作者: Linck Junior, Arnildo ; Amarante, Ana Cristina Alba ; Lopes, Gilselena Kerbauy ; Ferrari, Rosângela Aparecida Pimenta ; Capobiango, Jaqueline Dario

INTRODUCTIONHealth care-associated infections (HAIs) contribute to morbidity and mortality and to the dissemination of multidrug-resistant organisms. Children admitted to the intensive care unit undergo invasive procedures that increase their risk of developing HAIs and sepsis. The aim of the study was to analyse factors associated with mortality due to sepsis arising from HAIs.PATIENTS AND METHODSWe conducted a case-control study in a 7-bed multipurpose paediatric intensive care unit in a tertiary care teaching hospital. The sample consisted of 90 children admitted between January 2014 and December 2018. The case group consisted of patients who died from sepsis associated with the main health care-associated infections; the control group consisted of patients who survived sepsis associated with the same infections.RESULTSDeath was associated with age less than or equal to 12 months, presence of comorbidity, congenital disease, recurrent ventilator-associated pneumonia and septic shock. In the multiple regression analysis, heart disease (OR, 12.48; CI 2.55-60.93; P = .002), infection by carbapenem-resistant bacteria (OR, 31.51; CI 4.01-247.25; P = .001), cancer (OR, 58.23; CI 4.54-746.27; P = .002), and treatment with adrenaline (OR, 13.14; CI 1.35-128.02; P = .003) continued to be significantly associated with death.CONCLUSIONSHospital sepsis secondary to carbapenem-resistant bacteria contributed to a high mortality rate in this cohort. Children with heart disease or neoplasia or who needed vasopressor drugs had poorer outcomes.

2023-01-01·Biomedicine & Pharmacotherapy

Cisplatin-induced ototoxicity: From signaling network to therapeutic targets

Review

作者: Wang, Xilu ; Wang, Dali ; Liu, Xiaofang ; Wang, Yi ; Zhou, Yingying ; Ma, Xiulan ; Dong, Yaodong ; Zhou, Zhaoyu

Administration of cisplatin, a common chemotherapeutic drug, has an inevitable side effect of sensorineural hearing loss. The main etiologies are stria vascularis injury, spiral ganglion degeneration, and hair cell death. Over several decades, the research scope of cisplatin-induced ototoxicity has expanded with the discovery of the molecular mechanism mediating inner ear cell death, highlighting the roles of reactive oxygen species and transport channels for cisplatin uptake into inner ear cells. Upon entering hair cells, cisplatin disrupts organelle metabolism, induces oxidative stress, and targets DNA to cause intracellular damage. Recent studies have also reported the role of inflammation in cisplatin-induced ototoxicity. In this article, we preform a narrative review of the latest reported molecular mechanisms of cisplatin-induced ototoxicity, from extracellular to intracellular. We build up a signaling network starting with cisplatin entering into the inner ear through the blood labyrinth barrier, disrupting cochlear endolymph homeostasis, and activating inflammatory responses of the outer hair cells. After entering the hair cells, cisplatin causes hair cell death via DNA damage, redox system imbalance, and mitochondrial and endoplasmic reticulum dysfunction, culminating in programmed cell death including apoptosis, necroptosis, autophagic death, pyroptosis, and ferroptosis. Based on the mentioned mechanisms, prominent therapeutic targets, such as channel-blocking drugs of cisplatin transporter, construction of cisplatin structural analogues, anti-inflammatory drugs, antioxidants, cell death inhibitors, and others, were collated. Considering the recent research efforts, we have analyzed the feasibility of the aforementioned therapeutic strategies and proposed our otoprotective approaches to overcome cisplatin-induced ototoxicity.

2022-04-01·Journal of Cellular and Molecular Medicine2区 · 医学

Therapeutic potentials of cell death inhibitors in rats with cardiac ischaemia/reperfusion injury

2区 · 医学

ArticleOA

作者: Chattipakorn, Nipon ; Benjanuwattra, Juthipong ; Chattipakorn, Siriporn C. ; Luo, Ying ; Chunchai, Titikorn ; Yanpiset, Panat ; Arunsak, Busarin ; Liao, Suchan ; Apaijai, Nattayaporn ; Maneechote, Chayodom

AbstractGrowing evidence demonstrated that cell death pathways including ferroptosis, apoptosis and necroptosis contribute to cardiac ischaemia/reperfusion (I/R) injury. We hypothesized that ferroptosis, apoptosis and necroptosis contribute differently to myocardial damage during acute cardiac I/R injury. Rats underwent cardiac I/R or sham operation. I/R‐operated rats were divided into 4 groups: vehicle, apoptosis (Z‐vad), ferroptosis (Fer‐1) and necroptosis (Nec‐1) inhibition. Rats in each cell death inhibitor group were subdivided into 3 different dose regimens: low, medium and high. Infarct size, left ventricular (LV) function, arrhythmias and molecular mechanism were investigated. Cardiac I/R caused myocardial infarction, LV dysfunction, arrhythmias, mitochondrial dysfunction, mitochondrial dynamic imbalance, inflammation, apoptosis and ferroptosis. Infarct size, LV dysfunction, mitochondrial dysfunction, apoptosis and ferroptosis were all reduced to a similar extent in rats treated with Z‐vad (low and medium doses) or Fer‐1 (medium and high doses). Fer‐1 treatment also reduced mitochondrial dynamic imbalance and inflammation. No evidence of necroptosis was found in association with acute I/R injury, therefore Nec‐1 treatment could not be assessed. Apoptosis and ferroptosis, not necroptosis, contributed to myocardial damage in acute I/R injury. Inhibitors of these 2 pathways provided effective cardioprotection in rats with I/R injury though modulation of mitochondrial function and attenuated apoptosis and ferroptosis.

100 项与 CELL DEATH(Odyssey) 相关的药物交易

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