart development differentiate into interstitial fibroblasts, coronary smooth muscle cells, and atrio-ventricular endocardial cushions as mesenchymal cells. To date, the different faces of HCM have not been sufficiently liked or explained. We here attempt to address these issues by describing the various components of the disease, their origin, interaction, and clinical significance.
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Olmesartan medoxomil: recent clinical and experimental acquisitions.
Expert Opin Drug Metab Toxicol
PUBLISHED: 08-20-2009
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Angiotensin II is a vasoactive hormone of the renin-angiotensin system and plays an important role in the pathophysiology of several organ damages. Angiotensin II receptor blockers have been shown to be effective in treating both hypertension and connected organ damages. It is well known that although the angiotensin II receptor blockers have structural and pharmacokinetic differences, few pharmacological differences separate them. One of these is the degree of binding to the angiotensin II receptor type 1 compared with the angiotensin II receptor type 2; olmesartan medoxomil exhibits more than a 12,500-fold greater affinity for the angiotensin II receptor type 1 receptor than for the angiotensin II receptor type 2, making it theoretically the second most potent agent. However, olmesartans excellent receptor interaction is based on the combination of several specific pharmacokinetic factors. Potential advantages of this drug include once-daily dosing, a very low incidence of significant adverse reactions and/or events and a well-tolerated side effect profile. Nowadays, we have a lot of information about the pharmacology, antihypertensive efficacy and safety of olmesartan medoxomil, to further extend many clinical studies are still continuing to evaluate the potential benefits of high dosages and/or combination of this molecule.
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Characterization of a polyurethane-based controlled release system for local delivery of chlorhexidine diacetate.
Eur J Pharm Biopharm
PUBLISHED: 07-10-2009
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Conventional formulations of chlorhexidine usually provide short-term efficiency, requiring repeated applications to maintain antibacterial activity. Therefore, appropriate release system of chlorhexidine controlling local drug delivery would reduce the number of applications and enhance patient compliance. The aim of this study was to develop a controlled release system based on medical polyurethane for the local delivery of chlorhexidine diacetate (CDA). CDA-loaded polyurethane films (CDA-Films) and CDA-loaded polyurethane sandwiches (CDA-Sandwiches) were obtained by casting and solvent evaporation. The physico-chemical aspects of CDA-loaded polyurethane systems were investigated, and the crystalline state of CDA in the polymeric system was highlighted. CDA-Films exhibited appropriate mechanical properties for further applications. Drug release was measured in two different media: (i) distilled water and (ii) physiological saline solution to mimic in vivo conditions. Drug release studies were performed up to 11days on CDA-Films and 29days for CDA-Sandwiches. Release of CDA depended on drug loading and the structure of the system. In particular, release of CDA from the sandwich system followed zero-order kinetic. The release rate was significantly lower in physiological solution. Antibacterial studies were carried out on CDA-Films against Staphylococcus aureus and Staphylococcus epidermidis showing 35days persisting antibacterial activity. In conclusion, the polyurethane-based system developed in this study is potentially useful as a local delivery system for CDA and could be used not only in surgery but also in dental and clinical applications.
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Pharmacokinetics evaluation of soft agglomerates for prompt delivery of enteric pantoprazole-loaded microparticles.
Eur J Pharm Biopharm
PUBLISHED: 04-22-2009
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Soft agglomerates containing pantoprazole-loaded microparticles were developed with the aim of prompt delivery of gastro-resistant particles. The objective was to evaluate the relative bioavailability in dogs after the oral administration of soft agglomerates. Gastro-resistant pantoprazole-loaded microparticles prepared by spray drying were mixed with mannitol/lecithin spray-dried powder and agglomerated by vibration. One single oral dose (40mg) was administered to dogs. Each dog received either a reference tablet or hard gelatin capsules containing the agglomerates. The plasma profiles were evaluated by non-compartmental and compartmental approaches, and the pharmacokinetic parameters were determined. The agglomerates presented 100% of drug particle loading and a production yield of 80.5%. The amount of drug absorbed after oral dosing was similar after reference or agglomerate administration, leading to a relative bioavailability of 108%. The absorption lag-time was significantly reduced after agglomerate administration (from 135.5+/-50.6 to 15.0+/-2.5min). The agglomerated gastro-resistant pantoprazole-loaded microparticles reduced time to peak plasma. The agglomerates were equivalent to the reference tablets in terms of extent but not in terms of rate of absorption, showing that this formulation is an alternative to single-unit oral dosing with enteric coating and with the advantage of reducing time to effect.
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Muscle modifications in fibromyalgic patients revealed by surface electromyography (SEMG) analysis.
BMC Musculoskelet Disord
PUBLISHED: 04-15-2009
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Several studies have been carried out in order to investigate surface electromyography (SEMG) response on fibromyalgic (FM) patients. Some studies failed to demonstrate differences between FM patients and healthy individuals while others found differences in SEMG parameters. Different muscular region have been analyzed in FM patients and heterogeneity is also produced because of the different ways in which the SEMG technique is used. The aims of this study were to evaluate muscle modifications by SEMG analysis in FM women with respect to a sample of healthy controls and to investigate the relationships between SEMG parameters and the clinical aspects of the disease.
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Osteopontin is associated with increased arterial stiffness in rheumatoid arthritis.
Mol. Med.
PUBLISHED: 04-10-2009
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Rheumatoid arthritis (RA) patients are characterized by increased arterial stiffness, an independent predictor of cardiovascular risk. It has been suggested that osteopontin (OPN), a cytokine involved in RA pathogenesis, might have vascular effects. To study a possible relationship between OPN and arterial stiffness, aortic pulse wave velocity (PWV) was measured by tonometry in 69 patients (41 with RA, 28 with systemic sclerosis [SSc]) and 18 healthy controls. Plasma OPN levels, oxidative stress markers, and endothelin 1 (ET-1) were assessed. OPN levels were significantly (P < 0.05) higher in RA (median 9.93, range 4.36-47.80 ng/mL) than in SSc (4.3, 2.1-19.7 ng/mL) or controls (5.2, 4.1-9.4 ng/mL). In RA patients, log-OPN was related to log-C-reactive protein (log-CRP) (r = 0.30, P < 0.05), age (r = 0.38, P < 0.01), Health Assessment Questionnaire (HAQ) (r = 0.58, P < 0.0001), and inversely related to total cholesterol (r = -0.33, P < 0.05) and apolipoprotein A (apoA) (r = -0.58, P < 0.001), but not to oxidative stress markers and ET-1. PWV was similar in RA (median 8.1, range 4.7-16.4 m/s) and SSc (median 8.7, range 7.1-13.1 m/s), but significantly greater (P < 0.01) than controls (median 7.5, range 4.1-10.4 m/s). Aortic PWV was related to log-OPN (r = 0.40, P < 0.01) only in RA patients. It also was related to age (r = 0.34, P < 0.05), mean blood pressure (r = 0.44, P < 0.001), and HAQ (r = 0.48, P < 0.001). In multiple regression analysis (r(2) = 0.36), including confounders, log-OPN remained a significant predictor (P < 0.05) of PWV in RA. Elevated plasma OPN levels are associated with increased arterial stiffness in RA patients, suggesting that this protein might represent a bridge protein between inflammation and the consequent joint damage and cardiovascular risk in RA patients.
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The antiretroviral nucleoside analogue Abacavir reduces cell growth and promotes differentiation of human medulloblastoma cells.
Int. J. Cancer
PUBLISHED: 04-10-2009
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Abacavir is one of the most efficacious nucleoside analogues, with a well-characterized inhibitory activity on reverse transcriptase enzymes of retroviral origin, and has been clinically approved for the treatment of AIDS. Recently, Abacavir has been shown to inhibit also the human telomerase activity. Telomerase activity seems to be required in essentially all tumours for the immortalization of a subset of cells, including cancer stem cells. In fact, many cancer cells are dependent on telomerase for their continued replication and therefore telomerase is an attractive target for cancer therapy. Telomerase expression is upregulated in primary primitive neuroectodermal tumours and in the majority of medulloblastomas suggesting that its activation is associated with the development of these diseases. Therefore, we decided to test Abacavir activity on human medulloblastoma cell lines with high telomerase activity. We report that exposure to Abacavir induces a dose-dependent decrease in the proliferation rate of medulloblastoma cells. This is associated with a cell accumulation in the G(2)/M phase of the cell cycle in the Daoy cell line, and with increased cell death in the D283-MED cell line, and is likely to be dependent on the inhibition of telomerase activity. Interestingly, both cell lines showed features of senescence after Abacavir treatment. Moreover, after Abacavir exposure we detected, by immunofluorescence staining, increased protein expression of the glial marker glial fibrillary acidic protein and the neuronal marker synaptophysin in both medulloblastoma cell lines. In conclusion, our results suggest that Abacavir reduces proliferation and induces differentiation of human medulloblastoma cells through the downregulation of telomerase activity. Thus, using Abacavir, alone or in combination with current therapies, might be an effective therapeutic strategy for the treatment of medulloblastoma.
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Therapeutic paint of cidofovir/sucralfate gel combination topically administered by spraying for treatment of orf virus infections.
AAPS J
PUBLISHED: 03-25-2009
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The aim of the research was to study a new cidofovir/sucralfate drug product to be used as a spray for treating the mucosal and/or skin lesions. The product, i.e., a water suspension of sucralfate (15% w/w) and cidofovir (1% w/w), combines the potent antiviral activity of the acyclic nucleoside phosphonate cidofovir ((S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) and the wound healing properties of sucralfate gel (sucrose octasulphate basic aluminum salt). The product was characterized in vitro with respect to compatibility between drug and carrier, spray particle size, spray deposition, drying kinetics, and drug content and release. An interaction between the two active substances was found. The interaction between sucralfate and cidofovir was counteracted by introducing sodium dihydrogen phosphate (16% w/w) in the preparation. The spray formulation containing cidofovir/sucralfate gel painted the skin and dried quickly to a scab, remaining firmly adhered to the lesions. The therapeutic paint was tested in vivo on lambs infected with orf virus by treating the animals with different cidofovir/sucralfate formulations (0.5% or 1% cidofovir + sucralfate 15% + NaH(2)PO(4) 16% w/w) and with sucralfate gel suspension alone as control. The treatment with formulations containing cidofovir and phosphate salt for four consecutive days resulted in a rapid resolution of the lesions, with scabs containing significantly lower amounts of viable virus when compared with untreated lesions and lesions treated with sucralfate suspension alone.
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Hesperidin gastroresistant microparticles by spray-drying: preparation, characterization, and dissolution profiles.
AAPS PharmSciTech
PUBLISHED: 03-09-2009
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Gastroresistant microparticles for oral administration of hesperidin (Hd) were produced by spray-drying using cellulose acetate phthalate (CAP) as enteric polymer in different polymer/Hd weight ratio (1:1, 3:1, and 5:1), and a series of enhancers of the dissolution rate, such as sodium carboxymethylcellulose crosslinked (CMC), sodium dodecylbenzene sulfonate (SDBS), or Tween85. The raw materials and the microparticles were investigated by differential-scanning calorimetry, X-ray diffraction, infrared spectroscopy and imaged using scanning electron and fluorescence microscopy. In vitro dissolution tests were conducted using a pH-change method to investigate the influence of formulative parameters on the dissolution/release properties of the drug. CAP/Hd microparticles showed a good gastro-resistance but incomplete drug dissolution in the simulated intestinal fluid (SIF). The presence of the enhancers in the formulation produced well-formed microparticles with different size and morphology, containing the drug well coated by the polymer. All the enhancers were able to increase the dissolution rate of Hd in the simulated intestinal environment without altering CAP ability to protect Hd in the acidic fluid. The spray-drying technique and process conditions selected were effective in microencapsulating and stabilizing the flavonoid giving satisfactory encapsulation efficiency, product yield, and microparticles morphology, and a complete drug release in the intestine.
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Agglomerates containing pantoprazole microparticles: modulating the drug release.
AAPS PharmSciTech
PUBLISHED: 02-21-2009
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Pantoprazole-loaded microparticles were prepared using a blend of Eudragit S100 and Methocel F4M. The accelerated stability was carried out during 6 months at 40 degrees C and 75% relative humidity. In order to improve technological characteristics of the pantoprazole-loaded microparticles, soft agglomerates were prepared viewing an oral delayed release and gastro-resistant solid dosage form. The agglomeration was performed by mixing the pantoprazole microparticles with spray-dried mannitol/lecithin powders. The effects of factors such as the amount of lecithin in the spray-dried mannitol/lecithin powders and the ratio between pantoprazole microparticles and spray-dried mannitol/lecithin powders were evaluated. The pantoprazole-loaded microparticles present no significant degradation in 6 months. The agglomerates presented spherical shape, with smooth surface and very small quantity of non-agglomerated particles. The agglomerates presented different yields (35.5-79.0%), drug loading (58-101%), and mechanical properties (tensile strength varied from 44 to 69 mN mm(-2)), when the spray-dried mannitol/lecithin powders with different lecithin amounts were used. The biopharmaceutical characteristics of pantoprazole microparticles, i.e., their delayed-release properties, were not affected by the agglomeration process. The gastro-resistance of the agglomerates was affected by the amount of spray-dried mannitol/lecithin powders. The ratio of lecithin in the spray-dried mannitol/lecithin powders was the key factor in the agglomerate formation and in the drug release profiles. The agglomerates presenting better mechanical and biopharmaceutical characteristics were prepared with 1:2 (w/w) ratio of pantoprazole-loaded microparticles and mannitol/lecithin (80:20) powder.
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Altered amino acid homeostasis in subjects affected by fibromyalgia.
Clin. Biochem.
PUBLISHED: 01-07-2009
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To evaluate plasma amino acid (AA) concentrations in patients affected by fibromyalgia (FM) and to study the relationships between their levels and FM clinical parameters.
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FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration.
Oncotarget
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The transcription factor FOXP3 plays an essential role in regulatory T cell development and function. In addition, it has recently been identified as a tumor suppressor in different cancers. Here, we report that FOXP3 is expressed in normal brain but strongly down-regulated in glioblastoma (GB) and in corresponding GB stem-like cells growing in culture as neurospheres (GB-NS), as evaluated by real time-PCR and confirmed by immunohistochemistry on an independent set of GB. FOXP3 expression was higher in low-grade gliomas than in GB. Interestingly, we also found that neurosphere generation, a feature present in 58% of the GB that we examined, correlated with lower expression of FOXP3 and shorter patient survival. FOXP3 silencing in one GB-NS expressing measurable levels of the gene caused a significant increase in proliferation and migration as well as highly aggressive growth in xenografts. Conversely, FOXP3 over-expression impaired GB-NS migration and proliferation in vitro. We also demonstrated using ChiP that FOXP3 is a transcriptional regulator of p21 and c-MYC supporting the idea that dysregulated expression of these factors is a major mechanism of tumorigenesis driven by the loss of FOXP3 expression in gliomas. These findings support the assertion that FOXP3 exhibits tumor suppressor activity in glioblastomas.
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Dysfunctional syndromes and fibromyalgia: a 2012 critical digest.
Clin. Exp. Rheumatol.
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Medically unexplained chronic disorders remain a challenge for clinicians because the patients with these syndromes have a wide range of symptoms, including pain, impaired concentration, sleep disturbances, fatigue and mood disorders, as well as functional problems and difficulties in carrying out the activities of daily living. Such disorders are the result of a complex physiological interaction of central and peripheral nervous signaling that leads to a highly individual symptom complex, although some of them seem to be related to one another, especially in terms of the mechanism of chronicity and pain amplification, and the co-occurrence of fatigue, sleep alterations, mood disturbances and cognitive impairment. This review will discuss the recent literature concerning the most common dysfunctional disorders: fibromyalgia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, and irritable bowel syndrome.
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Chlorhexidine salt-loaded polyurethane orthodontic chains: in vitro release and antibacterial activity studies.
AAPS PharmSciTech
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The widespread use of indwelling medical devices has enormously increased the interest in materials incorporating antibiotics and antimicrobial agents as a means to prevent dangerous device-related infections. Recently, chlorhexidine-loaded polyurethane has been proposed as a material suitable for the production of devices which are able to resist microbial contamination. The aim of the present study was to characterize the in vitro release of chlorhexidine from new polymeric orthodontic chains realized with polyurethane loaded with two different chlorhexidine salts: chlorhexidine diacetate or chlorhexidine digluconate. The orthodontic chains constituted of three layers: a middle polyurethane layer loaded with chlorhexidine salt inserted between two layers of unloaded polymer. In vitro release of chlorhexidine diacetate and digluconate from orthodontic chains loaded with 10% or 20% (w/w) chlorhexidine salt was sustained for 42 days and followed Fickian diffusion. The drug diffusion through the polyurethane was found to be dependent not only on chlorhexidine loading, but also on the type of chlorhexidine salt. The antibacterial activity of 0.2% (w/w) chlorhexidine diacetate-loaded orthodontic chain was successfully tested towards clinically isolated biofilm forming ica-positive Staphylococcus epidermidis via agar diffusion test. In conclusion, the chlorhexidine salt-loaded chains could provide an innovative approach in the prevention of oral infections related to the use of orthodontic devices.
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Aromatase expression in human peripheral blood leucocytes (PBLs) and in various tissues in primates: studies in elderly humans and cynomolgus monkeys.
J. Med. Primatol.
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Previous analysis of aromatase gene and protein expression in peripheral blood leucocytes (PBLs), studied in children and adults, was extended to elderly subjects. In addition, we assessed whether aromatase expression in PBLs could be used as a parameter of aromatase expression in other tissues, using the cynomolgus monkey as model.
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Simian immunodeficiency virus-Vpx for improving integrase defective lentiviral vector-based vaccines.
Retrovirology
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Integrase defective lentiviral vectors (IDLV) represent a promising delivery system for immunization purposes. Human dendritic cells (DC) are the main cell types mediating the immune response and are readily transduced by IDLV, allowing effective triggering of in vitro expansion of antigen-specific primed CD8+ T cells. However, IDLV expression in transduced DC is at lower levels than those of the integrase (IN) competent counterpart, thus requiring further improvement of IDLV for future use in the clinic.
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Temperament and character traits associated with health-related quality of life in cancer patients.
Tumori
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There is an increase in the attention to factors influencing the quality of life of cancer patients. The aim of the present study was to evaluate temperament and character traits related to health-related quality of life (HRQoL) in patients with cancer.
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Successful therapeutic vaccination with integrase defective lentiviral vector expressing nononcogenic human papillomavirus E7 protein.
Int. J. Cancer
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Persistent infection with high risk genotypes of human papillomavirus (HPV) is the cause of cervical cancer, one of most common cancer among woman worldwide, and represents an important risk factor associated with other anogenital and oropharyngeal cancers in men and women. Here, we designed a therapeutic vaccine based on integrase defective lentiviral vector (IDLV) to deliver a mutated nononcogenic form of HPV16 E7 protein, considered as a tumor specific antigen for immunotherapy of HPV-associated cervical cancer, fused to calreticulin (CRT), a protein able to enhance major histocompatibility complex class I antigen presentation (IDLV-CRT/E7). Vaccination with IDLV-CRT/E7 induced a potent and persistent E7-specific T cell response up to 1 year after a single immunization. Importantly, a single immunization with IDLV-CRT/E7 was able to prevent growth of E7-expressing TC-1 tumor cells and to eradicate established tumors in mice. The strong therapeutic effect induced by the IDLV-based vaccine in this preclinical model suggests that this strategy may be further exploited as a safe and attractive anticancer immunotherapeutic vaccine in humans.
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The impact of mood, anxiety, and sleep disorders on fibromyalgia.
Compr Psychiatry
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Several studies carried out mainly in North America revealed high rates of mood, anxiety and sleep disorders in patients with fibromyalgia (FM), while the information in other countries is scant. Therefore, we aimed at investigating the prevalence and the impact of such conditions on the health-related quality of life (HRQoL) and the severity of pain in a sample of Italian FM patients.
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[Management of refractory symptoms in hypertrophic cardiomyopathy with restrictive pathophysiology: novel perspectives for ranolazine].
G Ital Cardiol (Rome)
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The management of patients with hypertrophic cardiomyopathy (HCM) and refractory symptoms due to massive hypertrophy and severe diastolic dysfunction represents a real challenge for the clinical cardiologist. Such patients often require novel therapeutic approaches, both invasive and pharmacological, involving multidisciplinary teamwork; however, the implementation of potentially viable treatment options is hindered by lack of disease-specific evidence. We report the case of a young woman with severe HCM and restrictive physiology, who underwent extensive myectomy via the transaortic and transapical approach, followed by biventricular pacing for cardiac resynchronization, with significant but incomplete symptomatic improvement. The subsequent introduction of ranolazine, based on promising preclinical data, has led to an excellent final result. An ongoing randomized clinical trial is currently testing the efficacy of ranolazine in symptomatic HCM.
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Spinal cord injury after ascending aorta and aortic arch replacement combined with antegrade stent grafting: role of postoperative cerebrospinal fluid drainage.
J Card Surg
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Ascending aorta and aortic arch replacement combined with antegrade stent grafting of the descending thoracic aorta represents an emerging hybrid surgical approach for complex and extensive thoracic aortic disease. We present a case of a patient at low risk for spinal cord ischemia who underwent hybrid thoracic aortic surgery (aortic arch replacement and E-vita prosthesis implantation) and developed a spinal cord injury (SCI) after the intervention. Treatment aimed at increasing spinal cord perfusion pressure with the aid of cerebrospinal fluid (CSF) drainage was effective in recovering neuromuscular function.
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Particles and powders: tools of innovation for non-invasive drug administration.
J Control Release
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The paper briefly illustrates several approaches applied in delivering particulate drugs as powders. Microparticulate drug powders are difficult to manipulate with respect to dosage form preparation, particularly when they have very small size as this leads to poor flow and packing properties. When the dosage form performance resides in the presence of individual intact drug particles, the particle characteristics have to be retained in their original state, i.e., not altered during manufacturing and/or within the dosage form. There are several examples of dry powder dosage forms intended for different administration routes whose performance is strictly dependent on particle characteristics. In addition, the preparation of the finished dosage form is dependent on powder properties. The paper addresses dry powder formulations with special focus on oral powders mainly for elderly people or children, nasal powders and inhalation dry powders. These dosage forms are very attractive for both researchers and companies. Their formulation requires deep investigation, mainly in order to define particle structure and performance. Indeed, this makes for a new breakthrough in pharmaceutics and may lead to innovative products.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.