Vitamin E inhibits lipid peroxidation-induced adhesion molecule expression in endothelial cells and decreases soluble cell adhesion molecules in healthy subjects

OBJECTIVE: In a combination of in vivo and in vitro studies, we investigated mechanisms via which alpha-tocopherol, a lipid soluble form of vitamin E, can directly affect endothelial activation as induced by H(2)O(2) and TNFalpha. METHODS: We measured effects of alpha-tocopherol on H(2)O(2)-induced lipid peroxidation as determined with a fluorescent C-11 BODIPY(581/591) probe and on adhesion molecule expression in cultured endothelial cells. In 20 healthy volunteers treated with increasing doses of alpha-tocopherol up to 800 IU/ml for 12 weeks, plasma levels of soluble cell adhesion molecules (sCAMs) and C-reactive protein were measured. RESULTS: We showed that alpha-tocopherol protects cultured endothelial cells against H(2)O(2)-induced lipid peroxidation, while TNFalpha did not induce lipid peroxidation. Moreover, alpha-tocopherol attenuated H(2)O(2)-, but not TNFalpha-induced increases in adhesion molecule expression. In healthy persons, alpha-tocopherol decreased plasma levels of sE-selectin from 65+/-6 to 60+/-6 ng/ml (P=0.002), sVCAM from 893+/-31 to 853+/-23 ng/ml (P=0.022), and sICAM from 483+/-21 to 463+/-16 ng/ml (P=0.048). C-Reactive protein, as a sensitive marker of low grade inflammation, was not significantly affected. CONCLUSION: alpha-Tocopherol specifically inhibits lipid peroxidation-induced endothelial activation in vitro. The observed vitamin E-induced decrease in sCAMs in control subjects suggests that lipid peroxidation can take place in healthy individuals. Although vitamin E supplementation may be especially effective in specific groups of patients exposed to increased oxidative stress, our study suggests that vitamin E supplementation can be of benefit in healthy individuals as well.     

Resting energy expenditure in lung and colon cancer

Elevated resting energy expenditure (REE) is a possible mechanism of cancer cachexia. We measured REE by whole-body direct calorimetry in patients with colon and non-small cell lung cancer and compared the results with REE in groups of healthy subjects and in patients with anorexia nervosa, with nonmalignant gastrointestinal (GI) disease, with miscellaneous reasons for weight loss, and with chronic lung disease. The mean REE of the cancer patients was not different from healthy subjects, those with GI disease, miscellaneous causes of cachexia, and chronic lung disease, and there was no significant difference in REE between those cancer patients with weight loss and controls with weight loss, except for the anorexia nervosa patients. The REE of the anorexia nervosa patients (female) was significantly lower than the REE of females with lung cancer. Weight loss correlated with REE in female lung cancer patients. Serial comparison of REE of ten cancer patients who lost 5% to 18% of their body weight during study showed no consistent change in REE. We conclude that patients with colon and non-small cell lung cancer, including those with weight loss, have REE similar to normal controls. Relative hypermetabolism may contribute to cancer cachexia, as may absolute hypermetabolism in some subsets of cancer patients.     

Association between HLA-D region antigens and disease-free survival in childhood non-T, non-B acute lymphocytic leukemia

The frequency of three serologically defined HLA-D region antigens--DR, MB, and MT--was determined in a group of 74 children with non-T, non-B acute lymphocytic leukemia (ALL). Statistically, there were no significant differences in the frequency of any antigen in these ALL patients as compared with a panel of 85 normal controls. However, significant differences in HLA-DR frequencies were observed between patients who relapsed or who remained disease-free during a 30-mo period of chemotherapy. An increased incidence of relapse was associated with DR5, while disease-free remission during chemotherapy was associated with DR7. Life table analysis also demonstrated that DR5 was significantly associated with a decrease in disease-free survival in these patients. These data suggest that HLA-associated genetic factors may influence the responses of ALL patients to chemotherapy.     

Clonality in juvenile chronic myelogenous leukemia

Juvenile chronic myelogenous leukemia (JCML) is a myeloproliferative disease in which morbidity and mortality are primarily caused by nonhematopoietic organ failure from myelomonocytic infiltration or by failure of the normal bone marrow. Morphologic evidence of maturation arrest, karyotypic abnormalities, and progression to blast crisis are infrequent events. Viral infections and other reactive processes can initially mimic the clinical course of JCML, creating diagnostic problems. Because of the rarity of JCML and technical limitations, formal clonality studies have not been reported previously. Nine female JCML patients were identified by clinical criteria, characteristic 'spontaneous' in vitro cell growth, and negative cultures and titers for various viral agents. Peripheral blood and bone marrow samples were obtained at the time of diagnosis for cell separation and RNA and DNA isolation. To assess clonality, X-chromosome inactivation patterns were evaluated using three different, recently developed polymerase chain reaction-based clonality assays. All nine female JCML patients showed evidence for monoclonal origin of mononuclear cells at the time of diagnosis. Cell separation studies further traced the monoclonal origin back to at least the most primitive myeloid progenitor cell. Reversion to a polyclonal state was demonstrated after bone marrow transplant and also in one patient following treatment with 13-cis retinoic acid. This demonstration of clonality in JCML delineates it from the reactive processes and provides a basis for molecular genetic strategies to identify causally associated mutations.     

Shortening of paced QRS duration after electrocardiographic optimization of left ventricular pacing vector in patients treated with Cardiac Resynchronization Therapy

Background

Choice of left ventricular pacing vector (LVPV) affects the QRS-duration (QRSd) in patients with Cardiac Resynchronization Therapy (CRT). It is not known whether testing all LVPVs reduces QRSd compared to device-based “standard-programming”.

Superiority of Step-up Approach vs Open Necrosectomy in Long-term Follow-up of Patients With Necrotizing Pancreatitis

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