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Biomedical subjects

J B Stokes

Publications and source records attributed to J B Stokes.

At least 91 records · Page 5Linked to original sources
PubMed1984

Cellular K+ permeation across the cortical collecting tubule: effects of Na+-K+ pump inhibition and membrane depolarization.

These experiments examined the possibility that alterations in cell cation content and/or membrane voltage could influence cell K+ permeability of the cortical collecting tubule. Using the amiloride-treated isolated perfused rabbit cortical collecting tubule, ouabain or a K+-free bath reduced the magnitude of the K+ diffusion voltage. In addition, both methods of Na+-K+-ATPase inhibition reduced the K+ efflux (lumen-to-bath) rate coefficient (KK) without affecting the Na+ efflux rate coefficient. The magnitude of the reduction of KK could not be explained by a model of simple diffusion across two membranes in series even if the intracellular voltage were abolished. Thus, pump inhibition reduced cell K+ permeability. To determine whether membrane depolarization could induce a change in membrane permeability, [K+] was increased to 20 mM in both perfusate and bath. The reduction in KK was within the range predicted by the three-compartment model (36%). Differential membrane depolarization by raising lumen [K+] or bath [K+] produced disparate results. Apical depolarization reduced KK but basolateral depolarization did not. Taken together these results indicate that intracellular ion content may play a major role in regulating cell K+ permeability independent of voltage-dependent effects. In addition, under these experimental conditions, the apical membrane may be the rate-limiting barrier to cellular transfer.

Animals↗
PubMed1984

Sodium chloride absorption by the urinary bladder of the winter flounder. A thiazide-sensitive, electrically neutral transport system.

The urinary bladder of the winter flounder absorbs NaCl by a process independent of the transepithelial voltage. In contrast to most other epithelia which have a neutral NaCl-absorptive system, the flounder bladder has a high transepithelial resistance. This feature simplifies analysis of the cellular transport system because the rate of ion transfer through the paracellular pathway is rather low. Experiments were designed to distinguish among three possible mechanisms of neutral NaCl absorption: (a) Na/K/2Cl cotransport; (b) parallel Na/H and Cl/OH exchange; (c) and simple NaCl cotransport. A clear interdependency of Na and Cl for net absorption was demonstrated. NaCl absorption was not dependent on mucosal K and was minimally sensitive to loop diuretics. Thus a Na/K/2Cl transport system was unlikely. The mechanism was not parallel exchange as evidenced by insensitivity to amiloride and to 4,4'-diisothiocyano-2,2'-disulfonic stilbene, an inhibitor of anion exchange. In addition, inhibitors of carbonic anhydrase had no effect. Net absorption was almost completely abolished by hydrochlorothiazide (0.1 mM). Its action was rapid, reversible, and effective only from the mucosal surface. Metolazone, a structurally dissimilar diuretic in the benzothiadiazide class had qualitatively similar actions. The mechanism of NaCl absorption in this tissue appears to be a simple interdependent process. Its inhibition by thiazide diuretics appears to be a unique feature. The flounder bladder may be a model for NaCl absorption in the distal renal tubule.

Animals↗
PubMed1982

Na and K transport across the cortical and outer medullary collecting tubule of the rabbit: evidence for diffusion across the outer medullary portion.

The rabbit collecting tubule displays functional axial heterogeneity with respect to Na ion transport. The present experiments compared cortical collecting tubule (CCT) and outer medullary collecting tubule (OMCT) Na and K transport. Na efflux across the CCT was inhibited by ouabain, whereas Na efflux across the OMCT was smaller and unaffected by ouabain. Assessment of the equivalent conductivities of Na and K across the CCT by imposition of a Na-K bi-ionic gradient demonstrated a higher K/Na conductivity across the CCT than would be predicted from their respective limiting equivalent conductivities in water. In contrast, the ratio of their conductivities across OMCT were not different than would be predicted by their ratio in water. The "selective" nature of the Na and K pathways across CCT was confirmed by measuring the tracer efflux rate coefficients. In the amiloride-treated CCT the K/Na rate coefficient ratio was 9.8 +/- 1.5; this ratio across the OMCT was 1.51 +/- 0.10. The latter value is not different from the ratio of the mobilities of these ions in water. The diffusional nature of Na and K transfer across OMCT was confirmed by the demonstration of the concentration-independent Na efflux rate coefficient and the demonstration of appropriate net Na and K transepithelial flows in response to imposition of oppositely directed chemical gradients. Although the permeability of the OMCT is low, the chemical gradients found in vivo might be sufficient to effect some K absorption and Na secretion without completely dissipating the steep gradients generated by the CCT. These transport characteristics might be important in the regulation of Na excretion and K recycling into the renal medulla.

Animals↗
PubMed1982

Consequences of potassium recycling in the renal medulla. Effects of ion transport by the medullary thick ascending limb of Henle's loop.

The consequences of K recycling and accumulation in the renal medulla were examined by measuring the effect of elevated K concentration on ion transport by the medullary thick ascending limb of Henle's loop. Perfused and bathed in vitro, thick limbs from both mouse and rabbit displayed a graded, reversible reduction of transepithelial voltage after increasing K concentration from 5 to 10, 15, or 25 mM. The effect was reproducible whether osmolality was 328 or 445 mosmol/kg H2O, and whether K replaced Na or choline. Net chloride absorption and transepithelial voltage were reduced by almost 90% when ambient K concentration was 25 mM. When either lumen or bath K was increased to 25 mM, net Na absorption was reduced. There was spontaneous net K absorption when perfusate and bath K concentration was 5 mM. Analysis of transepithelial K transfer after imposition of chemical gradients demonstrated rectification in the absorptive direction. Absorption of K by this segment provides a means to maintain high medullary interstitial concentration. Accumulation of K in the outer medulla, by reducing NaCl absorption, would increase volume flow through the loop of Henle and increase Na and water delivery to the distal nephron. K recycling thus might provide optimum conditions for K secretion by the distal nephron.

Absorption↗
PubMed1981

Heterogeneity of the rabbit collecting tubule: localization of mineralocorticoid hormone action to the cortical portion.

This study was designed to examine the sodium, potassium, and chloride transport rates across the cortical and outer medullary collecting tubule and to localize the action of mineralocorticoid hormone. Rabbit collecting tubules were dissected from the cortex (CCT), the outer stripe of the outer medulla (OMCT0), or the inner stripe of the outer medulla (OMCTi). From normal rabbits, the transepithelial voltage was -20.8 +/- 2.7 mV in CCT, -4.2 +/- 1.4 mV in OMCT0, and +10.6 +/- 2.3 mV in OMCTi. From DOCA-treated rabbits, only the CCT voltage was different (-42.9 mV). Net sodium absorption across the CCT increased ith DOCA-treatment from 23 +/- 5 to 54 +/- 8 pEq . mm-1 . min-1, whereas net potassium secretion increased from 15 +/- 2 to 43 +/- 5 pEq . min-1 . min-1. Net chloride absorption was significant only in DOCA-treated rabbits. The OMCTi, in contrast, displayed no net transport of sodium, potassium, or chloride and had a lower rate coefficient for sodium efflux than did the CCT. DOCA treatment had no effect on any transport rate measured in this segment. The OMCT0 has small potassium secretion, which did not increase with DOCA treatment. The collecting tubule is heterogeneous along its length with respect to ion transport. Mineralocorticoid-hormone-sensitive sodium absorption is present predominantly, if not exclusively, in the cortical collecting tubule.

Animals↗
PubMed1981

Effects of inhibition of prostaglandin synthesis on fetal renal function.

The role of renal prostaglandin production on the control of renal blood flow (RBF) and renal function was studied in eight chronically catheterized fetal lambs during the last trimester of gestation by using indomethacin as an inhibitor of prostaglandin synthesis. Following administration of indomethacin, RBF decreased significantly (-7.44 +/- 2.04 ml/min) whereas significant increases in filtration fraction (+3.92 +/- 0.85%) and renal vascular resistance (+ 0.41 +/- 0.13 mm Hg . ml-1 . min-1) were observed. Significant changes in glomerular perfusion rate were observed only in the inner portion of the cortex. No changes in GFR were demonstrated. Following administration of indomethacin, significant increases in fetal urinary sodium (+22.2 +/- 7.03 micro E/min) and chloride excretion (+18.2 +/- 6.26 micro E/min) were found despite a decrease in RBF. No changes in potassium excretion were seen. A significant increase in Uosm (+100 +/- 25.9 mOsm/kg H2O) not associated with significant changes in urinary flow rate was also demonstrated following indomethacin. Finally, fetal administration of indomethacin produced a significant decrease in plasma renin activity (-2.70 +/- 0.65 ng/ml/hr) not associated with changes in plasma aldosterone concentration. The present data are consistent with the idea that prostaglandins are important modulators of RBF and renin secretion during fetal life. The inability of indomethacin to render the urine hypertonic indicates that the inability of the fetal kidney to concentrate is probably not due to endogenous activity of the renal prostaglandin system. The increase in sodium chloride excretion with a concomitant reduction of RBF is a pattern not previously reported following inhibition of prostaglandin production. In addition to their effects on RBF and renin release, renal prostaglandins in the fetal kidney may have tubular effects on sodium and chloride absorption that are opposite to those generally ascribed to adult kidneys.

Animals↗
PubMed1981

Integrated actions of renal medullary prostaglandins in the control of water excretion.

The renal medulla is a rich source of prostaglandins. Two cell types, the collecting tubule epithelium and the interstitial cell, have the enzymatic machinery necessary to make prostaglandins. As a result of this localized production and the proximity to highly specialized medullary structures, the prostaglandins can exert potent effects on several aspects of medullary function. At least three physiologic effects have been clearly documented: reduction of vasopressin-dependent osmotic water permeability of the collecting tubule epithelium, enhancement of medullary blood flow, and inhibition of NaCl absorption from the thick ascending limb of Henle's loop. These three functions are the functions that primarily regulate axial solute content and water excretion. The effect of increasing medullary prostaglandin production is to reduce medullary solute content and increase water excretion. Each action in this regard. The medullary prostaglandins thus antagonize the ultimate action of vasopressin. In addition to the direct antagonistic effect on vasopressin-dependent osmotic water flow across the collecting tubule, prostaglandins and vasopressin may have antagonistic effects at other sites. These actions of medullary prostaglandins provide an integrated mechanism for the "fine tuning" of water excretion.

Animals↗
PubMed1981

Potassium secretion by cortical collecting tubule: relation to sodium absorption, luminal sodium concentration, and transepithelial voltage.

Sodium absorption and K secretion were measured in isolated perfused rabbit cortical collecting tubules. To increase the range of transport rates some tubules were dissected from rabbit pretreated with DOcA. K secretin was unaffected by varying axial volume flow from 4 to 15 nl/min. K secretion was, however, correlated with transepithelial voltage and Na absorption. The Na:K transfer ratio was 1.35. In tubules dissected from normal rabbits, K secretion was almost eliminated by reducing Na concentration in the lumen to near 0 and was unaffected by varying luminal Na concentration from 30 to 145 mM. These data, together with other experimental results reported by several investigators, are consistent with a model for K secretion that places the rate-limiting step at the Na-K pump located on the basolateral membrane. The apical (luminal) membrane appears to be highly permeable to K.

Absorption↗
PubMed1979

Intracranial abscess.

Thirty-one patients with intracranial abscess who were treated at Royal Perth Hospital during the past 10 years are reviewed. There were 17 males and 14 females with a mean age of 39.2 years. Fifteen deaths indicate an over-all mortality of 45%. However, the mortality was 62% in the first five years, and 39% during the latter five years. The clinical features of the patients are reviewed. Factors contributing to the high mortality were severe local and multisystem disease, delay in diagnosis and surgical drainage, and inappropriate or inadequate antibiotic therapy. The use of high doses of antibiotics is suggested and recommendations are made concerning appropriate regimens.

Adolescent↗
PubMed1979

Effect of prostaglandin E2 on chloride transport across the rabbit thick ascending limb of Henle. Selective inhibitions of the medullary portion.

Prostaglandins are present in large quantities in the kidney and have been shown to directly affect transepithelial transport. The present studies were designed to examine whether prostaglandin E2 could affect chloride transport across the thick ascending limb of Henle. Isolated segments of the cortical and medullary thick ascending limb of Henle were perfused in vitro and the transepithelial voltage and net chloride flux were measured. Exposure of the medullary thick ascending limb to 2 microM prostaglandin E2 resulted in a fall in net chloride transport of 40--50% with a concomitant fall in voltage. In contrast, net chloride transport in the cortical thick ascending limb was not affected by prostaglandin E2. Under similar conditions, the medullary thick ascending limb possessed twice the capacity to transport chloride than did the cortical thick ascending limb. The results suggest that endogenous renal prostaglandins may play a modulating role in the addition of salt to the renal medullary interstitium and may, under some circumstances, by chloruretic.

Animals↗
PubMed1979

Cortical and papillary micropuncture examination of chloride transport in segments of the rat kidney during inhibition of prostaglandin production. Possible role for prostaglandins in the chloruresis of acute volume expansion.

Prostaglandins have been postulated to participate in the regulation of salt excretion during acute volume expansion. The present papillary and cortical micropuncture studies were designed to examine the effect of prostaglandin synthesis inhibitors on segmental chloride transport during hydropenia (with and without meclofenamate) and 10% volume expansion (with and without both meclofenamate and indomethacin). Both inhibitors significantly decreased the urinary excretion rate of prostaglandins E(2) and F(2alpha). Clearance studies on the intact right kidney demonstrated no effect of either agent on glomerular filtration rate, but a significant reduction in chloride excretion during hydropenia and volume expansion was observed. To assess the specific site(s) of enhanced chloride reabsorption, absolute and fractional chloride delivery was measured in the late proximal tubule, thin descending limb of Henle, and the early and late distal tubules. In addition, the fraction of filtered chloride remaining at the base and tip of the papillary collecting duct was compared to that fraction remaining at the superficial late distal tubule. During hydropenia, meclofenamate had no effect on fractional chloride delivery out of the superficial late distal tubule or the juxtamedullary thin descending limb of Henle, but significantly reduced the fraction of chloride delivered to the base of the papillary collecting duct. During volume expansion, neither meclofenamate nor indomethacin had an effect on absolute chloride delivery out of the proximal tubule or the thin descending limb of Henle. However, absolute chloride delivery to the early distal tubule was significantly reduced, and was associated with a decrease in fractional chloride reabsorption in this segment. Furthermore, the fraction of chloride delivered to the base of the collecting duct was significantly reduced. Fractional reabsorption along the terminal 1 mm of the collecting duct was not altered by either meclofenamate or indomethacin. These results suggest that inhibitors of prostaglandin synthesis result in an increase in chloride reabsorption in the superficial loop of Henle, and in segments between the superficial late distal tubule and the base of the collecting duct. The results are consistent with the view that prostaglandins inhibit chloride transport in the thick ascending limb of Henle, and/or the cortical and outer medullary collecting tubule.

Animals↗
PubMed1978

Structural-functional heterogeneity along the rabbit collecting tubule.

The possibility that the rabbit collecting tubule is heterogeneous with respect to electrical and morphologic properties was examined in isolated segments. Collecting tubules from rabbits treated with desoxycorticosterone acetate were dissected from various locations within the cortex and outer medulla, and the transepithelial potential was measured. The cortical collecting tubule always displayed a negative potential. In contrast, collecting tubules dissected from the inner stripe of the outer medulla displayed a positive potential. That this change is a function of position within the kidney is supported by the observation that some tubules generated a negative potential at the superficial (cortical) end and a positive potential at the deep (medullary) end of the same tubule. Histologic evaluation of tubules after perfusion resulted in a striking correlation between the existence of a negative potential and the presence of dark cells. The results of this study provide evidence that the collecting tubule is heterogeneous with respect to active transport processes and suggest that these functional differences may correlate with morphologic differences between the cortical segment and the medullary segment of the collecting tubule.

Animals↗
PubMed1977

Inhibition of sodium transport by prostaglandin E2 across the isolated, perfused rabbit collecting tubule.

This study was designed to examine whether prostaglandin E2 can directly affect sodium transport across isolated perfused rabbit renal collecting tubules. Changes in transepithelial potential and isotopic sodium fluxes in response to peritubular prostaglandin E2 were measured. In addition, changes in transepithelial potential of the outer medullary collecting tubule in response to prostaglandin E2 were also measured. With few exceptions, all rabbits received 5 mg/day desoxycorticosterone acetate for 4-11 days before experimentation. The results of the experiments show that: (a) prostaglandin E2 inhibits the negative transepithelial potential in the cortical collecting tubule as well as the outer medullary collecting tubule; (b) prostaglandin E2 inhibits net sodium transport out of the lumen by inhibiting efflux while backflux is unaffected; (c) prostaglandin E2 produces this inhibition within 15 min, and the effects are dose dependent and reversible. These results suggest that prostaglandin E2 may modulate sodium transport in vivo and may contribute to the final regulation of sodium excretion.

Animals↗
PubMed1976

Amanita preissii "mushroom" poisoning.

"Mushroom" poisoning has rarely been reported in Australia. We present six cases of Amanita preissii poisoning successfully treated with atropine sulphate. The symptoms and signs were typical of muscarinic poisoning, which suggests that this alkaloid is the principal toxic component. A short time interval between the ingestion of poisonous fungi and the onset of symptoms, in our cases within one hour, indicates a good prognosis. The dangers of mistaking poisonous for edible varieties of fungi are emphasized, particularly in relation to immigrants not conversant with Australian fungi. Public education and control of marketing are advised.

Adult↗