Unfolding the Potential of Pyrrole- and Indole-Based Allylidene Hydrazine Carboximidamides as Antimicrobial Agents.

Antimicrobial drug resistance is a significant global health challenge, causing hundreds of thousands of deaths annually and severely impacting healthcare systems worldwide. Several reported antimicrobial compounds have a guanidine motif, as the positive charge on guanidine promotes cell lysis. Therefore, pyrrole- and indole-based allylidene hydrazine carboximidamide derivatives with guanidine motifs are proposed as antimicrobial agents that mimic cationic antimicrobial peptides (CAMPs).

Reactivity of N terminal histidine of peptides towards excipients/impurity of excipients: A case study of liraglutide excipient compatibility study.

The selection of quality excipients is a crucial step in peptide formulation development. Apart from excipient incompatibility, process-related impurities or degradants of an excipient can interact with peptide-active pharmaceutical ingredients, forming the interaction products. The formaldehyde has been reported as an impurity of excipient in polyethylene glycol, glycerol, magnesium stearate, microcrystalline cellulose, mannitol, etc.

A critical assessment on stability behaviour of Vorinostat using LC-MS-QTOF with H/D exchange and NMR.

Vorinostat is the first USFDA-approved HDAC inhibitor for the treatment of cutaneous t-cell lymphoma. Vorinostat was exposed to ICH-recommended hydrolytic (acid, base, and neutral), oxidative, thermal, and photolytic stress conditions to understand the degradation behaviour. A Stability indicating LC method was developed and validated for separating and identifying forced degradation products.

Drug-Excipient Compatibility Study Through a Novel Vial-in-Vial Experimental Setup: A Benchmark Study.

Drug-excipient compatibility study (DECS) is one of the critical steps during pre-formulation studies to select the appropriate excipient to obtain a stable formulation/dosage form. As such, there is no recommended guideline for DECS. Further, the previously reported studies and protocols followed by various pharmaceutical industries are very lengthy and laborious.

Modified NAP test: A simple and Responsive Nitrosating Methodology for Risk Evaluation of NDSRIs.

N-Nitroso compounds have been listed as one of the cohorts of concern as per ICH M7. In recent years, the regulatory focus has shifted from common nitrosamines to nitroso-impurities of drug products. Thus, the detection and quantification of unacceptable levels of nitrosamine drug substance-related impurities are of great concern for analytical scientists during drug development.

Hyphenated liquid chromatography - diode array detection - charged aerosol detection - high resolution - multistage mass spectrometry with online hydrogen/deuterium exchange: One stop solution for pharmaceutical impurity profiling.

Hyphenation of different analytical techniques has always been advantageous in structural characterization as it saves time, money and resources. In the pharmaceutical sector, chromatography-based impurity profiling, including identification, characterization, and quantification in drug substances or finished products, is of utmost importance to comply with quality, patient safety and regulatory requirements. These impurities are monitored using LC-UV/DAD and identified and/or characterized using HRMS and MS/MS.

Quantification of Anti-Osteoporotic Anabolic Peptide in Stealth Lipid Nanovesicles Through Validated RP-HPLC Method.

Background: Teriparatide is a recombinant fragment of human parathyroid hormone, a potent osteoanabolic agent used for osteoporosis.

Objective: The present study endeavored to develop a simple, rapid, and reliable reverse phase-high performance liquid chromatography (RP-HPLC) method for the determination of teriparatide in pegylated lipid nanovesicles for rapid formulation development/optimization.

Method: A rapid RP-HPLC-based analytical method was developed for the quantification of teriparatide in pegylated lipid nanovesicles.

Carbamazepine mitigates parenteral nutrition-associated liver disease in a novel ambulatory piglet model.

Background: Parenteral nutrition (PN) remains a critical therapeutic option in patients who cannot tolerate enteral feeding. However, although lifesaving, PN is associated with significant side effects, including liver injury, the etiology of which is multifactorial. Carbamazepine (CBZ), an antiepileptic medication, is known to modulate hepatic fibrosis and hepatocellular injury in a variety of liver diseases.

Effectiveness of social distancing interventions in containing COVID-19 incidence: International evidence using Kalman filter.

The epidemiological literature has widely documented the importance of social distancing interventions in containing the spread of the COVID-19 pandemic. However, the epidemiological measure of virus reproduction, R, provides a myopic view of containment, especially when the absolute number of cases is still high. The paper investigates cross-country variations concerning the impact of social distancing interventions on COVID-19 incidence by employing a statistical measure of containment, which models the daily number of cases as a structural time-series, state-space vector.

Is age just a number: Exploring fear, anxiety, and coping in individuals during COVID-19.

Introduction: The current pandemic coronavirus (COVID-19) is a novel disease with no standardized course of treatment and cure. This novelty, origin, and dispersion of COVID-19 have been reported to cause chaos, anxiety, and fear among the general population.

Aim: The present study aimed to explore the correlation between different age groups, in relation to their general coping strategies, fear, and anxiety due to COVID-19.

Role of Bile Acids and Gut Microbiota in Parenteral Nutrition Associated Injury.

Total Parenteral Nutrition (TPN) is a life-saving therapy where all nutritional requirements are provided intravenously. While this therapy is essential for individuals unable to process their nutritional needs enterically, significant complications arise such as intestinal failure associated liver injury (IFALD). IFALD includes hepatic steatosis, cholestasis, inflammation, ultimately progressing to cirrhosis and portal hypertension and some patients may need liver transplantation.

Target specific intracellular quantification of etoposide by quadrupole-time of flight based mass spectrometric method.

Etoposide (ETP), a widely used chemotherapeutic agent has an intracellular target site of action. Unfortunately, the concentration of ETP in plasma does not properly reflect the concentration in its intracellular site of action. As per our knowledge, no reported bioanalytical method is available for intracellular quantification of ETP.

Impaired Gut-Systemic Signaling Drives Total Parenteral Nutrition-Associated Injury.

Background: Total parenteral nutrition (TPN) provides all nutritional needs intravenously. Although lifesaving, enthusiasm is significantly tempered due to side effects of liver and gut injury, as well as lack of mechanistic understanding into drivers of TPN injury. We hypothesized that the state of luminal nutritional deprivation with TPN drives alterations in gut-systemic signaling, contributing to injury, and tested this hypothesis using our ambulatory TPN model.

Development and validation of an ambulatory piglet model for short bowel syndrome with ileo-colonic anastomosis.

Short bowel syndrome is associated with significant comorbidities and mortality. This study is important as unlike current systems, it provides a validated piglet model which mirrors anatomical, histological, and serological characteristics observed in human SBS. This model can be used to advance knowledge into mechanistic pathways and therapeutic modalities to improve outcomes for SBS patients.

An Exploration of Advancement in Analytical Methodology for Quantification of Anticancer Drugs in Biomatrices.

Significant numbers of newer anticancer drugs are regularly entering into the market worldwide to fight against different types of cancers. Analytical methodologies are being developed to quantitate those molecules in a variety of matrices during their drug development stages. Selection of biological matrices for developing bioanalytical methods is based on the mechanism of action, site of action, site of metabolism and route of excretion of the drugs or their metabolites.

Current Standing and Technical Guidance on Intracellular Drug Quantification: A New Site Specific Bioavailability Prediction Approach.

Determination of intracellular concentration becomes essential for the drugs having target receptors or bioactivation site inside the cells. Majority of the antiviral drugs are nucleoside analogs and their intracellular phosphorylated metabolites are active. The anticancer drugs of the cellular enzyme and nucleoside analog category are also required to be undergone intracellular drug level analysis.

An economic analysis of salmonella detection in fresh produce, poultry, and eggs using whole genome sequencing technology in Canada.

The study estimates the annual costs of nontyphoidal Salmonellosis (referred to as Salmonellosis from hereon) from fresh produce, poultry and eggs in Canada. It also estimates the economic benefits from introduction of Whole Genome Sequencing (WGS) in detection of Salmonellosis clusters and outbreaks. Monetary and non-monetary costs from Salmonellosis are estimated.

Antimicrobial susceptibility pattern of extended-spectrum beta- lactamase producing Klebsiella pneumoniae clinical isolates in an Indian tertiary hospital.

Objective: There is an increased prevalence of extended-spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-KP) worldwide including India, which is a major concern for the clinicians, especially in intensive care units and pediatric patients. This study aims to determine the prevalence of ESBL-KP and antimicrobial sensitivity profile to plan a proper hospital infection control program to prevent the spread of resistant strains.

Methods: KP isolates obtained from various clinical samples were evaluated to detect the production of ESBL by phenotypic methods.