RESUMO
Diabetic kidney disease (DKD) is the most frequent cause of end-stage renal disease in western countries. This implies that current methods based of renin angiotensin aldosterone system (RAAS) targeting for preventing, slowing or promoting regression of DKD are insufficient. Podocyte injury and albuminuria are thought to be key events in DKD. Indeed several DKD stages are recognized based on the magnitude of albuminuria. However, the spectrum of DKD has recently expanded, as lack of significant albuminuria is present in 30% of diabetics with kidney function impairment. This may result from the widespread use of drugs targeting the RAAS. However, it may also indicate that additional pathogenic factors contribute to renal function deterioration despite control of albuminuria. In this regard, double blockade of the RAAS is more effective in reducing albuminuria that blockade of a single component. However, clinical trials assessing double blockade for renal function preservation have been disappointing and raised safety issues. Non-biased -omics approaches have uncovered alternative therapeutic targets, including the cytokine TRAIL, the MIF receptor CD74 and the proapoptotic intracellular protein BASP1. In addition, urinary proteomics has uncovered a peptidomic fingerprint for DKD progression that precedes the onset of microalbuminuria. Studies are underway to validate this fingerprint for early treatment of high risk patients. Recent clinical trials suggest a potential role of bardoxolone methyl to improve renal function in advanced DKD, while trials of avosentan, pirfenidone, sulodexide and pyridoxamine have been disappointing and further data are needed for paricalcitol and vitamin D, newer generation endothelin receptor antagonists and pentoxifylline.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Fármacos Renais/uso terapêutico , Albuminúria/tratamento farmacológico , Albuminúria/etiologia , Inibidores da Enzima Conversora de Angiotensina , Antígenos de Diferenciação de Linfócitos B , Biomarcadores/análise , Ensaios Clínicos como Assunto , Nefropatias Diabéticas/complicações , Progressão da Doença , Quimioterapia Combinada/métodos , Antígenos de Histocompatibilidade Classe II , Humanos , Falência Renal Crônica/etiologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas do Tecido Nervoso/antagonistas & inibidores , Podócitos/fisiologia , Proteômica/métodos , Sistema Renina-Angiotensina/efeitos dos fármacos , Proteínas Repressoras/antagonistas & inibidores , Ligante Indutor de Apoptose Relacionado a TNF/antagonistas & inibidoresRESUMO
Background: The population of South America has been severely affected by the COVID-19 pandemic. In this region, during the year 2020, high seroprevalence percentages were reported, which have been associated with the socioeconomic characteristics of the population, mainly in urban areas. However, a relative lack of information on the dynamics of the pandemic in rural areas of these countries, where the population is more vulnerable, is still present. This study determined antibody prevalence against SARS-CoV-2 in urban and rural food producing workers in Colombia. Methods: A total of 1242 workers, urban and rural, linked to poultry, dairy, and meat production and supply chains, were analyzed through a sociodemographic survey and two serological tests against S and N proteins of SARS-CoV-2. Results: 78.7% were male. 50.9% of the participants were rural inhabitants, with an average age of 40.9 years old. 39.2% had IgM and IgG against SARS-CoV-2 S protein and 31.3% against N protein for the same virus; 83.6% had not been tested with an RT-PCR test for COVID-19 and 75.7% did not report symptoms related to the disease. The associated risk factors were low education, OR: 1.46, greater number of cohabitants, OR: 1.36, and contact with people infected with COVID-19, OR: 2.03. Conclusions: The seroprevalences found suggest an important interconnectivity between rural and urban areas, where asymptomatic subjects and sociodemographic factors facilitate the virus' spread in the population.
RESUMO
Evidence from Europe suggests establishing out-of-hospital, uncontrolled donation after circulatory determination of death (UDCDD) protocols has potential to substantially increase organ availability. The study objective was to derive an out-of-hospital UDCDD protocol that would be acceptable to New York City (NYC) residents. Participatory action research and the SEED-SCALE process for social change guided protocol development in NYC from July 2007 to September 2010. A coalition of government officials, subject experts and communities necessary to achieve support was formed. Authorized NY State and NYC government officials and their legal representatives collaboratively investigated how the program could be implemented under current law and regulations. Community stakeholders (secular and religious organizations) were engaged in town hall style meetings. Ethnographic data (meeting minutes, field notes, quantitative surveys) were collected and posted in a collaborative internet environment. Data were analyzed using an iterative coding scheme to discern themes, theoretical constructs and a summary narrative to guide protocol development. A clinically appropriate, ethically sound UDCDD protocol for out-of-hospital settings has been derived. This program is likely to be accepted by NYC residents since the protocol was derived through partnership with government officials, subject experts and community participants.
Assuntos
Morte , Obtenção de Tecidos e Órgãos/legislação & jurisprudência , Pesquisa Participativa Baseada na Comunidade , Humanos , Consentimento Livre e Esclarecido , Cidade de Nova Iorque , Parada Cardíaca Extra-Hospitalar , Obtenção de Tecidos e Órgãos/métodos , Isquemia QuenteRESUMO
Neospora caninum is a leading cause of abortion in cattle worldwide. The study of the immune response against N. caninum is critical to understand its epidemiology, pathogenesis, diagnosis and, ultimately, in preventing and controlling bovine neosporosis. Herein, we determined the gene expression of innate immune components endosomal RNA-sensing TLRs, BMAP28 cathelicidin, TNF-α and IL-10 and characterized the variation in both IgG ratio and avidity at delivery in N. caninum-infected heifers challenged at day 210 of gestation, colostrum and their calves. Increased BMAP28 expression was observed not only in colostrum but also in peripheral blood mononuclear cells (PBMC) and umbilical cord of calves from N. caninum-infected heifers in comparison with mock-infected control group. In addition, statistically significant decrease of TLR7 and IL-10 expression levels were observed in umbilical cord, suggesting an attempt to avoid an exacerbated immune response against the parasite. At delivery, serum and colostrum samples from infected group evidenced specific IgG anti-N. caninum. Infected heifers showed IgG1/IgG2 ratios <1 and high avidity specific IgG. As expected, colostrum samples of these animals exhibited a high IgG1 concentration and elevated avidity values. Three out of four calves from N. caninum-infected heifers had specific IgG with IgG1/IgG2 ratios>1 and lower avidity values before colostrum intake. Interestingly, both IgG1/IgG2 ratios and avidity values increased in seropositive calves after colostrum intake. Overall, this study provides novel information on neonatal immunity in congenitally infected calves, which is essential to understand how the immune pathways could be manipulated or immune components could be employed in order to improve protection against neosporosis.
Assuntos
Bovinos/imunologia , Colostro/imunologia , Regulação da Expressão Gênica no Desenvolvimento/imunologia , Imunidade Humoral , Imunidade Inata , Neospora/imunologia , Receptores Toll-Like/metabolismo , Animais , Anticorpos Antiprotozoários/imunologia , Bovinos/embriologia , Bovinos/metabolismo , Bovinos/parasitologia , Doenças dos Bovinos/genética , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/metabolismo , Doenças dos Bovinos/parasitologia , Feminino , Imunoglobulina G/imunologia , Interleucina-10/genética , Interleucina-10/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Gravidez , Proteínas/genética , Proteínas/metabolismo , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Receptores Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Cordão Umbilical/metabolismoRESUMO
The aim of this study was to describe bovine neosporosis in dairy cattle from the Sierra region, Ecuador. A case-control study was performed on 841 dairy cattle from 5 dairy herds. The overall seroprevalence was 23.4% having significant association between abortion and seropositivity (p < .05). Additionally, 46 fetuses were recovered from a local slaughterhouse to evaluate the frequency of vertical transmission. Seventeen and 3 fetuses were positive by PCR and had compatible histopathological lesions, respectively. N. caninum infection must be considered as a relevant cause of reproductive losses in Ecuador.
Assuntos
Aborto Animal/epidemiologia , Doenças dos Bovinos/epidemiologia , Coccidiose/veterinária , Neospora/isolamento & purificação , Aborto Animal/parasitologia , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Coccidiose/epidemiologia , Coccidiose/parasitologia , Indústria de Laticínios , Equador/epidemiologia , Feminino , Prevalência , Estudos SoroepidemiológicosRESUMO
The purpose of this work was to characterize the cellular phenotype in inflammatory infiltrates of fetal tissues from pregnant heifers immunized and experimentally challenged with Neospora caninum. Fetuses from 20 heifers separated into 5 groups were obtained. The experiment was designed as follow: Group A, heifers inoculated intravenously with live tachyzoites of Argentine strain NC-6 (nâ¯=â¯4); Group B heifers inoculated subcutaneously with soluble native antigen from the same strain formulated with immune stimulant complexes (ISCOMs) (nâ¯=â¯4); Group C heifers inoculated with recombinant proteins, rNcSAG1, rNcHSP20, rNcGRA7 formulated with ISCOMs (nâ¯=â¯4), Group D heifers inoculated subcutaneously with sterile phosphate buffered solution (nâ¯=â¯4) and Group E heifers inoculated subcutaneously with antigen-free ISCOMs (nâ¯=â¯4). Experimental challenge was performed at 70 days of gestation and all heifers were euthanized 34 days later. Fetal tissues were taken for histological studies. Inflammatory lesions were observed in brain and lung, and immunhistochemistry was used to identify CD3+, CD20+ and MHC II+ cells. The majority of the cells that infiltrate and circumscribe the lesions in the brain and lung tissue expressed MHC II antigen; varying between 70-90% of the total cellular infiltrate. CD3+ cells were also present within the lesions, contributing to up to 30% of the inflammatory cells. CD20+ cells appeared as a marginal group, in some cases, with a range between 10 and 25%. As expected, the immunolabeling of MHC II + and CD3 + cells in fetal tissues was associated with fetal infection with N. caninum. There were statistically significant differences in the distribution and population of the inflammatory infiltrate in relation to the immunogenic treatment and the type of tissue, with inflammatory cells being markedly less extensive fetuses from group A (dams previously exposed to N. caninum) and in brain tissue. This work showed that Neospora-infection induced MHC II+ and CD3+ cells in bovine fetuses from dams receiving experimental vaccines.
Assuntos
Coccidiose/imunologia , Feto/imunologia , Imunização/veterinária , Neospora/imunologia , Vacinas Protozoárias/imunologia , Animais , Encéfalo/citologia , Encéfalo/imunologia , Bovinos , Doenças dos Bovinos/imunologia , Feminino , Feto/citologia , Imuno-Histoquímica , Pulmão/citologia , Pulmão/imunologia , GravidezRESUMO
Double-phase scintigraphy using Tc-99m sestamibi MIBI is the study of choice for detecting parathyroid adenoma in patients with primary hyperparathyroidism. However, before parathyroid imaging, these patients may uncommonly present with multiple osteolytic lesions and bone scan findings consistent with metastatic disease. By excluding malignancy, the diagnosis of osteitis fibrosa cystica and parathyroid adenoma may subsequently be confirmed. The authors describe the case of an elderly patient who presented with imaging findings initially masquerading as metastatic disease. When parathyroid adenoma was finally diagnosed with Tc-99m MIBI imaging, radiopharmaceutical uptake was also noted within several brown tumors, including clinically significant brown tumors of the left lower extremity, a finding that has not been previously reported.
Assuntos
Adenoma/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Hiperparatireoidismo/diagnóstico por imagem , Osteíte Fibrosa Cística/diagnóstico por imagem , Neoplasias das Paratireoides/diagnóstico por imagem , Tecnécio Tc 99m Sestamibi , Idoso , Humanos , Masculino , CintilografiaAssuntos
Ventrículos do Coração/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Transposição dos Grandes Vasos/diagnóstico por imagem , Criança , Teste de Esforço , Humanos , Masculino , Radioisótopos de Tálio , Transposição dos Grandes Vasos/fisiopatologia , Transposição dos Grandes Vasos/terapia , Função Ventricular DireitaRESUMO
Evidence-based medicine (EBM) is defined as "the process of systematically finding, appraising and using contemporaneous research findings as the basis for clinical decisions". Although EBM has been extensively described across the Americas and Europe, no study has looked at the practice of EBM in Puerto Rico. A cross-sectional analysis based on a 23-item questionnaire was employed. We showed that there is a high use (88%) and familiarity (93%) with EBM, and that physicians keep a positive attitude towards EBM (80%) in Puerto Rico. There is an over-representation of academicians (58.9% vs. 34.6%, p = 0.02) and an under-representation of solo office practitioners (10.5% vs. 26.9%, p = 0.03) among EBM users. Additionally, patient workload (48%), time constraints (36%), and limited access to the Internet (28%) were the most frequently cited obstacles to the practice of EBM in Puerto Rico. Taken together, these results help create a cross-sectional profile of EBM practice among Puerto Rican physicians.