Role of Standardized Plant Extracts in Controlling Alcohol Withdrawal Syndrome-An Experimental Study.

Patients with alcohol use disorder experience alcohol withdrawal syndrome due to the sudden cessation of alcohol. This study was designed to evaluate the protective effect of Ashwagandha and Brahmi on alcohol withdrawal in rats. Thirty rats of either sex were taken and randomly divided into 6 groups (n = 5). Their normal diet was replaced by a modified liquid diet (MLD). Ethanol was added gradually except in the MLD group for a period of 21 days and withdrawn suddenly. Four treatment groups were administered Ashwagandha (3.75 mg of withanolide glycosides per kg body weight), Brahmi (10 mg of bacosides per kg body weight), Ashwagandha + Brahmi (3.75 mg withanolide glycosides + 10 mg bacosides per kg body weight) orally and diazepam (1 mg/kg body weight, i.p.) 45 min before alcohol withdrawal. Rats were assessed for behavioural changes (agitation score and stereotypic behaviour), anxiety and locomotor activity at 2nd and 6th hours of alcohol withdrawal. Pentylenetetrazol (PTZ) kindling seizures were assessed at 6th hour of alcohol withdrawal. Ashwagandha and Brahmi alone and in combination significantly reduced the behavioural changes in alcohol withdrawal rats at 2nd hour and their combination in 6th hour. Ashwagandha and Brahmi suppressed PTZ kindling seizures effectively and improved locomotory activity at 2nd hour and 6th hour of alcohol withdrawal. Reduction in anxiety was significant among Ashwagandha at 2nd hour and the combination group at 2nd and 6th hour. The results were comparable to diazepam. Ashwagandha and Brahmi have beneficial effects in controlling the behavioural changes, anxiety and seizures in alcohol withdrawal symptoms in rats and improved locomotory activity.

Bioavailable turmeric extract for knee osteoarthritis: a randomized, non-inferiority trial versus paracetamol.

BACKGROUND: To compare the efficacy and safety of bioavailable turmeric extract versus paracetamol in patients with knee osteoarthritis (OA). METHODS: In this randomized, non-inferiority, controlled clinical study, patients of knee OA were randomized to receive bioavailable turmeric extract (BCM-95®) 500 mg capsule two times daily or paracetamol 650 mg tablet three times daily for 6 weeks. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. The secondary outcome measures were WOMAC total, WOMAC stiffness, and WOMAC physical function scores. Responder analysis of individual patients at different levels (≥ 20%, ≥ 50%, and ≥ 70%) for WOMAC score was calculated. TNF alpha and CRP levels were evaluated and adverse events (AE) were also recorded. RESULTS: Seventy-one and seventy-three knee OA patients, respectively in bioavailable turmeric extract and paracetamol groups, completed the study. Non-inferiority (equivalence) test showed that WOMAC scores were equivalent in both the groups (p value < 0.05) in all the domains within the equivalence limit defined by effect size (Cohen's d) of 0.5 whereas CRP and TNF-α were better reduced with turmeric extract than paracetamol. After 6 weeks of treatment, WOMAC total score, pain, stiffness, and function scores got a significant improvement of 23.59, 32.09, 28.5, and 20.25% respectively with turmeric extract. In the turmeric extract group, 18% of patients got more than 50% improvement and 3% of patients got more than 70% improvement in WOMAC pain and function/stiffness score and none of the patients in the paracetamol group met the criteria. CRP and TNF-α got significantly reduced (37.21 and 74.81% respectively) in the turmeric extract group. Adverse events reported were mild and comparatively less in the turmeric extract group (5.48%) than in the paracetamol group (12.68%). CONCLUSION: The results of the study suggest that bioavailable turmeric extract is as effective as paracetamol in reducing pain and other symptoms of knee osteoarthritis and found to be safe and more effective in reducing CRP and TNF-α. TRIAL REGISTRATION: Clinical Trials Registry - India CTRI/2017/02/007962 . Registered on 27 February 2017.

Effect of sofosbuvir and daclatasvir on lipid profile, glycemic control and quality of life index in chronic hepatitis C, genotype 3 patients.

OBJECTIVES: The management of hepatitis C has progressed from interferon-based therapy to oral direct acting antiviral therapy. Deranged lipid levels (total cholesterol, triglyceride) after treatment with interferon-based therapy are well known. There is a paucity of data on changes in lipid profile, glycemic parameters and alteration in quality of life with the newer regimen. This study was designed to assess the changes in lipid profile, glycemic parameters, quality of life in chronic hepatitis C patients with genotype 3 after treatment with sofosbuvir and daclatasvir. METHODS: The study was a single-centre, prospective study, conducted at tertiary care hospital from January 2017 to December 2017. Fifty patients, who received sofosbuvir (400 mg) and daclatasvir (60 mg) orally once daily for a period of 12 weeks for chronic hepatitis C and genotype 3, were recruited. RESULTS: Total cholesterol levels (166.9 ± 23.8 to 192.4 ± 34.5 mg/dL, p-value < 0.0001) and low-density cholesterol (LDL) levels (100.9 ± 22.8 to 121.6 ± 37.2, p-value < 0.0001) were elevated after the treatment. A significant decrease in median levels of glycated hemoglobin (HbA1c) was observed (5.57% to 5.41%, p-value < 0.002). Quality of life markedly improved in all domains, i.e. physical, physiological, environmental, and social relationships according to an abbreviated form of World Health Organization quality of life assessment named WHOQOL-BREF questionnaire. Treatment was found to be effective with sustained virological response (SVR) achieved in 94% patients. CONCLUSIONS: Our study reports a substantial increment in total cholesterol, and low-density lipoprotein with sofosbuvir and daclatasvir treatment though it achieved SVR in 94% of patients and improved their quality of life.

Adverse Drug Reactions and their Impact on Quality of Life in Patients on Antipsychotic Therapy at a Tertiary Care Center in Delhi.

CONTEXT: Adverse drug reactions (ADR) due to antipsychotic therapy have significant impact on a psychiatric patient's quality of life. Few studies have been conducted in India to monitor adverse drug reactions due to antispsychotics and none has been done to determine their impact on quality of life. AIMS: The present study was conducted to monitor ADRs due to antipsychotics and ascertain the impact of ADRs on quality of life. SETTINGS AND DESIGN: This prospective observational study was conducted in the psychiatry outpatients department in New Delhi for 1 year. PATIENTS AND METHODS: A total of 224 patients enrolled were followed up for a period of 3 months. ADRs were monitored using the standard form of the Central Drugs Standard Control Organization and causality was determined using the Naranjo algorithm. The WHO Quality of Life BREF (WHOQOL-BREF) scale was used to study the effect of ADR on the quality of life. STATISTICAL ANALYSIS USED: The data were entered and analyzed using the statistical software SPSS 17.0. Unpaired t-test was used to compare the quality of life of patients who encountered ADRs and those who did not. P < 0.05 was considered statistically significant. RESULTS: Of the total 224 patients, 38 adverse drug events occurred. Adverse drug events were mostly with risperidone (10), followed by olanzapine (8) owing to high usage. Majority of the events were classified as probable (34). The occurrence of adverse drug events decreased the scores on physical and psychological domain scores of WHO-QOL BREF at 3 months compared to baseline. CONCLUSIONS: The study provides information on the existing incidence of ADRs in the setup with an established pharmacovigilance center. The nature of ADRs correlates with the prevalence pattern of usage of atypical antipsychotics. Clinicians need to weigh benefit versus the impact on quality of life while prescribing antipsychotics.

Advice on exercise for pregnant women with hypertensive disorders of pregnancy.

Reports on advice about exercise for women with hypertensive disorders of pregnancy are reviewed and how exercise could influence long-term cardiovascular risk is assessed. Exercise in pregnancy seems to be beneficial in pregnancies complicated by hypertension. However, the intensity of the exercise to be recommended remains unclear. Further research is required to inform national and international guidelines for women who develop hypertension during pregnancy.

Effect of addition of either sitagliptin or pioglitazone in patients with uncontrolled type 2 diabetes mellitus on metformin: A randomized controlled trial.

OBJECTIVE: To compare and study the dipeptidy1 peptidase-4 (DPP-4) inhibitors in combination with metformin against established combination therapies. MATERIALS AND METHODS: This 16-week study was designed to compare sitagliptin versus pioglitazone as add-on therapy in patients of type 2 diabetes mellitus inadequately controlled with metformin alone. Fifty-two patients were randomized into two groups to receive either sitagliptin 100 mg (group 1) or pioglitazone 30 mg (group 2) in addition to metformin. The primary efficacy end point was change in HbA1c. Secondary end points included change in fasting plasma glucose (FPG), body weight and lipid profile. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire. Both the groups had a significant decrease in HbA1c. RESULTS: There was no significant difference between mean reductions in FPG in both the groups. There was a significant decrease in the mean body weight and body mass index in group 1 in contrast to the significant increase in the same in group 2. Both the treatment groups reported a significant decrease in High-density lipoprotein (HDL-C) and Triglyceride. CONCLUSION: Sitagliptin was well tolerated without any incidence of hypoglycemia. It was concluded that sitagliptin as an add-on to metformin is as effective and well tolerated as pioglitazone.

SGLT2 inhibitors: a new emerging therapeutic class in the treatment of type 2 diabetes mellitus.

The incidence of type 2 diabetes mellitus is increasing worldwide. The existing therapeutic classes of antidiabetic drugs are not adequately effective in maintaining long-term glycemic control in most patients, even when used in combination. One emerging novel therapeutic class of antidiabetic drugs is sodium glucose cotransporter 2 (SGLT2) inhibitors. SGLT2 accounts for 90% of the glucose reabsorption in the kidney. The SGLT2 inhibitors increase urinary excretion of glucose and lower plasma glucose levels in an insulin-independent manner. Dapagliflozin, the most prominent molecule in this class, is currently in a phase III clinical trial. Other members of this class (eg, sergliflozin, remogliflozin) are also in different phases of clinical trials. This class of novel agents can effectively control blood sugar level without producing weight gain or hypoglycemia. Results of ongoing phase III clinical trials are crucial to determine whether the risk-benefit ratio will allow approval of this new class of drugs for the management of type 2 diabetes mellitus.

Recent advances in antiretroviral drugs.

IMPORTANCE OF THE FIELD: Acquired immunodeficiency syndrome (AIDS) is one of the leading causes of death worldwide. Although the combination therapies of highly active antiretroviral therapy (HAART) have significantly contributed to virological suppression, improved immune function and quality of life, issues such as tolerability, drug-drug interactions and cross-resistance amongst members of a particular drug class still pose a significant barrier to long-term successful treatment. There is a constant need for newer anti HIV drugs with increased potency and improved pharmacokinetic properties either in the existing classes or drugs from new classes that target several new steps in HIV replication cycle. AREAS COVERED IN THIS REVIEW: The authors have discussed newer antiretroviral drugs belonging to second-generation nucleoside analog reverse transcriptase inhibitors (amdoxovir, elvucitabine, apricitabine, racivir), non-nucleoside analog reverse transcriptase inhibitors (etravirine, rilpivirine), protease inhibitors (darunavir, tipranavir) as well as emerging new classes, i.e., fusion inhibitors (enfuvirtide, sifuvirtide), CCR5 inhibitors (maraviroc, vicriviroc, PRO 140, PRO 542), CD4-receptor inhibitors (ibalizumab), integrase inhibitors (raltegravir, elvitegravir, GSK-1349572), maturation inhibitors (bevirimat), cobicistat (pharmacoenhancer), lens epithelium-derived growth factor inhibitors and capsid assembly inhibitors. WHAT THE READER WILL GAIN: The reader will gain an understanding of the mechanism of action, mechanism of resistance, stages of development and important clinical trials related to the newer antiretroviral drugs and future potential of these drugs. TAKE HOME MESSAGE: The initial clinical trial data of these newer drugs are very encouraging for the long-term successful control of HIV in both treatment-naïve and treatment-experienced patients.

Pharmacogenomics--practice and challenges.

BACKGROUND: Generating revenue of over $1 billion annually to owner companies, blockbuster drugs have been a prominent feature of drug development over recent decades. However, a large number of patients have an inadequate therapeutic response to the 'one size fits all' blockbuster drugs. It is difficult to predict which patient subgroups will respond well to a drug and which will have significant adverse reactions. OBJECTIVE: This article outlines the potential role of pharmacogenomics in drug development and personalised medicine in order to examine possible treatment strategies targeted to patients according to their genetic profile. DISCUSSION: Drug development based on pharmacogenomics has the potential to result in medications that have predictable responses in ethnic or racial patient subpopulations and can be targeted to accommodate individual genetic variation. The key challenges for the successful implementation of this concept include finding suitable biomarkers, bringing down the cost of laboratory investigations, and making drug development processes based on pharmacogenomics economically viable for pharmaceutical companies.

Sexual function following pelvic floor surgery.

OBJECTIVE: To prospectively evaluate sexual function in women who underwent surgery for incontinence and/or prolapse using the Pelvic Organ Prolapse-Urinary Incontinence Sexual Questionnaire (PISQ), and to provide a preliminary evaluation of the PISQ's psychometric properties for a population of women in the United Kingdom. METHODS: Women who underwent surgery for pelvic organ prolapse and/or urinary incontinence completed the PISQ, the Sheffield Prolapse Symptoms Questionnaire, and the King's Health Questionnaire preoperatively and 4 months postoperatively. Rates of item completion were assessed to evaluate the performance of the PISQ, and Cronbach alpha values and item-total correlations were calculated for the full scale and each of the 3 domains (behavioral-emotive, physical, and partner-related). RESULTS: Thirty-five women responded to the questionnaire. Postoperatively an improvement was demonstrated for overall score (P=0.002), and for physical (P<0.001) and partner-related domains (P=0.004). CONCLUSION: Women reported a significant improvement in sexual function 4 months after surgery for incontinence and prolapse.

Evaluation of antidepressant activity of tramadol in mice.

OBJECTIVE: To evaluate antidepressant like effect of tramadol in mice. MATERIALS AND METHODS: Tramadol was administered at three different doses (10,20 and 40 mg/kg, i.p) once daily for 7 days to Swiss albino mice of either sex. The immobility period of control and drug treated mice were recorded in tail suspension test (TST).The antidepressant effect of tramadol was compared to that of fluoxetine (20 mg/kg, i.p), administered for seven days. RESULTS: Tramadol produced significant antidepressant effect at all the doses, as indicated by reduction in immobility times as compared to control. The efficacy of tramadol at doses of 20 and 40 mg/kg was comparable with that of fluoxetine. Tramadol at 10 mg/kg dose showed significantly less antidepressant activity compared to fluoxetine. CONCLUSION: The results of the present study indicate antidepressant like activity of tramadol.

Antidepressant-like activity of tramadol in mice.

OBJECTIVE: To evaluate antidepressant-like effect of tramadol in mice. MATERIALS AND METHODS: Tramadol was administered at three different doses (10, 20, and 40 mg/kg, i.p.) once daily for 7 days to Swiss albino mice of either sex. The immobility period of control and drug-treated mice was recorded in forced swim test (FST). The antidepressant effect of tramadol was compared to that of fluoxetine (20 mg/kg, i.p.), administered for seven successive days. RESULTS: Tramadol produced significant antidepressant effect at all the three (10, 20, and 40 mg/kg) doses, as indicated by reduction in immobility times of drug-treated mice compared to control mice. The efficacy of tramadol at doses of 10 and 20 mg/kg was comparable to that of fluoxetine, but antidepressant activity in animals administered with tramadol 40 mg/kg was significantly less as compared to fluoxetine-pretreated mice. CONCLUSION: The results of the present study indicate antidepressant-like activity of tramadol.