Neuromuscular preparations from third instar larvae of Drosophila are not well-maintained in commonly used physiological solutions: vacuoles form in the muscle fibers, and membrane potential declines. These problems may result from the Na:K ratio and total divalent cation content of these physiological solutions being quite different from those of haemolymph. Accordingly haemolymph-like solutions, based upon ion measurements of major cations, were developed and tested. Haemolymph-like solutions maintained the membrane potential at a relatively constant level, and prolonged the physiological life of the preparations. Synaptic transmission was well-maintained in haemolymph-like solutions, but the excitatory synaptic potentials had a slower time course and summated more effectively with repetitive stimulation, than in standard Drosophila solutions. Voltage-clamp experiments suggest that these effects are linked to more pronounced activation of muscle fiber membrane conductances in standard solutions, rather than to differences in passive muscle membrane properties or changes in postsynaptic receptor channel kinetics. Calcium dependence of transmitter release was steep in both standard and haemolymph-like solutions, but higher external calcium concentrations were required for a given level of release in haemolymph-like solutions. Thus, haemolymph-like solutions allow for prolonged, stable recording of synaptic transmission.

Improved stability of Drosophila larval neuromuscular preparations in haemolymph-like physiological solutions.

Young adult males who cannot produce or respond to estrogen (E) are osteopenic, suggesting that E may regulate bone turnover in men, as well as in women. Both bioavailable E and testosterone (T) decrease substantially in aging men, but it is unclear which deficiency is the more important factor contributing to the increased bone resorption and impaired bone formation that leads to their bone loss. Thus, we addressed this issue directly by eliminating endogenous T and E production in 59 elderly men (mean age 68 years), studying them first under conditions of physiologic T and E replacement and then assessing the impact on bone turnover of withdrawing both T and E, withdrawing only T, or only E, or continuing both. Bone resorption markers increased significantly in the absence of both hormones and were unchanged in men receiving both hormones. By two-factor ANOVA, E played the major role in preventing the increase in the bone resorption markers, whereas T had no significant effect. By contrast, serum osteocalcin, a bone formation marker, decreased in the absence of both hormones, and both E and T maintained osteocalcin levels. We conclude that in aging men, E is the dominant sex steroid regulating bone resorption, whereas both E and T are important in maintaining bone formation. J. Clin. Invest. 106:1553‐1560 (2000).

/pdf/relative-contributions-of-testosterone-and-estrogen-in-2affeeb2ub.pdf

Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men

Since it became clear that K+ shifts with exercise are extensive and can cause more than a doubling of the extracellular [K+] ([K+]s) as reviewed here, it has been suggested that these shifts may c...

https://www.physiology.org/doi/pdf/10.1152/physrev.2000.80.4.1411

Dynamics and Consequences of Potassium Shifts in Skeletal Muscle and Heart During Exercise

This review focuses on the more significant contributions to the understanding and use of ion-selective electrodes (ISE's). There is a strong interest in this field as over 1400 articles and abstracts were found during the writing of this review which covers the period from January 1986 through December 1987. The major analytical and electrochemical journals were read and a hand search of Chemical Abstracts uncovered the remaining articles. Unlike previous fundamental reviews, this paper will not attempt to list all the pertinent papers on ISE's. Rather, the more interesting works and applications are covered to illustrate examples of the general trends and directions of ISE interests.

Ion-Selective Electrodes.

In the circulation, testosterone and other sex hormones are bound to binding proteins, which play an important role in regulating their transport, distribution, metabolism, and biological activity. According to the free hormone hypothesis, which has been debated extensively, only the unbound or free fraction is biologically active in target tissues. Consequently, accurate determination of the partitioning of testosterone between bound and free fractions is central to our understanding of how its delivery to the target tissues and biological activity are regulated and consequently to the diagnosis and treatment of androgen disorders in men and women. Here, we present a historical perspective on the evolution of our understanding of the binding of testosterone to circulating binding proteins. On the basis of an appraisal of the literature as well as experimental data, we show that the assumptions of stoichiometry, binding dynamics, and the affinity of the prevailing models of testosterone binding to sex hormone-binding globulin and human serum albumin are not supported by published experimental data and are most likely inaccurate. This review offers some guiding principles for the application of free testosterone measurements in the diagnosis and treatment of patients with androgen disorders. The growing number of testosterone prescriptions and widely recognized problems with the direct measurement as well as the computation of free testosterone concentrations render this critical review timely and clinically relevant.

A Reappraisal of Testosterone's Binding in Circulation: Physiological and Clinical Implications.

The correlations between serum ionized calcium, serum total calcium, total calcium corrected for albumin and calculated ionized calcium were investigated in a prospective multicentre investigation of 1213 patients suspected of having calcium metabolic disease. Diagnostic discordance between serum total calcium and measured ionized calcium was found in 31% of the patients. With the calculation of albumin-corrected total calcium or calculated ionized calcium the discordance decreased to 17.9%. The diagnostic discordance which could be ascribed to the analytical imprecision (CV = 1.5%) amounted to only 6.7%. Although we found highly significant correlations between the parameters, a considerable scatter around the regression line made prediction of ionized calcium from albumin-corrected total calcium unreliable in many patients.

Comparison of serum total calcium, albumin-corrected total calcium, and ionized calcium in 1213 patients with suspected calcium disorders.

Transcutaneous carbon dioxide and oxygen tensions (tc-pCO2 and tc-pO2) were measured in seven healthy adult volunteers during hyperventilation in atmospheric air and during CO2 inhalation. Three skin sensors were applied to each subject: an O2 electrode, a CO2 electrode, and a combined O2-CO2 electrode, each heated to 44 degrees C. We observed close correlation between tc-pCO2 and capillary-pCO2, the relation being close to that calculated from the anaerobic temperature coefficient of pCO2 in blood. For O2, on the other hand, the relationship between transcutaneous and capillary values appeared more complex. Electrode drift during in-vivo monitoring was greater for pCO2 (up to 12%) than for pO2 (up to 7%), but generally we observed no differences in drift between the combined and the single electrodes. We conclude that tc-pCO2 measured with a single or a combined electrode reliably predicts capillary-pCO2 in healthy adults and that changes are rapidly observed. Our conclusions regarding tc-pO2 values are less definite because of uncertain interpretation of the capillary-pO2 values.

Transcutaneous and capillary pCO2 and pO2 measurements in healthy adults.

In an epidemiological study of 977 45-year-olds, both the mean concentration of ionized calcium in serum, [Ca2+]7.4, and arterial blood pressure were higher in men than in women. Among the men, there was a weak positive correlation between [Ca2+]7.4 and the systolic blood pressure, but no other significant correlation was found within each separate sex. Postmenopausal women had slightly increased [Ca2+]7.4 but normal blood pressure. Patients taking thiazide diuretics or beta-adrenergic blocking agents had normal [Ca2+]7.4.

Sex-dependent relation between ionized calcium in serum and blood pressure.

We report results for adjusted ionized calcium (at pH 7.4) and actual ionized calcium (at actual pH) in capillary blood from 183 patients with disorders of calcium metabolism (primary hyperparathyroidism, secondary hyperparathyroidism of malabsorption, primary hypoparathyroidism, Paget's disease, acromegaly, hypercalcemia of malignancy, osteoporosis, sarcoidosis, idiopathic hypercalciuria, and familial hypocalciuric hypercalcemia). The correlation and the equation for the linear regression between adjusted ionized calcium (y) and actual ionized calcium (x) were y = 1.011x + 0.005 mmol/L, r = 0.992, Sy,x = 0.021 mmol/L. Results were similar within each diagnostic group. Consistent agreement between adjusted and ionized calcium was observed in 96.7% of patients representing a variety of the most frequently encountered disorders of calcium metabolism. Thus we find adjusted ionized calcium to be as useful as actual ionized calcium for evaluation of patients with such disorders. Adjusted ionized calcium may therefore also be a logical choice for establishing agreement between laboratories for reference intervals in healthy adults.

Adjusted ionized calcium (at pH 7.4) and actual ionized calcium (at actual pH) in capillary blood compared for clinical evaluation of patients with disorders of calcium metabolism

We compared different sample-handling techniques for measurement of Na+ and K+ with ion-selective electrodes (ISE). Imprecision was less for venous blood (with a minimum of heparin) than for plasma, serum, or capillary blood. The results for K+ were higher for serum than for whole blood, and higher for whole blood than for plasma. The latter difference was apparently due to release of K+ during the analysis. Values were more stable for whole blood stored at 20 degrees C than at 4 degrees C or 37 degrees C. The molality of Na+ in the plasma of mixed whole blood changed by -10.5 mmol/kg per unit change in blood pH. This could be explained by the different H+ buffering capacities of plasma and erythrocyte fluid, because when the pH is changed, the concentration of small anions in erythrocytes changes more than it does in plasma, with a consequent osmotic movement of water across the erythrocyte membrane. When we took into account the residual liquid-junction potential and the mass concentration of water in each of 65 patients' sera, the molality determined for Na+ was 1% lower and that of K+ 3% lower by ISE than by flame photometry--differences that may be related to ionic binding or to a lower molal activity coefficient in serum than in the calibrator.

J Thode

Papers

Comparison of serum total calcium, albumin-corrected total calcium, and ionized calcium in 1213 patients with suspected calcium disorders.

Transcutaneous and capillary pCO2 and pO2 measurements in healthy adults.

Sex-dependent relation between ionized calcium in serum and blood pressure.

Adjusted ionized calcium (at pH 7.4) and actual ionized calcium (at actual pH) in capillary blood compared for clinical evaluation of patients with disorders of calcium metabolism

Determination of sodium and potassium with ion-selective electrodes.