Prescription-based cost analysis of medicines for cardiovascular risk factors at Indian Council of Medical Research-Rational Use of Medicine Centre Hospitals of India.

OBJECTIVES: India has taken several initiatives to provide health care to its population while keeping the related expenditure minimum. Since cardiovascular diseases are the most prevalent chronic conditions, in the present study, we aimed to analyze the difference in prices of medicines prescribed for three cardiovascular risk factors, based on (a) listed and not listed in the National List of Essential Medicines (NLEM) and (b) generic and branded drugs. MATERIALS AND METHODS: Outpatient prescriptions for diabetes mellitus, hypertension, and dyslipidemia were retrospectively analyzed from 12 tertiary centers. The prices of medicines prescribed were compared based on presence or absence in NLEM India-2015 and prescribing by generic versus brand name. The price was standardized and presented as average price per medicine per year for a given medicine. The results are presented in Indian rupee (INR) and as median (range). RESULTS: Of the 4,736 prescriptions collected, 843 contained oral antidiabetic, antihypertensive, and/or hypolipidemic medicines. The price per medicine per year for NLEM oral antidiabetics was INR 2849 (2593-3104) and for non-NLEM was INR 5343 (2964-14364). It was INR 806 (243-2132) for generic and INR 3809 (1968-14364) for branded antidiabetics. Antihypertensives and hypolipidemics followed the trend. The price of branded non-NLEM medicines was 5-22 times higher compared to generic NLEM which, for a population of 1.37 billion, would translate to a potential saving of 346.8 billion INR for statins. The variability was significant for sulfonylureas, angiotensin receptor blockers, beta-blockers, diuretics, and statins (P < 0.0001). CONCLUSION: The study highlights an urgent need for intervention to actualize the maximum benefit of government policies and minimize the out-of-pocket expenditure on medicines.

Evaluation of prescriptions from tertiary care hospitals across India for deviations from treatment guidelines & their potential consequences.

BACKGROUND OBJECTIVES: Irrational prescribing practices have major consequences on patient safety and also increase the economic burden. Real-life examples of impact of irrational prescription have potential to improve prescribing practices. In this context, the present study aimed to capture and evaluate the prevalence of deviations from treatment guidelines in the prescriptions, potential consequence/s of the deviations and corrective actions recommended by clinicians. METHODS: It was a cross-sectional observational study conducted in the outpatient departments of tertiary care hospitals in India wherein the 13 Indian Council of Medical Research Rational Use of Medicines Centres are located. Prescriptions not compliant with the standard treatment guidelines and incomplete prescriptions with respect to formulation, dose, duration and frequency were labelled as 'prescriptions having deviations'. A deviation that could result in a drug interaction, lack of response, increased cost, preventable adverse drug reaction (ADR) and/or antimicrobial resistance was labelled as an 'unacceptable deviation'. RESULTS: Against all the prescriptions assessed, about one tenth of them (475/4838; 9.8%) had unacceptable deviations. However, in 2667/4838 (55.1%) prescriptions, the clinicians had adhered to the treatment guidelines. Two thousand one hundred and seventy-one prescriptions had deviations, of which 475 (21.9%) had unacceptable deviations with pantoprazole (n=54), rabeprazole+domperidone (n=35) and oral enzyme preparations (n=24) as the most frequently prescribed drugs and upper respiratory tract infection (URTI) and hypertension as most common diseases with unacceptable deviations. The potential consequences of deviations were increase in cost (n=301), ADRs (n=254), drug interactions (n=81), lack of therapeutic response (n=77) and antimicrobial resistance (n=72). Major corrective actions proposed for consideration were issuance of an administrative order (n=196) and conducting online training programme (n=108). INTERPRETATION CONCLUSIONS: The overall prevalence of deviations found was 45 per cent of which unacceptable deviations was estimated to be 9.8 per cent. To minimize the deviations, clinicians recommended online training on rational prescribing and administrative directives as potential interventions.

Jigsaw Classroom: Perceptions of Students and Teachers.

Background: Various innovative teaching methods have been designed in an attempt to provide millennial students an interactive and stimulating learning environment. A jigsaw method is one such form of cooperative learning that enables students to develop critical-thinking and ability for effective communication and promotes positive student attitudes toward their own learning. The present study was thus undertaken to introduce a jigsaw-based cooperative learning method and to understand the perception of the students and faculty. Methodology: This was a cross-sectional study conducted among second year MBBS students. Students were randomly divided into 10 parent groups, with 10 students each. The topic was divided into 10 subtopics. Each student in the parent group was allotted a sub-topic. The students who were given the same sub-topic assembled to form an expert group. They interacted and discussed the subtopic. Students finally returned to their parent groups for peer teaching and presentation. A validated questionnaire was used to gather students and faculty feedback. Descriptive statistics were used to analyze responses to the Likert scale questions. Qualitative data was analyzed using thematic analysis. Results: The present study included 95 s year MBBS students. Majority (81%) students agreed that this teaching learning method enhanced their communication skills. Seventy-five percent of the students agreed that the activity helped in overcoming shyness and hesitation in the class. Overall the faculty also agreed that the jigsaw method was helpful for the students. Conclusions: Cooperative learning like jigsaw facilitates learning allowing student-student discussion, improving communication and teaching skills.

Assessment of prescribing pattern of drugs and completeness of prescriptions as per the World Health Organization prescribing indicators in various Indian tertiary care centers: A multicentric study by Rational Use of Medicines Centers-Indian Council of Medical Research network under National Virtual Centre Clinical Pharmacology activity.

OBJECTIVE: The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates. METHODS: Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees. RESULTS: Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation. CONCLUSION: Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

Adverse Drug Reactions in Psychiatry Outpatient Department of a Tertiary Care Hospital in Western Uttar Pradesh: An Observational Study.

Objective: Psychiatric disorders are chronic in nature which require medications for a long duration. These medications have been associated with many adverse events. Failure to recognize an adverse drug reaction (ADR) exposes the patient to continuing risk of ADR, leading to a significant impact on patient's quality of life. Thus, the present study carried out to identify the pattern of ADRs reported due to psychotropic medication. Methods: This was a cross-sectional study conducted to analyze ADRs reported from the psychiatry department of a tertiary care teaching hospital from October 2021 to March 2022. Findings: A total of 137 ADRs were identified from 102 patients. Majority of the ADRs were reported from antidepressants, with paroxetine being the leading offending drug. The central nervous system was most commonly affected, and dizziness (13.13%) was the most common ADR noted. On causality assessment, 97 ADRs (70.8%) were of "possible" type. Almost half of the patients with ADRs (47.5%) recovered spontaneously. No ADR encountered turned out to be fatal. Conclusion: The present study revealed that the majority of ADRs reported from psychiatry OPD were mild in nature. We reinforce the identification of ADR is crucial in the hospital setting process as it gives an insight into the risk-benefit ratio for rational use of the drug.

Use of drugs not listed in the National List of Essential Medicines: Findings from a prescription analysis by the Indian Council of Medical Research-Rational Use of Medicines Centres Network in tertiary care hospitals across India.

BACKGROUND: The concept of listing essential medicines can lead to improved supply and access, more rational prescribing, and lower costs of drugs. However, these benefits hinge on the prescription of drugs from an Essential Medicines List (EML). Several studies have highlighted the problem of underutilization of EMLs by prescribers. Therefore, as part of prescription research by the Indian Council of Medical Research-Rational Use of Medicines Centres Network, we evaluated the extent of prescription of drugs not listed in the National List of Essential Medicines (NLEM). MATERIALS AND METHODS: Prescriptions of outpatients from participating centers were included after obtaining verbal/written informed consent as approved by the Ethics Committee, and evaluated for prescription of drugs from the NLEM 2015. RESULTS: Analysis of 4838 prescriptions from 13 tertiary health-care institutes revealed that 2677 (55.33%) prescriptions had at least one non-NLEM drug prescribed. In all, 5215 (31.12%) of the total 16,758 drugs prescribed were not in NLEM. Of these, 2722 (16.24%) were single drugs and 2493 (14.88%) were fixed-dose combinations (FDCs). These comprised 700 different drug products - 346 single drugs and 354 FDCs. The average number of non-NLEM drugs prescribed per prescription was 1.08, while the average number of all drugs prescribed was 3.35 per prescription. It was also found that some of the non-NLEM drugs prescribed had the potential to result in increased cost (for example, levocetirizine), increased adverse effects (dextromethorphan), and less effectiveness (losartan) when compared to their NLEM counterparts. Nonavailability of an essential drug (oral hydroxocobalamin) was another important finding of our study. CONCLUSION: This study highlights the extent and pattern of drugs prescribed from outside the NLEM at the tertiary health-care level and the need for training and enhanced awareness among prescribers for greater utilization of the NLEM.

Safety of hydroxychloroquine in healthcare workers for COVID-19 prophylaxis.

BACKGROUND & OBJECTIVES: Hydroxychloroquine (HCQ), reported to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in in vitro studies, has been recommended for prophylaxis of COVID-19 in healthcare workers (HCWs). The objective of this study was to assess short-term adverse events (AEs) of HCQ in HCWs. METHODS: This cross-sectional study among consenting HCWs taking prophylaxis and working in hospitals with COVID-19 patients used online forms to collect details of HCWs, comorbidities, prophylactic drugs used and AEs after the first dose of HCQ. Verification of dose and AEs was done by personal contact. Multivariate logistic regression analysis was done to determine the effect of age, gender and dose of HCQ on AE. RESULTS: Of the 1303 HCWs included, 98.4 per cent (n=1282) took HCQ and 66 per cent (n=861) took 800 mg as first day's dose. Among the 19.9 per cent (n=259) reporting AEs, 1.5 per cent (n=20) took treatment for AE, none were hospitalized and three discontinued HCQ. Gastrointestinal AEs were the most common (172, 13.2%), with less in older [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.89], with more in females (OR 2.46, 95% CI 1.78-3.38) and in those taking a total dose of 800 mg on day one compared to a lower dose. Hypoglycaemia (1.1%, n=14), cardiovascular events (0.7%, n=9) and other AEs were minimal. INTERPRETATION & CONCLUSIONS: HCQ prophylaxis first dose was well tolerated among HCWs as evidenced by a low discontinuation. For adverse effects, a small number required treatment, and none required hospitalization. The study had limitations of convenience sampling and lack of laboratory and electrocardiography confirmation of AEs.

Spaced education and student learning: Results from a medical school.

BACKGROUND: It is critical for medical students to retain and apply their knowledge of basic sciences to become competent prescribing physicians. Poor long-term retention is a pervasive concern. We investigated the impact of 'spaced education' teaching modules to improve knowledge retention in medical students on a topic of public health: vitamin D and its role in health and disease. It is critical for medical students to retain and apply their knowledge of basic sciences to become competent prescribing physicians METHODS: In a self-matched design, 148 medical students were randomised and evaluated on vitamin D-related topics to assess reinforced and non-reinforced knowledge in a multiple-choice question format. Initial learning and long-term retention were assessed with an estimation of Cohen's effect size at 24 and 72 weeks, respectively. RESULTS: The administration of spaced educational material significantly improved composite formative test scores at 24 weeks (p < 0.001, effect size = 1.33). Although the scores dipped, there was a retention of knowledge at 72 weeks (effect size = 0.48). DISCUSSION: Spaced reinforcement and testing statistically improved knowledge retention among our medical students. Gaps in the present teaching could be bridged by motivating the students to extend their learning time by appropriate spacing intervals and to understand the relevance of course content in different scenarios as a physician. Further research could be instrumental in optimising interventions to enhance learning opportunities for medical students.

Epidemic of Vitamin D Deficiency and Its Management: Awareness among Indian Medical Undergraduates.

Vitamin D deficiency is prevalent across all age groups in epidemic proportions. The purpose of this study was to acquire a baseline assessment and create awareness among medical students regarding vitamin D. A cross-sectional, voluntary survey was conducted among undergraduate medical students. Data were collected using a questionnaire which assessed the level of knowledge students had with regard to where vitamin D comes from, what it does for health, how much is recommended, factors that affect its levels, and deficiency management. Majority of students were unaware that vitamin D deficiency has attained epidemic proportions. Though bone and skeletal disorders as a complication of vitamin D deficiency were known, a large number were unaware of systemic consequences (diabetes mellitus, cardiovascular diseases, and cancers). Only one-third of respondents were aware of duration and timing of sun exposure required for adequate serum vitamin D levels. However, we observed lack of awareness among students regarding the various biochemical forms, dose, and duration of vitamin D supplementation for treatment of nutritional deficiency. Our study highlighted a lack of knowledge about the importance of vitamin D, worldwide prevalence of vitamin D deficiency, and its management among medical students. Promoting vitamin D health awareness, if replicated across populations, could lead to positive health outcomes globally.

Vitamin D Supplements in the Indian Market.

It is now known that vitamin D deficiency is a worldwide health problem. In our country, as food fortification is lacking, supplementation with pharmaceutical preparations is the only means of treatment of vitamin D deficiency. We aimed to study the composition and availability of various vitamin D preparations in the Indian market, data about which was collected from annual drug compendium. The preparations were assessed for total number, different formulations, constituents and amount of each constituent present in the formulation. Vitamin D3 is available in the form of cholecalciferol, alfacalcidiol and calcitriol as single ingredient products and in combination with calcium and other micronutrients. Most of the supplements contain calcitriol (46.5%) or alfacalcidiol (43%) as tablets (51.1%) and capsules (35.2%). Cholecalciferol, the preferred form for prophylaxis and treatment of vitamin D deficient states, constitutes only 10% of the available market preparations. High market sales of calcium supplements containing calcitriol indicate increasing intake of calcitriol rather than cholecalciferol; which could predispose to toxicity. There is a need for marketing and rational prescribing of the appropriate vitamin D supplement in ostensibly healthy Indian population. Implementation of population-based education and intervention programmes with enforcement of strict regulations could generate awareness and curb unsupervised intake of vitamin D containing dietary supplements. This health challenge mandates effective nutritional policies, fortification and supplementation programmes and partnership between government, healthcare and industry to safeguard the health of Indian population at large.

Evaluation of the anti-inflammatory activity of the aqueous and ethanolic extracts of the leaves of Albizzia lebbeck in rats.

Albizzia lebbeck Benth. (Mimosaceae) is a medicinal tree used to treat several inflammatory ailments in the Indian traditional Ayurvedic system of medicine. The aim of the present study was to evaluate the possible anti-inflammatory activity of the aqueous (AE) and ethanolic (EE) extracts of the leaves of A. lebbeck to support the ethnopharmacological claims. The study was carried out using Wistar rats (100-150 g). The AE and EE were prepared using the Soxhlet extraction process. The anti-inflammatory activity of the AE and EE of the leaves of A. lebbeck were studied using carrageenan-induced paw edema and cotton pellet-induced granuloma models. The AE and EE of the leaves of A. lebbeck at doses of 50, 100, and 200 mg/kg p.o. (oral administration) showed a dose-dependent and significant (p < 0.05) inhibition of carrageenan-induced hind paw edema with maximum percentage inhibition (PI) values of 22.34, 30.85, 39.36 and 22.53, 32.98, 42.55, respectively. The AE and EE at doses of 50, 100, 200 mg/kg p.o. significantly (p < 0.05) inhibited granuloma formation with PI values of 19.07, 27.57, 38.55 and 23.93, 32.23, 42.33, respectively. The AE and EE of the leaves of A. lebbeck showed significant (p < 0.05) anti-inflammatory activity.

Immunoprotective responses of T helper type 1 stimulatory protein-S-adenosyl-L-homocysteine hydrolase against experimental visceral leishmaniasis.

It is well known that a patient in clinical remission of visceral leishmaniasis (VL) remains immune to reinfection, which provides a rationale for the feasibility of a vaccine against this deadly disease. In earlier studies, observation of significant cellular responses in treated Leishmania patients as well as in hamsters against leishmanial antigens from different fractions led to its further proteomic characterization, wherein S-adenosyl-L-homocysteine hydrolase (AdoHcy) was identified as a helper type 1 (Th1) stimulatory protein. The present study includes immunological characterization of this protein, its cellular responses [lymphoproliferation, nitric oxide (NO) production and cytokine responses] in treated Leishmania-infected hamsters and patients as well as prophylactic efficacy against Leishmania challenge in hamsters and the immune responses generated thereof. Significantly higher cellular responses were noticed against recombinant L. donovani S-adenosyl-L-homocysteine hydrolase (rLdAdoHcy) compared to soluble L. donovani antigen in treated samples. Moreover, stimulation of peripheral blood mononuclear cells with rLdAdoHcy up-regulated the levels of interferon (IFN)-γ, interleukin (IL)-12 and down-regulated IL-10. Furthermore, vaccination with rLdAdoHcy generated perceptible delayed-type hypersensitivity response and exerted considerably good prophylactic efficacy (∼70% inhibition) against L. donovani challenge. The efficacy was confirmed by the increased expression levels of inducible NO synthase and Th1-type cytokines, IFN-γ and IL-12 and down-regulation of IL-4, IL-10 and transforming growth factor (TGF)-ß. The results indicate the potentiality of rLdAdoHcy protein as a suitable vaccine candidate against VL.

Protective effect of pioglitazone on cardiomyocyte apoptosis in low-dose streptozotocin & high-fat diet-induced type-2 diabetes in rats.

BACKGROUND & OBJECTIVES: Cardiomyocyte apoptosis is one of the pathologic phenomena associated with diabetes and related conditions including obesity, insulin resistance and hyperlipidaemia. In the present study, the protective effects of pioglitazone on cardiomyocyte apoptosis was evaluated in experimental diabetes induced by low dose of streptozoticin (STZ) combined with high fat diet (HFD) in rats. METHODS: Male Wistar rats (150-200 g) were injected with low-dose STZ (45 mg/kg, i.v., single dose) and orally fed with a HFD (20 g/day/rat) for a period of 28 days and simultaneously treated with pioglitazone (20 mg/kg/p.o.) for a period of 21 days (from 8 th day to 28 th day). On 29 th day blood was collected, serum separated and used for biochemical parameters. Heart tissue was used for cardiomyocyte apoptosis measurement and also for histopathological examination. RESULTS: Pioglitazone treatment resulted in a decrease in cardiomyocyte apoptosis as revealed by a decrease in cardiac caspase-3, lactate dehydrogenase (LDH) levels and DNA fragmentation, and an increase in Na+K+ATPase levels in diabetic rats. Cardiac histology of diabetic control rats showed dense focal fatty infiltration in the myocardial cells whereas normal architecture with regular morphology and well preserved cytoplasm was observed with pioglitazone treatment. Pioglitazone treatment significantly reduced the heart rate, mean arterial blood pressure, body mass index (BMI) and levels of serum glucose, leptin, insulin, HOMA-IR, total cholesterol (TC) and triglycerides (TGs), apoliproprotein-B glycosylated haemoglobin (HbA1c) levels and atherogenic index, and increased the levels of serum high density lipoprotein cholesterol (HDL-C) and cardiac antioxidant enzymes. INTERPRETATION & CONCLUSIONS: The present study results suggest that pioglitazone possesses cardiac anti-apoptotic potential in diabetic rat model and can be further explored for its use for treatment of diabetic cardiomyopathy.

Central analgesic activity of the aqueous and ethanolic extracts of the leaves of Albizia lebbeck: role of the GABAergic and serotonergic pathways.

Albizia lebbeck Benth. is extensively used in Indian traditional medicine for treating several painful and inflammatory disorders. The possible central analgesic activity and the underlying mechanism of action of the aqueous (AE) and ethanolic extracts (EE) of the leaves of A. lebbeck were investigated in Wistar rats using Eddy's hot plate and the tail flick tests. In order to investigate the underlying mechanism of action, rats were pretreated with naloxone, bicuculline or methysergide and then were administered a per os (p.o.) dose of AE or EE. AE and EE caused a significant (p<0.05) elevation in the mean basal reaction time in the hot plate method and an increase in the latency time in the tail flick method. In rats pretreated with bicuculline and methysergide, a significant (p<0.05) reduction in the analgesic activity was observed in comparison to AE and EE. Thus, AE and EE exhibited significant central analgesic activity and act possibly via the GABAergic and serotonergic pathways. The flavonoids and saponins found in the leaves could be responsible for the observed effect.

Protective Effect of Gymnema sylvestre Ethanol Extract on High Fat Diet-induced Obese Diabetic Wistar Rats.

Obesity is associated with numerous co-morbidities such as cardiovascular diseases, type 2 diabetes, hypertension and others. Therefore, the present study was planned to investigate the effect of water- soluble fraction of Gymnema sylvestre ethanol extract on biochemical and molecular alterations in obese diabetic rats. Diabetes was induced by single i.v. injection of streptozotocin (45 mg/kg) via tail vein. Obesity was induced by oral feeding of high fat diet for a period of 28 days in diabetic rats. Body weight gain, food intake, water intake, hemodynamic parameters (systolic, diastolic, mean arterial blood pressures and heart rate), serum biochemical parameters (leptin, insulin, lipid levels, apolipoprotein B and glucose), cardiomyocyte apoptosis (cardiac caspase-3, Na(+)/K(+) ATPase activity and DNA fragmentation) organs and visceral fat pad weight and oxidative stress parameters were measured. Oral treatment with water soluble fraction of Gymnema sylvestre ethanol extracts (120 mg/kg/p.o.) for a period of 21 days, resulted in significant reduction in heart rate, mean arterial pressure, serum leptin, insulin, apolipoprotein B, lipids, glucose, cardiac caspase-3 levels, Na(+)/K(+) ATPase activity and DNA laddering, visceral fat pad and organ's weight and improved the antioxidant enzymes levels in the high fat diet induced obesity in diabetic rats. The results of present study reveal that water soluble fraction of Gymnema sylvestre ethanol extract could be useful intervention in the treatment of obesity and type-2 diabetes mellitus.

Efficacy of Withania somnifera chemotypes NMITLI - 101R, 118R and Withaferin A against experimental visceral leishmaniasis.

The immunoprophylactic and therapeutic potentials of root extracts of Withania somnifera chemotypes (NMITLI-118, NMITLI-101) and pure withanolide-withaferin A was investigated against Leishmania donovani infection in hamsters. The naive animals, fed orally with immunostimulatory doses of chemotypes 101R, 118R (10 and 3 mg/kg) and withaferin A (9 and 3 mg/kg) for five consecutive days and challenged with Leishmania parasites on day 6, were euthanized on days 30 and 45 p.c. for the assessment of parasite clearance, real-time analysis of mRNAs of Th1/Th2 cytokines (IFN-γ, IL-12, TNF-α, iNOS/IL-4, IL-10 and TGF-ß), NO production, reactive oxygen species (ROS) generation, lymphocyte transformation test and antibody responses. By day 45 p.c., there was a significant increase in the mRNA expression of iNOS, IFN-γ, IL-12 and TNF-α but decrease in IL-4, IL-10 and TGF-ß, an enhanced Leishmania-specific LTT response as well as ROS, NO and antileishmanial IgG2 levels in 101R-treated hamsters followed by 118R- and withaferin A-treated ones, respectively. When these chemotypes were given to L. donovani-infected hamsters at different doses, there was moderate therapeutic efficacy of chemotype 101R (~50%) at 30 mg/kg × 5 followed by the other two. The results established that the 101R is the most potential chemotype and can be evaluated for combination therapy along with available antileishmanials.

Anti-obesity effect of Gymnema sylvestre extract on high fat diet-induced obesity in Wistar rats.

Gymnema sylvestre R. BR. (Asclepiadaceae) has been used frequently in traditional Indian folk medicine for the treatment of diabetes. Study was performed in high fat diet (HFD)-induced obesity in murine model. Obesity was induced by oral feeding of HFD for 28 days. The anti obesity effect of water soluble fraction of Gymnema sylvestre extract (120 mg/kg, p.o. for 21 days) in HFD fed rats was evaluated by the measurement of body weight gain, food intake, hemodynamic changes (systolic, diastolic, mean blood pressure and heart rate), serum lipid profiles (triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol), leptin, insulin, glucose, apolipoproteins A1 and B, lactate dehydrogenase (LDH) and antioxidant enzymes such as reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S transferase (GST), superoxide dismutase (SOD) and catalase (CAT) levels in liver tissues. Organs and visceral fat pad weight were measured. Histopathological studies were also carried out. Water soluble fraction of G. sylvestre ethanolic extract and rimonabant significantly reduced serum lipids, leptin, insulin, glucose, apolipoprotein B and LDH levels while it significantly increased the HDL-cholesterol, apolipoprotein A1 and antioxidant enzymes levels in liver tissue as compared to the HFD fed rats. Histopathological studies of tissues showed no pathological changes. The results of this study show that water soluble fraction of G. sylvestre extract possess antiobesity effect.

Clinical review of sitagliptin: a DPP-4 inhibitor.

Type 2 Diabetes Mellitus is most common form of diabetes. Oral agents are the main stay of pharmacological treatment for type 2 diabetes mellitus. Dipeptidyl peptidase-4 (DPP-4) inhibitors represent a new therapeutic approach for type 2 diabetes. Sitagliptin is highly selective DPP-4 inhibitor that has been approved for type 2 diabetes therapy. It acts by increasing the levels of incretins by inhibiting their degradation by DPP-4. Sitagliptin has been shown to be effective, well tolerated and safe in the treatment of type 2 diabetes in monotherapy or in combination with metformin or thiozolidinediones with minimal side effects.

Efficacy of turmeric (curcumin) in pain and postoperative fatigue after laparoscopic cholecystectomy: a double-blind, randomized placebo-controlled study.

OBJECTIVE: Better patient-reported outcomes (PROs) of laparoscopic cholecystectomy (LC) are premised upon PROs such as postoperative pain and fatigue. These PROs are indices of convalescence and return to normal activity. Curcumin (turmeric) is used in India for traumatic pain and fatigue for its anti-inflammatory/antioxidant and tissue modulation/healing properties. We studied the effect of curcumin on pain and postoperative fatigue in patients of LC. METHODS AND PROCEDURES: From July to September 2009, 50 consecutive day-care LC candidates were enrolled for a prospective, double-blind randomized placebo-controlled study. A uniform general anesthesia and analgesia protocol was followed. Curcumin/placebo and rescue analgesic were prescribed at discharge. Patients were told to maintain pain/fatigue/adverse event diaries based upon 100-point visual analog pain scale (VAS) and 10-point interval rating fatigue scale (IRS). Patients were followed up at third day (D3), first week (W1), second week (W2), and third week (W3). The blind labels were opened at the end of study. RESULTS: Demographic characteristics, comorbidity, and gallbladder pathology profiles were comparable in the study (n = 25) and control groups (n = 25). There was no adverse surgical outcome, adverse PRO or withdrawal. Pain and fatigue scores at D3 were similar in the two groups. At W1 and W2, the study group showed significantly lower (p value 0.000) mean pain scores, i.e., 15 ± 5.204 versus 30 ± 13 in controls. Fatigue scores at W1, W2, and W3 were significantly lower (p value 0.000) in the study group, i.e., 2.16 ± 1.748, 1, and 0, respectively, versus 5.16 ± 1.375, 4.20 ± 1.633, and 1 in controls. All patients were pain free at W3. Analgesic tablet usage was significantly lower (p value 0.000) in the study group, i.e., 6.96 ± 1.837 versus 39.32 ± 16.509 in controls. CONCLUSIONS: Turmeric (curcumin) improves postoperative pain- and fatigue-related PROs following LC.

N-Methyl-D-aspartate receptor modulators block hyperalgesia induced by acute low-dose morphine.

1. Following opioid-induced antinociception in mice, hyperalgesic responses may be observed. The present study was designed to evaluate the effect of different N-methyl-d-aspartate (NMDA) receptor modulators (magnesium, dextromethorphan, d-serine) on the development of morphine-induced hyperalgesia in mice. The tail-flick test was used to assess the effects of morphine alone and in combination with the NMDA receptor modulators. 2. Administration of a single low dose (2 mg/kg) of morphine to mice produced antinociception that was followed by hyperalgesia. 3. Administration of magnesium sulphate (5 mg/kg) and d-serine (10 mg/kg) alone produced a transient antinociceptive response, whereas dextromethorphan (10 mg/kg) alone produced a prolonged antinociceptive response that had a relatively delayed onset after 4 h. 4. When coadministered with morphine, the NMDA receptor blockers magnesium (2 mg/kg) and dextromethorphan (2 and 5 mg/kg) and the NMDA receptor agonist d-serine (2, 5 and 10 mg/kg), maintained the duration of the antinociceptive response to morphine and inhibited the development of the hyperalgesic response. Coadministration of dextromethorphan (10 mg/kg) with morphine produced antinociception at 30-120 min and at 4-24 h. 5. The results of the present study suggest that coadministration of low-dose NMDA receptor antagonists, as well as the NMDA receptor agonist d-serine, with morphine can inhibit morphine-induced hyperalgesia.