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Sulfonylureas at the Glomerular Battlefield.

ABSTRACT: The kidney is important in the context of diabetes not only because it is involved in normal glucose homeostasis, but also because it is one of the most important end organs to be involved in diabetes complications. Glomeruli are the meeting point of both microvascular, or renal; and macrovascular, or cardiovascular, health in diabetes. Sulfonylureas are effective glucose-lowering drugs. While a sulfonylurea-based glucose-lowering strategy is nephro-safe and nephro-protective, this aspect of sulfonylurea pharmaco-biology has not been highlighted earlier. In this editorial, we discuss current preclinical and clinical trial evidence regarding the performance of modern sulfonylureas at the glomerular battlefield.

SUBMITTER: Kalra S

PROVIDER: S-EPMC6182921 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Sulfonylureas at the Glomerular Battlefield.

Kalra Sanjay S Khandelwal Deepak D Bajaj Sarita S Das Ashok Kumar AK

European endocrinology 20180910 2

The kidney is important in the context of diabetes not only because it is involved in normal glucose homeostasis, but also because it is one of the most important end organs to be involved in diabetes complications. Glomeruli are the meeting point of both microvascular, or renal; and macrovascular, or cardiovascular, health in diabetes. Sulfonylureas are effective glucose-lowering drugs. While a sulfonylurea-based glucose-lowering strategy is nephro-safe and nephro-protective, this aspect of sul ...[more]

PMID: 30349588

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Project description:Current diagnostics and clinical management strategies for combat wounds are based on decisions made by expert clinicians. However, even in the hands of experienced surgeons, wounds from combat injuries can exhibit failed healing and complications related to limitations in the rapid and comprehensive generation of diagnostic information. Previous studies have demonstrated the possible use of genomic sequencing approaches to detect microbial signatures involved in combat casualty care. While effective, whole metagenome sequencing is limited by the depth required to confidently detect all relevant signatures. To address this, we developed a targeted capture sequencing panel to detect microbial signatures relevant to wound healing. These targets include known microbial nosocomial pathogens, wound colonizers, and genes involved in virulence and antimicrobial resistance. A bioinformatics pipeline was built to identify genomic regions of interest and over 8,000 oligonucleotide probes were designed for capture. The panel was synthesized and validated using control reference genomes in human background and on wound-effluent samples from a cohort of combat-injured U.S. service members. Our panel was sensitive against wound-colonizing species, Acinetobacter baumannii and Pseudomonas aeruginosa, and was specific in detecting corresponding virulence and antimicrobial-resistance genes as well as other pathogenic species present in microflora mixtures. Random forest feature permutation confirmed the prevalence of Acinetobacter and Pseudomonas in critically colonized wounds and wounds that failed to heal, respectively. Our results demonstrate the capability of targeted sequencing tools and analysis platforms to profile and deliver information on pathogenic factors influencing wound progression, thereby guiding therapeutic intervention. IMPORTANCE Microbial contamination in combat wounds can lead to opportunistic infections and adverse outcomes. However, current microbiological detection has a limited ability to capture microbial functional genes. This work describes the application of targeted metagenomic sequencing to profile wound bioburden and capture relevant wound-associated signatures for clinical utility. Ultimately, the ability to detect such signatures will help guide clinical decisions regarding wound care and management and aid in the prediction of wound outcomes.

Dataset Information

Sulfonylureas at the Glomerular Battlefield.

Publications

Sulfonylureas at the Glomerular Battlefield.

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