Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
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J. Physiol. Pharmacol. · Aug 2013
Diazepam and its metabolites in the mothers' and newborns' hair as a biomarker of prenatal exposure.
Pregnant women are exposed to benzodiazepines for therapeutic purposes during gestation. The goal of this study was to evaluate prenatal exposure to benzodiazepines. Time of exposure during course of pregnancy is a significant aspect of fetal exposure to drugs. Benzodiazepine concentration assay in hair of mothers and newborns exposed prenatally to these drugs was performed in the studies. Development, validation and evaluation of benzodiazepine determination method in mothers and their newborns enables assessment of health risks for the child and implementation of adequate therapeutic procedures. We used A LC-ESI-MS/MS method that allowed determination of diazepam (the main benzodiazepine used by pregnant women was diazepam) and its metabolites (nordazepam, oxazepam) in hair of mothers and newborns. LOQ 10 pg/mg of hair was used in the study. ⋯ concentration of nordazepam was higher than parent drug (diazepam) and higher in newborns' hair when compared to mothers'. The mean concentrations of diazepam in mothers' hair were 31.6±36.0 and 34.1±42.4 pg/mg in the second and third trimester of pregnancy respectively. The mean concentration of diazepam in newborns' hair was higher and reached levels of 53.3±36.5 pg/mg. The mean concentration of nordazepam in the mothers' hair corresponding to the second and third trimester was 52.9±48.1 and 89.9±122.8 pg/mg, respectively. Nordazepam in the newborns' hair was detected at the mean level of 108.1±144.2 pg/mg. It was concluded that diazepam and nordazepam are permanently incorporated into the hair structure. Presence of diazepam and its metabolites in newborn's hair confirms that these benzodiazepines permeate placental barrier. Segmental analysis of mothers' hair enabled the assessment of drug administration time. Diazepam and its metabolites determined in hair of newborns may serve as biomarkers of prenatal exposure to these drugs. The performed LC-MS/MS analysis was accurate enough to determine even low concentrations of benzodiazepines, at the level of few pg/mg of hair. Levels of diazepam detected in hair of newborns were higher than levels determined in mothers. This may confirm the fact, that fetus's ability to metabolize diazepam is scarce. Nordazepam was found in higher concentrations in hair of newborns than in hair of mothers, which may suggest that it is cumulated in child's organism. Other metabolites of diazepam--oxazepam and temazepam--were detected in very few cases, in low concentrations.
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J. Physiol. Pharmacol. · Jun 2013
Spinal transient receptor potential ankyrin 1 channel induces mechanical hypersensitivity, increases cutaneous blood flow, and mediates the pronociceptive action of dynorphin A.
We characterized pain behavior and cutaneous blood flow response induced by activation of the spinal transient receptor potential ankyrin 1 (TRPA1) channel using intrathecal drug administrations in the rat. Additionally, we assessed whether the pronociceptive actions induced by intrathecally administered dynorphin A, cholecystokinin or prostaglandin F(2α) are mediated by the spinal TRPA1 channel. Cinnamaldehyde, a TRPA1 agonist, produced a dose-related (3-10 μg) cutaneous blood flow increase and mechanical hypersensitivity effect. ⋯ The results indicate that spinal TRPA1 channels promote mechanical pain hypersensitivity and due to antidromic activation of nociceptive nerve fibers increase cutaneous blood flow. The attenuation of the cinnamaldehyde-induced hypersensitivity effect by minocycline may be explained by action other than block of the TRPA1 channel. Moreover, the spinal TRPA1 channel is involved in mediating the pronociceptive action of dynorphin A, but not that of the spinal cholecystokinin or prostaglandin F(2α).
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J. Physiol. Pharmacol. · Apr 2013
Adiponectin and leptin receptors expression in Barrett's esophagus and normal squamous epithelium in relation to central obesity status.
Esophageal adenocarcinoma incidence is rapidly increasing which may be due to the growing incidence of Barrett's esophagus (BE) and obesity. The mechanisms linking obesity and progression of Barrett's carcinogenesis is poorly understood. The aim of the study was to evaluate the expression of adipokines receptors in BE and in normal squamous epithelium in the same patients in correlation with obesity parameters. ⋯ in opposite to the prior hypothesis adiponectin and leptin receptors activation in BE may be not caused by obesity.
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J. Physiol. Pharmacol. · Apr 2013
Modulation of metabolic and cardiac dysfunctions by swimming in overweight rats on a high cholesterol and fructose diet: possible role of adiponectin.
Western diet rich in cholesterol and sucrose with decreased physical activity cause overweight and metabolic syndrome. The aim of the present study was to investigate the effect of swimming on the cardiac adiponectin mRNA expression in high cholesterol and fructose fed rats. Forty Sprague-Dawley male rats divided into 2 equal groups. ⋯ Also, there was an over-expression of down-expressed cardiac adiponectin gene. Also, ventricular functions were ameliorated by swimming exercise training. Swimming exercise partially improved the ventricular function that could be possibly explained through increased the cardiac expression of adiponectin.
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J. Physiol. Pharmacol. · Dec 2012
Exogenous melatonin abolishes mechanical allodynia but not thermal hyperalgesia in neuropathic pain. The role of the opioid system and benzodiazepine-gabaergic mechanism.
Melatonin (MT) is a neurohormone synthesized and secreted by the pineal gland. MT plays an important role in the regulation of physiological and neuroendocrine functions. The purpose of this study was to assess the overall effect of melatonin on neuropathic pain, the type of melatonin receptor involved, and potential role of the opioid system and GABA(A) receptors. ⋯ The antiallodynic effect of MT was also abolished by flumazenil and picrotoxin. Melatonin influences the mechanical allodynia but not thermal hyperalgesia via activation of opioid system and benzodiazepine-GABAergic pathway. Antinociceptive effects of melatonin are mostly related to the MT1/MT2 receptors interaction.