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Oliveira C.R.P.,Federal University of Sergipe | Salvatori R.,Johns Hopkins University | Meneguz-Moreno R.A.,Federal University of Sergipe | Aguiar-Oliveira M.H.,Federal University of Sergipe | And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Background: GH deficiency (GHD) is often associated with cardiovascular risk factors, including abdominal fat accumulation, hypercholesterolemia, and increased C-reactive protein. Despite the presence of these risk factors, adults with congenital lifetime isolated GHD (IGHD) due to an inactivating mutation in the GHRH receptor gene do not have premature atherosclerosis. Objective: The aim was to study the serum levels of adiponectin and leptin (antiatherogenic and atherogenic adipokine, respectively), and the urinary albumin excretion (UAE) in these IGHD individuals. Design and Patients: We conducted a cross-sectional study of 20 IGHD individuals (seven males; age, 50.8 ± 14.6 yr) and 22 control subjects (eight males; age, 49.9 ± 11.5 yr). Main Outcome Measures: Anthropometric factors, body composition, blood pressure, serum adiponectin, leptin, and UAE were measured. Results: Adiponectin was higher [12.8 (7.1) vs. 9.7 (5) ng/ml; P = 0.041] in IGHD subjects, whereas no difference was observed in leptin [7.3 (6.3) vs. 9.3 (18.7 ng/ml] and UAE [8.6 (13.8) vs. 8.5 (11.1) μg/min]. Conclusions: Subjects with lifetime untreated IGHD have an adipokine profile with high adiponectin and normal leptin levels that may delay vascular damage and lesions of the renal endothelium. Copyright © 2010 by The Endocrine Society.


Forno E.,University of Pittsburgh | Gogna M.,University of Pittsburgh | Cepeda A.,Metropolitan University of Colombia | Yanez A.,Servicio de Alergia e Inmunologia Clinica | And 7 more authors.
Thorax | Year: 2015

Consistent with the diversity of Latin America, there is profound variability in asthma burden among and within countries in this region. Regional variation in asthma prevalence is likely multifactorial and due to genetics, perinatal exposures, diet, obesity, tobacco use, indoor and outdoor pollutants, psychosocial stress and microbial or parasitic infections. Similarly, non-uniform progress in asthma management leads to regional variability in disease morbidity. Future studies of distinct asthma phenotypes should follow-up well-characterised Latin American subgroups and examine risk factors that are unique or common in Latin America (eg, stress and violence, parasitic infections and use of biomass fuels for cooking). Because most Latin American countries share the same barriers to asthma management, concerted and multifaceted public health and research efforts are needed, including approaches to curtail tobacco use, campaigns to improve asthma treatment, broadening access to care and clinical trials of non-pharmacological interventions (eg, replacing biomass fuels with gas or electric stoves).


Dias A.C.,Federal University of Sao Paulo | Araujo M.R.,Instituto Nacional Of Politicas Do Alcool E Drogas | Laranjeira R.,Escola Paulista de Medicina
Revista de Saude Publica | Year: 2011

Objective: To analyze the evolution of drug use among treated crack cocaine users. Methods: A cohort originally comprising 131 crack addicts admitted to a detoxification unit in the city of São Paulo, Southeastern Brazil, between 1992 and 1994 were followed up on three occasions: 1995-96, 1998-99, and 2005- 06. Variables investigated included demographical data, risky sexual behaviors, intake patterns for crack and other substances, incarceration, disappearance, and death. Statistical analysis was carried out using chi-square tests, multinomial logistic regression and Cox regression. Results: Among the patients evaluated, 43 were crack-free (12 months or longer), 22 were users, 13 were imprisoned, two were missing, and 27 were deceased. Three groups with distinct post-discharge drug use patterns were identified. Safe sexual behavior (condom use) was correlated with stable abstinence (p=0.001). Positive HIV test upon admission (p=0.046), use of snorted cocaine in the last year (p=0.001), and lifetime use of snorted cocaine (132 months or longer) (p=0.000) were associated with long term use of crack cocaine. History of intravenous cocaine use increased the probability of death at 12 years by 2.5 fold (p=0.031) (95%CI: 1.08; 5.79). Conclusions: Recurrence and persistence of crack use in the years following discharge reflect new modalities of drug use. On the other hand, stable abstinence patterns provide evidence of the feasibility of recovery from crack addiction.


Almeida A.P.M.M.,Federal University of Minas Gerais | Dias M.O.,Federal University of Minas Gerais | Vieira C.D.A.F.,Federal University of Minas Gerais | Chavez-Olortegui C.,Federal University of Minas Gerais | And 4 more authors.
Vaccine | Year: 2014

The circumsporozoite protein (CSP), the most abundant surface antigen of sporozoites, has been extensively studied in different expression platforms as a vaccine candidate. Clinical trials have shown the necessity of broad and highly avid humoral immune responses together with high numbers of CSP-specific TCD4+ and TCD8+ cells, especially those producing IFN-γ, to induce protection. To this aim, we designed two distinct recombinant immunogens based on previously-described antigenic fragments of Plasmodium vivax CSP (PvCSP) to be used as vaccine candidates. The first one is a virus-like particle (VLP) comprising the repeat region of PvCSP (B and TCD4+ epitopes) within the loop of the hepatitis B virus core antigen (HBcAgPvCSP). The second one is a PvCSP multi-epitope polypeptide, rPvCSP-ME, designed based on antigenic regions of PvCSP recognized by lymphocytes of individuals from endemic areas.Mice immunized with 2 doses of these proteins, administered individually or combined and formulated in Montanide ISA 720 adjuvant, were able to induce strong effector and memory humoral responses with IgG titers ranging from 104 to 105 and avidity indexes toward full-length PvCSP reaching up to 66%, even 3 months after the last immunization. Furthermore, balanced Th1/Th2 responses were generated, as determined by titers of IgG subclasses and further confirmed by ELISPOT analyses, which detected that these vaccination protocols were able to elicit long-term IFN-γ and IL-2-secreting memory T-cells. Overall, these results show that our vaccine candidates generate, in mice, immune responses against regions within PvCSP that have been associated with protection against malaria in humans. © 2014 Elsevier Ltd.


Moretti A.I.S.,University of Sao Paulo | Souza Pinto F.J.P.,University of Sao Paulo | Cury V.,University of Sao Paulo | Jurado M.C.,University of Sao Paulo | And 3 more authors.
Acta Biomaterialia | Year: 2012

Prosthetic meshes are commonly used to correct abdominal wall defects. However, the inflammatory reaction induced by these devices in the peritoneum is not completely understood. We hypothesized that nitric oxide (NO), produced by nitric oxide synthase 2 (NOS2) may modulate the response induced by mesh implants in the abdominal wall and, consequently, affect the outcome of the surgical procedure. Polypropylene meshes were implanted in the peritoneal side of the abdominal wall in wild-type and NOS2-deficient (NOS2 -/-) mice. After 15 days tissues around the mesh implant were collected, and inflammatory markers (the cytokine interleukin 1β (IL-1β) and NO) and tissue remodeling (collagen and metalloproteinases (MMP) 2 and 9) were analyzed. The lack of NOS2-derived NO induced a higher incidence of visceral adhesions at the mesh implantation site compared with wild-type mice that underwent the same procedure (P < 0.05). Additionally, higher levels of IL-1β were present in the mesh-implanted NOS2 -/- animals compared with control and wild-type mice. Mesh implantation induced collagen I and III deposition, but in smaller amounts in NOS2 -/- mice. MMP-9 activity after the surgical procedure was similarly increased in both groups. Conversely, MMP-2 activity was unchanged in mesh-implanted wild-type mice, but was significantly increased in NOS2 -/- mice (P < 0.01), due to decreased S-nitrosylation of the enzyme in these animals. We conclude that NOS2-derived NO is crucial for an adequate response to and integration of polypropylene mesh implants in the peritoneum. NO deficiency results in a prolonged inflammatory reaction to the mesh implant, and reduced collagen deposition may contribute to an increased incidence of visceral adhesions. © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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