Genes for adiponectin and resistin are candidate genes of insulin resistance and type 2 diabetes mellitus. The aim of our study was to determine the frequency of single nucleotide polymorphisms (SNP) 45T>G and 276G>T of the adiponectin gene and 62G>A and -180C>G of the resistin gene in patients with obesity (OB), anorexia nervosa (AN) and in control healthy normal-weight women (NW) and to study the influence of particular genotypes on serum concentrations of these hormones and on insulin sensitivity. Serum adiponectin, resistin, tumor necrosis factor alpha (TNF-alpha), insulin, cholesterol, glycated hemoglobin (HbA1c) and blood glucose levels were measured in 77 patients with OB, 28 with AN and 38 NW. DNA analysis was carried out by polymerase chain reaction with restriction analysis of PCR product. The presence of SNP ADP+276 G>T allele was accompanied by higher cholesterol levels in AN patients, higher adiponectin concentrations in OB patients and lower HbA1c levels in NW. SNP of the resistin gene 62G>A was associated with lower HbA1c in NW and higher cholesterol concentrations in OB group. The carriers of the minor G allele in the position -180 of the resistin gene within AN group had significantly higher BMI relative to non-carriers. We conclude that polymorphisms in adiponectin and resistin genes can contribute to metabolic phenotype of patients with obesity and anorexia nervosa., J. Křížová, M. Dolinková, Z. Lacinová, Š. Sulek, R. Doležalová, J. Housová, J. Krajíčková, D. Haluzíková, L. Bošanská, H. Papežová, M. Haluzík., and Obsahuje bibliografii a bibliografické odkazy
The consequences of epileptic seizures related to postictal inhibition in early postictal period include postictal analgesia. We studied this phenomenon over 96 h following flurothyl-induced seizures in adult male Wistar rats. Nociception of control (no seizure) and seizured groups were tested using the plantar and von Frey hair tests. We determined latency of forepaw and hind paw reactions using plantar tests and the number of von Frey hairs reactions. Shortly after seizures, longer plantar test latencies were seen relative to the control group. Before the seizures the plantar test reaction times were significantly shorter in forepaws than in hind paws. The effect disappeared post-seizure and surprisingly, it also disappeared at the corresponding time in controls; it reappeared after 48 h in the seizure group and after 24 h in controls. Differences in the von Frey hairs test occurred at 5 and 60 min post-seizure, however, these differences could not be explained by limb anatomy; although, different thermal and mechanical nociception mechanisms could be significant. The unexpected reactions in controls could be related to brief social and physical interactions between the two groups. and J. Mareš, R. Rokyta.
Peritoneal dialysis (PD) is a well established method of depuration in uremic patients. Standard dialysis solutions currently in use are not biocompatible with the peritoneal membrane. Studying effects of dialysate on peritoneal membrane in humans is still a challenge. There is no consensus on the ideal experimental model so far. We, therefore, wanted to develop a new experimental non-uremic rabbit model of peritoneal dialysis, which would be practical, easy to conduct, not too costly, and convenient to investigate the long-term effect of dialysis fluids. The study was done on 17 healthy Chinchilla male and female rabbits, anesthetized with Thiopental in a dose of 0.5 mg/kg body mass. A catheter, specially made from Tro-soluset (Troge Medical GMBH, Hamburg, Germany) infusion system, was then surgically inserted and tunneled from animals' abdomen to their neck. The planned experimental procedure was 4 weeks of peritoneal dialysate instillation. The presented non-uremic rabbit model of peritoneal dialysis is relatively inexpensive, does not require sophisticated technology and was well tolerated by the animals. Complications such as peritonitis, dialysis fluid leakage, constipation and catheter obstruction were negligible. This model is reproducible and can be used to analyze the effects of different dialysis solutions on the rabbit peritoneal membrane., S. Zunic-Bozinovski, Z. Lausevic, S. Krstic, N. Jovanovic, J. Trbojevic-Stankovic, B. Stojimirovic., and Obsahuje bibliografii a bibliografické odkazy
High plasma levels of triglycerides (TG) are an independent risk factor in the development of cardiovascular disease, with about 50 % of the final levels being determined genetically. Apolipoprotein A5 ( APOA5 ) is the last discovered member of the apolipoprotein APOA1/C3/A4 gene cluster, found by comparative sequencing analysis. The importance of APOA5 gene for determination of plasma triglyceride levels has been suggested after development of transgenic and knock-out mice (transgenic mice displayed significantly reduced TG, whereas knock-out mice had high TG). In Czech population, alleles C-1131 and Trp19 are associated with elevated levels of plasma TG and higher risk of myocardial infarction development. These alleles also play some role in nutrigenetics and actigenetics of lifestyle interventions leading to the plasma cholesterol changes as well as in the pharmacogenetics of statin treatment. On the contrary, APOA5 mutations detected in Czech population did not show strict effect on plasma TG levels. Val153 → Met variant exhibit the sex-specific effect of HDL-cholesterol levels. The suggested roles of APOA5 variants in determination of the plasma remnant particles, plasma concentrations of C-reactive protein or some anthropometrical parameters were excluded., J. A. Hubáček ... [et al.]., and Obsahuje seznam literatury
A predominance of small, dense low-density lipoproteins (LDL) is characteristic of the dyslipidemic state seen in type 2 diabetes. However, no study has investigated the association in gestational diabetes mellitus (GDM), which is pathophysiologically similar to type 2 diabetes. We hypothesized that LDL particle size is reduced in GDM cases compared with controls. Gradient gel electrophoresis was used to characterize LDL subclass phenotypes in non-fasting intrapartum plasma from 105 GDM cases and 96 controls. All participants were free of pre-existing diabetes or hypertension. The authors used logistic regression to estimate odds ratios (OR) and 95 % confidence intervals (CI) adjusted for confounders. Women with this phenotype had a significant 4.9-fold (95 % CI: 1.1-23.2) increased risk of GDM compared with those with the large, buoyant phenotype. The magnitude of this association was attenuated when plasma triglyceride and other confounders were included in the model (OR=4.2, 95 % CI: 0.5-39.5). Mean LDL particle size in GDM cases was smaller compared with controls (270.1 vs. 272.7Å, p=0.003). The OR of GDM risk was 1.8 (95 % CI: 0.9-3.3) for every 10-Å reduction in LDL particle size. Large prospective studies are needed to evaluate the association between smaller LDL particle size in early pregnancy with subsequent GDM risk., C. Qiu, C. Rudra, M. A. Austin, M. A. Williams., and Obsahuje bibliografii a bibliografické odkazy
Sympathetic activation and parasympathetic withdrawal are commonly observed during acute exacerbations of chronic obstructive pulmonary disease (COPD). We have demonstrated previously that noninvasive positive-pressure ventilation (NPPV) improves parasympathetic neural control of heart rate in patients with obstructive sleep apnea. We hypothesized that NPPV may exert such beneficial effects in COPD as well. Therefore, we assessed the acute effects of NPPV on systemic blood pressure and indexes of heart rate variability (HRV) in 23 patients with acute exacerbations of COPD. The measurements of HRV in the frequency domain were computed by an autoregressive spectral technique. The use of NPPV resulted in significant increases of oxygen saturation (from 89.2±1.0 to 92.4±0.9 %, p<0.001) in association with reductions in systolic and diastolic blood pressures and heart rate (from 147±3 to 138±3 mm Hg, from 86±2 to 81±2 mm Hg, from 85±3 to 75±2 bpm, p<0.001 for all variables), and increases in ln-transformed high frequency band of HRV (from 6.4±0.5 to 7.4±0.6 ms2/Hz, p<0.01). Reductions in heart rate and increases in ln-transformed HF band persisted after NP PV withdrawal. In conclusion, these findings suggest that NPPV may cause improvements in the neural control of heart rate in patients with acute exacerbations of COPD., P. Skyba, P. Joppa, M. Orolín, R. Tkáčová., and Obsahuje bibliografii a bibliografické odkazy
The gold standard material in bypass surgery of blood vessels remains the patient’s own artery or vein. However, this material may be unavailable, or may suffer vein graft disease. Currently available vascular prostheses, namely polyethylene terephthalate (PET, Dacron) and expanded poly tetrafluoroethylene (ePTFE), perform well as large-caliber replacements, but their long-term patency is discouraging in small-caliber applications (<6 mm), such as in coronary, crural or microvessel surgery. This failure is mainly a result of an unfavorable healing process with surface thrombogenicity, due to lack of endothelial cells and anastomotic intimal hyperplasia caused by hemodynamic disturbances. An ideal small-diameter vascular graft has become a major focus of research. Novel biomaterials have been manufactured, and tissue-biomaterial interactions have been optimized. Tissue engineering technology has proven that the concept of partially or totally living blood vessels is feasible. The purpose of this review is to outline the vascular graft materials that are currently being implanted, taking into account cell-biomaterial physiology, tissue engineering approaches and the collective achievements of the authors., J. Chlupáč, E. Filová, L. Bačáková., and Obsahuje seznam literatury
1a_Caveolin-1 (CAV-1) is the main structural component of caveolae, acting as a modulator of signal transduction. CAV-1 might be involved in the pathophysiology of microvascular complications in Type 1 diabetes (DM). We sought to determine whether fractionation on sucrose gradient (SF), a method routinely utilized for isolation of caveolar fractions in homogenous cell lines, is applicable for CAV-1-related studies in tissues with multiple cell types, such as the normal rat kidney cortex (C). Using this method, we also determined whether streptozotocin- induced DM in rats (4-week duration) leads to changes in renal subcellular targeting of CAV-1, and evaluated the effects of tight metabolic control (insulin, 12 IU /day) and angiotensin receptor blocker, losartan (4 weeks, 20 mg/kg/day). Immunoblotting of individual fractions obtained from C revealed CAV-1 expression in fractions 4-6 that corresponded to light scattering band that typically forms after separating cellular fractions on SF. These fractions were considered to be caveolar fractions. In C, CAV-1 was also detectable in fracti ons 8-10. These and all other fractions except caveolar fractions were considered to be non-caveolar fractions. A ratio of caveolar/non-caveolar expression of CAV-1 (CNCR) was computed for each renal cortex allowing comparisons of CAV-1 subcellular distribution in C and DM rats, and effects of treatments., 2a_Using this approach, DM was characterized by marked increases in CNCR as compared to C (5.54±1.56 vs. 2.65±1.33, p<0. 05) that were reduced by treatment with insulin (0.78±0. 24, p<0.01 vs. DM) or losartan (0.84±0.06, p<0.01 vs. DM). In summary, analysis of CAV-1 following the SF of renal cortex detected similar distribution of the protein as in homogenous cell lines, DM-induced changes in CAV-1 targeting, and the effects of pharmacological treatments. This suggests applicability of SF in studies focusing on CAV-1 targeting in organs with various cell lines in vivo., H. Demová, R. Komers., and Obsahuje seznam literatury
Based on the biological significance of the ubiquitin-proteasome pathway (UPP) and its potential role during sepsis, burns and ischemia-reperfusion injury, we hypothesized that the systemic response to traumatic shock (TS) is accompanied by tissue-specific UPP alterations. Therefore, we studied tissue ubiquitin pools, chymotryptic- and tryptic-like proteasome peptidase activities and ubiquitin-protein ligation (UbPL) rates in skeletal muscle, heart, lung, liver, spleen and kidney using a clinically relevant porcine model (bilateral femur fracture/hemorrhage followed by fluid resuscitation). TS induced a systemic reduction of tissue- specific high molecular mass ubiquitin-protein conjugates (>50 kDa). Free ubiquitin was unaffected. The dynamic organ patterns of ubiquitin pools paralleled the typical physiological response to TS and resuscitation. Reduction of ubiquitin-protein conjugates was most pronounced in heart and lung (p<0.05 vs. control) and accompanied by significant increases in proteasome peptidase and UbPL activities in these organs. Unlike all other tissues, spleen proteasome peptidase and UbPL activities were significantly reduced 10 h after TS. These findings support the concept that the UPP could play an important role in regulation of cell functions during the early whole-body response to TS. The UPP might be a therapeutic target to improve the metabolic care after TS, particularly in the heart, lung, and spleen., M. B. Patel, S. A. Earle, M. Majetschak., and Obsahuje bibliografii a bibliografické odkazy
This study used an experimental early rehabilitation model combining an enriched environment, multisensory (visual, acoustic and olfactory) stimulation and motor training after traumatic brain injury (via fluid-percussion model) to simulate early multisensory rehabilitation. This therapy will be used by brain injured patients to improve neural plasticity and to restore brain integration functions. Motor dysfunction was evaluated using a composite neuroscore test. Direct structural effects of traumatic brain injury were examined using Fluoro-Jade staining, which allows identification of degenerating neural cell bodies and processes. Animals in the rehabilitation model group performed significantly better when tested for neuromotor function than the animals in standard housing in the 7-day and 15-day interval after injury (7d: p=0.005; 15d: p<0.05). Statistical analysis revealed significantly lower numbers of Fluoro-Jade positive cells (degenerating neurons) in the rehabilitation model group (n=5: mean 13.4) compared to the standard housing group (n=6: mean 123.8) (p<0.005). It appears that the housing of animals in the rehabilitation model led to a clear functional increase in neuromotor functions and to reduced neural loss compared with the animal group in standard housing., M. Lippert-Grüner. M. Maegele, J. Pokorný, D. N. Angelov, O. Švestková, M. Wittner, S. Trojan., and Obsahuje bibliografii a bibliografické odkazy