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G M Feldman

Publications and source records attributed to G M Feldman.

At least 55 records · Page 3Linked to original sources
PubMed1989

Effect of chronic metabolic acidosis on net electrolyte transport in rat colon.

Rats fed NH4Cl (5 meq.100 g body wt-1.day-1) for one week developed chronic metabolic acidosis and had an arterial blood pH and plasma HCO3- concentration of 7.27 +2- 0.02 and 16.2 +/- 0.8 meq/l, respectively; control animals had values of 7.36 +/- 0.01 and 22.4 +/- 0.5 meq/l, respectively. Net electrolyte transport was measured in proximal and distal colonic segments by in situ perfusion. In proximal colon, chronic metabolic acidosis increased HCO3- absorption from 3.3 +/- 0.8 to 6.4 +/- 0.6 mu eq.min-1.g-1 but did not alter Na+ absorption. In distal colon, although Na+ transport was unaffected, chronic acidosis reduced HCO3- secretion from -6.9 +/- 0.8 to -4.4 +/- 0.7 mu eq.min-1.g-1 and increased voltage from -18.9 +/- 2.0 to -51.1 +/- 4.2 mV. To evaluate the dependence of these effects on altered arterial pH and HCO3- concentration, NaHCO3 was infused intravenously, raising pH and HCO3- concentration to 7.53 +/- 0.04 and 23.9 +/- 1.7 meq/l, respectively. Although acute correction of chronic metabolic acidosis reduced HCO3- absorption in proximal colon, it did not affect HCO3- secretion or voltage in the distal segment, suggesting that proximal and distal colon respond differently to chronic metabolic acidosis. These results also suggest that chronic metabolic acidosis alters the mechanisms of ion transport in distal colon.

Acidosis↗
PubMed1988

Taurine and cell volume maintenance in the shark rectal gland: cellular fluxes and kinetics.

Tissue slices of shark rectal gland are studied to examine the kinetics of the cellular fluxes of taurine, a major intracellular osmolyte in this organ. Maintenance of high steady-state cell taurine (50 mM) is achieved by a ouabain-sensitive active Na+-dependent uptake process and a relatively slow efflux. Uptake kinetics are described by two saturable taurine transport components (high-affinity, Km 60 microM; and low-affinity, Km 9 mM). [14C]Taurine uptake is enhanced by external Cl-, inhibited by beta-alanine and unaffected by inhibitors of the Na+/K+/2Cl- co-transport system. Two cellular efflux components of taurine are documented. Incubation of slices in p-chloromercuribenzene sulfonate (1 mM) reduces taurine uptake, increases efflux of taurine and induces cell swelling. Studies of efflux in isotonic media with various cation and anion substitutions demonstrate that high-K+ markedly enhances taurine efflux irrespective of cell volume changes (i.e. membrane stretching is not involved). Moreover, iso-osmotic cell swelling induced in media containing propionate is not associated with enhanced efflux of taurine from the cells. It is suggested that external K+ exerts a specific effect on the cytoplasmic membrane to increase its permeability to taurine.

4-Chloromercuribenzenesulfonate↗
PubMed1988

Effect of renal impairment on disposition of pentopril and its active metabolite.

Disposition of pentopril was studied in 15 male volunteers with varying renal functions. Mild to moderate compromise in renal function did not demonstrate any appreciable changes in plasma concentration of pentopril, the prodrug ester of the active angiotensin-converting enzyme (ACE) inhibitor CGS 13934. This is consistent with the known elimination pattern for pentopril, which is eliminated primarily by hydrolysis to the active inhibitor. In contrast, the plasma concentration of the active ACE inhibitor was sensitive to moderate changes in renal function. Because of the reciprocal relationship of AUC and clearance, AUC did not change to any appreciable extent until creatinine clearance (CLCR) dropped to about 50 ml/min. Below 50 ml/min of CLCR, AUC and half-life increased sharply with reduced kidney function. Because of the significant contribution of the renal secretion process to total renal elimination of both pentopril and the active metabolite, prediction of renal clearance from CLCR was poor at relatively normal kidney function (CLCR greater than 80 ml/min). However, renal secretory clearances for both pentopril and metabolite were well correlated to p-aminohippuric acid clearance. In patients with moderately compromised renal function (glomerular filtration rate less than 40 ml/min), tubular secretion rate of creatinine approaches its glomerular filtration rate and hence CLCR could be used as a predictor of renal clearance and other disposition parameters. Plasma ACE activity also demonstrated prolonged inhibition with decreased renal function. Based on the prolonged blockade of plasma ACE activity, some correction in dose or dosing interval is anticipated in patients with moderately compromised renal function (CLCR less than 50 ml/min).

Adult↗
PubMed1988

Bicarbonate secretion in rat distal colon in vitro: a measurement technique.

To study HCO3- secretion in rat distal colon, we utilized a technique that permits control of electrical and chemical transepithelial gradients. With symmetrical solutions (pH 7.4, [HCO3-] 25 mM, and CO2 tension 40 mmHg) bathing both tissue surfaces and under short-circuit conditions, HCO3- secretion remained stable for greater than 4 h at 1 mueq. h-1.cm-2. As the mucosal solution was alkalinized, the serosal solution was acidified at 3.1 mueq.h-1.cm-2. Ninety-four percent of serosal acidification was accounted for by the rate of metabolic lactic acid generation and transepithelial HCO3- secretion. Clamping transepithelial voltage reversibly affected net HCO3- secretion, and a linear relationship existed between clamped mucosal voltage and net HCO3- flux (r = 0.99); mucosal voltage of -68 mV completely inhibited net secretion. The apparent permeability coefficient of the colon to HCO3- is 2.8 X 10(-6) cm/s. One millimolar ouabain completely inhibited net HCO3- secretion. Acetazolamide (10(-4) M) inhibited secretion by approximately 50%, whereas a 10(-3) M concentration inhibited secretion by 90%. These data demonstrate that net colonic HCO3- secretion can be measured without imposed electrical and chemical gradients and that this flux is voltage sensitive and depends on carbonic anhydrase and Na+-K+-ATPase activities.

Acetazolamide↗
PubMed1988

Bicarbonate secretion modulates ammonium absorption in rat distal colon in vivo.

Although the mammalian colon is thought to absorb large quantities of total ammonia, principally in the form of NH3, quantitative support for this hypothesis is lacking. In rat distal colon, we observed that NH3 was approximately 400 times more permeant than NH+4. In addition, colonic HCO-3 secretion influenced total ammonia (NH3 plus NH+4) absorption; that is, alteration of HCO-3 secretion caused a parallel change in total ammonia absorption. Perfusion with total ammonia also caused net HCO-3 secretion to switch to net absorption, and, in the setting of preexisting HCO-3 absorption, perfusate containing total ammonia enhanced HCO-3 absorption. These events suggest that colonic HCO-3 secretion titrates luminal NH+4 to NH3, permitting NH3 to diffuse from the lumen, while HCO-3 is titrated to carbon dioxide and also diffuses from the lumen. In support of titration of NH+4 and HCO-3, the magnitude of induced HCO-3 absorption approximated total ammonia absorption. This titration relationship suggests that, in kinetic studies, total ammonia absorption will be limited by a fixed rate of HCO-3 secretion. A model was developed that simulated these events.

Algorithms↗
PubMed1985

Effects of anethole dithiolthione and 2(3)-tert-butyl-4-hydroxyanisole on schistosome granuloma formation.

Administration of the antioxidants 2(3)-tert-butyl-4-hydroxyanisole (BHA) or 5-(P-methoxyphenyl)-3H-1,2-dithiol-3-thione (ADT) to female CD-1 mice starting 4 weeks after infection with 70 cercariae of Schistosoma mansoni resulted in a decrease in the size of the inner fibrotic region of the hepatic granuloma. The cellular composition of the granuloma was not altered by treatment with these two compounds. The administration of the specific superoxide scavenger copper diisopropylsalicylate (CuDIPS) resulted in a similar decrease in granuloma size, suggesting a role of superoxide radicals in the granulomatous response.

Anethole Trithione↗
PubMed1985

Differential effects of corticosteroids on Na+ transport in rat distal colon in vitro.

We studied rat distal colon during in vitro incubation with aldosterone and dexamethasone. Both hormones caused short-circuit current (Isc) to increase with a latency period of approximately 3 h. At the 7th h of incubation, control colons had a Isc of 72 +/- 8 microA . cm-2 while tissues incubated with 10(-5) M aldosterone and 10(-8) M dexamethasone, the respective maximal stimulatory concentrations, had similarly increased Isc, 211 +/- 21 and 185 +/- 18 microA . cm-2, respectively. The increase in Isc induced by steroids reflected increased net sodium transport: control, 3.4 +/- 0.8; aldosterone, 6.7 +/- 0.7 (P less than 0.05); and dexamethasone, 7.5 +/- 1.0 mueq . h-1 . cm-2 (P less than 0.025). Spironolactone inhibited the response to both steroids, but the molar ratio of antagonist to agonist was less for aldosterone (approximately 5,000:1) than for dexamethasone (approximately 50,000:1). Amiloride inhibited a greater fraction of aldosterone-induced Isc (0.70 +/- 0.07) than that of dexamethasone (0.37 +/- 0.07; P less than 0.025). The latter value was similar to the effect of amiloride on control tissues (0.35 +/- 0.04). These data provide evidence that the cellular mechanisms by which aldosterone and dexamethasone induce Na+ transport are different.

Aldosterone↗
PubMed1985

Stool electrolyte and osmolality measurements in the evaluation of diarrheal disorders.

Stool osmolality and electrolyte measurements were obtained from 12 patients with diarrheal disorders. Osmolality of diarrheal stool (285 to 330 mosmol) regardless of the cause is less than the reported osmolality of normal stool. Storage of stool at room temperature can artifactually increase stool osmolality as the result of bacterial metabolism. When stool samples are fresh, a negative osmotic gap (measured osmolality - 2 X [Na + K]) is commonly associated with secretory diarrhea, whereas a high osmotic gap (greater than 160 mosmol) is seen in patients with osmotic diarrhea. In many conditions fasting does not resolve diarrhea completely, and when the stool osmotic gap is greater than 50 mosmol, the pathogenesis of diarrhea is difficult to define.

Body Water↗
PubMed1984

On the mechanism of luminal CO2 generation during jejunal bicarbonate absorption.

The mechanism of the increase in luminal CO2 tension (PCO2) that accompanies jejunal HCO-3 absorption is unknown. One possibility is that mucosal metabolism and the reaction of absorbed HCO-3 with blood buffers in mucosal capillaries govern luminal PCO2. To evaluate this possibility, jejunal segments of anesthetized adult male Sprague-Dawley rats were perfused in vivo with modified Ringer solutions with varying PCO2 levels (0-141 mmHg). Arterial PCO2 was varied by mechanical ventilation (20-70 mmHg). The net flux of CO2 gas into bulk luminal fluid varied directly with the transmucosal PCO2 gradient both in the absence (r = 0.98, P less than 0.001) and presence of net HCO-3 absorption (r = 0.97, P less than 0.001). The apparent permeability coefficient for CO2 gas across the jejunal mucosa was relatively low (2 X 10(-4) cm3 X s-1 X cm length -1) and was not affected by net HCO-3 absorption. Under conditions of equal arterial blood and perfusate PCO2 levels (40 mmHg), the PCO2 in mucosa and effluent was 51 and 44 mmHg, respectively, in the absence and 62 and 48 mmHg, respectively, in the presence of net HCO-3 absorption. These results suggest that CO2 diffuses from the mucosal region into bulk liminal fluid during net HCO-3 absorption in the rat jejunum. In addition, we found in vitro that the elevation of mucosal PCO2 above arterial PCO2 during net HCO-3 absorption can be quantitatively accounted for by metabolism and the admixture of absorbed HCO-3 with blood buffers.

Absorption↗
PubMed1984

Systemic acid-base disorders and intestinal electrolyte transport.

Disorders of systemic acid-base balance have recently been shown to markedly alter intestinal electrolyte transport. These studies were based on earlier acid balance studies in humans and animals, data suggesting the presence of intestinal mucosal Na+-H+ and Cl-HCO-3 exchange processes and the reported effects of acid-base variables on other epithelia. In vivo studies have shown that intestinal net sodium and chloride absorption is markedly affected by systemic pH and carbon dioxide tension (Pco2). Specifically, systemic acidemia (in the rat ileum) and hypercapnia (in the rat colon) increase sodium and chloride absorption, while alkalemia and hypocapnia decrease absorption. In addition, net bicarbonate secretion (in both segments) varies directly with the plasma HCO3 concentration. The rabbit ileum has been studied both in vivo and in vitro and is affected in a similar way. The rat jejunum and rabbit distal colon and gallbladder do not respond to changes in blood pH and Pco2, consistent with the apparent absence of a mucosal Na+-H+ exchange process in these segments. Evidence suggests important roles for cellular carbonic anhydrase activity and the intracellular concentrations of hydrogen, bicarbonate, and calcium ions and calcium-calmodulin in mediating or modulating the effects of the systemic acid-base disorders. In addition, systemic pH may alter the effects of the neural and humoral mediators of intestinal transport.

Acid-Base Imbalance↗
PubMed1982

Brief clinical report: the dup(17p) syndrome.

In a 42-month-old girl a duplicated 17p chromosome anomaly was identified by trypsin-Giemsa banding techniques. The clinical findings are compared with those of previous case reports. Common phenotypics changes include failure to thrive; hypoplastic, apparently low-set ears; micrognathia; flexion abnormalities of fingers; and foot abnormalities.

Abnormalities, Multiple↗
PubMed1982

Effect of acute respiratory alkalosis and acidosis on intestinal ion transport in vivo.

The effects of acute respiratory alkalosis and acidosis on intestinal electrolyte transport were studied in adult Sprague-Dawley rats. During in situ intestinal perfusion, anesthetized animals were ventilated with 0, 3, or 8% CO2, creating states of alkalosis (pH 7.64 +/- 0.01), normocapnia (pH 7.45 +/- 0.01), or acidosis (pH 7.26 +/- 0.01), respectively. The plasma bicarbonate concentration decreased 2.0 mM during alkalosis and increased 2.1 mM during acidosis. The jejunum did not respond to the acid-base disturbances. In both the ileum and colon, alkalosis decreased the net absorption of water (-16%), sodium (-23%), and chloride (-42%) and the net secretion of bicarbonate (-33%), whereas acidosis had the opposite effect, i.e., the net absorption of water (41%), sodium (39%), and chloride (32%) increased as did net bicarbonate secretion (33%) (ileal values given). Changes in sodium chloride movement could be correlated with changes in systemic pH and CO2 tension (PCO2), and bicarbonate secretion paralleled changes in the plasma bicarbonate concentration. The acid-base disorders had no effect on ileal and colonic net potassium secretion and transmural potential difference. These studies suggest that systemic pH and/or PCO2 regulate sodium chloride absorption, and the plasma bicarbonate concentration regulates bicarbonate secretion.

Acidosis, Respiratory↗
PubMed1981

Effect of lithium ingestion on water and electrolyte transport in rat intestine.

The effect of lithium ingestion on intestinal electrolyte and water transport was studied in adult Sprague-Dawley rats. We fed animals a lithium-supplemented diet for 1, 2, 4, or 16 wk before in vivo perfusion of the jejunum and colon. Lithium feeding did not alter jejunal transport of water, electrolytes, or glucose, However, at 4 and 16 wk (16-wk data given) the colon increased net water (168%), sodium (160%), and chloride (140%) absorptions, and the transmural potential difference (396%) as compared with control animals. In addition, the colon absorbed both bicarbonate and potassium against an unfavorable electrochemical gradient. The increased colonic sodium absorption was not associated with an increase in mucosal Na+, K+-ATPase activity. Furthermore, in lithium-fed animals deoxycorticosterone acetate stimulated mucosal Na+, K+-ATPase activity, but it did not further increase net sodium absorption. Neither jejunal nor colonic electrolyte transport was affected 24 h after being gavage-fed lithium. These results suggest that chronic lithium ingestion has a unique mechanism of action as other means of chronically increasing sodium absorption are associated with increased mucosal Na+, K+-ATPase activity.

Animals↗
PubMed1980

Effect of acute metabolic alkalosis and acidosis on intestinal electrolyte transport in vivo.

The effects of acute metabolic alkalosis and acidosis on intestinal electrolyte transport were studied in adult Sprague-Dawley rats. Animals were made alkalotic or acidotic by gavage feeding of 1 M solutions of NaCl (pH = 7.42), NaHCO3 (pH = 7.52), NH4Cl (pH = 7.18), or 0.75 M (NH4)2SO4 (pH = 7.21). After 1-3 h, animals were anesthetized and prepared for in vivo perfusion of the jejunum, ileum, and colon. The jejunum exhibited increased net potassium absorption in alkalosis and decreased potassium absorption in acidosis. In the ileum, net sodium absorption and potassium secretion were decreased, and bicarbonate secretion was increased in alkalosis, and opposite effects were observed in acidosis. The ileal lumen minus blood gradient for PCO2 (an index of hydrogen ion secretion) was greater in acidotic than in alkalotic animals. The levels of ileal sodium, bicarbonate, and potassium transport and the PCO2 gradient correlated well with the plasma pH and bicarbonate concentration in individual animals. In the colon, net bicarbonate secretion and chloride absorption increased and potassium secretion decreased in alkalosis, and opposite effects were observed in acidosis. The colonic lumen minus blood PCO2 gradient was not affected by acid-base balance. Colonic bicarbonate transport correlated with the plasma chloride concentration as well as with the plasma pH. The acid-base disorders had no effect on transmural potential difference. These results suggest that acute metabolic alkalosis and acidosis alter sodium and hydrogen ion transport in the ileum and chloride and bicarbonate transport in the colon.

Acidosis↗
PubMed1980

Nodular glomerulopathy associated with nonamyloidotic kappa light chain deposits and excess immunoglobulin light chain synthesis.

A nodular glomerulopathy characterized by mesangial deposits of monoclonal kappa light chains was detected by immunofluorescence in a renal biopsy from a patient with proteinuria and hypertension. These nodules lacked the tinctorial and morphologic features of amyloid. Ultrastructurally, the nodules contained electron-dense granular deposits as well as fibrils in parallel arrangement. The fibrils measured 110-140 A in diameter. They were consistent in size with amyloid fibrils. However, they differed in lacking the randomly oriented network of typical amyloid fibrils and more closely resembled fibrils intrinsic to mesangial matrix. The patient had no bone marrow or X-ray evidence of myeloma and no evidence of free monoclonal light chains in serum or concentrated urines. Biosynthetic studies of the patient's bone marrow cells demonstrated unbalanced immunoglobulin synthesis with excess production of monoclonal kappa light chains. These observations suggest that the observed glomerulopathy results from direct deposition of monoclonal light chains. Deposits with kappa light chain determinants have been found in 7 other patients with similar nodular glomerulopathies, 4 of whom had diagnosed clinical myeloma. The lesion of nonamyloidotic nodular glomerulopathy previously described in 19 patients, nor examined by immunopathologic techniques or not shown to contain light chain determinants, may have a similar pathogenesis.

Adult↗
PubMed1978

The problem of partial trisomy 22 reconsidered.

A patient with partial trisomy 22(PT22) is presented. Inheritance is presumed to be due to secondary nondisjunction in her mother, who has a balanced translocation t(11;22)(q25;q13). The problem of the phenotypic heterogeneity observed with this chromosome change is discussed.

Abnormalities, Multiple↗