Erectile Dysfunction in Young Non-Obese Type II Diabetic Goto-Kakizaki Rats is Associated with Decreased eNOS Phosphorylation at Ser1177

Introduction. Diabetes mellitus (DM) is a risk factor for erectile dysfunction (ED). Although type 2 DM is responsible for 90-95% diabetes cases, type 1 DM experimental models are commonly used to study diabetes-associated ED. Aim. Goto-Kakizaki (GK) rat model is relevant to ED studies since the great majority of patients with type 2 diabetes display mild deficits in glucose-stimulated insulin secretion, insulin resistance, and hyperglycemia. We hypothesized that GK rats display ED which is associated with decreased nitric oxide (NO) bioavailability. Methods. Wistar and GK rats were used at 10 and 18 weeks of age. Changes in the ratio of intracavernosal pressure/mean arterial pressure (ICP/MAP) after electrical stimulation of cavernosal nerve were determined in vivo. Cavernosal contractility was induced by electrical field stimulation (EFS) and phenylephrine (PE). In addition, nonadrenergic-noncholinergic (NANC)- and sodium nitroprusside (SNP)-induced relaxation were determined. Cavernosal neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) mRNA and protein expression were also measured. Main Outcome Measure. GK diabetic rats display ED associated with decreased cavernosal expression of eNOS protein. Results. GK rats at 10 and 18 weeks demonstrated impaired erectile function represented by decreased ICP/MAP responses. Ten-week-old GK animals displayed increased PE responses and no changes in EFS-induced contraction. Conversely, contractile responses to EFS and PE were decreased in cavernosal tissue from GK rats at 18 weeks of age. Moreover, GK rats at 18 weeks of age displayed increased NANC-mediated relaxation, but not to SNP. In addition, ED was associated with decreased eNOS protein expression at both ages. Conclusion. Although GK rats display ED, they exhibit changes in cavernosal reactivity that would facilitate erectile responses. These results are in contrast to those described in other experimental diabetes models. This may be due to compensatory mechanisms in cavernosal tissue to overcome restricted pre-penile arterial blood supply or impaired veno-occlusive mechanisms. Carneiro FS, Giachini FRC, Carneiro ZN, Lima VV, Ergul A, Webb RC, and Tostes RC. Erectile dysfunction in young non-obese type II diabetic Goto-Kakizaki rats is associated with decreased eNOS phosphorylation at Ser1177. J Sex Med 2010;7:3620-3634.

Non-N-methyl-d-aspartate glutamate receptors in the lateral hypothalamus modulate cardiac baroreflex responses in conscious rats

P>In the present study, we investigated the effects of inhibition of the lateral hypothalamus (LH) neurotransmission with bilateral microinjection of CoCl(2), a non-selective blocker of neurotransmission, on modulation of cardiac baroreflex responses in conscious rats as well as the involvement of LH glutamatergic neurotransmission in this modulation. Reflex bradycardiac and tachycardiac responses to blood pressure increases (following i.v. infusion of phenylephrine) or decreases (following i.v. infusion of sodium nitroprusside) were investigated in conscious male Wistar rats. Responses were evaluated before and after microinjection of 1 nmol/100 nL CoCl(2), 2 nmol/100 nL 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulphonamide (NBQX; a selective non-N-methyl-d-aspartate (NMDA) glutamate receptor antagonist) or different doses (2, 4 or 8 nmol/100 nL) of the selective NMDA glutamate receptor antagonist LY235959. Microinjection of CoCl(2) into the LH had no effect on the tachycardiac baroreflex response, but did evoke a decrease in the reflex bradycardia caused by increases in blood pressure. Microinjection of NBQX into the LH had a similar effect on reflex bradycardia as CoCl(2), but had no effect on the tachycardiac response. Microinjection of increasing doses of LY235959 into the LH had no effect on the cardiac baroreflex response. In conclusion, the data suggest that the LH has a tonic facilitatory influence on the parasympathetic component of the baroreflex. The results also indicate that this facilitatory influence is mediated by local LH glutamatergic neurotransmission through non-NMDA glutamatergic receptors.

Lipopolysaccharide from Escherichia coli prevents indomethacin-induced gastric damage in rats: role of non-protein sulfhydryl groups and leukocyte adherence

To investigate the role of non-protein sulfhydryl groups (NP-SH) and leukocyte adhesion in the protective effect of lipopolysaccharide (LPS) from Escherichia coli against indomethacin-induced gastropathy. Male Wistar rats were divided into four groups: saline, LPS, saline + indomethacin and LPS + indomethacin, with six rats in each group. Rats were pretreated with LPS (300 mu g/kg, by intravenous) or saline. After 6 h, indomethacin was administered (20 mg/kg, by gavage). Three hours after treatments, rats were killed. Macroscopic gastric damage, gastric NP-SH concentration, myeloperoxidase (MPO) activity and mesenteric leukocyte adhesion (intravital microscopy) were assessed. Statistical analysis was performed using one-way analysis of variance followed by the Newman-Keuls test. Statistical significance was set at P < 0.05. LPS reduced the gastric damage, gastric MPO activity and increased gastric NP-SH concentration in indomethacin-induced gastropathy. LPS alone increased gastric NP-SH when compared to saline. Indomethacin increased leukocyte adhesion when compared to the saline, and LPS reduced indomethacin-induced leukocyte adhesion. In addition, LPS alone did not change leukocyte adhesion, when compared to the saline. LPS protective effect against indomethacin-induced gastropathy is mediated by an increase in the NP-SH and a decrease in leukocyte-endothelial adhesion.

Role of olfaction and vision cues in feeding behavior and alarm reaction in the catfish pintado, Pseudoplatystoma corruscans

Experiments were performed to investigate senses that are essential for mediating fright reaction and food behavior in Pseudoplatystoma corruscans, pintado. The dilemma ""to feed or to flee"" was also analyzed in fishes with intact and sectioned olfactory tracts, stimulated by alarm substance extracts and food. Fishes were arranged into five groups: fish with intact lateral olfactory tracts (LOT), fish with intact medial olfactory tract (MOT), fish with tracts totally sectioned (TOTAL, both LOT and MOT), sham operated, and nonoperated fish. The five groups were submitted to either alarm substance extract and food stimulus or to distilled water (control) and food stimulus. Fish reacted to food independently of which tract (LOT, MOT or TOTAL) was sectioned; vision seems necessary and elemental to detect and deflagrate food response. Latency of the responses to each reaction was different between groups. None of the fish with sectioned tracts reacted to alarm substance extract, while sham- and nonoperated fish showed the typical alarm behavior response, leading to the conclusion that olfaction is essential for mediating alarm response. These results indicate that others sense systems (e.g., vision) are sufficient to trigger and elicit feeding behavior and that olfaction is not necessary to fully maintain food detection to qualitative and quantitative extent. However, olfactory tract integrity seems to be required for mediation of alarm reaction in P. corruscans.

Infection control practices among a cohort of Brazilian dentists

Objective: To evaluate infection control practices among dentists in private and public practice. Design: Survey and cross-sectional analysis. Setting: Sertaozinho city, Brazil. Participants: All dentists who were currently working at the study city, and agreed to participate, resulting in a study population of 135 dentists. Methods: Participants were personally interviewed and variables were submitted to X(2) or Fisher`s exact test. Results: Hand washing before and after each patient was reported by 86.7% of dentists, but private practitioners used liquid soap and paper towels more often than their public colleagues (p<0.001). Most of the study population (97.8%) used gloves routinely during clinical sessions, but 8.2% reused them. Dry-heat was the main method employed for sterilisation of heat-stable devices by 80.0% of dentists, but adequate temperature and time of exposure was accomplished by only 32.1% of public and 70.0% of private professionals (p<0.001). Heat-sensitive devices were disinfected with an adequate substance by 60.0% of both affiliation dentists (p=0.908). Conclusions: There is a large gap between infection control recommendations and practices observed among the study population, and the situation is worse in public services. To reverse that situation, infection control issues must be openly debated by professional associations, dental schools and health authorities.

Knowledge and practices of medical students to prevent tuberculosis transmission in Rio de Janeiro, Brazil

Objectives. To describe knowledge, practices, and associated factors of medical students to prevent transmission of tuberculosis (TB) in five medical schools. Methods. Cross-sectional survey of undergraduate medical students in preclinical and in early and late clinical years. Information was obtained on sociodemographic profile, previous lectures on TB, knowledge about TB transmission, exposure to patients with active pulmonary TB, and use of respiratory protective masks. Results. Among 1 094 respondents, 575 (52.6%) correctly answered that coughing, speaking, and sneezing can transmit TB. Early [adjusted odds ratio = 4.0 (3.0, 5.5)] and late [adjusted odds ratio = 4.2 (3.1, 5.8)] clinical years were associated with correct answers, but having had previous lectures on TB was not. Among those who had previous lectures on TB, the rate of correct answers increased from 42.1% to 61.6%. Among 332 medical students who reported exposure to TB patients, 194 (58.4%) had not used protective masks. More years of clinical experience was associated with the use of masks [adjusted odds ratio = 2.9 (1.4, 6.1)], while knowledge was inversely associated with the use of masks [adjusted odds ratio = 0.4 (0.2, 0.6)]. Conclusions. Many medical students are not aware of the main routes of TB infection, and lectures on TB are not sufficient to change knowledge and practices. Regardless of knowledge about TB transmission, students engage in risky behaviors: more than two-thirds do not use a protective mask when examining an active TB case. We suggest innovative, effective active learning experiences to change this scenario.

Amygdala activation to masked happy facial expressions

The amygdala has a key role in automatic non-conscious processing of emotions. Highly salient emotional stimuli elicit amygdala activity, and happy faces are among the most rapidly perceived facial expressions. In backward masking paradigms, an image is presented briefly and then masked by another stimulus. However, reports of amygdala responses to masked happy faces have been mixed. In the present Study, we used functional magnetic resonance imaging (fMRI) to examine amygdala activation to masked happy, sad, and neutral facial expressions. Masked happy faces elicited greater amygdala activation bilaterally as compared to masked sad faces. Our findings indicate that the amygdala is highly responsive to non-consciously perceived happy facial expressions. (JINS, 2010, 16, 383-387.)

Angiogenic non-Hodgkin T/natural killer (NK)-cell lymphoma: Report of three cases

Angiogenic T/natural killer (NK)-cell lymphoma is a non-Hodgkin lymphoma characterized by necrosis and vascular destruction that is strongly associated with Epstein-Barr virus and AIDS. Early diagnosis is essential to improve the chances of patient survival, but severe local inflammatory infiltrate impairs histologic diagnosis by obscuring neoplastic cells. The most common markers are CD2, CD56, cytoplasmic CD3, and CD43 EBV We describe 3 cases of angiogenic T/NK-cell lymphoma that show the diverse Presentation of the same disease. Patient I was HIV positive and had nasal obstruction, facial edema, and ulceration of the nasal mucosa. Patient 2 had fever, a sore throat, and weight loss. Patient 3 had facial edema, fever, proptosis, and rapid development Of neurologic alterations. Several biopsies were needed for histologic confirmation in these patients, despite positivity for the CD3 and CD56 markers.

Exposure to maternal smoking during fetal life affects food preferences in adulthood independent of the effects of intrauterine growth restriction

Experimental animal studies have shown that nicotine exposure during gestation alters the expression of fetal hypothalamic neuropeptides involved in the control of appetite. We aimed to determine whether the exposure to maternal smoking during gestation in humans is associated with an altered feeding behavior of the adult offspring. A longitudinal prospective cohort study was conducted including all births from Ribeirao Preto (Sao Paulo, Brazil) between 1978 and 1979. At 24 years of age, a representative random sample was re-evaluated and divided into groups exposed (n = 424) or not (n = 1586) to maternal smoking during gestation. Feeding behavior was analyzed using a food frequency questionnaire. Covariance analysis was used for continuous data and the chi(2) test for categorical data. Results were adjusted for birth weight ratio, body mass index, gender, physical activity and smoking, as well as maternal and subjects` schooling. Individuals exposed to maternal smoking during gestation ate more carbohydrates than proteins (as per the carbohydrate-to-protein ratio) than non-exposed individuals. There were no differences in the consumption of the macronutrients themselves. We propose that this adverse fetal life event programs the individual`s physiology and metabolism persistently, leading to an altered feeding behavior that could contribute to the development of chronic diseases in the long term.

Bursts of transposition from non-long terminal repeat retrotransposon families of the RTE clade in Schistosoma mansoni

The genus Schistosoma is composed of blood flukes that infect vertebrates, from which three species are major causative agents of human schistosomiasis, a tropical disease that affects more than 200 million people. Current models of the recent evolution of Schistosoma indicate multiple events of migration and speciation from an Asian ancestral species. Transposable elements are important drivers of genome evolution and have been hypothesised to have an important role in speciation. In this work, we describe a comprehensive inventory of Schistosoma mansoni and Schistosoma japonicum retrotransposons, based on their recently published genomic data. We find a considerable difference in retrotransposon representation between the two species (22% and 13%, respectively). A large part of this difference can be attributed to higher representation of two previously described families of S. mansoni retrotransposons (SR2 and Perere-3/SR3), compared with the representation of their closest relative families in S. japonicum. A more detailed analysis suggests that these two S. mansoni families were the subject of recent bursts of transposition that were not paralleled by their S. japonicum counterparts. We hypothesise that these bursts could be a consequence of the evolutionary pressure resulting from migration of Schistosoma from Asia to Africa and their establishment in this new environment, helping both speciation and adaptation. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Involvement of hypothalamic paraventricular nucleus non-N-methyl-d-aspartate receptors in the pressor response to noradrenaline microinjected into the bed nucleus of the stria terminalis of unanesthetized rats

Microinjection of noradrenaline into the bed nucleus of the stria terminalis (BST) has been reported to cause a pressor response in unanesthetized rats, which was shown to be mediated by acute vasopressin release into the systemic circulation. In the present study we verified the involvement of magnocellular neurons of the hypothalamic paraventricular (PVN) or supraoptic (SON) nuclei and the local neurotransmitter involved in the pressor response to noradrenaline microinjection into the BST. The PVN pretreatment with the non-selective neurotransmission blocker CoCl(2) (1 nmol/100 nL) inhibited the noradrenaline-evoked pressor response. However, responses were not affected by SON treatment with CoCl(2). Further experiments were carried out to test if glutamatergic neurotransmission in the PVN mediates the pressor response evoked by noradrenaline microinjection into the BST. Pretreatment of the PVN with the selective N-methyl-d-aspartate (NMDA) receptor antagonist LY235959 (2 nmol/100 nL) did not affect the noradrenaline-evoked pressor response. However, PVN pretreatment with the selective non-NMDA receptor antagonist NBQX (2 nmol/100 nL) significantly reduced the pressor response to noradrenaline microinjection into the BST. In conclusion, our results suggest that pressor responses to noradrenaline microinjection into the BST are mediated by PVN magnocellular neurons without involvement of SON neurons. They also suggest that a glutamatergic neurotransmission through non-NMDA glutamate receptors in the PVN mediates the response.

Non-coding transcript in T cells (NTT): Antisense transcript activates PKR and NF-kappa B in human lymphocytes

T cell activation is a complex process involving many steps and the role played by the non-protein-coding RNAs (ncRNAs) in this phenomenon is still unclear. The non-coding T cells transcript (NTT) is differentially expressed during human T cells activation, but its function is unknown. Here, we detected a 426 m NTT transcript by RT-PCR using RNA of human lymphocytes activated with a synthetic peptide of HIV-1. After cloning, the sense and antisense 426 nt NTT transcripts were obtained by in vitro transcription and were sequenced. We found that both transcripts are highly structured and are able to activate PKR. A striking observation was that the antisense 426 nt NTT transcript is significantly more effective in activating PKR than the corresponding sense transcript. The transcription factor NF-kappa B is activated by PKR through phosphorylation and subsequent degradation of its inhibitor I-kappa B beta. We also found that the antisense 426 nt NTT transcript induces more efficiently the degradation Of I-kappa B beta than the sense transcript. Thus, this study suggests that the role played by NTT in the activation of lymphocytes can be mediated by PKR through NF-kappa B activation. However, the physiological significance of the activity of the antisense 426 nt NTT transcript remains unknown. (c) 2007 Elsevier Inc. All rights reserved.

Age-related deregulation of Aire and peripheral tissue antigen genes in the thymic stroma of non-obese diabetic (NOD) mice is associated with autoimmune type 1 diabetes mellitus (DM-1)

Gene expression of peripheral tissue antigens (PTAs) in stromal medullary thymic epithelial cells (mTECs) is a key process to the negative selection of autoreactive thymocytes. This phenomenon was termed ""promiscuous gene expression"" (PGE), which is partially controlled by the Aire gene. Nevertheless, reasons for the correlation of Aire and PTAs with the emergence of autoimmune diseases are largely unknown, though it may be a result of a chronological effect. Although the effect of Aire mutations in pathogenic autoimmunity is well know, it could not be a unique cause for autoimmunity. Independently of mutations, temporal deregulation of Aire expression may imbalance Aire-dependent PTAs and/or wide PGE. This deregulation may be an early warning sign for autoimmune diseases as it guarantees autoantigen representation in the thymus. To assess this hypothesis, we studied the expression levels of Aire, Aire-dependent (Ins2) and Aire-independent (Gad67 and Col2a1) PTAs using real-time-PCR of the thymic stromal cells of NOD mice during the development of autoimmune type 1 diabetes mellitus (DM-1). Wide PGE was studied by microarrays in which the PTA genes were identified through parallel CD80(+) mTEC 3.10 cell line expression profiling. The results show that Aire gene was down-regulated in young pre-autoimmune (pre-diabetic) NOD mice. PGE and specific PTA genes were down-regulated in adult autoimmune diabetic animals. These findings represent evidence indicating that chronological deregulation of genes important to negative selection may be associated with the development of an autoimmune disease (DM-1) in mice.

Clonal Complex Chromosome Aberration in Non-Ossifying Fibroma

Cytogenetic information of non-ossifying fibromas (NOFs) is exceptionally limited. This fact relies, in part, on their benign nature but mainly because most cases evolve undetected or there is no need for surgical intervention. We report the case of a NOF arising in the left tibia of a 14-year-old male with an invariable clonal translocation. The karyotype was denoted as 42-46,XY,t(11;3;14)(q23;p21;p11). There are only two previous reported cases of clonally aberrant NOF. Records from additional cases will be essential to assess whether consistent karyotypic aberrations define this lesion. Pediatr Blood Cancer 2010;54:764 767. (C) 2010 Wiley-Liss, Inc.

Syndromic and non-syndromic aneurysms of the human ascending aorta share activation of the Smad2 pathway

Common features such as elastic fibre destruction, mucoid accumulation, and smooth muscle cell apoptosis are co-localized in aneurysms of the ascending aorta of various aetiologies. Recent experimental studies reported an activation of TGF-beta in aneurysms related to Marfan (and Loeys-Dietz) syndrome. Here we investigate TGF-beta signalling in normal and pathological human ascending aortic wall in syndromic and non-syndromic aneurysmal disease. Aneurysmal ascending aortic specimens, classified according to aetiology: syndromic MFS (n = 15, including two mutations in TGFBR2), associated with BAV (n = 15) or degenerative forms (n = 19), were examined. We show that the amounts of TGF-beta 1 protein retained within and released by aneurysmal tissue were greater than for control aortic tissue, whatever the aetiology, contrasting with an unchanged TGF-beta 1 mRNA level. The increase in stored TGF-beta 1 was associated with enhanced LTBP-I protein and mRNA levels. These dysiregulations of the extracellular ligand are associated with higher phosphorylated Smad2 and Smad2 mRNA levels in the ascending aortic wall from all types of aneurysm. This activation correlated with the degree of elastic fibre fragmentation. Surprisingly, there was no consistent association between the nuclear location of pSmad2 and extracellular TGF-beta 1 and LTBP-I staining and between their respective mRNA expressions. In parallel, decorin. was focally increased in aneurysmal media, whereas biglycan was globally decreased in aneurysmal aortas. In conclusion, this study highlights independent dysregulations of TGF-beta retention and Smad2 signalling in syndromic and non-syndromic aneurysms of the ascending aorta. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.