Showing papers by "Federal University of São Paulo published in 2006"

Manipulation of Host Hepatocytes by the Malaria Parasite for Delivery into Liver Sinusoids

Abstract: The merozoite stage of the malaria parasite that infects erythrocytes and causes the symptoms of the disease is initially formed inside host hepatocytes. However, the mechanism by which hepatic merozoites reach blood vessels (sinusoids) in the liver and escape the host immune system before invading erythrocytes remains unknown. Here, we show that parasites induce the death and the detachment of their host hepatocytes, followed by the budding of parasite-filled vesicles (merosomes) into the sinusoid lumen. Parasites simultaneously inhibit the exposure of phosphatidylserine on the outer leaflet of host plasma membranes, which act as "eat me" signals to phagocytes. Thus, the hepatocyte-derived merosomes appear to ensure both the migration of parasites into the bloodstream and their protection from host immunity.

Quantitative imaging of Plasmodium transmission from mosquito to mammal

Abstract: Plasmodium, the parasite that causes malaria, is transmitted by a mosquito into the dermis and must reach the liver before infecting erythrocytes and causing disease. We present here a quantitative, real-time analysis of the fate of parasites transmitted in a rodent system. We show that only a proportion of the parasites enter blood capillaries, whereas others are drained by lymphatics. Lymph sporozoites stop at the proximal lymph node, where most are degraded inside dendritic leucocytes, but some can partially differentiate into exoerythrocytic stages. This previously unrecognized step of the parasite life cycle could influence the immune response of the host, and may have implications for vaccination strategies against the preerythrocytic stages of the parasite.

Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome

Abstract: Cardio-facio-cutaneous (CFC) syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. It phenotypically overlaps with Noonan and Costello syndrome, which are caused by mutations in PTPN11 and HRAS, respectively. In 43 individuals with CFC, we identified two heterozygous KRAS mutations in three individuals and eight BRAF mutations in 16 individuals, suggesting that dysregulation of the RAS-RAF-ERK pathway is a common molecular basis for the three related disorders.

Epidemiology of Candidemia in Brazil: a Nationwide Sentinel Surveillance of Candidemia in Eleven Medical Centers

Abstract: Candidemia studies have documented geographic differences in rates and epidemiology, underscoring the need for surveillance to monitor trends. We conducted prospective candidemia surveillance in Brazil to assess the incidence, species distribution, frequency of antifungal resistance, and risk factors for fluconazole-resistant Candida species. Prospective laboratory-based surveillance was conducted from March 2003 to December 2004 in 11 medical centers located in 9 major Brazilian cities. A case of candidemia was defined as the isolation of Candida spp. from a blood culture. Incidence rates were calculated per 1,000 admissions and 1,000 patient-days. Antifungal susceptibility tests were performed by using the broth microdilution assay, according to the Clinical and Laboratory Standards Institute guidelines. We detected 712 cases, for an overall incidence of 2.49 cases per 1,000 admissions and 0.37 cases per 1,000 patient-days. The 30-day crude mortality was 54%. C. albicans was the most common species (40.9%), followed by C. tropicalis (20.9%) and C. parapsilosis (20.5%). Overall, decreased susceptibility to fluconazole occurred in 33 (5%) of incident isolates, 6 (1%) of which were resistant. There was a linear correlation between fluconazole and voriconazole MICs (r = 0.54 and P < 0.001 [Spearman's rho]). This is the largest multicenter candidemia study conducted in Latin America and shows the substantial morbidity and mortality of candidemia in Brazil. Antifungal resistance was rare, but correlation between fluconazole and voriconazole MICs suggests cross-resistance may occur.

Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study

Abstract: Objective. Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. Methods. A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. Results. Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. Conclusion. This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome.

Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO2-sensitive neurons in rats.

Abstract: The rat retrotrapezoid nucleus (RTN) contains pH-sensitive neurons that are putative central chemoreceptors. Here, we examined whether these neurons respond to peripheral chemoreceptor stimulation and whether the input is direct from the solitary tract nucleus (NTS) or indirect via the respiratory network. A dense neuronal projection from commissural NTS (commNTS) to RTN was revealed using the anterograde tracer biotinylated dextran amine (BDA). Within RTN, 51% of BDA-labelled axonal varicosities contained detectable levels of vesicular glutamate transporter-2 (VGLUT2) but only 5% contained glutamic acid decarboxylase-67 (GAD67). Awake rats were exposed to hypoxia (n = 6) or normoxia (n = 5) 1 week after injection of the retrograde tracer cholera toxin B (CTB) into RTN. Hypoxia-activated neurons were identified by the presence of Fos-immunoreactive nuclei. CommNTS neurons immunoreactive for both Fos and CTB were found only in hypoxia-treated rats. VGLUT2 mRNA was detected in 92 +/- 13% of these neurons whereas only 12 +/- 9% contained GAD67 mRNA. In urethane-chloralose-anaesthetized rats, bilateral inhibition of the RTN with muscimol eliminated the phrenic nerve discharge (PND) at rest, during hyperoxic hypercapnia (10% CO(2)), and during peripheral chemoreceptor stimulation (hypoxia and/or i.v. sodium cyanide, NaCN). RTN CO(2)-activated neurons were recorded extracellularly in anaesthetized intact or vagotomized rats. These neurons were strongly activated by hypoxia (10-15% O(2); 30 s) or by NaCN. Hypoxia and NaCN were ineffective in rats with carotid chemoreceptor denervation. Bilateral injection of muscimol into the ventral respiratory column 1.5 mm caudal to RTN eliminated PND and the respiratory modulation of RTN neurons. Muscimol did not change the threshold and sensitivity of RTN neurons to hyperoxic hypercapnia nor their activation by peripheral chemoreceptor stimulation. In conclusion, RTN neurons respond to brain P(CO(2)) presumably via their intrinsic chemosensitivity and to carotid chemoreceptor activation via a direct glutamatergic pathway from commNTS that bypasses the respiratory network. RTN neurons probably contribute a portion of the chemical drive to breathe.

Cryptic Speciation and Recombination in the Fungus Paracoccidioides brasiliensis as Revealed by Gene Genealogies

Abstract: Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, a disease confined to Latin America and of marked importance in the endemic areas due to its frequency and severity. This species is considered to be clonal according to mycological criteria and has been shown to vary in virulence. To characterize natural genetic variation and reproductive mode in this fungus, we analyzed P. brasiliensis phylogenetically in search of cryptic species and possible recombination using concordance and nondiscordance of gene genealogies with respect to phylogenies of eight regions in five nuclear loci. Our data indicate that this fungus consists of at least three distinct, previously unrecognized species: S1 (species 1 with 38 isolates), PS2 (phylogenetic species 2 with six isolates), and PS3 (phylogenetic species 3 with 21 isolates). Genealogies of four of the regions studied strongly supported the PS2 clade, composed of five Brazilian and one Venezuelan isolate. The second clade, PS3, composed solely of 21 Colombian isolates, was strongly supported by the alpha-tubulin genealogy. The remaining 38 individuals formed S1. Two of the three lineages of P. brasiliensis, S1 and PS2, are sympatric across their range, suggesting barriers to gene flow other than geographic isolation. Our study provides the first evidence for possible sexual reproduction in P. brasiliensis S1, but does not rule it out in the other two species.

Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method.

Abstract: Methods: The clinical efficacy of SLIT for asthma was evaluated through a systematic review with meta-analysis. MEDLINE (1966-2005), EMBASE (1974-2005), LILACS (1982-2005), and the Cochrane Library were searched for related literature in any language. Randomized-controlled clinical trials (RCT) on SLIT in asthma treatment for adults and children were selected. From 119 citations, 25 studies with 1706 patients were included in this meta-analysis. For each report, quality scores were assigned and data were extracted in relation to the outcomes analyzed: asthmatic symptoms, use of asthma medications, lung function, and bronchial provocation. Results: According to the Jadad quality method, 64% of the studies were assigned scores of 4 or 5. Immunotherapy was seen to significantly reduce asthma severity when parameter compositions were all analyzed by categor- ical outcomes. There was a nonsignificant reduction in asthma symptoms when analyzed using standardized mean differences. No severe reactions were observed. Conclusions: This meta-analysis found that SLIT is beneficial for asthma treat- ment albeit the magnitude of the effect is not very large. Moreover, it is a safe alternative to the subcutaneous route. More RCT with standardization of symptom scores and medications are needed in order to contribute further to this subject.

Effects of Energy Drink Ingestion on Alcohol Intoxication

Abstract: Objective and Methods: The present study aimed at evaluating the effects of the simultaneous ingestion of an alcohol (vodka37.5%v/v) and an energy drink (Red Bull s —3.57 mL/kg), compared with those presented after the ingestion of an alcohol or an energy drink alone. Twenty-six young healthy volunteers were randomly assigned to 2 groups that received 0.6 or 1.0 g/kg alcohol, respectively. They all completed 3 experimental sessions in random order, 7 days apart: alcohol alone, energy drink alone, or alcohol plus energy drink. We evaluated the volunteers’ breath alcohol concentration, subjective sensations of intoxication, objective effects on their motor coordination, and visual reaction time. Results: When compared with the ingestion of alcohol alone, the ingestion of alcohol plus energy drink significantly reduced subjects’ perception of headache, weakness, dry mouth, and impairment of motor coordination. However, the ingestion of the energy drink did not significantly reduce the deficits caused by alcohol on objective motor coordination and visual reaction time. The ingestion of the energy drink did not alter the breath alcohol concentration in either group. Conclusions: Even though the subjective perceptions of some symptoms of alcohol intoxication were less intense after the combined ingestion of the alcohol plus energy drink, these effects were not detected in objective measures of motor coordination and visual reaction time, as well as on the breath alcohol concentration.

Prevalence of symptoms of asthma, rhinitis, and atopic eczema among Brazilian children and adolescents identified by the International Study of Asthma and Allergies in Childhood (ISAAC) - Phase 3.

Abstract: Objective: To determine the prevalence of symptoms of asthma, rhinitis, and atopic eczema among schoolchildren aged 6 to 7 years and adolescents aged 13 to 14 years in 20 Brazilian cities by using the standardized ISAAC written questionnaire, and to assess the association of this prevalence with latitude, altitude and average annual temperature of collaborating centers Methods: Schoolchildren and adolescents from five Brazilian regions participated in the study, totaling 23,422 ISAAC questionnaires answered by schoolchildrenis parents and 58,144 questionnaires answered by adolescents The values for latitude, altitude and average annual temperature were obtained from the Brazilian Institute of Geography and Statistics Results: The mean prevalence rates among schoolchildren and adolescents were respectively 243 and 190% for active asthma; 126 and 146% for rhinoconjunctivitis; and 82 and 50% for atopic eczema A significant negative association was observed between latitude and physician-diagnosed asthma among schoolchildren, severe asthma, physician-diagnosed asthma, eczema and atopic eczema among adolescents No association with altitude was found Conclusions: The prevalence of asthma, rhinitis and atopic eczema in Brazil varies considerably Higher prevalence rates, especially of asthma and eczema, were found at centers located closer to the equator

Molecular basis of mammalian cell invasion by Trypanosoma cruzi

Abstract: Establishment of infection by Trypanosoma cruzi, the agent of Chagasdisease, depends on a series of events involving interactions of diverse parasite molecules with host components. Here we focus on the mechanisms of target cell invasion by metacyclic trypomastigotes (MT) and mammalian tissue culture trypomastigotes (TCT). During MT or TCT internalization, signal transduction pathways are activated both in the parasite and the target cell, leading to Ca 2+ mobilization. For cell adhesion, MT engage surface glycoproteins, such as gp82 and gp35/50, which are Ca 2+ signal-inducing molecules. In T. cruzi isolates that enter host cells in gp82-mediated manner, parasite protein tyrosine kinase as well as phospholipase C are activated, and Ca 2+ is released from IP3-sensitive stores, whereas in T. cruzi isolates that attach to target cells mainly through gp35/50, the signaling pathway involving adenylate cyclase appears to be stimulated, with Ca 2+ release from acidocalciosomes. In addition, T. cruzi isolate-dependent inhibitory signals, mediated by MT-specific gp90, may be triggered both in the host cell and the parasite. The repertoire of TCT molecules implicated in cell invasion includes surface glycoproteins of gp85 family, with members containing binding sites for laminin and cytokeratin 18, enzymes such as cruzipain, trans-sialidase, and an oligopeptidase B that generates a Ca 2+ -agonist from a precursor molecule.

Immunology of canine leishmaniasis.

Abstract: The role of dogs as the main reservoir of visceral leishmaniasis has led to an increased interest in the immune responses and in Leishmania antigens implicated in protective cellular immunity in canine visceral leishmaniasis. The primary goal is to control the prevalence of human disease. Immune responses in canine visceral leishmaniasis are reviewed. Cellular immune responses toward a Th1 subset mediated by IFN-gamma and TNF-alpha predominate in asymptomatic dogs exhibiting apparent resistance to visceral leishmaniasis. On the other hand, while the role of Th2 cytokines, such as IL-4 and IL-10, in symptomatic animals is still controversial, there is increasing evidence for a correlation of these cytokines with progressive disease. CD8+ cytotoxic T cells seem also likely to be involved in resistance to visceral leishmaniasis. Several Leishmania antigens implicated in protective immune responses are described and some pivotal points for development of an effective vaccine against canine visceral leishmaniasis are discussed.

Contribuição dos domínios físico, social, psicológico e ambiental para a qualidade de vida global de idosos

Abstract: Este estudo investigou a contribuicao de cada dominio da qualidade de vida (fisico, social, psicologico e ambiental) na qualidade de vida global e em que extensao esses dominios explicam a qualidade de vida global de idosos residentes no municipio de Teixeiras, na Regiao Sudeste do Brasil. Trata-se de um estudo observacional de corte transversal, sendo a amostragem aleatoria estratificada por sexo, uso do Programa Saude da Familia e microarea de saude (n = 211, individuos com idade igual ou superior a 60 anos), representando 14,28% do total de idosos do municipio em estudo. O instrumento utilizado foi o Word Health Organization Quality of Life Instrument Bref (WHOQOL-Bref), proposto pela Organizacao Mundial de Saude, aplicado por um unico entrevistador, devidamente treinado. As analises de regressao linear mostraram que nenhuma das variaveis sociodemograficas interferiu significativamente no dominio global da qualidade de vida, e, entre os quatro dominios, o que mais explicou a qualidade de vida global foi o fisico, seguido do ambiental e do psicologico. O dominio social nao mostrou contribuicao significativa na qualidade de vida global. As possiveis explicacoes para os resultados encontrados foram discutidas.

Glyceraldehyde-3-Phosphate Dehydrogenase of Paracoccidioides brasiliensis Is a Cell Surface Protein Involved in Fungal Adhesion to Extracellular Matrix Proteins and Interaction with Cells

Abstract: The pathogenic fungus Paracoccidioides brasiliensis causes paracoccidioidomycosis, a pulmonary mycosis acquired by inhalation of fungal airborne propagules, which may disseminate to several organs and tissues, leading to a severe form of the disease. Adhesion to and invasion of host cells are essential steps involved in the infection and dissemination of pathogens. Furthermore, pathogens use their surface molecules to bind to host extracellular matrix components to establish infection. Here, we report the characterization of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of P. brasiliensis as an adhesin, which can be related to fungus adhesion and invasion. The P. brasiliensis GAPDH was overexpressed in Escherichia coli, and polyclonal antibody against this protein was obtained. By immunoelectron microscopy and Western blot analysis, GAPDH was detected in the cytoplasm and the cell wall of the yeast phase of P. brasiliensis. The recombinant GAPDH was found to bind to fibronectin, laminin, and type I collagen in ligand far-Western blot assays. Of special note, the treatment of P. brasiliensis yeast cells with anti-GAPDH polyclonal antibody and the incubation of pneumocytes with the recombinant protein promoted inhibition of adherence and internalization of P. brasiliensis to those in vitro-cultured cells. These observations indicate that the cell wall-associated form of the GAPDH in P. brasiliensis could be involved in mediating binding of fungal cells to fibronectin, type I collagen, and laminin, thus contributing to the adhesion of the microorganism to host tissues and to the dissemination of infection.

Prevalência de sintomas de asma, rinite e eczema atópico entre crianças e adolescentes brasileiros identificados pelo International Study of Asthma and Allergies (ISAAC): fase 3

Abstract: OBJETIVO: Determinar a prevalencia de sintomas relacionados a asma, rinite e eczema atopico em escolares (EC) entre 6 e 7 anos e adolescentes (AD) entre 13 e 14 anos, residentes em 20 cidades brasileiras, empregando o questionario escrito padronizado do ISAAC, e avaliar a sua associacao com a latitude, altitude e temperatura media anual dos centros de residencia. METODOS: Participaram do estudo EC e AD das cinco regioes do Brasil, totalizando 23.422 questionarios ISAAC respondidos pelos pais de EC e 58.144 pelos proprios AD. Os indices de latitude, altitude e temperatura media anual foram obtidos do Instituto Brasileiro de Geografia e Estatistica. RESULTADOS: As prevalencias medias para os EC e AD, respectivamente, foram: asma ativa, 24,3 e 19,0%; rinoconjuntivite, 12,6 e 14,6%; e eczema flexural, 8,2 e 5,0%. Associacao significante e negativa foi observada entre latitude e prevalencia de asma diagnosticada por medico para os EC, asma grave, asma diagnosticada por medico, eczema e eczema flexural para os AD. Nao houve associacao com a altitude dos centros. CONCLUSAO: A prevalencia de asma, rinite e eczema atopico no Brasil foi variavel. Valores mais altos, sobretudo de asma e eczema, foram observados nos centros localizados mais proximos ao Equador.

Haplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber hereditary optic neuropathy pedigrees.

Abstract: The mitochondrial DNA (mtDNA) of 87 index cases with Leber hereditary optic neuropathy (LHON) sequentially diagnosed in Italy, including an extremely large Brazilian family of Italian maternal ancestry, was evaluated in detail. Only seven pairs and three triplets of identical haplotypes were observed, attesting that the large majority of the LHON mutations were due to independent mutational events. Assignment of the mutational events into haplogroups confirmed that J1 and J2 play a role in LHON expression but narrowed the association to the subclades J1c and J2b, thus suggesting that two specific combinations of amino acid changes in the cytochrome b are the cause of the mtDNA background effect and that this may occur at the level of the supercomplex formed by respiratory-chain complexes I and III. The families with identical haplotypes were genealogically reinvestigated, which led to the reconnection into extended pedigrees of three pairs of families, including the Brazilian family with its Italian counterpart. The sequencing of entire mtDNA samples from the reconnected families confirmed the genealogical reconstruction but showed that the Brazilian family was heteroplasmic at two control-region positions. The survey of the two sites in 12 of the Brazilian subjects revealed triplasmy in most cases, but there was no evidence of the tetraplasmy that would be expected in the case of mtDNA recombination.

Drainage or nondrainage in elective colorectal anastomosis: a systematic review and meta‐analysis

Abstract: Background There is little agreement on prophylactic use of drains in anastomoses in elective colorectal surgery despite many randomized clinical trials. Once anastomotic leakage occurs it is generally agreed that drains Should be used for therapeutic purposes. However, Oil prophylactic use no such agreement exists. Aim To compare the safety and effectiveness of routine drainage and nondrainage regimes after elective colorectal surgery. The primary outcome was clinical anastomotic leakage. Methods A systematic search was undertaken to identify randomized clinical trials. Of the 1140 patients who were enrolled (six randomized controlled trials), 573 were allocated for drainage and 567 for no drainage. Outcome measures were: (i) mortality: 3% (18 of 573 patients) compared with 4% (25 of 567 patients); (ii) clinical anastomotic dehiscence: 2% (11 of 522 patients) compared with 1% (7 of 519 patients); (iii) radiological anastomotic dehiscence: 3% (16 of 522 patients) compared with 4% (19 of 519 patients); (iv) wound infection: 5% (29 of 573 patients) compared with 5% (28 of 567 patients); (v) reintervention: 6% (34 of 542 patients) compared with. 5% (28 of 539 patients); (vi) extra-abdominal complications: 7% (34 of 522 patients) compared with 6% (32 of 5 19 patients). None of these differences in outcome was significant. Conclusion There is insufficient evidence showing that routine drainage after colorectal anastomoses prevents anastomotic and other complications.

CD4+CD25+ T Cells in Skin Lesions of Patients with Cutaneous Leishmaniasis Exhibit Phenotypic and Functional Characteristics of Natural Regulatory T Cells

Abstract: Endogenous regulatory T (Treg) cells are involved in the control of infections, including Leishmania infection in mice. Leishmania viannia braziliensis is the main etiologic agent of cutaneous leishmaniasis (CL) in Brazil, and it is also responsible for the more severe mucocutaneous form. Here, we investigated the possible involvement of Treg cells in the control of the immune response in human skin lesions caused by L. viannia braziliensis infection. We show that functional Treg cells can be found in skin lesions of patients with CL. These cells express phenotypic markers of Treg cells—such as CD25, cytotoxic T lymphocyte–associated antigen 4, Foxp3, and glucocorticoid-induced tumor necrosis factor receptor—and are able to produce large amounts of interleukin-10 and transforming growth factor–b. Furthermore, CD4+CD25+ T cells derived from the skin lesions of 4 of 6 patients with CL significantly suppressed in vitro the phytohemagglutinin-inducedproliferative T cell responses of allogeneic peripheral-blood mononuclear cells (PBMCs) from healthy control subjects at a ratio of 1 Treg cell to 10 allogeneic PBMCs. These findings suggest that functional Treg cells accumulate at sites of Leishmania infection in humans and possibly contribute to the local control of effector T cell functions

Xanthine Oxidoreductase Inhibition Causes Reverse Remodeling in Rats With Dilated Cardiomyopathy

Abstract: Increased reactive oxygen species (ROS) generation is implicated in cardiac remodeling in heart failure (HF). As xanthine oxidoreductase (XOR) is 1 of the major sources of ROS, we tested whether XO...

Results of the Brazilian Osteosarcoma Treatment Group Studies III and IV: Prognostic Factors and Impact on Survival

Abstract: Purpose To evaluate the impact of chemotherapy and surgery on the outcome of osteosarcoma (OS) of the extremities and to identify prognostic factors in Brazilian patients. Patients and Methods A total of 225 patients with metastatic and nonmetastatic OS of the extremities were enrolled and assessed in two consecutive studies designed and implemented by the Brazilian Osteosarcoma Treatment Group. Results The 5-year survival and event-free survival rates for the 209 assessable patients were 50.1% and 39%, respectively; for the 178 patients with nonmetastatic disease at diagnosis, the rates were 60.5% and 45.5%, respectively. The multivariate analysis showed that the following variables were associated with a shorter survival: metastases at diagnosis (P < .001), necrosis grades 1 and 2 (P = .046), and tumor size (P = .0071). Conclusion The overall 5- and 10-year survival rates were lower than the rates reported in North American and European trials. A pattern of advanced disease at diagnosis was often presen...

Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43

Abstract: Connexin43 (Cx43) is involved in bone development, but its role in adult bone homeostasis remains unknown. To overcome the postnatal lethality of Cx43 null mutation, we generated mice with selective osteoblast ablation of Cx43, obtained using a Cx43fl allele and a 2.3-kb fragment of the alpha1(I) collagen promoter to drive Cre in osteoblasts (ColCre). Conditionally osteoblast-deleted ColCre;Cx43-/fl mice show no malformations at birth, but develop low peak bone mass and remain osteopenic with age, exhibiting reduced bone formation and defective osteoblast function. By both radiodensitometry and histology, bone mineral content increased rapidly and progressively in adult Cx43+/fl mice after subcutaneous injection of parathyroid hormone (PTH), an effect significantly attenuated in ColCre;Cx43-/fl mice, with Cx43-/fl exhibiting an intermediate response. Attenuation of PTH anabolic action was associated with failure to increase mineral apposition rate in response to PTH in ColCre;Cx43-/fl, despite an increased osteoblast number, suggesting a functional defect in Cx43-deficient bone-forming cells. In conclusion, lack of Cx43 in osteoblasts leads to suboptimal acquisition of peak bone mass, and hinders the bone anabolic effect of PTH. Cx43 represents a potential target for modulation of bone anabolism.

Sarcopenia associada ao envelhecimento: aspectos etiológicos e opções terapêuticas

Abstract: The high prevalence of inability and functional dependence is an important problem in elderly people It is closely related with aging decrease of lean muscle mass that occurs even in healthy subjects Skeletal muscle mass deficiency, or sarcopenia, results from complex interactions between innervations disturbances, hormones deficiency, inflammatory cytokines and restriction in caloric-proteic ingestion Loss of skeletal muscle mass and strength results in disability and functional dependency that are associated to frailty in many elderly people These conditions represent enormous economic and social budget In this article, we evaluate pathogenesis of sarcopenia and discuss potential therapies

Occurrence and Characterization of Carbapenemase-Producing Enterobacteriaceae: Report from the SENTRY Antimicrobial Surveillance Program (2000–2004)

Abstract: Emergence and dissemination of Enterobacteriaceae isolates harboring carbapenemases in various geographic regions represents a significant threat to the management of nosocomial infections. Enterobacteriaceae isolates from the SENTRY Antimicrobial Surveillance Program (2000–2004) demonstrating decreased susceptibility to imipenem and meropenem (minimum inhibitory concentration [MIC], ≥2 mg/L) were evaluated for the production of metallo-β-lactamases and serine carbapenemases using disk approximation and polymerase chain reaction (PCR) tests. Carbapenemase-producing strains were epidemiologically typed by automated riboprinting and pulsed-field gel electrophoresis (PFGE) to establish clonality. Among 37,557 Enterobacteriaceae (5 genus groups) evaluated, 119 (0.32%) had increased carbapenem MIC values, and a carbapenemase was identified in 51 (42.9%) of these strains. KPC-2 and KPC-3 were the most frequently occurring carbapenemases (24 isolates, 20.2%) in the United States and were detected in Klebsiella s...

Percepção e satisfação corporal em adolescentes e a relação com seu estado nutricional

Abstract: Background: The self-perception of and the satisfaction with their body image are determinant factors for the self-acceptance of the adolescents, and may generate inadequate attitudes that impair their growth and development. Objective: To investigate the association between nutritional state in adolescents and the self-perception of the satisfaction with body image. Methods: We obtained body mass index (BMI) through anthropometric data in order to classify the nutritional state of the adolescents. We also used standardized silhouettes to evaluate their self-perception of their body image, and a self-completing questionnaire to determine their satisfaction with their body image. Results: Most of the population was eutrophic. The girls, however, did not regard themselves that way. Even Perception and satisfaction with body image in adolescents and correlations with nutrition status