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
The aim of the present study was to investigate changes in the activity of branched-chain a-keto acid dehydrogenase (BCKAD) in skeletal muscle and the heart during brief and prolonged starvation. Fed control rats and rats starved for 2, 4 and 6 days were anesthetized with pentobarbital sodium before heart and hindlimb muscles were frozen in situ by liquid nitrogen. Basal (an estimate of in vivo activity) and total (an estimate of enzyme amount) BCKAD activities were determined by measuring the release of 14CO2 from a-keto[1-14C]isocaproate. The activity state of BCKAD complex was calculated as basal activity in percentages of total activity. Both basal and total activities and the activity state of the BCKAD were lower in skeletal muscles than in the heart. In both tissues, starvation for 2 or 4 days caused a decrease in the basal activity and activity state of BCKAD. On the contrary, in the heart and muscles of animals starved for 6 days a marked increase in basal activity and activity state of BCKAD was observed. The total BCKAD activity was increasing gradually during starvation both in muscles and the heart. The increase was significant in muscles on the 4th and 6th day of starvation. The demonstrated changes in BCKAD activity indicate significant alterations in branched-chain amino acid (BCAA) and protein metabolism during starvation. The decreased BCKAD activity in skeletal muscle and heart observed on the 2nd and 4th day of starvation prevents the loss of essential BCAA and is an important factor involved in protein sparing. The increased activity of BCKAD on the 6th day of starvation indicates activated oxidation of BCAA and accelerated protein breakdown., M. Holeček., and Obsahuje bibliografii
Abundant evidence indicates that ATP and adenosine act as neurotransmitters or co-transmitters, influencing nerve cell physiology in various ways. Therefore, regulation of ATP-metabolizing enzymes is essential for the normal development and function of neuronal tissue. In the present study we have examined the effect of gonadal (OVX) or adrenal (ADX) steroid hormone deprivation on the activity and expression of synaptic membrane ecto-ATPase in three extrahypothalamic brain areas of female rats, primarily not associated with reproductive function. It was shown that OVX significantly increased ecto-ATPase activity and the relative abundance of this enzyme in the hippocampal (Hip) and caudate nucleus (CN), but not in brain stem (BS) membrane preparations. ADX was followed by an upregulation of the enzyme activity and its relative abundance in all the brain areas investigated. The highest enzyme activity and the most profound effects of OVX and ADX were detected in the CN. The results obtained indicate that ADX and OVX upregulate the expression of ecto-ATPase, potentiating the production of adenosine in synaptic cleft thus modulating the activity of numerous neurotransmitter systems in distinct areas of the CNS., N. Nedeljkovic, V. Djordjevic, A. Horvat, G. Nikezic, D.T. Kanazir., and Obsahuje bibliografii
Activation of sublobule IX-b of the cerebellar vermis evokes hypotension, bradycardia and decrease of the phrenic nerve activity in the anesthetized animal. Cardiac performance during the isovolumic phases of systole and relaxation can be evaluated by dP/dt max, Vpm, dP/dt/DP40 and τ, respectively. In the present study, we evaluated the changes on cardiac function evoked by the stimulation of sublobule IX-b. New Zealand white rabbits were anesthetized, paralyzed and artificially ventilated. A posterior craniotomy was made to reveal and stimulate the cerebellar uvula (4 s train; 50 Hz; 1 ms; 20 μA). The femoral artery and veins were cannulated and a Swan-Ganz catheter was advanced in the upper abdominal aorta to control afterload when inflating the balloon. The left ventricle was catheterized with a Millar catheter. Blood pressure, heart rate, left ventricular pressure were monitored. Results showed a significant decrease on sublobule IX-b stimulation of all the indices of systolic function and an increase of τ indicating a decrease in the speed of the relaxation. These data provide the first evidence of the influence of sublobule IX-b on cardiac function. They may contribute to the understanding of the origin the cardiovascular changes that were observed in two patients with vermian and paravermian hemorrhage., I. Rochas, V. Gonçalves, M. J. Bettencourt, L. Silva-Carvalho., and Obsahuje bibliografii a bibliografické odkazy
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
The aim of this work was to study the effect of the daily ingestion of a purified anthocyanin extract from red grape skin on rat serum antioxidant capacity (ORAC) and its safety for the intestinal epithelium. The study was carried out in rats orally administered with the extract for 10 days in either normal physiological conditions or exposed to a pro-oxidant chemical (CCl4). The oral administration of the extract significantly (P<0.05) enhanced the ORAC va lue of the deproteinised serum of about 50 % after 10 days of ingestion. Anthocyanin administration was also able to reverse completely the decrease in the serum ORAC activity induced by the CCl4 treatment. Experiments with Ussing chamber mounted intestine allowed to exclude any toxicity of the extract for the intestinal epithelium. In conclusion, our results demonstrate that the purified anthocyanin extract from red grape skin e nhances the total antioxidant capacity of the serum in either normal physiological condition or during oxidative stress induction, revealing a protective role against the decrease in the serum antioxidant capacity induced by a pro-oxidant compound., M. G. Lionetto ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Creatine (Cr) is recommended as a dietary supplement especially for athletes but its therapeutic potential is also discussed. It is assumed that human body uses Cr for the formation of phosphocreatine, which is nece ssary for muscular work as a source of energy. Production of Cr in a body is closely connected to methionine cycle where guanidinoacetate (GAA) is in a final step methylated from S-adenos ylmethionine (SAM). Increased availability of SAM for phosphatidylcholine (PC) and sarcosine synthesis can potentially stimulate endogenous production of betaine a thus methylation of homocysteine (HCy) to form methionine. Our subject who was methylenetetrahydrofolate reductase ( MTHFR ) 677TT homozygote lowered plasma HCy from 33.3 μmol/l to 17.1 μmol/l following one-month Cr supplementation (5 g/day) opposite to 677CC and CT genotypes whose HCy levels tended to increase (but still in normal ranges). We suppose that Cr supplementation stimulates pathways leading to production of sarcosine which can serve to regenerate tetrahydrofolate (THF) to form 5,10-methylene-THF. This could potentially increase MTHFR enzyme activity which may later result in increased HCy methylation. Cr supplementation significantly effects metabolism of one carbon unit and potentially lower body's demands for methyl groups. This could be beneficial as in the case of reduced enzyme activity such as MTHFR 677C/T polymorphism., M. Petr, M. Šteffl, E. Kohlíková., and Obsahuje bibliografii a bibliografické odkazy
Time delay in the mediation of ventilation (VE) by arterial CO2 pressure (PaCO2) was studied during recovery from short impulse-like exercises with different work loads of recovery. Subjects performed two tests including 10-s impulse like exercise with work load of 200 watts and 15-min recovery with 25 watts in test one and 50 watts in test two. V . E, end tidal CO2 pressure (PETCO2) and heart rate (HR) were measured continuously during rest, warming up, exercise and recovery. PaCO2 was estimated from PETCO2 and tidal volume (VT). Results showed that predicted arterial CO2 pressure (PaCO2 pre) increased during recovery in both tests. In both tests, VE increased and peaked at the end of exercise. VE decreased in the first few seconds of recovery but started to increase again. The highest correlation coefficient between PaCO2 pre and V . E was obtained in the time delay of 7 s (r=0.854) in test one and in time delays of 6 s (r=0.451) and 31 s (r=0.567) in test two. HR was significantly higher in test two than in test one. These results indicate that PaCO2 pre drives VE with a time delay and that higher work intensity induces a shorter time delay., R. Afroundeh, T. Arimitsu, R. Yamanaka, C. S. Lian, K. Shirakawa, T. Yunoki, T. Yano., 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
Spontaneous activity of cortical neurons exhibits alternative fluctuations of membrane potential consisting of phased depolarization called "up-state" and persistent hyperpolarization called "down-state" during slow wave sleep and anesthesia. Here, we examined the effects of sound stimuli (noise bursts) on neuronal activity by intracellular recording in vivo from the rat auditory cortex (AC). Noise bursts increased the average time in the up-state by 0.81±0.65 s (rang e, 0.27-1.74 s) related to a 10 s recording duration. The rise times of the spontaneous up-events averaged 69.41±18.04 ms (range, 40.10-119.21 ms), while those of the sound-evoked up-events were significantly shorter (p<0.001) averaging on ly 22.54±8.81 ms (range, 9.31- 45.74 ms). Sound stimulation did not influence ongoing spontaneous up-events. Our data suggest that a sound stimulus does not interfere with ongoing spontaneous neuronal activity in auditory cortex but can evoke new depolarizations in addition to the spontaneous ones., Y. Zhang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy