ABSTRACT
In Japan, hyperuricemia is on the rise. The guideline for the management of hyperuricemia and gout recommends lifestyle changes before beginning drug therapy. This study aimed to evaluate the effectiveness of dietary counseling following the guideline. Thirty-three subjects (24 men and 9 women) with asymptomatic hyperuricemia underwent dietary counseling for 6 months based on the following recommendations : (1) prevent excessive purine intake, (2) prevent excessive fructose intake, (3) limit alcohol drinking, and (4) drink sufficient water. Obese subjects were counseled on adequate energy intake. Blood sampling, anthropometric measurements, dietary surveys, and 24-h urine collection were performed at baseline and at 6 months. Serum uric acid (S-UA) levels were significantly lower at 6 months compared to baseline. Water intake and urine volume were considerably higher at 6 months than at baseline. When compared to baseline, urine UA (U-UA) levels were significantly lower, and renal fractional excretion of UA (FEUA) was significantly higher at 6 months. Changes in renal function (serum creatinine, estimated glomerular filtration rate, and FEUA) were significantly associated with ?S-UA level. In this study, S-UA level was significantly decreased by dietary counseling in line with the guideline. This study illustrates the effectiveness of dietary counseling for asymptomatic hyperuricemia. J. Med. Invest. 70 : 34-40, February, 2023.
Subject(s)
Gout , Hyperuricemia , Male , Humans , Female , Uric Acid/therapeutic use , Uric Acid/urine , Obesity/complications , Glomerular Filtration RateABSTRACT
Organophosphates (OPs) inhibit cholinesterase and hyperactivate the acetylcholinergic nervous system in the brain, causing motor disorders (e.g., tremor and seizures). Here, we performed behavioral and immunohistochemical studies in mice and rats to investigate the tremorgenic mechanism of paraoxon, an active metabolite of parathion. Treating animals with paraoxon (0.15-0.6 mg/kg, i.p.) elicited kinetic tremor in a dose-dependent manner. Expressional analysis of Fos protein, a biomarker of neural excitation, revealed that a tremorgenic dose of paraoxon (0.6 mg/kg) significantly and region-specifically elevated Fos expression in the cerebral cortex (e.g., sensory cortex), hippocampal CA1, globus pallidus, medial habenula, and inferior olive (IO) among 48 brain regions examined. A moderate increase in Fos expression was also observed in the dorsolateral striatum while the change was not statistically significant. Paraoxon-induced tremor was inhibited by the nicotinic acetylcholine (nACh) receptor antagonist mecamylamine (MEC), but not affected by the muscarinic acetylcholine receptor antagonist trihexyphenidyl (THP). In addition, paraoxon-induced Fos expression in the IO was also antagonized by MEC, but not by THP, and lesioning of the IO markedly suppressed tremorgenic action of paraoxon. The present results suggest that OPs elicit kinetic tremor at least partly by activating IO neurons via nACh receptors.
Subject(s)
Brain/drug effects , Brain/metabolism , Dyskinesia, Drug-Induced/metabolism , Paraoxon/adverse effects , Tremor/chemically induced , Tremor/metabolism , Animals , Brain/pathology , Dose-Response Relationship, Drug , Dyskinesia, Drug-Induced/drug therapy , Dyskinesia, Drug-Induced/pathology , Gene Expression/drug effects , Male , Mecamylamine/pharmacology , Mice , Muscarinic Antagonists/pharmacology , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Nicotinic Antagonists/pharmacology , Oncogene Proteins v-fos/metabolism , Rats , Receptors, Nicotinic/metabolism , Tremor/drug therapy , Tremor/pathology , Trihexyphenidyl/pharmacologyABSTRACT
We previously demonstrated that nicotine elicited kinetic tremor by elevating the neural activity of the inferior olive via α7 nicotinic acetylcholine (nACh) receptors. Since α7 nACh receptors reportedly facilitate synaptic monoamine release, we explored the role of 5-HT receptors in induction and/or modulation of nicotine tremor. Treatment of mice with nicotine induced kinetic tremor that normally appeared during movement. The 5-HT1A agonist, 8-hydroxydipropylaminotetraline (8-OH-DPAT), significantly enhanced nicotine-induced tremor and the action of 8-OH-DPAT was antagonized by WAY-100135 (5-HT1A antagonist). In addition, the cerebral 5-HT depletion by repeated treatment with p-chlorophenylalanine did not reduce, but rather potentiated the facilitatory effects of 8-OH-DPAT. In contrast, the 5-HT2 agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), significantly attenuated nicotine tremor, which was antagonized by ritanserin (5-HT2 antagonist). The 5-HT3 agonist SR-57227 did not affect nicotine-induced tremor. Furthermore, when testing the direct actions of 5-HT antagonists, nicotine tremor was inhibited by WAY-100135, but was unaffected by ritanserin, ondansetron (5-HT3 antagonist) or SB-258585 (5-HT6 antagonist). These results suggest that postsynaptic 5-HT1A receptors are involved in induction of nicotine tremor mediated by α7 nACh receptors. In addition, 5-HT2 receptors have an inhibitory modulatory role in induction of nicotine tremor.
