Sodium valproate stimulates potassium and chloride urinary excretion in rats: gender differences

Background: The diuretic effect of valproates and its relation to urinary potassium (K+) and chloride (Cl-) excretion have not yet been investigated, so the aim of this study was to evaluate the influence of a single dose of sodium valproate (NaVPA) on 24-h urinary K+ and Cl- excretion in young adult Wistar rats of both genders. For measurement of K+ in urine, the same animals and samples as in our earlier publication were used (Pharmacology 2005 Nov, 75:111–115). The authors propose a new approach to the pathophysiological mechanisms of NaVPA effect on K+ and Cl- metabolism. Twenty six Wistar rats were examined after a single intragastric administration of 300 mg/kg NaVPA (13 NaVPA-male and 13 NaVPA-female), 28 control intact Wistar rats (14 males and 14 females) were studied as a control group. The 24-h urinary K+, Cl-, creatinine and pH levels were measured. Results: Total 24-h diuresis and 24-h diuresis per 100 g of body weight were found to be significantly higher in NaVPA-rats of both genders than in rats of the control group (p 0.05). 24-h urinary K+ excretion per 100 g of body weight in NaVPA-male rats was significantly higher than in control males (p = 0.025). NaVPA enhanced Cl- urinary excretion: 24-h Cl- urinary excretion, 24-h urinary Cl- excretion per 100 g of body weight and the Cl-/creatinine ratio were significantly higher in NaVPA-male and NaVPA-female rats than in gendermatched controls (p < 0.05). 24-h chloriduretic response to NaVPA in male rats was significantly higher than in female rats (p < 0.05). Conclusion: NaVPA causes kaliuretic and chloriduretic effects with gender-related differences in rats. Further investigations are necessary to elucidate the mechanism of such pharmacological effects of NaVPA

Correlation between 24-h diuresis and Kexcretion in NaVPA male and female rats

<p><b>Copyright information:</b></p><p>Taken from "Sodium valproate stimulates potassium and chloride urinary excretion in rats: gender differences"</p><p>http://www.biomedcentral.com/1471-2210/7/9</p><p>BMC Pharmacology 2007;7():9-9.</p><p>Published online 6 Aug 2007</p><p>PMCID:PMC1959196.</p><p></p> * – Statistically significant correlation

Correlation between 24-h diuresis and Clexcretion in NaVPA male and female rats

<p><b>Copyright information:</b></p><p>Taken from "Sodium valproate stimulates potassium and chloride urinary excretion in rats: gender differences"</p><p>http://www.biomedcentral.com/1471-2210/7/9</p><p>BMC Pharmacology 2007;7():9-9.</p><p>Published online 6 Aug 2007</p><p>PMCID:PMC1959196.</p><p></p> * – Statistically significant correlation

Correlation between urine pH and Clexcretion in NaVPA male and female rats

<p><b>Copyright information:</b></p><p>Taken from "Sodium valproate stimulates potassium and chloride urinary excretion in rats: gender differences"</p><p>http://www.biomedcentral.com/1471-2210/7/9</p><p>BMC Pharmacology 2007;7():9-9.</p><p>Published online 6 Aug 2007</p><p>PMCID:PMC1959196.</p><p></p> * – Statistically significant correlation

HINT1 neuropathy in Lithuania : clinical, genetic, and functional profiling

BACKGROUND: Recessive loss-of-function variations in HINT1 cause a peculiar subtype of Charcot-Marie-Tooth disease: neuromyotonia and axonal neuropathy (NMAN; OMIM[#137200]). With 25 causal variants identified worldwide, HINT1 mutations are among the most common causes of recessive neuropathy. The majority of patients are compound heterozygous or homozygous for a Slavic founder variant (c.110G>C, p.Arg37Pro) that has spread throughout Eurasia and America. RESULTS: In a cohort of 46 genetically unresolved Lithuanian patients with suspected inherited neuropathy, we identified eight families with HINT1 biallelic variations. Most patients displayed sensorimotor or motor-predominant axonal polyneuropathy and were homozygous for the p.Arg37Pro variant. However, in three families we identified a novel variant (c.299A>G, p.Glu100Gly). The same variant was also found in an American patient with distal hereditary motor neuropathy in compound heterozygous state (p.Arg37Pro/p.Glu100Gly). Haplotype analysis demonstrated a shared chromosomal region of 1.9 Mb between all p.Glu100Gly carriers, suggesting a founder effect. Functional characterization showed that the p.Glu100Gly variant renders a catalytically active enzyme, yet highly unstable in patient cells, thus supporting a loss-of-function mechanism. CONCLUSION: Our findings broaden NMAN’s genetic epidemiology and have implications for the molecular diagnostics of inherited neuropathies in the Baltic region and beyond. Moreover, we provide mechanistic insights allowing patient stratification for future treatment strategies