Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Mar 2014
Deliberate drug poisoning with slight symptoms on admission: are there predictive factors for intensive care unit referral? A three-year retrospective study.
Deliberate drug poisoning leads to 1% of emergency department (ED) admissions. Even if most patients do not exhibit any significant complication, 5% need to be referred to an intensive care unit (ICU). Emergency physicians should distinguish between low- and high-acuity poisoned patients at an early stage to avoid excess morbidity. ⋯ A presumed toxic dose ingestion (aOR = 2.27; 95% CI: 1.28-4.02), number of ingested tablets (aOR = 1.01; 95% CI: 1.01-1.02 for each tablet) and delay between ingestion and ED arrival <2 hr (aOR = 2.85; 95%CI: 1.62-5.03) were also factors for ICU referral. The Glasgow Coma Scale was the only clinical feature associated with ICU admission (aOR = 1.57; 95% CI: 1.44-1.70 for each point loss). These results suggest that emergency physicians should pay particular attention to toxicological data on ED admission to distinguish between low- and high-acuity self-poisoned patients.
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Basic Clin. Pharmacol. Toxicol. · Feb 2014
Review Case ReportsHypocalcaemia after an occult calcium channel blocker overdose: a case report and literature review.
Hypocalcaemia is a rare complication of calcium channel blocker overdose, having been reported only once previously (J Toxicol Clin Toxicol, 1992, 30, 309). In this article, we report a case of a 37-year-old woman who developed hypocalcaemia after a verapamil overdose, review the literature and propose a mechanism for this rare finding.
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Antibodies that block cytokine function provide a powerful therapeutic tool especially for the treatment of autoimmune diseases. Cytokines are a group of small hydrophilic glycoproteins that bind their receptors on the cell surface and subsequently activate intracellular signalling cascades, such as the JAK/STAT pathway. A bulk of evidence has demonstrated that genetic mutations in signalling molecules can cause immunodeficiencies and malignant cell growth. ⋯ Inhibiting JAK function has been shown to efficiently prevent the uncontrolled growth of cancerous cells and to harness overly active immune cells. In the future, other small molecule compounds are likely to come into clinical use, and intense work is ongoing to develop inhibitors that specifically target the constitutively active mutant JAKs. This MiniReview will summarize the basic features of the JAK/STAT pathway, its role in human disease and the therapeutic potential of JAK/STAT inhibitors.
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Basic Clin. Pharmacol. Toxicol. · Dec 2013
17β-Oestradiol Protects Primary-Cultured Rat Cortical Neurons from Ketamine-Induced Apoptosis by Activating PI3K/Akt/Bcl-2 Signalling.
Numerous studies in rodents have indicated that exposure to ketamine during the period when synaptogenesis is highly active induces neurodegeneration. Thus, there is a growing need to develop strategies to prevent ketamine-induced brain injury in the developing brain. Oestradiol is a neuroactive steroid that prevents neuronal cell death in different experimental models by activating cell survival signals and inhibiting apoptotic signals. ⋯ Furthermore, we found that 17β-oestradiol not only induced phosphorylation of the PI3K substrate Akt, but also increased the expression of Bcl-2, which down-regulated ketamine-induced caspase-3 activity and inhibited neuronal apoptosis. These data demonstrate that 17β-oestradiol exerts a neuroprotective effect against ketamine-induced neuronal apoptosis by activating the PI3K/Akt/Bcl-2 signalling pathway. Therefore, 17β-oestradiol appears to be a promising agent in preventing or reversing ketamine's toxic effects on neurons at an early developmental stage.
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Basic Clin. Pharmacol. Toxicol. · Oct 2013
Evaluation of the effectiveness of sugammadex for verapamil intoxication.
Previous studies have shown that medications from the cyclodextrin family bind to verapamil. The aim of our study was to determine whether sugammadex could bind to verapamil and prevent the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with verapamil at 37.5 mg/kg/h. ⋯ We found that treatment with 16 mg/kg sugammadex delayed verapamil cardiotoxicity in rats. However, 1000 mg/kg sugammadex accelerated verapamil cardiotoxicity in rats. Further studies must be conducted to investigate the interaction between verapamil and sugammadex.