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Chronic inflammation during morbid obesity significantly alters cutaneous tissue. Large weight loss achieved after bariatric surgery minimizes or halts damage caused by metabolic syndrome, but further deteriorates the clinical condition of skin. Postbariatric skin flaccidity produces major difficulties to plastic surgery. In this study, we analyzed differences in protein composition of the skin between patients with morbid obesity and those after large weight loss and established correlations between differentially expressed proteins and clinical characteristics of postbariatric skin tissue, to improve body contouring surgery techniques. METHODS: Skin fragments were removed from the abdomen of 32 patients, who were allocated into 3 groups: morbidly obese, large weight loss without surgery, and postbariatric surgery. Samples were subjected to proteomic analysis, and the protein profiles of the groups were compared. Six differentially expressed proteins of clinical interest were validated by immunohistochemistry and statistical analysis. RESULTS: Comparative analyses confirmed differences in protein profile of the skin between morbidly obese and large weight loss groups. A persistent increase in inflammatory markers such as haptoglobin was observed in all groups and decrease in the expression of collagen XIV, which regulates the physical properties of cutaneous tissue, was observed in the postbariatric group. CONCLUSIONS: High expression of haptoglobin associated with the decrease of Collagen XIV, vinculin, and periplakin in the groups after major weight losses, mainly postbariatric, confirm that the inflammatory lesion remains active in the skin and causes changes in its structural organization, with serious repercussions on its clinical characteristics and physical properties.
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BACKGROUND: Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteria for the diagnosis of nodal status remain limited. In the present study, we aimed to characterize the proteomic profile of lymph node metastasis from HNSCC patients. METHODS: In the present study, we used one- and two-dimensional electrophoresis and mass spectrometry analysis to characterize the proteomic profile of lymph node metastasis from HNSCC. RESULTS: Comparison of metastatic and non-metastatic lymph nodes showed 52 differentially expressed proteins associated with neoplastic development and progression. The results reinforced the idea that tumors from different anatomical subsites have dissimilar behaviors, which may be influenced by micro-environmental factor including the lymphatic network. The expression pattern of heat shock proteins and glycolytic enzymes also suggested an effect of the lymph node environment in controlling tumor growth or in metabolic reprogramming of the metastatic cell. Our study, for the first time, provided direct evidence of annexin A1 overexpression in lymph node metastasis of head and neck cancer, adding information that may be useful for diagnosing aggressive disease. CONCLUSIONS: In brief, this study contributed to our understanding of the metastatic phenotype of HNSCC and provided potential targets for diagnostic in this group of carcinomas.
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Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Proteômica , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/genética , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
ABSTRACT INTRODUCTION: The prostate gland plays an important role in male and female reproductive system. Data on this organ have not been fully explored in women since its first description, probably because it is considered a vestigial gland. OBJECTIVE: To correlate the morphology of the female prostate with age in autopsy. MATERIAL AND METHODS: Thirty-two female cadavers, 31 adults and one newborn, underwent dissection of the region corresponding to the prostate for histological analysis. The urethral region was divided into three portions: proximal, median, and distal. All the glands present in the samples were counted. Clinical data were collected, including age and previous diagnosis of menopause. RESULTS: There were no macroscopically visible prostate. Morphological analyses showed glands surrounding the urethra with a stratified epithelium, ranging from squamous to columnar types, with prevalence of basophilic cells and some presenting with secretion inside. A significant correlation with prostate tissue was found between the median and the proximal urethra, as well as between the median and distal urethra, suggesting that when the glandular structures increase in the median region, there is also an increase in the anterior and distal structures. Moreover, a prevalence of the glands in the median urethra was observed in post-menopausal women. CONCLUSION: This study suggests that the number of female prostate glands increases after menopause, with proliferative spread and growth of the median portion to the proximal and distal portions.
RESUMO INTRODUÇÃO: A próstata é uma glândula com papel importante no sistema reprodutor masculino e feminino. Dados sobre esse órgão não foram completamente explorados em mulheres desde a sua primeira descrição, provavelmente por ser considerada uma glândula vestigial. OBJETIVO: Correlacionar a morfologia da próstata feminina com a idade em autópsias. MATERIAL E MÉTODOS: Trinta e dois cadáveres do sexo feminino, sendo 31 adultos e um recém-nascido, tiveram sua região correspondente à próstata dissecada e avaliada por meio de histologia. A região uretral foi dividida em três partes: anterior, mediana e distal. As glândulas presentes nas amostras foram contadas. Dados clínicos foram coletados, incluindo idade e diagnóstico prévio de menopausa. RESULTADOS: Não foram observadas próstatas macroscopicamente. Análises morfológicas mostraram glândulas ao redor da uretra com epitélio estratificado, variando do tipo escamoso a colunar, com predomínio de células basófilas e algumas apresentando secreção em seu interior. Correlação significativa com tecido prostático foi detectada entre a uretra mediana e a proximal, assim como entre as uretras mediana e distal, sugerindo que quando as estruturas glandulares aumentam na região mediana, há também aumento nas estruturas anterior e distal. Além disso, o predomínio das glândulas na uretra mediana foi observado em mulheres pós-menopausa. CONCLUSÃO: Este estudo sugere que o número de glândulas prostáticas femininas aumenta após a menopausa, com disseminação e crescimento da região mediana para a proximal e distal.
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BACKGROUND: Iron-deficiency anemia is the most common type of nutritional disorder. New strategies for the treatment of anemia are very important for its reduction. The aim of this study was to assess the efficacy and feasibility of cyclical iron supplementation as a strategy to reduce the prevalence of anemia among preschoolers. METHODS: A randomized controlled trial was performed in the entire population of under five-year-old children who attended government daycare centers in a small town in the State of Sao Paulo, Brazil. The children were randomly allocated into two intervention groups: the Weekly and Cyclical Groups. During a ten-month period, the Weekly Group (n = 51) received weekly doses of 30 mg elemental iron (40 doses) and the Cyclical Group (n = 48) received two cycles of 20 daily doses of 30 mg elemental iron separated by a four-month period (40 doses). RESULTS: Overall, at the end of ten months, the prevalence of anemia of the children on both supplementation regimens showed a significant decrease from 20.20% to 5.05% (p-value < 0.0005). There was no significant difference in the anemia between the two groups (p-value = 0.35). The mean hemoglobin concentration increased by 0.27 g/dL (p-value < 0.016) and 0.47 g/dL (p-value < 0.0005) in the Weekly and Cyclical Groups, respectively; again there was no significant difference between groups (p-value = 0.17). However, the cyclical regimen was easier to manage. CONCLUSIONS: Both supplementation regimens significantly reduced the prevalence of anemia however administration of the Cyclical Group was easier to carry out and control. CLINICAL TRIAL REGISTRATION NUMBER: NCT00992823.
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Anemia Ferropriva/dietoterapia , Suplementos Nutricionais , Esquema de Medicação , Ferro/administração & dosagem , Anemia Ferropriva/prevenção & controle , Brasil , Pré-Escolar , Feminino , Ferritinas/sangue , Humanos , Lactente , Deficiências de Ferro , Masculino , Resultado do TratamentoRESUMO
The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread. In this study, we used one- and two-dimensional gel electrophoresis, mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas. Using a refinement for classifying oral carcinomas in regard to prognosis, we analyzed small but lymph node metastasis-positive versus large, lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination. Specific protein patterns favoring metastasis were observed in the "more-aggressive" group defined by the present study. This group displayed upregulation of proteins involved in migration, adhesion, angiogenesis, cell cycle regulation, anti-apoptosis and epithelial to mesenchymal transition, whereas the "less-aggressive" group was engaged in keratinocyte differentiation, epidermis development, inflammation and immune response. Besides the identification of several proteins not yet described as deregulated in oral carcinomas, the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas.
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Carcinoma de Células Escamosas/metabolismo , Cofilina 1/metabolismo , Neoplasias Bucais/metabolismo , Proteômica , Idoso , Carcinoma de Células Escamosas/patologia , Cofilina 1/genética , Eletroforese em Gel Bidimensional , Eletroforese em Gel de Poliacrilamida , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Invasividade NeoplásicaRESUMO
CONTEXT: Prolonged exposure to ambient particles is associated with premature mortality due to cardio-respiratory diseases and lung cancer. The size and composition of these particles determine their toxicity, which is aggravated by their long-term retention in the lungs. OBJECTIVE: To compare the elemental profile of particles retained along the bronchial tree and lymph nodes by combining laser capture microdissection (LCM) and elemental composition analysis through energy dispersive x-ray (EDX) and scanning electron microscopy (SEM). MATERIAL AND METHODS: Twenty-four right lung middle lobes from autopsied cases were obtained from two cities with different pollution backgrounds. Lung samples were collected from three distinct sites within the lung at the time of autopsy: peribronchial tissue, peripheral parenchyma and hilar lymph nodes. Areas of potentially increased particle deposition were microdissected using LCM and analyzed for elemental composition through EDX "allied" with SEM. RESULTS: Elemental analyses of the particles retained along the bronchial tree showed two groups of distribution: peribronchiolar or lymph node deposition. The elemental profile of peribronchial areas were significantly different between the two cities and were better discriminators of past air pollution exposure. CONCLUSION: Our data suggest that particle uptake varies along the bronchial tree and human lung tissue retains particles indicative of regional air pollution background.
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Poluentes Atmosféricos/toxicidade , Brônquios/efeitos dos fármacos , Exposição por Inalação/efeitos adversos , Linfonodos/efeitos dos fármacos , Metais/análise , Material Particulado/toxicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/análise , Brasil , Brônquios/química , Brônquios/ultraestrutura , Monitoramento Ambiental , Feminino , Humanos , Lasers , Linfonodos/química , Linfonodos/ultraestrutura , Masculino , Microdissecção , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Material Particulado/análise , Espectrometria por Raios X , Saúde da População UrbanaRESUMO
BACKGROUND: Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. CONCLUSIONS/SIGNIFICANCE: Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite.
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Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/fisiopatologia , Aracnídeos/patogenicidade , Rim/patologia , Rim/fisiopatologia , Venenos de Aranha/toxicidade , Injúria Renal Aguda/patologia , Animais , Taxa de Filtração Glomerular , Histocitoquímica , Imuno-Histoquímica , Rim/fisiologia , Masculino , Ratos , Ratos Wistar , Circulação Renal , UrodinâmicaRESUMO
Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury(AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo.In order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes.Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats.
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Animais , Ratos , Aranhas/classificação , Rim/fisiopatologia , Rim/irrigação sanguínea , Venenos de Aranha/síntese química , Venenos de Aranha/toxicidade , Néfrons/fisiopatologia , Rabdomiólise/complicações , VasoconstriçãoRESUMO
BACKGROUND: Membranous glomerulonephritis (MGN) can be found in patients with cancer as a paraneoplastic syndrome or it could be manifested clinically before tumor detection. The aim of this study was to evaluate the frequency and type of renal histopathological alterations in patients with malignancy that died without cancer treatment and were submitted to necropsy. METHODS: Patient's demographical and clinical data collection and laboratory tests (serum creatinine and urine sample) were evaluated. RESULTS: Kidney fragments from 21 patients were obtained and studied by light microscopy after habitual staining. Immunohistochemistry studies were performed with monoclonal immunoglobulin and tumor markers. Patients' mean age was 71 years and 62% were male. The most frequent tumor was gastric cancer (five cases), followed by colon and oral cavity (three cases each). In 67% of the cases, malignancy was the main cause of death. Serum creatinine was increased in 10 cases, proteinuria in 15, and hematuria was present in 8 cases. The most usual glomerular lesion found was thickening of basement membrane (BM) of the capillary loops. There were two cases of IgA nephropathy, three cases of focal segmental glomerulosclerosis, and one case of MGN. Only in the patient with MGN and metastatic melanoma specific tumor markers were identified in the kidney. CONCLUSIONS: We observed a wide range of glomerular pathological changes and abnormal urinary sediments in almost all patients, but we found tumor marker deposits only in the patient with MGN.
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Carcinoma/complicações , Glomerulonefrite/etiologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Melanoma/complicações , Neoplasias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Carcinoma/patologia , Estudos de Coortes , Feminino , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Humanos , Masculino , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
Introdução: Nas neoplasias intra-epiteliais cervicais (CIN), além da persistência do HPV, existem váriosfatores de risco coadjuvantes identificados que contribuem para o desenvolvimento de câncer cervical.Objetivo: Fazer uma caracterização do perfil de saúde e da causalidade em pacientes atendidas na FAMERP/FUNFARME, com CIN persistente em relação às pacientes sem persistência dessa doença. Casuística e Método: Foi aplicado um questionário para caracterização do perfil sócio econômico-cultural e fatores derisco para HPV em dois grupos de pacientes. Grupo estudo: 20 pacientes com CIN persistente do colo nosúltimos 4 anos; Grupo controle: 12 pacientes que tiveram esta lesão, foram tratadas e permanecem sem doença por, no mínimo, 36 meses. Resultados e Discussão: A média de idade das pacientes foi de 44,3 anos e mediana de 41 anos. Todas as 32 entrevistadas pertencem à classe social inferior, correspondendo positivamente ao perfil sócio-econômico-cultural dessa classe e estando submetidas aos fatores de riscopróprios da pobreza. Verificamos que CIN 2 e 3 estão associadas à idade, sendo 46,9% das pacientes abaixo de 41 anos e 15,6% acima dessa mediana (p=0,02). As diferenças entre os dois grupos, relacionadas à persistência de CIN são: maior número de casos de outras DST além do HPV (p=0,05), inclusive 26,6% das pacientes sendo HIV positivas; não usar preservativos na atividade sexual (p=0,05) e fumar cigarros (0,01). A carga viral alta de HPV oncogênico de alto risco é apontada por muitos autores como necessária à CIN para se tornar persistente, o que não avaliamos. Conclusão: A causalidade e o perfil de saúde investigados não estão diretamente relacionados à persistência da CIN, exceto nos itens: ter outras DST além de HPV, não utilizar preservativos e fumar cigarros; CIN 2 e 3 estão diretamente relacionadas à idade das pacientes, commaior pico de incidência entre 27 e 41 anos.
Introduction: In cervical intraepithelial neoplasia (CIN), besides the persistence of HPV, several factors of risk identified accomplices who contribute to the development of cervical cancer exist. Obejctive: Characterization of the profile of health and of the causality in patients assisted at FAMERP/FUNFARME,with persistent CIN in relation to the patients without recurrence of that disease. Patients and Method: Aquestionnaire was applied to characterize the economical-cultural profile and the risk factors for HPV in two groups of patients. Group study: 20 patients with persistent CIN of the uterine cervix in the last 4 years; Group control: 12 patients who had this lesion were treated and remain free of the disease at least within 36 months. Results and Discussion: Mean age was 44.3 years (median of 41 yrs). All the 32 female patients interviewed belong to a lower social class, positively corresponding to the economical-cultural profile of this class and submitted to the own poverty risk factors. We verified that CIN 2 and 3 is associated to the age; 46,9% of the patients under 41 years and 15,6% above this median age (p=0,02). The differences between the two groups related to the persistence of CIN are as follows: larger number of STD cases besides HPV (p=0.05), including 26.6% of the patients who were HIV-positive; noncompliance to the use of condoms insexual intercourse (p=0.05), and smoking (0.01). The high-risk of oncogenic high HPV viral load is pointed by many authors as necessary to CIN to become persistent. Our study did not evaluate this variable. Conclusion: Causality and health profiles investigated are not directly related to the persistence of CIN, except in the following variables: having other STDs besides HPV, noncompliance to use condoms, and smoking; CIN 2 and 3 are directly related to the patients age, with a higher pick incidence between 27 and 41 years.