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1.
Acta Endocrinol (Buchar) ; 14(3): 384-388, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31149287

RESUMO

PURPOSE: Assessing cardiovascular risk in patients with acromegaly using traditional cardiovascular risk factors is inadequate. Endothelial dysfunction seems to be a much better indicator for assessing cardiovascular risk in acromegaly. The study aims to compare from this point of view two groups of patients, with hypertension and with acromegaly. METHODS: The first group consists of 54 patients with acromegaly and the second group of 64 hypertensive patients. Endothelial dysfunction was evaluated by the FMD method. The relationship between endothelial dysfunction, specific humoral markers of acromegaly and traditional cardiovascular risk factors was analysed in both groups. RESULTS: Although the presence of cardiovascular risk factors was statistically significantly higher in the group of hypertensives (the most important were age, blood pressure, glycemia, hypertriglyceridemia and SCORE), the presence of endothelial dysfunction was higher in the acromegaly group (61.10% vs. 32.10%, p=0.02). The best correlation with endothelial dysfunction in acromegaly group was the level of GH (28.9±28 vs. 11.7±10.3, p=0.003). CONCLUSIONS: The presence of endothelial dysfunction in patients with acromegaly is highly dependent on the level of GH and traditional cardiovascular risk factors are less important. In these patients the cardiovascular risk should not be evaluated in the same way as in normal population.

2.
Chirurgia (Bucur) ; 109(3): 318-24, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24956335

RESUMO

INTRODUCTION: During 1993-2008 period, in the Surgical Clinic III were conducted several retrospective studies, in order to identify risk factors for complications after cephalic duodenopancreatectomy(DP). As a result of these studies, a preoperative protocol was developed for preparation of patients proposed for DPC, as well as a number of intraoperative technical changes in order to improve postoperative morbidity and mortality. Implementation of the protocol was gradually and inomogenic done in our service. METHODS: The study is prospective, conducted in 2009-2012, ina group of 180 patients and aims to evaluate immediate results after DPC for periampular malignancy, looking to analyze the effects of implementation of the protocol mentioned above.We analyzed the rates of complications (pancreatic fistula,blunt pancreatitis, bleeding from the pancreatic blunt, delayed gastric emptiness), and the factors that might influence their occurrence. RESULTS AND CONCLUSIONS: of the 180 patients, 10 (5.5%) developed pancreatic fistula and 24 (13.3%) had delayed gastric emptiness. Among the factors that have been significant associated with these complications we mention: the pancreatico-jejunalanastomosis and gastro-jejunal transmesocolic assembly. With the implementation of the protocol, the risk factors previously identified in retrospective studies performed in our service(elevated transaminases, experienced surgical team, etc.) have lost significance, but they have not disappeared entirely, due to fact that the conduit proposed was not entirely followed. We believe that the homogeneous application of a perioperative guide, together with a standardized surgical technique, will lead to improve immediate results after DP.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticojejunostomia/efeitos adversos , Pancreatite/etiologia , Idoso , Feminino , Esvaziamento Gástrico , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/cirurgia , Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/métodos , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
3.
Ultraschall Med ; 35(3): 259-66, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24563420

RESUMO

PURPOSE: To assess the value of contrast-enhanced ultrasound (CEUS) for differentiating malignant from benign focal liver lesions (FLLs) and for diagnosing different FLL types. MATERIAL AND METHODS: CEUS performed in 14 Romanian centers was prospectively collected between February 2011 and June 2012. The inclusion criteria were: age > 18 years; patients diagnosed with 1 - 3 de novo FLLs on B-mode ultrasound; reference method (computed tomography (CT), magnetic resonance imaging (MRI) or biopsy) available; patient's informed consent. FLL lesions were characterized during CEUS according to the European Federation of Societies for Ultrasound in Medicine and Biology guidelines. For statistical analysis, indeterminate FLLs at CEUS were rated as false classifications. RESULTS: A total number of 536 cases were included in the final analysis, 344 malignant lesions (64.2 %) and 192 benign lesions (35.8 %). The reference method was: CT/MRI - 379 cases (70.7 %), pathological exam - 150 cases (27.9 %) and aspiration of liver abscesses - 7 cases (1.4 %). CEUS was conclusive in 89.3 % and inconclusive in 10.7 % of cases. To differentiate between malignant and benign FLLs, CEUS had 85.7 % sensitivity, 85.9 % specificity, 91.6 % positive predictive value, 77.1 % negative predictive value and 85.8 % accuracy. The CEUS accuracy for differentiation between malignant and benign liver lesions was similar in tumors with diameter ≤ 2 cm and those with diameter > 2 cm. CONCLUSION: CEUS represents a useful method in clinical practice for differentiating between malignant and benign FLLs detected on standard ultrasonography, and the results of this study are in concordance with previous multicenter studies: DEGUM (Germany) and STIC (France).


Assuntos
Meios de Contraste , Aumento da Imagem/métodos , Hepatopatias/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Abscesso Hepático/diagnóstico por imagem , Abscesso Hepático/patologia , Hepatopatias/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto Jovem
4.
Chirurgia (Bucur) ; 107(4): 476-82, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23025114

RESUMO

AIM: Multi-organ resection for colorectal malignancy is a topic of interest nowadays as it raises the issue of benefits versus increased morbidity. This study aims to identify factors that may influence the development of postoperative complications and death following multivisceral resection. METHODS: The study included 107 patients hospitalized in the Surgical Clinic III of Cluj-Napoca, who underwent multivisceral resections for colorectal cancer pathology. This is a retrospective study covering the period between 2006 and 2010. This study compares the morbidity and mortality following multi-organ resections for locally advanced colorectal cancer, with results in patients with uncomplicated colorectal resections. The study also highlights the impact that certain factors have on the development of postoperative complications. RESULTS: This study shows a higher incidence of death and postoperative complications in the case of multiorgan resections. The differences were found to be statistically significant as follows: postoperative complications: 26% after multiorgan resection and 14% after uncomplicated resection respectively (p = 0.001); postoperative death: 11% after multi-organ resection and 3% after uncomplicated resection respectively (p < 0.001). The factors that have influenced in a negative way the postoperative evolution of the patients were: diabetes, personal history of malignant disease, associated heart disease, major abdominal surgery prior enrolling, the number of resected organs and increased intraoperative blood loss (over 500 ml). CONCLUSION: In cases of locally advanced colorectal neoplasm, multiorgan resection should become the standard indication, as it offers patients their only chance of survival, comparable to that obtained in less advanced stages of the disease. This indication is underlined by the high resecability rate (R0) accomplished in our service. Preoperative compensation of the associated pathologies, the surgery performed by experienced teams, as well as providing an adequate intensive care are required to reduce the postoperative risks.


Assuntos
Colectomia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Vísceras/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Perda Sanguínea Cirúrgica/mortalidade , Colectomia/efeitos adversos , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Seguimentos , Humanos , Incidência , Fístula Intestinal/etiologia , Fístula Intestinal/mortalidade , Fístula Intestinal/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/prevenção & controle , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Romênia/epidemiologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vísceras/patologia
5.
Chirurgia (Bucur) ; 107(4): 521-3, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23025121

RESUMO

Amyand's hernia is a rare form of inguinal hernia, where the appendix is included in the hernia sac. We present the emergency case of an 81-year-old patient with right inguinal pseudo-tumor, accompanied by marked local pain, nausea, low grade fever and bowel disorders. Emergency surgery is indicated due to a suspected incarcerated inguinal hernia with imminent strangulation. The intraoperatory findings reveal the presence of a periappendicular abscess as the cause of gangrenous appendicitis, perforated in the right indirect inguinal hernia sac. The practice includes the evacuation of the abscess, appendectomy and surgical cure of the inguinal hernia--Bassini's procedure, Douglas drainage and subcutaneous drainage. The postoperative outcome was favorable, the patient being discharged on the fifth postoperative day. Postoperative checks performed at 3 and 9 months have not revealed the presence of a hernia recurrence.


Assuntos
Abscesso Abdominal/etiologia , Apendicite/complicações , Hérnia Inguinal/complicações , Abscesso Abdominal/diagnóstico , Abscesso Abdominal/microbiologia , Abscesso Abdominal/cirurgia , Idoso de 80 Anos ou mais , Apendicectomia/métodos , Apendicite/diagnóstico , Apendicite/cirurgia , Diagnóstico Diferencial , Seguimentos , Hérnia Inguinal/diagnóstico , Hérnia Inguinal/cirurgia , Humanos , Masculino , Ruptura Espontânea , Resultado do Tratamento
6.
Chirurgia (Bucur) ; 107(2): 174-9, 2012.
Artigo em Romano | MEDLINE | ID: mdl-22712345

RESUMO

INTRODUCTION: Colon cancer represents a major health problem in the world. The outcome of newly diagnosed cases predominantly relies on stage as defined by the UICC-TNM and American Joint Committee on Cancer classifications. AIMS: The aim of this retrospective study was to identify the additional prognostic factors for patients with colon cancer. PATIENTS AND METHODS: We retrospectively analyzed the incidence and significance of 8 clinical and pathological factors in 225 patients treated over a 2-year period in Surgery Clinic No. III, Cluj-Napoca. In order to avoid selection bias, all cases with a prior diagnostic of colon cancer and intervention for recurrence or metastasis, as well as cases lacking more than 20% of necessary datawere excluded. The candidate variables were analyzed using the Cox Proportional Hazards Model in order to select those who influence the outcome. RESULTS: The overall 5-year survival rate was 42%. Patients treated with resection of the primary tumor had a survival rate of 50%, ranging from 82% in patients with stage I malignancy to 11% in the presence of metastatic disease. 21% of all patients underwent emergency operation for obstruction or perforation but this did not significantly influence survival (p = 0.1). TheTNM stage of the tumor (HR = 1.2-8.4), grade of tumor differentiation (HR = 2.1) and perineural invasion (HR = 1.8) were independent negative prognostic factors. Venous invasion and status of resection margins were found to influence the outcome on univariate analysis, but were discarded when integrated in the multivariate model. The number of lymph nodes analyzed (p = 0.9) and the tumor location (p = 0.3) did not significantly affect the outcome of patients. CONCLUSION: These results suggest that the prognosis of newly diagnosed cases of colon cancer is influenced by the TNM stage, the degree of tumor differentiation and the presence of perineural invasion.


Assuntos
Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Algoritmos , Neoplasias do Colo/cirurgia , Humanos , Incidência , Metástase Linfática , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Romênia/epidemiologia , Taxa de Sobrevida
7.
Chirurgia (Bucur) ; 107(1): 27-32, 2012.
Artigo em Romano | MEDLINE | ID: mdl-22480112

RESUMO

PURPOSE: To identify the risk and prognosis factors and their predictive value for anastomotic leakage after colorectal resections following cancer. PATIENTS AND METHODS: 1743 consecutive patients who underwent colic resections or rectal resections for colo-rectal cancer between 1996-2005 in Surgical Clinic no. 3 (Cluj-Napoca, Romania) were retrospectively analysed. RESULTS: A total of 54 (3.09 percent) anastomotic leaks were confirmed. Univariate analisys showed that the preoperative variables significantly associated with anastomotic leakage included weight loss, smoking, cardiovascular disease, lung disease, hypoproteinemia, diabetes, anemia, leukocitosis, presence of two or more underlying diseases. Use of alcohol, cerebrovascular disease, bowel preparation, mode of antibiotic prophylaxis, type of handsewn anastomosis, tumor location, tumor stage and tumor histology were nonsignificant variables. Hipoproteniemia (S - proteins < 60g/dl) and anemia (S Hb < 11) remained significant in logistic regression model. CONCLUSIONS: Our study shows that a value of S-proteins lower than 60 g/l and s-Hb lower than 99 g/l can be consider as predictive marker for anastomotik leak deshiscence.


Assuntos
Fístula Anastomótica/etiologia , Biomarcadores Tumorais/sangue , Colectomia/efeitos adversos , Neoplasias Colorretais/cirurgia , Deiscência da Ferida Operatória/etiologia , Deiscência da Ferida Operatória/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Hemoglobinas/metabolismo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Proteína S/metabolismo , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Resultado do Tratamento
8.
J Thromb Haemost ; 10(4): 680-91, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22303879

RESUMO

AIMS: This study aimed to (i) employ our newly designed model, the hypertensive-hypercholesterolemic hamster (HH), in order to find out whether a correlation exists between circulating microparticles (MPs), endothelial progenitor cells (EPCs) and their contribution to vascular dysfunction and (ii) to assess the effect of irbesartan treatment on HH animals (HHI). METHODS AND RESULTS: The results showed that compared with the control (C) group, HH displayed: (i) a significant increase in plasma cholesterol and triglyceride concentration, and an augmentation of systolic and diastolic arterial blood pressure, and of heart rate; (ii) a marked elevation of MPs and a significant decrease in EPCs; (iii) structural modifications of the arterial wall correlated with altered protein expression of MMP2, MMP9, MMP12, TIMP1, TIMP2 and collagen type I and III; (iv) a considerably altered reactivity of the arterial wall closely correlated with MPs and EPC adherence; and (v) an inflammatory process characterized by augmented expression of P-Selectin, E-Selectin, von Willebrand factor, tissue factor, IL-6, MCP-1 and RANTES. Additionally, the experiments showed the potential of irbesartan to correct all altered parameters in HH and to mobilize EPCs by NO, chemokines and adhesion molecule-dependent mechanisms. CONCLUSIONS: Hypertension associated with hypercholesterolemia is accompanied by structural modifications and expression of pro-inflammatory molecules by the vessel wall, the alteration of vascular tone, enhanced release of MPs and reduced EPCs; the ratio between the latter two may be considered as a marker of vascular dysfunction. Irbesartan, which exhibits a pharmacological control on the levels of MPs and EPCs, has the potential to restore homeostasis of the arterial wall.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Aterosclerose/prevenção & controle , Compostos de Bifenilo/farmacologia , Micropartículas Derivadas de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Hipercolesterolemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Células-Tronco/efeitos dos fármacos , Tetrazóis/farmacologia , Animais , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Micropartículas Derivadas de Células/metabolismo , Micropartículas Derivadas de Células/patologia , Colesterol/sangue , Cricetinae , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Colágenos Fibrilares/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipercolesterolemia/patologia , Hipercolesterolemia/fisiopatologia , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/patologia , Hipertensão/fisiopatologia , Mediadores da Inflamação/metabolismo , Irbesartana , Masculino , Metaloproteinases da Matriz/metabolismo , Mesocricetus , Células-Tronco/metabolismo , Células-Tronco/patologia , Inibidores Teciduais de Metaloproteinases/metabolismo , Triglicerídeos/sangue , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
9.
Chirurgia (Bucur) ; 106(4): 479-84, 2011.
Artigo em Romano | MEDLINE | ID: mdl-21991873

RESUMO

INTRODUCTION: Despite significant progress, the management of acute colonic obstruction still remains a challenging problem. The purpose of this study was represented by the evaluation of the clinical results of different techniques of resection for malignant colorectal (primary or staged) obstruction. METHODS: We performed a non-randomized clinical study. 590 patients with malignant colorectal occlusion who underwent surgery treatment an 3rd Surgical Clinic Cluj-Napoca between 1996-2005 were included. RESULTS: Patients with large bowel obstruction underwent one-stage primary resection with anastomosis in 267 cases or staged interventions in 323 cases. The groups were matched in: age, sex, comorbidities, tumor staging, serum preoperative levels of hemoglobin and proteins. The analysis of mortality and morbidity following surgical treatment for large bowel obstruction returned no significant difference among the two groups (p > 0.05). Moreover, the presented results showed a higher incidence of mortality (11.45% vs 9.33 %), morbidity (25.38% vs 14.6%) and increased hospitalization period (p = 0.029) among the patients that undergone seriate resections. CONCLUSIONS: One stage primary resections with anastomosis of the large bowel can be performed safely in case of emergency whenever patient comorbidities and local conditions do not stand as major restrictions.


Assuntos
Colectomia , Neoplasias do Colo/cirurgia , Obstrução Intestinal/cirurgia , Neoplasias Retais/cirurgia , Idoso , Idoso de 80 Anos ou mais , Colectomia/métodos , Neoplasias do Colo/complicações , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Feminino , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/mortalidade , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/complicações , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
10.
Chirurgia (Bucur) ; 106(2): 255-7, 2011.
Artigo em Romano | MEDLINE | ID: mdl-21698866

RESUMO

Ulcerative ischemic lesions of the small bowel represents a rare abdominal pathology. We present the case of a 68-year-old male who was admitted to our hospital for abdominal pain, nausea and vomiting. Ultrasound examination followed by upper endoscopy raised up the suspicion of a jejunal ulcerative perforated lesion. Surgery confirmed the diagnosis, revealing the jejunal ulcer, perforated and blocked by the adjacent enteral loops. Ischemic etiology of the ulceration was indicated by the mesenteric thrombus. The anatomopathologic finding together with the clinical and imagistic examinations lead us to the diagnosis of thromboangiitis obliterans, cause of the mesenteric ischemia; the future problems regarding this case are the long term follow up, in order to be able to recognise the visceral ischemic recurency that might occur.


Assuntos
Perfuração Intestinal/etiologia , Isquemia/complicações , Doenças do Jejuno/complicações , Jejuno/irrigação sanguínea , Úlcera/complicações , Dor Abdominal/etiologia , Idoso , Seguimentos , Humanos , Hipertensão/complicações , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/cirurgia , Isquemia/diagnóstico , Isquemia/cirurgia , Doenças do Jejuno/diagnóstico , Doenças do Jejuno/cirurgia , Masculino , Isquemia Miocárdica/complicações , Náusea/etiologia , Tromboangiite Obliterante/complicações , Resultado do Tratamento , Úlcera/diagnóstico , Úlcera/cirurgia , Vômito/etiologia
11.
J Med Life ; 4(1): 57-62, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21505575

RESUMO

During the past decade idiopathic venous thromboembolism has become a separate entity, a chronic illness which has required prolonged anticoagulation and other prevention strategies to avoid recurrences. This article reviews recent developments regarding unprovoked venous thromboembolism and its relation with thrombophilia. In the beginning, the latest definition of idiopathic venous thromboembolism is presented. The article continues with statistics about thrombophilia, related venous thromboembolism, and a classification of major thrombophilic factors according to their intrinsic risk of thrombosis and of thrombotic recurrences. Great interest is given to the predictors of recurrence and the importance of prolonged anticoagulation is underlined. The antiphospholipid antibody syndrome, the most common acquired thrombophilia, is presented separately. The revised diagnosis criteria are discussed. Some characteristics of the antiphospholipid syndrome are worth presenting: the risk of both venous and arterial thrombosis, the high risk of thrombotic recurrence and the diversity of antiphospholipid antibodies. Patients experiencing idiopathic venous thromboembolic event have a great risk of recurrence, and highly benefit from long time anticoagulation. Natural coagulation inhibitors deficiencies, homozygous factor V Leiden and prothrombin G20210A and the antiphospholipid syndrome, increase the risk of first venous thrombosis and their recurrences and require adequate prevention.


Assuntos
Trombofilia/epidemiologia , Tromboembolia Venosa/epidemiologia , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica , Humanos , Recidiva , Tromboembolia Venosa/tratamento farmacológico
12.
J Biol Chem ; 275(34): 26566-75, 2000 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-10858439

RESUMO

Hematopoietic cell development and function is dependent on cytokines and on intercellular interactions with the microenvironment. Although the intracellular signaling pathways stimulated by cytokine receptors are well described, little is known about the mechanisms through which these pathways modulate hematopoietic cell adhesion events in the microenvironment. Here we show that cytokine-activated Stat3 stimulates the expression and function of cell surface adhesion molecules in the myeloid progenitor cell line 32D. We generated an erythropoietin receptor (EpoR) isoform (ER343/401-S3) that activates Stat3 rather than Stat5 by substituting the Stat3 binding/activation sequence motif from gp130 for the sequences surrounding tyrosines 343 and 401 in the receptor cytoplasmic region. Activation of Stat3 leads to homotypic cell aggregation, increased expression of intercellular adhesion molecule 1 (ICAM-1), CD18, and CD11b, and activation of signaling through CD18-containing integrins. Unlike the wild type EpoR, ER343/401-S3 is unable to support long term Epo-dependent proliferation in 32D cells. Instead, Epo-treated ER343/401-S3 cells undergo G(1) arrest and express elevated levels of the cyclin-dependent kinase inhibitor p27(Kip1). Sustained activation of Stat3 in these cells is required for their altered morphology and growth properties since constitutive SOCS3 expression abrogates homotypic cell aggregation, signaling through CD18-containing integrins, G(1) arrest, and accumulation of p27(Kip1). Collectively, our results demonstrate that cytokine-activated Stat3 stimulates the expression and function of cell surface adhesion molecules, indicating that a role for Stat3 is to regulate intercellular contacts in myeloid cells.


Assuntos
Proteínas de Ciclo Celular , Citocinas/fisiologia , Proteínas de Ligação a DNA/metabolismo , Células-Tronco Hematopoéticas/citologia , Integrinas/metabolismo , Transativadores/metabolismo , Proteínas Supressoras de Tumor , Animais , Antígenos CD18/biossíntese , Adesão Celular , Inibidor de Quinase Dependente de Ciclina p27 , Ativação Enzimática , Fase G1 , Fator Estimulador de Colônias de Granulócitos/farmacologia , Molécula 1 de Adesão Intercelular/biossíntese , Antígeno de Macrófago 1/biossíntese , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Receptores da Eritropoetina/metabolismo , Fator de Transcrição STAT3 , Transdução de Sinais
13.
Mol Cell Biol ; 19(3): 2098-108, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10022897

RESUMO

Fas (CD95) and Fas ligand (CD95L) are an interacting receptor-ligand pair required for immune homeostasis. Lymphocyte activation results in the upregulation of Fas expression and the acquisition of sensitivity to FasL-mediated apoptosis. Although Fas upregulation is central to the preservation of immunologic tolerance, little is known about the molecular machinery underlying this process. To investigate the events involved in activation-induced Fas upregulation, we have examined mRNA accumulation, fas promoter activity, and protein expression in the Jurkat T-cell line treated with phorbol myristate acetate and ionomycin (P/I), pharmacological mimics of T-cell receptor activation. Although resting Jurkat cells express Fas, Fas mRNA was induced approximately 10-fold in 2 h upon P/I stimulation. Using sequential deletion mutants of the human fas promoter in transient transfection assays, we identified a 47-bp sequence (positions -306 to -260 relative to the ATG) required for activation-driven fas upregulation. Sequence analysis revealed the presence of a previously unrecognized composite binding site for both the Sp1 and NF-kappaB transcription factors at positions -295 to -286. Electrophoretic mobility shift assay (EMSA) and supershift analyses of this region documented constitutive binding of Sp1 in unactivated nuclear extracts and inducible binding of p50-p65 NF-kappaB heterodimers after P/I activation. Sp1 and NF-kappaB transcription factor binding was shown to be mutually exclusive by EMSA displacement studies with purified recombinant Sp1 and recombinant p50. The functional contribution of the kappaB-Sp1 composite site in P/I-inducible fas promoter activation was verified by using kappaB-Sp1 concatamers (-295 to -286) in a thymidine kinase promoter-driven reporter construct and native promoter constructs in Jurkat cells overexpressing IkappaB-alpha. Site-directed mutagenesis of the critical guanine nucleotides in the kappaB-Sp1 element documented the essential role of this site in activation-dependent fas promoter induction.


Assuntos
NF-kappa B/metabolismo , Regiões Promotoras Genéticas , Ativação Transcricional , Receptor fas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Ionomicina/farmacologia , Células Jurkat , Ativação Linfocitária , Mitógenos/farmacologia , Subunidade p50 de NF-kappa B , RNA Mensageiro , Fator de Transcrição Sp1/metabolismo , Linfócitos T/efeitos dos fármacos , Fator de Transcrição RelA , Ativação Transcricional/efeitos dos fármacos , Regulação para Cima
14.
Cesk Slov Oftalmol ; 54(3): 166-73, 1998 May.
Artigo em Tcheco | MEDLINE | ID: mdl-9721479

RESUMO

Psychovisual examination methods detect macular changes better and more subtly then hitherto commonly used examination methods, in particular in dynamic investigations. The authors used this method in a series of investigations of diabetes, glaucoma and haemodialysis. The group is formed by 19 eyes of 16 patients with a first attack of central serous chorioretinopathy. Two thirds of the patients were treated by conservative methods, one third by photocoagulation with an argon laser. The observation period was 3 months to 13 years, the mean being 3.5 years. The control group was formed by a group of healthy subjects of corresponding age. The authors proved a statistically significant (5%) reduction of the contrast sensitivity at medium spatial frequencies (6 and 12 c/dg) in patients with one or several attacks of CSCHR. Statistically significant deterioration of colour discrimination (5%) was proved in patients with one attack of CSCHR in 20% of the patients. In patients with two or more attacks of the disease the authors recorded a statistically significant deterioration of colour discrimination (1%) in 44% of the patients. They did not reveal, using psychovisual examination methods, statistically significant differences between groups of patients treated conservatively or by laser. In all cases of impaired colour discrimination a disorder in the blue-yellow region was involved, i.e. in the region of retinal receptors.


Assuntos
Doenças da Coroide/fisiopatologia , Percepção de Cores , Sensibilidades de Contraste , Doenças Retinianas/fisiopatologia , Adulto , Doenças da Coroide/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/terapia
15.
Cancer Lett ; 94(1): 1-8, 1995 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-7542559

RESUMO

Fas/APO-1, a member of the NGF/TNF receptor superfamily expressed on the cell-surface of normal and malignant cells, is known to induce cell death by apoptosis. In the present study, we have investigated Fas/APO-1 gene defects in a human osteosarcoma cell line resistant to the apoptosis-inducing effects of anti-Fas. cDNA cloning and sequencing revealed that these cells contained both 'authentic' and mutant Fas/APO-1 containing a 63 base pair in-frame deletion spanning the transmembrane domain, designated DFas/APO-1. Direct evidence for the existence of a soluble Fas/APO-1 protein was obtained by immunoprecipitation and Western blotting. Taken together with prior studies demonstrating a role for Fas/APO-1 and Fas ligand, respectively, in tumor target cell killing by cytotoxic T-lymphocytes, production of soluble Fas/APO-1 might have significant implications in malignant disease pathogenesis.


Assuntos
Antígenos de Superfície/genética , Apoptose/genética , Deleção de Genes , Osteossarcoma/química , Antígenos de Superfície/fisiologia , Apoptose/imunologia , Apoptose/fisiologia , Sequência de Bases , Humanos , Dados de Sequência Molecular , Osteossarcoma/imunologia , Osteossarcoma/patologia , Reação em Cadeia da Polimerase , Linfócitos T Citotóxicos/fisiologia , Células Tumorais Cultivadas , Receptor fas
16.
J Appl Physiol (1985) ; 78(1): 112-6, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7713799

RESUMO

Activated phagocytes possess an enormous capacity for O2 consumption via NADPH oxidase. NADPH oxidase partially reduces O2, forming superoxide (O2-). Host enzymes rapidly complete O2- reduction to H2O, leaving little trace of its prior existence. Our objectives were to estimate the magnitude of whole body phagocyte respiration and determine the contribution of NADPH-derived O2- to the ensuing phagocyte-induced pulmonary injury. These objectives were accomplished using specific inhibitors of NADPH oxidase, diphenyl iodonium (DPI) and di-2-thienyl iodonium (DTI). Guinea pigs received intravenous injections of DPI (3.5 mg/kg), DTI (7.5 mg/kg), or vehicle followed by phorbol myristate acetate (PMA). Phagocyte activation by PMA immediately increased whole body respiration from 13.6 to 16.1 ml O2.kg-1.min-1 (P < 0.05). DPI and DTI completely blocked the increase in respiration induced by PMA injection (P < 0.05). Baseline respiration was unchanged by the NADPH oxidase inhibitor alone. Likewise, there was no effect on the respiration of isolated heart and kidney mitochondria from animals receiving the inhibitor with or without PMA. DPI attenuated the pulmonary injury induced by PMA. DPI attenuated the pulmonary injury induced by PMA. The ratio of lung water weight to dry weight was lower (6.4 +/- 0.3 vs. 8.3 +/- 0.6) and arterial PO2 was higher (86 +/- 9 vs. 56 +/- 6 Torr) in animals receiving DPI plus PMA than in those receiving PMA alone. In conclusion, phagocyte activation in vivo increased total body respiration by approximately 18%. The burst in respiration is attributed to the phagocyte respiratory burst in which NADPH oxidase partially O2 to O2-.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Pneumopatias/fisiopatologia , Consumo de Oxigênio/fisiologia , Fagócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Anti-Infecciosos/farmacologia , Compostos de Bifenilo/farmacologia , Gasometria , Cobaias , Peróxido de Hidrogênio/metabolismo , Contagem de Leucócitos , Pneumopatias/induzido quimicamente , Masculino , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , NADH NADPH Oxirredutases/antagonistas & inibidores , NADH NADPH Oxirredutases/metabolismo , Oniocompostos/farmacologia , Tamanho do Órgão/fisiologia , Consumo de Oxigênio/efeitos dos fármacos , Fagócitos/enzimologia , Acetato de Tetradecanoilforbol/toxicidade , Tiofenos/farmacologia
17.
Cesk Oftalmol ; 50(3): 145-52, 1994 Jun.
Artigo em Tcheco | MEDLINE | ID: mdl-8050106

RESUMO

In 14 patients (7 men and 7 women), mean age 48 and 50 years resp. with chronic renal failure, having regular dialyzation treatment for more than 10 years (2 patients more than 20 years) the authors made ophthalmological and psychophysiological examinations in order to assess complications after prolonged dialysis. In three patients dialysis was discontinued while a graft was functional. In addition to known complications, calcification of the conjunctiva, osmotic cataract and retinal changes and changes of the optic disc the authors detected also changes of the visual field, contrast sensitivity and colour differentiation. They revealed changes of contrast differentiation in all spatial frequencies with a maximum in medium and upper frequencies. They revealed in more than 60% disorders of colour differentiation with a maximum in the blue-yellow and blue area of the spectrum. Ophthalmic complications the frequency of which is declining only rare by endanger the function of the eye.


Assuntos
Oftalmopatias/etiologia , Diálise Renal/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Transtornos da Visão/etiologia
18.
Anal Biochem ; 213(2): 241-4, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8238897

RESUMO

The currently described methods for determination of decarboxylation reaction rates in cultured cells require large quantities of cells and often involve cell manipulation prior to assay. We describe a simple microassay for the rapid measurement of various decarboxylation reaction rates in intact cultured cells. The assay is based on the traditional measurement of 14CO2 generated from 14C-labeled substrates. Key to the method is a novel modification of the standard petri dish. Pyruvate dehydrogenase, branched chain alpha-ketoacid dehydrogenase, alpha-ketoglutarate dehydrogenase, and ornithine decarboxylase activities were determined in adult cardiomyocyte cultures containing only 0.1-0.5 mg of protein per culture dish. Efficiency of 14CO2 collection ranged between 94 and 100%. Pharmacological enhancement or inhibition of pyruvate dehydrogenase activity was easily detected in the culture system. This new method simplifies the measurement of various decarboxylation reaction rates in cultured cells and allows rapid, reproducible measurements to be made on small numbers of cells without perturbation of the culture conditions or the cells themselves.


Assuntos
Dióxido de Carbono/análise , Miocárdio/citologia , Ornitina Descarboxilase/metabolismo , Oxirredutases/metabolismo , Animais , Dióxido de Carbono/metabolismo , Radioisótopos de Carbono , Células Cultivadas , Descarboxilação , Cinética , Masculino , Miocárdio/enzimologia , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
19.
Cesk Oftalmol ; 49(1): 35-43, 1993 Jan.
Artigo em Tcheco | MEDLINE | ID: mdl-8458090

RESUMO

The authors investigated a group of 42 patients (84 eyes) with primary glaucoma of the open angle and with glaucoma of a low tension. In addition to the basic examination they applied in all patients fluorescent angiography focused on the papilla of the optic nerve, static computer threshold perimetry using a Humphrey Field Analyzer, strategy 30-2, examination of the colour sense (Farnsworth-Munsell 100 HUE test and the desaturated HUE test with computer analysis) and examination of contrast sensitivity by means of the Cambridge low contrast test. They describe the results in the initial stage of an at least 5-year study. In patients aged 41-50 years (n = 10) they found small paracentral scotomas in the visual field in 90% and arcuate scotomas in 10%, minor absolute defects of filling of the papilla in 85%, in 15% only relative defects. In patients aged 51-60 years (n = 15) they revealed acute scotomas in 73% and marked quadrant losses in 27%. Changes in the fluoroangiogram were more marked than in the former groups. In patients aged 61-71 years (n = 15) the changes were analogous. Defects of colour sense of the blue-yellow area were recorded in 63 eyes. Changes of the colour sense and absolute defects of filling in fluorescent angiography correlated with the degree and site of affection of the visual field and the patient's age in primary open angle glaucoma. Conversely, in glaucoma with normal tension the values of colour sense remained normal even when the visual field was affected.


Assuntos
Glaucoma de Ângulo Aberto/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Métodos , Pessoa de Meia-Idade , Hipertensão Ocular/diagnóstico
20.
Circ Shock ; 36(2): 83-92, 1992 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1582008

RESUMO

Sepsis was induced in male rats by injections of live Escherichia coli No. 4 (or E. coli No. 3) and Bacteroides fragilis organisms into a preformed subcutaneous abscess. Body weight, food and water intake, and cardiac output were measured daily. After 1, 2, or 3 weeks, animals were sacrificed, and blood, liver, and muscle were collected for measurements of plasma glucose and carnitine, mitochondrial respiratory activity, mitochondrial cytochrome concentrations, and tissue adenine nucleotides. Compared with sham controls, no significant differences were found in state 3 respiratory activities of liver mitochondria isolated from rats with moderate (no weight loss, cardiac output increased to 150% of control) or severe (0.5% weight loss/day, cardiac output increased to 200% of control) sepsis at any time. After 1 week of severe, but not moderate, sepsis, pyruvate-supported respiration in muscle mitochondria was significantly decreased, while branched-chain ketoacid and beta-hydroxybutyrate-supported respiration remained unchanged. After 2 weeks of severe, but not moderate, sepsis, beta-hydroxybutyrate and branched-chain ketoacid oxidation increased severalfold; pyruvate utilization remained depressed. Severe or moderate sepsis did not uncouple mitochondrial respiration at any time. Total muscle carnitine concentration was significantly decreased after long-term but not short-term severe sepsis. Severe short-term sepsis caused a significant increase in liver short-chain acyl and total carnitines. Muscle energy charge was unaltered by either moderate or severe sepsis. These results represent the first demonstration of sepsis-induced fuel shifts at the mitochondrial level in muscle: Severe hyperdynamic sepsis is characterized by the reduced ability of muscle mitochondria to utilize pyruvate with a simultaneous increase in branched-chain ketoacid and ketone body utilization. These changes were not observed in liver mitochondria.


Assuntos
Ácidos Graxos/metabolismo , Fígado/metabolismo , Músculos/metabolismo , Piruvatos/metabolismo , Choque Séptico/metabolismo , Nucleotídeos de Adenina/análise , Animais , Bacteroides fragilis , Glicemia/análise , Carnitina/sangue , Carnitina/metabolismo , Citocromos/análise , Metabolismo Energético , Escherichia coli , Fígado/química , Masculino , Músculos/química , Ácido Pirúvico , Ratos , Ratos Endogâmicos
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