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L C Racusen

Publications and source records attributed to L C Racusen.

69 records · Page 4Linked to original sources
PubMed1985

Mechanisms of lysine-induced acute renal failure in rats.

We have previously found that lysine produces acute renal failure in rats. To define the acute effects of lysine, rats given lysine at 8.9 mg/kg/min, i.v. for 4.5 hr were compared with control rats receiving equiosmolar dextrose. Systemic blood pressure was stable in both groups. Mean intratubular pressure, inulin clearance (CIn), and renal blood flow were determined at 45-min intervals. Intratubular pressures measured with a servonulling micropressure device were elevated by 90 min in lysine-treated animals, with tubular heterogeneity, while pressures in dextrose-treated rats were normal and homogeneous. By 135 min CIn in lysine-treated rats was 45% of CIn in dextrose rats. Urine output fell in lysine-treated rats. Renal blood flow determined by flow probe remained normal in lysine-treated rats through 135 min and did not decline significantly until 180 min. Significant dilatation of surface tubules was documented by intravital microscopy beginning at 90 min in lysine-treated rats. The sequence of elevated intratubular pressure and tubular dilatation, followed by decreased CIn, and then by decreased renal blood flow suggests that lysine produces acute renal failure primarily through tubular obstruction. The tubular obstruction is followed later by an increase in renal vascular resistance.

Acute Kidney Injury↗
PubMed1985

Effects of lysine and other amino acids on kidney structure and function in the rat.

Lysine is a major constituent of amino acid parenteral nutrition solutions which have recently been shown to increase the severity of various types of acute renal failure in the rat. In previous studies the authors have shown that high-dose lysine alone is capable of causing acute renal failure. However, it has remained unclear what the morphologic expression of this type of acute renal failure is in the maintenance phase of the syndrome, whether other amino acids produce a similar lesion, and whether lysine in lower doses also produces acute renal failure. In the present study the authors show that lysine, when given in a dose of 600 mg/rat over 4 hours, produced persisting acute renal failure which at 48 hours was characterized morphologically by a picture similar to that in human "acute tubular necrosis"--little overt tubular necrosis, but a focal loss of individual tubular cells with regenerative changes and mitotic figures. Extensive hyaline cast formation was seen, particularly in the thin limbs of the loops of Henle, and these thin limb casts were shown to contain Tamm-Horsfall protein. Equivalent doses of glycine, arginine, and glutamic acid and lower doses of lysine produced no significant renal morphologic or functional changes.

Amino Acids↗
PubMed1984

Nephrotoxicity of lysine and of a single dose of aminoglycoside in rats given lysine.

Hyperalimentation solutions have been shown to increase aminoglycoside nephrotoxicity in rats and rabbits. Lysine is a major constituent of hyperalimentation solutions and is known to inhibit tubular reabsorption of protein. To test the effects of lysine on renal function and structure and on aminoglycoside nephrotoxicity, three groups of rats were prepared. Groups 1 and 2 were infused with lysine (55 mumol/kg/min, 1.9 gm/kg total) for 4 hours. In group 2, gentamicin (60 mg/kg) was also infused during the third hour. In group 3, dextrose was given instead of lysine, and gentamicin was given as in group 2. In group 1 (lysine-saline solution), there was a decrease in glomerular filtration rate (GFR) and an increase in 125I-albumin clearance factored by GFR. In group 2 (lysine-gentamicin), the same effects were seen, but the reduction in GFR was significantly greater. Group 3 (dextrose-gentamicin) showed no change in GFR over the 4-hour period, but did show an increase in 125I-albumin clearance factored by GFR. Fractional excretion of sodium rose in group 2 but not in groups 1 and 3. A gradual mild (20%) and nonsignificant fall in renal blood flow followed the combined administration of lysine and gentamicin. In separate 20-hour studies, lysine (1.9 gm/kg intraperitoneally) or gentamicin or tobramycin (60 mg/kg subcutaneously) produced mild renal failure, but the combination of lysine and an aminoglycoside produced substantially greater renal failure. Serum creatinine in experimental groups was significantly correlated with medullary cast formation and tubular necrosis (p less than 0.001). Giant lysosomes with crystalloid inclusions in proximal tubular cells, individual cell necrosis in the pars recta, and casts in the thin limb of the loop of Henle were seen in rats given lysine. We conclude that lysine alone and single large doses of aminoglycosides alone are nephrotoxic, and when the two are combined, toxicity is additive. The nephrotoxicity of lysine may be related to direct tubular toxicity and to tubular obstruction.

Acute Kidney Injury↗
PubMed1984

Glomerular epithelial cell changes after ischemia or dehydration. Possible role of angiotensin II.

Glomerular visceral epithelial cells (podocytes) undergo flattening and spreading of major processes detectable by scanning electron microscopy in early postischemic acute renal failure in both animals and man. The authors examined the kinetics of development of these epithelial cell changes in the renal pedicle-clamping model of ischemic renal failure in the rabbit. They found that these changes develop progressively, increasing with increasing length of ischemia, and occur while the pedicle clamp is still in place. To assess the possible role of angiotensin II and vasopressin in producing the epithelial changes, the authors compared glomerular morphology before and during pedicle clamping in hydrated rabbits and in dehydrated rabbits. Dehydration alone produced changes in glomerular epithelial cells comparable to those seen in the postischemic kidney. The angiotensin-converting enzyme inhibitor captopril did not prevent the podocyte changes in either group. In vitro incubation studies confirmed that both angiotensin II and vasopressin produce glomerular epithelial cell changes with a threshold between 10(-7) M and 10(-8) M, a concentration that may be physiologically significant for angiotensin II, which is synthesized at the glomerulus and may have local paracrine effects. Such local synthesis may not be inhibited by systemic administration of captopril. Angiotensin II may play a role in producing podocyte alterations during renal ischemia, as well as in the dehydrated state.

Angiotensin II↗
PubMed1981

Glomerular epithelial cell changes in early postischemic acute renal failure in rabbits and man.

Spreading and flattening of glomerular podocyte cell bodies and major processes and an apparent lack of foot processes were observed by scanning electron microscopy in a reversible pedicle-clamping model of acute renal failure in ADH-treated rabbits and in biopsy specimens taken 1 hour after transplantation from patients who later showed clinical signs of "acute tubular necrosis." Glomerular changes were quantified by morphometry in A) normal rabbit kidneys, B) rabbit kidneys obtained 2 hours after 1 hour of left pedicle clamping and right nephrectomy, C) kidneys similar to Group B except that the animals were treated with an agent that reliably lessens the eventual severity of renal failure (clonidine, 30 microgram/kg given intravenously 1/2 hour before unclamping), D) 1-hour-posttransplantation biopsy specimens from human kidneys that functioned well after transplantation (recipient serum creatinine less than 2.5 mg/dl on Day 3), and E) 1-hour-posttransplant biopsy specimens from kidneys that later manifested posttransplantation ischemic acute renal failure (recipient serum creatinine greater than or equal to 2.5 mg/dl on Day 3). The fraction of glomerular capillary surface covered only by podocyte processes smaller than 1 mu (and not by cell bodies and wider processes) was .65 +/- .02 (SEM) in A; .48 +/- .03 in B; .64 +/-.03 in C; .57 +/- .01 in D; and .38 +/- .04 in E (A vs B, P less than .01; B vs C, P less than .02; D vs E, P less than .01). In Groups D and E there was a significant negative correlation between the fraction of glomerular capillary surface covered only by podocyte processes less than 1 mu in width and serum creatinine on the third posttransplantation day (r = --.86, P less than .01 by the Spearman rank test). It is concluded that podocyte changes are seen by scanning electron microscopy early in clinical and experimental postischemic acute renal failure and are more pronounced in those groups that eventually develop more severe renal failure. It is unclear whether these changes reflect a decrease in glomerular hydraulic permeability or an increase in glomerular permeability to protein.

Animals↗
PubMed1980

Effect of prostaglandin on ion transport across isolated colonic mucosa.

The effect of prostaglandins (PG) on colonic ion transport was investigated in in vitro experiments in the rat. Both PGE1 and PGA1 increased short-circuit current (Isc), potential difference, and mucosal cyclic AMP levels, but PGE1 was more potent than PGA1. 10(-4) M PGE1 inhibited active sodium transport across short-circuited colonic mucosa (6.1-1.3 microEq/hr/cm2). This effect, coupled with an increase in Isc, is consistent with prostaglandin stimulation of active anion secretion and with the recent suggestions that prostaglandins may be important intermediaries in the process by which several laxatives alter large-intestinal fluid and electrolyte movement.

Animals↗
PubMed1979

Ricinoleic acid stimulation of active anion secretion in colonic mucosa of the rat.

Perfusion of the colon with ricinoleic acid produces fluid and electrolyte accumulation. The mechanism of these changes in water and electrolyte movement is uknown. These studies were designed to determine whether ricinoleic acid effects active ion transport across isolated rat colonic mucosa. 0.5 mM Na ricinoleate produced significant increases in potential difference (3.8 +/- 0.5 mV) and short-circuit current (Isc) (99.2 +/- 10.1 muA/cm2). The increases in Isc produced by Na ricinoleate were inhibited by both removal of bicarbonate and chloride and by the presence of theophylline. The hydroxy fatty acid also resulted in a significant decrease in net Na absorption from 4.7 +/- 0.8 to 0.1 +/- 0.7 mueq/h cm2 and reversed net Cl transport from absorption (+ 4.5 +/- 0.9) to secretion (-2.2 +/- mueq/h cm2). In parallel studies 0.5 mM Na ricinoleate increased mucosal cyclic AMP content by 58%. The concentrations of Na ricinoleate required to produce detectable and maximal increases in both Isc and cyclic AMP were the same. These results provide evidence in support of the concept that hydroxy fatty acid-induced fluid and electrolyte accumulation is driven by an active ion secretory process.

Animals↗
PubMed1978

Effect of propranolol on ricinoleic acid- and deoxycholic acid-induced changes of intestinal electrolyte movement and mucosal permeability. Evidence against the importance of altered permeability in the production of fluid and electrolyte accumulation.

Hydroxy fatty acids and bile acids produce both intestinal fluid and electrolyte accumulation and increases in inulin clearance, a parameter of mucosal permeability. The relationship of the changes in mucosal permeability to the production of fluid and electrolyte accumulation is uncertain. These experiments were designed to determine whether the alterations of mucosal permeability produced by ricinoleic acid and deoxycholic acid were related to production of hydroxy fatty acid- and bile acid-induced fluid and electrolyte accumulation in the rat colon. Propranolol (1 mg per 100 g of body weight) administered daily for 3 days inhibited ricinoleic acid- and deoxycholic acid-induced Na and water accumulation. In contrast, propranolol did not affect either the increase in inulin clearance or the decrease in electrical potential difference produced by ricinoleic acid and deoxycholic acid. Further, amphotericin B increased inulin clearance by the colon and also increased water and Na absorption. These studies suggest that changes in mucosal permeability are not primarily responsible for hydroxy fatty acid- and bile acid-induced fluid and Na accumulation.

Amphotericin B↗
PubMed1977

Effect of folate deficiency and ethanol ingestion on intestinal folate absorption.

The effects of folate deficiency, generalized malnutrition, and alcohol ingestion on jejunal transport, mucosal uptake, and reduction of folic acid were evaluated in rats. As measured by an everted gut sac technique, a folate-deficient diet fed ad libitum did not alter transport or mucosal uptake of folate. Partial starvation, which was produced in rats pair-fed with animals ingesting ethanol, increased jejunal folate transport and mucosal uptake in animals ingesting either a folate-deficient or control diet. A 20% ethanol ingestion by rats consuming folate-deficient or control diets resulted in transport and mucosal uptake rates intermediate in value compared to those from ad libitum fed and pair-fed groups. No differences in reduction of folic acid were found. These results suggest that folate depletion and ethanol ingestion, alone or in combination, do not affect the ability of the rat jejunal to transport folate but that partial starvation results in an increase in folate transport activity.

Animals↗
PubMedDate not supplied

Epithelial cell shedding in acute renal injury.

1. To address the postulate that sublethally injured tubular cells may be shed from renal epithelium while still viable, studies were undertaken in vivo in human 'acute tubular necrosis' and in rabbit models of renal tubular injury. 2. Substantial numbers of viable tubular cells were voided in the urine. When placed in culture, these cells gave rise to monolayers, confirming viability. The majority of intact cells demonstrated markers of proximal tubule. 3. In vitro studies of human renal proximal tubular cells exposed to hypoxia/anoxia showed rounding and retraction associated with disruption of actin microfilaments. Phalloidin stabilized the filaments and prevented the changes in cell shape indicative of altered adherence.

Actins↗
PubMedDate not supplied

Renal morphology and function and urine electrolytes in experimental acute renal failure produced by cyclosporine and ischemia.

It has been difficult to produce a good animal model for cyclosporine nephrotoxicity. It has been suggested that by following 20 minutes of renal ischemia with four daily doses of cyclosporine 60 mg/kg intraperitoneally, one can create a model of reproducible renal failure. We observed excessive mortality (65%), due in part to cyclosporine's CNS effects, with these combined insults in the Munich Wistar rat. In contrast, cyclosporine alone in this dosage produced only 17% mortality and resulted in a similar degree of renal failure. Pair-fed and pair-watered vehicle and saline controls were used. The morphologic changes brought about by the castor oil vehicle of the parenteral cyclosporine solution were qualitatively similar to those brought about by cyclosporine by light microscopy, although the severity of the changes was considerably less in the vehicle-treated groups. However, by electron microscopy, pale lipid vacuoles were seen only in the cyclosporine-treated groups, whereas dense alterations in lysosomes and dilated endoplasmic reticulum also were seen in other groups. Urine sodium determined by flame photometry and urine chloride determined by Saltex reagent strips tended to be high in the initiation phase of cyclosporine-induced acute renal failure and low in the maintenance phase. In animals that developed acute renal failure following the combination of ischemia and cyclosporine, the initial urine sodium and chloride were significantly correlated with the eventual degree of renal failure. The use of Saltex urine chloride sticks in clinical urine samples showed that the readings correlated well with urine sodium and chloride determined by conventional methods, suggesting that these strips may be useful in making a quick diagnosis in the setting of acute renal failure.

Acute Kidney Injury↗