In geriatric patients with weight loss or low body weight MA improves appetite and well-being after 12 weeks of treatment. During the 3 months of MA treatment, there was no statistically significant weight gain (> or =4 lbs). Three months after treatment, weight gain (> or =4 lbs) was significantly increased in MA-treated patients.

No abstract

Proton secretion in the urinary bladder of the fresh-water turtle is mediated by proton pumps located in the apical membrane of carbonic-anhydrase (CA)-rich cells. It has been proposed that the rate of proton transport is regulated by endocytotic and exocytotic fusion processes which alter the apical membrane area, and hence number of exposed pumps. Three techniques were used to study this process. Analyses of transepithelial impedance provided estimates of transport-associated changes in net membrane area, as well as other electrical parameters. Electron microscopy allowed visualization of the endocytotic vesicles thought to be involved in the process. Finally, uptake of a fluorescent fluid-phase marker provided measurements of the rates of endocytosis. We report the following: endocytotic and exocytotic processes occur primarily in the CA-rich cells; inhibition of proton transport resulting from 0.5 mM acetazolamide (AZ) results in a decrease in the apical membrane area of approximately 0.47 cm2/cm2 tissue; the apical membrane specific conductance of the CA-rich cells is approximately 220 microS/microF, and possibly represents a Cl- conductance that may function in counter-ion flow; the decline in transport following AZ is not directly proportional to the decline in apical membrane area, suggesting that changes in pump kinetics are also involved in the regulation of transport; the CA-rich cells exhibit a high rate of constitutive pinocytosis, and hence membrane shuttling, which appears to be independent of the rate of transport; AZ induces a transient increase in the rates of endocytosis and shuttling; and the transport-associated changes in apical membrane area may reflect an effect of AZ on a regulated endocytotic pathway which is distinct from the pinocytotic process.

Equivalent-circuit impedance analysis experiments were performed on the urinary bladders of freshwater turtles in order to quantify membrane ionic conductances and areas, and to investigate how changes in these parameters are associated with changes in the rate of proton secretion in this tissue. In all experiments, sodium reabsorption was inhibited thereby unmasking the electrogenic proton secretion process. We report the following: transepithelial impedance is represented exceptionally well by a simple equivalent-circuit model, which results in estimates of the apical and basolateral membrane ionic conductances and capacitances; when sodium transport is inhibited with mucosal amiloride and serosal ouabain, the apical and basolateral membrane conductances and capacitances exhibit a continual decline with time; this decline in the membrane parameters is most likely caused by subtle time-dependent changes in cell volume, resulting in changes in the areas of the apical and basolateral membranes; stable membrane parameters are obtained if the tissue is not treated with ouabain, and if the oncotic pressure of the serosal solution is increased by the addition of 2% albumin; inhibition of proton secretion using acetazolamide in CO2 and HCO3- -free bathing solutions results in a decrease in the area of the apical membrane, with no significant change in its specific conductance; stimulation of proton transport with CO2 and HCO3- -containing serosal solution results in an increase in the apical membrane area and specific conductance. These results show that our methods can be used to measure changes in the membrane electrophysiological parameters that are related to changes in the rate of proton transport. Notably, they can be used to quantify in the live tissue, changes in membrane area resulting from changes in the net rates of endocytosis and exocytosis which are postulated to be intimately involved in the regulation of proton transport.

Adverse proton electrochemical gradients (delta muH) applied across the turtle urinary bladder decrease active H+ transport in this epithelium. A delta muH of 180 mV abolishes both transport and its tightly coupled metabolic reaction. Larger gradients should, in theory, reverse the direction of H+ transport and the metabolic reaction leading to synthesis of ATP if the pump is an ATPase, or cause an increase in the oxidized state of a redox pair if it is a redox pump. To distinguish between these two possibilities, we measured ATP levels in epithelial cells that were poisoned to inhibit cellular mechanisms of ATP synthesis. At delta muH of 120 mV or less no ATP synthesis was found. At delta muH of greater than 120 mV there was a linear increase in ATP synthesis. Dinitrophenol, a H+ carrier, prevented synthesis at delta muH of 310 mV. Dicyclohexylcarbodiimide, an inhibitor of H+ transport that works at the cell surface, prevented ATP synthesis at delta muH of 310 mV. These results demonstrate that a reversible proton-translocating ATPase in the mucosal border of the bladder is the H+ pump responsible for urinary acidification.