The Expression of CTLA-4 in Breast Tumors and Tumor-Infiltrating Leukocytes Affects Patients' Systemic Inflammatory Status and Varies According to Their Molecular Subtypes.

Recent evidence has pointed out that the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression is a poor prognosis factor. However, the implications of CTLA-4 expression on circulating inflammatory mediators are unclear for breast cancer. Tumor biopsies and blood samples were collected from 117 breast cancer patients. Oxidative stress parameters were evaluated in plasma samples by measuring the lipoperoxidation profile and nitric oxide metabolites (NOx). Interleukins 12 (IL-12) and 4 (IL-4) were assessed by ELISA. CTLA-4 expression was determined by immunofluorescence assessed by its labeling in tumor-infiltrating leukocytes (TILs) or breast tumors. Correlations between CTLA-4 expression in breast tumors with TCD4/TCD8 infiltrating lymphocyte and inflammation-related genes were performed using data from TIMER 2.0/TCGA databases (n = 2160). CTLA-4 expression in TILs significantly correlated to triple-negative breast tumors. Patients carrying CTLA-4-positive tumors exhibited lower plasmatic NOx levels, and those expressing CTLA-4 in TILs had reduced levels of IL-12 in plasma. No changes in either IL-4 or lipid peroxidation profiles were detected concerning any CTLA4 status. Compared to the Luminal A ones, oxidative stress parameters and cytokines were observed in patients bearing triple-negative tumors. CTLA-4 expression in all breast cancer subtypes positively correlated to TCD4/TCD8 lymphocyte infiltrates, as well as to the pro-inflammatory genes IL12A, IL4, NFKB1, NFKB2, NOS1, NOS2, and NOS3. CTLA-4 expression in both tumor and TILs can affect the systemic inflammatory status of breast cancer patients, especially antitumor molecules such as IL-12 and NOx that correlate to more aggressive disease.

Aqueous ozone therapy improves the standard treatment of leishmaniasis lesions in animals leading to local and systemic alterations.

The current treatment of leishmaniasis presents some problems, such as cell toxicity, parenteral route, and time of treatment. Ozone emerges as an option to accelerate the standard treatment due to the immunomodulatory, antioxidant, and wound healing activity reported in the literature. This work aimed to evaluate the efficacy of aqueous ozone as an adjuvant to the standard treatment of cutaneous lesions caused by Leishmania amazonensis in an experimental model. For in vivo experiments, mice were randomly distributed in 6 groups, which were infected with L. amazonensis and treated in five different schedules using the standard treatment with Glucantime® with or without aqueous ozone. After the last day of treatment, the animals were euthanized and were analyzed: the thickness of lesions; collagen deposition, the parasitic burden of the lesions; blood leukocyte number; NO; and cytokine dosages and arginase activity from peritoneal macrophages. All treated groups showed a decrease in the lesion, but with a significative deposition of collagen in lesions with local ozone treatment. The parasite burden showed that ozone enhanced the leishmanicidal activity of the reference drug. The reduction of NO production and blood leukocyte count and increases in the arginase activity showed an immunomodulatory activity of ozone in the treated animals. Thus, ozone therapy has been shown to work as an adjuvant in the treatment of Leishmania lesions, enhancing leishmanicidal and wound healing activity of standard treatment.

Life-long Maternal Cafeteria Diet Promotes Tissue-Specific Morphological Changes in Male Offspring Adult Rats.

Here, we evaluated whether the exposure of rats to a cafeteria diet pre- and/or post-weaning, alters histological characteristics in the White Adipose Tissue (WAT), Brown Adipose Tissue (BAT), and liver of adult male offspring. Female Wistar rats were divided into Control (CTL; fed on standard rodent chow) and Cafeteria (CAF; fed with the cafeteria diet throughout life, including pregnancy and lactation). After birth, only male offspring (F1) were maintained and received the CTL or CAF diets; originating four experimental groups: CTL-CTLF1; CTL-CAFF1; CAF-CTLF1; CAF-CAFF1. Data of biometrics, metabolic parameters, liver, BAT and WAT histology were assessed and integrated using the Principal Component Analysis (PCA). According to PCA analysis worse metabolic and biometric characteristics in adulthood are associated with the post-weaning CAF diet compared to pre and post weaning CAF diet. Thus, the CTL-CAFF1 group showed obesity, higher deposition of fat in the liver and BAT and high fasting plasma levels of glucose, triglycerides and cholesterol. Interestingly, the association between pre and post-weaning CAF diet attenuated the obesity and improved the plasma levels of glucose and triglycerides compared to CTL-CAFF1 without avoiding the higher lipid accumulation in BAT and in liver, suggesting that the impact of maternal CAF diet is tissue-specific.

Life-long Maternal Cafeteria Diet Promotes Tissue-Specific Morphological Changes in Male Offspring Adult Rats

ABSTRACT Here, we evaluated whether the exposure of rats to a cafeteria diet pre- and/or post-weaning, alters histological characteristics in the White Adipose Tissue (WAT), Brown Adipose Tissue (BAT), and liver of adult male offspring. Female Wistar rats were divided into Control (CTL; fed on standard rodent chow) and Cafeteria (CAF; fed with the cafeteria diet throughout life, including pregnancy and lactation). After birth, only male offspring (F1) were maintained and received the CTL or CAF diets; originating four experimental groups: CTL-CTLF1; CTL-CAFF1; CAF-CTLF1; CAF-CAFF1. Data of biometrics, metabolic parameters, liver, BAT and WAT histology were assessed and integrated using the Principal Component Analysis (PCA). According to PCA analysis worse metabolic and biometric characteristics in adulthood are associated with the post-weaning CAF diet compared to pre and post weaning CAF diet. Thus, the CTL-CAFF1 group showed obesity, higher deposition of fat in the liver and BAT and high fasting plasma levels of glucose, triglycerides and cholesterol. Interestingly, the association between pre and post-weaning CAF diet attenuated the obesity and improved the plasma levels of glucose and triglycerides compared to CTL-CAFF1 without avoiding the higher lipid accumulation in BAT and in liver, suggesting that the impact of maternal CAF diet is tissue-specific.

Influenza pandêmica A/H1N1: análise comparativa de alterações histopatológicas pulmonares / Pandemic influenza A/H1N1: comparative analysis of microscopic lung histopathological findings

OBJETIVO: Analisar as alterações histológicas pulmonares de quatro casos fatais de influenza pandêmica H1N1, correlacionando-os a características clínico-epidemiológicas. MÉTODOS: Estudo retrospectivo e descritivo de dados de prontuários de quatro pacientes que faleceram por influenza H1N1 na Unidade de Terapia Intensiva de um hospital universitário, em 2009. Os pacientes haviam sido submetidos a aspirado de nasofaringe e as amostras foram analisadas pelo método de reação em cadeia da polimerase em tempo real. Biópsia pulmonar foi realizada no dia do óbito; um escore de intensidade das alterações histopatológica foi aplicado. RESULTADOS: Três pacientes apresentaram reação em cadeia da polimerase em tempo real com resultado positivo (embora todos tivessem diagnóstico de influenza H1N1). As principais alterações histológicas identificadas foram: dano alveolar difuso exsudativo, com atelectasia de alvéolos; graus variáveis de hemorragia e edema alveolar; necrose e descamação do epitélio respiratório de vários bronquíolos; e formação de trombos. Uma das pacientes (gestante) apresentou, à histopatologia, achado de inclusão citomegálica. CONCLUSÃO: Os achados histopatológicos pulmonares em pacientes com influenza H1N1 fatal revelaram dano alveolar grave, com hemorragia alveolar e bronquiolite. Foi descrita uma coinfecção com citomegalovírus em paciente gestante.

OBJECTIVE: To analyze the histopathological lung findings of four fatal cases of the 2009 H1N1 influenza pandemic and their correlation with clinical and epidemiological characteristics. METHODS: Descriptive data from medical records of four patients who died in the Intensive Care Unit of a university hospital in 2009. Nasopharyngeal aspirate specimens were collected from the patients and were analyzed by real-time polymerase chain reaction. Lung biopsy was performed post mortem; a score of intensity for pathological changes was applied. RESULTS: Three patients had positive real-time polymerase chain reaction (although all of them had a clinical diagnose of influenza H1N1). The main histopathological changes were: exudative diffuse alveolar damage with atelectasis; varying degrees of alveolar hemorrhage and edema, necrosis and sloughing of the respiratory epithelium in several bronchioli; and thrombus formation. One of the patients (the pregnant one) presented histopathological findings of cytomegalic inclusion. CONCLUSION: The pulmonary histopathological findings in patients with fatal 2009 H1N1 influenza pandemic disclosed intense alveolar damage and hemorrhage and severe bronchiolitis. A co-infection with cytomegalovirus was described in the pregnant patient.

Pandemic influenza A/H1N1: comparative analysis of microscopic lung histopathological findings.

OBJECTIVE: To analyze the histopathological lung findings of four fatal cases of the 2009 H1N1 influenza pandemic and their correlation with clinical and epidemiological characteristics. METHODS: Descriptive data from medical records of four patients who died in the Intensive Care Unit of a university hospital in 2009. Nasopharyngeal aspirate specimens were collected from the patients and were analyzed by real-time polymerase chain reaction. Lung biopsy was performed post mortem; a score of intensity for pathological changes was applied. RESULTS: Three patients had positive real-time polymerase chain reaction (although all of them had a clinical diagnose of influenza H1N1). The main histopathological changes were: exudative diffuse alveolar damage with atelectasis; varying degrees of alveolar hemorrhage and edema, necrosis and sloughing of the respiratory epithelium in several bronchioli; and thrombus formation. One of the patients (the pregnant one) presented histopathological findings of cytomegalic inclusion. CONCLUSION: The pulmonary histopathological findings in patients with fatal 2009 H1N1 influenza pandemic disclosed intense alveolar damage and hemorrhage and severe bronchiolitis. A co-infection with cytomegalovirus was described in the pregnant patient.

Padrão histológico de biópsias renais em rins nativos / Histological pattern of renal biopsies in native kidneys

JUSTIFICATIVA E OBJETIVOS: A biópsia renal constitui o padrão-ouro para diagnóstico, prognóstico e tratamento da maioria das doenças renais, especialmente das glomerulopatias. O objetivo deste estudo foi revisar as biópsias renais percutâneas realizadas na investigação de doenças renais. MÉTODO: Estudo retrospectivo de prontuários de 174 pacientes submetidos à biópsia renal percutânea no período compreendido entre 1988 e 2010. Foram coletados os seguintes dados: idade, sexo, apresentação clínica, padrão histológico e complicações.Os dados foram armazenados no banco de dados do Microsoft Excel. As variáveis contínuas foram expressas em média e desvio-padrão e as frequências relativas foram calculadas. RESULTADOS: A idade média dos pacientes foi de 33,7 ± 16,7 anose 51,4% eram do sexo masculino. Glomerulonefrites (GN) foram diagnosticadas em 60,9% do total. Doença de lesão mínima (DLM)foi a GN primária mais comum em adultos (17,9%), seguida por GN proliferativa (17%), GN membranosa e GN segmentar e focal cada uma com (14,2 %). Nefrite lúpica foi a GN secundária mais comum (12,6% do total de biópsias). A principal apresentação clínica foi a proteinúria. Complicações foram observadas em 10,3% das biópsias realizadas, hematúria em 15 (8,6%) e hematoma perirrenal em três (1,7%) pacientes, sendo um complicado com abscesso perirrenal. CONCLUSÃO: O padrão histológico mais comum foi o de glomerulonefrites. Doença de lesão mínima foi a glomerular primária mais frequente. Nefrite lúpica foi a doença glomerular secundária mais frequente. Proteinúria foi a principal indicação para biópsia renal. A biópsia renal percutânea é uma técnica segura no presente estudo.

BACKGROUND AND OBJECTIVES: The kidney biopsy constitutes the gold-standard procedure to diagnosis, prognosisand treatment of the most kidney diseases, specially the glomerulophaties.The objective of this study is to review renal biopsies performed for investigation of kidney disease. METHOD: This is a retrospective study of records of 174 patients submitted to percutaneous biopsies between 1988 and 2010. There was reviewed the following medical records: age, gender, clinical presentation, histological pattern and complications. The data were stored in the Microsoft Excel database. Continuous variables were expressed as mean and standard deviationand the relative frequencies were calculated. RESULTS: Mean age of these patients was 33.7 ± 16.7 years and 51.4% of them were male. Glomerulonephritis (GN) comprised 60.9% of the total. The most common primary GN in adults was minimal change disease (17.9%), followed by proliferative GN (17%), membranous GN and segmental and focal GN, each one with 14.2%. The most common secondary GN was lupus nephritis, with 12.6% of total biopsies. The main clinical presentation was proteinuria. Complications were observed in 10.3% of biopsies performed hematuria in 15 (8.6%) and perirrenal hematomain three (1.7%) patients, being one complicated with per perirrenal abscess. CONCLUSION: The most common histological pattern was GN. Minimal change disease was the most frequent primary glomerular disease. Lupus nephritis was the most frequent secondary glomerular disease. Proteinuria was the main indication for renalbiopsy. Percutaneous renal biopsy is a safe technique in study.

Postsplenectomy sclerosing extramedullary hematopoietic tumor with unexpected good clinical evolution: morphologic, immunohistochemical, and molecular analysis of one case and review of the literature.

Sclerosing extramedullary hematopoietic tumor has been described as a rare manifestation of chronic myeloproliferative neoplasm. The lack of knowledge about this entity has caused it to be mistaken for many types of nonhematopoietic and hematopoietic tumors. We present the case of a 71-year-old lady with a long history of primary myelofibrosis, which developed multiple abdominal sclerosing extramedullary hematopoietic tumors with good clinical evolution. Nonchronic myeloid leukemia myeloproliferative neoplasm included a JAK2 mutation as part of the diagnosis algorithm. Particularly, idiopathic myelofibrosis is related with a JAK2 mutation in 50% of the cases with a pejorative prognosis. The absence of JAK2 demonstrated in the paraffin samples of the tumors may be related to the unusual evolution in this particular case. Morphologically differential diagnoses considered in the evaluation of this entity and in our case included sarcomas mainly liposarcoma, anaplastic carcinoma, and Hodgkin lymphoma.