Acute,sub-acute and general pharmacological evaluation of 5-(3,4-methylenedioxyphenyl)-4-ethyl-2E,4E-pentadienoic acid piperidide (SK-20): A novel drug bioavailability enhancer

An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h.     

Canadian Cardiovascular Society/Canadian Heart Rhythm Society Joint Position Statement on the Cardiovascular Screening of Competitive Athletes

Sudden cardiac death (SCD), especially in a young seemingly healthy individual, is a tragic and highly publicized event, which is often followed by a strong emotional reaction from the public and medical community.” Although rare, SCD in the young is devastating to families and communities, underpinning our society’s desire to avoid any circumstances predisposing to the loss of human life during exertion. The Canadian Cardiovascular Society Position Statement on the cardiovascular screening of athletes provides evidence-based recommendations for Canadian sporting organizations and institutions with a focus on the role of routine electrocardiogram (ECG) screening in preventing SCD. We recommend that the cardiac screening and care of athletes within the Canadian health care model comprise a sequential (tiered) approach to the identification of cardiac risk, emphasizing the limitations of screening, the importance of shared decision-making when cardiac conditions are diagnosed, and the creation of policies and procedures for the management of emergencies in sport settings. Thus, we recommend against the routine (first-line or blanket mass performance of ECG) performance of a 12-lead ECG for the initial cardiovascular screening of competitive athletes. Organization/athlete-centred cardiovascular screening and care of athletes program is recommended. Such screening should occur in the context of a consistent, systematic approach to cardiovascular screening and care that provides: assessment, appropriate investigations, interpretation, management, counselling, and follow-up. The recommendations presented comprise a tiered framework that allows institutions some choice as to program creation.     

A novel sarsasapogenin glycoside from Asparagus racemosus elicits protective immune responses against HBsAg

The aim of the present investigation was to evaluate the adjuvant potential of a novel sarsasapogenin glycoside (immunoside) isolated from Asparagus racemosus in combination with hepatitis B surface antigen (HBsAg). Various in vitro and animal derived protocols were used to determine the response of immunoside adjuvanted with HBsAg and the results were compared with alum adjuvanted with HBsAg. Several biomarkers such as antibody titre (IgG, IgG1/IgG2a) were measured in mice sera. Cell proliferation, cytokines (IL-2, IFN-γ and IL-4), and lymphocyte sub-populations (CD4/CD8, CD3 and CD19) were determined in splenocytes from mice administered subcutaneously with test substances. In these cells CD4/CD8 derived IFN-γ release was also determined. Macrophage preparations were used for the determination of IL-12, IFN-γ and nitrite content. Seroconversion potential was compared with a standard vaccine. Acute safety evaluation of immunoside was done in mice. Effect of immunoside on red blood cell haemolysis was determined. The results have suggested that immunoside potentially enhanced anti-HBsAg immune response via augmenting Th1/Th2 response in a dose dependent manner.     

Sub-acute toxicity evaluation of an aqueous extract of Labisia pumila, a Malaysian herb

Labisia pumila (Myrsinaceae), is a popular herb among the women in Malaysia known locally as “Kacip Fatimah”. Recently many nutraceutical products containing the powdered or extracted parts of the plant have become available for women’s health care. However no evaluation of the effect of the repeated dosing of any herbal product of this plant had been undertaken prior to a 28-day sub-acute study presented in this report. The results showed that a dose of 50 mg/kg of an aqueous extract of L. pumila corresponded to no-adverse-effect-level (NOAEL), whereas higher doses were associated with some toxicity concerns.     

Impact of transcatheter aortic valve implantation on circulating von Willebrand factor in patients with severe aortic stenosis

Introduction

Severe aortic stenosis (AS) can lead to degradation of high molecular weight (HMW) von Willebrand factor (VWF) which can result in haemostatic abnormalities. While studies have explored changes in VWF profiles before and after surgical aortic valve replacement (SAVR), the longer-term changes in VWF profiles pre- and post-transcatheter aortic valve implantation (TAVI) are less understood.

Aim

Our primary objective was to identify differences in VWF multimer profiles and VWF function pre-TAVI and 1-month post-TAVI. Our secondary objective was to correlate VWF markers with measures of AS severity.

Methods

Adult patients with severe AS referred for TAVI at our institution were prospectively enrolled in this cohort study. Blood samples were collected for plasma analysis at three time points for all patients: 1 day pre-TAVI, 3 days post-TAVI, and 1-month post-TAVI. VWF antigen, activity, propeptide, collagen binding, multimers, and factor VIII coagulant activity were determined at each time point. Correlations between VWF parameters and severity of AS were assessed.

Results

Twenty participants (15 males, five females) with severe AS were recruited for the study. There was a significant increase in HMW VWF between pre-procedure and 1-month post-TAVI (p < .05). There was a transient increase in VWF antigen levels and activity at 3-days post TAVI that decreased to pre-TAVI levels at 1-month. There were no statistically significant correlations between VWF markers and AS severity.

Conclusions

This is the first study to elucidate longer-term (>1 week) improvements in HMW VWF after a TAVI procedure in severe AS patients.     

Natural Orifice Endoscopic Thyroidectomy via Transoral Vestibular Approach (TOVA): Single Surgeon Experience from North India

The transoral vestibular approach (TOVA) is the shortest route for endoscopic thyroidectomy (ET) to approach the thyroid and is a totally scar free procedure, hence it has a clear cosmetic advantage not only over conventional open thyroid surgery but also over other remote access approaches for ET like axilla, breast and chest wall approaches. The aim of this study was to evaluate the feasibility, safety and our initial outcomes of TOVA and highlight the advantages of 3D endoscopic equipment in remote access thyroid surgery. We reviewed our prospectively maintained database who underwent ET. 42 patients who fulfilled the stringent inclusion criteria were offered TOVA. We have used novel Trans-vestibular approach with 3D technology for endoscopic thyroid surgery in all cases. Clinico-demographic profile, investigations, operative details, histopathology and postoperative complications and follow-up data were analyzed by using statistical analysis with SPSS19.00 version. Out of 203 ET operated during study period, 42 (20.69%) patients were operated through TOVA. Hemithyroidectomy were performed in all the patients. There were 3 men and 39 women (M:F = 1:13). Mean tumor size was 3.54 ± 1.17 cm. All patients were euthyroid. All patient had cytological diagnosis of Bethesda category II-IV and all underwent hemithyroidectomy. Mean operation time was 107.71 ± 17.60 min and post-operative length of hospital stay was 2.90 ± 1.28 days. Besides magnification, 3D endoscopy provided excellent depth perception which helped in precise dissection in the restricted space and aided in identification and preservation of the two most vital structures i.e. recurrent laryngeal nerve and parathyroid glands. As most of our patients present with larger goitres, not many patients desirous of ET can be offered TOVA. This novel TOVA has fairly stringent inclusion criteria, however it is the only approach which offers completely scarless endoscopic thyroidectomy and should be offered to eligible patients desirous of ET.