Pharmacology
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Metformin is a widely used antidiabetic agent that is generally considered safe. However, metformin-associated lactic acidosis (MALA), though not common, occurs from time to time and results in significantly high mortality. A series of 23 MALA cases in a local major hospital in Hong Kong is reported in this article to demonstrate the epidemiological data, risk factors, clinical features as well as the clinical outcomes for better understanding of this disease entity. ⋯ The majority of patients were found to have significantly raised creatinine versus a normal baseline value before the acute illness. Concomitant illnesses taking place alongside MALA were common. With a high utility rate of renal replacement therapy (82.6%) in the study group, the mortality rate was 30.4%.
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Sevoflurane is widely used for anesthesia, and is commonly used together with opioids in clinical practice. However, the effects of sevoflurane on μ-opioid receptor (μOR) functions is still unclear. In this study, the effects of sevoflurane on μOR functions were analyzed by using Xenopus oocytes expressing a μOR fused to chimeric Gα protein G(qi5) (μOR-G(qi5)). ⋯ The inhibitory effects of sevoflurane on the DAMGO-induced currents were not observed in oocytes pretreated with the protein kinase C (PKC) inhibitor GF109203X. These findings suggest that sevoflurane would inhibit μOR function. Further, the mechanism of inhibition by sevoflurane would be mediated by PKC.
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Progesterone has been shown to play a role in pain perception. However, the effects of progesterone on P2X3 receptors, the nociception-related receptors in primary sensory neurons, remain unclear. ⋯ These results suggest that progesterone may modulate pain signal transmission on dorsal root ganglia via regulating P2X3 receptor function. The cAMP-PKA signaling pathway is involved in the downregulating effect of progesterone on P2X3 receptors.
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This study investigated the role of the cholinergic system in the modulation of inflammatory and neuropathic pain. The paw pressure test was used with inflammatory pain induced by intraplantar injection of carrageenan and neuropathic pain induced by sciatic nerve constriction. All drugs were locally administered into the right hindpaw of rats. ⋯ Atropine significantly decreased the nociceptive threshold only in the treated paw. On the other hand, in the presence of neuropathic pain, atropine (300 μg) did not alter the nociceptive threshold induced by constriction of the sciatic nerve. This study suggests that a peripheral endogenous cholinergic system involving muscarinic receptors may be activated during inflammation as a modulatory negative feedback control of inflammatory pain.
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The rewarding effects of drugs of abuse are often studied by means of the conditioned place preference (CPP) paradigm. CPP is one of the most widely used models in behavioral pharmacology, yet its theoretical underpinnings are not well understood, and there are very few studies on the methodological and theoretical aspects of this model. An important drawback of the classical CPP paradigm is that it often does not show dose-dependent results. ⋯ These findings suggest that the use of an extinction paradigm can extend the quantitative assessment of the rewarding effect of drugs - however, within certain limits only. The present paradigm appears to be less suited for comparing the rewarding efficacy of different drugs due to great test-retest variability. Finally, the additional potential gain of information using this paradigm has to be weighed against the considerably large amount of additional time and effort.