The decapeptide QLNLKEYNLV corresponding to the C-terminus of Gq/G11alpha guanine nucleotide-binding proteins (G-proteins) was synthesized by the solid-phase method and conjugated to keyhole limpet hemocyanin. The rabbits were immunized with these conjugates and an antiserum that reacted specifically with the alpha subunit of Gq/G11 proteins was used in this study. The antiserum exhibited no cross-reactivity with the alpha subunits of stimulatory (Gs) or inhibitory (Gi) G-proteins associated with adenylate cyclase. Immunoblots with the antiserum showed that it specifically recognized the Gq/G11 alpha-proteins in cholate extracts of adipose tissue membranes of goats. Treatment of young castrated male goats with bST had no effect on the quantity of Gq/G11 alpha-subunits in adipose tissue and the results thus obtained did not support the idea that the bST signal in adipose tissue is transmitted via Gq/G11 alpha-proteins., V. Krbeček, H. Kovářů, J. Škarda, T. Barth, J. Velek, V. Žižkovský., and Obsahuje bibliografii
Oxidative stress is a phenomenon associated with pathogenetic mechanisms of several diseases including atherosclerosis, neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, cancer, diabetes mellitus, inflammatory diseases, as well as psychological diseases or aging processes. Oxidative stress is defined as an imbalance between production of free radicals and reactive metabolites, so-called oxidants, and their elimination by protective mechanisms, referred to as antioxidative systems. This imbalance leads to damage of important biomolecules and organs with potential impact on the whole organism. Oxidative and antioxidative processes are associated with electron transfer influencing the redox state of cells and the organism. The changed redox state stimulates or inhibits activities of various signal proteins, resulting in a changed ability of signal pathways to influence the fate of cells. At present, the opinion that oxidative stress is not always harmful, has been accepted. Depending on the type of oxidants, intensity and time of redox imbalance as well as on the type of cells, oxidative stress can play a role in the regulation of other important processes through modulation of signal pathways, influencing synthesis of antioxidant enzymes, repair processes, inflammation, apoptosis and cell proliferation, and thus processes of malignity. Imprudent administration of antioxidants may therefore have a negative impact on the organism., Z. Ďuračková., and Obsahuje bibliografii a bibliografické odkazy
In the present in vitro experiments we examined FSH- and ghrelin-induced changes in ovarian hormone secretion by transgenic rabbits. Fragments of ovaries isolated from adult transgenic (carrying mammary gland-specific mWAP-hFVIII gene) and non-transgenic rabbits from the same litter were cultured with and without FSH or ghrelin (both at 0, 1, 10 or 100 ng/ml medium). The secretion of progesterone (P4), estradiol (E2) and insulin-like growth factor I (IGF-I) was assessed by RIA. It was observed that ovaries isolated from transgenic rabbits secreted much less P4, E2 and IGF-I than the ovaries of non-transgenic animals. In control animals FSH reduced E2 (at doses 1-100 ng/ml medium) and IGF-I (at 1-100 ng/ml), but not P4 secretion, whereas ghrelin promoted P4 (at 1 ng/ml) and IGF-I (at 100 ng/ml), but not E2 output. In transgenic animals, the effects were reversed: FSH had a stimulatory effect on E2 (at 100 ng/ml) and ghrelin had an inhibitory effect on P4 (at 10 ng/ml). No differences in the pattern of influence of FSH on P4 and IGF-I and of ghrelin on E2 and IGF-I were found between control and transgenic animals. The present observations suggest that 1) both FSH and ghrelin are involved in rabbit ovarian hormone secretion, 2) transgenesis in rabbits is associated with a reduction in ovarian secretory activity, and 3) transgenesis can affect the response of ovarian cells to hormonal regulators., A. V. Sirotkin, P. Chrenek, K. Darlak, F. Valenzuela, Ž. Kuklová., and Obsahuje bibliografii a bibliografické odkazy
Spatial navigation and memory is considered to be a part of the declarative memory system and it is widely used as an animal model of human declarative me mory. However, spatial tests typically involve only static settings, despite the dynamic nature of the real world. Animals, as well as people constantly need to interact with moving objects, other subjects or even with entire moving environments (flowing water, running stairway). Therefore, we design novel spatial tests in dynamic environments to study brain mechanisms of spatial processing in more natural settings with an interdisciplinary approach including neuropharmacology. We also translate data from neuropharmacological studies and animal models into development of novel therapeutic approaches to neuropsychiatric disorders and more sensitive screening tests for impairments of memory, thought, and behavior., A. Stuchlik ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Women with a positive history of gestational diabetes mellitus (GDM) face a higher risk of developing type 2 diabetes mellitus (T2DM) and metabolic syndrome later in life. The higher risk of these metabolic complications is closely associated with adipose tissue. In this review, the importance of adipose tissue is discussed in relation to GDM, focusing on both the quantity of fat deposits and the metabolic activity of adipose tissue in particular periods of life: neonatal age, childhood, adolescence, and pregnancy followed by nursing. Preventive measures based on body composition and lifestyle habits with special attention to the beneficial effects of breastfeeding are also discussed., D. Vejrazkova, M. Vankova, P. Lukasova, J. Vcelak, V. Cirmanova, M. Haluzik, B. Bendlova., and Obsahuje bibliografii
In this study we tested whether joint evaluation of the frequency (fcs) at which maxima of power in the cross-spectra between the variability in systolic blood pressure and inter-beat intervals in the range of 0.06-0.12 Hz occur together with the quantification of baroreflex sensitivity (BRS) may improve early detection of autonomic dysfunction in type 1 diabetes mellitus (T1DM). We measured 14 T1DM patients (age 20.3-24.2 years, DM duration 10.4-14.2 years, without any signs of autonomic neuropathy) and 14 age-matched controls (Co). Finger arterial blood pressure was continuously recorded by Finapres for one hour. BRS and fcs were determined by the spectral method. Receiver-operating curves (ROC) were calculated for fcs, BRS, and a combination of both factors determined as F(z)=1/(1+exp(-z)), z=3.09–0.013*BRS– 0.027*fcs. T1DM had significantly lower fcs than Co (T1DM: 88.8±6.7 vs. Co: 93.7±3.8 mHz; p<0.05), and a tendency towards lower BRS compared to Co (T1DM: 10.3±4.4 vs. Co: 14.6±7.1 ms/mm Hg; p=0.06). The ROC for Fz showed the highest sensitivity and specificity (71.4 % and 71.4 %) in comparison with BRS (64.3 % and 71.4 %) or fcs (64.3 % and 64.3 %). The presented method of evaluation of BRS and fcs forming an integrated factor Fz could provide further improvement in the risk stratification of diabetic patients., N. Honzíková ... [et al.]., and Obsahuje seznam literatury
Gluteal muscle contracture (GMC) is a chronic fibrotic disease of gluteal muscles due to multiple etiologies. The main pathologic process is characterized by proliferation of fibroblasts and excessive accumulation of collagen in the extracellular matrix of the muscle. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid and has been reported to be associated with various fibrotic diseases. However, the role of S1P in GMC remains unknown. Here in this articl e, High-perform ance liquid chromatography and immunohistochemistry were applied to evaluate S1P localization and expression in clinical samples from patients with GMC, Quantitative real time PCR, Western blot, and enzyme-linked immunosorbent assa y were used to explore the link between transforming growth factor-β 1 (TGF- β 1), plasminogen activator inhibitor-1 (PAI-1) and S1P. The results showed that S1P was enhanced in contraction band (CB) tissues. Studies using the cell proliferation and transformation assay indicated that exogenous S1P stimulated CB fibroblast proliferation in a time-depen dent manner and in higher concentration also in a dose-dependent manner. Furthermore, we demonstrated that S1P not only promoted collagen type I production, but also up-regulated mRNA and protein expression of transforming growth factor-β 1 and plasminogen activator inhibitor-1. These findings suggest that S1P may regulate increased synthesis of collagen and other fibrogenic factors, and significantly contributes to the process of gluteal muscle scarring in patients with GMC., C. G. Zhao ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Plasma endothelin-1 (ET-1) levels are elevated in spinal cord injury (SCI), and ET-1 may be involved in the pathophysiology of this condition. However, its effects on contractile function of the heart of SCI rats are still unknown. To define more clearly the possiblel role of ET-1 following SCI, we investigated the effect of ET-1 on the contraction, calcium transients and L-type calcium current (ICa,L) in the cardiomyocytes of control and SCI rats. Sixteen Sprague-Dawley male rats aged 80-100 days and weighing 250-350 g were randomized into control and SCI groups. Fourteen days following compression injury to the spinal cord, effects of ET-1 on the contraction, calcium transients and ICa,L were studied in the cardiomyocytes of control and SCI rats by the technique of simultaneous measurement of intracellular Ca2+ and contraction and by whole-cell configuration of the patch-clamp technique. In myocytes from control rats, ET-1 significantly increased contraction, the magnitude of Ca2+ transients and the peak amplitude of ICa,L. However, ET-1 had little effect on the amplitude of contraction, calcium transients and ICa,L in myocytes from SCI rats. These results suggest that the positive inotropic effects of ET-1 on control myocardial contraction may be altered in pathological states such as SCI., Y.-F. Guo ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Aldosterone receptor antagonist, spironolactone, has been shown to prevent remodeling of the heart in several models of left ventricular hypertrophy. The aim of the present study was to determine whether the treatment with spironolactone can prevent hypertension, reduction of tissue nitric oxide synthase activity and left ventricular (LV) and aortic remodeling in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Four groups of rats were investigated: control, spironolactone (200 mg/kg), L-NAME (40 mg/kg) and L-NAME + spironolactone (in corresponding dosage). Animals were studied after 5 weeks of treatment. The decrease of NO-synthase activity in the LV and kidney was associated with the development of hypertension and LV hypertrophy, with increased DNA concentration in the LV, and remodeling of the aorta in the L-NAME group. Spironolactone prevented the inhibition of NO-synthase activity in the LV and kidney and partially attenuated hypertension and LVH development and the increase in DNA concentration. However, remodeling of the aorta was not prevented by spironolactone treatment. We conclude that the aldosterone receptor antagonist spironolactone improved nitric oxide production and partially prevented hypertension and LVH development without preventing hypertrophy of the aorta in NO-deficient hypertension. The reactive growth of the heart and aorta seems to be controlled by different mechanisms in L-NAMEinduced hypertension., F. Šimko, J. Matúšková, I. L'upták, T. Pinčíková, K. Krajčírovičová, S. Štvrtina, J. Pomšár, V. Pelouch, L'. Paulis, O. Pecháňová., and Obsahuje bibliografii