Exercise Intensity, Inflammatory Signaling, and Insulin Resistance in Obese Rats

DA SILVA, A. S. R., J. R. PAULI, E. R. ROPELLE, A. G. OLIVEIRA, D. E. CINTRA, C. T. DE SOUZA, L. A. VELLOSO, J. B. C. CARVALHEIRA, and M. J. A. SAAD. Exercise Intensity, Inflammatory Signaling, and Insulin Resistance in Obese Rats. Med. Sci. Sports Exerc., Vol. 42, No. 12, pp. 2180-2188, 2010. Purpose: To evaluate the effects of intensity of exercise on insulin resistance and the expression of inflammatory proteins in the skeletal muscle of diet-induced obese (DIO) rats after a single bout of exercise. Methods: In the first exercise protocol, the rats swam for two 3-h bouts, separated by a 45-min rest period (with 6 h in duration-DIO + EXE), and in the second protocol, the rats were exercised with 45 min of swimming at 70% of the maximal lactate steady state-MLSS (DIO + MLSS). Results: Our data demonstrated that both protocols of exercise increased insulin sensitivity and increased insulin-stimulated tyrosine phosphorylation of insulin receptor and insulin receptor substrate 1 and serine phosphorylation of protein kinase B in the muscle of DIO rats by the same magnitude. In parallel, both exercise protocols also reduced protein tyrosine phosphatase 1B activity and insulin receptor substrate 1 serine phosphorylation, with concomitant reduction in c-jun N-terminal kinase and I kappa B kinase activities in the muscle of DIO rats in a similar fashion. Conclusions: Thus, our data demonstrate that either exercise protocols with low intensity and high volume or exercise with moderate intensity and low volume represents different strategies to restore insulin sensitivity with the same efficacy.

Stability analysis of core-annular flow and neutral stability wave number

A general transition criterion is proposed in order to locate the core-annular flow pattern in horizontal and vertical oil-water flows. It is based on a rigorous one-dimensional two-fluid model of liquid-liquid two-phase flow and considers the existence of critical interfacial wave numbers related to a non-negligible interfacial tension term to which the linear stability theory still applies. The viscous laminar-laminar flow problem is fully resolved and turbulence effects on the stability are analyzed through experimentally obtained shape factors. The proposed general transition criterion includes in its formulation the inviscid Kelvin-Helmholtz`s discriminator. If a theoretical maximum wavelength is considered as a necessary condition for stability, a stability criterion in terms of the Eotvos number is achieved. Effects of interfacial tension, viscosity ratio, density difference, and shape factors on the stability of core-annular flow are analyzed in detail. The more complete modeling allowed for the analysis of the neutral-stability wave number and the results strongly suggest that the interfacial tension term plays an indispensable role in the correct prediction of the stable region of core-annular flow pattern. The incorporation of a theoretical minimum wavelength into the transition model produced significantly better results. The criterion predictions were compared with recent data from the literature and the agreement is encouraging. (C) 2007 American Institute of Chemical Engineers.

Single Axis Controlled Hybrid Magnetic Bearing for Left Ventricular Assist Device: Hybrid Core and Closed Magnetic Circuit

In previous studies, we presented main strategies for suspending the rotor of a mixed-flow type (centrifugal and axial) ventricular assist device (VAD), originally presented by the Institute Dante Pazzanese of Cardiology (IDPC), Brazil. Magnetic suspension is achieved by the use of a magnetic bearing architecture in which the active control is executed in only one degree of freedom, in the axial direction of the rotor. Remaining degrees of freedom, excepting the rotation, are restricted only by the attraction force between pairs of permanent magnets. This study is part of a joint project in development by IDPC and Escola Politecnica of Sao Paulo University, Brazil. This article shows advances in that project, presenting two promising solutions for magnetic bearings. One solution uses hybrid cores as electromagnetic actuators, that is, cores that combine iron and permanent magnets. The other solution uses actuators, also of hybrid type, but with the magnetic circuit closed by an iron core. After preliminary analysis, a pump prototype has been developed for each solution and has been tested. For each prototype, a brushless DC motor has been developed as the rotor driver. Each solution was evaluated by in vitro experiments and guidelines are extracted for future improvements. Tests have shown good results and demonstrated that one solution is not isolated from the other. One complements the other for the development of a single-axis-controlled, hybrid-type magnetic bearing for a mixed-flow type VAD.

Extension of the core map of common bean with EST-SSR, RGA, AFLP, and putative functional markers

Microsatellites and gene-derived markers are still underrepresented in the core molecular linkage map of common bean compared to other types of markers. In order to increase the density of the core map, a set of new markers were developed and mapped onto the RIL population derived from the `BAT93` x `Jalo EEP558` cross. The EST-SSR markers were first characterized using a set of 24 bean inbred lines. On average, the polymorphism information content was 0.40 and the mean number of alleles per locus was 2.7. In addition, AFLP and RGA markers based on the NBS-profiling method were developed and a subset of the mapped RGA was sequenced. With the integration of 282 new markers into the common bean core map, we were able to place markers with putative known function in some existing gaps including regions with QTL for resistance to anthracnose and rust. The distribution of the markers over 11 linkage groups is discussed and a newer version of the common bean core linkage map is proposed.

Establishing a soybean germplasm core collection

Core collections are of strategic importance as they allow the use of a small part of a germplasm collection that is representative of the total collection. The objective of this study was to develop a soybean core collection of the USDA Soybean Germplasm Collection by comparing the results of random, proportional, logarithmic, multivariate proportional and multivariate logarithmic sampling strategies. All but the random sampling strategy used stratification of the entire collection based on passport data and maturity group classification. The multivariate proportional and multivariate logarithmic strategies made further use of qualitative and quantitative trait data to select diverse accessions within each stratum. The 18 quantitative trait data distribution parameters were calculated for each core and for the entire collection for pairwise comparison to validate the sampling strategies. All strategies were adequate for assembling a core collection. The random core collection best represented the entire collection in statistical terms. Proportional and logarithmic strategies did not maximize statistical representation but were better in selecting maximum variability. Multivariate proportional and multivariate logarithmic strategies produced the best core collections as measured by maximum variability conservation. The soybean core collection was established using the multivariate proportional selection strategy. (C) 2010 Elsevier B.V. All rights reserved.

Effects of oral supplementation with glutamine and alanyl-glutamine on glutamine, glutamate, and glutathione status in trained rats and subjected to long-duration exercise

Objective: We investigated the effect of supplementation with the dipeptide L-alanyl-L-glutamine (DIP) and a solution containing L-glutamine and L-alanine, both in the free form, on the plasma and tissue concentrations of glutamine, glutamate, and glutathione (GSH) in rats subjected to long-duration exercise. Methods: Rats were subjected to sessions of swim training. Twenty-one days before sacrifice, the animals were supplemented with DIP (1.5 g/kg, n = 6), a solution of free L-glutamine (1 g/kg) and free L-alanine (0.61 g/kg; GLN + ALA, n = 6), or water (CON, n = 6). Animals were sacrificed before (TR, n = 6) or after (LD, n = 6) long-duration exercise. Plasma concentrations of glutamine, glutamate, glucose, and ammonia and liver and muscle concentrations of glutamine, glutamate, and reduced and oxidized (GSSG) GSH were measured. Results: Higher concentrations of plasma glutamine were found in the DIP-TR and GLN + ALA-TR groups. The CON-LD group showed hyperammonemia, whereas the DIP-LD and GLN + ALA-LD groups exhibited lower concentrations of ammonia. Higher concentrations of glutamine, glutamate, and GSH/GSSG in the soleus muscle and GSH and GSH/GSSG in the liver were observed in the DIP-TR and GLN + ALA-TR groups. The DIP-LD and GLN + ALA-LD groups exhibited higher concentrations of GSH and GSH/GSSG in the soleus muscle and liver compared with the CON-LD group. Conclusion: Chronic oral administration of DIP and free GLN + ALA before long-duration exercise represents an effective source of glutamine and glutamate, which may increase muscle and liver stores of GSH and improve the redox state of the cell. (C) 2009 Published by Elsevier Inc.

A convergent approach for the generation of dendrimers containing the [Ru3O(CH3COO)(6)] electroactive core

We report on a convergent approach for the generation of dendrimers containing the [Ru3O(aC)(6)] electroactive core, of great interest as multielectron transfer catalysts. The proposed strategy is based on the generation of the trimeric complex [(Ru3O(ac)(6)(4-pic)(2)(pz))2-mu(2)-Ru3O(ac)(6)(CH3OH)](3+) (ac = acetate, 4-pic = 4-methylpyridine, pz = pyrazine). In this complex, the labile CH3OH ligand can be displaced by the bridging pyrazine ligand of [Ru3O(ac)(6)(pz)3](0), leading to the self-assembly of the [{[Ru3O(ac)(6)(4-pic)(2)(pz)](2)-mu(2)-Ru3O(ac)(6)(pz)}(3)- mu(3)-Ru3O(ac)(6)](n+) dendrimer containing 30 ruthenium atoms. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).

Increase of core temperature induced by corticotropin-releasing factor and urocortin: A comparative study

This study compared the ability of CRF and UCN1 to induce a thermoregulatory response when centrally injected into rats. The effects of antipyretic drugs and CRF receptor antagonists (CRF(1) and CRF(2)) on the temperature (T) changes induced by these peptides were also investigated. Rectal (rT) and tail skin (T(sk)) temperatures were measured with a thermistor probe while body (bT) temperature was measured with a battery-operated biotelemetry transmitter in male Wistar rats (200 g) every 30 min over a period of 6 h, after intracerebroventricular (i.c.v.) injection of 1 nmol of either CRF or UCN1. Rats were pre-treated with indomethacin (2 mg kg(-1), i.p.) or celecoxib (5 mg kg(-1), p.o.), dexamethasone (0.5 mg kg(-1), s.c.), astressin (a CRF(1)/CRF(2) antagonist, 7 nmol, icy.) or antalarmin (a CRF(1) antagonist, 20 mg kg 1, i.p.). The increase in body temperature induced by CRF was accompanied by a reduction in T(sk) while the response induced by UCN1 was accompanied by an elevation in T(sk). Indomethacin or celecoxib did not change the increases in rT caused by either CRF or UCN1. Although dexamethasone attenuated the increase in rectal temperature in response to CRF, dexamethasone did not modify the response induced by UCN1. Astressin blocked the UCN1-induced hyperthermia and reduced CRF-induced fever. Antalarmin did not modify the hyperthermia in response to UCN1, but reduced the fever evoked by CRF. This study demonstrated that CRF by acting on the CRF(1) receptor induces a prostaglandin-independent fever which seems to depend, at least in part, on the synthesis of other mediators while UCN1 acts on the CRF(2) receptor, promoting a hyperthermic response which seems to be independent on synthesis/release of any mediator. (C) 2010 Elsevier B.V. All rights reserved.

Involvement of dopaminergic mechanisms in the nucleus accumbens core and shell subregions in the expression of fear conditioning

The involvement of dopamine (DA) mechanisms in the nucleus accumbens (NAC) in fear conditioning has been proposed by many studies that have challenged the view that the NAC is solely involved in the modulation of appetitive processes. However, the role of the core and shell subregions of the NAC in aversive conditioning remains unclear. The present study examined DA release in these NAC subregions using microdialysis during the expression of fear memory. Guide cannulae were implanted in rats in the NAC core and shell. Five days later, the animals received 10 footshocks (0.6 mA, 1 s duration) in a distinctive cage A (same context). On the next day, dialysis probes were inserted through the guide cannulae into the NAC core and shell subregions, and the animals were behaviorally tested for fear behavior either in the same context (cage A) or in a novel context (cage B). Dialysates were collected every 5 min for 90 min and analyzed by high-performance liquid chromatography. The rats exhibited a significant fear response in cage A but not in cage B. Moreover, increased DA levels in both NAC subregions were observed 5-25 min after the beginning of the test when the animals were tested in the same context compared with accumbal DA levels from rats tested in the different context. These findings Suggest that DA mechanisms in both the NAC core and shell may play an important role in the expression of contextual fear memory. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64

Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its non-invasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective ""CORE-64"" trial (""Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors""). This multi-centre trial was unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.

Coronary Artery Stenoses: Accuracy of 64-Detector Row CT Angiography in Segments with Mild, Moderate, or Severe Calcification-A Subanalysis of the CORE-64 Trial

Purpose: To evaluate the influence of cross-sectional arc calcification on the diagnostic accuracy of computed tomography (CT) angiography compared with conventional coronary angiography for the detection of obstructive coronary artery disease (CAD). Materials and Methods: Institutional Review Board approval and written informed consent were obtained from all centers and participants for this HIPAA-compliant study. Overall, 4511 segments from 371 symptomatic patients (279 men, 92 women; median age, 61 years [interquartile range, 53-67 years]) with clinical suspicion of CAD from the CORE-64 multi-center study were included in the analysis. Two independent blinded observers evaluated the percentage of diameter stenosis and the circumferential extent of calcium (arc calcium). The accuracy of quantitative multidetector CT angiography to depict substantial (>50%) stenoses was assessed by using quantitative coronary angiography (QCA). Cross-sectional arc calcium was rated on a segment level as follows: noncalcified or mild (<90 degrees), moderate (90 degrees-180 degrees), or severe (>180 degrees) calcification. Univariable and multivariable logistic regression, receiver operation characteristic curve, and clustering methods were used for statistical analyses. Results: A total of 1099 segments had mild calcification, 503 had moderate calcification, 338 had severe calcification, and 2571 segments were noncalcified. Calcified segments were highly associated (P < .001) with disagreement between CTA and QCA in multivariable analysis after controlling for sex, age, heart rate, and image quality. The prevalence of CAD was 5.4% in noncalcified segments, 15.0% in mildly calcified segments, 27.0% in moderately calcified segments, and 43.0% in severely calcified segments. A significant difference was found in area under the receiver operating characteristic curves (noncalcified: 0.86, mildly calcified: 0.85, moderately calcified: 0.82, severely calcified: 0.81; P < .05). Conclusion: In a symptomatic patient population, segment-based coronary artery calcification significantly decreased agreement between multidetector CT angiography and QCA to detect a coronary stenosis of at least 50%.

The possible role of physical exercise on the treatment of idiopathic inflammatory myopathies

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases that share some symptoms such as muscular weakness and inflammation of skeletal muscle. Complete recovery of muscle function with pharmacological treatment does not always occur, suggesting that physical inability is a great concern for these patients. In this context, it has been speculated that physical exercise could result in functional benefits to patients with IIM, leading to an improvement in quality of life. In fact, recent studies of polymyositis (PM) and dermatomyositis (DM) support the notion that exercise training improves or at least stabilizes muscle strength and functional ability without inducing disease flares. Importantly, these benefits were observed not only during the chronic phase, but also in the course of active disease. This positive effect was found to be long term, as demonstrated by a six-month significant improvement in exercise capacity and strength. Together, these findings indicate that a well controlled exercise program can be recommended for patients with DM and PM. The optimal exercise modality training and the underlying mechanism for this encouraging response remain to be determined in future studies. (C) 2008 Elsevier B.V. All rights reserved.

Aerobic Exercise Improves Reverse Cholesterol Transport in Cholesteryl Ester Transfer Protein Transgenic Mice

We analyzed the effect of a 6-week aerobic exercise training program on the in vivo macrophage reverse cholesterol transport (RCT) in human cholesteryl ester transfer protein (CETP) transgenic (CETP-tg) mice. Male CETP-tg mice were randomly assigned to a sedentary group or a carefully supervised exercise training group (treadmill 15 m/min, 30 min sessions, five sessions per week). The levels of plasma lipids were determined by enzymatic methods, and the lipoprotein profile was determined by fast protein liquid chromatography (FPLC). CETP activity was determined by measuring the transfer rate of (14)C-cholesterol from HDL to apo-B containing lipoproteins, using plasma from CETP-tg mice as a source of CETP. The reverse cholesterol transport was determined in vivo by measuring the [(3)H]-cholesterol recovery in plasma and feces (24 and 48 h) and in the liver (48 h) following a peritoneal injection of [(3)H]-cholesterol labeled J774-macrophages into both sedentary and exercise trained mice. The protein levels of liver receptors were determined by immunoblot, and the mRNA levels for liver enzymes were measured using RT-PCR. Exercise training did not significantly affect the levels of plasma lipids or CETP activity. The HDL fraction assessed by FPLC was higher in exercise-trained compared to sedentary mice. In comparison to the sedentary group, a greater recovery of [(3)H]-cholesterol from the injected macrophages was found in the plasma, liver and feces of exercise-trained animals. The latter occurred even with a reduction in the liver CYP7A1 mRNA level in exercised trained animals. Exercise training increased the liver LDL receptor and ABCA-1 protein levels, although the SR-BI protein content was unchanged. The RCT benefit in CETP-tg mice elicited by exercise training helps to elucidate the role of exercise in the prevention of atherosclerosis in humans.

Cardiovascular, metabolic and hormonal responses to the progressive exercise performed to exhaustion in patients with type 2 diabetes treated with metformin or glyburide

Objectives: To evaluate the effects of Metformin and Glyburide on cardiovascular, metabolic and hormonal parameters during progressive exercise performed to exhaustion in the post-prandial state in women with type 2 diabetes (T2DM). Design and Methods: Ten T2DM patients treated with Metformin (M group), 10 with Glyburide (G group) and 10 age-paired healthy subjects exercised on a bicycle ergometer up to exercise peak. Cardiovascular and blood metabolic and hormonal parameters were measured at times -60 min, 0 min, exercise end, and at 10 and 20 minutes of recovery phase. Thirty minutes before the exercise, a standard breakfast was provided to all participants. The diabetic patients took Metformin or Glyburide before or with meal. Results: Peak oxygen uptake (VO2) was lower in patients with diabetes. Plasma glucose levels remained unchanged, but were higher in both diabetic groups. Patients with diabetes also presented lower insulin levels after meals and higher glucagon levels at exercise peak than C group. Serum cortisol levels were higher in G than M group at exercise end and recovery phase. Lactate levels were higher in M than G group at fasting and in C group at exercise peak. Nor epinephrine, GH and FFA responses were similar in all 3 groups. Conclusion: Progressive exercise performed to exhaustion, in the post-prandial state did not worsen glucose control during and after exercise. The administration of the usual dose of Glyburide or Metformin to T2DM patients did not influence the cardiovascular, metabolic and hormonal response to exercise.

Effects of carbohydrate supplementation on competitive runners undergoing overload training followed by a session of intermittent exercise

This study evaluated the effects of a micro cycle of overload training (1st-8th day) on metabolic and hormonal responses in male runners with or without carbohydrate supplementation and investigated the cumulative effects of this period on a session of intermittent high-intensity running and maximum-performance-test (9th day). The participants were 24 male runners divided into two groups, receiving 61% of their energy intake as CHO (carbohydrate-group) and 54% in the control-group (CON). The testosterone was higher for the CHO than the CON group after the overload training (694.0 +/- A 54.6 vs. CON 610.8 +/- A 47.9 pmol/l). On the ninth day participants performed 10 x 800 m at mean 3 km velocity. An all-out 1000 m running was performed before and after the 10 x 800 m. Before, during, and after this protocol, the runners received solution containing CHO or the CON equivalent. The performance on 800 m series did not differ in either group between the first and last series of 800 m, but for the all-out 1000 m test the performance decrement was lower for CHO group (5.3 +/- A 1.0 vs. 10.6 +/- A 1.3%). The cortisol concentrations were lower in the CHO group in relation to CON group (22.4 +/- A 0.9 vs. 27.6 +/- A 1.4 pmol/l) and the IGF1/IGFBP3 ratio increased 12.7% in the CHO group. During recovery, blood glucose concentrations remained higher in the CHO group in comparison with the CON group. It was concluded that CHO supplementation possibly attenuated the suppression of the hypothalamic-pituitary-gonadal axis and resulted in less catabolic stress, and thus improved running performance.