Importance of medullary events in ammonium excretion: studies in acute respiratory and acute metabolic acidosis

The renal medulla can play an important role in acid excretion by modulating both hydrogen ion secretion in the medullary collecting duct and the medullary PNH3. The purpose of these experiments was to characterize the intrarenal events associated with ammonium excretion in acute acidosis. Cortical events were monitored in two ways: first, the rates of glutamine extraction and ammoniagenesis were assessed by measuring arteriovenous differences and the rate of renal blood flow; second, the biochemical response of the ammoniagenesis pathway was examined by measuring glutamate and 2-oxoglutarate, key renal cortical metabolites in this pathway. There were no significant differences noted in any of these cortical parameters between acute respiratory and metabolic acidosis. Despite a comparable twofold rise in ammonium excretion in both cases, the urine pH, PNH3, and the urine minus blood PCO2 difference (U-B PCO2) were lower during acute hypercapnia. In these experiments, the urine PCO2 was 34 mmHg (1 mmHg = 133.322 Pa) lower than that of the blood during acute respiratory acidosis while the U-B PCO2 was 5 +/- 3 mmHg in acute metabolic acidosis. Thus there were significant differences in medullary events during these two conditions. Although the urine pH is critical in determining ammonium excretion in certain circumstances, these results suggest that regional variations in the medullary PNH3 can modify this relationship.     

Palytoxin induces an increase in the cation conductance of red cells

Palytoxin (PTX), isolated from the marine soft coral Palythoa tuberculosa, increases the cation conductance of human red cell membranes. In the presence of 10(-10) M PTX and 10(-5) M DIDS, the membrane potential approximates the equilibrium potential for Na+ or K+ rather than Cl-. Even in the absence of DIDS, the Na+ and K+ conductances were greater than the Cl- conductance. The selectivity of the PTX-induced cation conductance is K+ greater than Rb+ greater than Cs+ greater than Na+ greater than Li+ much greater than choline+ greater than TEA+ much greater than Mg2+. Measurements of K+ efflux revealed two apparent sites for activation by PTX, one with a Kal of 0.05 nM and a maximum flux, nu max1, of 1.4 mol/liter of cells per h and another with a Ka2 of 98 nM and a nu max2 of 24 mol/liter of cells per h. These effects of PTX are completely blocked by external ouabain (300 microM) and prevented by internal vanadate (100 microM). When the PTX channels are open, the Na,K pumps do not catalyze ATP hydrolysis. Upon thorough washout of cells exposed to about five molecules of PTX/pump, the Na,K pump of these cells operates normally. Blockage of the positively charged NH2 terminus of PTX with a p-bromobenzoyl group reduces the potency of the compound to induce Na and K fluxes by at least a factor of 100, and to compete with the binding of [3H]ouabain by at least a factor of 10. These data are consistent with the conclusion that PTX binds reversibly to the Na,K pumps in the red cell membrane and opens a (10-pS) channel equally permeable to Na and K at or near each pump site.     

Distribution-free confidence intervals for a parameter of Wilcoxon-Mann-Whitney type for ordered categories and progressive censoring

Halperin, Gilbert, and Lachin (1987, Biometrics 43, 71-80) obtain confidence intervals for Pr(X less than Y) based on the two-sample Wilcoxon statistic for continuous data. Their approach is applied here to ordered categorical data and right-censored continuous data, using the generalization zeta = Pr(X less than Y) + 1/2Pr(X = Y) to account for ties. Deviations from nominal coverage probability for various sample sizes and values of zeta are obtained via simulation of either three or six ordered categories based on underlying Poisson or exponential distributions. The simulation results indicate that the proposed method performs quite well, and it is apparently superior to the approach of Hochberg (1981, Communications in Statistics--Theory and Methods A10, 1719-1732) for values of zeta far from 1/2.     

The effects of total lymphoid irradiation upon corneal vascularization in the rat following chemical cautery

The effect of total lymphoid irradiation (TLI), a form of radiotherapy known to suppress the number of circulating lymphocytes, on corneal neovascularization was assessed in rats. The corneas of TLI-treated rats were cauterized with silver/potassium nitrate one day after delivering gamma irradiation in five equal fractions (10 Gy total dose). Corneal neovascularization was assessed quantitatively by computerized image analysis in corneal flat preparations 4 days after corneal injury following perfusion of the circulation with India ink. TLI reduced the total leukocyte, lymphocyte, neutrophil, and platelet counts below preirradiation levels. The number of circulating lymphocytes was reduced more than neutrophils and platelets. TLI caused a predominance of cytotoxic/suppressor lymphocytes. Tissue examinations 4 days after TLI disclosed an absence of the thymus, as well as a markedly reduced number and size of lymph nodes. TLI rats had less corneal vascularization than nonirradiated controls. Our findings are consistent with the hypothesis that leukocytes play an important role in the pathogenesis of corneal angiogenesis following chemical cautery, but this study does not indicate how TLI suppresses corneal neovascularization.     

Parasites of bark beetles [Col.: Scolytidae] on pine and cypress in Israel

Ten species of hymenopterous parasites were reared from logs of pine and cypress, naturally infested with 5 species of bark beetles,viz., Orthotomicus erosus Woll.,Pityogenes calcaratus Eichh., andTomicus destruens Woll. — on pine;Phloeosinus armatus Reitt. andP. aubei Perris — on cypress, in Israel. The parasites were:Dendrosoter chaenopachoides Rusch,D. hartigii (Ratz.),D. middendorfi (Ratz.),D. protuberans Nees (Braconidae), Eurytoma morio Boheman (Eurytomidae), Cerocephala eccoptogastri Masi,Heydenia pretiosa F?rster,Metacolus unifasciatus F?rster,Rhaphitelus maculatus Walker andRoptrocerus xylophagorum (Ratz.) (Pteromalidae). The most common wereM. unifasciatus on pine and cypress,D. chaenopachoides andR. xylophagorum on pine, andD. protuberans on cypress, occurring in samples collected during most seasons. Less common wasE. morio, which was reared from both conifers.D. middendorfi was found on pine, and only during winter. The other species were found only occasionally.     

Misdiagnosing ventricular tachycardia in patients with underlying conduction disease and similar sinus and tachycardia morphologies.

Six patients presented with wide-complex tachycardias with QRS morphologies similar to those seen on their electrocardiograms that showed normal sinus rhythms. During normal sinus rhythm, each patient had an underlying intraventricular conduction abnormality or bundle branch block. Despite the similarity of the QRS complexes to those seen during sinus rhythm, the tachycardias subsequently proved to be ventricular in origin in each patient. It is important not to misdiagnose these disorders as supraventricular tachycardia as an erroneous diagnosis may result in inappropriate management.     

Effect of glutamate on the control of fatty-acid synthesis in white adipose tissue of the rat. Inhibition of pyruvate dehydrogenase.

Glutamate (5mM) inhibited glucose conversion to fatty acids by approximately one-third in adipocytes from fed rats. This inhibition was significantly less in the pressence of pyruvate or 2-oxoglutarate. After incubation of adipose tissue from fed rats with glucose and insulin, pyruvate dehydrogenase activity was 180 plus or minus 17 mU/g wet weight. Addition of glutamine to the incubation medium decreased this activity significantly (118 plus or minus 14 mU/g wet weight). This inhibition by glutamate was also diminished when 2-oxoglutarate or pyruvate were present. Glutamate added to homohentates of adipose tissue had no effect on the activation of pyruvate dehydrogenase by Mg-2+. However, glutamate inhibited the active form of the enzyme and enhanced the rate of inactivation of the enzyme complex by ATP and Mg-2+. Aminooxyacetate, a transaminase inhibitor, did not reverse the effects of glutamate on pyruvate dehydrogenase nor fatty acid synthesis.     

Studies on the conversion of pyruvate into fatty acids in white adipose tissue. Effects of insulin, alloxan-diabetes and starvation

The effect of insulin on the conversion of pyruvate into fatty acids in the presence and in the absence of glucose was studied in epididymal adipose tissue of the rat. 1. In adipose tissue from the normal rat, conversion of pyruvate into fatty acids is directly related to its concentration, the maximal rates occurring with 40mm- and the half-maximal rates with approx. 4mm-pyruvate. Insulin treatment did not greatly influence the maximal rates, but the half-maximal rates were at much lower pyruvate concentrations. This effect of insulin could be seen with physiological concentrations of this hormone (50-100muunits/ml). 2. In adipose tissue from acute-alloxan-diabetic and 36h-starved rats the conversion of pyruvate into fatty acids was almost zero until its concentration exceeded 3mm and then increased markedly as the concentration of pyruvate was increased. The lag phase of this S-shaped curve was decreased but not eliminated when insulin was present. This could account for the very low rates of glucose conversion into fatty acids in these metabolic states. Maximum rates of fatty acid synthesis were similar in the presence and in the absence of insulin, but only when 30-40mm-pyruvate was employed. Re-feeding of the starved rats or insulin treatment of the diabetic rats in vivo for several days restored these patterns to normal.     

Lactic acidosis and ketoacidosis: biochemical and clinical implications.

A case of lactic acidosis presented the opportunity for review of the association between lactic acidosis and ketoacidosis. The diagnosis of lactic acidosis or the combination of lactic acidosis and ketoacidosis is established clinically by the detection of a metabolic acidosis of the "unmeasured anion gap" type in the absence of significant renal failure, poison intake or a strongly positive clinical test for ketones. Before treatment can be planned the biochemical basis of lactic acidosis and ketoacidosis must be understood -- especially the fact that lactic acidosis is not a single disease entity but has many possible causes. Among important considerations is the relation between the blood concentrations of bicarbonate and organic acid anions. After recovery from metabolic acidosis of the unmeasured anion gap type, metabolic alkalosis is common. Decreased bicarbonate excretion plays an important role in the pathogenesis of the latter and may be the result of potassium or chloride loss, or both. The deficits, if present, should be corrected with appropriate therapy.