RESUMEN
Leishmaniasis is an emerging tropical infectious disease caused by a protozoan parasite of the genus Leishmania. In this work, the molecular hybridization between a trimethoxy chalcone and a sulfonamide group was used to generate a series of sulfonamide-chalcones. A series of eight sulfonamide-chalcone hybrids were made with good yields (up to 95%). These sulfonamide-chalcones were tested against promastigotes of Leishmania amazonensis and cytotoxicity against mouse macrophages, which showed good antileishmanial activity with IC50 = 1.72-3.19 µM. Three of them (10c, 10g, and 10h) were also highly active against intracellular amastigotes and had a good selectivity index (SI > 9). Thus, those three compounds were docked in the cytosolic tryparedoxin peroxidase (cTXNPx) enzyme of the parasite, and molecular dynamics simulations were carried out. This enzyme was selected as a target protein for the sulfonamide-chalcones due to the fact of the anterior report, which identified a strong and stable interaction between the chalcone NAT22 (6) and the cTXNPx. In addition, a prediction of the drug-likeness, and the pharmacokinetic profile of all compounds were made, demonstrating a good profile of those chalcones.
Asunto(s)
Antiprotozoarios , Chalcona , Chalconas , Animales , Ratones , Chalconas/farmacología , Chalcona/farmacología , Relación Estructura-Actividad , Antiprotozoarios/farmacología , Sulfanilamida , Sulfonamidas/farmacologíaRESUMEN
Species of spider wasps (Hymenoptera: Pompilidae) are diverse in the tropical regions. The Neotropical genus Abernessia Arlé, 1947 was described from São Paulo and later found in Espírito Santo, Bahia and Minas Gerais, Brazil. Herein, we establish a neotype for the type-species A. irmgardae Arlé, discuss the previous distribution records of Abernessia in South America, add new records for Brazil, and expand the recorded distribution to San Pedro, Paraguay. The male of Abernessia giga is described and illustrated. Finally, an updated key to species known from males is provided.
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Avispas , Animales , MasculinoRESUMEN
OBJECTIVE: We evaluated acceptability of cervico-vaginal self-collection (CVSC) and prevalence of human papillomavirus (HPV) in Human immunodeficiency virus (HIV)-infected and HIV-uninfected women living in the Tapajós region, Amazon, Brazil. METHODS: Cross-sectional study recruited 153 non-indigenous women (HIV-uninfected, nâ¯=â¯112 and HIV-infected, nâ¯=â¯41) who voluntarily sought assistance in health services. Peripheral blood for HIV screening and cervical scraping (CS) for HPV detection were collected. Women who accepted to perform CVSC received instructions and individual collection kits. Risk factors for high-risk HPV genotypes (hrHPV) were identified by uni- and multivariate analyses. RESULTS: The overall acceptability of CVSC was 87%. Only HIV-infected women had cytological abnormalities (12.2%). Prevalence of any HPV and hrHPV infection was 42.9% and 47.9% for HIV-uninfected and 97.6% and 77.5% for HIV-infected women, respectively. There was significant agreement in the detection of HPV (88%, 0.76, 95% confidence interval [CI], 0.65-0.87) and hrHPV (79.7%, 0.56, 95% CI, 0.41-0.71) between self-collected and clinician-collected samples. The most prevalent hrHPV types were HPV16 and HPV18 in HIV-uninfected and HPV16, HPV51 and HPV59 in HIV-infected women. HIV-infected women with hrHPV infection had multiple hrHPV infections (pâ¯=â¯0.005) and lower CD4 count (pâ¯=â¯0.018). Risk factors for hrHPV infection included being HIV-infected and having five or more sexual partners. CONCLUSIONS: CVSC had high acceptability and high prevalence of hrHPV types in women living in the Tapajós region, Amazon, Brazil.
Asunto(s)
Detección Precoz del Cáncer/métodos , Tamizaje Masivo/métodos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Aceptación de la Atención de Salud/estadística & datos numéricos , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Adulto , Anciano , Brasil/epidemiología , Recuento de Linfocito CD4 , Cuello del Útero/patología , Cuello del Útero/virología , Estudios Transversales , ADN Viral/aislamiento & purificación , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Genotipo , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , Infecciones por VIH/patología , Infecciones por VIH/virología , Humanos , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/sangre , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Prevalencia , Factores de Riesgo , Manejo de Especímenes/métodos , Manejo de Especímenes/estadística & datos numéricos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Vagina/patología , Vagina/virología , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to evaluate secretory leukocyte protease inhibitor (SLPI) expression in anal biopsies from HIV-positive (HIV+) individuals, and compare that to anal intraepithelial neoplasia (AIN) diagnoses and human papillomavirus (HPV) status. DESIGN: This is a cross-sectional study of a cohort of 54 HIV+ (31 males and 23 females) from an AIDS clinic in Rio de Janeiro, Brazil. METHODS: The study material consisted of anorectal tissue biopsies obtained from HIV+ subjects, which were used to construct tissue microarray paraffin blocks for immunohistochemical analysis of SLPI expression. Biopsies were evaluated by an expert pathologist and classified as low-grade AIN1, high-grade AIN2/3, or normal squamous epithelium. In addition, DNA from the biopsies was extracted and analyzed for the presence of low- or high-risk HPV DNA. RESULTS: Histologically, normal squamous epithelium from the anorectal region showed strong positive SLPI staining in 17/20 (85%) samples. In comparison, 9/17 (53%) dysplastic squamous epithelial samples from AIN1 patients showed strong SLPI staining, and only 5/17 (29%) samples from AIN2/3 patients exhibited strong SPLI staining, which both were significantly fewer than those from normal tissue (P = 0.005). Furthermore, there was a significantly higher proportion of samples in which oncogenic high-risk HPV genotypes were detected in low SLPI-expressing tissues than that in tissues with high SLPI expression (P = 0.040). CONCLUSIONS: Taken together these results suggest that low SLPI expression is associated with high-risk HPV infections in the development of AIN.
Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Enfermedades del Ano/complicaciones , Infecciones por VIH/complicaciones , Inhibidor Secretorio de Peptidasas Leucocitarias/metabolismo , Adulto , Enfermedades del Ano/metabolismo , Enfermedades del Ano/patología , Enfermedades del Ano/virología , Biopsia , Brasil , Femenino , Infecciones por VIH/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings.
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Condiloma Acuminado/prevención & control , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/uso terapéutico , Displasia del Cuello del Útero/prevención & control , Neoplasias del Cuello Uterino/prevención & control , Vacunación/efectos adversos , Condiloma Acuminado/virología , Femenino , Humanos , Masculino , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus/efectos adversos , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/virologíaRESUMEN
Although several studies have evaluated the role of p16(INK4a) as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16(INK4a) in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16(INK4a) as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16(INK4a) was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16(INK4a) expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16(INK4a) in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16(INK4a) under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16(INK4a) expression in CIN 2-3.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Estudios de Casos y Controles , Femenino , Infecciones por VIH/complicaciones , VIH-1 , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Curva ROC , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/metabolismo , Displasia del Cuello del Útero/complicaciones , Displasia del Cuello del Útero/metabolismoRESUMEN
Although several studies have evaluated the role of p16INK4a as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16INK4a in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16INK4a as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16INK4a was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16INK4a expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16INK4a in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16INK4a under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16INK4a expression in CIN 2-3.