Reduced levels of vitamin or its metabolites have been reported in various psychiatric disorders. Insufficient levels of vitamin D in depressive patients have been confirmed by many authors, but there have been conflicting results in subjects with anxiety disorders. In the present cross-sectional study, levels of calcidiol were determined in groups of depressive men and women and in men and women with anxiety disorders and compared with age matched controls. Significantly lower levels of calcidiol were found in men and women with depression as well as in age matched patients with anxiety disorders., M. Bičíková, M. Dušková, J. Vítků, B. Kalvachová, D. Řípová, P. Mohr, L. Stárka., and Obsahuje bibliografii
The relationship between vitamin D receptor (VDR) intragenic polymorphisms FokI, BsmI, ApaI and TaqI and bone mineral density (BMD) or biochemical markers of bone remodeling were investigated in 114 Czech postmenopausal women, on the average 62.5±8.9 years of age. Restriction fragment length polymorphisms in the VDR gene were assessed by PCR amplification and digestion with restriction enzymes FokI, BsmI, ApaI, and TaqI recognizing polymorphic sites in the VDR locus. Bone mineral density was measured at the lumbar spine and at the hip by dual-energy X-ray absorptiometry (DEXA, g/cm2). After adjusting for age and the body mass index (BMI), subjects with the ff genotype had 9.4 % lower BMD at the hip than those with the Ff genotype (p=0.0459, Tukey´s test). FF individuals had an intermediate BMD at the hip. A similar pattern of lower lumbar spine BMD was also found in ff individuals, but it did not reach statistical significance. There was no relationship between BsmI, ApaI and TaqI VDR polymorphisms and BMD at any skeletal site. Subjects with Aa (ApaI) genotypes had higher levels of propeptide of type I collagen (PICP) than homozygous AA (p=0.0459, Tukey´s test). In FokI, BsmI and TaqI restriction sites the biochemical markers of bone remodeling did not differ by genotype. In addition, no significant difference was observed in VDR genotypic distribution between osteoporotic women and non-osteoporotic controls in the study group. To conclude, the FokI genotype of the vitamin D receptor gene is related to bone mass at the hip in Czech postmenopausal women, whereas the importance of remaining VDR genotypes was not evident., K. Zajíčková, I. Žofková, R. Bahbouh, A. Křepelová., and Obsahuje bibliografii
In women with chronic autoimmune thyroiditis and vitamin D deficiency we have found reference levels of relevant metabolichormonal parameters except for parathormone and total calcium. Three months supplementation with vitamin D (4300 IU/day, cholekalciferol) did not lead to significant changes of investigated hormonal parameters, while the levels of parathormone and calcium reached normal levels. However, a correlation analysis revealed marked changes in mutual relations. First, an inverse correlation of vitamin D with parathormone, insulin secretion (C peptide, insulin) and its efficiency (HOMA IR) disappeared. Relationships of vitamin D to hepatic insulin resistance (insulin/C peptide), to DHEA (both negative), and to DHEAS/DHEA ratio (positive) were newly found. Second, a positive correlation of CRP with insulin secretion remained, while its relation to insulin efficiency (HOMA IR, insulin/ C peptide) was newly observed. Analogical positive correlations appeared also among anti TPO and insulinemia, insulin/C peptide, HOMA IR, and anti Tg to C peptide. A relationship of the CRP with anti TPO became significant (+). Third, out of glucose metabolism parameters only insulin/C peptide and glycemia did not correlate with vitamin D during its deficiency, while after supplementation insulin/ C peptide alone correlated positively with both DHEAS and DHEA, and negatively with vitamin D., K. Vondra, R. Bílek, P. Matucha, M. Salátová, M. Vosátková, L. Stárka, R. Hampl., and Obsahuje bibliografii
We examined the upregulation of ET-1/ETBR/eNOS signaling in renoprotective effect of vitamin D in kidney fibrosis model in mice using unilateral ureteral obstruction (UUO). One group was treated with intraperitoneal injection of 0.125 mg/kg of Calcitriol (UUO+VD). Vascular remodeling was quantified based on lumen area and lumen/wall area ratio (LWAR) of intrarenal arteries using Sirius Red staining. ET-1, ETBR, eNOS, CD31 and VEGF mRNA expressions were quantified using qRT-PCR. Focusing on endothelin-1 (ET-1) signaling in endothelial cells (EC), siRNA of ET-1 was performed in human umbilical vein endothelial cells (HUVEC) for reducing ET-1 expression. Then HUVECs were treated with and without 100 nM Calcitriol treatment in hypoxic and normoxic conditions to elucidate ET-1/eNOS signaling. Our in vivo study revealed vascular remodeling and renal ischemia attenuation after Calcitriol treatment. Vascular remodeling was attenuated in the UUO+VD group as shown by increasing lumen areas and LWAR in intrarenal arteries. These findings were associated with significant higher CD31 and VEGF mRNA expression compared to the UUO group. Vitamin D treatment also increased ET-1, ETBR and eNOS mRNA expressions. Our in vitro study demonstrated Calcitriol induced ET-1 and eNOS mRNA expressions upregulation in HUVEC under normoxic and hypoxic condition. Meanwhile, siRNA for ET-1 inhibited the upregulation of eNOS mRNA expression after Calcitriol treatment. Vitamin D ameliorates kidney fibrosis through attenuating vascular remodeling and ischemia with upregulating ET-1/ETBR and eNOS expression., N. Arfian, M. H. H. Kusuma, N. Anggorowati, D. B. Nugroho, A. Jeffilano, Y. Suzuki, K. Ikeda, N. Emoto., and Seznam literatury
Vitamin D had been for a long time investigated for its effects on bone metabolism. Recently has been observed that the incidence of some neurodevelopmental disorders (including autism) increases hand in hand with vitamin D deficiency. Indeed, vitamin D was reported to modulate the biosynthesis of neurotransmitters and neurotrophic factors; moreover, its receptor was found in the central nervous system. Vitamin D deficiency was therefore assessed as a risk factor for autism, however the biological mechanism has not yet been revealed. In our review we focused on potential connections among vitamin D, steroids and autism. Potential mechanisms of vitamin D action are also discussed., L. Máčová, M. Bičíková, D. Ostatníková, M. Hill, L. Stárka., and Obsahuje bibliografii
Epileptic afterdischarges (ADs) elicited by electrical stimulation of sensorimotor cortical area were used as a model to study the role of neurotransmitter systems in cortical seizures in three age groups of developing rats. Drugs augmenting inhibition mediated by GABAA receptors were found to suppress ADs in all age groups, their activity was usually more marked in younger than in 25-day-old rat pups. Drugs potentiating GABAB receptors exhibit lower efficacy and more complicated developmental profile than GABAA-ergic drugs. Effects of an antagonist of GABAB receptor – marked prolongation of ADs in all three age groups – suggest an important role of GABAB receptors in arrest of cortical seizures. Drugs affecting glutamate receptors exhibit variable effects, usually better expressed in older animals than in 12-day-old ones. No specific role for ionotropic as well as metabotropic glutamate receptors could be predicted. Activation of adenosinergic inhibitory modulatory system also exhibited anticonvulsant action in the present model. All three neurotransmitter systems probably participate in mechanisms of generation, maintenance and arrest of cortical seizures., P. Mareš, H. Kubová., and Obsahuje bibliografii a bibliografické odkazy
The quality of stored blood can be deteriorated by hemolysis caused by free radicals. The purpose of this study was to elucidate whether neutrophile leukocytes are the source of free radicals in stored blood as in hemodialyzed patients. Resuspensions with low (LL) or high (HL) leukocyte concentrations were prepared from samples of twenty healthy volunteers. The samples were incubated for 10 days at 4 °C and then for one day at 37 °C. Markers of hemolysis and free radical metabolism were examined before and after incubation in LL and HL samples. In spite of the difference of leukocytes counts in LL and HL resuspensions (p<0.0001), the pre-incubation values of all laboratory parameters were practically identical. In post-storage samples, superoxide dismutase and glutathione peroxidase activities did not differ in either group. Reduced glutathione in erythrocytes and extracellular antioxidant capacity were insignificantly lower in HL resuspensions, but the increase of malondialdehyde was much more pronounced in the HL samples (p<0.0001). The degree of hemolysis, expressed as the extracellular increase of potassium (p<0.001), hemoglobin (p<0.05) and lactate dehydrogenase (p<0.05), was higher in the HL samples. Our results support the hypothesis that leukocytes participate in free radical production in stored blood., J. Racek, R. Herynková, V. Holeček, J. Faltysová, I. Krejčová., and Obsahuje bibliografii
The aim of the present study was to introduce methods for exome sequencing of two ATP-binding cassette (ABC) transporters ABCC8 and ABCD2 recently suggested to play a putative role in breast cancer progression and prognosis of patients. We performed next generation sequencing targeted at analysis of all exons in ABCC8 and ABCD2 genes and surrounding noncoding sequences in blood DNA samples from 24 patients with breast cancer. The revealed alterations were characterized by in silico tools. We then compared the most frequent functionally relevant polymorphism rs757110 in ABCC8 with clinical data of patients. In total, the study identified 113 genetic alterations (>70 % novel ones) in both genes. Of these alterations, 83 were noncoding, 13 synonymous, 10 frameshifts and 7 were missense alterations. Four in silico programs predicted pathogenicity of two polymorphisms and four newly identified alterations. Rs757110 polymorphism in ABCC8 did not significantly associate with clinical data of the patients. In conclusion, exome sequencing identified several functionally relevant alterations in ABCC8 and ABCD2 genes that may further be used for a larger follow-up study aiming to assess their clinical significance., P. Soucek, V. Hlavac, K. Elsnerova, R. Vaclavikova, R. Kozevnikovova, K. Raus., and Obsahuje bibliografii