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Objective: To investigate the effect of Ocimum sanctum hydroalcoholic extract (OSHE) on seizure control and neuronal injury in rats with lithium-pilocarpine-induced status epilepticus (SE). Methods: SE was induced by administering lithium chloride followed by pilocarpine 24 h later. OSHE was administered either alone or in combination with valproate (VPA) 3 days before SE induction until 14 days post-SE induction. Seizure parameters were recorded on day 1 (0-3 h), day 1-3 and day 4-14 post-SE. On day 14 post-SE, neurobehavioural tests (elevated plus maze and passive avoidance) were done followed by total antioxidant capacity, neuronspecific enolase, immunohistochemistry, and electron microscopic assessment in the hippocampus and cortex tissue. Results: OSHE+VPA provided more significant seizure protection (75%) than VPA (62.5%), OSHE (62.5%), or SE control (12.5%) (overall P=0.003). The latency to stage-3/4 seizures was increased and the number of stage-3/4 seizures was reduced in all treatment groups compared to the SE control group (P=0.002 and <0.001, respectively). The OSHE+VPA group also had better memory retention than other treatment groups (P<0.001) in the passive avoidance test. Total antioxidant capacity level was significantly higher and neuron-specific enolase was lower in the OSHE and OSHE+VPA groups compared to the SE control group. Electron microscopic study showed significant myelin sheath damage (67.5%, P<0.05) and axonal degeneration (51.8%, P<0.001) in the hippocampus of the SE control group, which were alleviated by OSHE or OSHE+VPA treatment. In immunohistochemical analysis, the OSHE, OSHE+VPA, and VPA groups had a significantly higher number of viable neurons and less neuronal loss compared to the SE control in the hippocampus (P<0.001). Conclusions: OSHE either alone or in combination with VPA shows better seizure control by preservation of neuronal echotexture and reducing oxidative stress in the hippocampus. [ABSTRACT FROM AUTHOR]

Along with the rising prevalence of inflammatory bowel disease (IBD) [Crohn's disease (CD) and ulcerative colitis (UC)], biological therapies need an update/insight. This review included randomized controlled trials (RCTs) from PubMed database (2000–October 2022) of approved biologics and small molecules with primary outcome analysis on efficacy (clinical response/remission/mucosal healing) and/or adverse events (AEs). Considered for this review under biologics classes are TNF-α inhibitors, leukocyte trafficking inhibitors, and anti IL-12/IL-23; and under small molecules are Janus-kinase inhibitors, and sphingosine-1-phosphate receptor modulators. In CD, clinical response and remission were better with tofacitinib (61.23%) and infliximab (44.86%), respectively, in the induction phase, and these were better with ustekinumab in the maintenance phase. In UC, the maximum rate of response, remission, and mucosal healing were obtained with infliximab during the induction phase (67.49%, 35.99%, and 60.25%, respectively). During the maintenance phase, response rate was better with ustekinumab, but remission and mucosal healing were better with vedolizumab. The combined percentage of AEs was highest with infliximab (174.45%) and least with ozanimod (23.04%), and most commonly belonged to the 'infection and infestation system organ class (SOC).' These efficacy and safety analyses will help in the optimization of biologic treatment in IBD. [ABSTRACT FROM AUTHOR]

With the advancement of clinical research and the increased burden on laboratory services, there is an unmet need for guidelines regarding proper laboratory functioning and reliable data generation. Several organizations from all over the world have published guidelines for these clinical and research laboratories. Good Clinical Laboratory Practices (GCLP) are stepwise procedures aimed at strengthening the quality of test results produced by all clinical laboratories engaged in human sample analysis. In this article, we attempt a comparison of the GCLP guidelines recently issued by the Indian Council of Medical Research with the guidelines released by the World Health Organization and the European Medicines Agency. Also, we have included and discussed several suggestions that, if included, will lead to the strengthening of the laboratory practices used for both research and patient care for overall improvement in the Indian healthcare system. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The National Formulary of India (NFI), a ready reckoner for medicines among healthcare-professionals aims for promoting rational drug use. This needs periodic update based on evidence-based medicines and suggestions from end-users. This study assessed the level of awareness among health-care professionals and sought suggestions for enhancement of utility/content of NFI. MATERIALS AND METHODS: This pan-India cross-sectional, questionnaire-based survey was conducted between November-2020 and March-2021. A Google-doc-based validated questionnaire (20 questions) was circulated through E-mail/social media groups and to 311 medical institutes/hospitals/clinics across India through the adverse drug reaction monitoring centers under the Pharmacovigilance Program of India. RESULTS: A total of 461 participants (39-interns, 167-resident doctors, and the rest practicing physicians/doctors) affiliated to 224 institutes/hospitals/clinics had responded. About 46% respondents consulted NFI for drug-related information and 82.3% stated that NFI provides balanced unbiased information. About 95% respondents were aware of NFI's content and 76% mentioned usefulness of NFI in their clinical practice; however, 34.4% had misconceptions about NFI, 28.7% had a false belief that NFI is a legal document to safeguard health-care providers and 22.2% had never used it. Suggestions to enhance NFI's utility included digital accessibility, incorporation of information like drugs for basic medical emergencies (71.3%), disposal of expired-pharmaceutical products (38.7%), pharmaceutical price control policy (36.3%), and drug-procurement practices in hospitals (35.6%). CONCLUSION: As per the survey findings, NFI is an effective tool for instant access to precise and unbiased drug-related information, and fostering rational use of drugs. Boosting its practical usefulness needs incorporation of suggested information, digital accessibility, and periodic update. [ABSTRACT FROM AUTHOR]

Introduction: Chronic neurological diseases are a major cause of mortality and morbidity in the world. With increasing life expectancy in the developing world, the incidence and prevalence of these diseases are predicted to rise even further. This has also contributed to an increase in disability-adjusted life years (DALYs) for noncommunicable diseases. Treatment for such diseases also poses a challenge with multiple genetic and epigenetic factors leading to a varied outcome. Personalization of treatment is one way that treatment outcome/prognosis of disease can be improved, and pharmacogenomics plays a significant role in this context.Methodology: This article reviewed the evidence pertaining to the association of genetic and epigenetic markers with major neurological disorders like multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD), which are a major source of burden among neurological disorders. Types of studies included are peer-reviewed original research articles from the PubMed database (1999-2018).Results: This study compiled data regarding specific genetic and epigenetic markers with a significant correlation between the clinical diagnosis of the disease and prognosis of therapy from 65 studies. In a single platform, this review highlights the clues to some vital questions, such as why interferon beta (IFN-β) therapy fails to improve symptoms in all MS patients? why cholinesterase inhibitors fail to improve cognitive impairment in a subset of people suffering from AD? or why some individuals on levodopa (L-DOPA) for PD suffer from side-effects ranging from dyskinesia to hallucination while others do not?Conclusion: This article summarizes the genetic and epigenetic factors that may either require monitoring or help in deciding future pharmacotherapy in a patient suffering from MS, AD, and PD. As the health care system develops and reaches newer heights, we expect more and more of these biomarkers to be used as pharmacotherapeutic outcome indicators. [ABSTRACT FROM AUTHOR]

Objectives: Antiepileptic drug (AED) tapering in persons with epilepsy (PWE) after 2‐3 years of seizure freedom is still debatable because of the risk of seizure recurrence. Tapering patterns have wide variability and could impact seizure recurrence; this study aimed to find out the correlation between them. Material and Methods: This prospective, observational independent assessor study enrolled PWE undergoing AED tapering in a tertiary care hospital. Data collected included demography, seizure history, AED treatment, and investigational findings. Tapering pattern was assessed based on seizure‐free period and AED dose before onset of tapering, dose reduction percentage and frequency, duration of tapering, and follow‐up. These variables were compared among the PWE with seizure recurrence and no seizure recurrence. Results: Among 408 enrolled PWE, 181 were on AED monotherapy: levetiracetam (73), valproate (45), carbamazepine (44), phenytoin (16), and clobazam (3). With a minimum 19 (maximum 41 months) follow‐up, seizure recurrence was reported in 119 (29.2%) PWE. The seizure recurrence was not significantly different in‐between mono and polytherapy groups; however, among monotherapy groups seizure recurrence was significantly higher (P =.023) in valproate (35.5%) followed by levetiracetam (28.8%) group. Parameters having significant association with seizure recurrence were duration of epilepsy (P =.03), frequency of seizures before control (P =.002), history of previously failed tapering (P =.04), and history of smoking/alcoholic/tobacco intake (P =.003). Conclusions: There is a wide variation in AEDs tapering pattern and seizure recurrence risk can be minimized by considering the risk factors like history of smoking/alcoholic/tobacco, longer duration of epilepsy, frequency of seizures before control, and previously failed tapering. [ABSTRACT FROM AUTHOR]

Phase I clinical trial is the first exposure of investigational medicinal product in humans and it sets the pillar for further clinical development. Substantial attention has been paid to the first in human clinical trials after TeGenero TGN1412 disaster in 2006 which led to serious toxicity including multi-organ failure in 6 healthy volunteers. Since then many recommendation and guidelines have been formulated for the safe and rational conduct of such trials. In January 2016, another catastrophe occurred in France during Phase I trial of BIA 10-2474, a fatty acid amide hydrolase inhibitor, which led to one death and caused serious neurological damage in few other healthy volunteers. This review will focus on potential issues in BIA 10-2474 trial, possible measures that should have been taken during trials to prevent this disaster and potential safety measures for the rational and safe conduct of Phase I trials. [ABSTRACT FROM AUTHOR]

Background & objectives: Though newer antiepileptic drugs are considered safer than conventional antiepileptics, the effects of lamotrigine, levetiracetam and topiramate on neurobehavioural functions are yet to be established. This study evaluated neurobehavioural parameters and oxidative stress markers in brain tissue of rats treated with lamotrigine, levetiracetam and topiramate compared to sodium valproate . Methods: Five groups of male Wistar rats were treated respectively with normal saline (control), sodium valproate (370 mg/kg), lamotrigine (50 mg/kg), levetiracetam (310 mg/kg) and topiramate (100 mg/kg) for 45 days. Neurobehavioural parameters were assessed using elevated plus maze (EPM), actophotometer, rotarod, passive avoidance and Morris water maze (MWM) at baseline and at the end of treatment. Oxidative stress parameters [malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD)] were estimated in rat brain at the end of treatment. Results: Valproate and lamotrigine showed no significant effect on learning and memory in passive avoidance and MWM tests. However, levetiracetam and topiramate reduced retention memory significantly as compared to control (P<0.01) and lamotrigine (P<0.05) groups. Performances on EPM, rotarod and actophotometer were not significantly different between the groups. In comparison to control group, MDA was higher in the levetiracetam and topiramate (360.9 and 345.9 nmol/g of homogenized brain tissue, respectively) groups. GSH and SOD activity were significantly reduced by valproate and levetiracetam treatment. Lamotrigine did not induce significant oxidative stress. Interpretation & conclusions: Long-term and therapeutic dose treatment with levetiracetam and topiramate significantly impaired learning and memory, which was not seen with valproate and lamotrigine in rats. Levetiracetam, topiramate and valproate augmented oxidative stress, whereas lamotrigine has little effect on it. These antiepileptic drugs are used in clinical practice, hence pharmacovigilance studies are required to evaluate their safety profile. [ABSTRACT FROM AUTHOR]

Background & objectives: Certain antiepileptic drugs (AEDs) such as valproic acid (VPA) are known to affect body weight, and lipid profile. However, evidences regarding effects of AEDs on the body composition are deficient. This cross-sectional study compared the body composition and lipid profile among patients with epilepsy on newer and conventional AEDs. Methods: The patients with epilepsy (n=109) on treatment with conventional and newer AEDs (levetiracetam, lamotrigine and clobazam) for > 6 months were enrolled. Of these, 70 were on monotherapy: levetiracetam (n=12), VPA (n=16), carbamazepine (n=20) and phenytoin (n=22) and the remaining on polytherapy. Their body composition [body fat mass, lean dry mass (LDM), total body water (TBW), intracellular water (ICW), extracellular water (ECW) and basal metabolic rate (BMR) was estimated and biochemical parameters were assessed. Results: Levetiracetam group had no significant difference with VPA, carbamazepine, phenytoin and control groups, except low LDM (17.8±2.4) than VPA groups (20.2±2.7, P<0.05). In comparison with control, AEDs monotherapy groups had no significant difference, except higher LDM and ECW in VPA group. Among groups based on conventional and newer AEDs, there was no significant difference in body composition parameters except for higher LDM (as % of BW) in conventional AEDs only treated group than control (P<0.01). Interpretation & conclusions: The alterations observed in body composition with valproic acid in contrast to other AEDs like levetiracetam, carbamazepine and phenytoin could affect treatment response in epilepsy especially in subjects with already altered body composition status like obese and thin frail patients, which needs to be established by prospective studies (CTRI/2013/05/003701). [ABSTRACT FROM AUTHOR]

Treatment of cancer is a major challenge even though the pathophysiology is becoming clearer with time. A number of new chemical entities are developed to target cancer growth inhibition, but the targeted delivery of these products still needs novel research. This is of utmost importance not only for higher efficacy but also for a reduction in systemic toxicity and cost of treatment. Although multiple novel targets and molecules are being researched, most of them could not pass the regulatory approval process, due to low benefit-risk ratio and lack of target specificity. Failure of a majority of these drugs was in part due to their superiority claimed via surrogate markers. Despite these, currently, more than 100 chemotherapeutic agents are in practice. This review paper discusses in detail the molecular basis, drug discovery, and pros and cons over conventional treatment approaches of three novel approaches in cancer therapy, i.e., (i) antibody-drug conjugates, (ii) cancer immunotherapy, and (iii) metronomic chemotherapy. All the drugs developed using these three novel approaches were compared against the established treatment regimens in clinical trials with clinical end points, such as overall survival, progression-free survival, and quality of life., Competing Interests: None

Background & Objectives: Pioglitazone was suspended for manufacture and sale by the Indian drug regulator in June 2013 due to its association with urinary bladder carcinoma, which was revoked within a short period (July 2013). The present questionnaire-based nationwide study was conducted to assess its impact on prescribing behaviour of physicians in India., Methods: Between December 2013 and March 2014, a validated questionnaire was administered to physicians practicing diabetes across 25 centres in India. Seven hundred and forty questionnaires fulfilling the minimum quality criteria were included in the final analysis., Results: Four hundred and sixteen (56.2%) physicians prescribed pioglitazone. Of these, 281 used it in less than the recommended dose of 15 mg/day. Most physicians (94.3%) were aware of recent regulatory events. However, only 333 (44.8%) changed their prescribing pattern. Seventeen of the 416 (4.1%) physicians who prescribed pioglitazone admitted having come across at least one type 2 diabetes mellitus patient (T2DM) who had urinary bladder carcinoma, and of these 13 said that it was in patients who took pioglitazone for a duration of more than two years. Only 7.8 per cent of physicians (n=58) categorically advocated banning pioglitazone, and the rest opined for its continuation or generating more evidence before decision could be taken regarding its use in T2DM., Interpretation & Conclusions: Majority of the physicians though were aware of the regulatory changes with regard to pioglitazone, but their prescribing patterns were not changed for this drug. However, it was being used at lower than the recommended dose. There is a need for generating more evidence through improved pharmacovigilance activities and large-scale population-based prospective studies regarding the safety issues of pioglitazone, so as to make effectual risk-benefit analysis for its continual use in T2DM., Competing Interests: None