Exercise training alters skeletal muscle microvascular endothelial cell properties in recent postmenopausal females.

The present study examined and compared the impact of exercise training on redox and molecular properties of human microvascular endothelial cells derived from skeletal muscle biopsies from sedentary recent (RPF, ≤ 5 years as postmenopausal) and late (LPF, ≥ 10 years as postmenopausal) postmenopausal females. Resting skeletal muscle biopsies were obtained before and after 8 weeks of intense aerobic exercise training for isolation of microvascular endothelial cells and determination of skeletal muscle angiogenic proteins and capillarisation. The microvascular endothelial cells were analysed for mitochondrial respiration and production of reactive oxygen species (ROS), glycolysis and proteins related to vascular function, redox balance and oestrogen receptors. Exercise training led to a reduced endothelial cell ROS formation (∼50%; P = 0.009 and P = 0.020 for intact and permeabilized cells (state 3), respectively) in RPF only, with no effect on endothelial mitochondrial capacity in either group. Basal endothelial cell lactate formation was higher (7%; P = 0.028), indicating increased glycolysis, after compared to before the exercise training period in RPF only. Baseline endothelial G protein-coupled oestrogen receptor (P = 0.028) and muscle capillarisation (P = 0.028) was lower in LPF than in RPF. Muscle vascular endothelial growth factor protein was higher (32%; P = 0.002) following exercise training in LPF only. Exercise training did not influence endothelial cell proliferation or skeletal muscle capillarisation in either group, but the CD31 level in the muscle tissue, indicating endothelial cell content, was higher (>50%; P < 0.05) in both groups. In conclusion, 8 weeks of intense aerobic exercise training reduces ROS formation and enhances glycolysis in microvascular endothelial cells from RPF but does not induce skeletal muscle angiogenesis. KEY POINTS: Late postmenopausal females have been reported to achieve limited vascular adaptations to exercise training. There is a paucity of data on the effect of exercise training on isolated skeletal muscle microvascular endothelial cells (MMECs). In this study the formation of reactive oxygen species in MMECs was reduced and glycolysis increased after 8 weeks of aerobic exercise training in recent but not late postmenopausal females. Late postmenopausal females had lower levels of G protein-coupled oestrogen receptor in MMECs and lower skeletal muscle capillary density at baseline. Eight weeks of intense exercise training altered MMEC properties but did not induce skeletal muscle angiogenesis in postmenopausal females.

Increased resting energy expenditure in children with attention-deficit-hyperactivity disorder.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most frequently reported neuropsychiatric disorders in childhood. However, there is limited data on the biological basis for this disorder. Disturbances in neurotransmitters have been suggested to play a pathophysiologic role. Phenotypically an increased prevalence of obesity has been reported. OBJECTIVE: To investigate resting energy expenditure (REE) and diet-induced thermogenesis in stimulant medication-naïve children with ADHD. DESIGN: Case control study of 12 pre-pubertal boys with ADHD of the hyperactive-impulsive type and 12 control boys without ADHD. Anthropometric testing and indirect calorimetry were performed before and after a standardized meal. REE and thermogenesis were measured in each subject at 2 time points. In an independent group of 60 boys with ADHD, BMI standard deviation scores (BMI-SDS) were compared to age-adapted reference values. RESULTS: REE was on average 6.5 kcal/kg fat free mass/day higher in the ADHD compared to the control group (p<0.01). In contrast, the thermogenic effect of food was not different between the two groups (average increase by 16%, p=n.s.). The repeat measurements, an average of 5±1 months apart, were highly reproducible in all subjects. Age and restlessness did not explain the differences in REE. Boys with ADHD had similar BMI-SDS values (mean BMI-SDS -0.10±0.98) as reference groups. CONCLUSIONS: REE, in contrast to diet-induced thermogenesis, is higher in medication-naïve boys with ADHD. The normal BMI levels suggest increased energy intake in these children.

Latitudinal effect of vegetation on erosion rates identified along western South America.

Vegetation influences erosion by stabilizing hillslopes and accelerating weathering, thereby providing a link between the biosphere and Earth's surface. Previous studies investigating vegetation effects on erosion have proved challenging owing to poorly understood interactions between vegetation and other factors, such as precipitation and surface processes. We address these complexities along 3500 kilometers of the extreme climate and vegetation gradient of the Andean Western Cordillera (6°S to 36°S latitude) using 86 cosmogenic radionuclide-derived, millennial time scale erosion rates and multivariate statistics. We identify a bidirectional response to vegetation's influence on erosion whereby correlations between vegetation cover and erosion range from negative (dry, sparsely vegetated settings) to positive (wetter, more vegetated settings). These observations result from competing interactions between precipitation and vegetation on erosion in each setting.

Quantifying landslide frequency and sediment residence time in the Nepal Himalaya.

Quantifying how Earth surface processes interact with climate, tectonics, and biota has proven challenging, in part due to the stochastic nature of erosion and sedimentation. Landsliding is a common stochastic erosional process that may account for >50% of the sediment produced in steep mountainous landscapes. Here, we calculate the effects of landsliding and the residence time of sediment in a steep drainage basin in the Nepal Himalaya using a numerical model of landslide erosion combined with published cooling age distributions from two river sediment samples collected several years apart. We find that the difference in the two samples can be explained by landsliding and that the age distributions suggest that the residence time of sediment in the catchment is no greater than 50 years. This sensitivity to landsliding thus offers potential to improve our understanding of stochastic erosional processes, and further suggests that sediment is rapidly evacuated from steep mountainous drainage basins.

Antiangiogenic agents: studies on fumagillin and curcumin analogs.

Cancer is a general term used to describe many disease states, each of which are characterized by abnormal cell proliferation. The causes which bring about this abnormal cellular behavior are specific to each type of cancer. The success of tumor-targeted therapy is limited by this diversity. One common denominator for all types of cancer is the requirement of a suitable blood supply. Therefore, tumor vasculature has emerged as a potential target for therapeutic intervention. New blood vessel growth from preexisting vasculature stimulated by biochemical signals is termed angiogenesis. Tumor masses require a constant supply of oxygen and nutrients, and a means of efficient waste removal to ensure sustained development. Diffusion from nearby capillaries can supply adequate nutrition for tumors less than 2 mm in size, but for continued growth the tumors must develop their own blood supply. Alteration of the delicate balance of angiogenic stimulating factors and angiogenic inhibitors results in the phenotypic change from quiescence to active endothelial proliferation. To date, this angiogenic switch is not completely understood. The goal of antiangiogenic therapy is to interfere with these mechanisms and prevent tumor cells from developing a viable blood supply. Fumagillin is a naturally occurring antifungal agent. Curcumin is a natural product isolated from the spice turmeric. Both compounds have been shown to have antiangiogenic properties in vitro and in vivo. This paper describes efforts to design and prepare fumagillin and curcumin analogs and evaluate their corresponding antiangiogenic activities.

Effects of the tetracyclic antidepressant pirlindole on sensorimotor performance and subjective condition in comparison to imipramine and during interaction of ethanol.

Two experiments were designed to investigate the side-effects on motor performance of the new tetracyclic antidepressant, pirlindole, in healthy volunteers. First, pirlindole was compared with imipramine and placebo. In the second study the interaction of pirlindole with a small amount of ethanol (0.4 g 17 vol%/kg) was analysed. Ratings of subjective feelings and measurements of sensorimotor performance (simple and choice reaction, tracking) of the pirlindole-treated group did not differ from those of the placebo group, whereas imipramine caused a change of the subjective condition to more lethargy and a greater delay of the simple reaction time. The effects of pirlindole proved to be unaffected by ethanol.

Proteoglycan synthesis by fibroblasts from different regions of bovine tendon cultured in alginate beads.

The ability of cell shape to modulate proteoglycan synthesis in tendon fibroblasts was investigated by placing freshly isolated tendon fibroblasts and chondrocytes into primary culture either as adherent cells on a polystyrene substratum or as rounded cells in alginate beads. Chondrocytes and cells from the compressed region of adult tendon synthesized predominantly large proteoglycan when maintained either as dense monolayers, where actin stress fibers in the cytoskeleton were prominent, or in alginate beads, where actin fibers could not be detected. After three rounds of proliferation as elongated adherent cells the synthesis of large proteoglycan was greatly reduced, i.e. the chondrocytic cells underwent 'dedifferentiation'. Cells from the tensional region of adult tendon synthesized predominantly small proteoglycan when in primary culture as a monolayer, after proliferation on a flat substratum, or as round cells in alginate beads. Fibroblasts from the tensional region of newborn tendon showed no tendency toward increased synthesis of large proteoglycan when maintained as round cells in alginate beads for 7 weeks. In tendon there appears to be a mechanically induced developmental transition from fibroblastic to chondrocytic cells. However, neither the change to a rounded cell shape nor the lack of organized cytoskeletal actin fibers was sufficient to induce chondrocyte-like proteoglycan synthesis in differentiated tendon fibroblasts in culture.