Contribution of insulin resistance to decreased baroreceptor sensitivity & cardiometabolic risks in pre-obesity & obesity

Background & objectives: Although insulin resistance (IR) is a known complication in obesity, the physiological mechanisms linking IR with cardiometabolic risks in obesity have not been well studied. This study was conducted to assess the difference in cardiovascular (CV) risk profile in IR and non-IR (NIR) conditions, and contribution of IR to cardiometabolic risks in pre-obese and obese individuals. Methods: Basal CV, blood pressure variability, autonomic function test and cardiometabolic parameters were recorded in pre-obese (n=86) and obese (n=77) individuals during 2012 and 2015. The association of altered cardiometabolic parameters with homeostatic model for IR (HOMA-IR) in pre-obese and obese groups and with baroreceptor sensitivity (BRS) in IR and NIR groups was calculated by appropriate statistical analysis. Results: Decreased BRS, a known CV risk and cardiometabolic parameters were significant in IR (pre-obese and obese) group compared to the NIR group. Sympathovagal imbalance in the form of increased sympathetic and decreased parasympathetic activities was observed in individuals with IR. There was no significant difference in the level of independent contribution of HOMA-IR to cardiometabolic parameters in pre-obese and obese groups. Adiponectin and inflammatory markers had an independent contribution to BRS in IR group. Interpretation & conclusions: Findings of the present study demonstrated that the intensity of cardiometabolic derangements and CV risk were comparable between IR, pre-obese and obese individuals. Pro-inflammatory state, dyslipidaemia and hypoadiponectinaemia might contribute to CV risk in these individuals with IR. IR could possibly be the link between altered metabolic profile and increased CV risks in these individuals independent of the adiposity status.

P-glycoprotein expression as a predictor of response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Chemoresistance is an important factor determining the response of tumor to neoadjuvant chemotherapy (NACT). P-glycoprotein (P-gp) expression-mediated drug efflux is one of the mechanisms responsible for multi-drug resistance. Our study was aimed to determine the role of P-gp expression as a predictor of response to NACT in locally advanced breast cancer (LABC) patients. MATERIALS AND METHODS: P-gp expression was performed by real-time quantitative polymerase chain reaction [qRT-PCR] in 76 patients with LABC. Response to adriamycin-based regimen was assessed both clinically and with contrast enhanced computed tomography (CECT) scan before and after NACT. The significance of correlation between tumor and P-gp levels was determined with Chi-square test. RESULTS: Twenty-one had high and 55 had low P-gp expression. On analyzing P-gp expression with response by World Health Organization (WHO) criteria, statistical significance was obtained (P = 0.038). Similarly, assessment of P-gp expression with response by Response Evaluation in Solid Tumors (RECIST) criteria in 48 patients showed statistical significance (P = 0.0005). CONCLUSION: This study proves that P-gp expression is a determinant factor in predicting response to NACT. Finally, detection of P-gp expression status before initiation of chemotherapy can be used as a predictive marker for NACT response and will also aid in avoiding the toxic side effects of NACT in non-responders.

Awareness of and attitude towards oral rehydration therapy.

Forty eight Medical practitioners, 56 pharmacists and 55 mothers of children with diarrhoea were interviewed, using a prepared questionnaire, in an attempt to evaluate in each group, the awareness of and attitude towards oral rehydration therapy. 69% of mothers interviewed were aware of oral rehydration therapy, but only 66% among them practised it. 48% of mothers interviewed, received advice regarding oral rehydration therapy from medical personnel and health care providers. It was found that the ORS preparations not conforming to WHO formulation were the most widely stocked and used and the most widely sold. 9% of pharmacists advocated only glucose as a treatment for diarrhoea on their own. 60% of doctors advised and prescribed ORS preparation not conforming to WHO formulation, 44% of medical practitioners were not sure of the exact method of dilution and preparation of the commercially available preparations. The study has shown that there is more to be done towards realising the total success of ORT. We recommend that ORS preparations not conforming to WHO formulation be withdrawn from the market and further that the responsibility of their manufacture be undertaken by governmental agencies.

Drug therapy of acute diarrhoea in children--actual practice and recommendations.

Forty eight private medical practitioners and fifty six pharmacists were interviewed, using a prepared questionnaire in each group, in an attempt to evaluate the awareness and practice in the treatment of acute diarrhoea in children among private medical practitioners and the role of pharmacists in the dispensing of drugs for diarrhoea in children. 83% of the doctors prescribed an antibacterial agent, 56% prescribed loperamide, 19% of them prescribed diphenoxylate plus atropine while 31% prescribed an absorbent in children for the treatment of acute diarrhoea. Of fifty six pharmacists interviewed, 30 of them sold diphenoxylate on their own and 26 of them honoured a doctor's prescription of the same. 80% of pharmacists interviewed dispensed loperamide, more than 50% of them dispensed an antibacterial agent while 14% dispensed a binding agent such as pectin or kaolin for the treatment of acute diarrhoea without a valid prescription from a doctor. We recommend that the pharmaceuticals prominently display the harmful effects in children of drugs such as the antimotility drugs and immediately withdraw from the market, all pediatric preparations of the same.