EFFECT OF DECEPTIVE VERSUS NON-DECEPTIVE PLACEBO ON PSYCHOMOTOR AND COGNITIVE FUNCTIONS IN HEALTHY ADULT HUMAN VOLUNTEERS: AN OPEN-LABEL CROSS-OVER RANDOMIZED CONTROLLED TRIAL.

This study was planned to evaluate the effect of a placebo administered with deception vs. without deception on psychomotor and cognitive functions in healthy human volunteers compared to no treatment as placebo responses tend to be circumstantial. An open-label, 3-period, 6-sequence randomized controlled cross-over trial was conducted with 54 participants in a tertiary care center.

Pharmacogenomic biomarkers in coronary artery disease: a narrative review.

Coronary artery disease (CAD) has a high mortality rate. Despite various therapeutic targets, non-responsiveness to drugs remains a prevalent issue. Pharmacogenomics assesses the way an individual's genetic attributes affect their likely response to drug therapy.

Therapeutic Drug Monitoring of Voriconazole in Children with Hematologic Malignancy and Invasive Fungal Infections: An RCT from a Tertiary Care Centre in India.

Introduction: Voriconazole is a triazole anti-fungal with non-linear kinetics and a narrow therapeutic range. The objective of our study was to monitor the voriconazole serum levels in children with hematological malignancy and clinically suspected invasive fungal infections.

Methods: The study was a prospective, randomized controlled trial conducted from June 2016 to December 2017.

Strategies to improve antibiotic access and a way forward for lower middle-income countries.

Antibiotics have substantially improved life expectancy in past decades through direct control or prevention of infections. However, emerging antibiotic resistance and lack of access to effective antibiotics have significantly increased the death toll from infectious diseases, making it one of the biggest threats to global health. Addressing the antibiotic crisis to meet future needs require considerable investment in both research and development along with ensuring a viable marketplace to encourage innovation.

Decanoic acid mitigates ischemia reperfusion injury by modulating neuroprotective, inflammatory and oxidative pathways in middle cerebral artery occlusion model of stroke in rats.

Objective: Amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) is an ionotropic transmembrane receptor for glutamate. AMPA receptor blockers have been reported to prevent neurological damage and enhance the post stroke recovery in rats. Decanoic acid, a medium-chain fatty acid, has been reported to exhibit non-competitive AMPA receptor antagonism.

AMPA receptor modulation through sequential treatment with perampanel and aniracetam mitigates post-stroke damage in experimental model of ischemic stroke.

The present study evaluates the effect of modulating α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) by inhibiting them in the acute phase and activating them in the sub-acute phase on post-stroke recovery in middle cerebral artery occlusion (MCAo) model of stroke in rats. After 90 min of MCAo, perampanel (an AMPAR antagonist, 1.5 mg/kg i.

Landscape of Push Funding in Antibiotic Research: Current Status and Way Forward.

The growing need for effective antibiotics is attributed to the intrinsic ability of bacteria to develop survival mechanisms. The speed at which pathogens develop resistance is at par or even faster than the discovery of newer agents. Due to the enormous cost of developing an antibiotic and poor return on investment, big pharmaceutical companies are stepping out of the antibiotic research field, and the world is now heading towards the silent pandemic of antibiotic resistance.

Drug development process and COVID-19 pandemic: Flourishing era of outsourcing.

Traditional drug development is a tedious process with involvement of enormous cost and a high attrition rate. Outsourcing drug development services to contract research organizations (CROs) has become an important strategy for cost and risk reduction, capacity building, and data generation. The therapeutic and operational expertise of these CROs has allowed pharmaceutical industry to reduce in-house infrastructure as well as research capacity.

Effect of add-on alpha lipoic acid on psychopathology in patients with treatment-resistant schizophrenia: a pilot randomized double-blind placebo-controlled trial.

Rationale: Alpha lipoic acid is known to reverse NMDA receptor hypofunction in addition to dopamine receptor blockade activity. It also enhances neurotrophic factors and has antioxidant potential. These properties combined together may be beneficial for treatment-resistant schizophrenia (TRS).

Lp-PLA2 as a biomarker and its possible associations with SARS-CoV-2 infection.

Lp-PLA2 is an enzyme encoded by the gene located at chromosome 6p12-21, which is included in different signal transduction pathways. The potential of serum levels of Lp-PLA2 as a marker of inflammation quantifying cardio-metabolic risk, renal impairment and oxidative stress has been explored in earlier studies. It has also been used in chronic obstructive pulmonary disease, hepatic disease, metabolic conditions and exercise tolerance.

Tideglusib Ameliorates Ischemia/Reperfusion Damage by Inhibiting GSK-3β and Apoptosis in Rat Model of Ischemic Stroke.

Objectives: Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, gets activated and worsen stroke outcome after ischemia/reperfusion (I/R) injury by inducing inflammation and apoptosis. In this study, tideglusib, a selective irreversible and non-ATP competitive inhibitor of GSK-3β, was explored in cerebral I/R damage using middle cerebral artery occlusion (MCAo) model in rats.

Materials And Methods: MCAo was done for 90 min in male Wistar rats (250-280 g) using doccol suture.

Efficacy and Safety of Adjunctive Serotonin-Dopamine Activity Modulators in Major Depression: A Meta-Analysis of Randomized Controlled Trials.

Serotonin-dopamine activity modulators (SDAMs) have been approved as an adjunctive treatment to antidepressants in patients with inadequate response. These drugs have been proposed to have a beneficial effect on cognition, sleep-related problems, and other affective symptoms in patients with depression. Previous studies have shown inconsistent evidence and have not reported a pooled effect of the 2 drugs of this class: aripiprazole and brexpiprazole.

Dihydromyricetin alleviates cerebral ischemia-reperfusion injury by attenuating apoptosis and astrogliosis in peri-infarct cortex.

Objectives: In ischemic stroke, reperfusion after thrombolysis is associated with secondary brain damage. Dihydromyricetin (DHM), a flavonoid, has shown neuroprotective effects through anti-oxidant, anti-inflammatory and anti-apoptotic properties. This study investigates the potential of DHM, given postreperfusion in middle cerebral artery occlusion (MCAo) model of stroke in rats.

Post Stroke Safinamide Treatment Attenuates Neurological Damage by Modulating Autophagy and Apoptosis in Experimental Model of Stroke in Rats.

Exploring and repurposing a drug have become a lower risk alternative. Safinamide, approved for Parkinson's disease, has shown neuroprotection in various animal models of neurological disorders. The present study aimed to explore the potential of safinamide in cerebral ischemia/reperfusion (I/R) in rats.

Chronic Neurological Disorders: Genetic and Epigenetic Markers for Monitoring of Pharmacotherapy.

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.

Preclinical Stroke Research and Translational Failure: A Bird's Eye View on Preventable Variables.

Despite achieving remarkable success in understanding the cellular, molecular and pathophysiological aspects of stroke, translation from preclinical research has always remained an area of debate. Although thousands of experimental compounds have been reported to be neuro-protective, their failures in clinical setting have left the researchers and stakeholders in doldrums. Though the failures described have been excruciating, they also give us a chance to refocus on the shortcomings.

Antibody-drug conjugates, cancer immunotherapy, and metronomic chemotherapy as novel approaches in cancer management.

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.

Heme oxygenase-1 modulation: A potential therapeutic target for COVID-19 and associated complications.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to infect hundred thousands of people every day worldwide. Since it is a novel virus, research continues to update the possible therapeutic targets when new evidence regarding COVID-19 are gathered. This article presents an evidence-based hypothesis that activating the heme oxygenase-1 (HO-1) pathway is a potential target for COVID-19.

First-in-human dose: current status review for better future perspectives.

Aim: The aim of this article is to understand the pros and cons of various methods involved in first-in-human (FIH) dose calculation and act decisively in dose escalations when calculating the maximum tolerated dose.

Subjects And Methods: We reviewed early phase clinical trials for methods of FIH dose and dose-escalation steps and discuss them in line with existing guidelines. We also reviewed the clinical trial registry to recognize trends in trial registration in recent years and after a massive failure in a few trials.

Evaluation of sodium valproate loaded nanoparticles in acute and chronic pentylenetetrazole induced seizure models.

Background And Purpose: Efficacy of sodium valproate in epilepsy is limited by its poor blood brain barrier penetration and side effects. Nanoparticles may offer a better drug delivery system to overcome these limitations. This study evaluated the efficacy of sodium valproate encapsulated in nanoparticles in pentylenetetrazole (PTZ) induced acute and kindling models of seizures in male Wistar rats.

Neuro-protective effect of monomethyl fumarate on ischemia reperfusion injury in rats: Role of Nrf2/HO1 pathway in peri-infarct region.

Post stroke recanalization has been associated with increased risk of oxidative stress. Stimulating endogenous antioxidant pathway by activation of nuclear factor erythroid-2-related factor-2 (Nrf2) plays a key role in neuronal defense against inflammation and oxidative stress in penumbra. Here, we explored whether monomethyl fumarate (MMF) could produce neuro-protection after ischemia/reperfusion (I/R) injury via Nrf2/HO1 activation.

Comparison of three different extracts of Centella asiatica for anti-amnesic, antioxidant and anticholinergic activities: in vitro and in vivo study.

Centella asiatica (CA) has been used by Ayurvedic medical practitioners in India for almost 3000 years. The neuropharmacological properties of CA and its constituents have been studied extensively. Anti-oxidant, free radical scavenging and cholinergic modulatory activities are the reported mechanisms of action for its efficacy in memory disorders.

Beneficial effects of fenofibrate in pulmonary hypertension in rats.

Pulmonary hypertension (PH) is a morbid complication of cardiopulmonary as well as several systemic diseases in humans. It is rapidly progressive and fatal if left untreated. In the present study, we investigated the effect of PPARα agonist fenofibrate (FF) on monocrotaline (MCT)-induced PH in rats.

Chronic treatment with taurine after intracerebroventricular streptozotocin injection improves cognitive dysfunction in rats by modulating oxidative stress, cholinergic functions and neuroinflammation.

The present study investigated the neuroprotective effects of taurine, an essential amino acid for growth and development of central nervous system. Intracerebroventricular streptozotocin (ICV-STZ) model of cognitive impairment was used in male Wistar rats (270 ± 20 g). Morris water maze, elevated plus maze and passive avoidance paradigm were used to assess cognitive performance.