Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice.

The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on the brain, often identified at school age, manifest as cognitive impairment, attention deficit, and reduced scholastic achievement. The neurobiological basis for these effects is poorly understood. Here, we examine how in utero exposure to heroin affects brain development into early adolescence in a mouse model. Pregnant C57BL/6J mice received escalating doses of heroin twice daily on gestational days 4-18. The brains of offspring were assessed on postnatal day 28 using 9.4 T diffusion MRI of postmortem specimens at 36 µm resolution. Whole-brain volumes and the volumes of 166 bilateral regions were compared between heroin-exposed and control offspring. We identified a reduction in whole-brain volume in heroin-exposed offspring and heroin-associated volume changes in 29 regions after standardizing for whole-brain volume. Regions with bilaterally reduced standardized volumes in heroin-exposed offspring relative to controls include the ectorhinal and insular cortices. Regions with bilaterally increased standardized volumes in heroin-exposed offspring relative to controls include the periaqueductal gray, septal region, striatum, and hypothalamus. Leveraging microscopic resolution diffusion tensor imaging and precise regional parcellation, we generated whole-brain structural MRI diffusion connectomes. Using a dimension reduction approach with multivariate analysis of variance to assess group differences in the connectome, we found that in utero heroin exposure altered structure-based connectivity of the left septal region and the region that acts as a hub for limbic regulatory actions. Consistent with clinical evidence, our findings suggest that prenatal opioid exposure may have effects on brain morphology, connectivity, and, consequently, function that persist into adolescence. This work expands our understanding of the risks associated with opioid misuse during pregnancy and identifies biomarkers that may facilitate diagnosis and treatment.

Establishment of multi-stage intravenous self-administration paradigms in mice.

Genetically tractable animal models provide needed strategies to resolve the biological basis of drug addiction. Intravenous self-administration (IVSA) is the gold standard for modeling psychostimulant and opioid addiction in animals, but technical limitations have precluded the widespread use of IVSA in mice. Here, we describe IVSA paradigms for mice that capture the multi-stage nature of the disorder and permit predictive modeling. In these paradigms, C57BL/6J mice with long-standing indwelling jugular catheters engaged in cocaine- or remifentanil-associated lever responding that was fixed ratio-dependent, dose-dependent, extinguished by withholding the drug, and reinstated by the presentation of drug-paired cues. The application of multivariate analysis suggested that drug taking in both paradigms was a function of two latent variables we termed incentive motivation and discriminative control. Machine learning revealed that vulnerability to drug seeking and relapse were predicted by a mouse's a priori response to novelty, sensitivity to drug-induced locomotion, and drug-taking behavior. The application of these behavioral and statistical-analysis approaches to genetically-engineered mice will facilitate the identification of neural circuits driving addiction susceptibility and relapse and focused therapeutic development.

Insufficient evidence for vitamin D use in COVID-19: A rapid systematic review.

BACKGROUND: Vitamin D deficiency has been linked to the increased severity of numerous viral infections. OBJECTIVE: To assess whether vitamin D supplementation is safe and effective for the treatment of COVID-19. METHODS: We searched MEDLINE, EMBASE, CENTRAL, LILACS and LOVE for randomised controlled trials (RCTs) published up to 2 March evaluating the effects of vitamin D for the treatment of coronavirus disease (COVID-19). Two authors selected the studies and analysed the data evidence following Cochrane Recommendations. RESULTS: We included three RCTs with a total of 385 participants. We found low certainty evidence indicating that hospitalised patients under calcifediol plus standard care (SC) treatment seem to present a significantly lower risk of being admitted to ICU but no difference in mortality. We found low to very low certainty evidence that the improvement in fibrinogen levels is slightly greater in mildly symptomatic or asymptomatic patients with COVID-19 that used cholecalciferol plus SC than in those treated with placebo plus SC (mean difference), and the patients who used cholecalciferol plus SC achieved more SARS-CoV-2 negativity, but not on d-dimer, c-reactive protein (CRP) or procalcitonin compared with the patients in the placebo plus SC group. We also found low to moderate certainty evidence that a single high dose of vitamin D does not seem to be effective for reducing mortality, length of hospital stay, ICU admissions and d-dimer or CRP levels when used in patients with moderate to severe COVID-19. CONCLUSIONS: As a practical implication, the use of vitamin D associated with SC seems to provide some benefit to patients with COVID-19. However, the evidence is currently insufficient to support the routine use of vitamin D for the management of COVID-19, as its effectiveness seems to depend on the dosage, on the baseline vitamin D levels, and on the degree of COVID-19 severity.

Risk of venous thromboembolism in users of contraception and menopausal hormone therapy during the COVID-19 pandemic.

OBJECTIVES: The outbreak of coronavirus disease (COVID-19) is a public health emergency of international concern. Inflammatory changes are part of COVID-19 pathophysiology and this might generate a higher thromboembolic risk in patients using combined hormonal contraception and menopausal hormone therapy. We aimed to discuss the main aspects related to this issue and propose management strategies for women affected by COVID-19. METHODS: This narrative review collected information from several articles published since the beginning of the outbreak of the new coronavirus disease about the pathophysiology, stage of the disease, the occurrence of thrombotic events, and the risk of thromboembolism in users of contraception and hormonal therapy. RESULTS: This article consolidates clinical parameters about the risk of venous thromboembolism in users of contraception and menopausal hormone therapy emphasizing the probable increase of that risk in women with suspected or confirmed COVID-19 and bringing safer recommendations. CONCLUSIONS: In this scenario, apart from the fundamental orientations of preventive measures, like social isolation and hygiene, it is important that all female health professionals have knowledge of the new rules and adopt safety measures, especially on the prescription of hormonal therapy and contraception.

Riscos ocupacionais dos profissionais de enfermagem na central de material e esterilização / Occupational risks of nursing professionals in the material and sterilization center

Objetivo: identificar os riscos ocupacionais aos quais os profissionais de enfermagem da CME, refletindo sobre a implementação de melhorias das condições de trabalho e qualidade de vida no ambiente laboral. Metodologia: realizou-se uma revisão integrativa da literatura, com caráter descritivo, utilizando as bases de dados LILACS, BDENF e Google Acadêmico, incluindo artigos com texto completo disponível eletronicamente e de forma gratuita, redigidos no idioma português, publicados no recorte temporal entre 2007 a 2018, que abordassem o tema e respondessem à questão norteadora do estudo. Resultados: de acordo com os estudos, o ambiente laboral da CME expõe os profissionais de enfermagem a riscos físicos (85,71%), químicos (42,86%), biológicos (42,86%), ergonômicos (71,43%), de acidentes (71,43%) e psicossociais (42,86%). Conclusão: a sensibilização dos gestores e a implementação de ações preventivas são necessárias para a melhoria das condições laborais e favorecem o bem estar e a satisfação dos profissionais de enfermagem na execução de suas tarefas cotidianas.

Objective: to identify the occupational hazards to which CME nursing professionals, reflecting on the implementation of improvements in working conditions and quality of life in the work environment. Methodology: an integrative review of the literature was carried out, with a descriptive character, using the databases LILACS, BDENF and Google Scholar, including full text articles available electronically and free of charge, written in the Portuguese language, published at the time frame between 2007 to 2018, to address the issue and respond to the guiding question of the study. Results: according to the studies, the CME work environment exposes nursing professionals to physical (85.71%), chemical (42.86%), biological (42.86%), ergonomic risks (71.43%), accidents (71.43%) and psychosocial (42.86%). Conclusion: the sensitization of managers and the implementation of preventive actions are necessary for the improvement of working conditions and further the well-being and satisfaction of the nursing professionals in the execution of their daily tasks.

Conhecimento de estudantes de medicina sobre hanseníase em uma região endêmica do Brasil / Knowledge of medical students from a Brazilian endemical region regarding leprosy / El conocimiento de estudiantes de medicina sobre la lepra en una región endémica de Brasil

A hanseníase é uma doença infecciosa, crônica, de grande importância para a saúde pública devido à sua prevalência e ao seu alto poder incapacitante. A Amazônia brasileira é região endêmica dessa moléstia. Este estudo teve como objetivo avaliar o conhecimento acerca da hanseníase dos estudantes do último ano do curso de Medicina de universidades públicas da capital do estado do Pará, comparando-o com variáveis da formação acadêmica. Trata-se de um estudo observacional de corte transversal. Para a coleta de dados, utilizaram-se questionários de perfil do acadêmico e avaliação em hanseníase. Os resultados apontaram que 55% dos acadêmicos tiveram índice de acertos maior que 50%. O menor índice de acertos ocorreu em questões sobre o contato intradomiciliar, diagnóstico e formas clínicas, nesta ordem. Não se evidenciou influência significativa/correlação entre as variáveis de participações em Iniciação Científica, Curso Preparatório de Residência Médica ou Ligas Acadêmicas com o nível de conhecimento dos acadêmicos em hanseníase. Concluiu-se que os estudantes avaliados apresentaram nível de conhecimento regular, o que aponta para a necessidade de aperfeiçoamento das estratégias de ensino-aprendizado em hanseníase.

Leprosy is a chronic infectious disease of great importance to public health because of its prevalence and its high incapacitating power. Brazilian Amazon is an endemic region for this disease. The objective of this study was to evaluate public universities last year medical students knowledge about leprosy Pará state capital, comparing it to variables of academic formation. It is an observational cross-sectional study. Academic profile and evaluation on leprosy questionnaires were used for data collection. The results showed that 55% of the students had scores higher than 50%. Questions about home contact, diagnosis and clinical forms, in this order, had the lowest rate of correct answers. There was no significant influence/correlation among the variables of participation in Scientific Initiation, Preparatory Course of Medical Residency or Academic Leagues with the level of knowledge on leprosy students. In conclusion, the students evaluated presented a regular level of knowledge, which points to the need of improvement to the teaching-learning strategies on leprosy.

La lepra es una enfermedad infecciosa crónica de gran importancia para la salud pública debido a su prevalencia y su alto poder incapacitante. La Amazonia brasileña es región endémica de esta enfermedad. Este estudio tuvo como objetivo evaluar el conocimiento de la lepra de los estudiantes de último año de la escuela de medicina de la universidad pública en la capital del estado de Pará, comparándolo con variables de la formación académica. Se trata de un estudio observacional transversal. Para recolectar los datos, utilizaron se cuestionarios de perfil académico y evaluación en la lepra. Los resultados mostraron que el 55% de los estudiantes había alcanzado tasa superior al 50%. Las puntuaciones más bajas se produjeron en preguntas sobre el contacto en el hogar, el diagnóstico y formas clínicas, en ese orden. No se muestra una influencia/correlación significativa entre las variables de participación en la Iniciación Científica, Curso Preparatorio de Residencia Médica y ligas académicas con el nivel de conocimiento de los estudiantes en la lepra. Se concluyó que los estudiantes evaluados tenían nivel regular de conocimientos, lo que apunta a la necesidad de mejorar las estrategias de enseñanza-aprendizaje en la lepra.

Dengue infection in pregnancy and its impact on the placenta.

A histopathological and immunohistochemical study was conducted in placental tissues and retained products of conception from 24 patients with confirmed dengue infection during pregnancy. The immunohistochemical assay was positive for dengue virus in 19 placental and three ovular remnants analyzed. The light microscopic findings were signs of hypoxia, choriodeciduitis, deciduitis and intervillositis and the viral antigens were found in cytoplasmic of the trophoblast, villous stroma and decidua. Our results suggest that immunohistochemistry could be used as a laboratory confirmation method for dengue in pregnant women, especially in endemic areas when embedded material is the only material available.

Cutaneous invasion from sarcomatoid urothelial carcinoma: clinical and dermatopathologic features.

In Brazil, without considering the non-melanoma skin tumors, bladder cancer in men is the eighth most common, and the urothelial carcinoma or transitional cell carcinoma is the most common among these. Cutaneous metastases from urothelial neoplasms appear as single or multiple erythematous, infiltrated nodules or plaques, and like other cases of distant disease, it is indicative of poor prognosis. The invasive urothelial carcinoma is recognized for its ability to present divergent differentiation and morphological variants. The sarcomatoid urothelial carcinoma is a rare cancer that consists of two different components: one composed of epithelial tissue and the other with sarcomatoid features of mesenchymal origin. The authors describe a case of cutaneous metastasis of sarcomatoid urothelial carcinoma in a 63-year-old male patient.

Cutaneous invasion from sarcomatoid urothelial carcinoma: clinical and dermatopathologic features

Abstract In Brazil, without considering the non-melanoma skin tumors, bladder cancer in men is the eighth most common, and the urothelial carcinoma or transitional cell carcinoma is the most common among these. Cutaneous metastases from urothelial neoplasms appear as single or multiple erythematous, infiltrated nodules or plaques, and like other cases of distant disease, it is indicative of poor prognosis. The invasive urothelial carcinoma is recognized for its ability to present divergent differentiation and morphological variants. The sarcomatoid urothelial carcinoma is a rare cancer that consists of two different components: one composed of epithelial tissue and the other with sarcomatoid features of mesenchymal origin. The authors describe a case of cutaneous metastasis of sarcomatoid urothelial carcinoma in a 63-year-old male patient.

Distance to parks and non-residential destinations influences physical activity of older people, but crime doesn't: a cross-sectional study in a southern European city.

BACKGROUND: Physical activity (PA) has numerous health benefits, but older adults live mostly sedentary lifestyles. The physical and social neighborhood environment may encourage/dissuade PA. In particular, neighborhood crime may lead to feeling unsafe and affect older adults' willingness to be physically active. Yet, research on this topic is still inconclusive. Older population, probably the age group most influenced by the neighborhood environment, has been understudied, especially in Southern Europe. In this study, we aimed to analyze the association between leisure-time physical activity (LTPA) in older adults and objective crime, alongside other neighborhood characteristics. METHODS: We obtained data from a population-based cohort from Porto (2005-2008) to assess LTPA. Only adults aged 65 years or more were included (n = 532). A Geographic Information System was used to measure neighborhood characteristics. Neighborhood crime was expressed as crime rates by category (incivilities, criminal offenses with and without violence and traffic crime). Neighborhood characteristics such as socioeconomic deprivation, land gradient, street density, transportation network, distance to parks, non-residential destinations and sport spaces were also included. Generalized Additive Models were fitted to estimate the association between neighborhood characteristics and the participation (being active vs. inactive) and frequency (min/day) of LTPA. RESULTS: Forty-six percent of the men and 61 % of the women did not engage in any kind of LTPA. Among the active participants, men spent on average 50.5 (35.2 Standard Deviation, SD) min/day in LTPA, whereas the average among women was 36.9 (35.1 SD) min/day (p < 0.001). Neighborhood crime was unrelated to the participation in, or frequency of, LTPA. On the other hand, two neighborhood characteristics - distance to the nearest park (ß = -0.0262, p = 0.029) and to the nearest non-residential destination (ß = -0.0735, p = 0.019) - were associated with time spent on LTPA, but only among active older women. No neighborhood characteristic was related to participation in LTPA. CONCLUSIONS: From a public health point of view, the provision of parks and non-residential destinations (shops, schools, cultural and worship places) might contribute to elevate PA levels of already active older women. On the other hand, in this setting, crime was not a big issue.

Correlation of MCM2 detection with stage and virology of cervical cancer.

UNLABELLED: The highly conserved mini-chromosome maintenance proteins (MCM) are important in the initiation of DNA replication. Few studies have correlated MCM expression with the progression of cancer. OBJECTIVES: (i) To analyze the expression of MCM2 in cervical cancer; (ii) to correlate MCM2 expression with the clinical tumor staging according to FIGO classification, and (iii) to relate HPV type to MCM2 expression. METHODS: Tissue micro-arrays (TMA) from patients with invasive cervical cancer and controls were analyzed. Human papillomavirus (HPV) DNA detection and HPV types were determined by in situ hybridization, PCR, and sequencing. MCM2 expression was analyzed by immunohistochemistry. RESULTS: The most prevalent HPV types found in invasive cancer were HPV 16 (66.6%), followed by HPV 33 (11.8%), and HPV 35 (3.6%). An increased (p<0.05) expression of MCM2 was found in invasive cervical cancers compared to controls. Moreover, a strong correlation was found between the MCM2-positive cells and the presence of HPV DNA detected by in situ hybridization. No statistically significant difference was observed between MCM2 expression and FIGO stage. CONCLUSIONS: The present study shows that HPV-infected cells strongly express MCM2; nevertheless, our data suggests that MCM2 is not a good biomarker when comparing the different clinical stages of cervical cancer.

Immunohistochemistry expression of TCF4 protein on carcinoma, adenoma and non neoplastic colorectal mucosa / Expressão imuno-histoquímica da proteína TCF4 no carcinoma, no adenoma e na mucosa não neoplásica colorretal

PURPOSE: To detect and quantify the immunoreactivity of TCF4 protein in colorectal carcinoma, colorectal adenoma and non-neoplasic colorectal epithelium. METHODS: We studied 129 individuals: 40 with colorectal cancer, 52 with colorectal adenoma and 37 with non-neoplastic colorectal epithelium. The colorectal adenoma and carcinoma samples were obtained from patients who underwent surgical procedures, and colonoscopies and samples of non-neoplastic colorectal epithelium were taken from patients who died from cardiovascular diseases, without diseases of the large intestine. Samples of different tissues were included in paraffin blocks, and the immunohistochemical expression of protein TCF4 was analyzed using the technique of tissue microarray (TMA) with polyclonal antibody TCF4. The immunoreactivity was analyzed and classified as positive and negative. RESULTS: The immunohistochemical expression of TCF4 protein was significantly higher (p < 0.01) in colorectal carcinoma than in the non-neoplastic colorectal epithelium and adenoma. There was no difference (p = 0.76) between TCF4 protein immunohistochemical expression in colorectal adenoma and non-neoplastic colorectal tissue. CONCLUSIONS: TCF4 protein showed a more intense expression in colorectal carcinoma than in non-neoplastic colorectal epithelium and adenoma, indicating that this protein is involved in colorectal carcinogenesis. (AU)

OBJETIVOS: Detectar e quantificar a imunoexpressão da proteína TCF4 no carcinoma e no adenoma colorretal e no epitélio colorretal não neoplásico. MÉTODO: Foram estudados 129 indivíduos: 40 com carcinoma colorretal, 52 com adenoma colorretal e 37 com epitélio colorretal não neoplásico. Os tecidos de adenoma e carcinoma colorretais foram representados por amostras da lesão retirada de doentes submetidos a procedimentos cirúrgicos e colonoscópicos, e as amostras de epitélio colorretal não neoplásico foram retiradas de doentes falecidos por afecções cardiovasculares e sem comprometimento do intestino grosso. As amostras dos diferentes tecidos foram incluídas em blocos de parafina e submetidas ao estudo da imunoexpressão da proteína TCF4 pela técnica do tissue microarray (TMA) com o anticorpo policlonal anti-TCF4. A imunorreatividade foi analisada e classificada como positiva e negativa. RESULTADOS: A imunoexpressão da proteína TCF4 foi significantemente maior (p < 0,01) no carcinoma colorretal do que nos adenomas e no epitélio colorretal não doente. Não houve diferença significante (p = 0,76) entre a imunoexpressão da proteína TCF4 no adenoma colorretal e no epitélio colorretal não doente. CONCLUSÃO: A maior expressão da proteína TCF4 no carcinoma colorretal em relação ao adenoma e ao epitélio não doente sugere que esta proteína possui participação na carcinogênese colorretal. (AU)

Imunoexpressão das proteínas COX-2, p53 e caspase-3 em adenoma colorretal e mucosa não neoplásica / Immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenoma and non-neoplastic mucosa

OBJETIVO: Analisar a imunoexpressão das proteínas COX-2, p53 e caspase-3 em adenomas colorretais e na mucosa não neoplásica. MÉTODOS: Foram submetidos à colonoscopia 72 indivíduos que forneceram 50 amostras de adenomas e 45 de mucosa colorretal não neoplásica. Os tecidos foram obtidos pela técnica de arranjo em matriz (tissue microarray) e submetidos a estudo imunoistoquímico com anticorpos primários p53, COX-2 e caspase-3. A positividade e intensidade da imunorreação foram classificadas. Foram estudadas as seguintes variáveis: localização do adenoma no colo, grau de displasia, tamanho, e escores de positividade e intensidade da imunoexpressão das proteínas p-53, caspase-3 e COX-2. RESULTADOS: Nos adenomas, a imunoexpressão da proteína p53 mutada foi positiva em 30 (60%) e negativa em 20 (40%) amostras. Na mucosa colorretal não neoplásica, a imunoexpressão da proteína p53 mutada foi negativa em 39 (86,6%) amostras e positiva em 6 (13,3%) (p<0,0001). Houve diferença significativa entre o maior tamanho (p=0,006) e o maior grau de displasia dos adenomas (p<0,0001) e a intensidade de imunoexpressão da proteína p53 mutada. A positividade e intensidade da imunoexpressão das proteínas COX-2 (p=0,14) e caspase-3 (p=0,23), nos adenomas e na mucosa colorretal não neoplásica, não apresentaram diferença significante. CONCLUSÃO: A proteína p53 mutada é hiperexpressada nos adenomas em comparação com a mucosa não neoplásica. Nos adenomas, o maior tamanho e o maior grau de displasia foram associados à maior expressão da proteína p53 mutada. A imunoexpressão das proteínas COX-2 e caspase nos adenomas não apresentou correlação com os aspectos anatomopatológicos e não foi diferente em termos de níveis de expressão correspondentes na mucosa não neoplásica.

OBJECTIVE: To analyze the immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenomas and non-neoplastic mucosa. METHODS: 72 individuals were subjected to colonoscopy, which provided 50 samples of adenomas and 45 samples of non-neoplastic colorectal mucosa. The tissue samples were obtained via the tissue microarray technique and subjected to immunohistochemical analysis using primary anti-p53, anti-COX-2, and anti-caspase-3 antibodies. The positivity and intensity of the immunoreaction were classified. The analyzed variables were as follows: site of the adenomas in the colon, degree of dysplasia, size, and score of positivity and intensity of immunoexpression of the p-53, caspase-3, and COX-2 proteins. RESULTS: The immunoexpression of mutated protein p53 was positive in 30 (60%) adenoma samples and negative in 20 (40%) adenoma samples. The immunoexpression of mutated protein p53 was negative in 39 (86.6%) samples and positive in 6 (13.3%) samples of the non-neoplastic colorectal mucosa (p<0.0001). Significant differences were seen between both the largest size (p=0.006) and the highest degree of dysplasia (p<0.0001) of the adenomas and the intensity of immunoexpression of mutated protein p53. The positivity and intensity of immunoexpression of COX-2 (p=0.14) and caspase-3 (p=0.23) showed no significant differences between the adenomas and the non-neoplastic colorectal mucosa. CONCLUSION: Mutated protein p53 was hyperexpressed in the adenomas compared with the non-neoplastic mucosa. Greater size and greater degree of dysplasia in the adenomas were associated with higher expression of mutated protein p53. The immunoexpression of COX-2 and caspase-3 in the adenomas did not exhibit a correlation with the anatomical-pathological features of the tumors and did not differ from the corresponding expression levels in the non-neoplastic mucosa.

Anatomopathological characterization of placentas from HIV+ patients associated with p24 expression / Caracterização anatomopatológica da placenta de pacientes HIV+ associada à expressão do p24

INTRODUCTION: The study of placentas from pregnant human immunodeficiency virus (HIV) positive women has become the subject of numerous studies in the literature. Morphological, viral, immune and inflammatory placental aspects have been analyzed in order to grasp the vertical transmission of the virus. OBJECTIVE: To identify the most frequent findings in the placentas by associating them with a viral antigen and correlating them with the infection of newborns. MATERIAL AND METHODS: Thirty-five placentas from HIV- positive pregnant women were pathologically and immunohistochemically analyzed with the use of p24 antibody in the period from 1992 to1997 in accordance with the routine laboratory testing from the Anatomopathological Department - Hospital Universitário Antônio Pedro - Universidade Federal Fluminense (APD/HUAP/UFF). RESULTS: The microscopic alterations detected in all cases, including those with vertical transmission, were arteriopathy in the fetal blood circulation, chorioamnionitis, perivillous fibrin deposition, syncytial knotting, villous edema and villous immaturity. No specific macroscopic or histopathological changes were found in these placentas. The neonatal infection was observed in five cases. Vertical transmission was identified in two out of five placentas that had low weight for the respective stage of pregnancy. Immunohistochemical analysis revealed 14 positive cases, two of which showed vertical transmission. The viral protein was not identified in 10 out of 14 placentas from patients who had been medicated with zidovudine (AZT). CONCLUSION: Our study has contributed to the anatomopathological investigation into placentas from HIV-positive patients, although p24 expression per se did not allow a definite and early diagnosis of the vertical transmission.

INTRODUÇÃO: A importância do estudo da placenta de gestantes com o vírus da imunodeficiência humana (HIV) soropositivas tornou-se alvo de inúmeros trabalhos na literatura. Aspectos morfológicos, virais, imunes e inflamatórios intrínsecos ao tecido placentário foram analisados para o entendimento da transmissão vertical do vírus. OBJETIVO: Identificar as lesões mais frequentes nas placentas, associando-as ao antígeno viral e correlacionando-as com a infecção dos recém-nascidos. MATERIAL E MÉTODOS: Trinta e cinco placentas de gestantes HIV soropositivas foram analisadas por estudo anatomopatológico e imuno-histoquímico, utilizando o anticorpo p24, no período de 1992 a 1997, segundo a rotina do laboratório do Serviço Anatomia Patológica/Hospital Universitário Antônio Pedro/Universidade Federal Fluminense (SAP/HUAP/UFF). RESULTADOS: As alterações microscópicas registradas em todos os casos, inclusive nos de transmissão vertical, foram arteriopatia no circuito vascular fetal, corionamnionite, depósito fibrinoide perivilositário, excesso de nós sinciciais, edema do estroma viloso e dismaturidade vilosa. Nenhuma alteração microscópica ou macroscópica específica do HIV foi encontrada nas placentas. A infecção neonatal pôde ser constatada em cinco casos. A transmissão vertical foi identificada em duas placentas entre cinco que tinham baixo peso para a idade gestacional. Análise da imuno-histoquímica do p24 mostrou 14 casos positivos, dois dos quais apresentaram transmissão vertical. A proteína viral não foi identificada em 10 das 14 placentas cujas pacientes foram medicadas com zidovudina (AZT). CONCLUSÃO: Nosso estudo contribuiu para o estudo anatomopatológico da placenta de pacientes soropositivas para o HIV, porém a expressão do p24 por si só não permitiu um diagnóstico definitivo e precoce da transmissão vertical.

A single dose of a DNA vaccine encoding apa coencapsulated with 6,6'-trehalose dimycolate in microspheres confers long-term protection against tuberculosis in Mycobacterium bovis BCG-primed mice.

Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.

A comparative analysis of clinical and molecular factors with the stage of cervical cancer in a Brazilian cohort.

UNLABELLED: Cell cycle protein expression plays an important role in the pathophysiology of cervical cancer. However, few studies have attempted to correlate the use of these biomarkers with the clinical progression of the tumor. OBJECTIVES: 1) To analyze the expression of Ki-67, p53 and p16(INK4a) in cervical cancer, 2) to correlate the relative expression of these proteins as well as clinical parameters with the stage of disease, and 3) to determine the HPV DNA prevalence and subtype distribution. METHODS: Tissue Micro-Arrays (TMA) from patients with invasive cervical cancer (ICC) and controls were analyzed. HPV DNA detection was done by PCR and in situ hybridization. Ki-67, p53 and p16(INK4a) were analyzed by immunohistochemistry; clinical data was derived from the chart review. RESULTS: Advanced tumor stage (III and IV) was strongly associated (p<0.005) with advanced age (>55 years old), with more than four pregnancies and with the lack of formal education. HPV DNA was found in 94.3% of cases with the most prevalent types being HPV16 (67.5%), followed by HPV33 (12.0%) and HPV35 (3.6%). High expression of Ki-67 and p16 was more common in the advanced FIGO stages (p = 0.023). Women with HPV16 tended to be younger (50.9 years; SE 1.9) compared to women with other types (59.9 years; SE 2.8). CONCLUSION: We found that Ki-67 and p16 expression were independently associated with the tumor stage. We also noted that about 1/3 of the cervical cancers in this Brazilian cohort were not associated with HPV types directly targeted by the current HPV vaccines.

Tamoxifen decreases the myofibroblast count in the healing bile duct tissue of pigs.

OBJECTIVE: The aim of this study was to evaluate the effect of oral tamoxifen treatment on the number of myofibroblasts present during the healing process after experimental bile duct injury. METHODS: The sample consisted of 16 pigs that were divided into two groups (the control and study groups). Incisions and suturing of the bile ducts were performed in the two groups. Tamoxifen (20 mg/day) was administered only to the study group. The animals were sacrificed after 30 days. Quantification of myofibroblasts in the biliary ducts was made through immunohistochemistry analysis using anti-alpha smooth muscle actin of the smooth muscle antibody. Immunohistochemical quantification was performed using a digital image system. RESULTS: In the animals treated with tamoxifen (20 mg/day), there was a significant reduction in immunostaining for alpha smooth muscle actin compared with the control group (0.1155 vs. 0.2021, p = 0.046). CONCLUSION: Tamoxifen reduced the expression of alpha smooth muscle actin in the healing tissue after bile duct injury, suggesting a decrease in myofibroblasts in the scarred area of the pig biliary tract. These data suggest that tamoxifen could be used in the prevention of biliary tract stenosis after bile duct surgeries.

Teste de contato atópico com aeroalérgenos: uma ferramenta promissora no diagnóstico da dermatite atópica / Atopy patch test with aeroallergens: a promising tool in the diagnosis of atopic dermatitis

Objetivos: Avaliar a padronização do método com relação à concentração do aeroalérgeno, tempo de oclusão, de interpretação; e determinar a especificidade e a sensibilidade do teste de contato alérgico (TCA) em relação ao teste por puntura e a dosagem de IgE específica, na verificação da sensibilização a ácaros em crianças com dermatite atópica (DA). Métodos: Foram selecionadas 72 crianças com idade entre 2 e 12 anos, acompanhadas no ambulatório de alergia do Hospital São Zacharias. Estas foram submetidas a teste de puntura, dosagem de IgEs específicas e TCA para ácaros (Dermatophagoides pteronyssinus, Dermatophagoides farinae e Blomia tropicalis). Os testes foram realizados em 3 grupos: (1) DA com ou sem rinite e asma, (2) Rinite e/ou asma sem DA, (3) Saudáveis (controle). Resultados: No grupo 1, 40% dos pacientes apresentaram reação positiva. A sensibilidade foi maior nos pacientes com maior tempo de exposição (48 h e 72 h). No grupo 2, o TCA foi mais específico que sensível para todos os extratos, com aumento da sensibilidade quanto maior o tempo de exposição (72 h). No grupo 3, apenas 8,3% apresentaram positividade a algum aeroalérgeno do TCA. Conclusão: O TCA mostrou ter valor diagnóstico em relação às reações de fase tardia a ácaros (D. pteronyssinus, D. farinae e B. tropicalis), com elevada especificidade. Ele demonstrou ser um teste confiável quando comparado aos resultados do grupo controle.

Objectives: To evaluate the standardization of the atopy patch test (APT) with regard toconcentration of aeroallergens, occlusion time, and interpretation, and to determine the specificityand sensitivity of the method in relation to prick test and serum specific IgE determination in theinvestigation of dust mite sensitization in children with atopic dermatitis (AD). Methods: Seventytwo children, ranging from 2 to 12 years of age, were selected among those receiving care at the allergy outpatient clinic of São Zacharias Hospital. Children underwent skin prick testing, specific IgE measurements, and APT for mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae,and Blomia tropicalis). Tests were performed in three groups: (1) AD with or without rhinitis andasthma; (2) rhinitis and/or asthma without AD; (3) healthy individuals (controls). Results: In group 1, 40% of the patients presented positive reactions. Sensitivity was higher in patients with longer exposure times (48 h and 72 h). In group 2, APT was more specific than sensitive for allextracts, with increasing sensitivity associated with longer times of exposure (72 h). In group 3,only 8.3% of the individuals were positive to any aeroallergen on APT. Conclusion: APT seemsto have diagnostic value in identifying late phase reactions to mites (D. pteronyssinus, D. farinae, and B. tropicalis), with high specificity, and proved to be a reliable test when compared with the results obtained for controls.

Tamoxifen decreases the myofibroblast count in the healing bile duct tissue of pigs

OBJECTIVE: The aim of this study was to evaluate the effect of oral tamoxifen treatment on the number of myofibroblasts present during the healing process after experimental bile duct injury. METHODS: The sample consisted of 16 pigs that were divided into two groups (the control and study groups). Incisions and suturing of the bile ducts were performed in the two groups. Tamoxifen (20 mg/day) was administered only to the study group. The animals were sacrificed after 30 days. Quantification of myofibroblasts in the biliary ducts was made through immunohistochemistry analysis using anti-alpha smooth muscle actin of the smooth muscle antibody. Immunohistochemical quantification was performed using a digital image system. RESULTS: In the animals treated with tamoxifen (20 mg/day), there was a significant reduction in immunostaining for alpha smooth muscle actin compared with the control group (0.1155 vs. 0.2021, p = 0.046). CONCLUSION: Tamoxifen reduced the expression of alpha smooth muscle actin in the healing tissue after bile duct injury, suggesting a decrease in myofibroblasts in the scarred area of the pig biliary tract. These data suggest that tamoxifen could be used in the prevention of biliary tract stenosis after bile duct surgeries.

Immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenoma and non-neoplastic mucosa.

OBJECTIVE: To analyze the immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenomas and non-neoplastic mucosa. METHODS: 72 individuals were subjected to colonoscopy, which provided 50 samples of adenomas and 45 samples of non-neoplastic colorectal mucosa. The tissue samples were obtained via the tissue microarray technique and subjected to immunohistochemical analysis using primary anti-p53, anti-COX-2, and anti-caspase-3 antibodies. The positivity and intensity of the immunoreaction were classified. The analyzed variables were as follows: site of the adenomas in the colon, degree of dysplasia, size, and score of positivity and intensity of immunoexpression of the p-53, caspase-3, and COX-2 proteins. RESULTS: The immunoexpression of mutated protein p53 was positive in 30 (60%) adenoma samples and negative in 20 (40%) adenoma samples. The immunoexpression of mutated protein p53 was negative in 39 (86.6%) samples and positive in 6 (13.3%) samples of the non-neoplastic colorectal mucosa (p<0.0001). Significant differences were seen between both the largest size (p=0.006) and the highest degree of dysplasia (p<0.0001) of the adenomas and the intensity of immunoexpression of mutated protein p53. The positivity and intensity of immunoexpression of COX-2 (p=0.14) and caspase-3 (p=0.23) showed no significant differences between the adenomas and the non-neoplastic colorectal mucosa. CONCLUSION: Mutated protein p53 was hyperexpressed in the adenomas compared with the non-neoplastic mucosa. Greater size and greater degree of dysplasia in the adenomas were associated with higher expression of mutated protein p53. The immunoexpression of COX-2 and caspase-3 in the adenomas did not exhibit a correlation with the anatomical-pathological features of the tumors and did not differ from the corresponding expression levels in the non-neoplastic mucosa.