Avaliação de biomarcadores de gravidade em cães naturalmente infectados por Leishmania infantum classificados clinicamente e estratificados quanto à carga parasitária em estudos de corte transversal / Evaluation of biomarkers of severity in dogs naturally infected with Leishmania infantum classified clinically and stratified for parasite load in cross-sectional studies

INTRODUÇÃO: A leishmaniose visceral (LV) é, principalmente, causada pelo protozoário Leishmania infantum nas Américas, podendo acometer o Homem e animais. Dentre estes, o cão é considerado o principal reservatório doméstico do parasito. O curso da LV canina (LVC) varia entre os animais, podendo alguns se mostrar resistentes à infecção, se mantendo subclínicos, e outros susceptíveis, que irão desenvolver sinais da doença. O estado de resistência ou susceptibilidade à LVC reflete na gravidade da infecção do animal, e não pode ser definido pelo quadro clínico apresentado ou por qualquer parâmetro isolado de resposta imune. OBJETIVO: Avaliar a carga parasitária como biomarcador parasitológico, as proteínas LJM11/LJM17 como biomarcadores de exposição à saliva do vetor, e identificar biomarcadores inflamatórios de gravidade da infecção por L. infantum em cães. Primeiramente, foi realizada a padronização de uma ferramenta diagnóstica de PCR quantitativa (qPCR), utilizando diferentes amostras biológicas (aspirado esplênico, linfonodos, pele, sangue, medula óssea e swab conjuntival) de cães sintomáticos provenientes da área endêmica de Jequié-BA. A avaliação da carga parasitária de L. infantum teve seu desempenho comparado com outras técnicas diagnósticas (cultura de aspirado esplênico, teste rápido e ELISA para LVC) empregando a análise de classe latente (ACL). Para essa análise, foi construída uma variável latente a ser empregada como padrão ouro para avaliação da acurácia desses métodos. Na avaliação inicia dos cães sintomáticos, a qPCR detectou DNA do parasita em 100%...

INTRODUCTION: In the Americas, visceral leishmaniasis (VL) is caused by the protozoan Leishmania infantum, which can affect humans and animals. Among these, dog is considered the main domestic reservoir of this parasite. Canine VL (CVL) clinical outcome varies among animals, some of which may be resistant to infection remaining subclinical, and others may be susceptible showing signs of the disease. The state of resistance or susceptibility to CVL reflects on the severity of infection in the animal and cannot be defined solely by the clinical condition presented or by any isolated parameter of the immune response. OBJECTIVE: Assess parasite load as parasitological biomarkers, LJM11/LJM17 proteins as sandfly saliva exposure biomarkers, and identify inflammatory biomarkers that indicates L. infantum infection severity in dogs. Firstly, we performed the standardization of a quantitative PCR diagnostic tool (qPCR) using different biological samples (splenic aspirate, lymph nodes, skin, blood, bone marrow and conjunctival swab) of symptomatic dogs from the endemic area of Jequié-BA. The evaluation of the parasitic load of L. infantum had its performance compared to other diagnostic techniques (splenic aspirate culture, rapid test and CVL ELISA) using latent class analysis (LCA). In this analysis, a latent variable was constructed to be used as a gold standard to evaluate the accuracy of these methods. In the initial evaluation of the symptomatic dogs, qPCR detected DNA from the parasite in 100%...

Diagnóstico precoz del cáncer de cuello uterino asociado a la infección por virus papiloma humano / Early diagnosis of cervical cancer associated to human papillomavirus

La infección persistente por ciertos tipos de alto riesgo oncogénico de virus papiloma humano (VPHAR) es el principal factor de riesgo para el desarrollo de cáncer de cuello uterino y sus lesiones precursoras. Los VPHAR inducen alteraciones moleculares durante todo el proceso de carcinogénesis cervical, que provocan la acumulación de errores genéticos, con la consecuente inestabilidad genética y transformación maligna. Estas alteraciones son producidas por la acción directa de las oncoproteínas virales E6 y E7 sobre las principales proteínas celulares supresoras de tumor, p53 y pRb, respectivamente, y pueden ser monitoreadas durante el surgimiento de la lesión neoplásica, mediante el uso de biomarcadores. En este artículo se revisan las últimas tendencias sobre el uso del estudio inmunocitoquímico, como una prueba complementaria a la citología y a la detección y tipificación de VPHAR en la evaluación de la expresión de biomarcadores como la proteína inhibidora de la proliferación celular p16INK4a, marcador único o combinada con otros biomarcadores, que puedan contribuir eficazmente en la detección de las pacientes con mayor riesgo a desarrollar neoplasia del cuello uterino asociada a la infección por VPHAR, durante la pesquisa de cáncer de cuello uterino de rutina y en el manejo clínico adecuado y oportuno.

Persistent infection with certain types of high oncogenic risk human papillomavirus (HR-HPV) is the main risk factor for developing cervical cancer and its precursor lesions. HR-HPV induces molecular changes during cervical carcinogenesis, causing the accumulation of genetic anomalies, with subsequent genetic instability and malignant transformation. These alterations are produced by the direct action of the E6 and E7 viral oncoproteins on principal tumor cell suppressor proteins, p53 and pRb, respectively, and can be monitored during growth of the neoplastic lesion using biomarkers. In this paper we review the latest trends on the use of immunocytochemistry as a complementary test to cytology and HR-HPV detection and typing in evaluating expression of biomarkers such as the p16INK4a cell proliferation inhibitor protein, as a single marker or combined with other biomarkers, which can contribute effectively to the detection of patients with increased risk of developing cervical neoplasia associated with HR-HPV infection during routine screening for cervical cancer and in appropriate clinical management.

Rapid Decrease of Intact Parathyroid Hormone Could Be a Predictor of Better Response to Cinacalcet in Hemodialysis Patients

PURPOSE: Cinacalcet is effective for treating refractory secondary hyperparathyroidism (SHPT), but little is known about the response rates and clinical factors influencing the response. MATERIALS AND METHODS: A prospective, single-arm, multi-center study was performed for 24 weeks. Cinacalcet was administered to patients with intact parathyroid hormone (iPTH) level greater than 300 pg/mL. Cinacalcet was started at a dose of 25 mg daily and titrated until 100 mg to achieve a serum iPTH level <300 pg/mL (primary end point). Early response to cinacalcet was defined as a decrease of iPTH more than 50% within one month. RESULTS: Fifty-seven patients were examined. Based on the magnitude of iPTH decrease, patients were divided into responder (n=47, 82.5%) and non-responder (n=10, 17.5%) groups. Among the responders, 38 achieved the primary end point, whereas 9 patients showed a reduction in serum iPTH of 30% or more, but did not reach the primary end point. Compared to non-responders, responders were significantly older (p=0.026), female (p=0.041), and diabetics (p<0.001). Additionally, early response was observed more frequently in the responders (30/47, 63.8%), of whom the majority (27/30, 90.0%) achieved the primary end point. Multivariate analysis showed that lower baseline iPTH levels [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.99], the presence of diabetes (OR 46.45, CI 1.92-1125.6) and early response (OR 21.54, CI 2.94-157.7) were significant clinical factors affecting achievement of iPTH target. CONCLUSION: Cinacalcet was effective in most hemodialysis patients with refractory SHPT. The presence of an early response was closely associated with the achievement of target levels of iPTH.