P. brasiliensis virulence is affected by SconC, the negative regulator of inorganic sulfur assimilation

Conidia/mycelium-to-yeast transition of Paracoccidioidesbrasiliensis is a critical step for the establishment of paracoccidioidomycosis, a systemic mycosis endemic in Latin America. Thus, knowledge of the factors that mediate this transition is of major importance for the design of intervention strategies. So far, the only known pre-requisites for the accomplishment of the morphological transition are the temperature shift to 37°C and the availability of organic sulfur compounds. In this study, we investigated the auxotrophic nature to organic sulfur of the yeast phase of Paracoccidioides, with special attention to P. brasiliensis species. For this, we addressed the role of SconCp, the negative regulator of the inorganic sulfur assimilation pathway, in the dimorphism and virulence of this pathogen. We show that down-regulation of SCONC allows initial steps of mycelium-to-yeast transition in the absence of organic sulfur compounds, contrarily to the wild-type fungus that cannot undergo mycelium-to-yeast transition under such conditions. However, SCONC down-regulated transformants were unable to sustain yeast growth using inorganic sulfur compounds only. Moreover, pulses with inorganic sulfur in SCONC down-regulated transformants triggered an increase of the inorganic sulfur metabolism, which culminated in a drastic reduction of the ATP and NADPH cellular levels and in higher oxidative stress. Importantly, the down-regulation of SCONC resulted in a decreased virulence of P. brasiliensis, as validated in an in vivo model of infection. Overall, our findings shed light on the inability of P. brasiliensis yeast to rely on inorganic sulfur compounds, correlating its metabolism with cellular energy and redox imbalances. Furthermore, the data herein presented reveal SconCp as a novel virulence determinant of P. brasiliensis.J.F.M. and J.G.R. were supported by a PhD grant from Fundacao para a Ciencia e Tecnologia (FCT). This work was supported by a grant from FCT (PTDC/BIA-MIC/108309/2008). M. Sturme. and M. Saraiva are Ciencia 2008 fellows. The authors would also like to thank FAPESP (Fundacao para Amparo a Pesquisa do Estado de Sao Paulo) and CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Efficacy of Lactic Acid Bacteria (LAB) supplement in management of constipation among nursing home residents

<p>Abstract</p> <p>Background</p> <p>Constipation is a significant problem in the elderly, specifically nursing home and/or extended-care facility residents are reported to suffer from constipation. Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as diarrhea and constipation effect. The objective of this study was to investigate the efficacy of this LAB supplement in the management of nursing home residents.</p> <p>Methods</p> <p>Nineteen subjects (8M, 11F; mean age 77.1 ± 10.1) suffering with chronic constipation were assigned to receive LAB (3.0 × 10¹¹CFU/g) twice (to be taken 30 minutes after breakfast and dinner) a day for 2 weeks in November 2008. Subjects draw up a questionnaire on defecation habits (frequency of defecation, amount and state of stool), and we collected fecal samples from the subjects both before entering and after ending the trial, to investigate LAB levels and inhibition of harmful enzyme activities. Results were tested with SAS and Student's t-test.</p> <p>Results</p> <p>Analysis of questionnaire showed that there was an increase in the frequency of defecation and amount of stool excreted in defecation habit after LAB treatment, but there were no significant changes. And it also affects the intestinal environment, through significantly increase (<it>p </it>< 0.05) fecal LAB levels. In addition, tryptophanase and urease among harmful enzyme activities of intestinal microflora were significantly decreased (<it>p </it>< 0.05) after LAB treatment.</p> <p>Conclusion</p> <p>LAB, when added to the standard treatment regimen for nursing home residents with chronic constipation, increased defecation habit such as frequency of defecation, amount and state of stool. So, it may be used as functional probiotics to improve human health by helping to prevent constipation.</p

Identification of glucose transporters in Aspergillus nidulans

o characterize the mechanisms involved in glucose transport, in the filamentous fungus Aspergillus nidulans, we have identified four glucose transporter encoding genes hxtB-E. We evaluated the ability of hxtB-E to functionally complement the Saccharomyces cerevisiae EBY.VW4000 strain that is unable to grow on glucose, fructose, mannose or galactose as single carbon source. In S. cerevisiae HxtB-E were targeted to the plasma membrane. The expression of HxtB, HxtC and HxtE was able to restore growth on glucose, fructose, mannose or galactose, indicating that these transporters accept multiple sugars as a substrate through an energy dependent process. A tenfold excess of unlabeled maltose, galactose, fructose, and mannose were able to inhibit glucose uptake to different levels (50 to 80 %) in these s. cerevisiae complemented strains. Moreover, experiments with cyanide-m-chlorophenylhydrazone (CCCP), strongly suggest that hxtB, -C, and –E mediate glucose transport via active proton symport. The A. nidulans ΔhxtB, ΔhxtC or ΔhxtE null mutants showed ~2.5-fold reduction in the affinity for glucose, while ΔhxtB and -C also showed a 2-fold reduction in the capacity for glucose uptake. The ΔhxtD mutant had a 7.8-fold reduction in affinity, but a 3-fold increase in the capacity for glucose uptake. However, only the ΔhxtB mutant strain showed a detectable decreased rate of glucose consumption at low concentrations and an increased resistance to 2-deoxyglucose.The authors would like to thank the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

S-adenosylmethionine in rat liver cirrhosis

An experimental model of cirrhosis in rats, by means carbon tetrachloride (CCl4) and ethanol during two months, was used to assess the effectiveness of S-adenosylmethionine. Histological studies of the liver and examination of different biochemical parameters of hepatic function were also employed. Bilirubin and lactic acid levels decreased significantly in the group treated with S-adenosylmethionine in comparison with the CCl4 + ethanol group. Histologic liver studies showed a significant improvement relative to fatty liver, Mallory bodies, infiltrate polymorphonuclear and perivenular fibrosis. A slight decrease in cirrhosis was observed in the animals treated with S- adenosylmethionine

Resultados auditivos com o implante coclear multicanal em pacientes submetidos a cirurgia no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Auditory results with multicanal cochlear implant in patients submitted to cochlear implant surgery at University of São Paulo Medical School - Hospital das Clínicas

A surdez profunda é uma deficiência que afeta a personalidade, o relacionamento e todo o estilo de vida do paciente. Incapacita os indivíduos de escutarem sons ambientes como sirenes e alarmes que constituem alerta em situações da vida diária e não permite a modulação vocal, tornando a voz esteticamente ruim. A prótese auditiva convencional é eficiente no tratamento de grande parte das deficiências auditivas, porém existem pacientes que não conseguem obter discriminação de palavras e sentenças mesmo com uma prótese auditiva potente. O implante coclear é a alternativa atual para estes pacientes. OBJETIVO: Avaliar o resultado auditivo dos pacientes adultos implantados com o implante coclear multicanal pelo Grupo de Implante Coclear da Disciplina de Otorrinolaringologia da Faculdade de medicina da Universidade de São Paulo. FORMA DE ESTUDO: Estudo de série. CASUÍSTICA E MÉTODO: Foram selecionados 61 pacientes com surdez profunda bilateral que utilizam o implante coclear multicanal por pelo menos seis meses e estudados os resultados auditivos através de testes de reconhecimento de palavras e sentenças. RESULTADOS: O PTA médio obtido pelos pacientes foi 38.7 dB NPS. A média em reconhecimento de sentenças em formato aberto foi de 71.3%, vogais em 86.5%, monossílabos em 52.60% e consoante medial em 52.6%. A maioria dos pacientes está apta ao uso do telefone. CONCLUSÃO: A avaliação auditiva obtida seis meses após a primeira programação do implante demonstra que pacientes de língua portuguesa obtêm excelentes resultados em testes de reconhecimento de palavras e sentenças em apresentação aberta, readquirindo uma audição útil.<br>Complete hearing loss is a very important handicap resulting in sensory deprivation and affecting an individual's personality, relationships and life style. Individuals with profound deafness are unable to hear environmental sounds as doorbells, telephones, traffic noises and sirens that are an important alert for dangerous situations in the daily life. They are also unable to hear their own voices and for this people with profound deaf do not modulate their voices. The hearing aids are the first choice to treat deafness, but there are patients with severe damage of the auditory systems who cannot receive a useful hearing from normal hearing aids. The cochlear implant is the alternative for patients that cannot have good discriminatory ability wearing a powerful hearing aid and wish or need a better hearing. AIM: To study the hearing results of the adult patients who are using a multichannel cochlear implant system at the Department of Otolaryngology - University of Sao Paulo. STUDY DESIGN: Series study. MATERIAL AND METHOD: We selected 61 patients with a severe bilateral hearing loss that have been using the cochlear implant for at least six months. The hearing evaluation performed after using the device for six months included word and sentence recognition tests. RESULTS: The PTA of four patients reached 38.7 dB. Speech perception tests showed 713% recognition of open set sentences, 86.5% of vowels and 52.60% of monosyllabic. Most of our patients are able to speak on the telephone. CONCLUSION: Most of patients showed excellent results in open-set sentence and word tests

Fatores associados à tuberculose pulmonar em pacientes que procuraram serviços de saúde de referência para tuberculose Factors associated with pulmonary tuberculosis among patients seeking medical attention at referral clinics for tuberculosis

OBJETIVO: A identificação de fatores comportamentais e clínicos associados à tuberculose pulmonar pode melhorar a detecção e o tratamento dessa doença, consequentemente reduzindo sua duração e transmissão. Nosso objetivo foi identificar fatores sociodemográficos, clínicos e comportamentais associados à tuberculose pulmonar. MÉTODOS: Estudo transversal realizado entre abril de 2008 e março de 2009 em três unidades de saúde na cidade de Fortaleza (CE). Foram selecionados 233 pacientes maiores de 14 anos que procuraram atendimento médico espontaneamente e que apresentavam tosse por > 2 semanas. Foram coletados dados sociodemográficos, clínicos e comportamentais. Foram realizadas baciloscopia direta para BAAR e cultura de micobactérias, bem como testes tuberculínicos e radiografias de tórax. Os pacientes foram divididos em dois grupos (com e sem tuberculose pulmonar). As variáveis categóricas foram comparadas com o teste do qui-quadrado, seguido de análise de regressão logística quando as variáveis foram consideradas significativas. RESULTADOS: A prevalência de tuberculose pulmonar foi 41,2%. As OR não ajustadas indicaram que as seguintes variáveis foram fatores de risco significativos para tuberculose pulmonar: febre (OR = 2,39; IC95%: 1,34-4,30), anorexia (OR = 3,69; IC95%: 2,03-6,75) e perda de peso (OR = 3,37; IC95%: 1,76-6,62). Na análise multivariada, apenas perda de peso (OR = 3,31; IC95%: 1,78-6,14) associou-se significativamente com tuberculose pulmonar. CONCLUSÕES: Em áreas com elevada prevalência de tuberculose, a perda de peso poderia ser utilizada como um indicador de tuberculose pulmonar em pacientes com tosse crônica por > 2 semanas.<br>OBJECTIVE: The identification of behavioral and clinical factors that are associated with pulmonary tuberculosis might improve the detection and treatment of the disease, thereby reducing its duration and transmission. Our objective was to identify sociodemographic, clinical, and behavioral factors that are associated with the diagnosis of pulmonary tuberculosis. METHODS: This was a cross-sectional study conducted between April of 2008 and March of 2009 at three health care clinics in the city of Fortaleza, Brazil. We selected 233 patients older than 14 years of age who spontaneously sought medical attention and presented with cough for > 2 weeks. Sociodemographic, clinical, and behavioral data were collected. Sputum smear microscopy for AFB and mycobacterial culture were also carried out, as were tuberculin skin tests and chest X-rays. The patients were divided into two groups (with and without pulmonary tuberculosis). The categorical variables were compared by the chi-square test, followed by logistic regression analysis when the variables were considered significant. RESULTS: The prevalence of pulmonary tuberculosis was 41.2%. The unadjusted OR showed that the following variables were statistically significant risk factors for pulmonary tuberculosis: fever (OR = 2.39; 95% CI, 1.34-4.30), anorexia (OR = 3.69; 95% CI, 2.03-6.75), and weight loss (OR = 3.37; 95% CI, 1.76-6.62). In the multivariate analysis, only weight loss (OR = 3.31; 95% CI, 1.78-6.14) was significantly associated with pulmonary tuberculosis. CONCLUSIONS: In areas with a high prevalence of tuberculosis, weight loss could be used as an indicator of pulmonary tuberculosis in patients with chronic cough for > 2 weeks