Effects of a carbohydrate-restricted diet on emerging plasma markers for cardiovascular disease

BACKGROUND: Increasing evidence supports carbohydrate restricted diets (CRD) for weight loss and improvement in traditional markers for cardiovascular disease (CVD); less is known regarding emerging CVD risk factors. We previously reported that a weight loss intervention based on a CRD (% carbohydrate:fat:protein = 13:60:27) led to a mean weight loss of 7.5 kg and a 20% reduction of abdominal fat in 29 overweight men. This group showed reduction in plasma LDL-cholesterol and triglycerides and elevations in HDL-cholesterol as well as reductions in large and medium VLDL particles and increases in LDL particle size. In this study we report on the effect of this intervention with and without fiber supplementation on plasma homocysteine, lipoprotein (a) [Lp(a)], C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). METHODS: Twenty nine overweight men [body mass index (BMI) 25–35 kg/m(2)] aged 20–69 years consumed an ad libitum CRD (% carbohydrate:fat:protein = 13:60:27) including a standard multivitamin every other day for 12 wk. Subjects were matched by age and BMI and randomly assigned to consume 3 g/d of either a soluble fiber supplement (n = 14) or placebo (n = 15). RESULTS: There were no group or interaction (fiber × time) main effects, but significant time effects were observed for several variables. Energy intake was spontaneously reduced (-30.5%). This was accompanied by an increase in protein intake (96.2 ± 29.8 g/d to 107.3 ± 29.7 g/d) and methionine intake (2.25 ± 0.7 g/d, to 2.71 ± 0.78 g/d; P < 0.001). Trans fatty acid intake was significantly reduced (-38.6%) while dietary folate was unchanged, as was plasma homocysteine. Bodyweight (-7.5 ± 2.5 kg) was reduced as was plasma Lp(a) (-11.3%). Changes in plasma Lp(a) correlated with reductions in LDL-cholesterol (r = .436, P < 0.05) and fat loss (r = .385, P < 0,05). At wk 12, both CRP (-8.1%) and TNF-α (-9.3%) were reduced (P < 0.05) independently of weight loss. IL-6 concentrations were unchanged. CONCLUSION: A diet based on restricting carbohydrates leads to spontaneous caloric reduction and subsequent improvement in emerging markers of CVD in overweight/obese men who are otherwise healthy

Regulation of Peripheral Nerve Regeneration by the mTOR Pathway

From the Washington University Senior Honors Thesis Abstracts (WUSHTA), Volume 2, Spring 2010. Published by the Office of Undergraduate Research. Henry Biggs, Director, Office of Undergraduate Research / Associate Dean, College of Arts & Sciences; Joy Zalis Kiefer, Undergraduate Research Coordinator / Assistant Dean in the College of Arts & Sciences; E. Holly Tasker, Editor. Mentor: Valeria Cavall

Phase II Study of the Antibody Drug Conjugate Trastuzumab-DM1 for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2) –Positive Breast Cancer After Prior HER2-Directed Therapy

Purpose The antibody-drug conjugate trastuzumab-DM1 (T-DM1) combines the biologic activity of trastuzumab with targeted delivery of a potent antimicrotubule agent, DM1, to human epidermal growth factor receptor 2 (HER2) –overexpressing cancer cells. Based on results from a phase I study that showed T-DM1 was well tolerated at the maximum-tolerated dose of 3.6 mg/kg every 3 weeks, with evidence of efficacy, in patients with HER2-positive metastatic breast cancer (MBC) who were previously treated with trastuzumab, we conducted a phase II study to further define the safety and efficacy of T-DM1 in this patient population. Patients and Methods This report describes a single-arm phase II study (TDM4258g) that assessed efficacy and safety of intravenous T-DM1 (3.6 mg/kg every 3 weeks) in patients with HER2-positive MBC who had tumor progression after prior treatment with HER2-directed therapy and who had received prior chemotherapy. Results With a follow-up of ≥ 12 months among 112 treated patients, the objective response rate by independent assessment was 25.9% (95% CI, 18.4% to 34.4%). Median duration of response was not reached as a result of insufficient events (lower limit of 95% CI, 6.2 months), and median progression-free survival time was 4.6 months (95% CI, 3.9 to 8.6 months). The response rates were higher among patients with confirmed HER2-positive tumors (immunohistochemistry 3+ or fluorescent in situ hybridization positive) by retrospective central testing (n = 74). Higher response rates were also observed in patients whose tumors expressed ≥ median HER2 levels by quantitative reverse transcriptase polymerase chain reaction for HER2 expression, compared with patients who had less than median HER2 levels. T-DM1 was well tolerated with no dose-limiting cardiotoxicity. Most adverse events (AEs) were grade 1 or 2; the most frequent grade ≥ 3 AEs were hypokalemia (8.9%), thrombocytopenia (8.0%), and fatigue (4.5%). Conclusion T-DM1 has robust single-agent activity in patients with heavily pretreated, HER2-positive MBC and is well tolerated at the recommended phase II dose