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Find video protocols related to scientific articles indexed in Pubmed.
Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration.
Cochrane Database Syst Rev
PUBLISHED: 09-16-2014
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Neovascular age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly populations of industrialised countries. Bevacizumab (Avastin®) and ranibizumab (Lucentis®) are targeted biological drugs (a monoclonal antibody) that inhibit vascular endothelial growth factor, an angiogenic cytokine that promotes vascular leakage and growth, thereby preventing its pathological angiogenesis. Ranibizumab is approved for intravitreal use to treat neovascular AMD, while bevacizumab is approved for intravenous use as a cancer therapy. However, due to the biological similarity of the two drugs, bevacizumab is widely used off-label to treat neovascular AMD.
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The importance of monitoring adverse drug reactions in pediatric patients: the results of a national surveillance program in Italy.
Expert Opin Drug Saf
PUBLISHED: 08-30-2014
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To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed 'Monitoring of the Adverse Effects in Pediatric population' (MEAP).
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Isolation and functional characterization of human ventricular cardiomyocytes from fresh surgical samples.
J Vis Exp
PUBLISHED: 05-07-2014
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Cardiomyocytes from diseased hearts are subjected to complex remodeling processes involving changes in cell structure, excitation contraction coupling and membrane ion currents. Those changes are likely to be responsible for the increased arrhythmogenic risk and the contractile alterations leading to systolic and diastolic dysfunction in cardiac patients. However, most information on the alterations of myocyte function in cardiac diseases has come from animal models. Here we describe and validate a protocol to isolate viable myocytes from small surgical samples of ventricular myocardium from patients undergoing cardiac surgery operations. The protocol is described in detail. Electrophysiological and intracellular calcium measurements are reported to demonstrate the feasibility of a number of single cell measurements in human ventricular cardiomyocytes obtained with this method. The protocol reported here can be useful for future investigations of the cellular and molecular basis of functional alterations of the human heart in the presence of different cardiac diseases. Further, this method can be used to identify novel therapeutic targets at cellular level and to test the effectiveness of new compounds on human cardiomyocytes, with direct translational value.
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Relative efficacy of antianginal drugs used as add-on therapy in patients with stable angina: A systematic review and meta-analysis.
Eur J Prev Cardiol
PUBLISHED: 04-28-2014
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First-line medical management of stable angina generally involves a beta-blocker (BB) or calcium channel blocker (CCB), with other classes of medication being added if symptom control is inadequate. Evidence supporting the appropriate choice of a second-line agent is currently unclear. The objective of this systematic review was to quantify the clinical benefit of BB, CCBs, long-acting nitrates (LANs), ranolazine, trimetazidine, ivabradine or nicorandil added to first-line monotherapy for stable coronary artery disease.
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Pharmacovigilance of herb-drug interactions among preoperative patients.
Altern Ther Health Med
PUBLISHED: 03-25-2014
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The Pharmacovigilance Center of the University of Florence conducted a survey across 3 hospitals in Tuscany (Empoli, Florence, and Prato) on a sample population consisting of 478 patients admitted to the hospital for a preoperative assessment before surgical intervention. The aim of the study was to assess the concomitant use of herbal remedies (HRs) and prescribed medications and to evaluate the most important potential interactions. Almost 50% of the patients surveyed-238 of 478 (49.8 %)-used at least 1 HR. Among them, 55 (23.1%) were actually exposed to at least 1 potential interaction. In particular, 42 participants had an HR-drug interaction and 17 participants had a dietary supplement drug interaction. A large percentage of patients undergoing surgery take HRs that could potentially interact with drugs administered perioperatively. Antihypertensive, antiplatelet, anticoagulant, and central nervous system (CNS) agents were the main products involved. The use of HRs is not devoid of risks and adverse effects due to potential interactions that may be serious or even lifethreatening. HR-drug interactions should be deeply investigated, especially in high-risk patient populations. Health care professionals should pay close attention and always investigate the consumption of HRs among their patients.
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Herbalists' perception of risks involving commonly sold medicinal plants in Italy.
Complement Ther Med
PUBLISHED: 02-25-2014
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Although there are several studies which have investigated pharmacists' knowledge of the safety of medicinal plants (MPs), no studies have examined herbalists' perception of risks associated with MPs.
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Human amniotic fluid stem cell differentiation along smooth muscle lineage.
FASEB J.
PUBLISHED: 08-30-2013
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Functional smooth muscle engineering requires isolation and expansion of smooth muscle cells (SMCs), and this process is particularly challenging for visceral smooth muscle tissue where progenitor cells have not been clearly identified. Herein we showed for the first time that efficient SMCs can be obtained from human amniotic fluid stem cells (hAFSCs). Clonal lines were generated from c-kit(+) hAFSCs. Differentiation toward SM lineage (SMhAFSCs) was obtained using a medium conditioned by PDGF-BB and TGF-?1. Molecular assays revealed higher level of ? smooth muscle actin (?-SMA), desmin, calponin, and smoothelin in SMhAFSCs when compared to hAFSCs. Ultrastructural analysis demonstrated that SMhAFSCs also presented in the cytoplasm increased intermediate filaments, dense bodies, and glycogen deposits like SMCs. SMhAFSC metabolism evaluated via mass spectrometry showed higher glucose oxidation and an enhanced response to mitogenic stimuli in comparison to hAFSCs. Patch clamp of transduced hAFSCs with lentiviral vectors encoding ZsGreen under the control of the ?-SMA promoter was performed demonstrating that SMhAFSCs retained a smooth muscle cell-like electrophysiological fingerprint. Eventually SMhAFSCs contractility was evident both at single cell level and on a collagen gel. In conclusion, we showed here that hAFSCs under selective culture conditions are able to give rise to functional SMCs.-Ghionzoli, M., Repele, A., Sartiani, L., Costanzi, G., Parenti, A., Spinelli, V., David, A. L., Garriboli, M., Totonelli, G., Tian, J., Andreadis, S. T., Cerbai, E., Mugelli, A., Messineo, A., Pierro, A., Eaton, S., De Coppi, P. Human amniotic fluid stem cell differentiation along smooth muscle lineage.
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Safety profile of antiviral medications: a pharmacovigilance study using the Italian spontaneous-reporting database.
Am J Health Syst Pharm
PUBLISHED: 05-31-2013
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The results of an analysis of suspected antiviral-associated adverse drug reactions (ADRs) in Italy over a 22-year period are presented.
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Chronic atrial fibrillation alters the functional properties of if in the human atrium.
J. Cardiovasc. Electrophysiol.
PUBLISHED: 05-24-2013
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Despite the evidence that the hyperpolarization-activated current (If ) is highly modulated in human cardiomyopathies, no definite data exist in chronic atrial fibrillation (cAF). We investigated the expression, function, and modulation of If in human cAF.
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Is green tea a potential trigger for autoimmune hepatitis?
Phytomedicine
PUBLISHED: 03-14-2013
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A case of autoimmune liver hepatitis is reported: the onset was triggered by consumption of green tea infusion in a patient taking oral contraceptives and irbesartan. We hypothesize that our patient, carrying genetic variant of hepatic metabolism making her particularly susceptible to oxidative stress, developed an abnormal response to a mild toxic insult, afforded by a combination of agents (oral contraceptives+irbesartan+green tea) that normally would not be able to cause damage. Her particular hepatic metabolism further increased the drugs concentration, favoring the haptenization of liver proteins, eventually leading to the development of an autoimmune hepatitis.
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Representativeness of the "Fiesole Misurata" study database for use in pharmaco-epidemiological investigations on adherence to antihypertensive medications.
Aging Clin Exp Res
PUBLISHED: 03-04-2013
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Poor adherence to medications is a major health concern especially among older subjects. To plan future studies to improve adherence, an epidemiological study, called "Fiesole Misurata", was conducted. The aim of the present paper was to verify the representativeness of the database in evaluating the AntiHyperTensives (AHTs)-taking behaviour.
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Molecular and functional evidence of HCN4 and caveolin-3 interaction during cardiomyocyte differentiation from human embryonic stem cells.
Stem Cells Dev.
PUBLISHED: 02-27-2013
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Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) is accompanied by changes in ion channel expression, with relevant electrophysiological consequences. In rodent CM, the properties of hyperpolarization-activated cyclic nucleotide-gated channel (HCN)4, a major f-channel isoform, depends on the association with caveolin-3 (Cav3). To date, no information exists on changes in Cav3 expression and its associative relationship with HCN4 upon hESC-CM maturation. We hypothesize that Cav3 expression and its compartmentalization with HCN4 channels during hESC-CM maturation accounts for the progression of f-current properties toward adult phenotypes. To address this, hESC were differentiated into spontaneously beating CM and examined at ?30, ?60, and ?110 days of differentiation. Human adult and fetal CM served as references. HCN4 and Cav3 expression and localization were analyzed by real time PCR and immunocyto/histochemistry. F-current was measured in patch-clamped single cells. HCN4 and Cav3 colocalize in adult human atrial and ventricular CM, but not in fetal CM. Proteins and mRNA for Cav3 were not detected in undifferentiated hESC, but expression increased during hESC-CM maturation. At 110 days, HCN4 appeared to be colocalized with Cav3. Voltage-dependent activation of the f-current was significantly more positive in fetal CM and 60-day hESC-CM (midpoint activation, V1/2, ? -82?mV) than in 110-day hESC-CM or adult CM (V1/2?-100?mV). In the latter cells, caveolae disruption reversed voltage dependence toward a more positive or an immature phenotype, with V1/2 at -75?mV, while in fetal CM voltage dependence was not affected. Our data show, for the first time, a developmental change in HCN4-Cav3 association in hESC-CM. Cav3 expression and its association with ionic channels likely represent a crucial step of cardiac maturation.
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Cardiovascular and metabolic safety profiles of the fluoroquinolones.
Expert Opin Drug Saf
PUBLISHED: 09-30-2011
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Certain fluoroquinolones share similar indications of use. A comparison among Cardiovascular and metabolic (i.e., dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes.
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Two contemporary cases of hepatitis associated with Teucrium chamaedrys L. decoction use: case reports and review of literature.
Basic Clin. Pharmacol. Toxicol.
PUBLISHED: 09-28-2011
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Teucrium chamaedrys L. is a herbaceous plant common in European woods that has been used for many purposes for centuries. Recently, T. chamaedrys L. has become popular as a slimming decoction without any scientific proof of efficacy notwithstanding its well-known hepatotoxicity. Hydroalcoholic extracts are currently used as flavourings in the preparation of wines, bitters and liqueurs. Teucrin A and teuchamaedryn A are the major toxic components of the diterpenoid fraction of T. chamaedrys L.
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Characterization of circulating and monocyte-derived dendritic cells in obese and diabetic patients.
Mol. Immunol.
PUBLISHED: 06-29-2011
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Dendritic cells (DCs) are suspected to be involved in the development of atherogenesis, but their role is still unclear. The aim of this study was to characterize circulating DCs and monocyte-derived DCs (Mo-DCs) of obese and diabetic patients (T2D), and to study their interaction with human coronary smooth muscle cells (CASMCs). Obese post-menopausal women with or without insulin resistance were enrolled and were compared to age-matched healthy women. Myeloid circulating DCs significantly increased in obese T2D patients compared to healthy donors and a smaller increase was observed for plasmacytoid one. Mature Mo-DCs from obese T2D patients significantly decreased when compared to control, but they were significantly more capable of adhering to CASMCs compared to that from healthy controls and from not-T2D obese subjects. Altogether these data suggest that in conditions of insulin-resistance and obesity there is an up-regulation of myeloid DCs that might contribute to pathological vascular remodeling.
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Inadequate cancer pain management in Italian clinical trials.
Intern Emerg Med
PUBLISHED: 02-25-2011
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Pain treatment in Italy is far from being optimal. In order to improve this situation, the reporting of a complete assessment of pain in the clinical record became compulsory by law. Pain-related cancer protocols (143) were selected from the National Monitoring Centre of Clinical Trials Database and reviewed. Our data indicate that pain management is not being reported as it should be: treatment has been taken into account in only 36.4% of the protocols, and assessment in 37.1%. Furthermore, breakthrough cancer pain has never been reported. The main aim of cancer therapy is obviously control the disease, however Ethics Committees should pay close attention to pain therapy when evaluating clinical protocols.
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Complementary and Alternative Drugs Use among Preoperative Patients: A Cross-Sectional Study in Italy.
Evid Based Complement Alternat Med
PUBLISHED: 01-24-2011
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Complementary and alternative drugs (CADs) are widely used in preoperative patients and may lead to potential interactions and adverse reactions. The aim of our study is to evaluate the prevalence and the predictors of CADs use among preoperative patients using data from an Italian survey. This cross-sectional study, which enrolled 478 patients (response rate: 83.5%), was carried out in three Tuscany hospitals (Italy). The prevalence of CADs use was 49.8%: 233 out of 238 participants used herbal products and/or dietary supplements. Valeriana officinalis was the most reported product (19.4%). According to univariate analysis, users were commonly identified among middle-aged or older patients; unadjusted ORs were 2.1 (95% CI: 1.3-3.3) for patients aged 48-69 years, and 3.0 (95% CI: 1.9-4.7) for those of 70-95 years, when compared with individuals aged 18-47 years. Except for education and gender, adjusted estimates showed consistent results with univariate analyses: direct association was observed with higher education, and-although not significantly-with female gender. The high prevalence of CAD use in preoperative period could be suggestive of a certain risk of adverse effects due to CADs interactions. A careful medical history of CADs consumption should be ascertained before surgery.
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Interactions between Natural Health Products and Oral Anticoagulants: Spontaneous Reports in the Italian Surveillance System of Natural Health Products.
Evid Based Complement Alternat Med
PUBLISHED: 01-09-2011
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Introduction. The safety of vitamin K antagonists (VKA) use can be compromised by many popular herbal supplements taken by individuals. The literature reports that 30% of warfarin-treated patients self-medicates with herbs. Possible interactions represent an health risk. We aimed to identify all herbs-oral anticoagulants interactions collected in the Italian database of suspected adverse reactions to "natural health" products. Methods. The Italian database of spontaneous reports of suspected adverse reactions to natural products was analyzed to address herb-VKAs interactions. Results. From 2002 to 2009, we identified 12 reports with 7 cases of INR reduction in patients treated with warfarin (n = 3) and acenocoumarol (n = 4), and 5 cases of INR increase (all warfarin associated). It was reported 8 different herbal products as possibly interacting. Discussion. Our study confirms the risk of interactions, highlighting the difficulty to characterize them and their mechanisms and, finally, prevent their onset. The reported data underline the urgent need of healthcare providers being aware of the possible interaction between natural products and VKA, also because of the critical clinical conditions affecting patients. This is the first step to have the best approach to understand possible INR alterations linked to herb-VKA interaction and to rightly educate patients in treatment with VKA.
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Heart rate reduction with ivabradine prevents the global phenotype of left ventricular remodeling.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 10-15-2010
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The aim of this study was to investigate the effect of chronic heart rate (HR) reduction with the hyperpolarization-activated current inhibitor ivabradine on the global phenotype of left ventricular (LV) remodeling in a ligated rat model. Seven days after coronary artery ligation, Wistar rats received ivabradine (10 mg · kg(-1) · day(-1) administered in drinking water) [myocardial infarction + ivabradine (MI+IVA), n = 22] or vehicle only (drinking water) (MI, n = 20) for 90 days. A sham group (n = 20) was included for model validation. MI+IVA rats had 12% lower HR (P < 0.01), improved LV volumes, 15% higher LV ejection fraction (LVEF, P < 0.01) than MI rats, and 33% reductions in both plasma atrial natriuretic peptide (ANP, P = 0.052) and cardiac hydroxyproline. Using patch-clamp, action potential duration was reduced and transient outward current density increased (P < 0.05). Cardiac energy metabolism was also improved (+33% creatine phosphate, P < 0.001; +15% ATP; and +9% energy charge, P < 0.05). Significant correlations were found between HR and parameters of cardiac metabolism, ANP, and LVEF (all P < 0.05). The HR-reducing properties of ivabradine prevent changes in the global phenotype of LV remodeling in the rat, optimize energy consumption, and avoid electrophysiological and structural remodeling.
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Design, synthesis, and preliminary biological evaluation of new isoform-selective f-current blockers.
J. Med. Chem.
PUBLISHED: 08-28-2010
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New I(f) blockers have been designed and tested on HEK293 cells stably expressing the HCN1, HCN2, and HCN4 channels to find compounds able to discriminate among the channel isoforms. Among the synthesized compounds, the cis-butene derivative (R)-5 shows some preference for HCN2 while the pseudodimeric product (R)-6 shows selectivity for HCN1. These compounds can be important pharmacological tools to study the channels in native tissues and may be useful to design safe drugs.
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Safety profile of the fluoroquinolones: analysis of adverse drug reactions in relation to prescription data using four regional pharmacovigilance databases in Italy.
Drug Saf
PUBLISHED: 08-13-2010
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Fluoroquinolones are widely used both in primary care and in hospital settings. Since the last comparison performed in Italy on the safety profiles of different fluoroquinolones, a new molecule, prulifloxacin, has been introduced into the market and several warnings concerning this class of drugs have been released. The aim of this study was to reassess the safety profiles of fluoroquinolones using the database of the Italian Interregional Group of Pharmacovigilance (IGP) and the administrative data of fluoroquinolone prescriptions.
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Prenatal exposure to carbon monoxide delays postnatal cardiac maturation.
Lab. Invest.
PUBLISHED: 07-19-2010
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Prenatal exposure to toxicants, such as maternal smoking, may impair cardiovascular autonomic maturation in infants. We recently showed that exposure of pregnant rats to a mild concentration of carbon monoxide (CO), a component of cigarette smoke, delays postnatal electrophysiological maturation of ventricular myocytes from newborns rats, likely predisposing to life-threatening arrhythmias. To get a comprehensive view of developmental molecular abnormalities induced, at cardiac level, by prenatal CO exposure, we used microarray analysis approach on the rat heart at 4, 7 and 20 days postnatal life. The relationship between molecular and functional alterations was investigated by assessing the ventricular expression of f-current, an electrophysiological marker of immature cardiac phenotype. Rats were prenatally exposed to 0 (CTR) or 150?p.p.m. CO and mRNA obtained from ventricular samples. Differential analysis and biological pathway analysis of microarray data were performed by using Newtons approach and the GENMAPP/MAPPFinder, respectively. The real-time RT-PCR reactions were performed by TaqMan probe-based chemistry. Freshly isolated patch-clamped ventricular cardiomyocytes were used to measure I(f). Genes and pathways controlling cell cycle and excitation-contraction coupling were significantly modified in CO-exposed rats. The higher effect was observed in cardiomyocytes harvested from 7-day-old rats, in which mRNA expression for crucial sarcomeric proteins (myosin and actin subunits, troponin I), transporters (Ca(2+) transporting ATPase) and enzymes (aldolase) were significantly downregulated. Accordingly, the molecular and functional expression of f-channels, which represents a marker of fetal ventricular phenotype, was transiently greater in CO-exposed rats (+200%) than in control ones. In conclusion, our study provides new insights into the molecular and functional mechanisms underlying cardiac maturation and its impairment by prenatal exposure to toxic components of smoking, such as CO.
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The effect of losartan treatment on the response of diabetic cardiomyocytes to ATP depletion.
Pharmacol. Res.
PUBLISHED: 06-20-2010
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The present work aimed to investigate the effect of losartan treatment of healthy and diabetic rats on cardiomyocyte response to ATP depletion. Cells were isolated from normoglycemic (N) and streptozotocin-injected (55 mg/kg) rats (D) treated or not treated with losartan (20 mg/kg/day in the drinking water; NL and DL, respectively) for 3 weeks. In each group of cells, enzyme activities such as glucose-6-phosphate (G6PDH) and glycerol-3-phosphate dehydrogenases (G3PDH), lactate/pyruvate, glycogen levels and citrate synthase were measured as an index of glycolytic dysregulation and mitochondrial mass, respectively. Cells were then challenged with NaCN (2 mM) in glucose-free Tyrode solution (metabolic intoxication, MI), a protocol to study ischemia at cell level. Under these conditions, the time to contractile failure up to rigor-type hyper-contracture in field-stimulated cells and K(ATP) current activation by patch-clamp recordings were measured. In comparison with N and NL, D cells presented higher G6PDH and cytoplasmic G3PDH activities, lactate/pyruvate, glycogen content but similar levels of citrate synthase, and decay time of contraction. When subjected to MI, D cells showed delayed activation of the K(ATP) current (25.7±7.1 min; p<0.001 vs. N and NL), increased time to contractile failure and rigor-type hyper-contracture (p<0.001 vs. N and NL). In cells from DL rats both functional (time to rigor and to K(ATP) current activation) and metabolic parameters, approached values similar to those measured in N and NL cells. These results demonstrate that diabetic cardiomyocytes from rats treated with losartan, maintain the capacity to respond promptly to ATP depletion reaching contractile failure, rigor-type hypercontracture and K(ATP) opening with a similar timing of N cells.
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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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Different implication of NEDD9 genetic variant in early and late-onset Alzheimers disease.
Neurosci. Lett.
PUBLISHED: 03-03-2010
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Alzheimers disease (AD) is a complex and multifactorial progressive neurodegenerative disease. Recently, two studies reported inconsistent results on a possible involvement of the NEDD9 (neural precursor cell expressed, developmentally down-regulated 9, 6p25-p24) as a candidate gene for the risk of developing AD and/or Parkinsons disease (PD). We analyzed the distribution of the rs760678 SNP polymorphism in 735 Italian subjects: 214 unrelated sporadic late-onset AD patients (LOAD, 64.5% females, mean age-at-onset 71.8+/-5.2 years), 135 early-onset AD patients (EOAD, 57.3% females, mean age-at-onset 57.5+/-5.5 years) and 386 healthy controls (68.9% females, mean age 83.4+/-17.9 years; SD). We observed a statistically significant difference between LOAD patients and controls according to genotypes (P=0.016) and allele frequency (P=0.007); CC genotype was more frequent in LOAD cases (44.4%) than controls (36.0%). No difference after stratification of the data in terms of gender and status of the APOE epsilon4 allele was observed. In conclusion, our data do support an implication of the NEDD9 allelic variant in late-onset AD, with an independent effect of the apolipoprotein E (APOE) epsilon4 allele in the risk of developing AD.
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Epidemiology of suboptimal prescribing in older, community dwellers: a two-wave, population-based survey in Dicomano, Italy.
Drugs Aging
PUBLISHED: 11-26-2009
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Because of co-morbidity, older persons are often exposed to use of an excessive number of drugs, which per se implies also use of inappropriate drugs or of potentially interacting drugs (suboptimal prescribing). Time trends of suboptimal prescribing in older, community dwellers have been poorly investigated, particularly in Italy.
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Cardiac and electrophysiological effects of primary and refined extracts from Leonurus cardiaca L. (Ph.Eur.).
Planta Med.
PUBLISHED: 11-16-2009
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Although several antiarrhythmic drugs of chemical origin are in clinical use since decades, their application is often limited by their adverse effects and especially by their inherited proarrhythmic risk, which can lead to a significantly increased mortality in patients receiving these compounds. On the other hand, aqueous extracts from the aerial parts of the European Lamiaceae Leonurus cardiaca (Ph.Eur.) have been used for centuries as a remedy against tachyarrhythmia and other cardiac disorders. Nevertheless, a scientific basis for the claim of direct cardiac electrophysiological, antiarrhythmic, or functional effects of Leonurus cardiacae herba (LCH) preparations has not been established until now. In order to enrich the active constituents from the primary extract which was tested as the most cardioactive, namely the aqueous Soxhlet extract, and to eliminate undesired substances such as the dichloromethanic fraction or potassium, a bioassay guided fractionation procedure was applied, resulting in the development of a Leonurus cardiaca refined extract (LCRE) which was characterised together with Leonurus crude extracts by a newly developed gradient elution HPLC fingerprint analysis for separation and quantification of six major phenolics as well as by qNMR for determining the stachydrine content. This refined extract was applied intracoronarily in isolated rabbit hearts perfused according to the Langendorff technique. Mapping experiments with 256 electrodes on the heart surface showed a reduction of left ventricular pressure and an increase of relative coronary flow at concentrations of 1.0 and 2.0 mg/mL LCRE. Furthermore, the PQ-interval was prolonged and both the basic cycle length and the activation recovery interval increased. In addition, voltage-clamp measurements were performed on the following cell models in order to characterise the electrophysiological profile of LCRE: neonatal rat ventricular cardiomyocytes to investigate the effect on I(Na) and I(Ca.L), sinoatrial node cells and ventricular myocytes isolated from adult guinea pigs to test effects on I(f) and action potential (AP) duration, as well as HERG-transfected HEK 293 cells to analyse the influence on the I (K.r). In these voltage clamp experiments LCRE exerted a calcium-antagonistic activity by I(Ca.L) blockade, reduced the repolarising current I(K.r), and prolonged the AP-duration, while I(Na) was not affected. Although LCRE displayed only weak effects on the I(f) amplitude and voltage dependence, it significantly prolonged the activation time constant of I(f). Thus, LCRE acts on multiple electrophysiological targets, specifically I(Ca.L), I(K.r), and I(f), observed both at whole organ and single cell level.
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Management of fever in children: summary of the Italian Pediatric Society guidelines.
Clin Ther
PUBLISHED: 04-20-2009
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This article summarizes the Italian Pediatric Society guideline on the management of the signs and symptoms of fever in children, prepared as part of the National Guideline Program (NGLP).
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Losartan counteracts the hyper-reactivity to angiotensin II and ROCK1 over-activation in aortas isolated from streptozotocin-injected diabetic rats.
Cardiovasc Diabetol
PUBLISHED: 04-20-2009
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In streptozotocin-injected rats (STZ-rats), we previously demonstrated a role for angiotensin II (AT-II) in cardiac remodelling and insulin resistance partially counteracted by in vivo treatment with losartan, an AT-II receptor antagonist.We now aimed to investigate the effect of treating diabetic STZ-rats with losartan on diabetes vascular response to vasoconstrictors.
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Antibiotic prescribing in paediatric populations: a comparison between Viareggio, Italy and Funen, Denmark.
Eur J Public Health
PUBLISHED: 04-05-2009
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High rates of antibiotic prescribing in paediatric populations represent a major issue because of the problem of antibiotic resistance. North European countries reported an appropriate use of antibiotics in general population; few studies on this issue have been conducted until now, especially in Italy. Therefore a comparison concerning paediatric antibiotic prescribing rates between an Italian administrative area in Tuscany (Viareggio) and the county of Funen (Denmark) was conducted.
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Electrophysiologic changes in heart failure: focus on pacemaker channels.
Can. J. Physiol. Pharmacol.
PUBLISHED: 02-24-2009
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Heart failure is a common clinical syndrome occurring as a result of cardiac overload, injury, and a complex interplay among genetic, neurohormonal, inflammatory, and biochemical factors. Occurrence of arrhythmias in heart failure is largely a consequence of disease-induced electrical remodeling of cardiac myocytes, a phenomenon consisting of alterations of ion channels and the ion-transport function that predispose patients to develop lethal arrhythmias. In most cases, the mechanism is the rapid onset of a ventricular tachyarrhythmia progressing to ventricular fibrillation and hemodynamic compromise. This paper highlights some of the important changes in ion channel expression and function that underlie electrical remodeling of the failing heart. Particular attention will be focused on the presence, features, and pharmacologic modulation of f channels expressed in ventricular cardiac myocytes.
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Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy.
Circulation
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Hypertrophic cardiomyopathy (HCM), the most common mendelian heart disorder, remains an orphan of disease-specific pharmacological treatment because of the limited understanding of cellular mechanisms underlying arrhythmogenicity and diastolic dysfunction.
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Outcome of patients aged ?80 years undergoing combined aortic valve replacement and coronary artery bypass grafting: a systematic review and meta-analysis of 40 studies.
Am. Heart J.
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This study was planned to evaluate the outcome of patients aged ?80 years undergoing combined conventional aortic valve replacement (AVR) and coronary artery bypass grafting (CABG).
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Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes.
Biomed Eng Online
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Human embryonic stem cell derived cardiomyocytes (hESC-CMs) hold high potential for basic and applied cardiovascular research. The development of a reliable simulation platform able to mimic the functional properties of hESC-CMs would be of considerable value to perform preliminary test complementing in vitro experimentations.
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Assessing pain in hospital in-patients: a cross-sectional study in Tuscany, Italy.
Intern Emerg Med
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Guidelines Towards a Pain-Free Hospital, published in 2001 in Italy, determined an increasing spread of No-Pain Hospital Committees across the country and supported a more effective pain control in hospital. However, few hospitals adopted such protocols. To date, a thorough investigation on quality of pain management documentation is lacking. The present survey aimed to evaluate the quality of pain management documentation reported in medical and hospital discharge records. The study reviewed records of 2,459 patients discharged every Wednesday of November 2006 in 29 Tuscany hospitals. Among 2,459 patients, 51.5 % were males. Patients were aged between 0 and 90 years or above and were mostly (24.93 %) between 70 and 79 years; most of them (47.1 %) were hospitalized in Medicine ward. At hospital admission, less than half of examined records (40.3 %) reported pain-related items, and only 8.1 % reported how it was treated. During hospitalization, 39.6 % of the records reported the use of scales for measuring pain intensity and 49.7 % reported the pharmacological therapy. The present study highlights the lack of an exhaustive documentation of pain recording and management in the hospital setting. Therefore, healthcare providers should pay close attention to this relevant issue, and the quality of such documentation should be constantly monitored.
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Update of the 2009 Italian Pediatric Society Guidelines about management of fever in children.
Clin Ther
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In 2009, the Italian Pediatric Society developed national guidelines for management of fever in children for health care providers and parents/caregivers; an update of these guidelines was scheduled after 2 years.
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Pharmacologically active microcarriers for endothelial progenitor cell support and survival.
Eur J Pharm Biopharm
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The regenerative potential of endothelial progenitor cell (EPC)-based therapies is limited due to poor cell viability and minimal retention following application. Neovascularization can be improved by means of scaffolds supporting EPCs. The aim of the present study was to investigate whether human early EPCs (eEPCs) could be efficiently cultured on pharmacologically active microcarriers (PAMs), made with poly(d,l-lactic-coglycolic acid) and coated with adhesion/extracellular matrix molecules. They may serve as a support for stem cells and may be used as cell carriers providing a controlled delivery of active protein such as the angiogenic factor, vascular endothelial growth factor-A (VEGF-A). eEPC adhesion to fibronectin-coated PAMs (FN-PAMs) was assessed by means of microscopic evaluation and by means of Alamar blue assay. Phospho ERK(1/2) and PARP-1 expression was measured by means of Western blot to assess the survival effects of FN-PAMs releasing VEGF-A (FN-VEGF-PAMs). The Alamar blue assay or a modified Boyden chamber assay was employed to assess proliferative or migratory capacity, respectively. Our data indicate that eEPCs were able to adhere to empty FN-PAMs within a few hours. FN-VEGF-PAMs increased the ability of eEPCs to adhere to them and strongly supported endothelial-like phenotype and cell survival. Moreover, the release of VEGF-A by FN-PAMs stimulated in vitro HUVEC migration and proliferation. These data strongly support the use of PAMs for supporting eEPC growth and survival and for stimulating resident mature human endothelial cells.
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