Effects of LDL-immunoapheresis on plasma concentrations of vitamin E and carotenoids in patients with familial hypercholesterolemia.

Recently very potent extracorporeal cholesterol-lowering treatment options have become available for patients with hypercholesterolemia. LDL immunoapheresis treatment selectively removes LDL and lipoprotein(a) from the circulation. Since LDL is the major carrier of lipophilic antioxidants in plasma, the purpose of the present study was to assess the effects of a single LDL apheresis treatment on plasma concentrations of tocopherols (alpha- and gamma-tocopherol) and carotenoids (alpha- and beta-carotene, zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, and retinol). Plasma antioxidant concentrations were determined by HPLC in 7 patients with familial hypercholesterolemia before and after LDL immunoapheresis treatment. Plasma concentrations of both alpha- and gamma-tocopherol and the different carotenoids were significantly reduced by LDL apheresis. However, when standardized for cholesterol to adjust for cholesterol removal, alpha- and gamma-tocopherol, retinol, and the more polar carotenoids lutein and zeaxanthin increased in response to apheresis treatment, while the more unpolar carotenoids such as beta-carotene and lycopene did not change. These data demonstrate that a single LDL immunoapheresis treatment affects tocopherols and individual carotenoids differently. This may be explained by differences in chemical structure and preferential association with different lipoproteins. These results further imply that tocopherols, lutein, zeaxanthin, and retinol, are associated in part with lipoproteins and other carriers such as retinol-binding protein that are not removed during apheresis treatment.

Plasma ghrelin in obesity before and after weight loss after laparoscopical adjustable gastric banding.

Weight reduction after gastric bypass surgery has been attributed to a decrease of the orexigenic peptide ghrelin, which may be regulated by insulin and leptin. This study examined effects of long-term weight loss after laparoscopical adjustable gastric banding on plasma ghrelin and leptin concentrations and their relationship with insulin action. Severely obese patients (15 women, three men, 36 +/- 12 yr) underwent clinical examinations every 3 months and modified oral glucose tolerance tests to assess parameters of insulin sensitivity and secretion every 6 months. After surgery, body mass index fell from 45.3 +/- 5.3 to 37.2 +/- 5.3 and 33.6 +/- 5.5 kg/m(2) at 6 and 12 months, respectively (P < 0.0001). This was associated with lower (P < 0.0001) plasma glucose, insulin, insulin resistance, waist circumference, and blood pressure. Plasma leptin decreased from 27.6 +/- 9.5 to 17.7 +/- 9.8 (P = 0.0005) and 12.7 +/- 5.1 ng/ml (P < 0.0001). Plasma ghrelin was comparable before and at 6 months (234 +/- 53; 232 +/- 53 pmol/liter) but increased at 12 months (261 +/- 72 pmol/liter; P = 0.05 vs. 6 months). At 6 and 12 months, ghrelin levels correlated negatively with fasting plasma insulin levels and hepatic insulin extraction but not with body mass or insulin action. In conclusion, prolonged weight loss results in a rise of fasting ghrelin concentrations that correlates with fasting insulin concentrations but not improvement of insulin sensitivity.

Improvement of insulin resistance and early atherosclerosis in patients after gastric banding.

OBJECTIVE: To evaluate the effect of massive weight loss on insulin sensitivity, soluble adhesion molecules, and markers of the insulin resistance syndrome (IRS). RESEARCH METHODS AND PROCEDURES: Eighteen morbidly obese patients underwent gastric banding and were evaluated before and 6 and 12 months after surgery. Total insulin secretion, hepatic insulin extraction, and insulin sensitivity were analyzed by oral glucose-tolerance test model analysis. In addition, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, leptin, high-sensitivity C-reactive protein, plasminogen activating factor-1 (PAI-1), and tissue plasminogen activator were measured. RESULTS: BMI dropped from 45.22 +/- 5.62 to 36.99 +/- 4.34 kg/m(2) after 6 months and 33.72 +/- 5.55 kg/m(2) after 12 months (both p < 0.0001). This intervention resulted in a significant reduction of blood pressure (p < 0.00001), triglycerides (p < 0.01), fasting blood glucose (p = 0.03), basal insulin (p < 0.001), and basal C-peptide (p = 0.008) levels. Total insulin secretion decreased (p < 0.05), whereas hepatic insulin extraction (p < 0.05) and oral glucose insulin sensitivity index (p < 0.0001) increased compared with baseline. Leptin (p < 0.0001) and E-selectin levels decreased significantly after 6 and 12 months (p = 0.05), whereas significantly lower levels of intercellular adhesion molecule-1 and PAI-1 were only seen after 6 months. Subclinical inflammation, measured by high-sensitivity C-reactive protein, was lowered to normal ranges. No changes were observed in vascular cell adhesion molecule-1 and tissue plasminogen activator levels. DISCUSSION: Although gastric banding ameliorates several features of the IRS, including 29.05% improvement in insulin sensitivity and blood pressure and reduction of soluble adhesion molecules and PAI-1, considerable weight loss did not normalize all components of the IRS in morbidly obese patients.

Effect of gastric banding on aminoterminal pro-brain natriuretic peptide in the morbidly obese.

OBJECTIVE: Aminoterminal pro-brain natriuretic peptide (NT-proBNP), like brain natriuretic peptide, might have diagnostic utility in detecting left ventricular hypertrophy and/or left ventricular dysfunction. The aim of the study was to investigate the relationship between morbid obesity and NT-proBNP and the effect of weight reduction on this parameter. RESEARCH METHODS AND PROCEDURES: A total of 34 morbidly obese patients underwent laparoscopic adjustable gastric banding (LAGB). NT-proBNP levels were measured before and 12 months after the surgery. RESULTS: Metabolic features and systolic and diastolic blood pressure were significantly decreased (p < 0.00001 for both) after a cumulative weight loss of 19.55 kg 1 year after LAGB. NT-proBNP concentration was significantly higher in morbidly obese patients before LAGB than in normal-weight control subjects (341.15 +/- 127.78 fmol/mL vs. 161.68 +/- 75.78 fmol/mL; p < 0.00001). After bariatric surgery, NT-proBNP concentration decreased significantly from 341.15 +/- 127.78 fmol/mL to 204.87 +/- 59.84 fmol/mL (p < 0.00001) and remained statistically significantly elevated (204.88 +/- 59.84 fmol/mL vs. 161.68 +/- 75.78 fmol/mL; p = 0.04) compared with normal-weight subjects. DISCUSSION: This investigation demonstrates higher levels of NT-proBNP in morbidly obese subjects and a significant decrease during weight loss after laparoscopic adjustable gastric banding. In obesity, NT-proBNP might be useful as a routine screening method for identifying left ventricular hypertrophy and/or left ventricular dysfunction.

Treatment of psoriatic arthritis and psoriasis vulgaris with the tumor necrosis factor inhibitor infliximab.

OBJECTIVE: The aim was to evaluate the efficacy and safety of multiple infusions with achimeric, anti-tumor necrosis factor (TNF)alpha monoclonal antibody (infliximab) in patients with psoriatic arthritis (PsA) and psoriasis vulgaris. METHODS: Over 22 weeks, nine patients with both active psoriasis and PsA received five infusions of 3 mg/kg infliximab. The endpoints included changes in the swollen and tender joints counts, American College of Rheumatology (ACR) preliminary criteria for improvement response rates 20, 50, and 70, and improvement in the psoriasis area and severity index (PASI). RESULTS: The swollen count (SJC) and tender joint count (TJC) fell from means of 5.33+/-2.22 and 17.80+/-4.21 to 1.44+/-1.09 and 9.77+/-0.92, respectively, by week 2 ( P=0.02, P=0.02). This benefit was sustained through week 22 (2.00+/-1.12/7.77+/-3.68, P=0.05/ P=0.002). The ACR 20/50/70 response was achieved in 89%/56%/22% of cases. The mean PASI score improved from 19.04+/-5.41 to 4.91+/-2.51 ( P=0.002). CONCLUSION: Multiple infusions of infliximab were effective and well tolerated in patients with active psoriasis and PsA.