Intracellular mechanisms of specific beta-adrenoceptor antagonists involved in improved cardiac function and survival in a genetic model of heart failure

beta-blockers, as class, improve cardiac function and survival in heart failure (HF). However, the molecular mechanisms underlying these beneficial effects remain elusive. In the present study, metoprolol and carvedilol were used in doses that display comparable heart rate reduction to assess their beneficial effects in a genetic model of sympathetic hyperactivity-induced HF (alpha(2A)/alpha(2C)-ARKO mice). Five month-old HF mice were randomly assigned to receive either saline, metoprolol or carvedilol for 8 weeks and age-matched wild-type mice (WT) were used as controls. HF mice displayed baseline tachycardia, systolic dysfunction evaluated by echocardiography, 50% mortality rate, increased cardiac myocyte width (50%) and ventricular fibrosis (3-fold) compared with WT. All these responses were significantly improved by both treatments. Cardiomyocytes from HF mice showed reduced peak [Ca(2+)](i) transient (13%) using confocal microscopy imaging. Interestingly, while metoprolol improved [Ca(2+)](i) transient, carvedilol had no effect on peak [Ca(2+)](i) transient but also increased [Ca(2+)] transient decay dynamics. We then examined the influence of carvedilol in cardiac oxidative stress as an alternative target to explain its beneficial effects. Indeed, HF mice showed 10-fold decrease in cardiac reduced/oxidized glutathione ratio compared with WT, which was significantly improved only by carvedilol treatment. Taken together, we provide direct evidence that the beneficial effects of metoprolol were mainly associated with improved cardiac Ca(2+) transients and the net balance of cardiac Ca(2+) handling proteins while carvedilol preferentially improved cardiac redox state. (C) 2008 Elsevier Inc. All rights reserved.

Radicicol improves regeneration of skeletal muscle previously damaged by crotoxin in mice

This work investigates the influence of heat shock proteins (HSPs) on necrosis and subsequent skeletal muscle regeneration induced by crotoxin (CTX), the major component of Crotalus durissus terrificus venom. Mice were treated with radicicol, a HSP inductor, followed by an intramuscular injection of CTX into the gastrocnemius muscle. Treated groups were sacrificed 1, 10 and 21 days after CTX injection. Muscle histological sections were stained with toluidine blue and assayed for acid phosphatase or immunostained with either neuronal cell adhesion molecule (NCAM) or neonatal myosin heavy chain (MHCn). Muscle samples were also submitted to Western blotting analysis. The results show that CTX alone and CTX combined with radicicol induced a similar degree of myofiber necrosis. CTX-injured muscles treated with radicicol had increased cross-sectional areas at 10 and 21 days post-lesion compared with untreated CTX-injured muscles. Additionally, radicicol significantly increased the number of NCAM-positive satellite cells in the gastrocnemius at one day post-CTX injury. CTX-injured Muscles treated with radicicol contained more MHCn-positive regenerating myofibers compared with untreated CTX-injured muscles. These results suggest that HSPs contribute to the regeneration of myofibers damaged by CTX. Additionally, further studies should investigate the potential therapeutic effects of radicicol in skeletal muscles affected by Crotalus venom. (C) 2008 Elsevier Ltd. All rights reserved.

Intercepting moving targets: does memory from practice in a specific condition of target displacement affect movement timing?

This investigation aimed at assessing the extent to which memory from practice in a specific condition of target displacement modulates temporal errors and movement timing of interceptive movements. We compared two groups practicing with certainty of future target velocity either in unchanged target velocity or in target velocity decrease. Following practice, both experimental groups were probed in the situations of unchanged target velocity and target velocity decrease either under the context of certainty or uncertainty about target velocity. Results from practice showed similar improvement of temporal accuracy between groups, revealing that target velocity decrease did not disturb temporal movement organization when fully predictable. Analysis of temporal errors in the probing trials indicated that both groups had higher timing accuracy in velocity decrease in comparison with unchanged velocity. Effect of practice was detected by increased temporal accuracy of the velocity decrease group in situations of decreased velocity; a trend consistent with the expected effect of practice was observed for temporal errors in the unchanged velocity group and in movement initiation at a descriptive level. An additional point of theoretical interest was the fast adaptation in both groups to a target velocity pattern different from that practiced. These points are discussed under the perspective of integration of vision and motor control by means of an internal forward model of external motion.

Effect of eccentric contraction velocity on muscle damage in repeated bouts of elbow flexor exercise

Eccentric exercise induces muscle damage, but controversy exists concerning the effect of contraction velocity on the magnitude of muscle damage, and little is known about the effect of contraction velocity on the repeated-bout effect. This study examined slow (60 degrees.s(-1)) and fast (180 degrees.s(-1)) velocity eccentric exercises for changes in indirect markers of muscle damage following 3 exercise bouts that were performed every 2 weeks. Fifteen young men were divided into 2 groups based on the velocity of eccentric exercise: 7 in the Ecc60 (60 degrees.s(-1)) group, and 8 in the Ecc180 (180 degrees.s(-1)) group. The exercise consisted of 30 maximal eccentric contractions of the elbow flexors at each velocity, in which the elbow joint was forcibly extended from 60 degrees to 180 degrees (full extension) on an isokinetic dynamometer. Changes in maximal voluntary isometric contraction strength, range of motion, muscle soreness, and plasma creatine kinase activity before and for 4 days after the exercise were compared in the 2 groups using a mixed-model analysis (group x bout x time). No significant differences between groups were evident for changes in any variables following exercise bouts; however, the changes were significantly smaller (p < 0.05) after the second and third bouts than after the first bout. These results indicate that the contraction velocity does not influence muscle damage or the repeated-bout effect.

Treatment of vitamin D deficiency increases lower limb muscle strength in institutionalized older people independently of regular physical activity: a randomized double-blind controlled trial

Aims: To investigate the effects of a 6-month supplementation with calcium and cholecalciferol on biochemical parameters and muscle strength of institutionalized elderly. Methods: This prospective, double-blind, placebo-controlled, randomized trial included Brazilian institutionalized people 6 60 years of age receiving a 6-month supplementation ( December to May) of daily calcium plus monthly placebo (calcium/placebo group) or daily calcium plus oral cholecalciferol (150,000 IU once a month during the first 2 months, followed by 90,000 IU once a month for the last 4 months; calcium/vitamin D group). Fasting blood samples for 25-(OH) D, PTH and calcium determination were collected (n = 56) and muscle tests were performed ( n = 46) to measure the strength of hip flexors (SHF) and knee extensors (SKE) before ( baseline) and after the 6-month intervention ( 6 months). Results: Due to seasonal variations, serum 25( OH) D significantly enhanced in both groups after treatment, but the calcium/vitamin D group had significantly higher 25-(OH) D levels than the calcium/placebo group (84 vs. 33%, respectively; p < 0.0001). No cases of hypercalcemia were observed. While the calcium/placebo group showed no improvement in SHF and SKE at 6 months (p = 0.93 and p = 0.61, respectively), SHF was increased in the calcium/vitamin D group by 16.4% (p = 0.0001) and SKE by 24.6% (p = 0.0007). Conclusions: The suggested cholecalciferol supplementation was safe and efficient in enhancing 25(OH)D levels and lower limb muscle strength in the elderly, in the absence of any regular physical exercise practice. Copyright (C) 2009 S. Karger AG, Basel

Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene

Negrão M.V, Alves CR, Alves G.B, Pereira A.C, Dias R.G, Laterza M.C, Mota G.F, Oliveira E.M, Bassaneze V, Krieger J.E, Negrão C.E, Rondon M.U.P. Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene. Physiol Genomics 42A: 71-77, 2010. First published July 6, 2010; doi:10.1152/physiolgenomics.00145.2009.-Allele T at promoter region of the eNOS gene has been associated with an increase in coronary disease mortality, suggesting that this allele increases susceptibility for endothelial dysfunction. In contrast, exercise training improves endothelial function. Thus, we hypothesized that: 1) Muscle vasodilatation during exercise is attenuated in individuals homozygous for allele T, and 2) Exercise training improves muscle vasodilatation in response to exercise for TT genotype individuals. From 133 preselected healthy individuals genotyped for the T786C polymorphism, 72 participated in the study: TT (n = 37; age 27 +/- 1 yr) and CT + CC (n = 35; age 26 +/- 1 yr). Forearm blood flow (venous occlusion plethysmography) and blood pressure (oscillometric automatic cuff) were evaluated at rest and during 30% handgrip exercise. Exercise training consisted of three sessions per week for 18 wk, with intensity between anaerobic threshold and respiratory compensation point. Resting forearm vascular conductance (FVC, P = 0.17) and mean blood pressure (P = 0.70) were similar between groups. However, FVC responses during handgrip exercise were significantly lower in TT individuals compared with CT + CC individuals (0.39 +/- 0.12 vs. 1.08 +/- 0.27 units, P = 0.01). Exercise training significantly increased peak VO(2) in both groups, but resting FVC remained unchanged. This intervention significantly increased FVC response to handgrip exercise in TT individuals (P = 0.03), but not in CT + CC individuals (P = 0.49), leading to an equivalent FVC response between TT and CT + CC individuals (1.05 +/- 0.18 vs. 1.59 +/- 0.27 units, P = 0.27). In conclusion, exercise training improves muscle vasodilatation in response to exercise in TT genotype individuals, demonstrating that genetic variants influence the effects of interventions such as exercise training.

Branched-chain amino acids supplementation enhances exercise capacity and lipid oxidation during endurance exercise after muscle glycogen depletion

Aim. It has been demonstrated that branched-chain amino acids (BCAA) transaminase activation occurs simultaneously with exercise-induced muscle glycogen reduction, suggesting that BCAA supplementation might play an energetic role in this condition. This study aimed to test whether BCAA supplementation enhances exercise capacity and lipid oxidation in glycogen-depleted subjects. Methods. Using a double-blind cross-over design, volunteers (N.=7) were randomly assigned to either the BCAA (300 mg . kg . day (-1)) or the placebo (maltodextrine) for 3 days. On the second day, subjects were submitted to an exercise-induced glycogen depletion protocol. They then performed an exhaustive exercise test on the third day, after which time to exhaustion, respiratory exchange ratio (RER), plasma glucose, free fatty acids (HA), blood ketones and lactate were determined. BCAA supplementation promoted a greater resistance to fatigue when compared to the placebo (+17.2%). Moreover, subjects supplemented with BCAA showed reduced RER and higher plasma glucose levels during the exhaustive exercise test. Results. No significant differences appeared in FFA, blood ketones and lactate concentrations. Conclusion. In conclusion, BCAA supplementation increases resistance to fatigue and enhances lipid oxidation during exercise in glycogen-depleted subjects.

The cultural adaptation and validation of the ""Burn Specific Health Scale-Revised"" (BSHS-R): Version for Brazilian burn victims

Background: The Burns Specific Health Scale-Revised (BSHS-R) is of easy application, can be self-administered, and it is considered a good scale to evaluate various important life aspects of burn victims. Objectives: To translate and culturally adapt the BSHS-R into the Brazilian-Portuguese language and to evaluate the internal consistency and convergent validity of the translated BSHS-R. Methods: The cultural adaptation of the BSHS-R included translation and back-translation, discussions with professionals and patients to ensure conceptual equivalence, semantic evaluation, and pre-test of the instrument. The Final Brazilian-Portuguese Version (FBPV) of the BSHS-R was tested on a group of 115 burn patients for internal consistency and validity of construct (using the Rosenberg Self-Esteem Scale (RSES) and the Beck Depression Inventory (BDI)). Results: All values of Cronbach`s alpha were greater than. 8, demonstrating that the internal consistency of the FBPV was very high. Self-esteem was highly correlated with affect and body image (r = .59, p < .001), and with interpersonal relationships (T = .51, p < .001). Correlations between the domains of the FBPV and the BDI were all negative but larger in magnitude than the correlations with RSES. Depression was highly correlated with affect and body image (r = -77, p < .001), and with interpersonal relationships (r = -67, p < .001). Conclusions: The results showed that the adapted version of the BSHS-R into Brazilian-Portuguese fulfills the validity and reliability criteria required from an instrument of health status assessment for burn patients. (C) 2008 Elsevier Ltd and ISBI. All rights reserved.

Effect of specific feed volume on the performance of an anaerobic sequencing batch biofilm reactor (AnSBBR) with circulation treating different wastewaters under different organic loads

The objective of this research was to study the behavior of two anaerobic sequencing batch reactors, containing immobilized biomass (AnSBBR), as a function of the ratio of the volume of treated medium in each cycle to the total volume of reaction medium. The reactors, in which mixing was accomplished by recirculation of the liquid phase, were maintained at 30 +/- 1 degrees C and treated different wastewaters in 8-h cycles. The operational conditions imposed had the objective to investigate whether maintenance of a residual volume in the reactor would affect, at the end of each cycle, process efficiency and stability, as well as to verify the intensity of the effect for different types of wastewaters and organic loading rates. The first reactor, with work volume of 2.5 L, treated reconstituted cheese whey at an organic loading rate of 12 g COD.L(-1).d(-1) and presented similar effluent quality for the four conditions under which it was operated: renewal of 100, 70, 50 and 25 % of its work volume at each cycle. Despite the fact that reduction in the renewed volume did not significantly affect effluent quality, in quantitative terms, this reduction resulted in an increase in the amount of organic matter removed by the first reactor. The second reactor, with work volume of 1.8 L, treated synthetic wastewater at organic loading rates of 3 and 5 g COD.L(-1).d(-1) and operated under two conditions for each loading: renewal of 100 and 50 % of its work volume. At the organic loading rate of 3 g COD.L(-1).d(-1), the results showed that both effluent quality and amount of organic matter removed by the second reactor were independent of the treated volume per cycle. At the organic loading rate of 5 g COD.L(-1).d(-1), although the reduction in the renewed volume did not affect the amount of organic matter removed by the reactor, effluent quality improved during reactor operation with total discharge of its volume. In general, results showed process stability under all conditions, evidencing reactor flexibility and the potential to apply this technology in the treatment of different types of wastewater.

Specific methanogenic activity in an anaerobic-aerobic reactor applied to the treatment of domestic residual water

The specific methanogenic activity (SMA) test is an important tool for the monitoring of anaerobic digestion. This paper presents the behavior of the methanogenic archaea of an anaerobic sludge under different conditions of oxygenation in a fixed-bed anaerobic-aerobic reactor treating domestic sewage. The reactor was operated in a continuous manner under different liquid recycle ratios from aerobic to anaerobic zones in order to remove carbon and nitrogen. The application of the SMA test was adapted from several authors and the measurement of the accumulated methane in the reactor was carried out by means of gas chromatography. Methanogenic organisms were not inhibited by the presence of oxygen. In contrast, the values of CH, production rate by sludge exposed to oxygen were greater than those obtained for strictly anaerobic sludge.

Recombinant rabies virus glycoprotein synthesis in bioreactor by transfected Drosophila melanogaster S2 cells carrying a constitutive or an inducible promoter

S2 cell populations (S2AcRVGP2K and S2MtRVGP-Hy) were selected after transfection of gene expression vectors carrying the cDNA encoding the rabies virus glycoprotein (RVGP) gene under the control of the constitutive (actin) or inductive (metallothionein) promoters. These cell populations were cultivated in a 1 L bioreactor mimicking a large scale bioprocess. Cell cultures were carried out at 90 rpm and monitored/controlled for temperature (28 degrees C) and dissolved oxygen (10 or 50% air saturation). Cell growth attained similar to 1.5-3 x 10(7) cells/mL after 3-4 clays of cultivation. The constitutive synthesis of RVGP in S2AcRVGP2K cells led to values of 0.76 mu g/10(7) cells at day 4 of culture. The RVGP synthesis in S2MtRVGP-Hy cell fraction increased upon CuSO(4) induction attaining specific productivities of 1.5-2 mu g/10(7) cells at clays 4-5. RVGP values in supernatant as a result of cell lysis were always very low (<0.2 mu g/mL) indicating good integrity of cells in culture. Overall the RVGP productivity was of 1.5-3 mg/L. Our data showed an important influence of dissolved oxygen on RVGP synthesis allowing a higher and sustained productivity by S2MtRVGP-Hy cells when cultivated with a DO of 10% air saturation. The RVGP productivity in bioreactors shown here mirrors those previously observed for T-flasks and shaker bottles and allow the preparation of the large RVGP quantities required for studies of structure and function. (C) 2010 Elsevier B.V. All rights reserved.

High frequency tendon reflexes in the human soleus muscle

Tendon reflexes have been often used in studies of the human nervous system in health and disease. They have been investigated either in response to single tendon taps or to long duration vibrations. Tendon reflexes are described here in response to a high frequency vibration burst (3 cycles of a 100 Hz sine wave) applied to the Achilles tendon of standing subjects, either in quiet stance or during a forward leaning posture. The electromyogram from the soleus muscle usually showed three components separated by 10 ms which were interpreted as being three reflexes, each reflex induced by each of the three cycles in a burst. This result indicates that soleus tendon reflexes can respond in fast succession in a phasic manner when a brief high frequency vibration is applied to the Achilles tendon. This occurs in spite of possible depression of the la to motoneuron synapses and the long after hyperpolarization of the motoneurons. An interpretation of the results is that motoneurons from different subsets of the motoneuron pool respond to different cycles of the sinusoidal vibratory burst. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Penetration of hydrolysed soy protein-added brine and its effect on yield and pH of beef steaks from the biceps femoris muscle

This study was aimed to evaluate the penetration behaviour of different brines with tumbled beef steaks from the biceps femoris muscle, specifically their interactions with pH and effects on yield. Six muscles from different animals, divided into origin (OP) and insertion (IP) portions, were cut into 60 steaks of 2.5 cm thickness and tumbled for 30 or 60 min. The steaks were tumbled with two brines, with (WTB/HSP) or without (WTB) hydrolysed soy protein (HSP), and steaks that were not tumbled with brine or water were used as controls. Brine penetration was verified by measuring the amount of dye-containing brine (absorbance at 627 nm) recovered from homogenates of four thin (2 mm) slices from the surface of the beef steaks after tumbling. The WTB/HSP steaks exhibited greater (P < 0.05) brine penetration when tumbled for 60 min than for 30 min. The OP steaks showed greater yield and lower pH (P < 0.05) than IP steaks. HSP-added brine increased the water absorption and retention in the first slices of the steaks, and its efficiency was increased with a longer tumbling time. The portion of the biceps femoris muscle used influenced brine absorption and retention, impacting meat yield. (C) 2010 Elsevier Ltd. All rights reserved.

Molecular detection and differentiation of Brazilian and African isolates of the entomopathogen Neozygites tanajoae (Entomophthorales: Neozygitaceae) with PCR using specific primers

Neozygites tanajoae is an entomopathogenic fungus which has been used for biocontrol of the cassava green mite (Mononychellus tanajoa, CGM) in Africa. Establishment and dispersal of Brazilian isolates which have been introduced into some African countries in recent years to improve CGM control was followed with specific PCR assays. Two primer pairs, NEOSSU_F/NEOSSU_R and 8DDC_F/8DDC_R, were used to differentiate isolates collected from several locations in Brazil and from three countries in Africa, Benin, Ghana and Tanzania. The first primer pair enabled the species-specific detection of Neozygites tanajoae, while the second differentiated the Brazilian isolates from those of other geographical origin. PCR assays were designed for detection of fungal DNA in the matrix of dead infested mites since N. tanajoae is difficult to isolate and culture on selective artificial media. Our results show that all isolates (Brazilian and African) that sporulated on mummified mites were amplified with the first primer pair confirming their Neozygites tanajoae identity. The second pair amplified DNA from all the Brazilian isolates, but did not amplify any DNA samples from the African isolates. None of the two primers showed amplification neither from any of the non-sporulating mite extracts nor from the dead uninfected mites used as negative controls. We confirmed that the two primer pairs tested are suitable for the detection and differential identification of N. tanajoae isolates from Brazil and Africa and that they are useful to monitor the establishment and spread of the Brazilian isolates of N. tanajoae introduced into Benin or into other African countries for improvement of CGM biocontrol.

Flow rate sprinkler development for site-specific irrigation

Due to the rapid depletion of water resources, water must be used more efficiently in agriculture to maintain current levels of yield in irrigated areas. The efficiency of irrigation systems can be increased by adjusting the amount of water applied to specific conditions of soil and crop, which may vary in a field. Taking into account spatial and temporal variability, it is evident that an equipment capable of providing different irrigation levels is necessary to meet the water requirement of the soil. This work aims to develop and evaluate a flow rate sprinkler to be used in center pivots or linear moving irrigation systems, with potential for utilization in irrigation scheduling. A prototype was developed by duplicating its calibrations, and discharge coefficient adjustment was carried out in the laboratory. To predict the flow rate, a successful model that represented the operation of the flow rate sprinkler was established. The calibration of the flow rate sprinkler prototype showed satisfactory statistical and technical results. Automation of the prototype was achieved by driving a step motor using communication from the parallel port of a microcomputer, which was controlled by a software developed for this purpose. The results were satisfactory and technically feasible.