Role of apathy in the effectiveness of weight management programmes.

AIMS: Obesity, which is at epidemic proportions in the USA, is associated with a higher risk of several co-morbid diseases including, cardiovascular disease, cancer and sleep apnea. Weight loss and weight maintenance programmmes are difficult to sustain for long term. Mental health problems such as apathy may be a major factor in patients unsuccessful in adhering to weight loss programmes. We propose that treating apathy will result in better weight loss in obese patients. METHODS: This was a randomized prospective pilot study. Obese patients (n = 101) were randomized in a 1:2:2 ratio to either (i) standard nutrition counselling; or (ii) the Department of Veterans Affairs weight loss programme called 'motivate obese veterans everywhere ' (MOVE); or (iii) methylphenidate treatment plus the MOVE programme together. The intervention was for 6 months (26 weeks). RESULTS: For the within groups analysis, the absolute changes in weight (kg) are as follows, for MOVE (mean: -1.84; 95% confidence interval (CI): -4.56 to 0.87; p = 0.25), Methylphenidate (mean: -4.61; 95% CI: -7.90 to -1.33; p = 0.04), standard nutrition counselling (mean: -0.60; 95% CI: -2.59 to 1.39; p = 0.21), which indicates that although all three groups lost weight, only the methylphenidate group achieved statistical significance. The between group differences of the relative change in weight were not statistically different. The apathy evaluation score and the patient activation measure improved in all groups. CONCLUSION: Together these data suggest that treating apathy might be an important factor in the success of weight management programmes.

Phosphatidylserine efflux and intercellular fusion in a BeWo model of human villous cytotrophoblast.

Phosphatidylserine (PS) efflux characterizes cytotrophoblast apoptosis and differentiation. To evaluate whether PS externalization and intercellular fusion were secondary to apoptosis, BeWo cells were induced to differentiate by forskolin or undergo apoptosis by staurosporine. PS externalization was measured by FITC-annexin V binding, and intercellular fusion was quantified by counting nuclei in syncytial cells. During forskolin treatment, vanadate decreased PS efflux by 78.0 per cent from 68.0 [5.3] (mean [SD]) to 15.0 [8.8] Lum (x10(3)) (P<0.001), whereas Z-VAD-fmk had no effect (66.5 [7.3]). Vanadate decreased intercellular fusion from 78.1 per cent [4.1] fusion in uninhibited cultures to 23.4 per cent [2.5], compared with 10.0 per cent [1.7] in media alone. Z-VAD-fmk did not affect fusion (80.4 per cent [6.8]). Staurosporine induced PS efflux was not affected by vanadate (69.6 [5.5] Lum x10(3)), but was inhibited 87.8 per cent by Z-VAD-fmk; from 71.5 [6.2] to 8.7 [3.6] Lum (x10(3)) (P<0.001). Apoptosis was measured by the TUNEL and COMET assays, lamin B fragmentation, activation of procaspase 3, mitochondrial membrane potential, and release of mitochondrial cytochrome c and apoptosis inducing factor. There was no indication of apoptosis associated with differentiation. Thus, PS efflux and intercellular fusion occurred through a vanadate-sensitive mechanism that was independent of apoptosis.

Ferrous-iron induces lipid peroxidation with little damage to energy transduction in mitochondria.

Addition of ferrous sulfate, but not ferric chloride, in micromolar concentrations to rat liver mitochondria induced high rates of consumption of oxygen. The oxygen consumed was several times in excess of the reducing capacity of ferrous-iron (O:Fe ratios 5-8). This occurred in the absence of NADPH or any exogenous oxidizable substrate. The reaction terminated on oxidation of ferrous ions. Malondialdehyde (MDA), measured as thiobarbituric acid-reacting material, was produced indicating peroxidation of lipids. The ratio of O2:MDA was about 4:1. Pretreatment of mitochondria with ferrous sulfate decreased the rate of oxidation (state 3) with glutamate (+ malate) as the substrate by about 40% but caused little damage to energy transduction process as represented by ratios of ADP:O and respiratory control, as well as calcium-stimulated oxygen uptake and energy-dependent uptake of [45Ca]-calcium. Addition of succinate or ubiquinone decreased ferrous iron-induced lipid peroxidation in intact mitochondria. In frozen-thawed mitochondria, addition of succinate enhanced lipid peroxidation whereas ubiquinone had little effect. These results suggest that ferrous-iron can cause peroxidation of mitochondrial lipids without affecting the energy transduction systems, and that succinate and ubiquinone can offer protection from damage due to such ferrous-iron released from the stores within the cells.