RESUMEN
OBJECTIVE: To investigate whether antioxidant polyphenols from fruit juices or a fruit-vegetable-concentrate increase the plasma antioxidant capacity in HIV-infected and healthy subjects. DESIGN: Twenty-three HIV-seropositive and 18 seronegative adults were randomized to ingest either 1 l of fruit juice or 30 ml fruit-vegetable-concentrate per day over 16 weeks in addition to their normal Western diet. METHODS: Plasma antioxidant capacity was determined as Trolox equivalent antioxidant capacity (TEAC) at baseline, after 1 and 16 weeks of intervention, and after a 6 week washout. RESULTS: There was no difference in plasma antioxidant capacity between HIV-infected and healthy subjects at baseline (P=0.1). After 16 weeks of intervention TEAC increased in HIV-positive subjects with both types of polyphenol supplementation (juice, 1.38+/-0.07 to 1.42+/-0.04 mM, P=0.034; concentrate, 1.40+/-0.09 to 1.46+/-0.08 mM, P=0.025). TEAC was not altered by either type of supplementation in HIV-seronegative subjects. CONCLUSION: Plasma antioxidant capacity can be increased by long-term ingestion of polyphenols from fruit juices or fruit-vegetable-concentrate in HIV-seropositive but not in HIV-seronegative subjects. SPONSORSHIP: This study was supported by a grant and Cellagon aurum from HG Berner GmbH, Altenholz, and fruit juices from Eckes Granini GmbH & Co. KG, Nieder-Olm.
Asunto(s)
Antioxidantes/metabolismo , Flavonoides , Frutas/química , Seronegatividad para VIH/fisiología , Seropositividad para VIH/metabolismo , Verduras/química , Adulto , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Fenoles , Polímeros , PolifenolesRESUMEN
BACKGROUND: The aim of this work was to study the effects of combined oral administration of N-acetylcysteine (NAC) and sodium selenite (Se) on plasma glutathione (GSH), lymphocyte subpopulations and viral load in asymptomatic human immunodeficiency virus (HIV)-infected patients. METHODS: We used a prospective, randomized and controlled therapy trial with partial crossover. Twenty-four antiretroviral-naive HIV-infected outpatients at Centers for Disease Control (CDC)'93 stages I and II were randomized to receive the antioxidant combination NAC 600 mg t.i.d. and Se 500 micrograms per day for either 24 weeks (group A, n = 13) or from the end of week 12 (group B, n = 11) until the end of week 24. Thus, group B served as untreated control during the first 12 weeks. RESULTS: There was (a) a trend towards an increase in the percentage of CD4+ lymphocytes after 6 weeks (P = 0.08); (b) an increase in the CD4/CD8 ratio after 6 and 12 weeks (P = 0.02 and P = 0.04 respectively); and (c) a decrease in the absolute CD8/CD38 count and percentage of lymphocytes after 6 weeks (P = 0.002 and P = 0.033 respectively) and 12 weeks (P = 0.033, P = 0.1 respectively) in group A compared with the control period of group B. The effects observed in group A were, however, not paralleled to the same extent by group B after crossing-over to treatment after 12 weeks. In addition, erythrocyte glutathione peroxidase (GSH-Px) activity and GSH, glutathionedisulphide (GSSG) concentrations and the reduced/total GSH ratio were not affected by the treatment. Serum selenium levels increased significantly (P < 0.001) upon treatment. Viral load was not altered. CONCLUSIONS: The changes in lymphocyte subsets after NAC/Se treatment were not comparable to those after standard antiretroviral drug therapy. This, however, does not preclude per se possible benefits of antioxidant supplementation in HIV disease.
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Acetilcisteína/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Selenito de Sodio/uso terapéutico , Administración Oral , Adulto , Eritrocitos/enzimología , Femenino , Glutatión/sangre , Disulfuro de Glutatión/sangre , Glutatión Peroxidasa/sangre , Infecciones por VIH/sangre , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Valores de Referencia , Selenio/sangre , Subgrupos de Linfocitos T/efectos de los fármacos , Carga ViralRESUMEN
OBJECTIVES: Antioxidant defense status was investigated in HIV-infected patients by measuring serum selenium, erythrocyte glutathione peroxidase (GSH-Px) activity, plasma thiol (-SH) and glutathione (GSH) concentrations along with the assessment of the clinical stage and surrogate markers of HIV-disease. DESIGN, SETTING AND SUBJECTS: Serum selenium levels were determined cross-sectionally in 104 sequentially selected HIV-infected patients (83 outpatients and 21 patients with ongoing AIDS defining events). The patients were classified into three stages of the disease, I, II and III according to the 1993 Centers For Disease Control (CDC) classification system for HIV-infection. GSH-Px activities, plasma SH and plasma GSH concentrations were determined in a subset of 24 patients at stage I and 12 patients at stage III with an active AIDS-defining disease. RESULTS: Mean serum selenium levels were lower in CDC stage II (68.7 +/- 20.9 micrograms/l; P < 0.01; n = 34) and stage III (51.4 +/- 14.7 micrograms/l; P < 0.01; n = 37) HIV-infected patients than in healthy subjects (89.2 +/- 20.9 micrograms/l; n = 72) and stage I patients (82.3 +/- 20.5; microgram/l; n = 33). Serum selenium levels were positively correlated with CD4-count (r = 0.42; P < 0.001; n = 104) and inversely with levels of soluble tumor necrosis factor receptors type II (r = -0.58; P < 0.01; n = 35), neopterin (r = -0.5; P < 0.001; n = 80) and beta 2-microglobulin (r = -0.4; P < 0.001; n = 94). Hepatitis C virus (HCV) and HIV-coinfected patients at CDC stages I and II showed markedly lower selenium concentrations compared to HIV-infected patients without concomitant HCV-infection. Serum selenium and GSH-Px activity in hospitalized AIDS patients was significantly lower as compared to asymptomatic patients and healthy subjects, whereas plasma SH and GSH concentrations were lower in both, asymptomatic -and AIDS-patients, than in the controls. CONCLUSION: The results show that stages I-III of HIV-disease are characterized by significant impairments of antioxidative defenses provided by selenium, GSH-Px, SH-groups and GSH.
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Eritrocitos/enzimología , Glutatión Peroxidasa/sangre , Glutatión/sangre , Infecciones por VIH/sangre , VIH-1 , Selenio/sangre , Adulto , Anciano , Antioxidantes/análisis , Antioxidantes/metabolismo , Femenino , Glutatión Peroxidasa/análisis , Humanos , Masculino , Persona de Mediana Edad , Espectrofotometría Atómica , Compuestos de Sulfhidrilo/sangreRESUMEN
The interaction between calmodulin and iodothyronines and the effect of iodothyronines on the calmodulin activation of cyclic AMP phosphodiesterase were investigated. Binding of [L-125I]triiodothyronine to calmodulin from pig brain, studied by equilibrium dialysis, was dependent on Ca2+, was saturable and reversible, with an apparent Kd of 2.79 microM and binding capacity of 0.5 nmol/20 micrograms of calmodulin L- and D-thyroxine, D-triiodothyronine and tetrac displaced [L-125I]triiodothyronine at concentrations of 8-10 microM; triac, 3,3'-diiodothyronine and reverse-triiodothyronine were weak displacers. In the presence of the antipsychotic drug trifluoperazine, binding decreased in a dose-related manner. Ultraviolet irradiation of calmodulin in the presence of trifluoperazine reduced the binding of [L-125I]triiodothyronine to calmodulin irreversibly. Calmodulin activation of cyclic AMP phosphodiesterase decreased when iodothyronines were bound to calmodulin; the calmodulin-L-triiodothyronine complex was the most active among the stereoisomers of thyroxine and triiodothyronine. These results suggest that, when triiodothyronine was bound to Ca2+-calmodulin, the activation of cyclic AMP phosphodiesterase by the latter is suppressed.
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3',5'-AMP Cíclico Fosfodiesterasas/metabolismo , Calmodulina/metabolismo , Hormonas Tiroideas/metabolismo , Triyodotironina/metabolismo , Animales , Encéfalo/metabolismo , Calmodulina/farmacología , Calmodulina/efectos de la radiación , Interacciones Farmacológicas , Activación Enzimática , Cinética , Unión Proteica , Relación Estructura-Actividad , Porcinos , Hormonas Tiroideas/farmacología , Trifluoperazina/farmacología , Triyodotironina/farmacología , Triyodotironina/efectos de la radiación , Rayos UltravioletaRESUMEN
Exposure of freshly isolated hepatocytes to phalloidin produced blebs on their surfaces: this phenomenon was time- and dose-dependent and irreversible. When hepatocytes were pretreated with somatostatin or with some of its synthetic analogues, formation of blebs was dramatically reduced. This cytoprotective effect was dose-dependent: the dose-response profiles enabled the determination of the CD50 values, i.e., the concentrations of analogues that yielded 50% cytoprotection. The analogues with sequences of amino acids in the retro form, compared to those in somatostatin-14, exhibited higher cytoprotection; the retro hexapeptide, cyclo(-Phe-Thr-Lys-D-Trp-Phe-D-Pro-), was 27 times more active than somatostatin-14. Specificity of cytoprotection was examined by pretreating hepatocytes with biologically active peptide hormones prior to exposure to phalloidin. On a molar basis, prolactin and thyroid-stimulating hormone possessed activity comparable to that of somatostatin-14, whereas glucagon was twice as active. Insulin, vitamin A and propranolol exercised less than 10% protection. The synthetic analogues of somatostatin are potent protective agents against cell lesions induced by phalloidin. Formation of blebs on hepatocytes by toxins and their prevention by agents of interest may serve as a suitable morphological assay for screening of cytotoxicity and cytoprotection.