Psychostimulant, cardiovascular, and temperature actions of stimulants involve adrenergic (norepinephrine), dopaminergic (dopamine), and serotonergic (serotonin) pathways. Stimulants such as amphetamine, 3,4‐methylenedioxymethamphetamine (MDMA), or mephedrone can act on the neuronal membrane monoamine transporters NET, DAT, and SERT and/or the vesicular monoamine transporter 2 to inhibit reuptake of neurotransmitter or cause release by reverse transport. Stimulants may have additional effects involving pre‐ and postsynaptic/junctional receptors for norepinephrine, dopamine, and serotonin and other receptors. As a result, stimulants may have a wide range of possible actions. Agents with cocaine or MDMA‐like actions can induce serious and potentially fatal adverse events via thermodysregulatory, cardiovascular, or other mechanisms. MDMA‐like stimulants may cause hyperthermia that can be life threathening. Recreational users of stimulants should be aware of the dangers of hyperthermia in a rave/club environment.
Introduction The association between inflammatory bowel disease (IBD) - particularly its two main subtypes, ulcerative colitis (UC) and Crohn’s disease (CD) - and celiac disease (CeD) has been attributed to an overlap in the mechanism of immune dysregulation that characterizes these conditions. Owing to the paucity of studies that have explored this condition in pediatric patients, we examined the prevalence of CeD in children with IBD. Materials and methods This is a cross-sectional study of children aged two to 18 years with IBD that were diagnosed between 2016 and 2018. Clinical, demographic, laboratory, and endoscopic data were analysed. Serology for CeD measured the immunoglobulin A tissue transglutaminase (IgA-tTG) antibodies, and the diagnosis was confirmed histologically through small bowel biopsies. Results The study included 101 patients with IBD (83.2% with UC and 16.8% with CD). The mean age was 8.7±4.0 years. Males constituted 59.4% of the cohort, and only 3% had perianal disease. Ileocolonic involvement was reported in 64.7% and non-stricturing and non-penetrating behaviour in 76.7% of CD patients. Pancolitis constituted 45.2% of UC patients. Ten patients (9.9%) had positive serology based on IgA-tTG antibodies, three (approximately 3%) had CeD based on biopsy findings, two patients (2%) had CD, and one patient (1%) had UC. Patients with confirmed CeD had a significantly higher frequency of symptoms of gaseous sensation and bloating (P=0.003) and abdominal distension (P=0.04). Conclusions The prevalence of CeD in Egyptian children with IBD is higher than previously reported in a number of similar studies. Abdominal bloating and gaseous sensation were identified as associated symptoms.
The vast majority of illicit stimulants act at monoaminergic systems, causing both psychostimulant and adverse effects. Stimulants can interact as substrates or antagonists at the nerve terminal monoamine (MA) transporter that mediates reuptake of MA across the nerve synaptic membrane and at the vesicular monoamine transporter (VMAT-2) that mediates storage of MA in vesicles. Stimulants can act directly at pre-or postsynaptic receptors for MA's or have indirect monoaminomimetic actions due to release of MA's. Cocaine and other stimulants can acutely increase the risk of sudden cardiac death. Stimulants, particularly MDMA, in hot conditions, such as that occurring at a 'Rave', have caused fatalities from the consequences of hyperthermia, often compounding cardiac adverse actions. This review examines the pharmacology of the cardiovascular and temperature adverse actions of stimulants.
We have studied gender differences in the direct and indirect sympathomimetic cardiovascular effects of the stimulant cathinone (from Khat) (and for comparison methylenedioxymethamphetamine [MDMA]) and the archetypal indirect sympathomimetic agent tyramine, employing male and female Wistar rats. Animals were sympathectomized by treatment with 6-hydroxydopamine or treated with vehicle. In male and female vehicle-treated pentobarbitone-anaesthetized rats, all three agonists (0.001-1 mg/kg) produced significant tachycardia, tyramine produced large pressor, and in high doses small depressor responses, MDMA produced small pressor responses, and cathinone produced only minor pressor effects. In sympathectomized rats, pressor responses, even those to tyramine, were virtually abolished, and depressor responses to tyramine were abolished. In vehicle-treated rats, the tachycardia to tyramine, but not the tachycardia to cathinone or MDMA, was significantly greater in male than female rats. This may suggest that the mechanism of the tachycardia to tyramine differs from those of the stimulants cathinone and MDMA. Following sympathectomy, there were no differences between male and female rats in the tachycardia to any agent. Hence, there were gender differences in the tachycardia response for tyramine, but no gender differences in the cardiovascular responses to the widely used recreational stimulants cathinone and MDMA. Cardiac stimulant actions of cathinone and MDMA were similar in male and female rats.
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