Nutritional co-therapy with vitamin D and L-theanine reduces unpredictable mild chronic stress (UCMS) in aged mice by restoring alpha-oscillations, dopamine levels and behavioral improvement.

Late-life depression (LLD) arises from the confluence of neurochemical dysfunction, oxidative stress, and neural network disintegration, presenting a formidable therapeutic challenge. Here, we demonstrated that combined vitamin D (Vit D) and L-theanine (L-thea) administration exerts multimodal neurorestorative effects in an aged murine model of unpredictable chronic mild stress (UCMS), addressing the core triad of LLD pathology: dopaminergic decline, redox imbalance, and thalamocortical dyssynchrony. Using a comprehensive battery of behavioral assays (Open Field Test, Elevated Plus Maze, Hole Board Test, Tail Suspension Test, Forced Swim Test, Sucrose Preference Test), we observed profound anxiogenic and anhedonic phenotypes in the UCMS-exposed mice, accompanied by elevated immobility and suppressed exploratory drive.

Clinical pharmacokinetics of metronidazole: a systematic review and meta-analysis.

Metronidazole (MTZ) is used in various clinical settings; however, its pharmacokinetics may vary across patient populations due to physiological and pathological differences. Understanding these variations is important for personalized dosing and optimization of therapeutic outcomes. This study aimed to systematically review clinical pharmacokinetic studies of MTZ and perform a meta-analysis of the area under the concentration-time curve (AUC).

A PBPK modeling approach for personalized dose optimization of nicardipine in renal and hepatic dysfunction.

Nicardipine is a calcium channel blocker employed to manage hypertension and angina. It is primarily metabolized in the liver; therefore, hepatic impairment patients may experience drug accumulation, potentially resulting in adverse events. This research aims to design physiologically based pharmacokinetic (PBPK) model capable of accurately predicting the exposure of nicardipine in healthy individuals as well as hepatic and renal impairment patients.

Evaluation of the effects of Tempol on oxidative stress and angiotensin-II induced hypertension in mice exposed to nicotine from electronic and tobacco cigarettes.

Electronic cigarette (E-Cig) is commonly used as an alternative to tobacco cigarette (T-Cig), as it lacks many of the toxicants present in T-Cigs. However, the toxicological mechanisms underlying E-Cig-induced hypertension are not yet well understood. The goal of this research was to explore the effects of Tempol in reducing hypertension caused by T-Cig and E-Cig exposure by mitigating oxidative stress and regulating angiotensin-II production in mouse models subjected to T-Cig and E-Cig smoke.

Exploring the Pharmacokinetics of Drugs in Disabled Saudi Patients: A Systematic Review.

: Disability is a term that involves mental, intellectual, or sensory impairment resulting in the loss of one's ability to walk or perform the activities necessary to live in a society. This study aims to collect all the data regarding the absorption, distribution, and disposition of drugs in disabled Saudi patients, i.e.

Erqember Mitigates Neurotoxic Effects of Aluminum Chloride in Mice: Phytochemical Insights With Neurobehavioral and In Silico Approaches.

The increasing popularity of herbal preparations has prompted people around the world to incorporate herbal products into their balanced diet, aiming to improve brain health and protect against neurological disorders. Erqember(Erq-Em) possesses a blend of various neuroprotective phytocompounds. The present study aimed to phytochemically analyze this polyherbal product and scientifically validate its neurological benefits.

Polypharmacy with tiagabine, levetiracetam, and perampanel in status epilepticus: Insights from EEG, biochemical, and histopathological studies in rats.

Objective: Status epilepticus (SE) is a condition of neurological emergency, which precipitates various functional and morphological changes in the brain. Due to the risk of drug resistance associated with SE, this study aimed to evaluate a multitargeted approach to treat SE by combining clinically used antiseizure drugs.

Methods: In this study, we intraperitoneally administered tiagabine (TGB), levetiracetam (LEV), and perampanel (PER) alone and in combination as a duo and trio therapy after 30 min of SE in electrode-implanted male Sprague-Dawley rats subjected to lithium-pilocarpine-induced convulsive SE.

Oxytocin Protects PC12 Cells Against β-Amyloid-Induced Cell Injury.

: Neurodegenerative diseases, particularly Alzheimer's disease (AD), are characterized by progressive cognitive decline and non-cognitive symptoms that significantly affect health and quality of life. Beta-amyloid (Aβ) protein accumulation is a key factor in AD pathology, leading to neuronal damage. Oxytocin (OXT), a neuropeptide with neuroprotective potential, has garnered interest owing to its ability to mitigate neurotoxicity.

Probiotics and pregabalin combination prevented ictogenesis, neurobehavioral abnormalities and neurodegeneration in pentylenetetrazole kindling model of epilepsy.

The microbiota-gut-brain axis (MGBA) has emerged as a critical frontier in understanding neurological disorders, including epilepsy. Microbial disequilibrium potentially alters brain homeostasis and could potentiate an inflammatory state linking intestinal dysbiosis and intractable seizures. The current study sought to probe the anti-kindling, electrographical, behavioral and neuropathological impacts of combined intervention of probiotics (PRO; 10 ml/kg) and pregabalin (PRG; 10 mg/kg) in PTZ-induced epileptic mice for 21 days.

The Clinical Pharmacokinetics and Pharmacodynamics of Glimepiride-A Systematic Review and Meta-Analysis.

Glimepiride (GLM), a commonly used sulphonylurea drug for the management of type 2 diabetes mellitus (T2DM), has been the subject of numerous studies exploring its kinetic behaviors. However, a comprehensive evaluation that synthesizes all available pharmacokinetic (PK) data across diverse populations remains limited. This systematic review aims to provide detailed knowledge about the pharmacokinetics (PK), the associated pharmacodynamics (PD), and the drug interactions of GLM, which can be used to assess key parameters and identify factors influencing variability across diverse populations and clinical settings.

Unraveling the neuroprotective effect of perampanel and lacosamide combination in the corneal kindling model for epilepsy in mice.

Background: Scientific evidence to guide clinicians on the use of different antiseizure drugs in combination therapy is either very limited or lacking. In this study, the impact of lacosamide and perampanel alone and in combination was tested in corneal kindling model in mice, which is a cost-effective mechanism for screening of antiseizure drugs.

Methods: The impact of lacosamide (5 mg/kg) and perampanel (0.

Clinical Pharmacokinetics of Fexofenadine: A Systematic Review.

Fexofenadine hydrochloride is a widely prescribed drug for treating histamine-mediated allergic reactions. This review systematically collates existing research on the clinical pharmacokinetics (PK) of fexofenadine, with a copious emphasis on examining the impact of stereoisomerism, disease states, and drug interactions. The search engines PubMed, Science Direct, Google Scholar, and Cochrane were scanned systematically for articles concerning the clinical PK of fexofenadine in humans.

Integration of Ontogeny-Based Changes for Predicting the Exposure of Diphenhydramine in the Pediatric Population: A PBPK Modeling Approach.

Background: Diphenhydramine is an anti-tussive used periodically to treat seasonal colds, contact dermatitis, and anaphylactic reactions. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of diphenhydramine in predicting its systemic exposure among healthy pediatrics (children and adolescents) by leveraging data files from adults (young and elderly).

Methods: The data profiles comprising serum/plasma concentration over time and parameters related to diphenhydramine were scrutinized via exhaustive literature analysis and consolidated in the PK-Sim software version 11.

Model-Based Dose Selection of a Sphingosine-1-Phosphate Modulator, Etrasimod, in Patients with Various Degrees of Hepatic Impairment.

Etrasimod is a newly FDA-approved Sphingosine-1-Phosphate modulator indicated for moderate and severe ulcerative colitis. It is extensively metabolized in the liver via the cytochrome P450 system and may accumulate markedly in patients with hepatic dysfunction, exposing them to toxicity. The aim of the current study is to utilize a physiologically-based pharmacokinetic modeling approach to evaluate the impact of hepatic impairment on the pharmacokinetic behavior of etrasimod and to appropriately select dosage regimens for patients with chronic liver disease; Methods: PK-Sim was used to develop the etrasimod PBPK model, which was verified using clinical data from healthy subjects and subsequently adapted to reflect the physiological changes associated with varying degrees of hepatic dysfunction; Results: Simulations indicated that hepatic clearance of etrasimod is clearly reduced in patients with Child-Pugh B and C liver impairment.

Co-administration of coenzyme Q10 and curcumin mitigates cognitive deficits and exerts neuroprotective effects in aluminum chloride-induced Alzheimer's disease in aged mice.

Aluminum chloride (AlCl), a known neurotoxic and Alzheimerogenic metal disrupts redox homeostasis which plays a pivotal role in pathophysiology of neurodegenerative disorders, particularly cognitive decline. The current study was designed to unveil the long-term neuroprotective outcomes and efficacy of CoQ10 and curcumin low dose (100 mg/kg each) combination in 18-months old geriatric male Balb/c mice subjected to AlCl-prompted memory derangements (200 mg/kg in water bottles) for 28 days. The neuroprotective properties driven by antioxidant mechanisms were assessed via observing cellular pathology in key-memory related brain regions including the cornuammonis (CA3 and DG) and cortex 2/3 layer.

Probiotics by Modulating Gut-Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole-Kindled Mice.

Background: The microbiota-gut-brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications.

Methods: In the current study, we investigated the impact of long-term oral bacteriotherapy (probiotics; 10 mL/kg; 10 colony-forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice.

Brivaracetam and rufinamide combination increased seizure threshold and improved neurobehavioral deficits in corneal kindling model of epilepsy.

Background: Besides seizures, a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy, which further debilitates their quality of life. This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses, respectively, on corneal kindling-induced generalized seizures and behavioral alterations. Furthermore, observed convulsive frequency and behavioral changes were correlated to post-kindling-induced changes in the activity of markers of oxidative stress.

The Economic Burden of Type 2 Diabetes Mellitus in Pakistan: A Cost of Illness Study.

Background: Type 2 Diabetes Mellitus (T2DM) is a highly prevalent disease with a chronic nature and poses a significant health burden worldwide, with no exception in Pakistan. Hence, this study aimed to explore the financial burden of T2DM in Pakistan through cost of illness analysis.

Methods: A prevalence-based, cross-sectional study was conducted using a structured data collection tool from the patient's perspective.

Clinical pharmacokinetics of glipizide: a systematic review.

Introduction: Glipizide is an oral antidiabetic drug widely used to treat non-insulin-dependent type II diabetes mellitus (NIDDM). This systematic review extensively examines all reported pharmacokinetic (PK) parameters of glipizide in healthy and diseased populations.

Areas Covered: A total of 31 articles were retrieved after screening various databases, i.

Clinical pharmacokinetics and pharmacodynamics of nicardipine; a systematic review.

Introduction: Nicardipine is a type of calcium channel blocker that is commonly used in the treatment of angina pectoris, hypertension, and related cardiovascular disorders. This systematic review assesses the reported pharmacokinetic (PK) and associated pharmacodynamic (PD) parameters of nicardipine in humans.

Areas Covered: An exhaustive literature search using four internet databases was conducted up to 5 October 2023, which yielded 871 papers, of which 32 fulfilled the eligibility requirements by including human PK and related PD data.

Dulaglutide rescues the elevated testicular dysfunction in a mouse model of high-fat diet-induced obesity.

Obesity is a well-known risk factor for testicular function; however, dulaglutide's effect on the testis in obesity has received little attention. Currently, clinicians prescribe the antidiabetic drug dulaglutide only off-label for weight management in non-diabetics. Investigating the impact of this novel compound on obesity is critical for determining whether it has any disruptive effects on testicular cells.

Polycaprolactone-Vitamin E TPGS Micellar Formulation for Oral Delivery of Paclitaxel.

This study aimed to investigate the potential of polycaprolactone-vitamin E TPGS (PCL-TPGS) micelles as a delivery system for oral administration of paclitaxel (PTX). The PCL-TPGS copolymer was synthesized using ring opening polymerization, and PTX-loaded PCL-TPGS micelles (PTX micelles) were prepared via a co-solvent evaporation method. Characterization of these micelles included measurements of size, polydispersity, and encapsulation efficiency.

Clinical pharmacokinetics of cefpodoxime: a systematic review.

Introduction: Cefpodoxime, a third-generation cephalosporin, is a broad-spectrum antibiotic widely used to treat acute upper respiratory tract infections (RTI). This systematic review aims to present a comprehensive view of all the available pharmacokinetics (PK) data associated with the pharmacodynamics (PD) parameters of cefpodoxime in humans.

Areas Covered: The PubMed, Google Scholar, Cochrane Library, and Science Direct, were systematically searched to identify studies on the PK of cefpodoxime.

A Comprehensive Physiologically Based Pharmacokinetic Model for Predicting Vildagliptin Pharmacokinetics: Insights into Dosing in Renal Impairment.

Physiologically based pharmacokinetic (PBPK) modeling is of great importance in the field of medicine. This study aims to construct a PBPK model, which can provide reliable drug pharmacokinetic (PK) predictions in both healthy and chronic kidney disease (CKD) subjects. To do so, firstly a review of the literature was thoroughly conducted and the PK information of vildagliptin was collected.

Increased Permeability of the Blood-Brain Barrier in a Diabetic Mouse Model ( Mice).

Type 2 Diabetes Mellitus (T2DM) is linked to multiple complications, including cognitive impairment, and the prevalence of memory-related neurodegenerative diseases is higher in T2DM patients. One possible theory is the alteration of the microvascular and macrovascular environment of the blood-brain barrier (BBB). In this study, we employed different approaches, including RT-PCR, functional pharmacokinetic studies using sodium fluorescein (NaFL), and confocal microscopy, to characterize the functional and molecular integrity of the BBB in a T2DM animal model, leptin receptor-deficient mutant mice ( mice).