Elevated levels of glucocorticoids lead to the development of obesity and metabolic syndrome. Local glucocorticoid levels are regulated through the enzyme 11 β -hydroxysteroid dehydrogenase 1 (11 β -HSD 1), an enzyme that regenerates active cortisol from inert cortis one. Increased expression of 11 β - HSD 1 in adipose tissue promotes higher body mass index (BMI), insulin resistance, hypertension, and dyslipidemia. Human 11 β - HSD 1 is also responsible for inter-conversion of 7-hydroxylate metabolites of dehydroepiandrosterone (7-OH-DHEA) to their 7-oxo-form. To better understanding the mechanism of the action, we focused on 7-OH- and 7-ox o-DHEA, and their circulating levels during the reductive treatment in adolescent obese patients. We determined plasma levels of 7 α -OH-DHEA, 7 β -OH- DHEA, and 7-oxo-DHEA in 55 adolescent patients aged 13.04- 15.67 years, BMI greater than 90 th percentile. Samples were collected before and after one month of reductive therapy. Circulating levels of 7 α -OH-DHEA decreased during the reductive therapy from 1.727 (1.614; 1.854 , transformed mean with 95 % confidence interval) to 1.530 nm ol/l (1.435; 1.637, p<0.05) in girls and from 1.704 (1.583; 1. 842) to 1.540 nmol/l (1.435; 1.659, p<0.05) in boys. With regard to the level of 7-oxo-DHEA, a significant reduction from 1. 132 (1.044; 1.231) to 0.918 nmol/l (0.844; 1.000, p<0.05) was found after the treatment, but only in boys. No significant difference in 7 β -OH-DHEA levels was observed. In conclusions, diminished levels of 7 α -OH-DHEA indicate its possible effect on activity of 11 β -HSD 1. Further studies are necessary to clarify whether competitive substrates for 11 β -HSD 1 such as 7 α -OH-DHEA could inhibit production of glucocorticoids and may be involved in metabolic processes leading to reduction of obesity., L. Máčová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The effects of ionizing radiation on pineal melatonin and on key enzymes of its metabolism have been studied in our laboratory. After adaptation to an artificial light/dark cycle of 12:12 h, male Wistar rats were fractionally whole-body irradiated with a dose of 2.4 Gy of gamma-rays twice a week up to total doses of 4.8, 9.6 or 14.4 Gy. Irradiation and sham-irradiation were performed in the late afternoon. The rats were sacrificed at 24:00 to 01:00 h in darkness, 6 h, 3 or 5 days after the last exposure. Pineal and serum melatonin concentrations, pineal activities of serotonin N-acetyltransferase (NAT) and of monoamine oxidase (MAO) were determined. The NAT activities in the rats irradiated with 4.8 and 9.6 Gy decreased at some intervals without changes of melatonin concentration. Irradiation with a total dose of 14.4 Gy decreased NAT activity and the concentration of pineal and serum melatonin 6 h and 3 days after the last exposure. The activity of MAO, estimated only in the rats irradiated with the dose of 14.4 Gy, increased significantly 3 days after irradiation. The fractionated irradiation up to the dose of 14.4 Gy caused a transient decrease in pineal melatonin synthesis. This could be the consequence of preferential oxidative deamination of serotonin in comparison with its N-acetylation, leading to melatonin biosynthesis.
In this review, we focused on the intersection between steroid metabolomics, obstetrics and steroid neurophysiology to give a comprehensive insight into the role of sex hormones and neuroactive steroids (NAS) in the mechanism controlling pregnancy sustaining. The data in the literature including our studies show that there is a complex mechanism providing synthesis of either pregnancy sust aining or parturition provoking steroids. This mechanism includes the boosting placental synthesis of CRH with approaching parturition inducing the excessive synthesis of 3β-hydroxy-5-ene steroid sulfates serving primarily as precursors for placental synthesis of progestogens, estrogens and NAS. The distribution and changing activities of placental oxidoreductases are responsible for the activation or inactivation of the aforementioned steroids, which is compartment-specific (maternal and fetal compartments) and dependent on gestational age, with a tendency to shift the production from the pregnancy-sustaining steroids to the parturition provoking ones with an increasing gestational age. The fetal and maternal livers catabolize part of the bioactive steroids and also convert some precursors to bioactive steroids. Besides the progesterone, a variety of its 5α/β-reduced metabolites may significantly influence the maintenance of human pregnancy, provide protection against excitotoxicity following acute hypoxic stress, and might also affect the pain perception in mother and fetus. and M. Hill ... [et al.].
Steroids are important components in the pathophysiology of Alzheimer’s disease (AD). Although their role has been studied, the corresponding metabolomic data is limited. In the present study we evaluate the role of steroid sulfotransferase SULT2A1 in the pathophysiology of AD on the basis of circulating steroids (measured by GC-MS), in which the sulfation catalyzed by SULT2A1 dominates over glucuronidation (pregnenolone/sulfate, DHEA/sulfate, androstenediol/sulfate and 5α-reduced pregnane and androstane catabolites). To estimate a general trend of SUL2A1 activity in AD patients we compared the ratios of steroid conjugates to their unconjugated counterparts (C/U) in controls (11 men and 22 women) and AD patients (18 men and 16 women) for individual circulating steroids after adjustment for age and BMI using ANCOVA model including the factors AD status and gender. Decreased C/U ratio for the C19 steroids demonstrate an association between attenuated sulfation of C19 steroids in adrenal zona reticularis and the pathophysiology of AD., M. Vaňková, M. hill, M. Velíková, J. Včelák, G. Vacínová, P. Lukášová, D. Vejražková, K. Dvořáková, R. Rusina, I. Holmerová, E. Jarolímová, H. Vaňková, B. Bendlová., and Obsahuje bibliografii
We examined the involvement of phosphatidylinositol 3-kinase (PI3K) and its effector protein ki nase B (Akt) in cardioprotective effects of ischemic preconditioning (PC) with particular regards to its role in the protection against ischemia-induced arrhythmias in isolated perfused rat heart. PI3K/Akt inhibitor wortmannin (100 nM) was administered 15 min prior to 30-min regional (left anterior descending coronary artery occlusion) ischemia for the study of ischemic arrhythmias in the hearts perfused at constant coronary flow or prior to 30-min global ischemia followed by 2-h reperfusion for the infarct size (IS) determination (tetrazolium staining) in the hearts perfused at constant pressure. PC procedure (one cycle of isch emia/reperfusion, 5 min each) significantly reduced the total number of ventricular premature complexes (PVC) and severity of arrhythmias (arrhythmia score; AS) over the whole period of left anterior descending coronary artery occlusion in comparison with non-PC controls (PVC 166±40; AS 1.6±0.2 vs . 550±60 and 3.2±0.2; respectively; P<0.05). In a setting of global ischemia/reperfusion, PC decreased IS (in % of the left ventricle, LV) by 73 %. Pretreatment with wortmannin modified neither arrhythmogenesis nor IS in the non-PC hearts. Bracketing of PC with wortmannin did not abolish antiarrhythmic protection (PVC 92±25; AS 1.7±0.2; P<0.05 vs . non-PC hearts). On the other hand, wortmannin increased IS/LV in the PC hearts to 24±1.2 % as compared with 9 ± 0.6 % in the untreated ones (P<0.05). In conclusion, PI3K/Akt inhibition did not affect reduced arrhythmogenesis during ischemia in the PC hearts indicating that in contrast to its positive role in the irreversible myocardial injury, PI3K/Akt activity is not required for protection induced by PC against ischemic arrhythmias in the rat heart., T. Ravingerová, J. Matejíková, D. Pancza, F. Kolář., and Obsahuje bibliografii
The flexible supports make it possible to decrease the forces transmitted between the working machines and their foundations. As rotating machinery, the hydrodynmic bearings exhibiting compliance and considerable damping together with high load capacity are ofen used for this purpose. Nevertheless, on certain operating conditions, the hydraulic forces produced in the thin oil film can destabilize the rotor equilibrion position, which consequently leads to development of the rotor self-excited vibration of large amplitude. There are several ways how to increase the critical speed of the rotor rotation at which the self-excited vibration starts. Recently, the attention was focused on increasing damping in the rotor supports or on modification of the bearings geometry. At present time there are available many active control devices working on various physical principles. In this paper the research of the concept based on controlled kinematic excitation of the bearings shells is carried out. The performed computer simulations prove that the investigated technique enables to reduce amplitude of the self-excited vibration and to increase the rotor angular speed of rotation, at which the self-excited vibration begins. Suppression of the rotor oscillation is always connected with increasing the force by which the turning rotor acts on its stationary part. The developed computational procedures and results of the performed analyses are intended for finding properties and behaviour of the active control devices for mitigation of excessive vibration of rotating machines and to contribute to their proper design in this way. and Obsahuje seznam literatury
Livestock depredation can be devastating to both farmers and the species considered responsible if they are subsequently persecuted. Many proposed conflict solutions are limited in their uptake because they may be short-term, localised, expensive or species-specific. Livestock guarding dogs have been a successful solution in many parts of the world, however recommended imported breeds are generally expensive or inaccessible to many rural farmers. In this study, we report on a program placing local Tswana dogs with farmers in Botswana as a tool to reduce livestock loss. Seventy-five farmers who experienced high conflict from carnivores in both rangelands and wildlife areas were selected to receive a Tswana puppy. Puppies were monitored regularly to determine their performance, survival and owner attitudes toward wildlife. From initial baseline reports of goat losses before farmers received a puppy, loss declined by at least 85% over the following three years. Farmers were very satisfied with the performance of their livestock guarding dog and attitudes toward protection and tolerance of wildlife improved after one year of receiving a puppy. Our study suggests locally bred Tswana dogs are an effective solution for livestock at risk to depredation, particularly for rural farmers and development of community-led programs can be further used to reduce conflict.
The paper applies the pseudo-linear algebra to unify the results on reducibility, reduction and transfer equivalence for continuous- and discrete-time nonlinear control systems. The necessary and sufficient condition for reducibility of nonlinear input-output equation is presented in terms of the greatest common left factor of two polynomials describing the behaviour of the `tangent linearized system' equation. The procedure is given to find the reduced (irreducible) system equation that is transfer equivalent to the original system equation. Besides unification, the tools of pseudo-linear algebra allow to extend the results also for systems defined in terms of difference, q-shift and q-difference operators.
Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca2+, respectively. Blood glucose in STZ rats was 4-fold higher (469.64±22.23 mg/dl, n=14) than in Controls (104.06±3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76±2.91 %, n=20) and Control (83.72±2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12±2.28 %, n=20) and Control (76.69±1.92 %, n=30) myocytes. The amplitude of intracellular Ca2+ was also reduced by PHLOR in STZ (82.37±3.16 %, n=16) and Control (73.94±5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62±5.83 %, n=18) and Control (78.32±3.54 %, n=41) myocytes. Myofilament sensitivity to Ca2+ was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca2+ in STZ or Control myocytes. Altered mechanisms of Ca2+ transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats., N. N. Hamouda, M. A. Qureshi, J. M. Alkaabi, M. Oz, F. C. Howarth., and Obsahuje bibliografii
It has been reported that the virulence of axenically cultivated Entamoeba histolytica increases following growth with cholesterol. The purpose of this study was to determine whether cholesterol would enhance the virulence of axenically cultivated Naegleria fowleri. Amoebae were cultivated in axenic medium with (100 pg/ml) or without cholesterol for 6 months and tested in mice for changes in virulence. After 6 months of continuous cultivation, N. fowleri grown with cholesterol was less virulent for mice than the same strain grown without cholesterol.