CAPACITAÇÃO DOS ACS DO TERRITÓRIO DO SISAL PARA O DIAGNÓSTICO PRECOCE DE LESÕES POTENCIALMENTE MALIGNAS

O câncer oral é considerado um problema de saúde pública, uma vez que ainda nos dias atuais, seu diagnóstico é realizado de forma tardia

Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

C7a, a Biphosphinic Cyclopalladated Compound, Efficiently Controls the Development of a Patient-Derived Xenograft Model of Adult T Cell Leukemia/Lymphoma

Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive disease that occurs in individuals infected with the human T lymphotropic virus type 1 (HTLV-1). Patients with aggressive ATLL have a poor prognosis because the leukemic cells are resistant to conventional chemotherapy. We have investigated the therapeutic efficacy of a biphosphinic cyclopalladated complex {Pd2 [S(−)C2, N-dmpa]2 (μ-dppe)Cl2}, termed C7a, in a patient-derived xenograft model of ATLL, and investigated the mechanism of C7a action in HTLV-1-positive and negative transformed T cell lines in vitro. In vivo survival studies in immunocompromised mice inoculated with human RV-ATL cells and intraperitoneally treated with C7a led to significantly increased survival of the treated mice. We investigated the mechanism of C7a activity in vitro and found that it induced mitochondrial release of cytochrome c, caspase activation, nuclear condensation and DNA degradation. These results suggest that C7a triggers apoptotic cell death in both HTLV-1 infected and uninfected human transformed T-cell lines. Significantly, C7a was not cytotoxic to peripheral blood mononuclear cells (PBMC) from healthy donors and HTLV-1-infected individuals. C7a inhibited more than 60% of the ex vivo spontaneous proliferation of PBMC from HTLV-1-infected individuals. These results support a potential therapeutic role for C7a in both ATLL and HTLV-1-negative T-cell lymphomas

Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Small molecule glucagon release inhibitors with activity in human islets

PurposeType 1 diabetes (T1D) accounts for an estimated 5% of all diabetes in the United States, afflicting over 1.25 million individuals. Maintaining long-term blood glucose control is the major goal for individuals with T1D. In T1D, insulin-secreting pancreatic islet β-cells are destroyed by the immune system, but glucagon-secreting islet α-cells survive. These remaining α-cells no longer respond properly to fluctuating blood glucose concentrations. Dysregulated α-cell function contributes to hyper- and hypoglycemia which can lead to macrovascular and microvascular complications. To this end, we sought to discover small molecules that suppress α-cell function for their potential as preclinical candidate compounds. Prior high-throughput screening identified a set of glucagon-suppressing compounds using a rodent α-cell line model, but these compounds were not validated in human systems. ResultsHere, we dissociated and replated primary human islet cells and exposed them to 24 h treatment with this set of candidate glucagon-suppressing compounds. Glucagon accumulation in the medium was measured and we determined that compounds SW049164 and SW088799 exhibited significant activity. Candidate compounds were also counter-screened in our InsGLuc-MIN6 β-cell insulin secretion reporter assay. SW049164 and SW088799 had minimal impact on insulin release after a 24 h exposure. To further validate these hits, we treated intact human islets with a selection of the top candidates for 24 h. SW049164 and SW088799 significantly inhibited glucagon release into the medium without significantly altering whole islet glucagon or insulin content. In concentration-response curves SW088799 exhibited significant inhibition of glucagon release with an IC50 of 1.26 µM. ConclusionGiven the set of tested candidates were all top hits from the primary screen in rodent α-cells, this suggests some conservation of mechanism of action between human and rodents, at least for SW088799. Future structure-activity relationship studies of SW088799 may aid in elucidating its protein target(s) or enable its use as a tool compound to suppress α-cell activity in vitro

Adaptation of Ritchie's Method for Parasites Diagnosing with Minimization of Chemical Products

Latin America, Africa, and Asia present wide dissemination and high prevalence rates of waterborne parasitic diseases, which is a strong indicative of the fragility of public sanitation systems. In this context, parasitological analyses represent extremely relevant instruments. Several parasite diagnosis methods exist, among which Ritchie’s method (1948) stands out. This method uses formaldehyde and ether, two reagents of toxicological importance that can cause damages to environmental and occupational health. The present study aimed to compare Ritchie’s method modified by Régis Anécimo, without use of solvents, with the traditional Ritchie’s method, routinely used for helminth and protozoa diagnosing in Brazil. Some changes were introduced in the modified method, such as controlled increase of water temperature used after stool dilution and substitution of formaldehyde and ether by a neutral detergent before material centrifugation for observation of parasites. In examined samples by both methods, multiple infections were commonly observed; the modified method presented a similar sensitivity to identify the parasites. The development of analytic diagnosis methods that minimize the use of chemical products like ether and formaldehyde represents an important tool to prevent occupational diseases among exposed professionals, as well as to preserve environmental quality through the use of clean techniques

Monilethrix: the use of tricoscopy in clinical diagnosis

Monilethrix is a Greco-Latin term that mean “hair stick”1. It is a rare genetic disorder with autosomal dominant inheritance, characterized by degeneration of the hair matrix and formation of defective cuticle. The hairs are brittle and not exceed a few inches length. The scalp is the most affected region and the most common clinical presentation is alopecia associated with keratosis follicularis2,3. The diagnosis is clinical and the tricoscopia evidence moniliformes changes (switching between wide and narrow band)Monilethrix é termo de origem greco-latina que significa “cabelo em colar”1. Trata-se de doença genética rara, com herança autossômica dominante, caracterizada por degeneração da matriz do cabelo e forma- ção de uma cutícula defeituosa. Os cabelos são quebradiços e não excedem poucos centímetros de comprimento. O couro cabeludo é a região mais afetada e a apresentação clínica mais comum é alopecia associada à queratose folicular2,3. O diagnóstico é clínico e a tricoscopia evidencia alterações moniliformes (alternância entre bandas largas e estreitas

High success and low mortality rates with non-invasive ventilation in influenza A H1N1 patients in a tertiary hospital

<p>Abstract</p> <p>Background</p> <p>In 2009, an outbreak of respiratory illness caused by influenza A H1N1 virus occurred worldwide. Some patients required Intensive Care Unit (ICU) admission. The use of non-invasive ventilation (NIV) in these patients is controversial, as the aerosol dispersion may contaminate the environment and health-care co-workers.</p> <p>Methods</p> <p>Describe the respiratory profile, the mortality rate, and the benefit of using NIV in patients with confirmed diagnosis of influenza AH1N1 who were admitted in the ICU during the year 2009.</p> <p>Results</p> <p>A total of 1, 401 cases of influenza A H1N1 were confirmed in our hospital by real-time RT-PCR in 2009, and 20 patients were admitted to the ICU. The patients' ages ranged from 18 to 74 years (median of 42). Acute Respiratory Failure (ARF) was present in 70% of patients. The median Acute Physiology and Chronic Health Evaluation II score was 7 (range 7 to 25). Of the 14 patients who developed ARF, 85.7% needed NIV and 14% needed invasive MV at admission. Our success rate (41.6%) with NIV was higher than that described by others. The hospital mortality rate was 2.1%. When influenza A H1N1 arrived in Brazil, the disease was already on endemic alert in other countries. The population was already aware of the symptoms and the health-care system of the treatment. This allowed patients to be properly and promptly treated for influenza A H1N1, while health-care workers took protective measures to avoid contamination.</p> <p>Conclusion</p> <p>In our study we found a high success and low mortality rates with non-invasive ventilation in patients with influenza A H1N1.</p