Angiotensin involvement in kidney injury induced by rheumatoid arthritis in rat.

Renal injury induced by rheumatoid arthritis is not clear and may be related to the angiotensin II. We aim to investigate the adjuvant-induced arthritis (AIA) injury in rat kidney, focusing the angiotensin II/AT1 pathway. Male Wistar rats were allocated in to three groups: Control, AIA and AIA plus losartan. The AIA was induced by injection of 100 µL of an emulsion of dissected Mycobacterium tuberculosis (50 mg/mL) on the paw. Treatment with losartan was initiated on the first day of immunization (daily subcutaneous injection, 1 mg/kg). After 60 days post immunization, we evaluated kidney function by plasma creatinine, urea and uric acid levels and creatinine depuration; kidney injury by apoptosis analysis and inflammation markers such as macrophages, transforming growth factor beta (TGF-ß) and inducible nitric oxide synthase (iNOS) expression; oxidative stress by plasma thiobarbituric acid reactive substances (TBARS); renal expression of angiotensin receptors subtype 1 (AT1 ) and 2 (AT2 ) and plasma concentration of angiotensin II. AIA rats showed elevated plasma levels of creatinine, urea, uric acid, TBARS and Ang II and reduced creatinine depuration, and enhanced kidney macrophage number, TGF-ß, caspase-3, iNOS and AT1 /AT2 receptors expression. The losartan reduced plasma creatinine and its clearance, reduced macrophages and the expression of TGF-ß and iNOS in renal tissues, and reduced plasma TBARS. We conclude that AIA causes kidney injury by a physiopathological mechanism that involves AT1  stimulation in renal tissue, elevating the presence of macrophages, the expression of TGF-ß and iNOS, as well the local oxidative stress, which contribute to renal function deterioration.

Does protein supplementation and exercise interfere with renal function and structure? / A suplementação de proteína e o exercício interferem na função e estrutura renal? / ¿la suplementación de proteínas y el ejercicio interfieren en la función y estructura renal?

ABSTRACT Introduction: During physical activity, the body diverts blood to essential areas such as skeletal muscle, reducing the supply to non-essential areas such as the kidney. Whey protein is one of the most widely used supplements in gyms. Objectives: To evaluate renal function and renal structure in rats submitted to physical exercise with and without the use of protein supplementation. Methods: The protein used was Whey Hydro PRO 2 - Probiotica®. It was administered orally (by gavage), diluted in mineral water (1.8 g/kg of body weight, shortly after swimming training). The rats were divided into four groups: rats with exercise (Exc), rats without exercise (ñExc), rats with exercise and with protein supplementation (Prot/Exc) and rats without exercise and with protein supplementation (Prot/ñExc). The training consisted of swimming for 30 minutes, using load equivalent to 2% of body weight, five times a week for a total of 10 weeks. The protein was administered by gavage, once daily, immediately after the training. Results: A reduced glomerular filtration rate was observed in the animals of the Exc group compared to those of the Prot/Exc group. Plasma creatinine values were similar between the groups submitted to exercise and those not submitted to exercise. Plasma sodium and the sodium excretion fraction were lower in the Prot/Exc group compared to the Exc group. Urinary excretion was similar between groups. Histological analysis: Significant hydropic degeneration was observed in the animals that received protein supplementation and submitted to exercise. Conclusion: These results show that exercise associated with protein supplementation (2g/day/kg) leads to changes in the tubular mechanisms of sodium adjustments and structural changes in the renal parenchyma. Level of evidence II; Therapeutic studies - Investigation the results of treatment.

RESUMO Introdução: Durante a atividade física o corpo faz remanejamento sanguíneo para áreas essenciais como a musculatura esquelética, reduzindo o suprimento em áreas não essenciais como o rim. O whey protein (proteína do soro do leite) é um dos suplementos mais usados nas academias. Objetivos: Avaliar a função e a estrutura renal em ratos submetidos ao exercício físico sem e com o uso da suplementação de proteína. Métodos: A proteína usada foi Whey Hydro PRO 2 - Probiótica®, sendo administrada por via oral (gavagem), diluída em água mineral (1,8 g/kg de peso corporal logo após o treino de natação). Os ratos foram divididos em quatro grupos: ratos com exercício (Exc), ratos sem exercício (ñExc), ratos com exercício e com suplementação alimentar de proteína (Prot/Exc) e ratos sem exercício e com suplementação alimentar de proteína (Prot/ñExc). O treinamento consistia em natação por 30 minutos, com utilização de carga, equivalente a 2% do peso corporal, 5 vezes por semana em um total de 10 semanas. A proteína foi administrada por gavagem, uma vez ao dia e logo depois do treino. Resultados: Observou-se queda da filtração glomerular renal nos animais do grupo Exc vs. Prot/Exc. Os valores de creatinina plasmática foram semelhantes entre os grupos que praticaram o exercício vs. os que não praticaram. Para o sódio plasmático e a fração de excreção de sódio, os valores foram menores no grupo Prot/Exc quando comparados com o grupo Exc. A excreção urinária de ureia foi semelhante entre os grupos. Análise histológica: Observou-se degeneração hidrópica significativa nos animais que receberam a suplementação de proteína e realizaram o exercício. Conclusão: Esses resultados mostram que o exercício em conjunto com a suplementação de proteína (2 g/dia/Kg), determina alterações nos mecanismos tubulares de ajustes do sódio e alterações estruturais no parênquima renal. Nível de evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.

RESUMEN Introducción: Durante la actividad física el cuerpo hace reubicación sanguínea hacia áreas esenciales como la musculatura esquelética, reduciendo el suministro en áreas no esenciales como el riñón. La whey protein (proteína del suero de la leche) es uno de los suplementos más usados en los gimnasios. Objetivos: Evaluar la función y la estructura renal en ratones sometidos al ejercicio físico sin y con el uso de la suplementación de proteína. Métodos: La proteína utilizada fue Whey Hydro PRO 2 - Probiótica® siendo administrada vía oral (gavaje), diluida en agua mineral (1,8 g/kg de peso corporal luego después del entrenamiento de natación). Los ratones fueron divididos en cuatro grupos: ratones con ejercicio (Exc), ratones sin ejercicio (ñExc), ratones con ejercicio y con suplementación alimentaria de proteína (Prot/Exc) y ratones sin ejercicio y con suplementación alimenticia de proteína (Prot/ñExc). El entrenamiento consistía en natación por 30 minutos, con uso de carga, equivalente al 2% del peso corporal, 5 veces por semana en un total de 10 semanas. La proteína fue administrada por gavaje, una vez al día y luego después del entrenamiento. Resultados: Se observó caída de la filtración glomerular renal en los animales del grupo Exc vs Prot/Exc. Los valores de creatinina plasmática fueron semejantes entre los grupos que practicaron el ejercicio vs los no practicaron. Para el sodio plasmático y la fracción de excreción de sodio, los valores fueron menores en el grupo Prot/Exc cuando comparados con el Exc. La excreción urinaria de urea fue semejante entre los grupos. Análisis histológico: Se observó degeneración hidrópica significativa en los animales que recibieron la suplementación de proteínas y no realizaron el ejercicio. Conclusión: Estos resultados muestran que el ejercicio en conjunto con la suplementación de proteína (2 g/día/Kg), determina alteraciones en los mecanismos tubulares de ajustes del sodio y alteraciones estructurales en el parénquima renal. Nivel de evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamiento.

Confidence in palliative care issues by medical students and internal medicine residents.

BACKGROUND: Palliative care (PC) is a relatively new field in Brazil, but this knowledge is of great importance in medical practice. OBJECTIVE: To evaluate the degree of confidence among medical students and first-year and second-year internal medicine residents in addressing issues of death and terminal illness with patients and their families. METHOD: A modified version of the Self-Efficacy in Palliative Care Scale was applied to 293 students in their first year to sixth year at the School of Medicine of São José do Rio Preto and to 43 residents in their first year or second year of medical practice at the same institution in Brazil, in 2015. The questionnaire evaluated students' opinions on the need to include theoretical and practical classes on PC in the medical school. RESULTS: Students in their fifth year of medical school were more confident than the students in their first, second, third and fourth years; there were no statistically significant differences between fifth-year students, sixth-year students and the internal medicine residents. CONCLUSION: Residents were more confident than all of the medical school students except those in their fifth year (P<0.05) because they have more contact with terminally ill patients than other students do; fifth-year medical students are likely overestimating their abilities.

Sextuple Tumors in Head and Neck Area: Evidence of Field Cancerization.

BACKGROUND: Field cancerization is a phenomenon in which prolonged exposure to carcinogens induces changes throughout the epithelium leaving the field ready for the appearance of premalignant or malignant lesions. These alterations can promote the development of multiple carcinomas and explain the appearance of recurrences and second primary tumors. The objective of this study was to report the case of a patient who developed six oral cavity tumors in five years of treatment and, also, demonstrate the immunohistochemical changes for p53 and Ki-67, routinely used to assess dysplasic regions. CASE REPORT: When altered, p53 and Ki-67 suggest the presence of field cancers, an area with genetically altered cells, presenting a high risk of developing premalignant and malignant lesions. This phenomenon explains the recurrence of malignant neoplasms after tumor resections. CONCLUSION: In addition, early identification of potentially malignant lesions in cases of second primary tumors is essential for effective treatment and patient survival, which usually have an unwelcoming prognosis.

Prevalência de alterações no ultrassom de calcâneo em Centro de Saúde Escola / Prevalence of ultrasound calcaneus changes in School Health Center

Objetivo: Verificar a prevalência de alterações no exame de ultrassonometria óssea de calcâneo (UOC) entre usuários de uma Unidade de Saúde Escola do Sistema de Atenção Primária í Saúde de um municí­pio do interior do estado de São Paulo, Brasil. Métodos: Estudo transversal entre indiví­duos que participaram da campanha de rastreamento de alterações ósseas realizada em um Centro de Saúde Escola, no perí­odo de 6 a 13 de setembro de 2013. Realizou-se a medida da UOC dos indiví­duos maiores de 18 anos que participaram da campanha, utilizando-se a Achilles Express®. Os indiví­duos com resultados alterados foram subdivididos em: Grupo de médio risco (GMR) quando o T-score ≤ -1 e > -2,5 e Grupo de alto risco (GAR) quando o T-score ≤ -2,5. Resultados: Foram realizados 389 exames de UOC, sendo 349 (89,71%) em mulheres e 40 (10,28%) em homens. Cento e sessenta e três (41,90%) usuários apresentaram alterações, dos quais 141 (86,50%) eram de médio risco e 22 (13,40%) eram de alto risco; não houve diferenças estatí­sticas significantes quanto í comparação dos fatores de riscos avaliados nestes grupos, exceto para a idade (p = 0,003). Conclusão: A idade foi um fator de risco não modificável, no entanto, deve-se atuar nos fatores de riscos modificáveis para melhorar a saúde óssea. (AU)

Objective: To assess the prevalence of altered quantitative ultrasound (QUS) between individuals of a School Health Unit of Primary Health Care System in a municipality in the State of São Paulo, Brazil. Methods: Cross-sectional study among individuals who attended the screening campaign of bone alterations carried out in a Teaching Health Center, in the period 6 to 13, September 2013. The measure of the QUS of individuals > 18 years who participated in the campaign was carried out, using the Achilles Express®. Individuals with altered results were subdivided into: medium-risk group (MRG) when the T-score ≤ -1 and > -2.5 and high-risk group (HRG) when the T-score ≤ -2.5. Results: We performed 389 tests QUS, 349 (89.71%) in women and 40 (10.28%) in men. One hundred sixty-three (41.90%) users showed changes, which 141 (86.50%) were medium-risk and 22 (13.49%) were high-risk. We did not observe statistically significant differences in the comparison between assessed risk factors, in these groups, except for age (p = 0.003). Conclusion: Age is a non-modifiable risk factor, however, we must act on the modifiable risk factors for improving bone health. (AU)

Prior intake of Brazil nuts attenuates renal injury induced by ischemia and reperfusion.

INTRODUCTION: Ischemia-reperfusion (IR) injury results from inflammation and oxidative stress, among other factors. Because of its anti-inflammatory and antioxidant properties, the Brazil nut (BN) might attenuate IR renal injury. OBJECTIVE: The aim of the present study was to investigate whether the intake of BN prevents or reduces IR kidney injury and inflammation, improving renal function and decreasing oxidative stress. METHODS: Male Wistar rats were distributed into six groups (N=6/group): SHAM (control), SHAM treated with 75 or 150 mg of BN, IR, and IR treated with 75 or 150 mg of BN. The IR procedure consisted of right nephrectomy and occlusion of the left renal artery with a non-traumatic vascular clamp for 30 min. BN was given daily and individually for 7 days before surgery (SHAM or IR) and maintained until animal sacrifice (48h after surgery). We evaluated the following parameters: plasma creatinine, urea, and phosphorus; proteinuria, urinary output, and creatinine clearance; plasmatic TBARS and TEAC; kidney expression of iNOS and nitrotyrosine, and macrophage influx. RESULTS: Pre-treatment with 75 mg of BN attenuated IR-induced renal changes, with elevation of creatinine clearance and urinary output, reducing proteinuria, urea, and plasmatic phosphorus as well as reducing kidney expression of iNOS, nitrotyrosine, and macrophage influx. CONCLUSION: Low intake of BN prior to IR-induced kidney injury improves renal function by inhibition of macrophage infiltration and oxidative stress.

PAI-1, CAIX, and VEGFA expressions as prognosis markers in oral squamous cell carcinoma.

BACKGROUND: In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX), and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC. MATERIALS AND METHODS: Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery. The correlations between protein expressions and clinicopathological parameters and prognosis were analyzed. RESULTS: Positive PAI-1 membrane expression was significantly associated with local disease relapse (P = .027). Multivariate analysis revealed that the positive PAI-1 membrane expression is an independent marker for local disease relapse, with approximately 14-fold increased risk when compared to negative expression (OR = 14.49; CI = 1.40-150.01, P = .025). Strong PAI-1 cytoplasmic expression was significantly associated with the less differentiation grade (P = .027). Strong CAIX membrane expression was significantly associated with local disease-free survival (P = .038). Positive CAIX cytoplasmic expression was significantly associated with lymph node affected (P = .025) and with disease-specific survival (P = .022). Multivariate analysis revealed that the positive CAIX cytoplasmic expression is an independent risk factor for disease-related death, increasing their risk approximately 3-fold when compared to negative expression (HR = 2.84; CI = 1.02-7.87, P = .045). Positive VEGFA cytoplasmic expression was significantly associated with less differentiation grade (P = .035). CONCLUSION: Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients.

Prior intake of Brazil nuts attenuates renal injury induced by ischemia and reperfusion / A ingestão prévia de castanha-do-brasil atenua a lesão renal induzida por isquemia e reperfusão

ABSTRACT Introduction: Ischemia-reperfusion (IR) injury results from inflammation and oxidative stress, among other factors. Because of its anti-inflammatory and antioxidant properties, the Brazil nut (BN) might attenuate IR renal injury. Objective: The aim of the present study was to investigate whether the intake of BN prevents or reduces IR kidney injury and inflammation, improving renal function and decreasing oxidative stress. Methods: Male Wistar rats were distributed into six groups (N=6/group): SHAM (control), SHAM treated with 75 or 150 mg of BN, IR, and IR treated with 75 or 150 mg of BN. The IR procedure consisted of right nephrectomy and occlusion of the left renal artery with a non-traumatic vascular clamp for 30 min. BN was given daily and individually for 7 days before surgery (SHAM or IR) and maintained until animal sacrifice (48h after surgery). We evaluated the following parameters: plasma creatinine, urea, and phosphorus; proteinuria, urinary output, and creatinine clearance; plasmatic TBARS and TEAC; kidney expression of iNOS and nitrotyrosine, and macrophage influx. Results: Pre-treatment with 75 mg of BN attenuated IR-induced renal changes, with elevation of creatinine clearance and urinary output, reducing proteinuria, urea, and plasmatic phosphorus as well as reducing kidney expression of iNOS, nitrotyrosine, and macrophage influx. Conclusion: Low intake of BN prior to IR-induced kidney injury improves renal function by inhibition of macrophage infiltration and oxidative stress.

RESUMO Introdução: a lesão por isquemia-reperfusão (IR) resulta, entre outros fatores, de inflamação e estresse oxidativo. Devido às suas propriedades anti-inflamatórias e antioxidantes, a castanha-do-brasil (BN) pode atenuar a lesão renal causada por IR. Objetivo: O objetivo foi investigar se a ingestão prévia de BN reduz a lesão e a inflamação renal causadas por IR, melhorando a função renal e o estresse oxidativo. Métodos: Ratos Wistar machos foram distribuídos em seis grupos (N=6/grupo): SHAM (controle), SHAM tratado com 75 ou 150 mg de BN, IR, e IR tratado com 75 ou 150 mg de BN. O procedimento de IR consistiu na nefrectomia à direita e oclusão da artéria renal esquerda por 30 minutos. A castanha foi administrada diariamente e individualmente por sete dias antes da cirurgia (SHAM ou IR), e mantida até o sacrifício (48h pós-cirurgia). Os seguintes parâmetros foram avaliados: creatinina, ureia e fósforo plasmáticos; proteinúria, volume urinário e depuração de creatinina; TBARS e TEAC (capacidade antioxidante) plasmáticos; expressão renal de iNOS e nitrotirosina, e influxo de macrófagos. Resultados: O pré-tratamento com 75 mg de BN atenuou os parâmetros de função renal alterados pela IR, com elevação da depuração de creatinina e o volume urinário, redução da proteinúria, ureia e fósforo plasmáticos, e diminuição da expressão de iNOS, nitrotirosina e da infiltração de macrófagos. Conclusão: A ingestão de baixa quantidade de BN, previamente ao processo de IR, melhora a função renal pela inibição da infiltração de macrófagos e do estresse oxidativo.

Small RNAs in metastatic and non-metastatic oral squamous cell carcinoma.

BACKGROUND: Small non-coding regulatory RNAs control cellular functions at the transcriptional and post-transcriptional levels. Oral squamous cell carcinoma is among the leading cancers in the world and the presence of cervical lymph node metastases is currently its strongest prognostic factor. In this work we aimed at finding small RNAs expressed in oral squamous cell carcinoma that could be associated with the presence of lymph node metastasis. METHODS: Small RNA libraries from metastatic and non-metastatic oral squamous cell carcinomas were sequenced for the identification and quantification of known small RNAs. Selected markers were validated in plasma samples. Additionally, we used in silico analysis to investigate possible new molecules, not previously described, involved in the metastatic process. RESULTS: Global expression patterns were not associated with cervical metastases. MiR-21, miR-203 and miR-205 were highly expressed throughout samples, in agreement with their role in epithelial cell biology, but disagreeing with studies correlating these molecules with cancer invasion. Eighteen microRNAs, but no other small RNA class, varied consistently between metastatic and non-metastatic samples. Nine of these microRNAs had been previously detected in human plasma, eight of which presented consistent results between tissue and plasma samples. MiR-31 and miR-130b, known to inhibit several steps in the metastatic process, were over-expressed in non-metastatic samples and the expression of miR-130b was confirmed in plasma of patients showing no metastasis. MiR-181 and miR-296 were detected in metastatic tumors and the expression of miR-296 was confirmed in plasma of patients presenting metastasis. A novel microRNA-like molecule was also associated with non-metastatic samples, potentially targeting cell-signaling mechanisms. CONCLUSIONS: We corroborate literature data on the role of small RNAs in cancer metastasis and suggest the detection of microRNAs as a tool that may assist in the evaluation of oral squamous cell carcinoma metastatic potential.

Correlação entre ressonância magnética, expressão do Ki-67 e p53, e prognóstico em astrocitomas / Correlation between Magnetic Ressonance Image, Expression of Ki-67 and p53, and Prognosis in Astrocytomas

Objetivos Avaliar a correlação entre a expressão do Ki-67 e do p53 em astrocitomas graus II a IV, as características da RM e seu prognóstico. Métodos e Resultados Este é um estudo longitudinal retrospectivo do tipo coorte histórico que avaliou 45 pacientes. O prognóstico foi avaliado mediante revisão dos prontuários. A avaliação imuno-histoquímica foi realizada no Serviço de Patologia do HB. A avaliação das imagens de RMfoi feita no Serviço de Radiologia. A sobrevidamédia dos pacientes foi de 581,4 dias no grau IV; 1.704,8 dias no grau III; e 1.044,8 dias no grau II. Para cada grau, os seguintes percentuais de células positivas de Ki-67 e p53 tiveram respectivamente: 97,8 e 80% de positividade no grau IV; 72,7 e 73,4% de positividade no grau III; e 70 e 80% de positividade no grau II. Observou-se diferença estatística na expressão de Ki-67 entre os graus III e IV (P » 0,014). A RM mostrou especificidade de 64% e sensibilidade de 100% para a presença de necrose tumoral. Conclusão Concluímos que a análise da positividade do Ki-67 e do p53 não permite sua correlação com a sobrevida dos pacientes, apesar de ambos terem sua frequência distribuída de maneira semelhante. A RM tem especificidade moderada em relação ao exame patológico.rada em relação ao exame patológico.

Objectives To evaluate the correlation between the expression of Ki -67 and p53 in astrocytomas grades II to IV, the characteristics of MRI and its prognosis. Methods This was a retrospective longitudinal cohort study of its kind that evaluated 45 patients. Prognosis was assessed by review of medical records. The immunohistochemical evaluation was performed at the Pathology Service of HB. The evaluation of MRI images was taken in the Radiology Department. The median survival of patients was 581.4 days in grade IV; 1704.8 days in grade III; 1044.8 days in grade II. For each grade, the following percentages of cells positive for Ki -67 and p53 , respectively : 97.8% and 80% had a positive grade IV ; 72.7% and 73.4% positivity in grade III ; 70% and 80% in stage II positivity . There was statistical difference in Ki -67 between grades III and IV (P » 0.014).MRI showed 64% specificity and 100% sensitivity for the presence of tumor necrosis Conclusion We conclude that the analysis of the positivity of Ki -67 and p53 expression does not allow correlation with patient survival, although both their frequency distributed similarly. MRI hasmoderate specificity in relation to pathological examination.

Preoperative tranilast as adjunctive therapy to primary pterygium surgery with a 1-year follow-up.

PURPOSE: To determine the efficacy of tranilast as an adjunctive therapy in conjunctival autograft. METHODS: Twenty-nine patients were randomly allocated to the Tranilast Group (n=15) or the Control Group (n=14). The Tranilast Group received a subconjunctival injection of 0.5% tranilast 30 days prior to surgery. Conjunctival autograft was performed in both groups using fibrin sealant and 0.02% subconjunctival mitomycin C at the end of the surgery. After the resection of the pterygium, immunohistochemistry was performed with 100 cells to identify epithelial cells positive for transforming growth factor-ß (TGF-ß). Subjective symptoms were evaluated using a 5-point scale, and the recurrence rate was assessed. RESULTS: Both groups showed improvements in their symptoms and similar clinical results. Compared with the Control Group, the Tranilast Group failed to show a decreased recurrence rate (p=0.59). However, the number of epithelial cells expressing TGF-ß was lower in the Tranilast Group (5 cells; 95% CI: 2.56-13.15; Control Group, 16 cells, 95% CI: 11.53-24.76; p=0.01). Minimal but reversible complications, including glaucoma secondary to corticosteroids and granuloma, occurred during the study. CONCLUSION: Tranilast was effective in decreasing the number of pterygium epithelial cells expressing TGF-ß.

Preoperative tranilast as adjunctive therapy to primary pterygium surgery with a 1-year follow-up / Terapia auxiliar com o tranilast pré-operatório na cirurgia do pterígio primário com um ano de seguimento

Purpose: To determine the efficacy of tranilast as an adjunctive therapy in conjunctival autograft. Methods: Twenty-nine patients were randomly allocated to the Tranilast Group (n=15) or the Control Group (n=14). The Tranilast Group received a subconjunctival injection of 0.5% tranilast 30 days prior to surgery. Conjunctival autograft was performed in both groups using fibrin sealant and 0.02% subconjunctival mitomycin C at the end of the surgery. After the resection of the pterygium, immunohistochemistry was performed with 100 cells to identify epithelial cells positive for transforming growth factor-β (TGF-β). Subjective symptoms were evaluated using a 5-point scale, and the recurrence rate was assessed. Results: Both groups showed improvements in their symptoms and similar clinical results. Compared with the Control Group, the Tranilast Group failed to show a decreased recurrence rate (p=0.59). However, the number of epithelial cells expressing TGF-β was lower in the Tranilast Group (5 cells; 95% CI: 2.56-13.15; Control Group, 16 cells, 95% CI: 11.53-24.76; p=0.01). Minimal but reversible complications, including glaucoma secondary to corticosteroids and granuloma, occurred during the study. Conclusion: Tranilast was effective in decreasing the number of pterygium epithelial cells expressing TGF-β. .

Objetivo: Determinar a eficácia do tranilast, como terapia auxiliar no transplante autólogo de conjuntiva. Métodos: Vinte e nove pacientes foram randomizados em dois grupos: Grupo Tratado (15) e Grupo Controle (14). Trinta dias antes da cirurgia, o Grupo Tratado recebeu uma injeção subconjuntival de tranilast a 0,5%. O transplante autólogo de conjuntiva foi realizado em ambos os grupos, usando-se a cola de fibrina e a mitomicina 0,02% subconjuntival, ao final da cirurgia. Cada paciente foi examinado por 12 meses de acompanhamento. A imuno-histoquímica foi realizada, mediante um total de 100 células, a fim de que se contassem as células epiteliais positivas, para o fator de crescimento transformador beta (TGF-β), após a cirurgia do pterígio. Os sintomas subjetivos foram avaliados usando-se uma escala de cinco pontos, e a taxa de recorrência foi avaliada. Resultados: Os 2 grupos apresentaram melhora dos sintomas e com resultados clínicos similares. Quando comparado com o Grupo Controle, o Grupo Tratado falhou em mostrar uma diminuição da taxa de recorrência (p=0,59). Entretanto o número de células epiteliais expressando o TGF-β foi menor no Grupo Tratado (5 células; 95% CI=2,56-13,15; Grupo Controle, 16 células; 95% CI: 11,53-24,76, p=0,01). Complicações mínimas, mas reversíveis, ocorreram durante o estudo, incluindo glaucoma secundário ao uso de corticoide e granuloma. Conclusão: O tranilast foi efetivo em diminuir o número células epiteliais do pterígio expressando o TGF-β. .

Image-Guided Cryoablation of the Spine in a Swine Model: Clinical, Radiological, and Pathological Findings with Light and Electron Microscopy.

PURPOSE: This study was designed to present the feasibility of an in vivo image-guided percutaneous cryoablation of the porcine vertebral body. METHODS: The institutional animal care committee approved this study. Cone-beam computed tomography (CBCT)-guided vertebral cryoablations (n = 22) were performed in eight pigs with short, 2-min, single or double-freezing protocols. Protective measures to nerves included dioxide carbon (CO2) epidural injections and spinal canal temperature monitoring. Clinical, radiological, and pathological data with light (n = 20) or transmission electron (n = 2) microscopic analyses were evaluated after 6 days of clinical follow-up and euthanasia. RESULTS: CBCT/fluoroscopic-guided transpedicular vertebral body cryoprobe positioning and CO2 epidural injection were successful in all procedures. No major complications were observed in seven animals (87.5 %, n = 8). A minor complication was observed in one pig (12.5 %, n = 1). Logistic regression model analysis showed the cryoprobe-spinal canal (Cp-Sc) distance as the most efficient parameter to categorize spinal canal temperatures lower than 19 °C (p < 0.004), with a significant Pearson's correlation test (p < 0.041) between the Cp-Sc distance and the lowest spinal canal temperatures. Ablation zones encompassed pedicles and the posterior wall of the vertebral bodies with an inflammatory rim, although no inflammatory infiltrate was depicted in the surrounding neural structures at light microscopy. Ultrastructural analyses evidenced myelin sheath disruption in some large nerve fibers, although neurological deficits were not observed. CONCLUSIONS: CBCT-guided vertebral cryoablation of the porcine spine is feasible under a combination of a short freezing protocol and protective measures to the surrounding nerves. Ultrastructural analyses may be helpful assess the early modifications of the nerve fibers.

Inflammation and cancer: role of annexin A1 and FPR2/ALX in proliferation and metastasis in human laryngeal squamous cell carcinoma.

The anti-inflammatory protein annexin A1 (ANXA1) has been associated with cancer progression and metastasis, suggesting its role in regulating tumor cell proliferation. We investigated the mechanism of ANXA1 interaction with formylated peptide receptor 2 (FPR2/ALX) in control, peritumoral and tumor larynx tissue samples from 20 patients, to quantitate the neutrophils and mast cells, and to evaluate the protein expression and co-localization of ANXA1/FPR2 in these inflammatory cells and laryngeal squamous cells by immunocytochemistry. In addition, we performed in vitro experiments to further investigate the functional role of ANXA1/FPR2 in the proliferation and metastasis of Hep-2 cells, a cell line from larynx epidermoid carcinoma, after treatment with ANXA1(2-26) (annexin A1 N-terminal-derived peptide), Boc2 (antagonist of FPR) and/or dexamethasone. Under these treatments, the level of Hep-2 cell proliferation, pro-inflammatory cytokines, ANXA1/FPR2 co-localization, and the prostaglandin signalling were analyzed using ELISA, immunocytochemistry and real-time PCR. An influx of neutrophils and degranulated mast cells was detected in tumor samples. In these inflammatory cells of peritumoral and tumor samples, ANXA1/FPR2 expression was markedly exacerbated, however, in laryngeal carcinoma cells, this expression was down-regulated. ANXA1(2-26) treatment reduced the proliferation of the Hep-2 cells, an effect that was blocked by Boc2, and up-regulated ANXA1/FPR2 expression. ANXA1(2-26) treatment also reduced the levels of pro-inflammatory cytokines and affected the expression of metalloproteinases and EP receptors, which are involved in the prostaglandin signalling. Overall, this study identified potential roles for the molecular mechanism of the ANXA1/FPR2 interaction in laryngeal cancer, including its relationship with the prostaglandin pathway, providing promising starting points for future research. ANXA1 may contribute to the regulation of tumor growth and metastasis through paracrine mechanisms that are mediated by FPR2/ALX. These data may lead to new biological targets for therapeutic intervention in human laryngeal cancer.

Significant differences in demographic, clinical, and pathological features in relation to smoking and alcohol consumption among 1,633 head and neck cancer patients.

OBJECTIVE: As a lifestyle-related disease, social and cultural disparities may influence the features of squamous cell carcinoma of the head and neck in different geographic regions. We describe demographic, clinical, and pathological aspects of squamous cell carcinoma of the head and neck according to the smoking and alcohol consumption habits of patients in a Brazilian cohort. METHODS: We prospectively analyzed the smoking and alcohol consumption habits of 1,633 patients enrolled in five São Paulo hospitals that participated in the Brazilian Head and Neck Genome Project - Gencapo. RESULTS: The patients who smoked and drank were younger, and those who smoked were leaner than the other patients, regardless of alcohol consumption. The non-smokers/non-drinkers were typically elderly white females who had more differentiated oral cavity cancers and fewer first-degree relatives who smoked. The patients who drank presented significantly more frequent nodal metastasis, and those who smoked presented less-differentiated tumors. CONCLUSIONS: The patients with squamous cell carcinoma of the head and neck demonstrated demographic, clinical, and pathological features that were markedly different according to their smoking and drinking habits. A subset of elderly females who had oral cavity cancer and had never smoked or consumed alcohol was notable. Alcohol consumption seemed to be related to nodal metastasis, whereas smoking correlated with the degree of differentiation.

Significant differe nces in demographic, clinical, and pathological features in relation to smoking and alcohol consumption among 1,633 head and neck cancer patients

OBJECTIVE: As a lifestyle-related disease, social and cultural disparities may influence the features of squamous cell carcinoma of the head and neck in different geographic regions. We describe demographic, clinical, and pathological aspects of squamous cell carcinoma of the head and neck according to the smoking and alcohol consumption habits of patients in a Brazilian cohort. METHODS: We prospectively analyzed the smoking and alcohol consumption habits of 1,633 patients enrolled in five São Paulo hospitals that participated in the Brazilian Head and Neck Genome Project - Gencapo. RESULTS: The patients who smoked and drank were younger, and those who smoked were leaner than the other patients, regardless of alcohol consumption. The non-smokers/non-drinkers were typically elderly white females who had more differentiated oral cavity cancers and fewer first-degree relatives who smoked. The patients who drank presented significantly more frequent nodal metastasis, and those who smoked presented less-differentiated tumors. CONCLUSIONS: The patients with squamous cell carcinoma of the head and neck demonstrated demographic, clinical, and pathological features that were markedly different according to their smoking and drinking habits. A subset of elderly females who had oral cavity cancer and had never smoked or consumed alcohol was notable. Alcohol consumption seemed to be related to nodal metastasis, whereas smoking correlated with the degree of differentiation. .

The influence of physical activity in the progression of experimental lung cancer in mice.

Lung cancer is one of the most incident neoplasms in the world, representing the main cause of mortality for cancer. Many epidemiologic studies have suggested that physical activity may reduce the risk of lung cancer, other works evaluate the effectiveness of the use of the physical activity in the suppression, remission and reduction of the recurrence of tumors. The aim of this study was to evaluate the effects of aerobic and anaerobic physical activity in the development and the progression of lung cancer. Lung tumors were induced with a dose of 3mg of urethane/kg, in 67 male Balb - C type mice, divided in three groups: group 1_24 mice treated with urethane and without physical activity; group 2_25 mice with urethane and subjected to aerobic swimming free exercise; group 3_18 mice with urethane, subjected to anaerobic swimming exercise with gradual loading 5-20% of body weight. All the animals were sacrificed after 20 weeks, and lung lesions were analyzed. The median number of lesions (nodules and hyperplasia) was 3.0 for group 1, 2.0 for group 2 and 1.5-3 (p=0.052). When comparing only the presence or absence of lesion, there was a decrease in the number of lesions in group 3 as compared with group 1 (p=0.03) but not in relation to group 2. There were no metastases or other changes in other organs. The anaerobic physical activity, but not aerobic, diminishes the incidence of experimental lung tumors.

A new model of a self-expanding tracheal stent made in Brazil: an experimental study in rabbits.

We aimed to test a new model of self-expanding tracheal stent so that it might be made available for clinical use. Using direct laryngoscopy, we placed polyurethane-coated, nitinol stents into the middle third of the trachea in 25 New Zealand rabbits. After a mean observation period of 26 days, we evaluated stent migration, degree of expansion, attachment, adherence, formation of granulation tissue, presence of inflammatory infiltrate, parietal involvement, and epithelial lining. The results showed complete radial expansion, little adherence to the tracheal mucosa, and low tissue attachment, as well as high rates of granuloma formation and stent migration. This new model proved to be biocompatible and showed a behavior similar to that of other stents on the market.

Discrepâncias clínico-patológicas em pacientes graves com difícil diagnóstico pre-mortem / Clinical-pathological discrepancies in critically ill patients with difficult premortem diagnoses

INTRODUÇÃO: A importância das autópsias é um tema comum de discussão tanto no Brasil como em todo o mundo, já que pode elucidar as causas de óbito e tem um valor social muito amplo. Entretanto, esta prática vem sendo gradualmente considerada desnecessária, tendo ocorrido um declínio no número de exames post-mortem. OBJETIVOS: Comparar o diagnóstico clínico e patológico em pacientes com difícil diagnóstico pre-mortem. MÉTODOS: Foram analisados todos os casos de autópsias (em um total de 98) de pacientes oriundos de três unidades de terapia intensiva médico-cirúrgicas (total de 78 leitos) pertencentes a uma faculdade de medicina, realizadas no período de janeiro de 2003 a dezembro de 2006. Analisamos os diagnósticos clínicos e patológicos segundo os critérios de Goldman. RESULTADOS: Em 49 casos (50 por cento) foram encontradas discordâncias classes I e II de Goldman. Por outro lado, apenas 30 (30,6 por cento) dos casos tiveram uma concordância completa entre os diagnósticos pre-mortem e post-mortem sendo classificados como classe V. As infecções tiveram uma taxa de concordância significantemente maior do que as doenças cardiovasculares. CONCLUSÃO: Encontramos discrepâncias significantes entre os achados clínicos e patológicos, o que reforça o valor dos exames post-mortem.

INTRODUCTION: The importance of autopsies is a common theme of discussions both in Brazil and around the world as it elucidates causes of death and has wide ranging social value. However this is a practice that is gradually being considered unnecessary and there have been a decline in the number of postmortems examinations. OBJECTIVES: To compare clinical and pathological diagnosis in critically ill patients with difficult premortem diagnosis. METHODS: All autopsy cases (total of 98) from any of the three general medical/surgical intensive care units (78 beds in total) affiliated to the medical school from January 2003 to December 2006 were analyzed. We analyzed the clinical and pathological diagnosis based on the Goldman criteria. RESULTS: In 49 (50 percent) cases, there were class I and II of Goldman. In contrast, only 30 (30.6 percent) had a complete agreement between premortem and postmortem diagnosis and were classified as class V. Infections had a significantly greater rate of concordant diagnosis than cardiovascular diseases. CONCLUSION: We found significant discrepancies between clinical and pathological findings, reinforcing the value of postmortem examination.

Discrepâncias clínico-patológicas e achados cardiovasculares em 409 autópsias consecutivas / Clinical and pathological discrepancies and cardiovascular findings in 409 consecutive autopsies

FUNDAMENTO: As discrepâncias entre os diagnósticos clínicos e em autópsia persistem em todo o mundo. OBJETIVO: Avaliamos as autópsias em um hospital-escola para analisar a precisão dos diagnósticos cardiovasculares clínicos em comparação aos achados post-mortem. MÉTODOS: As 409 autópsias consecutivas entre 2003 e 2006 foram analisadas em um hospital terciário de São José do Rio Preto, São Paulo (SP), Brasil. A comparação dos achados cardiovasculares clínicos e patológicos foi realizada por meio da classificação de discrepâncias de Goldman. RESULTADOS: A taxa de autópsia no hospital foi de 8 por cento. As causas cardiovasculares de óbito representavam 42,8 por cento (175 de 409 pacientes) dos diagnósticos de autópsia. Em 98 pacientes (56 por cento), houve discrepâncias significativas (classes I e II), o que representa uma grande proporção de diagnósticos equivocados de infarto mesentérico (84,6 por cento), infarto agudo do miocárdio (64,7 por cento), dissecção da aorta (64,2 por cento) e embolia pulmonar (62,5 por cento). Foram observadas maiores taxas de concordância para a insuficiência cardíaca congestiva (59 por cento) e para o acidente vascular cerebral isquêmico agudo (58,8 por cento). A idade, o sexo, o tempo de permanência e a última unidade de admissão no hospital não foram associados aos critérios de Goldman. CONCLUSÃO: As discrepâncias dos diagnósticos clínicos e em autópsia relativos à morte cardiovascular permanecem elevados no Brasil, a despeito dos recursos tecnológicos disponíveis. Além disso, nossos achados reforçam a importância do exame post-mortem como uma contribuição para a melhoria da assistência médica.

BACKGROUND: Discrepancies between clinical and autopsy diagnoses persists worldwide. OBJECTIVE: We evaluated autopsies in a university hospital in order to assess the accuracy of clinical cardiovascular diagnosis compared to postmortem findings. METHODS: Four hundred nine consecutive autopsies between 2003 and 2006 were analyzed in a tertiary-care hospital in São José do Rio Preto, SP, Brazil. The comparison of clinic-pathological cardiovascular findings was performed using Goldman's discrepancies classification. RESULTS: Autopsy rate at the hospital was 8 percent. Cardiovascular causes of death represented 42.8 percent (175 out of 409 patients) of autopsy diagnoses. In 98 (56 percent) patients, there were major discrepancies (class I and II), representing a large proportion of misdiagnoses for mesenteric infarction (84.6 percent), acute myocardial infarction (64.7 percent), aorta dissection (64.2 percent), and pulmonary embolism (62.5 percent). Highest concordance rates were observed in congestive heart failure (59 percent) and acute ischemic stroke (58.8 percent). Age, sex, length of stay and the last admission unit at the hospital were not associated with Goldman criteria. CONCLUSION: Clinic-autopsy discrepancies concerning cardiovascular death remain high in Brazil, despite technological resources available. Moreover, our findings reinforce the importance of postmortem examination in contributing to medical care improvement.