Skin Protein Profile after Major Weight Loss and Its Role in Body Contouring Surgery.

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.

Differentially expressed proteins in positive versus negative HNSCC lymph nodes.

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.

Features of the female prostate according to age: an autopsy study / Características da próstata feminina de acordo com a idade: um estudo de autópsia

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.

Cyclical iron supplementation to reduce anemia among Brazilian preschoolers: a randomized controlled trial.

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.

Proteomic approaches identify members of cofilin pathway involved in oral tumorigenesis.

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.

Differential elemental distribution of retained particles along the respiratory tract.

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.

Loxosceles gaucho venom-induced acute kidney injury--in vivo and in vitro studies.

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.

Loxosceles gaucho Venom-Induced Acute Kidney Injury In Vivo and In Vitro Studies

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.

Renal glomerular alterations in patients with cancer: a clinical and immunohistochemical autopsy study.

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.

Perfil sócio-econômico-cultural e fatores de risco em pacientescom neoplasia intra-epitelial cervical persistente / Socioeconomic and cultural profile, and risk factors of patients with persistent cervical intraepithelial neoplasia

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.

Endomyocardial fibrosis as a cause of Budd-Chiari syndrome and fatal pulmonary embolism.

A 24-year-old-man had right-sided heart failure of 3 months' duration. A Doppler echocardiogram revealed atrium and right ventricular enlargement, obliteration of the right ventricular apex, and a mass with an echolucent center measuring 20x21 mm in the right ventricular outlet. He died of pulmonary embolism. At autopsy, a huge organized thrombus obliterating the right ventricular apex passing through the tricuspid valve to the right atrium and then extending to the inferior vena cava up to the suprahepatic veins was seen. Histologically, an intense fibrotic thickening of the endomyocardium extending into the myocardium was observed. Cardiac thrombosis associated with endomyocardial fibrosis should be added to the list of causes of Budd-Chiari syndrome.

Coronary emergency and diabetes as manifestations of pheochromocytoma.

We report on a woman with refractory hypertension and diabetes suffering from hypertensive crises, one with chest pain suggesting acute coronary syndrome, and another with an abdominal pain, after which a para-aortic abdominal mass was diagnosed, by ultrasound, as pheochromocytoma, later confirmed by an adrenal scintigraphic study with (131)I-labeled metaiodobenzylguanidine. The patient was successfully treated with complete reversal of hypertension and diabetes. Our case illustrates the importance of maintaining a high index of suspicion in patients simultaneously presenting with an acute myocardial event and hypertensive crises.

Epigenetic silencing of CRABP2 and MX1 in head and neck tumors.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Conditions of most patients are diagnosed at late stages of the disease, and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined rapid subtractive hybridization and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) in HNSCC cell lines (FaDu, UM-SCC-14A, UM-SCC-17A, UM-SCC-38A). This combined analysis identified 78 genes, 35 of which were reactivated in at least 2 cell lines and harbored a CpG island at their 5' region. Reactivation of 3 of these 35 genes (CRABP2, MX1, and SLC15A3) was confirmed by quantitative real-time polymerase chain reaction (PCR; fold change, >or=3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using methylation-specific PCR, we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease-free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients.

The effect of different doses of cigarette smoke in a mouse lung tumor model.

Few studies have used Balb/c mice as an animal model for lung carcinogenesis. In this study, we investigated the effect of different doses of cigarette smoking in the urethane-induced Balb/c mouse lung cancer model. After injection of 3mg/kg urethane intraperitoneally, the mice were then exposed to tobacco smoke once or twice a day, five times a week, in a closed chamber. The animals were randomly divided into four groups. The control group (G0) received urethane only. The experimental groups (G1, G2 and G3) received urethane and exposure to the smoke of 3 cigarettes for 10 minutes once a day, 3 cigarettes for 10 minutes twice a day, and 6 cigarettes for 10 minutes twice a day, respectively. The mice were sacrificed after 16 weeks of exposure, and the number of nodules and hyperplasia in the lungs was counted. The results showed no statistically significant difference in the mean number of nodules and hyperplasia among the different groups, suggesting that the Balb/c mice are not suitable to study the pathogenesis of tobacco smoking-induced tumor progression in the lungs.

Treatment of chronic systolic heart failure secondary to Chagas heart disease in the current era of heart failure therapy.

The treatment of chronic heart failure secondary to Chagas disease has been based on extrapolation of data achieved in the treatment of non-Chagas disease heart failure. Because beta-blockers decrease the incidence of sudden cardiac death in non-Chagas disease heart failure and sudden cardiac death occurs preferentially in patients with mild Chagas disease heart failure, beta-blockers may be administered first to class I/II patients with Chagas disease heart failure. In advanced Chagas disease heart failure, angiotensin-converting enzyme inhibitor and diuretics may be given at first to compensate for congestive symptoms. After clinical status improvement, beta-blockers should be given at targeted doses, if necessary reducing angiotensin-converting enzyme inhibitor doses. Primary and secondary prevention of sudden cardiac death may be accomplished with implantable cardioverter defibrillators because of the high recurrence of life-threatening arrhythmias despite amiodarone administration. In refractory heart failure, heart transplantation is the treatment of choice.

Changes in lymphocyte phenotype and increased skin allograft survival after FTY720+FK506 therapy / Modificação do fenótipo linfocitário e aumento da sobrevida do enxerto de pele após a terapia com FTY720 + FK506

The development of new drugs to be associated with calcineurin inhibitors and promote additional immunosuppression with fewer side effects is the goal in transplantation. FTY720 is a new synthetic compound which presents immunomodulatory properties which are not fully understood. It has been reported that the main mechanism of action of FTY720 is to reduce the peripheral lymphocyte count by redirecting these cells toward secondary lymphoid organs. Skin allograft transplantation in a fully mismatched strain combination was used to investigate the potential of FTY720 alone or in combination with a calcineurin inhibitor - FK506 - in preventing rejection. The number and phenotype of immune system cells was also evaluated. FTY720 alone or in combination with FK506 provided significant skin allograft survival. FTY720+FK506 therapy was associated with decreases of total lymphocyte numbers in spleen and blood, and increases in apoptosis levels in splenocytes. In FTY720 isolated treatment, a significant decrease in the CD4 expression and significantly lower expressions of MHC II and ICAM-1 molecules were observed in spleen lymphocytes. Despite of allograft survival being the same in both FTY720 and FTY720+FK506 treated groups, the association of drugs was associated with the absence of macroscopic skin necrosis for a longer period than the other treatments (FTY720, FK506) and histology showed less cell infiltration. Our results suggest that a decrease of effector T cells due to elevated levels of apoptosis and impairment in the appearance of antigens were events associated with FTY720+FK506 administration.

O objetivo na área dos transplantes é o desenvolvimento de novas drogas que possam ser associadas a inibidores da calcineurina para evitar o processo de rejeição e causar menos efeitos colaterais. FTY720 é um novo composto sintético que apresenta propriedades imunomoduladoras não completamente elucidadas. Foi relatado que o principal mecanismo de ação do FTY720 é a redução do número de linfócitos periféricos através do redirecionamento dessas células para órgãos linfóides secundários. O alotransplante de pele entre linhagens de camundongos completamente incompatíveis quanto ao MHC foi usado para investigar o potencial de FTY720 isolado ou em combinação com um inibidor da calcineurina - FK506 - na prevenção da rejeição. Também foram avaliados o número e fenótipo das células do sistema imune. A administração de FTY720 como monoterapia ou FTY720+FK506 associou-se a uma diminuição do número total de linfócitos no baço e no sangue e aumento dos níveis de apoptose nos esplenócitos. No grupo tratado somente com FTY720, foi observada uma diminuição mais importante da expressão de CD4 e expressão significativamente menor de moléculas de MHC II e ICAM-1. Apesar de a sobrevida do aloenxerto ter sido igual para os grupos tratados com FTY720 ou FTY720 +FK506, a associação das drogas promoveu ausência de necrose macroscópica da pele por um período maior do que os outros tratamentos (FTY720, FK506) e os achados histológicos mostraram menor infiltrado celular. Nossos resultados sugerem que uma diminuição do número de células T efetoras devido a elevados níveis de apoptose e o prejuízo da apresentação de antígenos foram os eventos associados à administração de FTY720+FK506.

Annexin 1: differential expression in tumor and mast cells in human larynx cancer.

Annexin 1 protein (ANXA1) expression was evaluated in tumor and mast cells in human larynx cancer and control epithelium. The effect of the exogenous ANXA1 (peptide Ac 2-26) was also examined during the cellular growth of the Hep-2 human larynx epidermoid carcinoma cell line. This peptide inhibited the proliferation of the Hep-2 cells within 144 hr. In surgical tissue specimens from 20 patients with larynx cancer, ultrastructural immunocytochemistry analysis showed in vivo down-regulation of ANXA1 expression in the tumor and increased in mast cells and Hep-2 cells treated with peptide Ac2-26. Combined in vivo and in vitro analysis demonstrated that ANXA1 plays a regulatory role in laryngeal cancer cell growth. We believe that a better understanding of the regulatory mechanisms of ANXA1 in tumor and mast cells may lead to future biological targets for the therapeutic intervention of human larynx cancer.

Colo do Útero: alterações citológicas mais freqüentes e fatores de risco predisponentes em uma população de São José do Rio Preto – SP / Uterine Cervical: more frequently atipias and risk factors in a population of São José do Rio Preto – SP

Com o objetivo de identificar os fatores de risco e a faixa etária mais acometida por alterações pré-malignas ou malignas em mulheres que realizaram citologias cervicais no período de 15 de março a 30 de abril de 2002, foi aplicado um questionário em 72,41 das mulheres com colpocitologia alterada, de São José do Rio Preto, identificando dados epidemiológicos e sócio-econômicos. As alterações foram encontradas em mulheres com média de idade de 42,1 anos (mediana 36 anos), sendo 33,34

Pneumonia-induced sepsis and gut injury: effects of a poly-(ADP-ribose) polymerase inhibitor.

BACKGROUND: Pseudomonas aeruginosa is commonly associated with nosocomial pneumonia. Ileal mucosal injury may be induced by severe lung infection. During septic shock, peroxynitrite-mediated DNA strand-breaks activate the enzyme poly-(ADP)-ribose polymerase (PARP) resulting in cellular energetic suppression and cell dysfunction. The aim of this study was to determine whether gut injury could be demonstrated in sepsis induced by P. aeruginosa and the effects of a PARP inhibitor (PJ34) on the associated gut injury. MATERIALS AND METHODS: After baseline measurements, 20 rabbits were randomized into three groups: Sham (n = 5): transtracheally inoculated (TI) with 2 ml of phosphate buffer solution (PBS); P. aeruginosa + saline (n = 8), TI with 4 x 10(12) CFU/ml of P. aeruginosa in 2 ml/kg of PBS + i.v. saline; and P. aeruginosa + PJ34 (n = 7), TI with 4 x 10(12) CFU/ml of P. aeruginosa and i.v. treatment with PJ34. RESULTS: P. aeruginosa caused a hyperdynamic response with increased blood flow also in the superior mesenteric artery. No significant differences were found in luminal gut lactate concentrations or PCO(2)-gap between groups. Histological specimens showed moderate or diffuse alveolar infiltrate in the P. aeruginosa + saline group (6/8) and in the P. aeruginosa + PJ34 group (6/7). Gut wet-to-dry weight ratio was significantly higher in the P. aeruginosa + saline group than in Shams (7.5 +/- 0.8 versus 6.4 +/- 0.7, P < 0.05) and significantly lower in the P. aeruginosa + PJ34 group (6.1 + 0.5, P < 0.05 versus the other groups). Blood cultures were positive in 1/5 (Sham), 8/8 (P. aeruginosa + saline group) and 4/7 (P. aeruginosa + PJ34 group) (RR 0.57 CI 95% 0.30-1.08). CONCLUSIONS: Pharmacological inhibition of PARP reduces gut inflammation and may limit bacterial translocation.

Angina-like chest pain and syncope as the clinical presentation of left ventricular endomyocardial fibrosis: a case report.

A 47-year-old woman complained of angina-like chest pain, near-syncope, and syncopal episodes of 17 years' duration. Physical examination was unremarkable. A 12-lead resting ECG showed symmetrically inverted T waves in the inferior and anterolateral leads. A graded treadmill exercise stress test precipitated angina-like chest pain accompanied by a near-syncopal episode associated with a systemic arterial pressure of 60/40 mm Hg. Echocardiography disclosed left ventricular apical obliteration. Left ventriculogram showed a typical "ace of heart'' shadow as well as filling defects and apical obliteration. Endomyocardial biopsy of the left ventricle diagnosed left ventricular endomyocardial fibrosis. Thus, angina-like chest pain and near-syncopal episodes should be added to the list of clinical manifestations of pure left ventricular endomyocardial fibrosis.