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1.
Eur J Med Res ; 13(5): 209-14, 2008 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-18559303

RESUMO

BACKGROUND: In HIV patients, disorders in glucose metabolism seem to be side effects of highly active antiretroviral therapy (HAART) which may be favoured by obesity, abdominal fat accumulation and familial disposition for diabetes mellitus (DM). The aim of our study was to identify patients at high risk for abnormalities in glucose metabolism taking into account HAART, familial disposition for DM and anthropometric parameters. METHODS: Plasma glucose, insulin, c-peptide and insulin resistance (homeostasis model assessment, HOMA) were determined in 44 HIV patients [16 without HAART, 19 with protease inhibitors (PI), 9 without PI (non-PI)] and in 11 healthy subjects. Glucose tolerance was determined by standard procedures. Body mass index (BMI), triceps skin fold thickness and waist circumference were measured and the waist-to-hip-ratio was calculated. Familial disposition for DM was assessed by questionnaire. RESULTS: Impaired fasting glucose was observed in 28% of HAART-treated patients (21% with PI, 7% non-PI), in 13% of HAART-naive but none in healthy controls. 58% of PI, 44% of non-PI, 38% of HAART-naive and none of healthy controls had a HOMA-index > 2.5 which indicates insulin resistance. HAART-treated patients had significantly higher fasting glucose levels (PI: 97 +/- 11 mg/dL, p = 0.048; non-PI: 109 +/- 58 mg/dL, p = 0.009) compared to healthy controls (72 +/- 8 mg/dL). HOMA-Index was higher in PI treated patients (3.74 +/- 3.08) than in HIV negative controls (0.95 +/- 0.28, p = 0.018). The duration of HAART (p = 0.045), overweight and familial disposition for DM (p = 0.017) significantly affected fasting glucose among PI users. Waist circumference affected c-peptide (p = 0.046) concentration in these patients. CONCLUSION: HIV patients on long-term PI therapy with overweight and familial disposition for DM are at high risk to develop abnormalities of glucose metabolism. Thus, measurements of HOMA-Index, BMI and waist circumference should be routinely done especially in PI medicated patients.


Assuntos
Gordura Abdominal/metabolismo , Terapia Antirretroviral de Alta Atividade , Glucose/metabolismo , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Sobrepeso/metabolismo , Adulto , Idoso , Feminino , Infecções por HIV/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade
2.
Am J Clin Pathol ; 111(3): 387-96, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10078115

RESUMO

We describe a new, easy-to-use reagent, Cyto-Chex (Streck Laboratories, Omaha, Neb), that preserves fresh whole blood in a non-cross-linking, nonformalin manner. Target values assigned to fresh blood were essentially met after preservation and storage of up to 31 days. Respective mean analytic inaccuracies and short-term intra-assay coefficients of variation (n = 30) were as follows: WBCs, 6.7% and 1.99%; RBCs, 0.7% and 0.76%; hemoglobin, -1.8% and 0.79%; hematocrit, -0.3% and 0.75%; mean corpuscular volume, -1.0% and 0.78%; and platelets, 6.9% and 3.12%. Linearity of dilution-sensitive analytes was satisfactory over a wide range of dilutions after preservation of blood samples. Ten independent laboratories using 10 different instruments determined day-to-day interassay imprecision during four 7-day periods after blood preservation. Mean interassay coefficients of variation for participating laboratories were WBC, 1.92%; RBC, 1.00%; hemoglobin, 1.29%; hematocrit, 2.00%; and platelets 3.29%. Cyto-Chex enables long-term monitoring of instrument accuracy and precision with retained blood specimens of healthy persons. Blood from patient cohorts with various hematologic disorders and with a wide range of numeric abnormalities and/or parameter aberrations can be preserved satisfactorily with this reagent. The reanalysis of preserved patient blood samples is an important adjunct to the use of commercial control material in quality control programs of multichannel hematology analyzers.


Assuntos
Preservação de Sangue/métodos , Testes Hematológicos/métodos , Indicadores e Reagentes , Diagnóstico por Computador , Estudos de Avaliação como Assunto , Testes Hematológicos/instrumentação , Testes Hematológicos/estatística & dados numéricos , Humanos , Laboratórios/estatística & dados numéricos , Controle de Qualidade , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo
3.
Surgery ; 119(3): 316-25, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8619187

RESUMO

BACKGROUND: Measuring serum cytokines, pituitary hormones, or acute phase proteins during or after surgery is not an optimal method for quantifying the impact of surgical procedures. In an effort to assess surgical stress by means of the immune response, we focused on changes in cell-mediated and antibody-mediated immunity as illustrated by the type 1/type 2 T-helper (Th1/Th2) cell balance. The sensitivity of this approach was evaluated by comparing laparoscopic and conventional cholecystectomy (LCE, CCE). METHODS: In a pragmatic prospective study 43 patients with symptomatic cholelithiasis were operated on either by LCE (n = 25) or CCe (n = 18). Blood sampling was done 24 hours before surgery, immediately before incision, and 2, 24, and 48 hours after surgery. Cell surface markers and cytokine production were used to characterize the Th1/Th2 balance and were measured by means of flow cytometry and enzyme-linked immunosorbent assay techniques. RESULTS: Activation of Th2 cells evokes the production and secretion of interleukin-4 (IL-4), which up-regulates the expression of immunoglobulin E receptors (Fo epsilon RII, CD23) on B cells. Phytohemagglutinin-induced IL-4 production in freshly isolated peripheral blood mononuclear cells from patients increased more after CCE than LCE (IL-4, +41% versus +17%; p < 0.05). Also the expression of CD23 on B cells was higher after CCE than LCE (+146% versus +63%; P < 0.01). CD30, a membrane molecule that belongs to the tumor necrosis factor receptor superfamily and probably is an important indicator of Th2 activity, was more evaluated on T cells from patients who underwent CCE. The Th1 response, characterized by phytohemagglutinin-induced IFN-gamma secretion in peripheral blood mononuclear cells and up-regulation of human leukocyte antigen-DR expression on monocytes, was lower after CCE than after LCE. CONCLUSIONS: This study shows that surgical stress induces a shift in the Th1/Th2 balance toward Th2, suggesting that cell-mediated immunity is down-regulated and antibody-mediated immunity is up-regulated after surgery. The evaluation of this shift may be clinically meaningful and help quantify even less invasive surgical procedures. When comparing CCE and LCE in this not strictly randomized study, we found LCE to be the less stressful procedure.


Assuntos
Estresse Fisiológico/imunologia , Procedimentos Cirúrgicos Operatórios , Células Th1/imunologia , Células Th2/imunologia , Regulação para Baixo , Feminino , Antígenos HLA-DR/análise , Humanos , Imunidade , Interferon gama/biossíntese , Interleucina-4/biossíntese , Antígeno Ki-1/análise , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Receptores de IgE/análise , Regulação para Cima
4.
Clin Nutr ; 19(3): 147-56, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10895104

RESUMO

In this article, we outline how metabolic stress and catabolism are set off and influenced by the neuroendocrine network that interacts intensely with the immune system. When evaluating metabolic stress in individuals, the vast ocean of mediators, cell-surface markers and intracellular components that participate in metabolism and catabolic or anabolic changes make it necessary to focus on specific entities that may best mirror all these events. T cell responsiveness and factors that orchestrate the T helper type 1 and type 2 balance form an immunological mirror that can competently reflect catabolism and metabolic stress.


Assuntos
Metabolismo Energético/imunologia , Sistemas Neurossecretores/metabolismo , Estresse Fisiológico/metabolismo , Apoptose , Biomarcadores , Moléculas de Adesão Celular , Quimiocinas , Citocinas , Estudos de Avaliação como Assunto , Humanos , Testes Imunológicos , Sistemas Neurossecretores/imunologia , Estresse Fisiológico/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo
5.
Hybridoma ; 18(1): 41-5, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10211787

RESUMO

In a first clinical trial, 45 patients with advanced ovarian carcinoma and recurrences were treated with the murine monoclonal anti-idiotypic antibody (Ab2) designated ACA125 for active immunotherapy. The monoclonal antibody (MAb) ACA125 mimics a specific epitope of the tumor-associated antigen CA125 expressed by most malignant ovarian tumors. Patients with CA125-positive tumors are immunologically tolerant to CA125, which could be overcome by the use of an anti-idiotypic antibody as a surrogate for the tumor antigen CA125. An immunological response to the anti-idiotype ACA125 in these patients was associated with a statistically significant survival prolongation. Humoral immunity to ACA125 was assessed by induction of anti-anti-idiotypic antibodies (Ab3) directed against CA125. Using flow cytometric detection methods we observe alterations of the intracellular cytokines IFN-gamma, IL-2, and IL-4 at the single-cell level during the course of immunization. There was a strong increase of intracellular IFN-gamma and IL-2 characteristic for a Th1 cell type immune response after treatment with ACA125. A delayed induction of Th2 type response, which promotes antibody-mediated immunity by B cells, could also be detected. The understanding of the kinetics of Th1 and Th2 responses could be important to improve treatment schedules for effective immunotherapy with anti-idiotype vaccines.


Assuntos
Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Antineoplásicos/imunologia , Antígeno Ca-125/imunologia , Vacinas Anticâncer/imunologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/terapia , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Antineoplásicos/sangue , Anticorpos Antineoplásicos/uso terapêutico , Antígenos CD/metabolismo , Vacinas Anticâncer/uso terapêutico , Citocinas/biossíntese , Feminino , Humanos , Imunofenotipagem , Linfócitos/imunologia , Neoplasias Ovarianas/mortalidade
7.
Clin Lab Haematol ; 17(2): 163-72, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8536420

RESUMO

The correct enumeration of platelets is still an elusive matter. This is mainly due to the fact that commercial instruments which are used for platelet counting cannot discriminate platelets from other cellular particles and precipitates that cause similar signals. Visual (chamber counting) methods are still frequently used in routine laboratories to verify low automated platelet counts (< 50 x 10/l) despite obvious technical and statistical drawbacks. The following report shows how platelet counts can be measured by multiparameter flow cytometry with the help of reference particles (fluorescent latex beads) and platelet-specific antibodies i.e. anti-GPIIb/IIIa(CD41a), anti-GP Ib-alpha (CD42b) and anti-GP IIIa (CD61). The linearity of this method was highly satisfactory and the observed imprecision was within acceptable limits. At a platelet concentration of 10 x 10(9)/l the coefficient of variation (CV, n = 10) ranged from 5.3% (PCV = 0.456) to 5.6% (PCV = 0.148). Accuracy was evaluated by comparing results to the ICSH-selected method for platelet counting. The correlation of both methods was significant (P < 0.005) and Passing-Bablok's linear regression analysis showed no systematic differences between the two methods. Comparisons of this new platelet counting technique were also performed with routine visual methods, automated blood analysers (Technicon H-1, Sysmex E-5000) and a different flow cytometric method using only forward and side light scatter properties of platelets for their discrimination. The linear correlation of all methods was significant (P < 0.01) at platelet concentrations above 50 x 10(9)/l. At lower platelet concentrations, our new platelet counting technique correlated significantly only with the visual and the forward/side scatter methods.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Contagem de Plaquetas/métodos , Trombocitopenia/sangue , Anticorpos/imunologia , Plaquetas/imunologia , Plaquetas/patologia , Citometria de Fluxo/métodos , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Humanos , Sensibilidade e Especificidade
8.
Klin Padiatr ; 207(6): 321-5, 1995.
Artigo em Alemão | MEDLINE | ID: mdl-8569133

RESUMO

About 70% of all patients with sickle cell disease suffer from pain crises. Pain crises are recurrent episodes of pain that range in severity from mild to severe, usually occur very abruptly and are often localized around joints. Pain crises are caused by vaso-occlusions in the vascular bed of the bone marrow, leading to necrosis, edema and increased pressure. For effective analgesia morphine or morphine analogues are often required. When treating a pain crisis the patient's complaints need to be taken seriously and analgesic therapy should be started promptly with analgesics in proportion to the severity of the patient's pain. With mild pain oral non-opioid analgesics are sufficient, in moderate pain they are given in combination with oral codeine. Severe pain requires IV morphine, also combined with a non-opioid analgesic. Intravenous morphine makes a thorough monitoring of ventilation and level of consciousness mandatory. Sickle cell patients do not become drug dependent if given morphine for adequate analgesia. While bone marrow transplantation has become an accepted treatment modality for sickle cell patients with severe pain crises, treatment with hydroxyurea to increase HbF levels and reduce incidence and severity of pain crises, however, is still experimental.


Assuntos
Analgésicos Opioides/uso terapêutico , Anemia Falciforme/fisiopatologia , Dor/tratamento farmacológico , Analgésicos Opioides/efeitos adversos , Medula Óssea/irrigação sanguínea , Transplante de Medula Óssea , Criança , Humanos , Hidroxiureia/efeitos adversos , Hidroxiureia/uso terapêutico , Infusões Intravenosas , Isquemia/fisiopatologia , Monitorização Fisiológica , Morfina/efeitos adversos , Morfina/uso terapêutico , Dor/fisiopatologia , Medição da Dor
9.
J Pediatr ; 137(5): 629-32, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11060527

RESUMO

OBJECTIVE: To demonstrate the result of watchful waiting without specific therapy in unselected children with acute immune thrombocytopenic purpura (ITP). STUDY DESIGN: Between May 1992 and October 1999, 55 consecutive children (aged 2 months to 16 years; 28 boys and 27 girls) with acute ITP did not receive intravenously administered immune globulin G (IVIG) or sustained prednisone treatment. Patients with extensive mucosal bleeding were given prednisone, 2 mg/kg/d, for 3 days. RESULTS: In 37 of 55 patients the initial platelet count was <10,000/microL. Ten of these patients had active mucosal bleeding. Five additional patients with bleeding had platelet counts between 10,000 and 20,000/microL. Four patients were given a 3-day course of prednisone. Chronic ITP occurred in 7 (13%) of the patients; 29 patients achieved remission within 6 weeks, and 19 patients, between 6 weeks and 6 months. No life-threatening bleeding occurred, and no patient died. CONCLUSION: Most children with severe thrombocytopenia do not have active mucosal bleeding. This management approach, which did not administer specific therapy, avoided side effects, reduced cost, and was effective.


Assuntos
Púrpura Trombocitopênica Idiopática/fisiopatologia , Púrpura Trombocitopênica Idiopática/terapia , Doença Aguda , Adolescente , Criança , Pré-Escolar , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Masculino , Educação de Pacientes como Assunto , Prednisona/uso terapêutico , Estudos Retrospectivos
10.
Klin Padiatr ; 210(1): 10-6, 1998.
Artigo em Alemão | MEDLINE | ID: mdl-9522298

RESUMO

In Germany about 300 sickle cell patients are being seen at more than 100 different hospitals. One third of these patients are adolescents and young adults. Since this is a congenital chronic disease, the majority of these teenagers and young adults are being cared for by pediatricians. Sickle cell disease in patients older than 15 years is characterized by the development of chronic organ damage, in addition to the occurrence of acute manifestations of disease such as pain crises, splenic sequestration, aplastic crises and Acute Chest Syndrome. Pediatricians who care for older sickle cell patients have to handle not only internal medicine problems but also to answer questions concerning pregnancy and contraception. In this paper the specific problems of adolescents and young adults with sickle cell disease are presented and suggestions are offered for the care of this group of patients.


Assuntos
Anemia Falciforme/diagnóstico , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/terapia , Criança , Terapia Combinada , Feminino , Humanos , Masculino , Equipe de Assistência ao Paciente , Gravidez
11.
Biochem Biophys Res Commun ; 197(2): 549-55, 1993 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-8267589

RESUMO

Changes in cytosolic free Ca2+ influence important granulocyte functions like chemotactic behavior, adherence to endothelia, and phagocytosis. In the following study we used a simple reproducible procedure involving flow cytometry in combination with the fluorescent dye Fluo-3 to measure Ca2+ changes in human granulocytes. The aim of our study was to investigate the involvement of protein kinase C in regulating cytosolic free Ca2+ concentrations after stimulation of cells with IL-8 and fMLP. Both reagents induced a 5-6 fold increase in cytosolic Ca2+. Experiments conducted in Ca(2+)-free media showed a minor 18-29% decrease in cytosolic Ca2+ response, suggesting that intracellular Ca(2+)-stores are the main source for Ca2+ release after fMLP or IL-8 stimulation. Activators of protein kinase C, phorbol myristate acetate (PMA) and 1-oleyl-2-acetyl-sn-glycerol (OAG), inhibited cytosolic Ca(2+)-increase completely when induced by IL-8 and by 68-82% in the case of fMLP. Staurosporine, an inhibitor of protein kinase C, was able to attenuate or even abolish the PMA/OAG-effect. Our results show that changes in cytosolic Ca2+ due to IL-8 and fMLP signalling can be regulated by protein kinase C in human granulocytes. This regulatory role of protein kinase C involves some form of receptor modulation (i.e. phosphorylation, internalization, shedding).


Assuntos
Cálcio/sangue , Granulócitos/metabolismo , Interleucina-8/farmacologia , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Proteína Quinase C/metabolismo , Receptores Imunológicos/fisiologia , Receptores de Peptídeos/fisiologia , Alcaloides/farmacologia , Compostos de Anilina , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Diglicerídeos/farmacologia , Citometria de Fluxo , Corantes Fluorescentes , Granulócitos/efeitos dos fármacos , Humanos , Técnicas In Vitro , Cinética , Proteína Quinase C/antagonistas & inibidores , Receptores de Formil Peptídeo , Receptores Imunológicos/efeitos dos fármacos , Receptores de Peptídeos/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Estaurosporina , Acetato de Tetradecanoilforbol/farmacologia , Xantenos
12.
Klin Wochenschr ; 66(2): 78-80, 1988 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-2964539

RESUMO

Atrial natriuretic peptide (ANP) counteracts the destabilization and aggregation of platelets which is induced by vasopressin, angiotensin, and adrenaline.


Assuntos
Fator Natriurético Atrial/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Angiotensina II/farmacologia , Relação Dose-Resposta a Droga , Epinefrina/farmacologia , Feminino , Humanos , Masculino , Vasopressinas/farmacologia
13.
Pediatr Res ; 18(7): 594-9, 1984 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6206464

RESUMO

A disorder of calcium (Ca2+) metabolism may be central to the pathogenesis of cystic fibrosis (CF). Average cellular Ca2+ levels in fibroblasts derived from patients with CF (ages, 14-25 yr; n = 25) were 36-77% higher than in matched controls depending on age of cell culture (9.0-10.6 versus 5.1-7.8 nmol/mg cellular protein). Cellular Ca2+ was significantly elevated in CF, but was not a reliable criterion for identifying CF cells because of the high variability of results. Studies of Ca2+ fluxes in cell organelles showed that mitochondria isolated from CF fibroblasts accumulate 2-3 times more Ca2+ than controls [79.5 +/- 8.2 versus 33.7 +/- 4.7 nmols X mg mitochondrial protein-1 X 10 min-1 (+/- SD)], Ca2+ accumulation in mitochondrial reliably distinguished between CF and control or heterozygote cells (P less than 0.0005, n = 11). In vitro experiments showed that Ca2+ influx and efflux are increased in isolated CF mitochondria, resulting in net Ca2+ accumulation. Ca2+ uptake in mitochondria is energy-dependent; some inhibitors of mitochondrial energy metabolism (atractyloside, oligomycin) influenced Ca2+ intake significantly more in CF than in control mitochondria. Furthermore, the average activities of NADH oxidase, NADH- and succinate-cytochrome c reductase were 77, 58, and 48% higher in CF mitochondria, respectively. This indicates that many functions associated with energy metabolism and the mitochondrial membrane (electron transport, ATP transport, and ATP hydrolysis) are not operating properly in CF, thus possibly causing the derangement of Ca2+ metabolism found in CF mitochondria and cells.


Assuntos
Cálcio/metabolismo , Fibrose Cística/metabolismo , Membranas Intracelulares/metabolismo , Mitocôndrias/metabolismo , Trifosfato de Adenosina/metabolismo , Adolescente , Adulto , Antimicina A/farmacologia , Atractilosídeo/farmacologia , Transporte de Elétrons , Feminino , Fibroblastos/ultraestrutura , Heterozigoto , Humanos , Masculino , Microssomos/metabolismo , Oligomicinas/farmacologia , Rotenona/farmacologia , Rutênio Vermelho/farmacologia
14.
Klin Wochenschr ; 67(20): 1042-7, 1989 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-2586010

RESUMO

We studied the effect of coronary-artery bypass surgery on blood cells and platelets. Hematological parameters of eighty-three patients were measured by an automated cell counting and sizing analyzer. Sampling time was from 24 h prior to 10 days after surgery. During this time leukocytes and platelets showed characteristic changes in numbers and size, whereas red blood cells revealed no typical modifications. Even though it seems clear that changes of hematological parameters occur after bypass surgery, it is important to be aware of the actual extent of such changes. Therefore the data of 50 patients who had had no post-operative clinical complications were combined to generate diagrams of those parameters that had changed in a characteristic fashion. The diagrams showing average changes, and 99% confidence intervals in mean platelet volume and platelet count were able to identify seven (out of 7) cases with complications up to 48 h before clinical signs were apparent. Complications ranged from mild (3 cases with infections) to severe (4 cases with thrombosis, embolic thrombosis and/or reinfarction). Diagrams showing changes in leukocyte parameters were able to identify only two cases with infections. Even though the number of cases is yet small, the results suggest that surveillance of platelet parameters may be useful in postoperative care. Furthermore, this study was able to confirm the recent findings of Trowbridge and Martin that an abnormal increase in platelet volume distribution width and low platelet counts found in patients with coronary heart disease may serve as good indicators for the prethrombotic state and the risk of myocardial infarction.


Assuntos
Ponte de Artéria Coronária , Doença das Coronárias/cirurgia , Oclusão de Enxerto Vascular/sangue , Contagem de Leucócitos , Contagem de Plaquetas , Complicações Pós-Operatórias/sangue , Adulto , Contagem de Eritrócitos , Humanos , Pessoa de Meia-Idade , Ativação Plaquetária , Infecção da Ferida Cirúrgica/sangue
15.
J Clin Chem Clin Biochem ; 27(9): 531-7, 1989 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2558149

RESUMO

Elevated concentrations of atrial natriuretic peptide reportedly mitigate acute renal failure in vivo and in the isolated perfused kidney (M. Nakamoto, J.I. Shapiro, P.F. Shanley, L. Chan & R.W. Shrier (1987) J. Clin. Invest. 80, 698-705; S.G. Shaw, J. Weidmann, J. Hodler, A. Zimmermann & A. Paternostro (1987) J. Clin. Invest. 80, 1232-1237). Since atrial natriuretic peptide has been shown to be a potent vasodilator, this beneficial effect may be due entirely to improved haemodynamics. To determine whether atrial natriuretic peptide also has a protective effect at the cellular level, rat hepatocyte cell cultures were treated with atrial natriuretic peptide prior to or after induction of cell damage by hypoxia (0.5% O2 for 4 h) or reactive oxygen (hypochlorous acid). Bleb formation, degradation of radiolabeled trichloroacetic acid-precipitable peptides, release of lactate dehydrogenase and trypan blue exclusion were used as indicators of cell damage. Atrial natriuretic peptide treatment distinctly protected the cell cultures against damage in both cases. This beneficial effect of atrial natriuretic peptide was partly mimicked by sodium nitroprusside, which, like atrial natriuretic peptide, largely increased the cellular cGMP content. 6-Anilino-5,8-quinolinedione (Ly 83583), an inhibitor of particulate guanylate cyclase, blocked the protective effect of atrial natriuretic peptide. Therefore a cGMP-mediated mechanism seems to be involved in the cytoprotective action of atrial natriuretic peptide. Fluorometric measurements using the Ca2+-sensitive dye Quin-2 showed that the elevation of intracellular Ca2+ after cellular insult by hypochlorous acid is prevented by atrial natriuretic peptide. These results suggest that atrial natriuretic peptide may attenuate hypoxic and toxic cell damage by increasing cGMP and reducing intracellular Ca2+.


Assuntos
Fator Natriurético Atrial/farmacologia , Cálcio/fisiologia , Ácido Hipocloroso/efeitos adversos , Fígado/efeitos dos fármacos , Oxigênio/farmacologia , Aminoquinolinas/farmacologia , Animais , Cálcio/análise , Células Cultivadas , AMP Cíclico/análise , GMP Cíclico/análise , Relação Dose-Resposta a Droga , Interações Medicamentosas , Fígado/citologia , Fígado/metabolismo , Masculino , Nitroprussiato/farmacologia , Ratos , Ratos Endogâmicos , Fatores de Tempo
16.
Zentralbl Chir ; 122(3): 157-63; discussion 163-4, 1997.
Artigo em Alemão | MEDLINE | ID: mdl-9206909

RESUMO

UNLABELLED: Elective surgical approaches and trauma cause changes in the production of different cytokines, an increased production of acute phase protein and changes in the expression of different cell surface markers. METHODS: In a prospective study we examined the C-reactive protein level, the production of the cytokines IL-6, IL-8 and IL-1 RA in 25 laparoscopic and 21 conventional cholecystectomies. In addition the cell surface markers CD25 and CD30 on different cell populations and HLA-DR on monocytes were measured. Statistical analysis was made by Student's-t-test and Mann-Whitney's rank sum test. RESULTS: The humoral markers showed a more distinct increase in patients operated on conventionally two and 24 hours after surgery, the differences between the two surgical approaches were significant (p < 0.01). The cell surface markers CD25 and CD30 showed the same reaction. The HLA-DR expression on monocytes was significantly lower in patients operated on conventionally. CONCLUSIONS: Elective surgical approaches cause changes in the immune system, which can be evaluated by the reaction of cytokines and cell surface markers. Laparoscopic cholecystectomies cause less activation of the immune system than conventional operations.


Assuntos
Reação de Fase Aguda/imunologia , Colecistectomia Laparoscópica , Colecistectomia , Citocinas/sangue , Antígenos HLA-DR/sangue , Antígeno Ki-1/sangue , Complicações Pós-Operatórias/imunologia , Receptores de Interleucina-2/sangue , Reação de Fase Aguda/diagnóstico , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sialoglicoproteínas/sangue , Linfócitos T/imunologia
17.
Surg Endosc ; 13(4): 335-9, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10094742

RESUMO

BACKGROUND: In this study we tried to estimate the local surgical trauma in patients undergoing endoscopic or conventional hernia repair via the changes in peripheral blood T cell subpopulations (i. e., T-helper 1 (TH1) and TH2 cells), recently shown to be recruited differentially to inflammatory sites. METHODS: Cells were identified flow-cytometrically by intracellular cytokine staining on a single cell level in 30 patients undergoing conventional (Shouldice) or total extraperitoneal patch (TEPP) hernia repair. RESULTS: The TH1 cells decreased postoperatively in Shouldice patients on an average of 20.8-31.4%, whereas in TEPP patients only a minor decline (mean, 7.8-9.2%) was observed. The TH2 cells did not change significantly in TEPP patients, and a small increase (mean, 7.7%) was detected in Shouldice patients. CONCLUSIONS: Our results suggest that the postoperative reduction in TH1 cells reflects local surgical trauma and can be helpful in evaluating different surgical procedures. When conventional and endoscopic hernia repair were compared, the latter proved less traumatizing.


Assuntos
Citocinas/sangue , Endoscopia/efeitos adversos , Herniorrafia , Estresse Fisiológico/imunologia , Células Th1/metabolismo , Células Th2/metabolismo , Adulto , Regulação para Baixo , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Regulação para Cima
18.
Biochem Biophys Res Commun ; 163(2): 836-42, 1989 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-2783125

RESUMO

We investigated the effects of oxygen-based radicals induced by t-butyl hydroperoxide or H2O2/Cu2+ on cultured hepatocytes. Radical exposure caused membrane lesions (blebs), lactate dehydrogenase release and lipid peroxidation (i.e. formation of malondialdehyde) in cells. As expected, radical scavengers (catalase, alpha-tocopherol) strongly inhibited these phenomena. A similar or even superior inhibitory effect was achieved by the protein kinase C (PKC) inhibitors H-7 and phloretin. These agents did not reveal notable radical scavenging properties as assessed by their ability to break down H2O2. The PKC stimulators 4 beta-phorbol-12-myristate-13 and 1-olyeoyl-2-acetyl-sn-glycerol intensified the detrimental actions of the radical-inducing agents. [3H]Phorbol-12,13-dibutyrate-binding studies showed that membrane association of PKC is markedly increased in hepatocytes after exposure to H2O2/Cu2+ or t-butyl hydroperoxide. These results suggest that PKC membrane translocation and activation may be important for mediating membrane damage and lipid peroxidation after cells are exposed to oxygen-based radicals.


Assuntos
Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Oxigênio/farmacologia , Proteína Quinase C/metabolismo , Animais , Membrana Celular/efeitos dos fármacos , Radicais Livres , L-Lactato Desidrogenase/metabolismo , Fígado/citologia , Masculino , Ratos , Ratos Endogâmicos
19.
Cytokine ; 12(9): 1385-90, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10975999

RESUMO

Cytotoxicity and proliferation of NK-like T (CIK) cells are dependent on the continuous presence of exogenous cytokines, but it is not known which cytokine is optimal. Here, we compared the effect of exogenous interleukin 2 (IL-2), interleukin 7 (IL-7) or interleukin 12 (IL-12) on the generation of CIK cells in addition to IL-1, interferon-gamma and anti-CD3 antibodies. Cell surface markers important for cytotoxic activity and adhesion were defined and cytokines leading to their optimal expression were determined. The most important findings were: (a) IL-12 generates the most CD3/CD56-double-positive CIK cells, (b) the expression of LFA-1/CD11a which is important for cytotoxic activity is highest with IL-7, and (c) IL-7 also generates the most CD28-positive cells which may enhance T cell receptor co-stimulation. In summary, essential differences concerning antigen expression were found when generating CIK cells using IL-7 or IL-12 instead of IL-2. In particular, IL-12 may be of interest due to the high expansion of CD56 positive cells in CIK cell cultures and the important role of these cells in mediating cytotoxicity towards malignant tissues.


Assuntos
Interleucina-12/farmacologia , Interleucina-2/farmacologia , Interleucina-7/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Antígenos CD28/biossíntese , Complexo CD3/imunologia , Complexo CD3/farmacologia , Antígeno CD56/biossíntese , Adesão Celular/efeitos dos fármacos , Separação Celular , Sobrevivência Celular/efeitos dos fármacos , Citometria de Fluxo , Humanos , Interferon gama/farmacologia , Interleucina-1/farmacologia , Células Matadoras Naturais/metabolismo , Antígeno-1 Associado à Função Linfocitária/biossíntese , Microscopia de Fluorescência , Receptores de Interleucina-2/biossíntese , Linfócitos T/metabolismo
20.
Eur J Vasc Endovasc Surg ; 25(3): 254-61, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12623338

RESUMO

OBJECTIVE: to evaluate local surgical trauma induced by endovascular (TPEG) and conventional infrarenal aortic aneurysm repair (AAA-C), the inflammatory response and changes in cell-mediated and antibody-mediated immunity as illustrated by the type-1/type-2 T-helper (TH1/TH2) cell balance were investigated. DESIGN: prospective study. PATIENTS AND METHODS: sixteen patients were included, eight patients underwent AAA-C and eight TPEG. Venous peripheral blood samples were collected 24h preoperatively and 24, 48, 72h, 5 and 7 days postoperatively. Besides the WBC, intracellular TH1/TH2 cytokines (IFN-gamma/IL-4) and the cell surface markers HLA-DR on monocytes and CD23 on B cells were measured by four colour flow cytometry. RESULTS: statistically significant higher values in the AAA-C group were demonstrated for neutrophiles. The TH1/TH2 immunobalance (expressed by forming the ratio of IFN-(gamma/IL-4 producing T cells as well as by the ratio of HLA-DR(pos) monocytes/CD23(pos) B-cells) showed a significant shift towards TH2 immunity in the AAA-C group whereas TPEG led to a significant lesser shift 24-72h after surgery (p < 0.05). CONCLUSIONS: TPEG leads to a minor distortion of the TH1/TH2 immunobalance. This implies that TPEG is a less stressing procedure, that is especially beneficial in patients whose conditions are considered less suitable for AAA-C due to age and serious comorbidity.


Assuntos
Aneurisma da Aorta Abdominal/imunologia , Aneurisma da Aorta Abdominal/cirurgia , Células Th1/imunologia , Células Th2/imunologia , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Citometria de Fluxo , Antígenos HLA-DR/análise , Humanos , Imunidade Celular/fisiologia , Interferon gama/sangue , Interleucina-4/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/fisiologia , Estudos Prospectivos , Receptores de IgE/análise
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