836 research outputs found

    Lineage-specific serology confirms Brazilian Atlantic forest lion tamarins, Leontopithecus chrysomelas and Leontopithecus rosalia, as reservoir hosts of Trypanosoma cruzi II (TcII).

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    BACKGROUND: Trypanosoma cruzi, the agent of Chagas disease in humans, has a vast reservoir of mammalian hosts in the Americas, and is classified into six genetic lineages, TcI-TcVI, with a possible seventh, TcBat. Elucidating enzootic cycles of the different lineages is important for understanding the ecology of this parasite, the emergence of new outbreaks of Chagas disease and for guiding control strategies. Direct lineage identification by genotyping is hampered by limitations of parasite isolation and culture. An indirect method is to identify lineage-specific serological reactions in infected individuals; here we describe its application with sylvatic Brazilian primates. METHODS: Synthetic peptides representing lineage-specific epitopes of the T. cruzi surface protein TSSA were used in ELISA with sera from Atlantic Forest Leontopithecus chrysomelas (golden-headed lion tamarin), L. rosalia (golden lion tamarin), Amazonian Sapajus libidinosus (black-striped capuchin) and Alouatta belzebul (red-handed howler monkey). RESULTS: The epitope common to lineages TcII, TcV and TcVI was recognised by sera from 15 of 26 L. chrysomelas and 8 of 13 L. rosalia. For 12 of these serologically identified TcII infections, the identity of the lineage infection was confirmed by genotyping T. cruzi isolates. Of the TcII/TcV/TcVI positive sera 12 of the 15 L. chrysomelas and 2 of the 8 L. rosalia also reacted with the specific epitope restricted to TcV and TcVI. Sera from one of six S. libidinous recognised the TcIV/TcIII epitopes. CONCLUSIONS: This lineage-specific serological surveillance has verified that Atlantic Forest primates are reservoir hosts of at least TcII, and probably TcV and TcVI, commonly associated with severe Chagas disease in the southern cone region of South America. With appropriate reagents, this novel methodology is readily applicable to a wide range of mammal species and reservoir host discovery

    Clinical outcome of renal transplant patients after coronary stenting

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    OBJECTIVE: To assess the clinical outcome of renal transplant patients who developed coronary artery disease and were treated with coronary stenting (TCA-ST). METHODS: A total of 3,334 renal transplants were performed in our service - Hospital do Rim e Hipertensão - HRH (Kidney and Hypertension Hospital) from July, 1998 to November, 2004. During this period, 33 of the renal transplant patients underwent TCA-ST to treat 62 severe stenoses in 54 coronary arteries. A retrospective analysis was performed with renal transplant patients undergoing TCA-ST at HRH. The clinical events were registered using medical charts, medical visits and phone calls. RESULTS: During the 30-month clinical follow-up after TCA-ST, 67% of the patients remained asymptomatic, 18% presented stable angina, 6% presented acute coronary syndrome without ST-segment elevation (ACSWSTE), and 3% presented acute coronary syndrome with ST-segment elevation (ACSSTE). No strokes, CHF or cardiac deaths were observed. Three non-cardiac deaths occurred. A restenosis rate of 9% was observed, which is comparable to those found in studies on drug-eluting stents. CONCLUSION: In conclusion, renal transplant patients who developed CAD and were treated with coronary stenting had a low rate of in-stent restenosis, probably related to the immunosuppressive regimen given to prevent kidney rejection.OBJETIVO: Avaliar a evolução clínica de pacientes submetidos a transplante de rim, portadores de doença arterial coronariana, que foram tratados com implante de stent coronariano (ATC-ST). MÉTODOS: Entre julho de 1998 e novembro de 2004, foram realizados, no total, 3.334 transplantes de rim em nossa Instituição (Hospital do Rim e Hipertensão). Desse total, 33 pacientes previamente submetidos a transplante de rim fizeram ATC-ST para o tratamento de 62 estenoses graves em 54 artérias coronárias, nos quais foi realizada análise retrospectiva. O registro dos eventos clínicos foi feito por meio de análise do prontuário médico, consulta médica e ligações telefônicas. RESULTADOS: No seguimento clínico de 30 meses, após a ATC-ST, observou-se que 67% dos pacientes permaneceram assintomáticos, 18% dos pacientes apresentaram quadro de angina estável, 6% apresentaram síndrome coronariana aguda sem supra de ST e 3% apresentaram síndrome coronariana aguda com supra de ST. Não houve pacientes com acidente vascular cerebral, insuficiência cardíaca congestiva ou morte cardíaca. Houve três mortes não-cardíacas. Foi observado índice de reestenose de 9%, que é comparável ao dos estudos de stent farmacológico. CONCLUSÃO: Concluímos que pacientes submetidos a transplante de rim que desenvolveram doença arterial coronariana e que foram tratados com stent coronariano tiveram baixo porcentual de reestenose clínica, provavelmente relacionado ao regime de imunossupressão administrado para evitar rejeição renal.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Hospital do Rim e HipertensãoUNIFESP, EPM, Hospital do Rim e HipertensãoSciEL

    Prevalence of antibodies against Chlamydophila spp. in herds with bovine abortion of Paraná state, Brazil

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    Chlamydophila abortus é o agente etiológico do aborto epizoótico bovino, cujas manifestações clínicas mais freqüentes são aborto, nascimento de bezerros prematuros e de animais fracos, natimorto e repetição de cio em intervalos irregulares. O objetivo deste trabalho foi estimar a prevalência de anticorpos anti-Chlamydophila spp. em fêmeas bovinas de propriedades rurais com histórico de aborto, selecionadas dentro do delineamento amostral do Plano Nacional de Controle e Erradicação da Brucelose e Tuberculose no estado do Paraná. Foram testadas pela prova de fixação de complemento 3.102 amostras de soro de fêmeas bovinas (idade > 24 meses), provenientes de 373 propriedades. Ao total, 44 (1,42%) animais foram positivos com títulos > 32. A prevalência de focos foi de 8,82% (6,15%-12,17%). Animais confinados ou semi-confinados (OR=3.339, P=0.004), propriedade com menos de 35 matrizes (OR=3.339, P=0.017), presença de produtos do aborto na pastagem (OR=2.372, P=0.037) e aluguel de pasto (OR=3.398, P=0.006) foram considerados fatores de risco para Chlamydophila spp. A infecção por Chlamydophila spp. acometeu um número pequeno de animais, oriundos de propriedades com histórico de aborto. A importância deste agente como causa de aborto em bovinos no estado do Paraná, se existir, é muito pequena.Chlamydophila abortus is a recognized cause of bovine epizootic abortion. Abortion, premature birth and weak lamb/calf, stillbirth and repeat breeding in irregular intervals are the most frequent disease manifestations. The complement fixation test is the recommended by the World Organization of Animal Health (OIE) for Chlamydophila spp. serologic diagnosis. The aim of this study was estimate the prevalence of antibodies against Chlamydophila spp. in cattle herds with abortion, selected inside the sampling design of National Program of Control and Erradication of Brucellosis in Paraná state. Serum samples of 3,102 cows (age > 24 months) from 373 herds were analyzed by complement fixation test. Totally, 44 (1.42%) animal were positive with titers > 32. The seroprevalence of Chlamydophila spp. in the herds was 8.82% (6.15%-12.17%). Four variables were associated with seroprevalence for Chlamydophila spp. in the final model of logistic regression: confined or semi-confined breeding (OR=3.339, P=0.004), farms with less than 35 cows (OR=3.339, P=0.017), abortion in the pasture (OR=2.372, P=0.037) and pasture rent (OR=3.398, P=0.006) were risk factors for Chlamydophila spp. This bacterium infected a small number of cattle from herds with abortion in Paraná state. Chlamydophila spp impact as abortion cause is reduced in this state

    Glucocorticoid-induced leucine zipper modulates macrophage polarization and apoptotic cell clearance.

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    Macrophages are professional phagocytes that display remarkable plasticity, with a range of phenotypes that can be broadly characterized by the M1/M2 dichotomy. Glucocorticoid (GC)-induced leucine zipper (GILZ) is a protein known to mediate anti-inflammatory and some pro-resolving actions, including as neutrophil apoptosis. However, the role of GILZ in key macrophage function is not well understood. Here, we investigated the role of GILZ on macrophage reprogramming and efferocytosis. Using murine bone-marrow-derived macrophages (BMDMs), we found that GILZ was expressed in naive BMDMs and exhibited increased expression in M2-like macrophages (IL4-differentiated). M1-like macrophages (IFN/LPS-differentiated) from GILZ-/- mice showed higher expression of the M1 markers CD86, MHC class II, iNOS, IL-6 and TNF-α, associated with increased levels of phosphorylated STAT1 and lower IL-10 levels, compared to M1-differentiated cells from WT mice. There were no changes in the M2 markers CD206 and arginase-1 in macrophages from GILZ-/- mice differentiated with IL-4, compared to cells from WT animals. Treatment of M1-like macrophages with TAT-GILZ, a cell-permeable GILZ fusion protein, decreased the levels of CD86 and MHC class II in M1-like macrophages without modifying CD206 levels in M2-like macrophages. In line with the in vitro data, increased numbers of M1-like macrophages were found into the pleural cavity of GILZ-/- mice after LPS-injection, compared to WT mice. Moreover, efferocytosis was defective in the context of GILZ deficiency, both in vitro and in vivo. Conversely, treatment of LPS-injected mice with TAT-GILZ promoted inflammation resolution, associated with lower numbers of M1-like macrophages and increased efferocytosis. Collectively, these data indicate that GILZ is a regulator of important macrophage functions, contributing to macrophage reprogramming and efferocytosis, both key steps for the resolution of inflammation

    Depression as a determinant of frailty in late life

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    Objectives Accumulating evidence shows depression as a risk factor for frailty, but studies are mainly population-based and widely differ in their assessment of either depression or frailty. We investigated the association between depression and frailty among geriatric outpatients using different assessment instruments for both conditions. Method Among 315 geriatric outpatients (mean age 72.1 years, 68.3% female sex) participating the MiMiCS-FRAIL cohort study, major and subthreshold depression were measured with psychiatric diagnostic interview according to DSM-5 criteria (SCID-5) as well as with instruments to screen and measure severity of depressive symptoms (GDS-15 and PHQ-9). Frailty was assessed according to a screening instrument (FRAIL-BR) and a multidimensional Frailty Index (FI-36 items). Multiple logistic and linear regression were performed to assess the association between depression (independent variable) and frailty (dependent variable) adjusted for confounders. Results Frailty prevalence in patients with no, subthreshold or major depressive disorder increases from either 14.5%, 46.5% to 65.1% when using the FRAIL-BR questionnaire, and from 10.2%, 20.9%, to 30.2% when using the FI-36 index. These association remain nearly the same when adjusted for covariates. Both the FRAIL-BR and the FI-36 were strongly associated with major depressive disorder, subthreshold depression, and depressive symptoms by PHQ-9 and GDS-15. Conclusion Late life depression and frailty are associated in a dose-dependent manner, irrespective of the used definitions. Nonetheless, to avoid residual confounding, future research on underlying biological mechanisms should preferably be based on formal psychiatric diagnoses and objectively assessment frailty status

    Endothelium-mediated action of analogues of the endogenous neuropeptide kyotorphin (tyrosil-arginine) : mechanistic insights from permeation and effects on microcirculation

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    © 2016 American Chemical SocietyKyotorphin (KTP) is an endogenous peptide with analgesic properties when administered into the central nervous system (CNS). Its amidated form (l-Tyr-l-Arg-NH2; KTP-NH2) has improved analgesic efficacy after systemic administration, suggesting blood-brain barrier (BBB) crossing. KTP-NH2 also has anti-inflammatory action impacting on microcirculation. In this work, selected derivatives of KTP-NH2 were synthesized to improve lipophilicity and resistance to enzymatic degradation while introducing only minor changes in the chemical structure: N-terminal methylation and/or use of d amino acid residues. Intravital microscopy data show that KTP-NH2 having a d-Tyr residue, KTP-NH2-DL, efficiently decreases the number of leukocyte rolling in a murine model of inflammation induced by bacterial lipopolysaccharide (LPS): down to 46% after 30 min with 96 μM KTP-NH2-DL. The same molecule has lower ability to permeate membranes (relative permeability of 0.38) and no significant activity in a behavioral test which evaluates thermal nociception (hot-plate test). On the contrary, methylated isomers at 96 μM increase leukocyte rolling up to nearly 5-fold after 30 min, suggesting a proinflammatory activity. They have maximal ability to permeate membranes (relative permeability of 0.8) and induce long-lasting antinociception.FCT-MCTES is acknowledged for PhD fellowship SFRH/BD/52225/2013 to J.P. Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE) is acknowledged for funding: call H2020-MSCA-RISE-2014, Grant agreement 644167, 2015-2019.info:eu-repo/semantics/publishedVersio

    Identification of hereditary cancer in the general population: development and validation of a screening questionnaire for obtaining the family history of cancer

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    One of the challenges for Latin American countries is to include in their healthcare systems technologies that can be applied to hereditary cancer detection and management. The aim of the study is to create and validate a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The primary screening questionnaire (PSQ) was developed to identify families at-risk for HCPS. The PSQ was validated using discrimination measures, and the reproducibility was estimated through kappa coefficient. Patients with at least one affirmative answer had the pedigree drawn using three alternative interview approaches: in-person, by telephone, or letter. Validation of these approaches was done. Kappa and intraclass correlation coefficients were used to analyze data’s reproducibility considering the presence of clinical criteria for HCPS. The PSQ was applied to a convenience sample of 20,000 women of which 3121 (15.6%) answered at least one affirmative question and 1938 had their pedigrees drawn. The PSQ showed sensitivity and specificity scores of 94.4% and 75%, respectively, and a kappa of 0.64. The strategies for pedigree drawing had reproducibility coefficients of 0.976 and 0.850 for the telephone and letter approaches, respectively. Pedigree analysis allowed us to identify 465 individuals (24.0%) fulfilling at least one clinical criterion for HCPS. The PSQ fulfills its function, allowing the identification of HCPS at-risk families. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.Research supported by Barretos Cancer Hospital. EIP has a grant from FAPESP (FAPESP, SP, Brazil, #2013/24633-2). N Campacci is supported by a PhD fellowship from FAPESP (FAPESP, SP, Brazil, #2015/02444-9).info:eu-repo/semantics/publishedVersio
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