Beta-alanine (Carnosyn (TM)) supplementation in elderly subjects (60-80 years): effects on muscle carnosine content and physical capacity

The aim of this study was to investigate the effects of beta-alanine supplementation on exercise capacity and the muscle carnosine content in elderly subjects. Eighteen healthy elderly subjects (60-80 years, 10 female and 4 male) were randomly assigned to receive either beta-alanine (BA, n = 12) or placebo (PL, n = 6) for 12 weeks. The BA group received 3.2 g of beta-alanine per day (2 x 800 mg sustained-release Carnosyn (TM) tablets, given 2 times per day). The PL group received 2 x (2 x 800 mg) of a matched placebo. At baseline (PRE) and after 12 weeks (POST-12) of supplementation, assessments were made of the muscle carnosine content, anaerobic exercise capacity, muscle function, quality of life, physical activity and food intake. A significant increase in the muscle carnosine content of the gastrocnemius muscle was shown in the BA group (+85.4%) when compared with the PL group (+7.2%) (p = 0.004; ES: 1.21). The time-to-exhaustion in the constant-load submaximal test (i.e., TLIM) was significantly improved (p = 0.05; ES: 1.71) in the BA group (+36.5%) versus the PL group (+8.6%). Similarly, time-to-exhaustion in the incremental test was also significantly increased (p = 0.04; ES 1.03) following beta-alanine supplementation (+12.2%) when compared with placebo (+0.1%). Significant positive correlations were also shown between the relative change in the muscle carnosine content and the relative change in the time-to-exhaustion in the TLIM test (r = 0.62; p = 0.01) and in the incremental test (r = 0.48; p = 0.02). In summary, the current data indicate for the first time, that beta-alanine supplementation is effective in increasing the muscle carnosine content in healthy elderly subjects, with subsequent improvement in their exercise capacity.

Hemolytic activity of alternative complement pathway as an indicator of innate immunity in pacu (Piaractus mesopotamicus)

The objective of this study was to evaluate the methodology to establish the hemolytic activity of alternative complement pathway as an indicator of the innate immunity in Brazilian fish pacu (Piaractus mesopotamicus), in addition to verifying the influence of beta-glucan as an immunostimulant. Fish were fed with diets containing 0, 0.1 and 1% beta-glucan, during seven days, and then inoculated with Aeromonas hydrophila. Seven days after the challenge, they were bled for serum extraction. The methodology consisted of a kinetic assay that allows calculating the required time for serum proteins of the complement to promote 50% lysis of a rabbit red blood cell suspension. The method developed in mammals was successfully applied for pacu and determined that the hemolytic activity of the proteins of the complement system (alternative pathway) increased after the pathogen challenge, but was not influenced by the beta-glucan treatment.

Interaction between bradykinin potentiating nonapeptide (BPP9a) and beta-cyclodextrin: A structural and thermodynamic study

Herein, we demonstrate the physical and chemical characterizations of the supramolecular complex formed between beta-cyclodextrin (beta CD) and bradykinin potentiating nonapeptide (BPP9a), an endogenous toxin found in Bothrops jararaca. Circular dichroism results indicate a conformational change in the BPP9a secondary structure upon its complexation with beta CD. Nuclear magnetic resonance results, mainly from NOESY experiments, and theoretical calculations showed a favorable interaction between the tryptophan residue of BPP9a and the beta CD cavity. Thermodynamic inclusion parameters were investigated by isothermal titration calorimetry, demonstrating that beta CD/BPP9a complex formation is an exothermic process that results in a reduction in entropy. Additionally, in vitro degradation study of BPP9a against trypsin (37 degrees C, pH 7.2) showed higher stability of peptide in presence of beta CD. This beta CD/BPP9a complex, which presents new chemical properties arising from the peptide inclusion process, may be useful as an antihypertensive drug in oral pharmaceutical formulations. (C) 2011 Elsevier B.V. All rights reserved.

A comparative thermoluminescence and electron spin resonance study of synthetic carbonated A-type hydroxyapatite

Intensity of the 150 degrees C thermoluminescence peak of beta-irradiated carbonated synthetic A-type hydroxyapatite is approximately 12 times higher than that of the noncarbonated material. Deconvolution of the glow curve showed that this peak is a result of a trap distribution. An attempt was made to relate this thermoluminescence peak enhanced by carbonation with the ESR signal of the CO2- radical in natural or synthetic hydroxyapatite. (C) 2011 Elsevier Ltd. All rights reserved.

beta(1) Adrenergic receptor is key to cold- and diet-induced thermogenesis in mice

Brown adipose tissue (BAT) is predominantly regulated by the sympathetic nervous system (SNS) and the adrenergic receptor signaling pathway. Knowing that a mouse with triple beta-receptor knockout (KO) is cold intolerant and obese, we evaluated the independent role played by the beta(1) isoform in energy homeostasis. First, the 30 min i.v. infusion of norepinephrine (NE) or the beta(1) selective agonist dobutamine (DB) resulted in similar interscapular BAT (iBAT) thermal response in WT mice. Secondly, mice with targeted disruption of the beta(1) gene (KO of beta(1) adrenergic receptor (beta 1KO)) developed hypothermia during cold exposure and exhibited decreased iBAT thermal response to NE or DB infusion. Thirdly, when placed on a high-fat diet (HFD; 40% fat) for 5 weeks, beta 1KO mice were more susceptible to obesity than WT controls and failed to develop diet-induced thermogenesis as assessed by BAT Ucp1 mRNA levels and oxygen consumption. Furthermore, beta 1KO mice exhibited fasting hyperglycemia and more intense glucose intolerance, hypercholesterolemia, and hypertriglyceridemia when placed on the HFD, developing marked non-alcoholic steatohepatitis. In conclusion, the beta(1) signaling pathway mediates most of the SNS stimulation of adaptive thermogenesis. Journal of Endocrinology (2012) 214, 359-365

Etiological diagnosis reduces the use of antibiotics in infants with bronchiolitis

OBJECTIVE: Acute bronchiolitis is a leading cause of infant hospitalization and is most commonly caused by respiratory syncytial virus. Etiological tests are not required for its diagnosis, but the influence of viral screening on the therapeutic approach for acute bronchiolitis remains unclear. METHODS: A historical cohort was performed to assess the impact of viral screening on drug prescriptions. The study included infants up to one year of age who were hospitalized for bronchiolitis. Virus screening was performed using immunofluorescence assays in nasopharyngeal aspirates. The clinical data were obtained from the patients' medical records. Therapeutic changes were considered to be associated with viral screening when made within 24 hours of the release of the results. RESULTS: The frequency of prescriptions for beta agonists, corticosteroids and antibiotics was high at the time of admission and was similar among the 230 patients. The diagnosis of pneumonia and otitis was associated with the introduction of antibiotics but did not influence antibiotics maintenance after the results of the virus screening were obtained. Changes in the prescriptions were more frequent for the respiratory syncytial virus patients compared to patients who had negative viral screening results (p=0.004), especially the discontinuation of antibiotics (p<0.001). The identification of respiratory syncytial virus was associated with the suspension of antibiotics (p=0.003), even after adjusting for confounding variables (p=0.004); however, it did not influence the suspension of beta-agonists or corticosteroids. CONCLUSION: The identification of respiratory syncytial virus in infants with bronchiolitis was independently associated with the discontinuation of antibiotics during hospitalization.

Impaired beta-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced K-Ca channel activity

beta-Adrenoceptor (beta-AR)-mediated relaxation plays an important role in the regulation of vascular tone. beta-AR-mediated vascular relaxation is reduced in various disease states and aging. We hypothesized that beta-AR-mediated vasodilatation is impaired in DOCA-salt hypertension due to alterations in the cAMP pathway. beta-AR-mediated relaxation was determined in small mesenteric arteries from DOCA-salt hypertensive and control uninephrectomized (Uni) rats. To exclude nitric oxide (NO) and cyclooxygenase (COX) pathways, relaxation responses were determined in the presence of L-NNA and indomethacin, NO synthase inhibitor and COX inhibitors, respectively. Isoprenaline (ISO)-induced relaxation was reduced in arteries from DOCA-salt compared to Uni rats. Protein kinase A (PKA) inhibitors (H89 or Rp-cAMPS) or adenylyl cyclase inhibitor (SQ22536) did not abolish the difference in ISO-induced relaxation between the groups. Forskolin (adenylyl cyclase activator)-induced relaxation was similar between the groups. The inhibition of IKCa/SKCa channels (TRAM-34 plus UCL1684) or BKCa channels (iberiotoxin) reduced ISO-induced relaxation only in Uni rats and abolished the relaxation differences between the groups. The expression of SKCa channel was decreased in DOCA-salt arteries. The expression of BKCa channel a subunit was increased whereas the expression of BKCa channel p subunit was decreased in DOCA-salt arteries. The expression of receptor for activated C kinase 1 (RACK1), which is a binding protein for BKG, channel and negatively modulates its activity, was increased in DOCA-salt arteries. These results suggest that the impairment of beta-AR-mediated relaxation in DOCA-salt mesenteric arteries may be attributable to altered IKCa/SKCa and/or BKCa channels activities rather than cAMP/PKA pathway. Impaired beta-AR-stimulated BKCa channel activity may be due to the imbalance between its subunit expressions and RACK1 upregulation. (C) 2012 Elsevier Ltd. All rights reserved.

Phylogeography of an Atlantic forest passerine reveals demographic stability through the last glacial maximum

In this study we analyzed the phylogeographic pattern and historical demography of an endemic Atlantic forest (AF) bird, Basileuterus leucoblepharus, and test the influence of the last glacial maximum (LGM) on its population effective size using coalescent simulations. We address two main questions: (i) Does B. leucoblepharus present population genetic structure congruent with the patterns observed for other AF organisms? (ii) How did the LGM affect the effective population size of B. leucoblepharus? We sequenced 914 bp of the mitochondrial gene cytochrome b and 512 bp of the nuclear intron 5 of beta-fibrinogen of 62 individuals from 15 localities along the AF. Both molecular markers revealed no genetic structure in B. leucoblepharus. Neutrality tests based on both loci showed significant demographic expansion. The extended Bayesian skyline plot showed that the species seems to have experienced demographic expansion starting around 300,000 years ago, during the late Pleistocene. This date does not coincide with the LGM and the dynamics of population size showed stability during the LGM. To further test the effect of the LGM on this species, we simulated seven demographic scenarios to explore whether populations suffered specific bottlenecks. The scenarios most congruent with our data were population stability during the LGM with bottlenecks older than this period. This is the first example of an AF organism that does not show phylogeographic breaks caused by vicariant events associated to climate change and geotectonic activities in the Quaternary. Differential ecological, environmental tolerances and habitat requirements are possibly influencing the different evolutionary histories of these organisms. Our results show that the history of organism diversification in this megadiverse Neotropical forest is complex. Crown Copyright (c) 2012 Published by Elsevier Inc. All rights reserved.

Regulation of neurogenesis and gliogenesis of retinoic acid-induced P19 embryonal carcinoma cells by P2X2 and P2X7 receptors studied by RNA interference

Embryonic carcinoma cells are widely used models for studying the mechanisms of proliferation and differentiation occurring during early embryogenesis. We have now investigated how down-regulation of P2X2 and P2X7 receptor expression by RNA interference (RNAi) affects neural differentiation and phenotype specification of P19 embryonal carcinoma cells. Wild-type P19 embryonal carcinoma cells or cells stably expressing shRNAs targeting P2X2 or P2X7 receptor expression were induced to differentiate into neurons and glial cells in the presence of retinoic acid. Silencing of P2X2 receptor expression along differentiation promoted cell proliferation and an increase in the percentage of cells expressing glial-specific GFAP, while the presence of beta-3 tubulin-positive cells diminished at the same time. Proliferation induction in the presence of stable anti-P2X2 receptor RNAi points at a mechanism where glial proliferation is favored over growth arrest of progenitor cells which would allow neuronal maturation. Differently from the P2X2 receptor, inhibition of P2X7 receptor expression during neural differentiation of P19 cells resulted in a decrease in cell proliferation and GFAP expression, suggesting the need of functional P2X7 receptors for the progress of gliogenesis. The results obtained in this study indicate the importance of purinergic signaling for cell fate determination during neural differentiation, with P2X2 and P2X7 receptors promoting neurogenesis and gliogenesis, respectively. The shRNAs down-regulating P2X2 or P2X7 receptor gene expression, developed during this work, present useful tools for studying mechanisms of neural differentiation in other stem cell models. (C) 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Summary of the II Brazilian Guideline Update on Acute Heart Failure 2009/2011

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

beta-ZnMoO4 microcrystals synthesized by the surfactant-assisted hydrothermal method: Growth process and photoluminescence properties

In this communication, we investigate the effect of different surfactants: cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone (PVP-K40) on the growth process of zinc molybdate (beta-ZnMoO4) microcrystals synthesized under hydrothermal conditions at 140 degrees C for 8 h. These microcrystals were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and photoluminescence (PL) measurements. XRD patterns proved that these crystals are monophasic and present a wolframite-type monoclinic structure. FE-SEM images revealed that the surfactants modified the crystal shapes, suggesting the occurrence of distinct crystal growth processes. The CTAB cationic surfactant promotes the hindrance of small nuclei that leads to the formation of rectangle-like crystals, SDS anionic surfactant induces a growth of irregular hexagons with several porous due to considerable size effect of counter-ions on the crystal facets, PVP-K40 non-ionic surfactant allows a reduction in size and thickness of plate-like crystals, while without surfactants have the formation of irregular plate-like crystals. Finally, the PL properties of beta-ZnMoO4 microcrystals were explained by means of different shape/size, surface defects and order-disorder into lattice. (C) 2011 Elsevier B.V. All rights reserved.

Conjunctival Autograft Alone or Combined With Adjuvant Beta-Radiation? A Randomized Clinical Trial

Purpose: To evaluate the effectiveness and safety of postoperative low single-dose of beta-irradiation (beta-RT) in pterygium comparing conjunctival autograft (CAG) surgery with CAG plus adjuvant beta-RT in a randomized clinical trial. Methods: This trial was designed as a prospective, randomized, single-center study. Surgery was performed in all cases according to the CAG technique. One hundred and eight pterygia were post-operatively randomized to CAG + beta-RT or CAGalone. In the case of beta-RT, a (90) Sr eye applicator was used to deliver 10 Gy to the sclera surface at a dose rate of between 200 and 250 cGy/min. After treatment, both an ophthalmologist and a radiation oncologist performed the follow-up examinations. The accumulated data were analyzed using a group sequential test. Results: Between February 2008 and September 2008, 116 eyes with primary pterygium were operated on according to the trial protocol. Adjuvant treatment was performed within 24 h post-operatively. Eight patients were lost to follow-up, resulting in 108 patients who could be analyzed. At a mean follow-up of 18 months (range, 8-33), in the 54 eyes randomized to receive CAG + beta-RT, 5 relapses occurred compared with 12 recurrences in the 54 eyes in CAG, for a crude control rate of 90.8 % vs. 78%; p = 0.032, respectively. The treatment complications as hyperemia, total dehiscence of the autograft and dellen were significantly more frequent in the CAG (p < 0.05). The arm of beta-RT resulted in better cosmetic results and improves of symptoms than CAG. Conclusions: A low single-dose of beta-RT of 10 Gy after CAG surgery was a simple, effective, and safe treatment that reduced the risk of primary pterygium recurrence, improved symptoms after surgery, resulting in a better cosmetic effect than only CAG. (C) 2012 Elsevier Inc.

Expression of laminin-5 and integrins in actinic cheilitis and superficially invasive squamous cell carcinomas of the lip

The progression of carcinogenesis entails the detachment of cells, invasion and migration of neoplastic cells. Alterations in epithelial adhesion and basement membrane proteins might mediate the early stages of carcinogenesis. This study investigated the expression of adhesion molecules and the basement membrane protein laminin-5 in actinic cheilitis (AC) and incipient squamous cell carcinoma of the lower lip to understand early photocarcinogenesis. Ln-5 gamma 2 chain as well as alpha 3, beta 1 subunits of alpha 3 beta 1 heterodimer and beta 4 subunit of integrin alpha 6 beta 4 were evaluated by immunohistochemistry in 16 cases of AC and 16 cases of superficially invasive squamous cell carcinoma (SISCC). Most AC cases showed reduced expression of beta 1, beta 4 and alpha 3 integrins, and SISCCs lacked beta 1, beta 4 and alpha 3 integrins in the invasive front. AC cases were negative for the Ln-5 gamma 2 chain. Five cases of SISCC (31%) showed heterogeneous Ln-5 gamma 2 chain expression in the invasive front of the tumor. Integrin beta 1, beta 4 and alpha 3 expression is lost during the early stages of lip carcinogenesis. Expression of Ln-5 gamma 2 in the invasive front in cases and its correlation with tumor progression suggest that it mediates the acquisition of the migrating and invading epithelial cell phenotype. (C) 2012 Elsevier GmbH. All rights reserved.

Stem cell therapy for type 1 diabetes mellitus: a review of recent clinical trials

Stem cell therapy is one of the most promising treatments for the near future. It is expected that this kind of therapy can ameliorate or even reverse some diseases. With regard to type 1 diabetes, studies analyzing the therapeutic effects of stem cells in humans began in 2003 in the Hospital das Clínicas of the Faculty of Medicine of Ribeirão Preto - SP USP, Brazil, and since then other centers in different countries started to randomize patients in their clinical trials. Herein we summarize recent data about beta cell regeneration, different ways of immune intervention and what is being employed in type 1 diabetic patients with regard to stem cell repertoire to promote regeneration and/or preservation of beta cell mass.

Influence of nanoparticle size on the nonlinear optical properties of magnetite ferrofluids

The nonlinear index of refraction (n(2)) and the two-photon absorption coefficient (beta) of water-based ferrofluids made of magnetite nanocrystals of different sizes and with different coatings have been measured through the Z-scan technique, with ultrashort (femtoseconds) laser pulses. Their third-order susceptibility is calculated from the values of n(2) and beta. The influence of different particles' coatings and sizes on these nonlinear optical properties are investigated. The values of n(2) and beta depend more significantly on the nanoparticles' size than on the particular coating. We observe a decrease of beta as the nanoparticles' diameters decrease, although the optical gap is found to be the same for all samples. The results are interpreted considering modifications in the electronic orbital shape due to the particles' nanosize effect.