We investigated the impact of a high-fat (HF) diet during pre- and post-weaning periods on the intestinal microbiota and alkaline phosphatase (AP) activity in male rats. Nutrition from birth was influenced by feeding rat dams with either a standard or HF diet. After weaning male pups nursed by control dams continued on a standard diet (CC) or HF diet (C-HF), while offspring nursed by HF dams continued on HF diet (HF) or standard diet (HF-C). The numbers of Bacteroides/Prevotella (BAC) and Lactobacillus/Enterococcus (LAB) in the gut were determined by FISH technique. HF pups displayed enhanced adiposity and increased AP activity (19 %), as well as higher LAB (P<0.001) and lower numbers of BAC (P<0.001) in the jejunum and colon than controls. In HF-C rats, post-weaning lower fat intake resulted in decreased fat deposition accompanied by reduced AP activity (20 %) compared to HF rats. Composition of the intestinal microbiota in these rats was not influenced. In contrast, in comparison with controls, C-HF rats displayed higher LAB (P<0.001) and lower BAC (P<0.001) together with increased adiposity and AP activity (14 %). These results indicate that consumption of diet with different fat content could modulate gut microbial/functional conditions depending on the period when the nutritional manipulation occurs., Z. Šefčíková, D. Bujňáková., and Obsahuje bibliografii
This study aimed to examine how regular aerobic training can affect the muscle hypertrophy induced by overloading. Male C57BL/6J mice were randomly divided into three groups: rest group, low-intensity aerobic exercise group, and high-intensity aerobic exercise group. Mice in the exercise groups were assigned to run at a speed of 10 m/min (low-intensity) or 25 m/min (high-intensity) for 30 min/day, five days/week, for four weeks. Then, the right hind leg gastrocnemius muscles were surgically removed to overload the plantaris and soleus muscles, while the left hind leg was subjected to a sham-operation. Both the plantaris and soleus muscles grew larger in the overloaded legs than those in the sham-operated legs. Muscle growth increased in the plantaris muscles in the low-intensity exercise group compared to that in the rest or high-intensity exercise groups at one and two weeks after overloading. This enhancement was not observed in the soleus muscles. Consistently, we observed changes in the expression of proteins involved in anabolic intracellular signaling, including Akt, mechanistic target of rapamycin (mTOR), and p70S6K, in the plantaris muscles. Our data showed for the first time that chronic low-intensity aerobic exercise precipitates overload-induced muscle growth., Siriguleng, T. Koike, Y. Natsume, S. Iwama, Y. Oshida., and Obsahuje bibliografii
Baclofen is the only clinically available metabotropic GABAB receptor agonist. In our experiment, we tested the hypothesis that long-term baclofen administration can impair learning and memory in rats. The experiment consisted of three parts. In the first part of the study the drug was administered simultaneously with the beginning of the behavioral tests. In the second and third part of the experiment baclofen was administered daily for 14 days and for one month before the tests. In each part of the experiment, adult rats were randomly divided into four treatment groups. Three groups were given an injection of baclofen at doses of 1 mg/kg, 5 mg/kg, 10 mg/kg, while the fourth group was injected with saline. The injections were given after each session. Spatial learning and memory were tested using the Morris water maze, involving three types of tests: Acquisition, Probe, and Re-acquisition. This work reveals that baclofen did not affect spatial learning at any of the tested doses and regardless of the length of administration. Memory was observed to be affected, but only at the highest dose of baclofen and only temporarily. This conclusion is in line with previously published clinical cases., M. Holajová, M. Franěk., and Seznam literatury
Sophoridine is a type of alkaloid extract derived from the Chinese herb Sophora flavescens Ait (kushen) and possess a variety of pharmacological effects including anti- inflammation, anti - anaphylaxis, anti - cancer, anti - arrhythmic and so on. However, the effect of sophoridine on heart failure has not been known yet. In this study, the effect of sophoridine on heart failure was investigated using Sprague -Dawley (SD) rat model of chronic heart failure. Morphological results showed that in medium and high dose group, myofilaments were arranged orderly and closely, intermyofibrillar ly sis disappeared and mitochondria contained tightly packed cristae compared with heart failure group. We investigated the Ca 2+ induced Ca 2+ transients and assessed the expression of ryanodine receptor (RyR2) and L-type Ca 2+ channel (dihydropyridine receptor, DHPR). We found that the cytosolic Ca 2+ transients were markedly increas ed in amplitude in medium ( ΔF/F 0 =43.33±1.92 ) and high dose groups ( ΔF/F 0 =47.21 ±1.25 ) compared with heart failure group ( ΔF/F 0 =16.7±1.29, P <0.0 1), Moreover, we demonstrated that the expression of cardiac DHPR was significantly increased in medium - and high dose -group compared with heart failure rats. Our results suggest that sophoridine could improve heart failure by ameliorating cardiac Ca 2+ induced Ca 2+ transients, and that thi s amelioration is associated with upregulation of DHPR., S.-T. Hu, Y.-F. Shen, J.-M. Gong, Y.-J. Yang., and Obsahuje bibliografii
This study investigates the effects of long-term treatment with sulodexide (SLX) on norepinephrine (NE)-induced contractions, acetylcholine(Ach)-induced relaxations, acute cyclooxygenase blockade by diclofenac (DIC) in isolated femoral arteries (FA) and the parameters of oxidative phosporylation in liver mitochondria. 15-weeks old Wistar rats were divided into four groups: control (C; injected with saline solution), treated control (C+SLX), diabetic (DM) and treated diabetic (DM+SLX). Diabetes was induced with a single i.v. dose of streptozotocin (STZ) 45 mg.kg-1. SLX was administered i.p., at dose 100 IU.kg-1 daily for 5 weeks. Vascular responses of isolated femoral arteries were measured using Mulvany-Halpern myograph. Respiratory function of the mitochondria was determined using voltamperometric method on oxygraph Gilson. In diabetic rats the amplitude of maximal response to NE was elevated. DIC pretreatment decreased the amplitudes of NE-induced contractions in all groups of rats. SLX treatment decreased sensitivity of FA to NE and caused higher relaxatory responses to Ach in C and DM. Oxygen consumption and phosphorylation rates ([QO2(S3)], [QO2(S4)] and (OPR)) and respiratory control ratio (RCR) were decreased in the mitochondria of DM rats. Mitochondria of C rats were not affected with SLX treatment. Administration of SLX in DM rats was associated with increase of RCR, other parameters were not affected. Our findings suggest that SLX treatment might be associated with vasculoprotective effects during diabetes and improvement of mitochondrial function., L. Dobiaš, M. Petrová, R. Vojtko, O. Uličná, O. Vančová, V. Kristová., and Obsahuje bibliografii
Several diseases induce hypermetabolism, which is characterized by increases in rest ing energy expenditures (REE) and whole body protein loss. Exaggerated protein degradation is thought to be the driving force underlying this response. The effects of caspase and calpain inhibitors on REE in physiological and hypermetabolic conditions, how ever, are unknown. Thus, we studied whether MDL28170 (calpain inhibitor) or z-VAD-fmk (caspase inhibitor) affect REE under physiological conditions and during hypermetabolism post -burn. Rats were treated five times weekly and observed for 6 weeks. Treatmen t was started 2 h (early) or 48 h ( late) after burn. In normal rats, MDL28170 transiently increased REE to 130 % of normal during week 2-4. z-VAD-fmk reduced REE by 20-25 % throughout the observation period. Within 14 days after burns, REE increased to 13 0±5 % . Whereas MDL28170/ early treatment did not affect REE, MDL28170/ late transiently increased REE to 180±10 % of normal by week 4 post- burn. In contrast, with z -VAD -fmk/ early REE remained between 90-110 % of normal post- burn. z-VAD-fmk/ late did not affect burn-induced increases in REE. These data suggest that caspase cascades contribute to the development of hypermetabolism and that burn-induced hypermetabolism can be pharmacologically modulated. Our data point towards caspase cascades as po ssible therapeutic targets to attenuate hypermetabolism after burns, and possibly in other catabolic disease processes., P. G. Vana, H. M. LaPorte, R. H. Kennedy, R. L. Gamelli, M. Majetschak., and Obsahuje bibliografii
Ultraviolet-radiation exerts a well-known role in the development of various ocular diseases and may contribute to the progress of age-related macular degeneration. Therefore, the use of compounds able to protect the eyes from UV-induced cellular damage is challenging. The aim of this study has been to test the protective effects of an antioxidant topical formulation against UV-induced damage in rabbit eyes. Twelve male rabbits were used. Animals were divided into 4 groups of 3 animals each. Control group (CG) did not receive any irradiation and/or eye drop. The other three experimental groups were treated as follows: the first group received only UVR irradiation for 30 min, without eye drop supplementation (Irradiation group, IG), the second (G30) and the third (G60) groups received UV irradiation for 30’ and 60’, respectively, and eye drop supplementation (riboflavin, d-α-tocopheryl polyethylene glycol, proline, glycine, lysine and leucine solution) every 15 min for three hours. In the IG group a significant increase of oxidized glutathione (GSSG) and hydrogen peroxide (H2O2) was recorded in the aqueous humor, whereas ascorbic acid levels were significantly lower when compared to control eyes. In the groups exposed to UVR rays for 30 min, and treated with the topical antioxidant formulation, the GSSG, H2O2 and ascorbic acid levels were similar to those recorded in controls, whereas in the G60 group the three markers significantly differ from control group. In the lens, a significant decrease of alpha tocopherol and total antioxidant capacity (TAC) was recorded in IG-animals as compared to control group, whereas malondialdehyde (MDA) levels were significantly higher in UV-induced eye than in control eyes. In the G30 groups the alpha tocopherol, MDA and TAC levels do not significantly differ from those recorded in controls, whereas in the G60 group these three markers significantly differ from control group. Present findings demonstrate that topical treatment with the antioxidant formulation used herein protects ocular structures from oxidative stress induced by UV exposure in in vivo animal model, F. Vizzarri, M. Palazzo, S. Bartollino, D. Casamassima, B. Parolini, P. Troiano, C. Caruso, C. Costagliola., and Obsahuje bibliografii
Various types of mechanosensitive ion channels, including cationic stretch-activated channels (SAC NS ) and stretch-activated BKca (SAKca) channels, modulate heart rhythm. Bepridil has been used as an antiarrhythmic drug with multiple pharmacological effects; however, whether it is effective for mechanically induced arrhythmia has not been well investigated. To test the effects of Bepridil on SAKca channels activity, cultured chick embryo nic ventricular myocytes were used for single - channel recordings. Bepridil significantly reduced the open probability of the SAKca channel (PO). Next, to test the effects of bepridil on stretch-induced extrasystoles (SIE), we used an isolated 2-week-old Langendorff-perfused chick heart. The left ventricle (LV) volume was rapidly changed, and the probability of SIE was calculated in the presence and absence of bepridil, and the effect of the drug was compared with that of Gadolinium (Gd3+). Bepridil decreased the probability of SIE despite its suppressive effects on SAKca channel activity. The effects of Gd3+, which blocks both SAKca and SACNS , on the probability of SIE were the same as those of bepridil. Our results suggest that bepridil blocks not only SAKc a channels but possibly also blocks SACNS , and thus decreases the stretch -induced cation influx (stabilizing membrane potential) to compensate and override the effects of the decrease in outward SAKca current (destabilizing membrane potential)., H. Jin, G. Iribe, K. Naruse., and Obsahuje bibliografii
Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effects. Since HMB is synthesized in the liver, unique effects of exogenous HMB intake may be hypothesized in subjects with liver disease, in which muscle wasting is frequently found. We studied effects of HMB on the liver and soleus (SOL) and extensor digitorum longus (EDL) muscles in partially-hepatectomized (PH) rats. HMB or saline was infused using osmotic pumps to PH or sham-operated rats for 7 days. We found lower body weight and protein content in EDL of PH rats treated with saline than in sham-operated animals. These effects were insignificant in HMB treated animals. In blood plasma of PH rats treated with HMB we found lower concentrations of creatinine and higher concentrations of urea and branched-chain amino acids (BCAA; valine, leucine, and isoleucine) than in PH animals treated with saline. HMB increased BCAA concentrations in SOL and EDL of PH animals and decreased proteolysis in EDL of both sham-operated and PH animals. In the livers of PH rats treated with HMB we found higher DNA content, DNA fragmentation, and BCAA concentrations than in saline-treated animals. The results indicate that HMB affects metabolism of BCAA and has positive influence on protein balance in muscles. Further studies are needed to clarify the effect of HMB on liver regeneration., M. Holeček, M. Vodeničarovová., and Obsahuje bibliografii
The effects of exercise on mechanical hyperalgesia, joint contracture, and muscle injury resulting from immobilization are not completely understood. This study aimed to investigate the effects of cyclic stretching on these parameters in a rat model of chronic post-cast pain (CPCP). Seventeen 8-week-old Wistar rats were randomly assigned to (1) control group, (2) immobilization (CPCP) group, or (3) immobilization and stretching exercise (CPCP+STR) group. In the CPCP and CPCP+STR groups, both hindlimbs of each rat were immobilized in full plantar flexion with a plaster cast for a 4-week period. In the CPCP+STR group, cyclic stretching exercise was performed 6 days/week for 2 weeks, beginning immediately after cast removal prior to reloading. Although mechanical hyperalgesia in the plantar skin and calf muscle, ankle joint contracture, and gastrocnemius muscle injury were observed in both immobilized groups, these changes were significantly less severe in the CPCP+STR group than in the CPCP group. These results clearly demonstrate the beneficial effect of cyclic stretching exercises on widespread mechanical hyperalgesia, joint contracture, and muscle injury in a rat model of CPCP., Kazuhiro Hayashi, Saori Fukuyasu-Matsuo, Takayuki Inoue, Mitsuhiro Fujiwara, Yuji Asai, Masahiro Iwata, Shigeyuki Suzuki., and Obsahuje bibliografii