Toxicokinetic profiling of VRP-034: Evaluating its potential in mitigating polymyxin-B-associated nephrotoxicity.

This study assessed the nephrotoxicity and toxicokinetic profile of VRP-034 [a novel formulation of polymyxin B (PMB)] compared with marketed PMB over a 7-day repeat-dose regimen. Three objectives were pursued: evaluating PMB pharmacokinetics in both groups, alongside assessing the impact of VRP-034 on mitigating PMB-associated kidney injury; analysing the reversibility of kidney injury; and validating novel kidney injury biomarkers against traditional markers using histopathological scoring. Sixty-eight Sprague-Dawley rats were divided into three groups: 30 in each of the marketed PMB and VRP-034 groups, and eight in the control group.

Evaluating nephrotoxicity reduction in a novel polymyxin B formulation: insights from a 3D kidney-on-a-chip model.

This study aimed to assess the nephrotoxicity associated with VRP-034 (novel formulation of polymyxin B [PMB]) compared to marketed PMB in a three-dimensional (3D) kidney-on-a-chip model. To model the human kidney proximal tubule for analysis, tubular structures were established using 23 triple-channel chips seeded with RPTEC/hTERT1 cells. These cells were exposed to VRP-034 or PMB at seven concentrations (1-200 µM) over 12, 24, and 48 h.

Polymyxin B-Induced Kidney Injury Assessment of a Novel Formulation of Polymyxin B (VRP-034) in Rats.

Despite the crucial role of Polymyxin-B in treating life-threatening gram-negative infections, its clinical utility is limited due to the risk of acute kidney injury. In response, a novel formulation of polymyxin-B is being developed to mitigate drug-induced kidney injury. In this study, we have assessed the toxicity of four variants of that novel formulation (VRP034_F21-F24) in comparison with standard polymyxin-B using kidney injury biomarkers in rats.

CSE (Ceftriaxone+ Sulbactam+ Disodium EDTA) Versus Meropenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: PLEA, a Double-Blind, Randomized Noninferiority Trial.

Background: CSE is a novel combination of ceftriaxone, sulbactam and disodium EDTA with activity against multidrug resistant gram-negative pathogens.

Methods: Adult patients aged ≥18 years with a diagnosis of complicated urinary tract infections (cUTI), including acute pyelonephritis (AP), were randomized 1:1 to receive either intravenous CSE (1000mg ceftriaxone/500mg sulbactam/37mg disodium EDTA) every 12h or intravenous meropenem (1000mg) every 8h for up to 14 days. The primary objective was to show the noninferiority of CSE to meropenem at the test-of-cure visit (8-12 days after the end of therapy), with a noninferiority margin of 10 percent.

Molecular characterization and in vitro susceptibilities of β-lactamase producing Escherichia coli, Klebsiella species, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus to CSE1034 and other β-lactams.

Objective: To study the prevalence of extended-spectrum β-lactamases (ESBLs) among 663 clinical isolates obtained from various parts of India and to study the occurrence of different variants of ESBLs among these isolates.

Methods: Phenotypic characterization and susceptibility studies were performed according to the methods described in Clinical and Laboratory Standards Institute guidelines. The occurrence of ESBL variants was analyzed with PCR using the previously reported primers.

Comparative antibacterial activity of a novel semisynthetic antibiotic: etimicin sulphate and other aminoglycosides.

Etimicin is a novel fourth generation semisynthetic aminoglycoside. It has good antimicrobial activity against both gram-positive and gram-negative bacterial infections and also against aminoglycoside resistant strains. In the present study, in vitro antibacterial activity of etimicin was determined by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time kill curve tests against type strains and 407 clinical isolates (obtained in a surveillance study), in comparison to other aminoglycosides.

Sub-acute toxicity study of a new aminoglycoside etimicin sulphate in swiss albino mice.

Etimicin sulfate, an ethylization derivative of gentamicin, is a new soluble wide-spectrum synthetic aminoglycoside drug. It has wide antibacterial spectrum with high effect and less cross resistance as compared to other aminoglycosides. In order to further explore its safety and tolerance, we have conducted a subactute toxicity study on swiss albino mice.

Pharmacokinetic study of sulbactomax.

We have evaluated pharmacokinetics of a fixed dose combination (FDC) of ceftriaxone and sulbactam (2:1) or sulbactomax in eight healthy volunteers. A 1.5 g dose of sulbactomax, 1 g dose of ceftriaxone and 0.

Biochemistry of fruit softening: an overview.

Softening is a developmentally programmed ripening process, associated with biochemical changes in cell wall fractions involving hydrolytic processes resulting in breakdown of cell-wall polymers such as cellulose, hemicelluloses and pectin etc. Various hydrolytic reactions are brought about by polygalacturonase, pectin methyl esterase, pectate lyase, rhamnogalacturonase, cellulase and β-galactosidase etc. Besides these enzymes, expansin protein also plays an important role in softening.

Pathogenicity and drug resistance in Candida albicans and other yeast species. A review.

Pathogenic yeasts from the genus Candida can cause serious infection in humans particularly, in immunocompromised patients and are now recognized as major agents of hospital acquired (nosocomial) infections. In the recent years, there has been a marked increase in the incidence of treatment failures in candidiasis patients receiving long-term antifungal therapy, which has posed a serious problem in its successful use in chemotherapy. Candida cells acquire drug resistance (MDR) during the course of the treatment.

Purification and characterization of pectate lyase from banana (Musa acuminata) fruits.

Pectate lyase (PEL) has been purified by hydrophobic, cation exchange and size exclusion column chromatographies from ripe banana fruit. The purified enzyme has specific activity of 680 +/- 50 pkat mg protein(-1). The molecular mass of the enzyme is 43 kDa by SDS-PAGE.

Effect of phytohormones on pectate lyase activity in ripening Musa acuminata.

A differential activity peak of pectate lyase (PEL) was observed during ripening of banana fruits (Musa acuminata Harichhal) receiving different hormone treatments. Exposure of fruits to 25 ppm ethylene for 24 h, as well as dipping of M. acuminata fruits in 1 mM 2,4-dichlorophenoxy acetic acid (2,4-D) for 4 h, hastened fruit ripening.

Pectate lyase activity during ripening of banana fruit.

Pectate lyase (PEL) activity was demonstrated in ripe banana fruits on supplementing the homogenizing medium with cysteine and Triton X-100. The enzyme was characterized on the basis of alkaline pH optimum, elimination of the activity by EDTA and activation by Ca(2+). PEL activity was not detected in preclimacteric banana fruits.