Synthesis of 1,2,3-triazole tethered bifunctional hybrids by click chemistry and their cytotoxic studies

In view of the drug resistance with most of the currently used anticancer drugs, molecular hybrids of pyrazolyl chalcones and p-nitro benzyl functionalities tethered by triazole ring have been synthesised and evaluated for cytotoxic studies against three human cancer cell lines (THP, COLO-205, A-549). The results of the preliminary investigation exhibited marked dependence of the cytotoxic activity on the electronic factors. Placement of naphthyl (JGPT-11) and trimethoxy phenyl ring (JGPT-6) as ring A proved to be extremely beneficial in enhancing the cytotoxic potential. Thus we herein report the synthesis and cytotoxic studies of a new class of molecular hybrids. Detailed investigation on the biological mechanistic insights of JGPT-11 and 6 is under progress.     

Purification and identification of a polysaccharide from medicinal mushroom Amauroderma rude with immunomodulatory activity and inhibitory effect on tumor growth

Medicinal mushrooms in recent years have been the subject of many experiments searching for anticancer properties. We previously screened thirteen mushrooms for their potential in inhibiting tumor growth, and found that the water extract of Amauroderma rude exerted the highest activity. Previous studies have shown that the polysaccharides contained in the water extract were responsible for the anticancer properties. This study was designed to explore the potential effects of the polysaccharides on immune regulation and tumor growth. Using the crude Amauroderma rude extract, in vitro experiments showed that the capacities of spleen lymphocytes, macrophages, and natural killer cells were all increased. In vivo experiments showed that the extract increased macrophage metabolism, lymphocyte proliferation, and antibody production. In addition, the partially purified product stimulated the secretion of cytokines in vitro, and in vivo. Overall, the extract decreased tumor growth rates. Lastly, the active compound was purified and identified as polysaccharide F212. Most importantly, the purified polysaccharide had the highest activity in increasing lymphocyte proliferation. In summary, this molecule may serve as a lead compound for drug development.     

Comparing Cortical Plasticity Induced by Conventional and High-Definition 4 × 1 Ring tDCS: A Neurophysiological Study

BackgroundTranscranial direct current stimulation (tDCS) induces long-lasting NMDA receptor-dependent cortical plasticity via persistent subthreshold polarization of neuronal membranes. Conventional bipolar tDCS is applied with two large (35 cm²) rectangular electrodes, resulting in directional modulation of neuronal excitability. Recently a newly designed 4 × 1 high-definition (HD) tDCS protocol was proposed for more focal stimulation according to the results of computational modeling. HD tDCS utilizes small disc electrodes deployed in 4 × 1 ring configuration whereby the physiological effects of the induced electric field are thought to be grossly constrained to the cortical area circumscribed by the ring.ObjectiveWe aim to compare the physiological effects of both tDCS electrode arrangements on motor cortex excitability.MethodstDCS was applied with 2 mA for 10 min. Fourteen healthy subjects participated, and motor cortex excitability was monitored by transcranial magnetic stimulation (TMS) before and after tDCS.ResultsExcitability enhancement following anodal and a respective reduction after cathodal stimulation occurred in both, conventional and HD tDCS. However, the plastic changes showed a more delayed peak at 30 min and longer lasting after-effects for more than 2 h after HD tDCS for both polarities, as compared to conventional tDCS.ConclusionThe results show that this new electrode arrangement is efficient for the induction of neuroplasticity in the primary motor cortex. The pattern of aftereffects might be compatible with the concept of GABA-mediated surround inhibition, which should be explored in future studies directly.     

Impact of COVID 19 pandemic on patients requiring renal biopsy

Introduction

The disruption of healthcare services in coronavirus disease (COVID)19 pandemic was widespread particularly due to lockdown curbs. This study was undertaken to see the effect of this pandemic on subjects requiring renal biopsy.

Materials and method

Renal biopsies performed during the COVID 19 pandemic between April 2020 and December 2020 (Group 1) were compared with those in pre-COVID period between June 2019 and February 2020 (Group 2). Indication of biopsies, syndromic diagnosis and all baseline laboratory characteristics were retrieved from the hospital records.

Results

130 and 191 patients were biopsied in groups 1 and 2, respectively. Patients in group 1 were younger compared with group 2 (32.55?±?15.60 and 36.37?±?16.96 years, respectively, p value 0.038). The mean serum creatinine value in group 1 was significantly higher than in group 2 (3.21?±?2.08 and 2.68?±?2.02 mg/dl respectively, p value: 0.023). Group 1 comprises a significantly higher percentage of rapidly progressive renal failure patients (RPRF) (39.3 vs 28, p value 0.046). A higher percentage of nephrotics was biopsied in group 2 vs group 1 (46.9 vs 30.4 respectively, p value 0.008). The treatment protocol remained similar in both the groups. Evaluation of the transplant biopsies revealed a nonsignificant higher number of rejections in group 1 (11 out of 18) as compared to group 2 (5 out of 16), p value 0.100. Combined rejection saw a lesser use of rATG in group 1.

Conclusion

COVID pandemic induced restrictive measures could have led to selective high risk patients with RPRF as presumptive diagnosis and higher creatinine values getting biopsied. Higher rejections were noticed in transplant recipients pointing towards the need of establishing a more efficient support system for managing such patients.

     

Aprepitant’s Prophylactic Efficacy in Decreasing Postoperative Nausea and Vomiting in Morbidly Obese Patients Undergoing Bariatric Surgery

Background

Postoperative nausea and vomiting is a major cause of patient dissatisfaction towards surgery. For bariatric surgery, increased vomiting/retching is detrimental to surgical anastomosis. The present study evaluated the efficacy of aprepitant (neurokinin-1 inhibitor) as a prophylactic antiemetic in morbidly obese patients for laparoscopic bariatric surgery.

Methods

After institutional review board approval, 125 morbidly obese patients were recruited into this double-blind placebo-controlled trial. On random division, the patients received a tablet of aprepitant (80 mg) in group A, or a similar-appearing placebo in group P, an hour prior to surgery. All patients received intravenous ondansetron (4 mg) intraoperatively. Postoperatively, the patients were evaluated for nausea and vomiting by a blinded evaluator at 30 min, 1, 2, 6, 24, 48, and 72 h.

Results

Both groups were evenly distributed for age, body mass index, type, and length of surgery. Cumulative incidence of vomiting at 72 h was significantly lower in group A (3 %) compared to group P (15 %; p?=?0.021). Odds ratio for vomiting in group P compared to group A was 5.47 times. On Kaplan–Meier plot, time to first vomiting was also significantly delayed in group A (p?=?0.019). A higher number of patients showed complete absence of nausea or vomiting in group A compared to group P (42.18 vs. 36.67 %). On the other hand, nausea scores were unaffected by aprepitant, and no significant difference between groups was found at any of the measured time points.

Conclusions

In morbidly obese patients undergoing laparoscopic bariatric surgery, addition of aprepitant to ondansetron can significantly delay vomiting episodes simultaneously lowering the incidence of postoperative vomiting.