Diabetic heart is suggested to exhibit either increased or decreased resistance to ischemic injury. Ischemic preconditioning suppresses arrhythmias in the normal heart, whereas relatively little is known about its effects in the diseased myocardium. Our objective was to investigate whether development of diabetes mellitus modifies the susceptibility to ischemia-induced arrhythmias and affects preconditioning in the rat heart. Following 1 and 9 weeks of streptozotocin-induced (45 mg/kg, i.v.) diabetes, the hearts were Langendorff-perfused at constant pressure of 70 mm Hg and subjected to test ischemia induced by 30 min occlusion of the left anterior descending (LAD) coronary artery. Preconditioning consisted of one cycle of 5 min ischemia and 10 min reperfusion, prior to test ischemia. Susceptibility to ischemia-induced arrhythmias was lower in 1-week diabetics: only 42 % of diabetic hearts exhibited ventricular tachycardia (VT) and 16 % had short episodes of ventricular fibrillation (VF) as compared to VT 100 % and VF 70 % (including sustained VF 36 %) in the non-diabetics (P<0.05). Development of the disease was associated with an increased incidence of VT (VT 92 %, not significantly different from non-diabetics) and longer total duration of VT and VF at 9-weeks, as compared to 1-week diabetics. Preconditioning effectively suppressed arrhythmias in the normal hearts (VT 33 %, VF 0 %). However, it did not provide any additional antiarrhythmic protection in the acute diabetes. On the other hand, in the preconditioned 9-weeks diabetic hearts, the incidence of arrhythmias tended to decrease (VT 50 %, transient VF 10 %) and their severity was reduced. Diabetic rat hearts are thus less susceptible to ischemia-induced arrhythmias in the acute phase of the disease. Development of diabetes attenuates increased ischemic tolerance, however, diabetic hearts in the chronic phase can benefit more from ischem preconditioning, due to its persisting influence., T. Ravingerová, R. Štetka, D. Pancza, O. Uličná, A. Ziegelhöffer, J. Styk., and Obsahuje bibliografii
The goal of this study is to evaluate if promotion of angiogenesis by systemic treatment with an antagomir against miR-92a, a well established inhibitor of angiogenesis, will maximize the benefits of exercise on bone. Ten week old female C57BL6/J mice were subjected to two weeks of external load by four point bending. During the first week of mechanical loading (ML), mice were injected (2.7 mg/kg of bodyweight) with antagomir against miR-92 or control antagomir (3 alternate days via retro-orbital). No difference in tissues weights (heart, kidney, liver) were found in mice treated with miR-92 vs. control antagomir suggesting no side effects. Two weeks of ML increased tibia TV, BV/TV and density by 6-15 %, as expected, in the control antagomir treated mice. Similar increases in the above parameters (7-16 %) were also seen in mice treated miR-92 antagomir. Administration of miR-92 antagomir was effective in reducing levels of mir-92 in heart, liver and skeletal muscle and in contrast, expression levels of two other microRNA’s miR-93 and miR-20a remain constant, thus suggesting specificity of the antagomir used. Surprisingly, we failed to detect significant changes in the expression levels of vascular genes (VEGF, CD31 and Tie2) in heart, liver or skeletal muscle. Based on these findings, we conclude that systemic administration of antagomir against miR-92 while reduced expression levels of miR-92 in the tissues; it did not significantly alter either angiogenic or osteogenic response, thus suggesting possible redundancy in miR-92 regulation of angiogenesis., A. Sengul, ... [et al.]., and Obsahuje seznam literatury
The association of transcription factor 7-like 2 (TCF7L2) gene variants with the pathogenesis of T2D, gestational diabetes and polycystic ovary syndrome (PCOS) was examined. The study involved 1460 individuals: 347 T2D patients (D); 261 gestational diabetics (G); 147 offspring of T2D (O); 329 women with PCOS, and 376 controls (C). The SNPs: rs7901695; rs7903146; rs12255372 in the TCF7L2 gene were genotyped. Anthropometric and biochemical parameters, oGTT derived indices were assessed. In addition, free fatty acids (FFAs) were evaluated in 183 non-diabetic women. The CTT haplotype showed the strongest association with T2D with OR 1.57, p=0.0003. The frequency of the CTT/CTT haplotype was decreasing in following order: D 10.6, O 9.5, G 6.1, C 5.3 and PCOS 4.9 [%]. Among CTT carriers, significantly decreased levels of oGTT-stimulated insulin and C-peptide as well as proportions of fasting PUFAs were observed. The carriership of CTG/TCG was associated with gestational diabetes, OR 2.59, p=0.036. The association of TCF7L2 haplotypes with T2D and gestational diabetes but not with PCOS was confirmed. Novel association of TCF7L2 with FFAs composition was found., J. Včelák ... [et al.]., and Obsahuje seznam literatury
Metabolic complications are frequent in primary aldosteronism (PA) and adiponectin gene polymorphisms seem to confer a genetic risk for metabolic alterations. Aim of the study was to evaluate the prevalence of metabolic symptoms in patients with PA compared to controls and the prevalence of two single nucleotide polymorphisms (SNPs), T45G and G276T, in the adiponectin gene and their relationship to metabolic syndrome (MS). The study involved 47 patients with PA and 90 controls selected from general population. Body mass index (BMI), and selected biochemical parametres were examined, and the mentioned SNPs were genotyped in all subjects. PA pati ents had a significantly higher BMI (p < 0.0001), blood glucose level (p < 0.01), and triglycerides (p < 0.0005) compared to controls. There were no significant differences in the prevalence of the studied genotypes of adiponectin gene polymorphisms. The 276GT genotype was linked with lower levels of triglycerides (p ≤ 0.05), while 276GG was related to higher levels of triglycerides (p=0.01). A similar but non- significant tendency was observed in relation to cholesterol levels. We can conclude that PA patients with the 276GT genotype have lower triglycerides levels, but there are not significant differences in the distribution of genotypes and alleles among PA patients and controls in an East Slovak population., I. Jochmanová, ... [et al.]., and Obsahuje seznam literatury
Chronic volume overload (VO) on the left ventricle (LV) augments redox stress and activates matrix metalloproteinase (MMP) which causes the endocardial endothelial-myocyte (EM) disconnection leading to myocardial contractile dysfunction. VO-induced MMP-9 activation impairs cardiac functions, in part by endothelial endocardial apoptosis, but the role of MMP-9 on EM functions remains obscure. We conjecture that chronic VO activates MMP-9 and causes EM uncoupling. Arteriovenous fistula (AVF) was created in genetically identical wild type (WT) mice (FVB/NJ) and MMP-9 knockout mice (MMP-9KO, FVB.Cg-MMP9tm1Tvu/J). Sham-operated mice were used as controls. Before experimentation the phenotype analysis of MMP-9KO mice was carried out. In-gel-gelatin zymography for MMP-9 activation was performed on LV homogenates. The EM functions were determined on LV rings using tissue myobath. We report a decrease in MMP-9 activity in left ventricular myocardial extracts in MMP-9 deficient mice after AVF. The responses to drugs affecting cardiac functions (acetylcholine (Ach), nitroprusside and bradykinin) were attenuated in AVF mice suggesting the impairment of EM coupling. Interestingly, the EM functions were restored in the MMP-9 deficient mice after AVF. We suggest a direct cause-and-effect relationship between MMP-9 activation and EM uncoupling in LV myocardium after chronic VO and the possible involvement of MMP-9 in myocardial contractile performance., K. S. Moshal, W. E. Rodriguez, U. Sen, S. C. Tyagi., and Obsahuje bibliografii a bibliografické odkazy
The relationship between hippocampal function and aging was explored in Wistar rats using taste aversion learning by comparing the performance of adult dorsal hippocampal lesioned and fifteen-month-old intact rats with that of adult intact rats. In experiment 1 the conditioned blocking phenomenon was absent in the hippocampal and the aging rats. Unlike the adult intact rats, the hippocampal and aging rats were not impaired in acquiring a learned aversion to a cider vinegar solution (3 %) presented as a serial compound with a previously conditioned saccharin solution (0.1 %). In experiment 2 both the hippocampal and the aging rats developed reduced aversions to a saline solution (0.5 %) followed by an i.p. injection of lithium chloride (0.15 M; 2 % b.w.) if the taste solution was previously preexposed without consequences. This latent inhibition effect was similar to that seen in intact adult rats. In both experiments, the aging rats exhibited enhanced conventional learned taste aversions. It is concluded that aging is not a unitary process but induces both hippocampal dependent and hippocampal independent complex changes in the functioning of the neural circuits, implementing taste aversion learning., I. Moron, M.A. Ballesteros, A. Candido, M. Gallo., and Obsahuje bibliografii
Whole blood surface tension of 15 healthy subjects recorded by the ring method was investigated in the temperature range from 20 to 40 °C. The surface tension σ as a function of temperature t (°C) is described by an equation of linear regression as σ(t) = (-0.473 t + 70.105) × 10-3 N/m. Blood serum surface tension in the range from 20 to 40 °C is described by linear regression equation σ(t) = (-0.368 t + 66.072) × 10-3 N/m and linear regression function of blood sediment surface tension is σ(t) = (-0.423 t + 67.223) ×10-3 N/m., J. Rosina, E. Kvašňák, D. Šuta, H. Kolářová, J. Málek, L. Krajči., and Obsahuje bibliografii
We used a rat model to assess the role of nephrin, podocin, and desmin in the pathogenesis of IgA nephropathy (IgAN). A rat IgAN model was established by administration of BSA, CCl4, and lipopolysaccharide (LPS) and compared with healthy control rats. Urinary protein, urine red blood cells, and biochemical parameters were measured for 12 weeks. Renal morphology and ultrastructure were examined by light and electron microscopy. Immunofluorescence was used to assess IgA deposition in the glomeruli and to measure expression of nephrin, podocin, and desmin. Real-time quantitative PCR was used to measure expression of nephrin, podocin, and desmin mRNAs. IgAN rats developed proteinuria at week-6 and this worsened over time. Pathological changes were evident under light microscopy at week-8 and under electron microscopy at week-4. Immunofluorescence analysis showed deposition of IgA in the kidneys of IgAN rats, but not control rats. IgAN rats had increased expression of glomerular podocin, nephrin, and desmin mRNAs and proteins at week-4. The expression of nephrin, podocin and desmin proteins and the expression of podocin and desmin mRNAs preceded the increase in urinary protein. Taken together, our study of a rat model of IgAN indicates that changes in the expression and distribution of nephrin, podocin, and desmin precede and may cause foot process fusion and proteinuria., H.-Y. Lu, ... [et al.]., and Obsahuje seznam literatury
Glucose tolerance, serum insulin, insulin receptors in epididymal fat tissue, circulating total cholesterol and triglyceride concentrations as well as serum prolactin were studied in obese and lean spontaneously hypertensive rats (SHR) of both sexes. Obese animals displayed insulin resistance and elevated insulin and triglyceride concentrations. Moreover, in obese rats the increased mass of epididymal fat tissue was accompanied with decreased capacity of high affinity binding sites of insulin receptors in the tissue plasma membranes. Terguride treatment lowered prolactin serum levels which was accompanied by ameliorated insulin sensitivity in obese animals of both sexes. In addition, terguride treatment decreased serum insulin and triglyceride concentrations in obese females and at the same time enhanced the affinity of high affinity insulin binding sites. Our results show that obesity in SHR is associated with a decreased capacity of insulin receptors and that prolactin may play a role in obesity-induced insulin resistance, particularly in female rats., V. Golda +, M. Ficková, L. Pinterová, J. Jurčovičová, L. Macho, Š. Zórad., and Obsahuje bibliografii