Níveis plasmáticos de taurina e de seus precursores em pacientes com câncer de esôfago / Plasma taurine levels in patients with esophagus cancer

RACIONAL: O câncer de esôfago tem impacto relevante no metabolismo protéico do hospedeiro, mas pouco se conhece sobre as implicações no metabolismo protéico sulfurado. Deste, destaca-se a taurina, composto participante de várias funções fisiológicas importantes como a manutenção do sistema de defesa celular e possível sobrevida do paciente. OBJETIVO: Estudar as variações plasmáticas da taurina e de seus precursores em pacientes com câncer de esôfago. MÉTODO: Em estudo transversal foram triados 16 pacientes (43-73 anos) com câncer de esôfago e 20 voluntários (27-65 anos) controles sadios que preencheram os critérios clínicos e éticos da pesquisa. Para caracterização do estado geral de saúde efetuou-se avaliação antropométrica, hematimétrica (Hb, Ht, glóbulos brancos, linfócitos) e bioquímica (albumina, glicose, lipídios, aminotransferases). Adicionalmente, foram realizadas, no plasma, análises cromatográficas de taurina e seus precursores cisteína e homocisteína. Foi registrado o tempo de sobrevivência dos pacientes, a partir do diagnóstico histopatológico. RESULTADOS: Os pacientes com câncer de esôfago foram predominantemente do sexo masculino, raça branca, classe socioeconômica baixa, tipo carcinoma espinocelular de localização no terço superior, em estádio IV, sobrevida de 7,8 ± 5,5 anos, referindo perda de peso em 16,4 por cento e apresentando hipoalbuminemia em 50 por cento, com massa muscular e adiposa semelhante ao controle. Os pacientes apresentaram valores estatisticamente menores do que os controles para Hb, Ht, colesterol total, HDL-colesterol e cisteína e maiores de AST, ALT, taurina e homocisteína. Dentre os pacientes houve correlação positiva da taurina tanto com a contagem total de linfócitos, como com a sobrevida dos pacientes. CONCLUSÃO: Os níveis reduzidos de cisteína e elevados de homocisteína, taurina e as associações positivas da taurina com os indicadores da imunocompetência celular e da mortalidade sugerem participação ...

BACKGROUND: The esophagus cancer-host has a two way close relationship as seen in its sulphur-amino acid metabolism. Taurine one of these compounds has ubiquous role in host defense and other physiological mechanisms related to survival. AIM: To study the plasma levels of taurine and its precursors in patients with esophagus cancer. METHODS: In a sectional design both groups, patients (n = 16, 43-73 yrs old) and healthy controls (n = 20, 27-65 yrs old) were assessed for anthropometry, body-weight lost, hematology (Hb, Ht, total leukocytes and lymphocyte counts), general biochemistry (albumin, glucose, lipids and aminotransferases) and chromatographic analysis for taurine, cysteine, and homocysteine. The survival time was registered there since from the clinical-histopathological diagnosis. All participants had a written ethical consent for the research. RESULTS: The cancer patients were predominantly, white males of low social economic class, with spinocellular carcinoma stage IV located at upper 3rd half of them presented hypoalbuminemia and 16 percent referred significant body-weight loss. The patients showed statistically lower values of Hb, Ht, total and HDL cholesterol and cysteine and significantly higher values of taurine, homocysteine and aminotransferases than healthy controls. A positive relationship was found between taurine and either TLC (r = 0.50) and survival (r = 0.81). CONCLUSIONS: Lower plasma cysteine along with higher levels of taurine and homocysteine and the positive direct association of taurine with indications of survival suggest an effective role of this compound and therefore a prospective special nutritional care in its precursors (cysteine, methionine and B vitamins) of these patients.

Clinical usefulness of a HPLC method for simultaneous quantitation of plasma homocysteine and cysteine.

OBJECTIVE: Homocysteine (Hcy) is a risk for vascular occlusion. It is metabolized via remethylation to methionine and transsulfuration to cysteine which has also been related to vascular occlusion. Simultaneous determination of Hcy and cysteine has additional clinical usefulness in providing a presumptive clue to the nature of hyperhomocysteinemia. MATERIAL AND METHOD: A manual HPLC method has been worked out for simultaneous determination of plasma Hcy and cysteine. Concentrations of Hcy were validated with the widely used automated Abbott AxSYM assay. Its usefulness was tested in 87 omnivores and 111 vegans. RESULTS: Excellent correlation between the values of Hcy was found between the manual HPLC method and the automated Abbott assay. The vegans had significantly higher levels of Hcy but lower levels of cysteine than the omnivores (mean +/- SD, micromol/L 23.6 +/- 18.0 vs. 8.8 +/- 2.1 p < 0.001, 225 +/- 30 vs. 245 +/- 34 p < 0.001, respectively). In contrast, the vegans had significantly lower levels of serum vitamin B12 and plasma vitamin B6 than the omnivores (median values 186 vs 565 pg/ml, p < 0.001; 37.4 vs. 47.4 nmol/L, p < 0.001 respectively). These findings indicate that the hyperhomocysteinemia in the vegans results from impairment of both remethylation and transsulfuration pathways of Hcy secondary to inadequacy of vitamins B12 and B6 respectively. Thus simultaneous determination of Hcy and cysteine is more useful than determination of only Hcy in that it provides a clue to the nature of hyperhomocysteinemia. CONCLUSION: The manual HPLC method and the Abbott assay gave comparable Hcy values, and thus can be used interchangeably. The HPLC method is economical, useful for hospitals with less demand for determination of Hcy, and capable of simultaneously determining cysteine which has implication in clinical practice.

Effect of N-acetyl-L-cysteine on lymphocyte apoptosis, lymphocyte viability, TNF-alpha and IL-8 in HIV-infected patients undergoing anti-retroviral treatment

N-acetyl-L-cysteine (NAC) has been proposed as an additional therapeutic agent for AIDS patients because it reduces human immunodeficiency virus type 1 (HIV-1) replication in stimulated CD4+ lymphocytes, and it ameliorates immunological reactivity. In a randomized, 180-day, double-blind, placebo-controlled trial performed with HIV-infected patients classified as A2 and A3 according to the criteria of the Center for Disease Control and Prevention, we investigated the effects of oral administration of NAC on HIV-infected patients undergoing their first anti-retroviral therapy; viral load, CD4+ lymphocyte, lymphocyte viability and apoptosis, and TNF-alpha and IL-8 levels were determined. Sixteen patients who received anti-retroviral therapy plus a placebo formed the control group and the study group consisted of 14 patients who received anti-retroviral therapy and NAC supplementation. A significant decrease was seen in viral load, TNF-alpha and IL-8 levels, and lymphocyte apoptosis, and a significant increase was found in levels of CD4+ lymphocytes and lymphocyte viability in both groups after anti-retroviral treatment, but no measurable benefits of anti-retroviral therapy plus NAC oral supplementation (600 mg/day) were found in relation to anti-retroviral therapy alone, and the baseline levels of cysteine and glutathione in plasma were not recovered by this treatment. In conclusion, the daily doses of NAC necessary for the total recuperation of plasma cysteine and glutathione levels in HIV-infected patients and the additional benefits following the supplementation of NAC in patients submitted to anti-retroviral therapy, need to be studied further.

Assessment of the role of hypephomccysteinemia and its metabolic consequences in the vascular access thrombosis among hemodialysis patients

The aim of this work was, to determine whether hyperhomocysteinemia and its metabolic consequences are associated with vascular access thrombosis in patients with end stage renal disease [ESRD], undergoing chronic hemodiahysis [HD]. This study included 3 groups. Group I: 15 ESRD patients on regular HD, with history of more than one episode of vascular access thrombosis. Group II: 15 ESRD patients on regular HD, with no episodes of vascular access thrombosis. Group III: 10 healthy, age and sex matched individuels as a control group. Plasma total homocysfeine [tHcy] and Von Willebrand Factor [vWF] were estimated by ELISA. Determination of plasma folate was done by Radioimmunoassay [RIA]. Plasma glutathione peroxidase activity was estimated by modified Paglia and Valentine method. Plasma methionine and cysteine levels were estimated by amino acid autoanalyser. plasma Hcy levels of both HD groups [GI and GII] were significantly higher than control groups [GIII] [F value = 44,487, P<0.0001], while no significant difference was found between GI and GII. Plasma folic acid levels of both patients' groups were significantly higher than control group [F value = 29.063, P<0.0001], while there was no significant difference between its level in GI and GII. Plasma vWF of HD patients with vascular access thrombosis [GI] was significantly higher than that of both GII and GIII and that of GII was significantly higher than GIII [F value = 62.010, P<0.0001]. Plasma glutathione peroxidase activity of both HD groups [GI and GII] was significantly lower than the control group [GIII] [F value = 69.446, P<0.0001], also its activity in patients with vascular access thrombosis [GI] was significantly lower than that of patients without vascular access thrombosis [GII]. Plasma cysteine and methionine levels of both HD groups were not significantly different from control group, also there was no significant difference in their levels between GI and GII. Plasma Hcy levels showed no significant correlation with number of vascular access thrombosis, whereas it showed a significant positive correlation with plasma vWF [r = 0.474, P<0.01] and negative correlation with plasma glutathione peroxidase activity [r = 0.643, P<0.0001]. From the previous study we concluded that: Hyperhomocyteinemia is not a direct cause of vascular access thrombosis. It is linked with increased plasma vWF levels. Endlothelial injury induced by hyperhomocysteinemia may be the cause. The lower levels of plasma glutathione peroxidase activity reflect increased oxidative stress induced by hyperhomocyteinemia in hemodialysis patients

Levels of plasma cysteine and blood glatathione in patients with cardiovascular diseases

The aim of this study was to determine whether the levels of aminothiols such as glutathione [GSH], cysteine [Cys] and homocysteine [Hcys] were affected by various cardiovascular diseases [CVD] and the relation between these two thiols Cys and GSH. Blood samples from 62 patients with atherosclerosis and 34 CV diseased subjects were analyzed and matched with control subjects. In the CV patients, free plasma Cys was significantly high and blood GSH levels were normal. In patients with ATH, bound plasma Cys was 21% higher than in control subjects and in patients with other CV diseases, it was 14% higher. There were no differences related to the duration of the disease or the functional disability. The abnormal levels of plasma Cys occurred in both ATH and other CV diseases indicated that high levels of oxidized and bound Cys in CV patients create an oxidative state which may increase the incidence to vascular damage

The reaction between ABTS radical cation and antioxidants and its use to evaluate the antioxidant status of serum samples

The 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation can be generated by incubation of ABTS and 2,2'-azo-bis(2-amidinopropane) at 45 degrees Celsius. The ABTS radical cation is stable for several minutes at room temperature and reacts quantitatively and instantaneously with several antioxidants, such as Trolox, ascorbic acid, uric acid, cysteine, glutathione and bilirubin. In contrast, the ABTS radical cation reacts slowly with albumin. When serum is added to a solution of the ABTS radical cation, the bleaching of the radical follows biphasic kinetics, with a fast decay followed by a slow decay that takes place within several minutes. The fast decay is primarily due to uric acid, while the slow decay is related to the protein content of the sample. We propose that this procedure can provide an independent and simultaneous evaluation of the low molecular weight and protein antioxidants present in biological samples such as serum.

A Bothrops jararaca plasma cysteine proteinase inhibitor related to Mammalian kininogen

A kininogen-like protein was purified from Bothrops jararaca plasma by DEAE-Sephadex ion-exchange and carboxy-methul-papain-Sepharose affinity chromatography. The molecular weight, estimated by SDS-gel electrophoresis, is about 100,000 and a species of about 75,000 is formed after incubation with hosrse urinary kallikrein. After incubation with rrypsin, only traces of biological activity were detected in tests on guinea pig ileum. The purified protein inhibits papain and bromelain, does not correct the clotting time of a kininogen-depleted human plasma, and does not affect the clotting time ogf plasma from Waglerophis merremii, a nonpoisonous snake; the same type of inhibitor was foind in this nonpoisonous snake. The dissociation cosntant (Ki) for the papain-inhibitor complex is approximately 1.6 nM

Glutatioma redutase e grupos SH reativos intra-eritrocitários: revisäo / Glutathione reductase and recting SH groups in erythrocytes: review

A glutationa, tripeptídeo constituída de glutomato, cisteína e glicinia, possui atividade química através do grupo SH. A glutationa apresenta-se normalmente na forma reduzida porém pode oxidar-se formando pontes dissulfeto entre duas moléculas. A síntese dA glutationa ocorre no interior da hemácia necessitando, para tanto, além dos aminoácidos constituintes da molécula,das enzimas y-glutamil cisteína sintetase e gglutationa sintetase. A glutationa reduzida, uma vez formada, näo tem capacidade de deixar o eritrócito. Existem pórem evidência de que A glutationa oxidada atravessa a membrana eritrocitária consumindo energia. Isto se faz necessário porque a gglutationa oxidada, entre outras atividades, tem a capacidade de inibir a enzima hexoquinase e reagir com a molécula de hemoglobina, alterando desta forma o funcionamento normal do eritrócito. A principal funçäo dA glutationa no interior do eritrócito é manter os grupos SH reativos na forma reduzida. Para que isso ocorra de forma adequada, é necessária a presença da enzimA glutationa redutase, catalisadora da reduçäo da glutationa oxidada. A glutationa redutase näo atua apenas nas pontes dissulfeto formadas pelA glutationa, mas também sobre outras ligaçöes dissulfeto formadas por proteínas eritrocitárias, tais como as da membrana celular. A hemoglobina é a principal constituinte do eritrócito e possui dois grupos SH reativos correspondentes à cisteína 93, constituintes das cadeias beta normais. Esses grupos säo preservados pelA glutationa redutase. Para que a açäo dA glutationa redutase seja adequada ela necessita de NADPH, gglutationa reduzida e flavina adenina dinucleotídeo (FAD). O NADPH é reduzido na via das pentoses pela açäo da glicose-6-fosfato desidrogenase (G6PD). O FAD é derivado fosforilado da riboflavina e atua como grupo prostético dA glutationa redutase...