Biomedical subjects

H H Bengele

Publications and source records attributed to H H Bengele.

At least 19 recordsLinked to original sources

PubMed1994

Biodistribution of an ultrasmall superparamagnetic iron oxide colloid, BMS 180549, by different routes of administration.

The ultrasmall superparamagnetic iron oxide colloid BMS 180549 can be found lymph nodes by either subcutaneous (SC) or intravenous (IV) injection. With an SC injection in the front extremities, the axillary and brachial nodes attain the highest accumulations of the agent. With an SC injection in the rear extremities, the popliteal, iliac, and axillary nodes attain highest accumulations of the agent. With IV injection of the agent, the iliac, mediastinal and mesenteric nodes attain highest accumulations of the agent. Though the spleen is not involved with the drainage of the interstitial space near the site of SC injections, the mobility of BMS 180549 from such injection sites increases splenic relaxation rates. Based on a knowledge of the lymphatic system, a route of administration of BMS 180549 can be chosen to maximize the delivery of the agent to specific lymph nodes.

Animals↗

PubMed1990

Vasopressin-enhanced urea transport by rat inner medullary collecting duct cells in culture.

The distal inner medullary collecting duct (IMCD) is critical in the urinary concentrating process, in part because it is the site of vasopressin (AVP)-regulated permeability to urea. The purpose of these experiments was to develop a cell culture model of the IMCD on permeable structure and to characterize the responsiveness to AVP. Rat IMCD cells were grown to confluence on collagen-coated Millipore filters glued onto plastic rings. To assess the time required to achieve confluence, the transepithelial resistance was measured periodically and was found to be stable after 2 weeks, at a maximal value of 595 +/- 22 omega cm2. In separate monolayers the effect of AVP on inulin and urea permeability was determined. While inulin permeability was unchanged after AVP, urea permeability increased from 6.0 +/- 0.4 to peak values of 16.0 +/- 3.8 (10 nM), 23.1 +/- 3.9 (1 microM) and 28.1 +/- 4.9 (10 microM) x 10(-6) cm s-1 (n = 24). In 10 other monolayers, after the addition of 1 mM 8-Br-cAMP, urea permeability increased from 5.1 +/- 0.3 to 8.1 +/- 1.6 x 10(-6) cm s-1 and, after 8-Br-cAMP + 3-isobutyl-1-methylxanthine, to 12.2 +/- 0.7 x 10(-6) cm s-1. We conclude that rat IMCD cells grown in culture exhibit the characteristics of a 'tight' epithelium. Inulin and urea permeability are not different in the absence of AVP, consistent with high resistance junctional complexes. Furthermore, IMCD cells retain the capacity for AVP-regulated urea permeability, a characteristic feature of this nephron segment in vivo.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1990

Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging.

An ultrasmall superparamagnetic iron oxide (USPIO) preparation was developed that is small enough to migrate across the capillary wall, a prerequisite in the design of targetable particulate pharmaceuticals. Seventy percent of particles were smaller than 10 nm; 26%, smaller than 5 nm. The blood half-life of USPIO in rats was 81 minutes, considerably longer than that of larger superparamagnetic iron oxide preparations such as AMI-25 (6 minutes). Electron microscopy demonstrated that USPIO particles transmigrate the capillary wall by means of vesicular transport and through interendothelial junctions. Twenty-four hours after intravenous administration, 3.6% of the injected dose per gram of tissue was found in lymph nodes, 2.9% per gram in bone marrow, 6.3% per gram in liver, and 7.1% per gram in spleen. The major potential applications for USPIO are as (a) an intravenous contrast agent for the lymphatic system, (b) a bone marrow contrast agent, (c) a long-half-life perfusion agent for brain and heart, and (d) the magnetic moiety in organ-targeted superparamagnetic contrast agents for magnetic resonance imaging.

Animals↗

PubMed1988

Mechanisms of H+ secretion by inner medullary collecting duct cells.

Inner medullary collecting duct cells were isolated from rat papillae and grown to confluence on cover slips. H+ secretion was estimated by intracellular pH (pHi) changes measured with the fluorescent probe 2,7-biscarboxyethyl-5(6)-carboxyfluorescein. In buffered NaCl, pHi was 7.14 +/- 0.04 (n = 78). After acidification about 40% of monolayers exhibited Na+-independent alkalinization. In 5 mM glucose, cell alkalinization occurred at a rate of 47 +/- 4 nM H+/min. However, cell alkalinization did not occur in the presence of 2-deoxy-D-glucose (5-15 mM), iodoacetate (5 mM), or KCN (5 mM). All monolayers tested exhibited amiloride-inhibitable Na+-dependent cell alkalinization that appeared to be a first-order kinetic process; Km [Na+] was approximately 52 mM and Vmax was approximately 250 nM [H+]/min. At a constant extracellular [Na+] (110 mM), Na+-dependent H+ efflux was a first-order function of pHi; Km for intracellular [H+] = 321 nM and Vmax = 182 nM H+/min. The data are consistent with the presence of a primary active H+ pump and a secondary active Na+ exchanger. The metabolic energy for the active H+ pump can be provided by glycolysis and oxidative phosphorylation.

Alkalies↗

PubMed1988

Suppression of acidification along inner medullary collecting duct.

The purpose of these experiments was to evaluate the effect of acute respiratory alkalosis (ARA) and chronic bicarbonate drinking (CBD) on inner medullary collecting duct (IMCD) acidification. Microcatheterization was used to measure pH and PCO2, and samples were simultaneously obtained for measurement of bicarbonate, titratable acid (TA), and ammonium. In ten ARA rats (arterial pH was 7.54 +/- 0.02; PCO2 was 20 +/- 1 mmHg), IMCD equilibrium pH was not different (deep pH was 5.65 +/- 0.06 and PCO2 was 20 +/- 1 mmHg; tip pH was 5.54 +/- 0.07 and PCO2 was 22 +/- 1 mmHg). Delivery of bicarbonate, TA, and ammonium also did not differ between collection sites. Thus net acidification along the IMCD was negligible. Nine rats drank NaHCO3 for 5-8 days (pH = 7.48 +/- 0.02) but did not receive NaHCO3 during the experiment so that arterial pH fell to 7.40 +/- 0.01. IMCD equilibrium pH was different at deep (pH was 5.68 +/- 0.06; PCO2 was 32 +/- 1 mmHg) and tip (pH was 5.57 +/- 0.04; PCO2 was 27 +/- 1 mmHg; P less than or equal to 0.05) collection sites. However, only minimal changes in the delivery of bicarbonate, TA, and ammonium were noted, and net acidification along the IMCD was negligible. In ten control rats, net acidification was 219 nmol/min between collection sites (P less than 0.001). We conclude that ARA and CBD abolish acidification along the IMCD. In addition, CBD produces an intrinsic modification along the IMCD, which suppresses acid secretion and persists after acute recovery from alkalemia.

Alkalosis, Respiratory↗

PubMed1988

Acidification adaptation along the inner medullary collecting duct.

Chronic acid feeding (ACD) stimulates and chronic alkali (AKL) feeding suppresses acid secretion along the inner medullary collecting duct (IMCD) of the rat. The purpose of these experiments was to determine whether these stimuli produce IMCD acidification adaptation. We tested this hypothesis by acutely changing systemic PCO2 in rats chronically fed ACD or ALK. Microcatheterization was used to measure pH and PCO2 and samples were simultaneously obtained for measurement of bicarbonate, titratable acid (TA), and ammonium. In 10 ACD rats (arterial pH, 7.26 +/- 0.01; PCO2, 88 +/- 1 mmHg) acid secretion along the IMCD was 506 +/- 88 nmol/min. In 10 ALK rats with similar arterial gases (pH, 7.16 +/- 0.02; PCO2, 82 +/- 1 mmHg) IMCD acid secretion was only 284 +/- 57 nmol/min, P less than 0.05. In ACD rats made hypocarbic (pH, 7.26 +/- 0.03; PCO2, 24 +/- 1 mmHg), IMCD acid secretion was 163 +/- 55 nmol/min. These data were compared with previously studied rats eating a regular diet. Acute hypocarbia (pH, 7.54 +/- 0.02; PCO2, 20 +/- 1 mmHg) completely suppressed acid secretion, 4 +/- 23 nmol/min, along the IMCD. We conclude that chronic alterations in acid-base status provide an IMCD "set" where comparable stimuli produce significant differences in IMCD acidification. These data provide additional support for the concept of IMCD acidification adaptation.

Acclimatization↗

PubMed1987

Inner medullary collecting duct function during rebound alkalemia.

Rats, made acidemic when fed NH4Cl, become alkalemic with discontinuation of the NH4Cl. This phenomenon has been called rebound metabolic alkalemia (RMA). This study examines the function of the inner medullary collecting duct (IMCD) during RMA. Rats drank only 1.5% NH4Cl for 5 days and then water for 16 h prior to study, yielding an arterial pH = 7.50 +/- 0.01, PCO2 = 39 +/- 1 mmHg, and bicarbonate = 29.5 +/- 1.0 mM. The IMCD data were obtained by microcatheterization from deep (1.5-3.0 mm) and tip (0.2-0.5 mm) samples. Equilibrium pH decreased from 5.92 +/- 0.09 (n = 20) to 5.38 +/- 0.04 (n = 20) and PCO2 increased from 32 +/- 1 to 38 +/- 1 mmHg between deep and tip samples. Bicarbonate delivery decreased from 37 +/- 8 to 7 +/- 1 nmol/min. Titratable acid and ammonium delivery increased from 284 +/- 52 to 347 +/- 62 nmol/min and from 549 +/- 38 to 685 +/- 40 nmol/min, respectively. Calculated net acid excretion increased from 796 +/- 88 to 1,026 +/- 95 nmol/min. Thus during RMA, proton secretion continues along the IMCD, although there is a systemic alkalemia. It appears that factors in addition to systemic acid-base parameters are important in the regulation of proton secretion by the IMCD.

Acidosis↗

PubMed1987

Biphasic 19-nor-deoxycorticosterone excretion after adrenal enucleation is associated with altered adrenal mitochondrial cytochrome P450 11 beta-, 18-, and 19-hydroxylase activities.

After adrenal enucleation (AE) rats avidly retain sodium (early phase), but after 7-10 days they lose this sodium avidity (late phase). Although increased production of a mineralocorticoid, 19-nor-deoxycorticosterone (19-Nor-DOC), has been implicated, 19-Nor-DOC levels during the early and late phases of AE have not been systematically measured. Furthermore it is not known why 19-Nor-DOC production should increase during a time when production of 11 beta- and 18-hydroxylated corticosteroids are decreased in AE. The purpose of this study was to examine the 11 beta, 18-, and 19-hydroxylase pathways in the early and late phases of AE. The results demonstrate increased urinary 19-Nor-DOC and decreased 18-OH-DOC and corticosterone excretion in the early phase of AE at a time when adrenal mitochondrial 11 beta- and 18-hydroxylase activities were decreased but 19-hydroxylase activity was unchanged. During the late phase of AE, urinary 19-Nor-DOC had decreased and 18-OH-DOC and corticosterone had increased to levels indistinguishable from those in sham controls. This reduction in 19-Nor-DOC was associated with a decrease in 19-hydroxylase activity in AE. Since the 11 beta, 18-, and 19-hydroxylases have a common substrate (DOC), it is possible that differential flux of DOC through these pathways could account for the changes in steroid production in AE. These data suggest that the increased 19-Nor-DOC excretion in AE may be due to alterations in enzyme activity leading to a shunting of DOC into the 19-Nor-DOC pathway. In addition, the synchronicity of 19-Nor-DOC with sodium excretion suggests that it has an important role in the pathogenesis of the sodium retention in AE.

Adrenal Glands↗

PubMed1986

Kinetics of the Na+-H+ antiporter as assessed by the change in intracellular pH in MDCK cells.

The Na+-H+ antiporter regulates both H+ secretion and cell pH in renal epithelia. The present study was designed to further define the Na+ dependency and kinetics of proton efflux in MDCK cells. Intracellular pH (pHi) was determined with a pH-sensitive fluorescent probe, 2,7-bis-carboxyethyl-5,6-carboxyfluorescein (BCECF). Data were obtained from confluent monolayers grown on plastic cover slips and studied in media free of added CO2 and HCO-3, pH = 7.2 (pHo). Monolayers in NaCl maintain a pHi of 7.48 +/- 0.03 (n = 13). When cells were acidified with NH4Cl, pHi decreased to 6.73 +/- 0.07 (n = 10) and remained stable in Na+-free choline chloride. When monolayers were subsequently exposed to NaCl, pHi increased 0.28 +/- 0.04 pH units/min. Amiloride (2.5 mM) inhibited this Na+-dependent rise in pHi by more than 75%. The rate of pHi recovery after exposure to Na+ exhibited saturation kinetics; the apparent Km(Na) was 30.4 +/- 4.2 mM and maximum velocity was 107.1 +/- 17.1 delta [H+]i nmol X l-1 X min-1. We conclude that pHi regulation in the MDCK cell is in part mediated by a Na+-H+ antiporter, and the kinetics of this process can be reliably assessed by the pH-sensitive fluorometric probe, BCECF.

Amiloride↗

PubMed1986

Sodium retention after adrenal enucleation.

Adrenal enucleation (removal of the adrenal gland, leaving the capsule intact) results in regeneration of the adrenal cortex. During the first 1-2 wk of adrenal regeneration, marked renal sodium avidity and positive sodium balance are noted. This renal sodium avidity appears mediated via adrenocorticotropin-stimulated secretion of a potent mineralocorticoid by the regenerating adrenal cortex. In this review, we have examined relationships between the histology and ultrastructure of the regenerating adrenal cortex, renal sodium handling, and adrenal steroid production at various times after the initiation of adrenal regeneration. Plasma levels of known mineralocorticoids are subnormal during the period of most intense sodium avidity, while urinary excretion of a potent mineralocorticoid, 19-nordeoxycorticosterone, has been found to be increased in rats with regenerating adrenals during this period of most intense sodium avidity. This hormone, however, is not elevated in rats with regenerating adrenals after resolution of the period of sodium avidity. In this article, we review the experimental evidence regarding the potency of this mineralocorticoid and its likely role in the sodium retention after adrenal enucleation.

Adrenal Glands↗

PubMed1986

Effect of buffer infusion during acute respiratory acidosis.

We previously reported that acute respiratory acidosis (ARA) did not stimulate inner medullary collecting duct (IMCD) acidification. It was possible that the failure to find enhanced IMCD acidification was a function of insufficient buffer delivery. To answer this question we studied IMCD acidification in rats with ARA during the infusion of the buffer creatinine. We employed the microcatheterization technique to directly measure pH and PCO2 with glass membrane electrodes and also obtained fluid samples for the measurement of titratable acid and ammonium. Arterial pH was 7.19 +/- 0.01 and PCO2 was 93 +/- 2 mmHg. The IMCD data were analyzed as a function of IMCD length (approximately 6 mm). Equilibrium pH decreased from 5.99 +/- 0.05 to 5.58 +/- 0.02 and PCO2 increased from 71 +/- 11 to 132 +/- 6 mmHg between origin and tip. Bicarbonate delivery decreased from 111 +/- 14 to 38 +/- 2 nmol/min; titratable acid increased from 867 +/- 87 to 1,625 +/- 61 nmol/min, but ammonium delivery did not change along the duct. Thus, estimated net acid increased from 1,772 +/- 155 to 2,709 +/- 88 nmol/min. We conclude that during the presence of increased buffer delivery to the IMCD, rats with ARA markedly increased proton secretion along the terminal nephron.

Acidosis, Respiratory↗

PubMed1986

Chronic metabolic acidosis augments acidification along the inner medullary collecting duct.

The inner medullary collecting duct (IMCD) of the rat is a major site of acidification. However, previous micropuncture studies have failed to demonstrate acidification along the terminal IMCD during chronic acid feeding. To more completely evaluate this question we used the microcatheterization method in rats fed ammonium chloride for 3-7 days. Arterial pH was 7.30 +/- 0.015, and PCO2 was set at 40 +/- 0.6 mmHg. The IMCD data were analyzed as a function of IMCD length between 40% and the tip. Equilibrium pH decreased from 6.21 +/- 0.11 to 5.47 +/- 0.03, whereas PCO2 was unchanged (28 +/- 1 mmHg between the deep samples and tip). Bicarbonate delivery decreased from 92 +/- 14 to 10 +/- 1 nmol/min, titratable acid increased from 462 +/- 33 to 762 +/- 40 nmol/min, and ammonium delivery increased from 2,235 +/- 121 to 3,528 +/- 140 nmol/min. Thus estimated net acid increased from 2,638 +/- 134 to 4,303 +/- 161 nmol/min. To determine whether increasing delivery of buffer to the IMCD would stimulate acid secretion in acute acidosis, rats were studied during the infusion of HCl and creatinine. Arterial pH was 7.18 +/- 0.02. IMCD acidification was not increased compared with our previously published studies during HCl infusion [Am. J. Physiol. 241 (Renal Fluid Electrolyte Physiol. 10): F669-F676, 1981]. We conclude that chronic ammonium chloride ingestion stimulates IMCD acidification and that this increase may be an intrinsic modification of the acidification mechanism of the IMCD.

Acidosis↗

PubMed1984

Effect of aldosterone and dexamethasone pretreatment on sodium transport in rat distal colon in vitro.

Aldosterone and dexamethasone stimulate sodium absorption in the rat colon in vivo. In vitro, increased amiloride inhibitable short-circuit current (ISC) has been demonstrated following aldosterone or dexamethasone treatment. Since ISC bears no relationship to sodium flux (JNa) in the untreated rat colon, we measured JNa in partially stripped voltage clamped segments of rat distal colon. Our results demonstrate directly that continuous infusion of aldosterone or dexamethasone for 4-7 days stimulated amiloride inhibitable JNa by stimulating JNaM -S. The amiloride inhibitable portion of JNaM -S was highly correlated with and approximately equal to the amiloride inhibitable ISC. Amiloride had no effect in controls. We conclude that JNaM -S in the rat distal colon is only sensitive to mucosal amiloride after treatment with aldosterone or dexamethasone. The amiloride sensitive ISC in these treated tissues was a good measure of the amiloride sensitive JNa. Small differences between aldosterone and dexamethasone treatment were noted in the effect on transepithelial resistance, potential difference, and the ISC after amiloride.

Aldosterone↗

PubMed1984

Effect of acute thyroparathyroidectomy on nephron acidification.

The effect of the absence of parathyroid hormone on nephron acidification was determined in rats after acute thyroparathyroidectomy (TPTX). Tubular fluid samples were obtained from the superficial late proximal tubule (LPT), the early distal tubule ( EDT ), and along the inner medullary collecting duct (IMCD), and the results were compared with those obtained from control rats. In the LPT after TPTX, pH was lower, 6.66 +/- 0.01 vs. 6.73 +/- 0.01, and ammonium and net acid delivery were increased significantly. In the EDT no differences in pH, bicarbonate, or net acid were found between groups, whereas ammonium and acid phosphate were significantly different. Along the IMCD in control rats, pH decreased from 6.58 to 5.21 and the addition of about 430 nmol/min of net acid was observed. After TPTX more net acid entered the duct and pH was lower, 5.66, but did not change; neither did the amount of bicarbonate, ammonium, acid phosphate, or net acid change significantly along the duct. Net acid excretion was not different, however, among groups. These results demonstrate that TPTX markedly affects nephron acidification, increasing net acid along the proximal tubule. In contrast to that in control rats, however, net acidification is completed prior to the IMCD. We conclude that the acute absence of parathyroid hormone may significantly affect local nephron acidification but does not alter acid excretion.

Acid-Base Equilibrium↗

PubMed1984

Mineralocorticoid activity of 19-nor-corticosterone and 19-nor-progesterone in the toad bladder.

19-Nor-corticosteroids are potentially important mineralocorticoids and hypertensive agents. We tested the mineralocorticoid potency of 19-nor-progesterone (19-NOR-P) and 19-nor-corticosterone (19-NOR-B) compared with aldosterone using the toad bladder short-circuit current as a measure of sodium transport. 19-NOR-B (10(-7) M) increased sodium transport to a degree not different from that caused by aldosterone (10(-7) M). The onset of action and duration of activity also were not different from those of aldosterone. 19-NOR-P (10(-7) M), however, had no effect on sodium transport. We conclude that 19-NOR-B has significant mineralocorticoid activity, while under the conditions of these studies, 19-NOR-P exhibited no effect on sodium transport.

Aldosterone↗

PubMed1983

Impaired renal and extrarenal potassium adaptation in old rats.

Young (3 to 4 months) and old (21 to 22 months) rats were fed either a regular or high potassium (K) diet. After acute potassium chloride infusion, the fraction of infused K excreted (K efficiency) was similar in rats on a normal diet (57 +/- 3%, young, vs. 61 +/- 2%, old). With high K feeding there was a significant increase in the young, 69 +/- 4%, but not in the old rats, 62 +/- 2%. Na-K ATPase activity was markedly reduced in the renal medulla of old rats on a regular or high K diet. In addition, the response to acute K loading was compared in acutely nephrectomized rats. In the young rats on a regular diet plasma K increased from 3.72 +/- 0.09 to 5.28 +/- 0.16 mEq/liter while with K ingestion the increase was significantly less, 3.62 +/- 0.07 to 4.75 +/- 0.12 mEq/liter. In the old rats plasma K increased similarly on a regular or high K diet, 3.68 +/- 0.10 to 5.68 +/- 0.33 mEq/liter and 3.76 +/- 0.06 to 5.97 +/- 0.30 mEq/liter, respectively. Thus, old rats have impaired renal and extrarenal adaptation, but they have a normal response to an acute K challenge. A reduction in Na-K ATPase may account for the defect in renal adaptation in the aged rats.

Adaptation, Physiological↗

PubMed1983

Effect of respiratory acidosis on acidification by the medullary collecting duct.

The effect of acute respiratory acidosis (ARA) on inner medullary collecting duct (IMCD) acidification was studied and the results were compared with previously obtained data by our laboratory in rats with acute metabolic acidosis (AMA). We employed the microcatheterization technique to directly measure pH and PCO2 with glass-membrane electrodes, and fluid samples were obtained for measurement of bicarbonate, phosphate, and ammonium. Arterial pH was 7.18 +/- 0.01 and PCO2 was 88 +/- 2 mmHg. The IMCD data were analyzed as a function of IMCD length (approximately 6 mm). pH decreased from 5.78 +/- 0.07 to 5.27 +/- 0.03 and PCO2 increased from 55 +/- 4 to 75 +/- 2 mmHg between origin and tip. Bicarbonate delivery decreased from 154 +/- 34 to 25 +/- 3 nmol/min but no change was noted in acid phosphate, ammonium, or net acid addition along the IMCD. However, net acid excretion was not different from that found previously in AMA. We conclude that during ARA acidification is augmented prior to, but not along, the IMCD. In contrast, during AMA we previously found that IMCD plays a major regulatory role in urinary acidification, accounting for about 50% of the excreted hydrogen ion.

Acidosis↗

PubMed1982

Elevated urinary PCO2 in the rat: an intrarenal event.

During a bicarbonate diuresis, final urine Pco2 considerably exceeds systemic Pco2, an effect thought to reflect the postpapillary delayed dehydration of carbonic acid. To test this explanation, Pco2 tensions along the inner medullary collecting duct (IMCD) of bicarbonate-loaded rats were measured directly using Pco2 microelectrodes. With systemic Pco2 held at 40 mm Hg, IMCD Pco2 exceeded systemic Pco2 in every measurement by an average of 20 to 30 mm Hg. A significant increment in Pco2 was seen between 50% IMCD length and the papilla tip. During the infusion of carbonic anhydrase, IMCD Pco2 was reduced but not to systemic levels. Finding elevated Pco2 along the terminal IMCD deemphasizes the importance of postpapillary delayed dehydration and suggests the possibility that bicarbonaturia is associated with papillary accumulation of carbon dioxide.

Animals↗