The study objective was to investigate a possible sodium dichloroacetate (DCA) pharmacological mechanism causing an increase in diuresis in rats. The aim was to define characteristics of 24-hour urinary Na+, K+, Cl−, Ca2+, and Mg2+ excretion in Wistar male rats and to evaluate effect of a single-dose DCA and repeated DCA dosage on diuresis. Six control and 6 DCA-treated male rats aged 5 to weeks after a single DCA dose and repeated dosage were tested. The single DCA dose treatment caused a significantly higher 24-hour diuresis when compared to control (P < .05), and it was related to increased Cl−, Na+, and K+ urine excretion and a significant increase in Ca2+ and Mg2+ excretion (P < .05); after the repeated 4-week DCA dosage, the diuresis was not increased, but the excretion of the Na+, Cl−, Ca2+, and Mg2+ ions was significantly higher. Kidney immunohistochemistry has revealed that DCA continuous treatment results in an increase in the size of Henle loop thick ascending limb epithelial cells (P < .001). The study results show a significantly reduced RNA expression of Na-K-2Cl co-transporter (NKCC1) in thymus of 4-week DCA-treated rats (P < .03). The study data have indicated a possible mechanism of such pharmacological effect to be NKCC inhibition.
ObjectiveErythema multiforme (EM) is an immune-mediated condition characterized by the appearance of target-like lesions on the skin and often accompanied by erosions or bullae involving the oral, genital, and/or ocular mucosae. 70% of recurrent EM cases are associated with HSV reactivation and it is labelled as herpes-associated erythema multiforme (HAE M). Recurrences are seen in approximately 20-25% of EM cases and managing these conditions are challenging for both the patient and the doctor. The effectiveness of antiviral drugs is proven for Herpes simplex infection, however most patients use a multiplicity of alternative and complementary therapies.Clinical presentationWe present clinical data of 3 patients with recurrent HAE M managed by long-term valacyclovir therapy and immunostimulation with Echinacea or replacement immunoglobulin therapy in the case of IgG1 subclass deficiency. The presented cases have demonstrated that immune mechanisms are relevant for HAEM recurrences.ConclusionsThe immune abnormalities, such as antibody deficiency, in the patients with HSV-associated EM can lead to frequent relapses of disease and should be evaluated. Long-term antiviral therapy with immunomodulation can control the relapses of HAEM.
The study aim was to investigate the effect of dichloroacetate (DCA) on thymus and the thymocyte cycle in rats. Wistar male gonad-intact and castrated rats (4-5 weeks) were investigated in the following groups: (1) control; (2) treated with DCA; and (3) treated with the DCA and sodium valproate (NaVP) combination. Rats were treated for 4 weeks with DCA 200 mg/kg/day alone and 300 mg/kg/day of NaVP plus 200 mg/kg/day of DCA (every second week, beginning with NaVP). After the experiment, the thymus was weighted, and the thymus lobe was taken for thymocyte flow cytometry. In gonad-intact rats, the thymus weight of the control was higher than in rats treated with DCA (P <0.001) or with the NaVP-DCA combination (P <0.04); a comparison of thymus weight between DCA- and NaVP-DCA-treated groups revealed a higher thymus weight loss in the DCA-treated group (P <0.03). Flow cytometry shows that DCA treatment increased the percentage of cells in the G-M phase (P <0.03) and reduced in G-G (P <0.02). The DCA treatment effect was determined only in gonad-intact but not in castrated rats. The authors discuss the possible DCA and NaVP interaction mechanisms.
The aim was to investigate the effect of dichloroacetate (DCA) on thymus weight, Hassall’s corpuscle number (HCs), and NKCC1 RNA expression in Wistar rats aged 4–5 weeks. They were investigated in the controls and DCA-treated gonad-intact and castrated males and females. The treatment lasted 4 weeks with DCA 200 mg/kg/day. At the end of the experiment, rat thymus was weighted, and its lobe was taken for the expression of NKCC1 RNA determined by the PCR method and of Hassall’s corpuscles by immunohistochemistry. DCA caused a thymus weight decrease in DCA-treated gonad-intact rats of both genders as compared with their controls (p < 0.05), and no such impact was found in castrated DCA-treated males and females. DCA caused an increase of the HCs in gonad-intact males (p < 0.05), and no such increase in the DCA-treated gonad-intact females was found. There was gender-related difference in the HCs when comparing DCA-treated gonad-intact males and females: males showed significantly higher HCs (p < 0.05); no gender-related differences were found in the castrated DCA-treated groups. The Slc12a2 gene RNA expression level was found to be significantly decreased only in gonad-intact and in castrated DCA-treated males. The authors discuss the gender-related DCA effects on the thymus.
Objective: The NKCC1 is a recognized tumorigenesis marker as it is important for tumor cell proliferation, differentiation, apoptosis, and tumor progression. The study aim was to investigate the effect of sodium valproate (VPA) on thymus NKCC1 RNA expression. Material and Methods: Wistar rats, age 4 to 5 weeks, were investigated in the control and VPA-treated male and female gonad-intact and castrated groups. The treatment duration with VPA 300 mg/kg/d was 4 weeks. Rat thymus was weighted; its lobe was taken for the expression of NKCC1 RNA determined by the real-time polymerase chain reaction method. Results: The RNA expression of the Slc12a2 gene was found to be significantly higher in the gonad-intact male control compared with the gonad-intact female control ( P = .04). There was a gender-related VPA treatment effect on NKCC1 RNA expression in thymus: The Slc12a2 gene RNA expression level was found to be decreased in VPA-treated gonad-intact males ( P = .015), and no significant VPA effects were found in the castrated males and in the gonad-intact and castrated females compared with the respective controls ( P > .05). Conclusions: The study showed a gender-related difference in the NKCC1 RNA expression in rat thymus. The VPA decreases the NKCC1 expression in the thymus only in gonad-intact male rats. The NKCC1 RNA expression downregulation by VPA could be important for further VPA pharmacological studies in oncology.
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