Role of a Novel Tetrodotoxin-Resistant Sodium Channel in the Nitrergic Relaxation of Corpus Cavernosum from the South American Rattlesnake Crotalus Durissus Terrificus

Introduction. Coitus in snakes may last up to 28 hours; however, the mechanisms involved are unknown. Aim. To evaluate the relevance of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-phosphodiesterase type 5 (PDE5) system in snake corpus cavernosum reactivity. Methods. Hemipenes were removed from anesthetized South American rattlesnakes (Crotalus durissus terrificus) and studied by light and scanning electronic microscopy. Isolated Crotalus corpora cavernosa (CCC) were dissected from the non-spiny region of the hemipenises, and tissue reactivity was assessed in organ baths. Main Outcome Measures. Cumulative concentration-response curves were constructed for acetylcholine (ACh), sodium nitroprusside (SNP), 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine (BAY 41-2272), and tadalafil in CCC precontracted with phenylephrine. Relaxation induced by electrical field stimulation (EFS) was also done in the absence and presence of N omega nitro-L-arginine methyl ester (L-NAME; 100 mu M), 1H-[1, 2, 4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 mu M) and tetrodotoxin (TTX; 1 mu M). Results. The hemipenes consisted of two functionally concentric corpora cavernosa, one of them containing radiating bundles of smooth muscle fibers (confirmed by alpha-actin immunostaining). Endothelial and neural nitric oxide synthases were present in the endothelium and neural structures, respectively; whereas soluble guanylate cyclase and PDE5 were expressed in trabecular smooth muscle. ACh and SNP relaxed isolated CCC, with the relaxations being markedly reduced by L-NAME and ODQ, respectively. BAY 41-2272 and tadalafil caused sustained relaxations with potency (pEC(50)) values of 5.84 +/- 0.17 and 5.10 +/- 0.08 (N = 3-4), respectively. In precontracted CCC, EFS caused frequency-dependent relaxations that lasted three times longer than those in mammalian CC. Although these relaxations were almost abolished by either L-NAME or ODQ, they were unaffected by TTX. In contrast, EFS-induced relaxations in marmoset CC were abolished by TTX. Conclusions. Rattlesnake CC relaxation is mediated by the NO-cGMP-PDE5 pathway in a manner similar to mammals. The novel TTX-resistant Na channel identified here may be responsible for the slow response of smooth muscle following nerve stimulation and could explain the extraordinary duration of snake coitus. Capel RO, Monica FZ, Porto M, Barillas S, Muscara MN, Teixeira SA, Arruda AMM, Pissinatti, L, Pissinatti A, Schenka AA, Antunes E, Nahoum C, Cogo JC, de Oliveira MA, and De Nucci G. Role of a novel tetrodotoxin-resistant sodium channel in the nitrergic relaxation of corpus cavernosum from the South American rattlesnake Crotalus durissus terrificus. J Sex Med 2011;8:1616-1625.

Macrophage suppression following phagocytosis of apoptotic neutrophils is mediated by the S100A9 calcium-binding protein

The clearance of apoptotic cells by phagocytes is a fundamental process during tissue remodeling and resolution of inflammation. In turn, the phagocytosis of apoptotic cells generates signals that suppress pro-inflammatory activation of macrophages. These events occur during the resolution phase of inflammation and therefore the malfunctioning of this process may lead to inflammation-related tissue damage. Here, we demonstrate that the calcium-binding protein S100A9, normally abundant in the cytoplasm of neutrophils and also released by apoptotic neutrophils, is involved in the suppression of macrophages after the uptake of apoptotic neutrophils. Both, spontaneous and induced production of inflammatory species (nitric oxide, hydrogen peroxide and TNF-alpha) as well as the phagocytic activity were inhibited when macrophages were in presence of apoptotic neutrophils, conditioned medium from neutrophil cultures or a peptide corresponding to the C-terminal region of S100A9 protein. On the other hand, macrophages kept in the conditioned medium of neutrophils that was previously depleted of S100A9 were shown to resume the activated status. Finally, we demonstrate that the calcium-binding property of S100A9 might play a role in the suppression process, since the stimulation of intracellular calcium release with ionomycin significantly reversed the effects of the uptake of apoptotic neutrophils in macrophages. In conclusion, we propose that S100A9 is a novel component of the regulatory mechanisms of inflammation, acting side-by-side with other suppressor factors generated upon ingestion of apoptotic cells. (C) 2009 Elsevier GmbH. All rights reserved.

Innovations in microinsurance: evidence from the Philippines

A popularidade e o interesse em microsseguro, especialmente nos países em desenvolvimento, tem aumentado nos últimos anos. Parte do sucesso se deve às inovações desenvolvidas principalmente para a indústria de microsseguros, que é bastante diferente do seguro tradicional. No entanto, há pouca informação sobre o impacto real dessas inovações em termos de aumento da demanda por microsseguro. Este estudo investiga quais as inovações de fato ajudaram a aumentar a demanda de microsseguros. Um método de estudo de caso qualitativo é aplicado sobre a MicroEnsure Filipinas , uma das empresas de microsseguro de maior sucesso no país. Os resultados mostram que as inovações precisam ser implementadas em vários aspectos de uma empresa de microsseguros para que elas sejam um meio eficaz de aumentar a demanda por microsseguro. As descobertas podem apoiar os gestores de microsseguros e formuladores de políticas na tomada de medidas para a criação de inovações de microsseguros benéficas em toda a Filipinas.

Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Combined Tevatron upper limit on gg -> H -> W+W- and constraints on the Higgs boson mass in fourth-generation fermion models

We combine results from searches by the CDF and D0 collaborations for a standard model Higgs boson (H) in the process gg -> H -> W+W- in p (p) over bar collisions at the Fermilab Tevatron Collider at root s = 1.96 TeV. With 4.8 fb(-1) of integrated luminosity analyzed at CDF and 5.4 fb(-1) at D0, the 95% confidence level upper limit on sigma(gg -> H) x B(H -> W+W-) is 1.75 pb at m(H) = 120 GeV, 0.38 pb at m(H) = 165 GeV, and 0.83 pb at m(H) = 200 GeV. Assuming the presence of a fourth sequential generation of fermions with large masses, we exclude at the 95% confidence level a standard-model-like Higgs boson with a mass between 131 and 204 GeV.

Macrophage suppression following phagocytosis of apoptotic neutrophils is mediated by the S100A9 calcium-binding protein

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Morphometric analysis of treatment effects of the Balters bionator in growing Class II patients

Objective: To investigate the effects of the standard (Class II) Balters bionator in growing patients with Class II malocclusion with mandibular retrusion by using morphometrics (thin-plate spline [TPS] analysis). Materials and Methods: Thirty-one Class II patients (17 male and 14 female) were treated with the Balters bionator (bionator group). Mean age at the start of treatment (T0) was 10.3 years, while it was 13 years at the end of treatment (T1). Mean treatment time was 2 years and 2 months. The control group consisted of 22 subjects (14 male and 8 female) with untreated Class II malocclusion. Mean age at T0 was 10.2 years, while it was 12.2 years at T1. The observation period lasted 2 years on average. TPS analysis evaluated statistical (permutation tests) differences in the craniofacial shape and size between the bionator and control groups. Results: Through TPS analysis (deformation grids) the bionator group showed significant shape changes in the mandible that could be described as a mandibular forward and downward displacement. The control group showed no statistically significant differences in the correction of Class II malocclusion. Conclusions: Bionator appliance is able to induce significant mandibular shape changes that lead to the correction of Class II dentoskeletal disharmony. © 2013 by The EH Angle Education and Research Foundation, Inc.

The effect of dimethyl sulfoxide (DMSO) on dentin bonding and nanoleakage of etch-and-rinse adhesives

Objective The objective was to examine the effect of a solvent dimethyl sulfoxide (DMSO) on resin-dentin bond durability, as well as potential functional mechanisms behind the effect. Methods Microtensile bond strength (μTBS) was evaluated in extracted human teeth in two separate experiments. Dentin specimens were acid-etched and assigned to pre-treatment with 0.5 mM (0.004%) DMSO as additional primer for 30 s and to controls with water pre-treatment. Two-step etch-and-rinse adhesive (Scotchbond 1XT, 3M ESPE) was applied and resin composite build-ups were created. Specimens were immediately tested for μTBS or stored in artificial saliva for 6 and 12 months prior to testing. Additional immediate and 6-month specimens were examined for interfacial nanoleakage analysis under SEM. Matrix metalloproteinase (MMP) inhibition by DMSO was examined with gelatin zymography. Demineralized dentin disks were incubated in 100% DMSO to observe the optical clearing effect. Results The use of 0.5 mM DMSO had no effect on immediate bond strength or nanoleakage. In controls, μTBS decreased significantly after storage, but increased significantly in DMSO-treated group. The control group had significantly lower μTBS than DMSO-group after 6 and 12 months. DMSO also eliminated the increase in nanoleakage seen in controls. 5% and higher DMSO concentrations significantly inhibited the gelatinases. DMSO induced optical clearing effect demonstrating collagen dissociation. Significance DMSO as a solvent may be useful in improving the preservation of long-term dentin-adhesive bond strength. The effect may relate to dentinal enzyme inhibition or improved wetting of collagen by adhesives. The collagen dissociation required much higher DMSO concentrations than the 0.5 mM DMSO used for bonding. © 2013 Academy of Dental Materials.

Serotonergic modulation in neuropathy induced by oxaliplatin: Effect on the 5HT(2C) receptor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Integrative aspects of the relationship between stress and heart rate variability

The literature indicates stress as a response of the organism to a stimulation that requires enormous efforts to adapt to the changes in the environment and the body. When an individual is subjected to stress, the autonomic nervous system is triggered, the sympathetic pathway is activated, and the parasympathetic system is suppressed, which exerts several effects on the cardiovascular system and affects heart rate variability. This research aimed to conduct a literature review to find and analyze the studies that address clearly the implications of stress on heart rate variability. The methodology employed was an active search in the databases SciELO, PubMed and Lilacs. The results were five articles, most of which suggest a relationship between stress and heart rate variability. We observed that the majority of the studies indicated a strong association between stress and cardiac autonomic activity. The stress is present in the daily activities of the population, especially in labor. The subject is vast, however, were observed in the references the effects of stress on the body making it vulnerable to diseases. Thus, this information may contribute to the aid of preventive strategies against stress and diseases of the cardiovascular system.

First detection of Leishmania infantum DNA within the brain of naturally infected dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The Role of Lipotoxicity in Smoke Cardiomyopathy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Low levels of taurine introgression in the current Brazilian Nelore and Gir indicine cattle populations

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Saving the Vaquita: Immediate Action, Not More Data

The recent likely extinction of the baiji (Chinese river dolphin [Lipotes vexillifer]) (Turvey et al. 2007) makes the vaquita (Gulf of California porpoise [Phocoena sinus]) the most endangered cetacean. The vaquita has the smallest range of any porpoise, dolphin, or whale and, like the baiji, has long been threatened primarily by accidental deaths in fishing gear (bycatch) (Rojas-Bracho et al. 2006). Despite repeated recommendations from scientific bodies and conservation organizations, no effective actions have been taken to remove nets from the vaquita’s environment. Here, we address three questions that are important to vaquita conservation: (1) How many vaquitas remain? (2) How much time is left to find a solution to the bycatch problem? and (3) Are further abundance surveys or bycatch estimates needed to justify the immediate removal of all entangling nets from the range of the vaquita? Our answers are, in short: (1) there are about 150 vaquitas left, (2) there are at most 2 years within which to find a solution, and (3) further abundance surveys or bycatch estimates are not needed. The answers to the first two questions make clear that action is needed now, whereas the answer to the last question removes the excuse of uncertainty as a delay tactic. Herein we explain our reasoning.