Modular kinetic analysis of the adenine nucleotide translocator-mediated effects of palmitoyl-CoA on the oxidative phosphorylation in isolated rat liver mitochondria

To test whether long-chain fatty acyl-CoA esters link obesity with type 2 diabetes through inhibition of the mitochondrial adenine nucleotide translocator, we applied a system-biology approach, dual modular kinetic analysis, with mitochondrial membrane potential (Deltapsi) and the fraction of matrix ATP as intermediates. We found that 5 mumol/l palmitoyl-CoA inhibited adenine nucleotide translocator, without direct effect on other components of oxidative phosphorylation. Indirect effects depended on how oxidative phosphorylation was regulated. When the electron donor and phosphate acceptor were in excess, and the mitochondrial "work" flux was allowed to vary, palmitoyl-CoA decreased phosphorylation flux by 38% and the fraction of ATP in the medium by 39%. Deltapsi increased by 15 mV, and the fraction of matrix ATP increased by 46%. Palmitoyl-CoA had a stronger effect when the flux through the mitochondrial electron transfer chain was maintained constant: Deltapsi increased by 27 mV, and the fraction of matrix ATP increased 2.6 times. When oxidative phosphorylation flux was kept constant by adjusting the rate using hexokinase, Deltapsi and the fraction of ATP were not affected. Palmitoyl-CoA increased the extramitochondrial AMP concentration significantly. The effects of palmitoyl-CoA in our model system support the proposed mechanism linking obesity and type 2 diabetes through an effect on adenine nucleotide translocator.     

Monovalent cation-dependent histamine release from rat peritoneal mast cells by ionophore X537A

Conclusions The results indicate that X537A exerts its histamine-releasing action only in the presence of monovalent cations. The release is not dependent on either extra- or intracellular calcium, in fact extracellular calcium depressed the release. The finding that the release occurred faster in a potassium medium indicates that high potassium increased the permeability of the plasma membrane for X537A or that X537A carries potassium more efficiently over the cell membrane as compared to sodium, in spite of the finding that the affinity of X537A is of the same order for both cations [5]. According to the latter possiblity, monovalent cations would accumulate in the cell and be available for exchange with histamine bound to the granular matrix. Furthermore, the observation that lack of cellular metabolic energy slows down the release process might indicate that metabolic energy influences the penetration of X537A at limiting concentrations. The slow release of histamine induced by X537A in comparison to many calcium- and energy-dependent releasing agents further indicates a different type of mechanism for release.     

Successful treatment of acrodermatitis continua of Hallopeau with sequential combination of calcipotriol and tacrolimus ointments

Acrodermatitis continua of Hallopeau (ACH) is a rare type of pustular psoriasis affecting the digits. We report on a 43-year-old female patient who had been suffering from ACH for more than 20 years. Despite the fact that the disease was localized on one finger during the whole period, several topical and systemic treatments resulted in only temporary or partial improvement of the lesion. Although the monotherapies with calcipotriol and tacrolimus ointments gave no satisfying results in the long-term management of the disease, the combination of both agents led to a continuous improvement of the patient's skin condition.     

Leading by example: a local health department-community collaboration to incorporate physical activity into organizational practice.

A multisectoral model promoting sociocultural environmental change to increase physical activity levels among African Americans in Los Angeles County, California, was developed and implemented. This model represents a true collaboration between a local health department and a community lead agency. Community organizations serving targeted areas of the county participated in one or more interventions incorporating physical activity into routine organizational practice, which centered around modeling the behaviors promoted ("walking the talk"). In the current study, level of organizational support for physical activity integration was assessed, as reflected in the extent of organizational commitment associated with each intervention. Individual-level data, characterizing the sociodemography, health status, and health behaviors of organization staff, members, and clients, are presented to document the average risk burden in the targeted population. Nearly half of the more than 200 participating organizations actively embraced incorporating physical activity into their regular work routines, with more than 25 percent committed at the highest level of involvement. Broad capacity and support for organizational integration of physical activity was demonstrated, with the observed level of commitment varying by organization type. Similar to the successful evolution of tobacco control, some of the responsibility ("cost") for physical activity adoption and maintenance can and should be shifted from the individual to organizational entities, such as workplaces.     

Leukocyte alkaline phosphatase in newborn infants after delivery and in the puerperium.

Leukocyte alkaline phosphatase (LAP) activity increases progressively during pregnancy, returning to non-pregnant levels 6 weeks post-partum. This enzymatic activity is under the influence of placental steroid hormones, thus reflecting placental function. LAP activity is thus a reflection of the dynamic relations between estrogenic, progestational and corticoid activity during pregnancy. LAP activity was studied in 60 women and in their 61 newborn infants at delivery and during the first five days of the puerperium. The Kaplow cytochemical technique was employed. The average maternal LAP score as well as the average newborn infant LAP score was considerably higher than the LAP score of the normal adult. The level of the enzyme in the maternal granulocytes was significantly higher than that of the newborn (Tab. I). During the first five days after labor, there was progressive decrease in the LAP score in the maternal and the newborn blood; on the fifth day the LAP scores of both were only slightly above the normal adult score (Figs. 1, 2). An inverse relation between the LAP score and the birth weight of the infant was found (Tab. III). These results confirm the view that LAP activity in the fetus in utero, are dependent on placental steroid function. The lower LAP values in the newborn, as compared to those of the mother are probably dependent on the lower newborn hormone levels. The significance of the relation between LAP scores and the infants birth weight is not clear.