Quantitative determination of bioactive phenylethanoid glycosides in Clerodendrum phlomidis using HPTLC

A new validated high performance thin layer chromatographic method has been developed for the simultaneous determination of three bioactive phenylethanoid glycosides verbascoside (1), leucosceptoside A (2) and martynoside (3) in the roots of Clerodendrum phlomidis. Extraction efficiency of marker compounds was studied using normal (cold and hot), ultrasonic as well as microwave assisted extraction techniques with various solvents. Well resolved separation of marker compounds was achieved on silica gel 60F₂₅₄ plates using the mobile phase consisting of chloroform–methanol–water (7.8:2.0:0.2, v/v/v). Quantitation of marker compounds was carried out using the densitometric reflection/absorption mode at 460 nm after post-chromatographic derivatization with vanillin–sulphuric acid reagent. Method was validated for peak purity, precision, robustness and sensitivity etc., as per ICH guidelines. Report on the occurrence of phenylethanoid glycosides for the first time in C. phlomidis is of chemotaxonomic importance.     

Intestinal Ischemia After Allogeneic Stem Cell Transplantation: A Report of Four Cases

Gastrointestinal ischemia after allogeneic bone marrow transplantation is a rare complication not well-described in the literature. Herein we retrospectively review charts of four patients who developed intestinal ischemia after allogeneic bone marrow transplantation at our institution. The patients were found to be predominately younger males who presented with nonspecific abdominal pain. Graft-versus-host disease was a common finding among all patients. Laboratory values suggestive of microangiopathy were present in two patients. Obesity and hypertriglyceridemia were cardiovascular risk factors found in these patients. The development of thrombotic microangiopathy and cardiovascular risk factors after allogeneic bone marrow transplantation may predispose patients to gastrointestinal ischemia and may portend a poor prognosis.     

Dissolution Improvement of Atorvastatin Calcium using Modified Locust Bean Gum by the Solid Dispersion Technique

The present research was aimed at the enhancement of the dissolution rate of atorvastatin calcium by the solid dispersion technique using modified locust bean gum. Solid dispersions (SD) using modified locust bean gum were prepared by the modified solvent evaporation method. Other mixtures were also prepared by physical mixing, co-grinding, and the kneading method. The locust bean gum was subjected to heat for modification. The prepared solid dispersions and other mixtures were evaluated for equilibrium solubility studies, content uniformity, FTIR, DSC, XRD, in vitro drug release, and in vivo pharmacodynamic studies. The equilibrium solubility was enhanced in the solid dispersions (in a drug:polymer ratio of 1:6) and other mixtures such as the co-grinding mixture (CGM) and kneading mixture (KM). Maximum dissolution rate was observed in the solid dispersion batch SD3 (i.e. 50% within 15 min) with maximum drug release after 2 h (80%) out of all solid dispersions. The co-grinding mixture also exhibited a significant enhancement in the dissolution rate among the other mixtures. FTIR studies revealed the absence of drug-polymer interaction in the solid dispersions. Minor shifts in the endothermic peaks of the DSC thermograms of SD3 and CGM indicated slight changes in drug crystallinity. XRD studies further confirmed the results of DSC and FTIR. Topological changes were observed in SEM images of SD3 and CGM. In vivo pharmacodynamic studies indicated an improved efficacy of the optimized batch SD3 as compared to the pure drug at a dose of 3 mg/kg/day. Modified locust bean gum can be a promising carrier for solubility enhancement of poorly water-soluble drugs. The lower viscosity and wetting ability of MLBG, reduction in particle size, and decreased crystallinity of the drug are responsible for the dissolution enhancement of atorvastatin. The co-grinding mixture can be a good alternative to solid dispersions prepared by modified solvent evaporation due to its ease of preparation and significant improvement in dissolution characteristics.     

Rapid assessment of glycoprotein IIb/IIIa blockade with the platelet function analyzer (PFA-100) during percutaneous coronary intervention

BACKGROUND: The platelet function analyzer PFA-100 (Dade Behring, Miami, Fla) evaluates platelet function by determining the time to occlusion of an aperture in a membrane coated with collagen and adenosine diphosphate or epinephrine as whole blood flows under shear stress conditions. Platelet aggregation causes aperture occlusion, and results are reported as closure time (CT). Interindividual variability is observed in the level of platelet inhibition achieved with use of the current abciximab dosing regimen (0.25-mg/kg bolus + 10-microg/min infusion for 12 hours). The relationships between specific levels of platelet inhibition and clinical efficacy and safety have not been fully established. METHODS AND RESULTS: We prospectively studied platelet function in 27 patients receiving abciximab during percutaneous coronary intervention. This evaluation included determinations of platelet-rich plasma aggregometry, receptor occupancy studies (D3 assay), and CT measurements at baseline and 10 minutes, 4 hours, 12 hours, and 24 hours after the bolus. All patients received abciximab, aspirin, and heparin; patients undergoing coronary stent implantation received aspirin and ticlopidine after the procedure. CT results were reported within 10 minutes after initiation of testing. For 96% of patients, CT was 300 seconds (maximum CT) immediately after abciximab bolus and remained so throughout the infusion. At 24 hours we observed variable recovery from platelet inhibition and in 72% of patients CT returned to normal (< or =130 seconds). CONCLUSIONS: Findings with the PFA-100 were similar to results observed with platelet aggregometry and receptor occupancy measurements. Most patients treated with abciximab exhibit normalized platelet function at 24 hours despite moderate levels of receptor occupancy, suggesting dissociation between occupancy and function.     

Comparative redox status in alcoholic liver disease and nonalcoholic fatty liver disease

Purpose Altered redox status has been implicated in pathogenesis of alcoholic liver disease (ALD) as well as in nonalcoholic fatty liver disease (NAFLD). This study was planned to find the relative role of redox status in these two diseases. Methods A total of 44 patients with ALD and 32 patients with NAFLD and 25 apparently healthy controls were included in the study. Redox status was estimated by measuring oxidative stress (superoxide dismutase (SOD) and lipid peroxidation products as thiobarbituric acid reactive substances (TBARS)) and antioxidant status (ferric reducing ability of plasma (FRAP) and vitamin C). Results TBARS level was raised significantly in both ALD (3.5 (2.3–9.4) vs. 1.8 (0.5–4.1) nmol/ml; P = 0.0001) and NAFLD (5.1 (1–10.2) vs. 1.82 (0.51–4.1) nmol/ml; P = 0.0001) as compared with controls, but was not different between ALD and NAFLD. SOD was significantly higher in ALD as compared to NAFLD (2.4 (1.3–7.8) vs. 0.68 (0.05–19.1) U/ml; P = 0.0001) and controls (1.12 (0.01–3.5) U/ml; P = 0.001). FRAP was lower in ALD as compared with NAFLD (345.4 (56–615.9) vs. 434.1 (197.6–733.3) μmol of Fe⁺² liberated; P = 0.001) but similar to that of controls (340.9 (141.5–697.5) μmol of Fe⁺² liberated). Conclusions ALD patients have a higher degree of redox imbalance as compared with NAFLD patients     

A comparison of clinical outcomes between Canadian and American patients after nonurgent coronary stenting

BACKGROUND: Practice patterns for percutaneous coronary interventions (PCIs) may differ between Canada and the United States. Few data are available comparing PCI outcomes between the two countries in the era of coronary stenting and adjunctive glycoprotein IIb/IIIa inhibition. METHODS: In the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, 2064 patients were randomly assigned to receive eptifibatide or placebo during nonurgent PCI. The 30-day and one-year rates of death, myocardial infarction (MI) and target vessel revascularization (TVR) were compared between Canadian and American patients enrolled in the ESPRIT trial. RESULTS: There were 1531 American patients and 533 Canadian patients enrolled. Americans were older and heavier, and had a higher incidence of cardiac risk factors than Canadians (P<0.05 for all variables). Canadian patients had a lower incidence of death, MI and TVR at 30 days (6.2% versus 10.4%, P=0.004) and at one year (14.8% versus 21.5%, P=0.0006). After adjusting for known baseline differences, enrollment in Canada remained a significant predictor of reduced ischemic complications at 30 days (OR=0.53, c2=9.0, P=0.003). Similar results were observed at one year. Eptifibatide was superior to placebo in both groups of patients. CONCLUSIONS: This analysis is among the first to show Canadian patients to have fewer adverse events than American patients after nonurgent PCI. This effect was independent of known baseline differences between the patients in each country. The relative treatment effect of eptifibatide in Canadian patients paralleled that observed in the main ESPRIT trial and in American patients.     

Sex Differences in Atrial Fibrillation—Update on Risk Assessment,Treatment, and Long-Term Risk

Purpose of review

Atrial fibrillation (AF) is a growing health problem worldwide. While the disease plagues both men and women, this arrhythmia does not affect both sexes equally. Women are more likely to have major adverse outcomes such as stroke and its sequela; however, recent data on stroke prevention show improving outcomes. The purpose of this review of the recent literature is to summarize important updates on risk scores and management of patients with AF.

Recent findings

It has been well known that women have a higher risk of strokes than men when untreated or when treated with warfarin. Current risk scores emphasizing new risk factors such as the higher risk of strokes in women have been incorporated into clinical guidelines. However, with the use of direct oral anticoagulants, this sex disparity on stroke is no longer seen and women have less major bleeding than men. The use of cardiac glycosides is associated with increased incidence of breast cancer, and this medication is used more in women. Procedural complications for the management of AF are higher in women.

Summary

The study of the pathophysiology of AF and its management is a rapidly evolving area of cardiovascular medicine. Sex-specific data is necessary to achieve advances in the field and improve the outcomes in both men and women.

     

Multinational data on cumulative radiation exposure of patients from recurrent radiological procedures: call for action

European Radiology - To have a global picture of the recurrent use of CT imaging to a level where cumulative effective dose (CED) to individual patients may be exceeding 100 mSv at which organ...