Recently, we derived “humanized” spontaneously hypertensive rats (SHR-CRP) in which transgenic expression of human CRP induces inflammation, oxidative stress, several features of metabolic syndrome and target organ injury. In addition, we found that rosuvastatin treatment of SHR-CRP transgenic rats can protect against pro-inflammatory effects of human CRP and also reduce cardiac inflammation and oxidative damage. In the current study, we tested the effects of rosuvastatin (5 mg/kg) on kidney injury in SHR-CRP males versus untreated SHR-CRP and SHR controls. All rats were fed a high sucrose diet. In SHR-CRP transgenic rats, treatment with rosuvastatin for 10 weeks, compared to untreated transgenic rats and SHR controls, was associated with significantly reduced systemic inflammation which was accompanied with activation of antioxidative enzymes in the kidney, lower renal fat accumulation, and with amelioration of histopathological changes in the kidney. These findings provide evidence that, in the presence of high CRP levels, rosuvastatin exhibits significant anti-inflammatory, anti-oxidative, and renoprotective effects., J. Šilhavý, V. Zídek, V. Landa, M. Šimáková, P. Mlejnek, O. Oliyarnyk, H. Malínská, L. Kazdová, M. Mancini, M. Pravenec., and Obsahuje bibliografii
To date, a single report has appeared on the use of salivary cortisol for adrenal function testing with a low dose ACTH, although 1 μg has become preferred as a more physiological stimulus than the commonly used 250 μg ACTH test. Our present study was aimed to obtain physiological data on changes of free salivary cortisol after 1 μg ACTH stimulation. This approach was compared with the common method based on the changes of total serum cortisol. Intravenous, low-dose ACTH test was performed in 15 healthy women (aged 22-40 years) with normal body weight, not using hormonal contraceptives, in the follicular phase of the menstrual cycle. Blood and saliva for determination of cortisol were collected before ACTH administration and 30 and 60 min after ACTH administration. Basal concentration of salivary cortisol (mean ± S.E.M., 15.9±1.96 nmol/l) increased after 1 μg ACTH to 29.1±2.01 nmol/l after 30 min, and to 27.4±2.15 nmol/l after 60 min. The differences between basal and stimulated values were highly significant (p<0.0001). The values of salivary cortisol displayed very little interindividual variability (p<0.04) in contrast to total serum cortisol values (p<0.0001) A comparison of areas under the curve (AUC) related to initial values indicated significantly higher AUC values for salivary cortisol than for total serum cortisol (1.89±0.88 vs. 1.22±0.19, p<0.01). Correlation analysis of serum and salivary cortisol levels showed a borderline relationship between basal levels (r=0.5183, p=0.0525); correlations after stimulation were not significant. Low-dose ACTH administration appeared as a sufficient stimulus for increasing salivary cortisol to a range considered as a normal adrenal functional reserve., K. Šimůnková, R. Hampl, M. Hill, J. Doucha, L. Stárka, K. Vondra., and Obsahuje bibliografii a bibliografické odkazy
The present study was undertaken to provide more information on the incidence of satellite nucleoli in developmental stages of the megakaryocytic lineage. Satellite nucleoli representing solitary silver stained nucleolus organizer regions (AgNORs) present in nuclei in addition to other nucleolar types were observed in all stages of megakaryocytic development. However, the incidence of satellite nucleoli was more frequent in mature megakaryocytes than in less differentiated immature megakaryoblasts and naked megakaryocytic nuclei representing the terminal stages of megakaryocytic development after loss of the cytoplasm transformed to thrombocytes. There is a possibility that the increased incidence of satellite nucleoli in mature megakaryocytes might be due to the loss of AgNORs from active nucleoli characteristic for immature cells. The decreased incidence of satellite nucleoli in naked megakaryocytic nuclei might reflect their disintegration in the terminal stages of the megakaryocytic development., J. Janoutová, Z. Likovský, K.Smetana., and Obsahuje bibliografii
The laboratory rat, a non-photoperiodic rodent, exhibits seasonal fluctuations of melatonin. Melatonin has been found to be readily transferred from the maternal to the fetal circulation. No data exist on the possible influence of maternal pineal gland upon seasonal variations of the offspring. The aim of the present study was to asses the influence of the maternal melatonin rhythm on the offspring postnatal development of the reproductive hormones LH, FSH and prolactin. Male offspring from control, pinealectomized (PIN-X) and PIN-X + melatonin (PIN-X+MEL) mother Wistar rats were studied at 21, 31, and 60 days of age. Seasonal age-dependent variations were found for all hormones studied in control offspring but PIN-X offspring showed a tendency to have reduced duration or altered seasonal variations. Maternal melatonin treatment to PIN-X mothers partially restored the effect of pinealectomy. The chronological study of LH, FSH, and prolactin in PIN-X offspring also showed an altered pattern as compared to control-offspring. Melatonin treatment to the mothers partially restored the developmental pattern of reproductive hormones. Results of this study indicate that maternal pineal gland of the laboratory rat is involved in the seasonal postnatal development variations of reproductive hormones of the offspring., N. Vásquez, E. Díaz, C. Fernández, V. Jiménez, A. Esquifino, B. Díaz., and Obsahuje bibliografii a bibliografické odkazy
Serotonin (5-hydroxytryptamine) is an ubiquitary monoamine acting as one of the neurotransmitters at synapses of nerve cells. Serotonin acts through several receptor types and subtypes. The profusion of 5-HT receptors should eventually allow a better understanding of the different and complex processes in which serotonin is involved. Its role is expected in the etiology of several diseases, including depre ssion, schizophreni a, anxiety and panic disorders, migraine, hypert ension, pulmonary hypertension, eating disorders, vomiting and irritable bowel syndromes. In the past 20 years, seven distinct families of 5-HT receptors have been identified and various subpo pulations have been described for several of them. Increasing number of 5-HT receptors has made it difficult to unravel the role of 5-HT receptor subpopulations due to the lack of suitable selective agents. The present review describes the different populations and nomenclature of recently discovered 5-HT receptors and their pharmacological relevance. and M. Pytliak ... [et al.].
Neurotransmitter substrate of spatial cognition belongs to current topics in behavioral neuroscience. The present study examined the effects of serotonin depletion with p-chlorophenylalanine on learning of rats in active place avoidance, a spatial task requiring allothetic mapping and cognitive coordination and highly dependent upon hippocampus. Serotonin depletion transiently increased locomotor activity in response to footshocks, but it did not change the avoidance efficiency measured by three spatial parameters. These results suggest that serotonin neurotransmission is not crucial for cognitive coordination and allothetic learning, i.e. the processes, which are crucial for active place avoidance performance., T. Petrásek, A. Stuchlík., and Obsahuje seznam literatury
Recent studies have demonstrated that adipocyte fatty acid binding proteins (FABP) may play a role in the etiopathogenesis of insulin resistance. The aim of our study was to assess serum FABP levels in obese patients with type 2 diabetes mellitus (T2DM) before and after 3 months of treatment with PPAR-α agonist fenofibrate (F) and to explore the relationship of FABP to biochemical parameters and measures of insulin sensitivity assessed by hyperinsulinemic-isoglycemic clamp. We measured biochemical parameters by standard laboratory methods, insulin sensitivity by hyperinsulinemic-isoglycemic clamp and serum concentrations of FABP by commercial ELISA kit in 11 obese females with T2DM before and after three months of treatment with PPAR-α agonist fenofibrate and in 10 lean healthy control women (C). Serum FABP levels were 2.5-fold higher in T2DM group relative to C and were not affected by fenofibrate treatment (C: 20.6±2.1 μg/l, T2DM before F: 55.6±5.7 μg/l, T2DM after F: 54.2±5.4 μg/l, p<0.0001 for C vs. T2DM before F). Hyperinsulinemia during the clamp significantly suppressed FABP levels in both C and T2DM group. FABP levels positively correlated with BMI, triglyceride levels, blood glucose, glycated hemoglobin, atherogenic index and insulin levels. An inverse relationship was found between FABP and HDL levels, metabolic clearance rate of glucose, M/I and MCRglc/I sensitivity indexes. We conclude that FABP levels are closely related to BMI, parameters of insulin sensitivity, HDL levels and measures of diabetes compensation. This combination makes FABP a valuable marker of metabolic disturbances in patients with type 2 diabetes mellitus., M. M. Haluzík ... [et al.]., and Obsahuje seznam literatury
Visfatin is an adipose tissue-derived hormone shown to correlate with visceral fat mass in patients with obesity. Its possible role in patients with different types of eating disorders is unknown. We measured fasting serum levels of visfatin and leptin and surrogate measures of insulin sensitivity in 10 untreated patients with anorexia nervosa (AN), 10 untreated patients with bulimia nervosa (BN) and 20 age-matched healthy women (C) to study the possible role of visfatin in these disorders. Patients with AN had severely decreased body mass index (BMI) and body fat content. BMI of BN group did not significantly differ from that of C group, whereas body fat content of BN group was significantly lower compared to C and higher compared to AN group, respectively. Serum glucose levels did not significantly differ among the groups studied, whereas serum insulin and leptin levels and HOMA index were significantly decreased in AN group relative to both C and BN group. In contrast, serum visfatin levels in both patients with AN and BN did not differ from those of C group. We conclude that circulating visfatin levels are not affected by the presence of chronic malnutrition in AN or binge/purge eating behavior in BN., I. Dostálová ...[et al.]., and Obsahuje seznam literatury
The aim of the study was to evaluate serum α-glutathione S-transferase (s-GSTA) levels in patients with cystic fibrosis (CF) and to compare s-GSTA with other liver function tests and with a hepatic ultrasound scan (US). The cytosolic enzyme, a-glutathione S-transferase is predominantly found in the liver and is distributed uniformly in the liver tissue. In our study s-GSTA levels were measured in 37 CF patients aged 1 to 28 years (mean age 10.4 years, 24 males). The control group consisted of 27 patients aged 2 to 17 years (mean age 8.5 years, 18 males). The presence of hepatobiliary abnormalities was assessed by clinical examination, ultrasound scan, s-GSTA, and conventional liver enzymes: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and g-glutamyl transferase (GMT). The calculated 5-95 % range of s-GSTA for the control group was 0.098-2.54 mg/l, for the CF group 0.43-9.76 mg/l. Mean s-GSTA level in the control group was 1.55 mg/l (S.D.=1.57), and 2.05 mg/l (S.D.=2.60) in the CF group. In the group of CF patients, the serum levels were significantly higher than in the control group (P<0.01). No significant correlation existed in the CF group between s-GSTA and conventional liver tests (ALT, AST, ALP and GMT). Four patients in the CF group had hepatobiliary abnormalities detectable by conventional liver tests, s-GSTA and US. Four patients had abnormal s-GSTA, while conventional liver tests and US were normal. One other patient had abnormal hepatic US, but normal standard liver tests and s-GSTA. The study has suggested that a raised s-GSTA level might be a marker of possible pathological changes of the hepatobiliar system in CF patients. Serum GSTA seems to be a more sensitive marker than transaminases for the monitoring of hepatocellular integrity and as an early predictor of hepatic damage., K. Šídlová, V. Skalická, K. Kotaška, M. Pechová, M. Chada, J. Bartošová , Z. Hříbal, J. Nevoral, V. Vávrová, R. Průša., and Obsahuje bibliografii
We have studied natural killer (NK) activity, lymphoproliferative response, the release of several cytokines (IL-2, TNFa and IL-1b) and the ROS production in peritoneal leukocytes obtained 0, 2, 4, 12 and 24 h after lipopolysaccharide (LPS) injection. Lethal septic shock (100 % mortality occurred at 30 h after LPS administration) was caused in female BALB/c mice by intraperitoneal injection of 100 mg/kg of E. coli LPS. Cytotoxicity and lymphoproliferation assay were preformed together with the measurement of IL-1b, IL-2 and TNFa production, and quantification of ROS. Natural killer activity, spontaneous lymphoproliferative response, IL-2, TNFa, IL-b release and ROS production were increased after LPS injection. In conclusions, ROS and proinflammatory mediators produced by immune cells in response to LPS are involved in the oxidative stress of endotoxic shock. This oxidative state alters some functional characteristics of leukocytes (proliferation and NK activity)., V. M. Víctor, M. De la Fuente., and Obsahuje bibliografii