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1.
J Cardiovasc Pharmacol Ther ; : 1074248419887708, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714152

RESUMO

We previously showed that digitoxin prolongs the survival of rats with heart failure due to myocardial infarction (MI). In this study, we evaluated the effect of digitoxin on myocardial structure, ventricular function, and proteins involved in calcium kinetics. Seventy-two rats with MI >35% of the left ventricle were randomly assigned to 4 treatment groups: sham (n = 15), digitoxin (n = 11), infarction (n = 20), and infarction + digitoxin (n = 26). The rats were assessed 120 days after surgery by echocardiogram, hemodynamics, papillary muscle mechanics, collagen content, cardiomyocyte nuclear volume, and Western blot analysis of proteins involved in calcium kinetics. Digitoxin was administered via the rat chow. Two-way analysis of variance was used for comparisons. Myocardial infarction caused inotropic impairment, pulmonary congestion, increase of nuclear volume, myocardial collagen, and Na+/Ca2+ exchanger levels, and decreased SERCA2 and phosphorylated phospholamban levels. Treatment with digitoxin showed improvements in cardiac remodeling, inotropism, ventricular performance, pulmonary congestion, collagen accumulation, nuclear volume, and proteins involved in calcium kinetics. In rats with heart failure due to MI, long-term treatment with digitoxin attenuates congestive heart failure, mitigates myocardial remodeling and contractile impairment, and preserves myocardial levels of proteins involved in calcium kinetics.

2.
Rev Bras Hematol Hemoter ; 36(5): 322-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25305163

RESUMO

OBJECTIVE: The aim of this work was to demonstrate a possible relationship between anti-latency-associated peptide human latent transforming growth factor beta 1 (latent TGF-ß1) expression in megakaryocytes and microvascular density in bone marrow biopsies from patients with essential thrombocythemia and primary myelofibrosis. METHODS: Microvascular density was evaluated by immunohistochemical analysis and the expression of latent TGF-ß1 in samples (100 megakaryocytes per bone marrow sample) from 18 essential thrombocythemia and 38 primary myelofibrosis (19 prefibrotic and 19 fibrotic) patients. Six bone marrow donor biopsies were used as controls. Fibrosis in the bone marrow biopsies was evaluated according to the European Consensus. RESULTS: The average fibrosis grade differed between essential thrombocythemia and primary myelofibrosis groups when compared to the control group. Latent TGF-ß1 expression differed significantly between the fibrotic primary myelofibrosis (PMF) group and the control group (p-value<0.01). A high degree of neo-angiogenesis (demonstrated by analysis of CD34 expression) was detected in patients with myelofibrosis. There were correlations between latent TGF-ß1 expression and microvascular density (r=0.45; p-value<0.0009) and between degree of microvascular density and fibrosis grade (r=0.80; p-value<0.0001). Remarkable differences for neo-angiogenesis were not observed between patients with essential thrombocythemia and controls. CONCLUSION: Angiogenesis participates in the pathogenesis of primary myelofibrosis, in both the prefibrotic and fibrotic stages, while latent TGF-ß is differentially expressed only in the prefibrotic stage.

3.
Rev. bras. hematol. hemoter ; 36(5): 322-328, Sep-Oct/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-725668

RESUMO

Objective: The aim of this work was to demonstrate a possible relationship between anti-latency-associated peptide human latent transforming growth factor beta 1 (latent TGF-β1) expression in megakaryocytes and microvascular density in bone marrow biopsies from patients with essential thrombocythemia and primary myelofibrosis. Methods: Microvascular density was evaluated by immunohistochemical analysis and the expression of latent TGF-β1 in samples (100 megakaryocytes per bone marrow sample) from 18 essential thrombocythemia and 38 primary myelofibrosis (19 prefibrotic and 19 fibrotic) patients. Six bone marrow donor biopsies were used as controls. Fibrosis in the bone marrow biopsies was evaluated according to the European Consensus. Results: The average fibrosis grade differed between essential thrombocythemia and primary myelofibrosis groups when compared to the control group. Latent TGF-β1 expression differed significantly between the fibrotic primary myelofibrosis (PMF) group and the control group (p-value < 0.01). A high degree of neo-angiogenesis (demonstrated by analysis of CD34 expression) was detected in patients with myelofibrosis. There were correlations between latent TGF-β1 expression and microvascular density (r = 0.45; p-value < 0.0009) and between degree of microvascular density and fibrosis grade (r = 0.80; p-value < 0.0001). Remarkable differences for neo-angiogenesis were not observed between patients with essential thrombocythemia and controls. Conclusion: Angiogenesis participates in the pathogenesis of primary myelofibrosis, in both the prefibrotic and fibrotic stages, while latent TGF-β is differentially expressed only in the prefibrotic stage...


Assuntos
Humanos , Indutores da Angiogênese , Fibrose , Mielofibrose Primária , Fator de Crescimento Transformador beta1
4.
Eur J Pharmacol ; 735: 211-8, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24751710

RESUMO

Our purpose was to verify if alcohol causes alterations on translocation of Ca(2+) and tension induced by KCl or noradrenaline in vas deferens of periadolescent Wistar rats. A single dose of alcohol (i.p. 3.0g/kg) or saline as control, was given 4h before sacrifice. Longitudinal strips of prostatic portion were mounted in vitro for simultaneous measurements of intracellular Ca(2+) and contractions. Fluorescence and tension were measured in strips loaded with the fluorescent dye fura-2. The mean values (±S.E.M.) of fluorescence ratios (F340/380) evoked by KCl were significantly lower by about 70% after alcohol, in relation to control. It was about 50% lower when evoked by noradrenaline. In relation to tension, the respective mean values (±S.E.M.) were lower by about 60% in organs treated with KCl or by about 80% after noradrenaline. In some experiments, before noradrenaline contraction, the vas deferens was incubated with verapamil 10(-6)M for 30min. In these experiments, contractions by noradrenaline in the presence of verapamil were decreased by about 70% by alcohol. Alcohol decreases cytosolic calcium and contractility after KCl and noradrenaline, as compared with controls. In addition, alcohol promoted damage of lumen structures. Prostatic portion showed no striking morphometric change after treatment, but the number of TUNEL positive cells in muscular layer, basal lamina and lumen were increased by alcohol, indicating apoptosis, compared with controls. This investigation shows that alcohol treatment alters signaling of calcium which in turn compromises the contraction associated with a process of apoptosis of periadolescent rats.


Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Etanol/farmacologia , Ducto Deferente/efeitos dos fármacos , Envelhecimento/fisiologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Ratos Wistar , Ducto Deferente/fisiologia
5.
Nitric Oxide ; 37: 53-60, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24406684

RESUMO

This study aimed at assessing the effects of Kefir, a probiotic fermented milk, on oxidative stress in diabetic animals. The induction of diabetes was achieved in adult male Wistar rats using streptozotocin (STZ). The animals were distributed into four groups as follows: control (CTL); control Kefir (CTLK); diabetic (DM) and diabetic Kefir (DMK). Starting on the 5th day of diabetes, Kefir was administered by daily gavage at a dose of 1.8 mL/day for 8 weeks. Before and after Kefir treatment, the rats were placed in individual metabolic cages to obtain blood and urine samples to evaluate urea, creatinine, proteinuria, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and C-reactive protein (CRP). After sacrificing the animals, the renal cortex was removed for histology, oxidative stress and NOS evaluation. When compared to CTL rats, DM rats showed increased levels of glycemia, plasmatic urea, proteinuria, renal NO, superoxide anion, TBARS, and plasmatic CRP; also demonstrated a reduction in urinary urea, creatinine, and NO. However, DMK rats showed a significant improvement in most of these parameters. Despite the lack of differences observed in the expression of endothelial NO synthase (eNOS), the expression of inducible NO synthase (iNOS) was significantly lower in the DMK group when compared to DM rats, as assessed by Western blot analysis. Moreover, the DMK group presented a significant reduction of glycogen accumulation within the renal tubules when compared to the DM group. These results indicate that Kefir treatment may contribute to better control of glycemia and oxidative stress, which is associated with the amelioration of renal function, suggesting its use as a non-pharmacological adjuvant to delay the progression of diabetic complications.


Assuntos
Produtos Fermentados do Leite , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Progressão da Doença , Nefropatias/complicações , Nefropatias/dietoterapia , Estresse Oxidativo/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/metabolismo , Teste de Tolerância a Glucose , Glicogênio/metabolismo , Hiperglicemia/dietoterapia , Nefropatias/metabolismo , Nefropatias/patologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/enzimologia , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Óxido Nítrico/metabolismo , Probióticos/farmacologia , Probióticos/uso terapêutico , Ratos , Ratos Wistar , Estreptozocina
6.
J. coloproctol. (Rio J., Impr.) ; 33(3): 118-125, July-Sept/2013. tab, graf
Artigo em Inglês | LILACS-Express | ID: lil-695203

RESUMO

BACKGROUND: activation of the Wnt pathway by mutated APC gene is considered the initial event in colorectal carcinogenesis. The identification of these mutations can improve the specific treatment of the adenocarcinoma. OBJECTIVE: detect and evaluate wild-type APC protein in tissue from colorectal adenoma, adenocarcinoma and adjacent mucosa. METHODS: 42 patients that underwent surgery for adenocarcinoma and 53 patients with resected adenomas were studied. Tissue samples from the adenocarcinoma were obtained from the tumor and from adjacent non-neoplastic mucosa located 10 cm from the proximal margin of the tumor. Adenoma tissue was obtained from representative areas. Blocks of tissue microarray (TMA) were submitted to immunohistochemistry with anti-APC, with readings of positivity and intensity of immunostaining and the score of immune expression of APC protein was obtained. RESULTS: the APC protein immune expression score showed a significantly lower expression of APC protein in the adenoma when compared with the adenocarcinoma (p < 0.0001) and adjacent mucosa (p < 0.0001). The APC protein immune expression score in the colorectal mucosa and adjacent to the adenocarcinoma showed no significant difference (p = 0.24). CONCLUSIONS: the finding of decreased expression of APC protein in adenoma tissue may indicate that the mutated APC gene may contribute to the changes in the adenoma-carcinoma process of carcinogenesis sequence. The strong expression of protein APC in tissues from the carcinoma and adjacent mucosa suggests that in most patients in this series, the mutation of the APC gene did not participate in the oncogenesis mechanism. .


RACIONAL: a ativação da via Wnt pelo gene APC mutado é considerado evento inicial da carcinogênese colorretal. A identificação dessas mutações pode tornar o tratamento do adenocarcinoma mais específico. OBJETIVO: detectar e avaliar a proteína APC não mutada em tecidos de adenoma, adenocarcinoma e mucosa adjacente. MÉTODO: estudados 42 doentes operados de adenocarcinoma e 53 com adenomas ressecados. Tecidos de adenocarcinoma foram obtidas da neoplasia e da mucosa adjacente não neoplásica situadas a 10 cm da margem proximal do tumor. Tecidos do adenoma foram obtidas de área representativa. Blocos de tissue microarray (TMA) foram submetidos a imuno-histoquímica com anticorpo anti-APC. Avaliadas a positividade e intensidade da expressão e obtidos escores da imunoexpressão da proteína APC. RESULTADOS: o escore da imunoexpressão da proteína APC no adenoma foi significantemente menor do que no adenocarcinoma (p < 0,0001) e na mucosa adjacente (p < 0,0001). O escore da imunoexpressão da proteína APC na mucosa adjacente e no adenocarcinoma não mostraram diferença significante (p = 0,24). CONCLUSÕES: a menor expressão da proteína APC no adenoma pode indicar que o gene APC mutado participa das alterações do processo adenoma-carcinoma. A forte expressão da proteína APC no CCR e na mucosa adjacente sugerem que a mutação do gene APC não participou da oncogênese. .

7.
J Mol Med (Berl) ; 91(7): 851-60, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23385644

RESUMO

Kinins B1 and B2 receptors (B1R and B2R) are classically associated with inflammation, but our group has recently demonstrated new roles for B1R in metabolism using a knockout model (B1 (-/-)). B1 (-/-) mice display improvement on leptin and insulin sensitivity and is protected from high fat diet (HFD)-induced obesity. Here, we evaluate the hepatic effects of the B1R ablation and its role on hepatic function. Despite no expression of hepatic B1R, HFD-induced hepatic lipid accumulation was lower than in control animals. B1 (-/-) mice also presented lower hepatic lipogenesis and SCD1 protein content in the liver. When stimulated with exogenous leptin, B1 (-/-) mice exhibited increased hepatic pJAK2. Similarly, leptin signaling was enhanced in the liver of ob/ob-B1 (-/-) mice, as demonstrated by increased levels of pSTAT3 compared to ob/ob. Plasma concentrations of intercellular adhesion molecule 1, fetuin A, leukemia inhibitory factor, tissue inhibitor of metalloprotease-1, resistin, and oncostatin M were reduced in B1 (-/-). Finally, B1 (-/-) mice have increased gene expression of hepatic B2 receptor, but no difference in leptin receptor expression. Our results show that B1 (-/-) mice are protected from non-alcoholic fatty liver disease (NAFLD) after HFD treatment. Since B1R expression was not observed in the liver after HFD, we propose that the cross talk between the adipose tissue and the liver, mainly through leptin, is an important factor contributing to the observed results. Besides that, several other inflammatory mediators already correlated with NAFLD or liver function were found to be altered in our model. Taken together, our data suggest that B1R plays an important role in hepatic steatosis development.


Assuntos
Fígado Gorduroso/metabolismo , Leptina/metabolismo , Fígado/metabolismo , Receptor B1 da Bradicinina/deficiência , Adipocinas/sangue , Animais , Dieta Hiperlipídica , Masculino , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica , Receptor B1 da Bradicinina/genética , Receptor B2 da Bradicinina/metabolismo , Receptores para Leptina/metabolismo , Estearoil-CoA Dessaturase/metabolismo
8.
Anticancer Res ; 33(2): 647-53, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23393362

RESUMO

The aim of this study was to analyze the immunoexpression of (Smac) DIABLO, AIF, cytochrome c, Ki-67 and cleaved caspase-3 in gastric cancer. A tissue microarray (TMA) paraffin block was constructed using gastric adenocarcinoma tissue and adjacent normal adjacent mucosa from 87 patients who had not previously undergone radiotherapy or chemotherapy. Immunohistochemistry was used to evaluate the protein levels. Samples were positive for (Smac) DIABLO in 37 (45.6%) and 37 (46.8%), for AIF in 31 (36.9%) and 36 (45.6%), for cytochrome c in 60 (68.9%) and 44 (54.4%), for Ki-67 in 63 (72.4%) and 52 (61.9%) and for cleaved caspase-3 in 21 (24.1%) and 3 (3.4%) cases of tumor and adjacent normal tissues, respectively. Our results suggest that increased expression of Ki-67 and cleaved caspase-3 could contribute to carcinogenesis. The expression of these proteins indicates an attempt of cells to maintain tissue homeostasis.


Assuntos
Adenocarcinoma/metabolismo , Fator de Indução de Apoptose/biossíntese , Citocromos c/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Proteínas Mitocondriais/biossíntese , Neoplasias Gástricas/metabolismo , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Fator de Indução de Apoptose/análise , Proteínas Reguladoras de Apoptose , Biomarcadores Tumorais/análise , Citocromos c/análise , Feminino , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/análise , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/análise , Neoplasias Gástricas/mortalidade , Análise Serial de Tecidos
9.
Acta Cir Bras ; 27(10): 681-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23033128

RESUMO

PURPOSE: To examine histological and histomorphometric techniques for measuring collagen in skeletal muscle. METHODS: The following staining methods were used in the study: hematoxylin and eosin, Masson's trichrome, reticulin, and picrosirius red, and immunostaining for collagen types I, II, III, IV, and V. Histomorphometric measurements were performed using Corel PhotoPaint and UTHSCSA Image Tool 3.0 software. RESULTS: Both the Masson's trichrome and picrosirius red staining provided the best visualization for the measurement of collagen content. CONCLUSION: This methodology is important for the identification and quantification of the different types of collagen in muscles and can be used in the investigation of the qualitative and quantitative influence of collagen on physical activities, aging, and diseases.


Assuntos
Colágeno/análise , Modelos Biológicos , Músculo Esquelético/química , Reto do Abdome/química , Cadáver , Humanos , Imuno-Histoquímica , Reprodutibilidade dos Testes
10.
Acta cir. bras ; 27(10): 681-686, Oct. 2012. ilus
Artigo em Inglês | LILACS | ID: lil-650556

RESUMO

PURPOSE: To examine histological and histomorphometric techniques for measuring collagen in skeletal muscle. METHODS: The following staining methods were used in the study: hematoxylin and eosin, Masson's trichrome, reticulin, and picrosirius red, and immunostaining for collagen types I, II, III, IV, and V. Histomorphometric measurements were performed using Corel PhotoPaint and UTHSCSA Image Tool 3.0 software. RESULTS: Both the Masson's trichrome and picrosirius red staining provided the best visualization for the measurement of collagen content. CONCLUSION: This methodology is important for the identification and quantification of the different types of collagen in muscles and can be used in the investigation of the qualitative and quantitative influence of collagen on physical activities, aging, and diseases.


OBJETIVO: Examinar os procedimentos empregados na quantificação do colágeno por métodos histológicos e histomorfométricos. MÉTODOS: Foram utilizadas colorações histológicas por HE, Tricrômico de Masson, Reticulina, Picrossírius e reação imuno-histoquímica para colágeno I, II, III, IV e V. A quantificação histomorfométrica foi realizada utilizando-se os programas Corel PhotoPaint e Image Tool versão 3.0. RESULTADOS: Os métodos histológicos de Masson e Picrossírius apresentaram uma maior facilidade na quantificação do colágeno. CONCLUSÃO: Este modelo é importante para que possa ser identificado e quantificado os diferentes tipos de colágenos nos músculos e relacionar com a atividade física, envelhecimento e doenças.


Assuntos
Humanos , Colágeno/análise , Modelos Biológicos , Músculo Esquelético/química , Reto do Abdome/química , Cadáver , Imuno-Histoquímica , Reprodutibilidade dos Testes
11.
Leuk Res ; 36(1): 93-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21752469

RESUMO

To evaluate the grading of fibrosis and immunohistochemical expression of MPL in bone marrow biopsies of ET and PMF. Fibrosis in bone marrow biopsies (BMBs) was evaluated according to the European Consensus for grading of fibrosis, according to reticulin proliferation. Immunohistochemical analysis was performed in samples from 18 ET and 38 PMF patients: 19 were classified as pre-fibrotic and 19 were classified as fibrotic according to the World Health Organization (WHO) criteria, by means of the MPL antibody. Six bone marrow donors' biopsies were used as controls. Average reticulin (p<0.003) and MPL (p<0.008) values differed significantly between the ET group and the pre-fibrotic stage PMF group. The MPL immunohistochemical expression may represent a new marker for differential diagnosis between ET and pre-fibrotic stage PMF.


Assuntos
Biomarcadores Tumorais , Mielofibrose Primária/diagnóstico , Receptores de Trombopoetina/metabolismo , Trombocitemia Essencial/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/fisiologia , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Mielofibrose Primária/metabolismo , Mielofibrose Primária/patologia , Receptores de Trombopoetina/análise , Receptores de Trombopoetina/fisiologia , Trombocitemia Essencial/metabolismo , Trombocitemia Essencial/patologia , Adulto Jovem
12.
J Atheroscler Thromb ; 19(3): 237-45, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22139433

RESUMO

AIM: Euterpe Oleracea (açai) is a fruit from the Amazon region whose chemical composition may be beneficial for individuals with atherosclerosis. We hypothesized that consumption of Euterpe Oleracea would reduce atherosclerosis development by decreasing cholesterol absorption and synthesis. METHODS: Male New Zealand rabbits were fed a cholesterol-enriched diet (0.5%) for 12 weeks, when they were randomized to receive Euterpe Oleracea extract (n = 15) or water (n = 12) plus a 0.05% cholesterol-enriched diet for an additional 12 weeks. Plasma phytosterols and desmosterol were determined by ultra-performance liquid chromatography and mass spectrometry. Atherosclerotic lesions were estimated by computerized planimetry and histomorphometry. RESULTS: At sacrifice, animals treated with Euterpe Oleracea had lower levels of total cholesterol (p =0.03), non-HDL-cholesterol (p = 0.03) and triglycerides (p = 0.02) than controls. These animals had smaller atherosclerotic plaque area in their aortas (p = 0.001) and a smaller intima/media ratio (p = 0.002) than controls, without differences in plaque composition. At the end of the study, campesterol, ß-sitosterol, and desmosterol plasma levels did not differ between groups; however, animals treated with Euterpe Oleracea showed lower desmosterol/campesterol (p = 0.026) and desmosterol/ ß-sitosterol (p =0.006) ratios than controls. CONCLUSIONS: Consumption of Euterpe Oleracea extract markedly improved the lipid profile and attenuated atherosclerosis. These effects were related in part to a better balance in the synthesis and absorption of sterols.


Assuntos
Arecaceae/química , Aterosclerose/tratamento farmacológico , Colesterol na Dieta/efeitos adversos , Lipídeos/análise , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Aterosclerose/etiologia , Colesterol/análogos & derivados , Colesterol/sangue , Cromatografia Líquida de Alta Pressão , Desmosterol/sangue , Técnicas Imunoenzimáticas , Masculino , Fitosteróis/sangue , Coelhos , Sitosteroides/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
13.
Med Oncol ; 29(4): 2337-44, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22200991

RESUMO

The aim of this study was to perform an immunohistochemical analysis from 100 megakaryocytes per sample, analyzing positivity and intensity levels of anti-LAP human TGF-ß1 (or Latent TGF-ß1) and anti-TGF-ß1 (or Active TGF-ß1) antibodies from 18 essential thrombocythemia (ET) and 38 primary myelofibrosis (PMF) patients (being 19 pre-fibrotic and 19 fibrotic). Six bone marrow donor biopsies were used as controls. Fibrosis in bone marrow biopsies (BMB) was evaluated according to the European Consensus. The average fibrosis grade differed between each group (P=0.001 or P=0.003). Latent TGF-ß1 values differed significantly between pre-fibrotic (P=0.018) and fibrotic (P=0.031) groups when compared with the control group. The high immunoexpression level of Latent TGF-ß1 in the megakaryocytes from patients with myelofibrosis, which was not observed in patients with essential thrombocythemia, may be associated with the development of bone marrow fibrosis.


Assuntos
Medula Óssea/patologia , Mielofibrose Primária/patologia , Trombocitemia Essencial/patologia , Fator de Crescimento Transformador beta1/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrose , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta1/análise
14.
Cancer Genomics Proteomics ; 8(6): 307-10, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22086898

RESUMO

The goal of this study was to investigate the expression of some metalloendopeptidases in squamous cell carcinomas of the oropharynx as well as its relation to histological differentiation, staging of disease, and prognosis. Paraffin blocks from 21 primary tumors were obtained from archives of the Department of Pathology, Paulista Medical School, Federal University of Sao Paulo, UNIFESP/EPM. Immunohistochemistry was used to detect the expression of EP24.15 and EP24.16 by means of tissue microarrays. Expression of EP24.15 or EP24.16 was not correlated with the stage of disease, histopathological grading or recurrence in squamous cell carcinomas of the oropharynx. In summary, our results support the notion that EP24.15 and EP24.16 are expressed in carcinoma of the oropharynx; however, these do not appear to be suitable biomarkers for histological grading, disease stage or recurrence as depicted by tissue microarrays and immunohistochemistry.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Metaloendopeptidases/análise , Neoplasias Orofaríngeas/enzimologia , Neoplasias Orofaríngeas/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Orofaringe/patologia , Prognóstico , Análise Serial de Tecidos
15.
Acta Cir Bras ; 26 Suppl 2: 3-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22030807

RESUMO

PURPOSE: To assess the collagen content and types in the rectus abdominis muscle of cadavers of different ages. METHODS: Forty fresh adult male cadavers, at room temperature, were obtained from the Institute of Legal Medicine of Franca and dissected within 24 hours of death. The cadavers were divided into two groups: Group A (n=20), 18 to 30 years of age, and Group B (n=20), 31 to 60 years of age. Bilateral incisions were made in the middle portion of anterior rectus sheath 3 cm superiorly and 2 cm inferiorly to the umbilicus and four fragments of the rectus abdominis muscle were dissected. The samples were fixed in 10% buffered formalin and sent for immunohistochemical analysis to determine collagen content and types. RESULTS: Immunohistochemical results revealed higher amounts of type I and type III collagen in Group A. However, no difference in the amount of type IV collagen was found between the groups. CONCLUSION: The amount of type I and type III collagen was higher in group A.


Assuntos
Colágeno Tipo III/análise , Colágeno Tipo IV/análise , Colágeno Tipo I/análise , Reto do Abdome/química , Adolescente , Adulto , Fatores Etários , Cadáver , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reto do Abdome/patologia , Adulto Jovem
16.
Hepatol Int ; 5(4): 965-74, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21691717

RESUMO

PURPOSE: The goal of this study was to investigate whether daily administration of green tea is able to protect the liver injury induced by cholesterol. METHODS: Male Wistar rats (n = 24) were distributed into four groups: group 1, negative control; group 2, cholesterol at 1% (w/w) in the diet treated for 5 weeks; group 3, cholesterol at 1% treated for 5 weeks and green tea at 1% (w/v) in drinking water in the last week only and group 4, cholesterol and green tea at 1% in drinking water for 5 weeks. RESULTS: The results pointed out that treatment with green tea in the last week (group 3) showed mild degenerative changes of liver tissue in cholesterol exposed group when compared to group 2. Green tea aqueous extract was not able to reduce cholesterol levels, that is, no significant statistical differences (p > 0.05) were noticed when compared to positive control group. Nevertheless, green tea was able to decrease oxidative deoxyribonucleic acid (DNA) damage either to peripheral blood or to liver cells as depicted by significant statistical differences (p < 0.05) in the mean tail moment between groups treated with green tea and cholesterol and cholesterol only. Furthermore, histomorphometric analysis of COX-2 expression revealed that in groups exposed to green tea they were significantly decreased (p < 0.05), regardless of time exposure adopted. CONCLUSION: Taken together, our results suggest that daily administration of green tea for at least 7 days displays some preventive properties as indicated by COX-2 downregulation and decreased oxidative DNA damage.

17.
Br J Nutr ; 105(5): 694-702, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21324234

RESUMO

The goal of the present study was to investigate whether subchronic treatment with grape juice concentrate is able to protect liver and peripheral blood cells against cholesterol-induced injury in rats. The effects of the grape juice concentrate treatment on histopathological changes, immunohistochemistry for cyclo-oxygenase-2 (COX-2), and basal and oxidative DNA damage induced by H2O2 using a single-cell gel (comet) assay were evaluated. Male Wistar rats (n 18) were divided into three groups: group 1--negative control; group 2--cholesterol at 1 % (w/w) in their diet, treated for 5 weeks; group 3--cholesterol at 1 % in their chow, treated for 5 weeks, and grape juice concentrate at 222 mg/d in their drinking-water in the final week only. The results indicated that the treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in group 3 compared with group 2. However, grape juice concentrate was able to decrease oxidative DNA damage induced by H2O2 in peripheral blood cells, as depicted by the tail moment results. COX-2 expression in the liver did not show statistically significant differences (P>0·05) between groups. Taken together, the present results suggest that the administration of subchronic grape juice concentrate prevents oxidative DNA damage in peripheral blood cells.


Assuntos
Antioxidantes/farmacologia , Células Sanguíneas/efeitos dos fármacos , Dano ao DNA , Hipercolesterolemia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Vitis , Animais , Antioxidantes/uso terapêutico , Colesterol na Dieta/efeitos adversos , Ensaio Cometa , Ciclo-Oxigenase 2/metabolismo , Dieta Aterogênica , Frutas , Peróxido de Hidrogênio , Hipercolesterolemia/imunologia , Hipercolesterolemia/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico , Ratos , Ratos Wistar
18.
Int J Exp Pathol ; 92(1): 40-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21272105

RESUMO

UNLABELLED: With the increasing prevalence of diabetes mellitus and metabolic syndrome worldwide, experimental models are required to better understand the pathophysiology and therapeutic approaches to preserve pancreatic beta cells, attenuate atherosclerosis and protect target organs. The aims of this study were to develop an experimental model of impaired glucose tolerance combined with hypercholesterolaemia induced by diet and assess metabolic alterations and target organ lesions. New Zealand male rabbits were fed high-fat/high-sucrose (10/40%) and cholesterol-enriched diet for 24 weeks, when they were sacrificed. Biochemistry, fundus photographs with fluorescein angiography and pathological analyses were performed. Cholesterol-fed and normal animals of same age were compared. RESULTS: The animals with diet-induced impaired glucose tolerance combined with hypercholesterolaemia gained weight, increased blood glucose, total cholesterol, LDL-C and triglycerides and decreased HDL-C (P < 0.05 vs. baseline). Fructosamine levels and the homeostasis model assessment of insulin resistance (HOMA-IR) index were increased, while there was a reduction in the HOMA-ß (P < 0.05 for all vs. baseline). Histomorphologic findings of this model were aortic atherosclerosis, hepatic steatofibrosis and glomerular macrophage infiltration. Early clinical features of diabetic retinopathy with hyperfluorescent dots consistent with presence of retina microaneurysms were seen since week 12, progressing up to the end of the experiment (P < 0.0005 vs. baseline and 12 weeks). Our model reproduced several metabolic characteristics of human diabetes mellitus and promoted early signs of retinopathy. This non-expensive model is suitable for studying mechanistic pathways and allowing novel strategic approaches.


Assuntos
Aneurisma/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/patologia , Intolerância à Glucose/fisiopatologia , Hiperlipidemias/fisiopatologia , Aneurisma/etiologia , Aneurisma/fisiopatologia , Animais , Aorta/patologia , Aterosclerose/etiologia , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/fisiopatologia , Dieta , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Fígado Gorduroso/fisiopatologia , Intolerância à Glucose/complicações , Intolerância à Glucose/patologia , Hiperlipidemias/complicações , Hiperlipidemias/patologia , Imuno-Histoquímica , Masculino , Coelhos , Retina/patologia
19.
Acta cir. bras ; 26(supl.2): 3-7, 2011. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-602636

RESUMO

PURPOSE: To assess the collagen content and types in the rectus abdominis muscle of cadavers of different ages. METHODS: Forty fresh adult male cadavers, at room temperature, were obtained from the Institute of Legal Medicine of Franca and dissected within 24 hours of death. The cadavers were divided into two groups: Group A (n=20), 18 to 30 years of age, and Group B (n=20), 31 to 60 years of age. Bilateral incisions were made in the middle portion of anterior rectus sheath 3 cm superiorly and 2 cm inferiorly to the umbilicus and four fragments of the rectus abdominis muscle were dissected. The samples were fixed in 10 percent buffered formalin and sent for immunohistochemical analysis to determine collagen content and types. RESULTS: Immunohistochemical results revealed higher amounts of type I and type III collagen in Group A. However, no difference in the amount of type IV collagen was found between the groups. CONCLUSION: The amount of type I and type III collagen was higher in group A.


OBJETIVO: Avaliar o colágeno no músculo reto do abdome em cadáveres de diferentes faixas etárias. MÉTODOS: Foram dissecados 40 cadáveres adultos masculinos, não fixados, com tempo de óbito de até 24 horas, em temperatura ambiente, provenientes do Instituto Médico-Legal de Franca (SP - Brasil). Os cadáveres foram distribuídos em dois grupos: GRUPO A (n=20) - 18 a 30 anos e GRUPO B (n=20) -31 a 60 anos. Realizou-se incisão na porção mediana da lâmina anterior da bainha do músculo reto a 3 cm superiormente e 2 cm inferiormente ao umbigo em ambos os lados, sendo retirados quatro fragmentos de músculo reto do abdome. Esse material foi conservado em formalina tamponado a 10 por cento e enviado para imuno-histoquímica para determinação do tipo de colágeno. RESULTADOS: Na Imunihistoquímica os colágenos I e III foram estatisticamente maiores no grupo A, porém não houve diferença entre os grupos em relação ao colágeno IV. CONCLUSÃO: A quantidade de colágeno tipo I e III foi maior no grupo A.


Assuntos
Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Colágeno Tipo I/análise , Colágeno Tipo III/análise , Colágeno Tipo IV/análise , Reto do Abdome/química , Fatores Etários , Cadáver , Imuno-Histoquímica , Reto do Abdome/patologia
20.
J Atheroscler Thromb ; 17(4): 378-85, 2010 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-20215709

RESUMO

AIM: Based on evidence that ionizing radiation can ameliorate chronic and autoimmune diseases in patients and experimental animals, we investigated the effects of radiation on the induction and development of experimental atherogenesis. METHODS: Male New Zealand rabbits were divided into 5 groups and given an atherogenic diet for 90 days. Peritoneal and thoracic areas (9 Gy) were irradiated on the 1st and 45th days for groups 1 and 2, the 45th day for groups 3 and 4, and not at all for group 5. Prior to irradiation, the peritoneal cavity of animals from groups 1 and 3 was washed with buffered saline. Cells collected by peritoneal washing were reinfused into the peritoneal cavity of the same animal after irradiation. Animals from groups 2 and 4 were intraperitoneally injected with saline as a control. RESULTS: Despite similar lipid profiles among the experimental groups, the percentage of aortas covered by plaques was remarkably reduced (p<0.001) among animals submitted to irradiation (groups 2 and 4). These differences were completely abolished in irradiated animals reconstituted with their own peritoneal cells. CONCLUSIONS: These findings point to an important role of resident inflammatory peritoneal cells in experimental atherogenesis.


Assuntos
Líquido Ascítico/imunologia , Aterosclerose/etiologia , Inflamação/etiologia , Macrófagos Peritoneais/fisiologia , Monócitos/fisiologia , Cavidade Peritoneal/citologia , Animais , Citometria de Fluxo , Masculino , Cavidade Peritoneal/efeitos da radiação , Lavagem Peritoneal , Cavidade Pleural/citologia , Cavidade Pleural/efeitos da radiação , Coelhos , Radiação Ionizante
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