In patients with HIV infection, total energy expenditure is reduced during episodes of weight loss. Reduced energy intake, not elevated energy expenditure, is the prime determinant of weight loss in HIV-associated wasting.

Chloride-dependent cation transport systems in a number of cells and tissues are inhibited by 5-sulfamoylbenzoic acid loop diuretics, such as furosemide and bumetanide. Interactions between chloride and bumetanide have been examined in the catecholamine-activated (Na + K + 2Cl) co-transport pathway of the duck red blood cell. Levels of chloride were varied while maintaining a constant ratio of internal to external chloride across the cell membrane. Increasing external chloride from 20 to 100 mM shifted the dose-response curve for the effect of bumetanide on co-transport toward higher concentrations of the drug. The bumetanide concentration producing half-maximal inhibition (IC50) was increased from approximately 6 X 10(-8) to approximately 2 X 10(-7) M. When cells were incubated in the presence of a constant, submaximal inhibitory dose of bumetanide (10(-8) M), increasing external chloride (in increments of 20 mM) from 20 to 140 mM progressively decreased the level of inhibition of the co-transport system. Kinetic analysis of the data demonstrates that bumetanide and chloride compete for a common site.

The transient increase in cation permeability observed in duck red cells incubated with norepinephrine has been shown to be a linked, bidirectional, co-transport of sodium plus potassium . This pathway, sensitive to loop diuretics such as furosemide, was found to have a [Na + K] stoichiometry of 1 :1 under all conditions tested . Net sodium efflux was inhibited by increasing external potassium, and net potassium efflux was inhibited by increasing external sodium . Thus, the movement of either cation is coupled to, and can be driven by, the gradient of its co-ion . There is no evidence of trans stimulation of cotransport by either cation . The system also has a specific anion requirement satisfied only by chloride or bromide . Shifting the membrane potential by varying either external chloride (at constant internal chloride) or external potassium (at constant internal potassium in the presence of valinomycin and DIDS [4,4'-diisothiocyano-2,2'-disulfonic acid stilbene]), has no effect on norepinephrine-stimulated net sodium transport . Thus, this co-transport system is unaffected by membrane potential and is therefore electrically neutral . Finally, under the latter conditions-when E,n was held constant near Ex and chloride was not at equilibrium-net sodium extrusion against a substantial electrochemical gradient could be produced by lowering external chloride at high internal concentrations, thereby demonstrating that the anion gradient can also drive co-transport . We conclude, therefore, that chloride participates directly in the co-transport of [Na + K + 2Cl] .

In the duck red blood cell, Na-K-2Cl cotransport exhibits two modes of ion movement: net cotransport and obligate cation exchange. In high-K cells, the predominant exchange is K/K (or K/Rb). In high-Na cells, it becomes Na/Na (or Na/Li). Both represent partial reactions in which a fully loaded carrier releases part of its cargo, rebinds fresh ions, and returns back across the membrane fully loaded. Net cotransport occurs when the carrier unloads completely and returns empty. This mode has a fixed stoichiometry of 1Na:1K:2Cl under all conditions tested. The ion requirements of the two exchanges differ: K/K exchange requires only K and Cl outside but all three ions inside. Na/Na exchange requires all three ions outside but only Na inside. We propose a simple model in which the carrier can only move when either fully loaded or completely empty and in which the ions bind in a strictly ordered sequence. For example, externally, a Na binds first and then a Cl, followed by a K and a second Cl. Internally, the first on is the first off (glide symmetry), so the Na is released first and then the first Cl, followed by the K and finally by the second Cl. Only then can the empty form return to the outside to start a new cycle.

Na-K-2Cl cotransporter (NKCC) and K-Cl cotransporter (KCC) play key roles in cell volume regulation and epithelial Cl(-) transport. Reductions in either cell volume or cytosolic Cl(-) concentration ([Cl(-)](i)) stimulate a corrective uptake of KCl and water via NKCC, whereas cell swelling triggers KCl loss via KCC. The dependence of these transporters on volume and [Cl(-)](i) was evaluated in model duck red blood cells. Replacement of [Cl(-)](i) with methanesulfonate elevated the volume set point at which NKCC activates and KCC inactivates. The set point was insensitive to cytosolic ionic strength. Reducing [Cl(-)](i) at a constant driving force for inward NKCC and outward KCC caused the cells to adopt the new set point volume. Phosphopeptide maps of NKCC indicated that activation by cell shrinkage or low [Cl(-)](i) is associated with phosphorylation of a similar constellation of Ser/Thr sites. Like shrinkage, reduction of [Cl(-)](i) accelerated NKCC phosphorylation after abrupt inhibition of the deactivating phosphatase with calyculin A in vivo, whereas [Cl(-)] had no specific effect on dephosphorylation in vitro. Our results indicate that NKCC and KCC are reciprocally regulated by a negative feedback system dually modulated by cell volume and [Cl(-)]. The major effect of Cl(-) on NKCC is exerted through the volume-sensitive kinase that phosphorylates the transport protein.

Incidents of nonconsensual sexual activity among 930 homosexually active men living in England and Wales are analyzed. Of these men, 27.6% said they had been sexually assaulted or had sex against their will at some point in their lives; one third had been forced into sexual activity (usually anal intercourse) by men with whom they had previously had, or were currently having, consensual sexual activity. The contention that male rape is usually committed by heterosexually identified men, primarily as an expression of power and control, is not supported. Recognition that gay men rape other gay men is needed, both by the gay community and support services for victims.

Weight loss is a major manifestation of infection with the human immunodeficiency virus (HIV). Prospective analysis of weight change was performed in 30 male subjects with stage IV HIV infection over a period of 9-49 mo and weight change events (> 4 kg) related to contemporaneous clinical events. Two distinct patterns of weight loss were observed: episodes of acute severe weight loss and episodes of chronic unremitting progressive weight loss. Thirty-three acute episodes (median 9.1 kg in 1.7 mo) and 23 chronic episodes (13.2 kg in 9.5 mo) were identified. Twenty-seven of 33 (82%) acute weight-loss episodes were associated with nongastrointestinal opportunistic infections and 15 of 23 (65%) chronic episodes with gastrointestinal disease (P < 0.01). Weight loss was neither inevitable nor unremitting. Periods of weight stability (> 4 mo) occurred in 13 individuals (43%); 35 episodes of weight gain were identified, mostly related to recovery from opportunistic infection. These findings have important implications for our understanding of the natural history of weight loss in HIV infection.

Duck red cells in hypertonic media experience rapid osmotic shrinkage followed by gradual reswelling back toward their original volume. This uptake of salt and water is self limiting and demands a specific ionic composition of the external solution. Although ouabain (10(-4)M) alters the pattern of cation accumulation from predominantly potassium to sodium, it does not affect the rate of the reaction, or the total amount of salt or water taken up. To study the response without the complications of active Na-K transport, ouabain was added to most incubations. All water accumulated by the cells can be accounted for by net salt uptake. Specific external cation requirements for reswelling include: sufficient sodium (more than 23 mM), and elevated potassium (more than 7 mM). In the absence of external potassium cells lose potassium without gaining sodium and continue to shrink instead of reswelling. Adding rubidium to the potassium- free solution promotes an even greater loss of cell potassium, yet causes swelling due to a net uptake of sodium and rubidium followed by chloride. The diuretic furosemide (10(-3)M) inhibits net sodium uptake which depends on potassium (or rubidium), as well as inhibits net sodium uptake which depends on sodium. As a result, cell volume is stabilized in the presence of this drug by inhibition of shrinkage, at low, and of swelling at high external potassium. The response has a high apparent energy of activation (15-20 kcal/mol). We propose that net salt and water movements in hypertonic solutions containing ouabain are mediated by direct coupling or cis-interaction, between sodium and potassium so that the uphill movement of one is driven by the downhill movement of the other in the same direction.