Search results for "Toxicity"
showing 10 items of 2261 documents
Oestrogen receptor subtype-specific repression of calpain expression and calpain enzymatic activity in neuronal cells - implications for neuroprotect…
2006
Calpains represent a superfamily of Ca2+-activated cysteine-proteases, which are important mediators of apoptosis and necrosis. In the brain, m-calpain and micro-calpain, the two ubiquitous calpain-isoforms, are strongly activated in neurones after an excitotoxic Ca2+ influx occurring, for example, during cerebral ischemia. Because oestrogen and its receptors (ERalpha/ERbeta) can exert neuroprotective activity, we investigated their influence on expression of calpains and their endogenous inhibitor, calpastatin. We found that ectopic expression of ERalpha in human neuroblastoma SK-N-MC cells led to a ligand-independent constitutive down-regulation of m-calpain accompanied by an up-regulatio…
Inhibition of intracellular Ca2+ release by a Rho-kinase inhibitor for the treatment of ischemic damage in primary cultured rat hippocampal neurons.
2008
The effects of hydroxy fasudil, a specific Rho-kinase inhibitor, on behavior and brain neuronal activity in animal studies have been described previously. However, whether a Rho-kinase inhibitor can directly protect neurons against ischemic damage and the molecular mechanisms underlying these effects are poorly understood. The present work was designed to investigate the effect of hydroxy fasudil against oxygen-glucose deprivation (OGD) induced acute neuronal injury and the underlying mechanisms in vitro. Pretreatment with hydroxy fasudil at 5 and 10 microM could concentration-dependently improve cell viability and decrease Lactate dehydrogenase (LDH) level in extracellular solution of neur…
Arsenic Through the Gastrointestinal Tract
2015
Intestinal barrier function regulates (micro-)nutrient absorption and host defense mechanisms at the mucosal interface with the external environment. Maintaining gut homeostasis is essential for human health; however, many factors including food and water pollutants may affect the physiological balance at the intestinal level. One of the contaminants of highest health concern is arsenic, which affects more than 200 million people worldwide, causing cancer and cardiovascular and metabolic diseases. Arsenic affects intestinal health by disrupting barrier function and inducing inflammatory responses. Processes involved in the transiting of arsenic through the gastrointestinal tract can affect …
TH-302 + Gemcitabine (G + T) vs Gemcitabine (G) in Patients with Previously Untreated advanced Pancreatic Cancer (PAC)
2012
ABSTRACT Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G…
Hepatotoxicity caused by mebendazole in a patient with Gilbert's syndrome
2019
What is known and objective Mebendazole (MBZ) is a broad-spectrum antihelminthic agent of the benzimidazole type. Although MBZ has been reported to cause hepatic injury, case reports of severe hepatic injury are very rare. We report a case of severe hepatitis after administration of MBZ in a patient with Gilbert's syndrome affected by pinworms infestation. Case summary Differently from other cases of hepatitis due to MBZ reported in the scientific literature, our patient received standard doses of MBZ for a short period of time. After 18 days from the start of therapy, he developed hepatomegaly, and increases in hepatic enzymes and bilirubin. Hepatic enzymes returned to normal over the foll…
Sirolimus versus cyclosporine in haploidentical stem cell transplantation with posttransplant cyclophosphamide and mycophenolate mofetil as graft‐ver…
2021
Sirolimus has emerged as an alternative to calcineurin inhibitors-based (CNI) graft-versus-host disease (GVHD) prophylaxis. This retrospective study compares the outcome of 133 consecutive adult patients with haematological malignancies undergoing haploidentical stem cell transplantation with posttransplant cyclophosphamide (PTCy) and mycophenolate mofetil (MMF), combined with cyclosporine A (PTCy-CsA-MMF,
Effects of lindane on fish carbohydrate metabolism.
1991
Exposure of the European eel (Anguilla anguilla) to a high sublethal concentration of 0.335 ppm (0.50 of the 96-hr LC50) of lindane for 6, 12, 24, 48, 72, and 96 hr affected carbohydrate metabolism. Muscle glycogen levels decreased significantly (P less than 0.05) at 6, 12, 24, 48, 72, and 96 hr; liver glycogen content did not decline at any time. Muscle glucose levels in fish were elevated at 6, 12, 24, 48, 72, and 96 hr but in liver, the levels increased only at 96 hr. Mean values of muscle and liver pyruvate were elevated significantly (P less than 0.05) at 6, 12, 24, 48, and 72 hr. Muscle lactate levels increased at 6, 12, 24, and 48 hr in pesticide-treated fish. Liver lactate levels we…
Sex-specific reaction of liver ultrastructure in zebra fish (Brachydanio rerio) after prolonged sublethal exposure to 4-nitrophenol
1989
Abstract Morphological alterations of the liver of zebra fish ( Brachydanio rerio ) following prolonged exposure to 0.1, 1 and 5 mg · l −1 4-nitrophenol (4-NP) were investigated by means of light and electron microscopy. Based on marked sexual dimorphism in control animals, liver recactions were both sex- and dose-dependent. Whereas at 0.1 mg·1 −1 only minor changes could be revealed, there were numerous structural modifications at 1 mg·1 −1 : Whereas male fish primarily react with a proliferation of smooth endoplasmic reticulum, female fish display a high degree of fenetrastion within cisternate of the rough endoplasmic reticulum. Both sexes exhibit infiltration of macrophages and lymphocy…
A human hepatocellular in vitro model to investigate steatosis
2006
The present study was designed to define an experimental model of hepatocellular steatosis with a fat overaccumulation profile in which the metabolic and cytotoxic/apoptotic effects could be separated. This was accomplished by defining the experimental conditions of lipid exposure that lead to significant intracellular fat accumulation in the absence of overt cytotoxicity, therefore allowing to differentiate between cytotoxic and apoptotic effects. Palmitic (C16:0) and oleic (Cl 8: 1) acids are the most abundant fatty acids (FFAs) in liver triglycerides in both normal subjects and patients with nonalcoholic fatty liver disease (NAFLD). Therefore, human hepatocytes and HepG2 cells were incub…
Direct-acting antivirals for hepatitis C virus infections in patients co-infected with human immunodeficiency virus
2011
Summary Nearly three-quarters of human immunodeficiency virus–hepatitis C virus (HIV-HCV) coinfected patients in France currently need to be cured of their chronic HCV infection. The increase in sustained virological response rates obtained with the recently available HCV protease inhibitors in treatment-naive genotype-1 patients has generated considerable hope in these co-infected patients. However, several particularities (such as a higher baseline HCV load, more advanced liver fibrosis, frequent co-morbidities, and the risk of toxicity and drug–drug interactions) have not allowed the direct extrapolation of the results observed in HCV-monoinfected patients to patients with HIV-HCV co-inf…