Search PubMed⌕ Search

Biomedical subjects

M Brezis

Publications and source records attributed to M Brezis.

At least 127 records · Page 7Linked to original sources
PubMed1986

Lactate increases potassium secretion by perfused rat kidney.

The effect of exogenous metabolic substrates on K+ secretion was evaluated in the isolated perfused rat kidney in the presence of 2-deoxyglucose and 2-tetradecylglycidic acid to inhibit utilization of glucose and fatty acids from endogenous sources. L-Lactate (15 mM) added to the perfusion medium enhanced renal oxygen consumption (4.0 +/- 1.1 mumol X min-1 X g-1 vs. 2.0 +/- 1.0 without lactate) while decreasing fractional excretion of sodium (19.3 +/- 2.4% vs. 47.3 +/- 1.8). L-Lactate markedly increased the fractional excretion of K+ to 181 +/- 29% compared with 68 +/- 12% without lactate (P less than 0.001). The poorly metabolized isomer D-lactate did not alter these parameters. The addition of alpha-ketoglutarate only slightly increased K+ excretion. In the absence of metabolic inhibitors and in the presence of glucose (5 mM), L-lactate also increased K+ excretion significantly more than did D-lactate (108 +/- 19% vs. 69 +/- 11, P less than 0.02). At the end of 90 min of perfusion with L-lactate medium, K+ concentration in the perfusate dropped from 4.7 +/- 0.05 to 3.2 +/- 0.2 meq/liter (vs. 3.8 +/- 0.1 meq/liter with D-lactate, P less than 0.005) without differences in glomerular filtration rate or sodium excretion. L-Lactate appears to increase K+ secretion by preferential metabolic stimulation of the distal tubule, a process that may help in vivo to prevent hyperkalemia in lactic acidosis.

Amiloride↗
PubMed1986

Inhibition of prostaglandin synthesis in rat kidney perfused with and without erythrocytes: implication for analgesic nephropathy.

A marked defect in renal concentration ability associated with hypoxic lesions in the medullary thick ascending limb (mTAL) characterizes the isolated rat kidney perfused with cell-free solutions. Addition of erythrocytes to the perfusion medium, a maneuver known to eliminate signs of hypoxic cellular injury to mTALs, greatly improved renal concentrating ability. When indomethacin was given to kidneys perfused with erythrocyte-enriched medium, concentrating ability was further improved by the drug to an average U/Posm of 2.45 +/- 0.81, and medullary cellular structure remained normal in appearance. Since renal hypoperfusion predisposes to acute renal failure from non-steroidal antiinflammatory drugs (NSAIDs) and medullary ischemia might play a role in chronic analgesic nephropathy, a synergism between NSAIDs and medullary hypoxia was evaluated in the isolated perfused rat kidney. Indomethacin and naproxen added to the perfusion medium (at 10(-4) and 5 X 10(-4) M, respectively) effectively depressed prostaglandin E2 (PGE2) production by the isolated kidney but did not improve its concentrating ability when perfused with cell-free medium. Quantitation of hypoxic injury to mTALs, regularly observed in this model, indicated that both indomethacin and naproxen increased the extent and severity of damage in the deeper, most hypoxic portions of the inner stripe. Addition of PGE2 to cell-free perfusate reduced the extent of hypoxic damage to the mTAL. These results suggest that in medullary hypoxia, prostaglandins protect mTAL cells by either vasodilatation or reduction in active transtubular transport. NASAIDs, by suppressing prostaglandin production, could predispose the renal medulla to hypoxic injury.

Amino Acids↗
PubMed1986

Tumor genesis syndrome. Hypophosphatemia accompanying Burkitt's lymphoma cell leukemia.

A case of Burkitt's lymphoma cell leukemia with recurrent hypophosphatemia that coincided with tumor growth, and hyperphosphatemia during tumor lysis is presented. Redistribution of body phosphorus with increased uptake by the rapidly replicating tumor cells is suggested. Tumor genesis syndrome seems to us to be a proper term to include metabolic abnormalities that result directly from tumor growth.

Adult↗
PubMed1986

Topography of focal proximal tubular necrosis after ischemia with reflow in the rat kidney.

The topography of renal injury after ischemia-reflow was studied in intact rats by clamping the right renal artery for variable periods of time and examining the histologic appearance of the kidney in large 1-mu plastic sections. As reported by others, the straight portion of the proximal tubule (S3) was especially susceptible to ischemia-reflow injury. The pattern of focal necrosis produced in S3 by short (15-30-minute) and longer (45-60-minute) periods of arterial occlusion appeared related to gradients to oxygenation during reflow, in that more extensive injury was seen in areas remote from blood vessels, while perivascular tubules were protected. A similar pattern was seen in S1 and S2 after a longer period (45-60-minutes) of ischemia, which produced extensive but incomplete necrosis in these convoluted segments, with protected tubules lying within zones surrounding arcuate and interlobular arteries. The immediate postglomerular portion of S1, a tubular segment normally well supplied with oxygen, was an exception to this rule. Selective necrosis limited to this portion of the nephron appeared after only 15-30 minutes of ischemia, recalling the special sensitivity of S1 cells to inhibition of mitochondrial respiration. These results suggest that in different segments of the proximal tubule, injury after ischemia-reflow is determined not only by changes that occur during complete ischemia but also by the adequacy of oxygenation during the reflow period.

Animals↗
PubMed1985

An unsuspected cause for metabolic acidosis in chronic renal failure: sorbent system hemodialysis.

A severe metabolic acidosis was produced in a patient with chronic renal failure by hemodialysis using a sorbent system to regenerate bicarbonate dialysate with an initial bicarbonate concentration of 60 mEq/L. The acidosis resolved with standard single-pass hemodialysis. In five additional patients, the bicarbonate concentration of the dialysate with the sorbent system was noted to be low and quite variable (mean +/- SD, 16.5 +/- 8.3 mEq/L, range 5 mEq/L to 39 mEq/L). The low dialysate bicarbonate failed to correct metabolic acidosis and, in fact, was capable of further lowering the serum bicarbonate. The capacity of the regenerating cartridge to release protons makes this form of dialysis a potential cause for metabolic acidosis. The safety of the sorbent system dialysis, at least in the bicarbonate mode, requires further evaluation.

Absorption↗
PubMed1985

Disparate mechanisms for hypoxic cell injury in different nephron segments. Studies in the isolated perfused rat kidney.

Hypoxic injury was evaluated morphologically in the proximal tubule and in the medullary thick ascending limb of isolated rat kidneys perfused for 90 min without O2 or with various metabolic inhibitors. Inhibition of mitochondrial respiration (with rotenone, antimycin, oligomycin) or of intermediary metabolism (with monofluoroacetate, malonate, 2-deoxyglucose) caused reduction in renal oxygen consumption, renal function, and ATP content comparable with those elicited by oxygen deprivation. Metabolic inhibition produced hypoxiclike injury in the first portions of the proximal tubule, S1 and S2 ("clubbing" of microvilli, mitochondrial swelling), and the extent of damage was correlated with the degree of ATP depletion. In the third portion of the proximal tubule, S3, hypoxiclike damage (cytoplasmic edema or fragmentation) occurred most consistently when both aerobic and anaerobic metabolism were inhibited simultaneously. In the medullary thick ascending limb, none of the metabolic or mitochondrial inhibitors used could reproduce the injury of oxygen deprivation. Thus, the proximal tubule and the thick ascending limb have markedly different responses to cellular energy depletion, suggesting disparate mechanisms for hypoxic injury along the nephron.

Adenosine Triphosphate↗
PubMed1984

Polyene toxicity in renal medulla: injury mediated by transport activity.

Polyene antibiotics such as amphotericin and nystatin increase membrane permeability and thus increase the amount of oxygen consumed in active electrolyte transport. In isolated perfused rat kidneys, the polyenes produced extensive injury to the medullary thick ascending limb, a segment of the nephron with limited oxygen supply. This damage was prevented if reabsorptive transport was inhibited by ouabain. Cell death under these circumstances thus appears to be mediated by increased oxygen demand for transport activity.

Amphotericin B↗
PubMed1984

Selective anoxic injury to thick ascending limb: an anginal syndrome of the renal medulla?

Cortico-medullary gradients of O2 availability within the renal parenchyma have been appreciated for some time, but not their pathophysiological significance. During isolated perfusion of the rat kidney with cell-free albumin-Ringer's medium, a specific anatomical lesion is consistently observed, confined to the medullary thick ascending limb of Henle's loop (mTAL), that progresses over 90 min from mitochondrial swelling to nuclear pyknosis and complete cellular disruption. The lesion is exaggerated by oxygen deprivation and ameliorated by increasing the oxygen content of the perfusion or by reducing the transport work of mTAL cells. Because of its anatomical location associated with a low O2 supply imposed by the medullary vascular system and its high rate of electrolyte transport, the mTAL appears to be exquisitely sensitive to O2 deprivation. The consequent anoxic lesion, resulting from an imbalance between O2 supply and demand, may have important implications for the understanding of ischemic renal injury.

Animals↗
PubMed1984

Transport activity modifies thick ascending limb damage in the isolated perfused kidney.

The thick ascending limb of Henle's loop ( TAL ) develops a specific and consistent structural lesion during perfusion of the isolated rat kidney that progresses from mitochondrial swelling at 15 min to complete cellular disruption at 90 min. Because it seemed possible that damage localized to this metabolically active portion of the nephron might be correlated with cellular transport, the histology of perfused kidneys was examined when transport activity in the TAL was varied. The fraction of TAL tubules showing severe damage (44 +/- 2% in kidneys perfused with glucose) was dramatically reduced by furosemide (7 +/- 2%; P less than 0.001). The lesion was eliminated by perfusion with ouabain or by preventing glomerular filtration. On the other hand, protection of TAL cells was not obtained with the proximal diuretic acetazolamide. These results suggest that the lesion of TAL cells that develops during perfusion of the isolated kidney is influenced by the work of cellular transport.

Acetazolamide↗
PubMed1984

Amino acids induce renal vasodilatation in isolated perfused kidney: coupling to oxidative metabolism.

Renal vasodilatation regularly accompanies protein feeding and amino acid infusions, but the mechanism is unknown. The effects of several different amino acids on renal hemodynamics were studied in the isolated rat kidney, perfused with glucose as the only other substrate. Addition of amino acids produced a dose-dependent, brisk, and sustained decrease in renal vascular resistance (by 5-35%) without change in glomerular filtration rate (GFR). The vasodilatation was associated with a parallel increase in O2 consumption (increases QO2). The effect was most marked with amino acids actively metabolized by the kidney, such as glutamine (at 2 mM), but was seen with most amino acids at 8 mM. The amino acid analogues alpha-aminobutyrate, taurine, and cycloleucine, cotransported with sodium but not metabolized, did not cause significant vasodilatation or increases QO2. Blocking active transport with ouabain blunted the amino acid-induced vasodilatation and increases QO2. Similar resistance to amino acids was produced by halting GFR with hyperoncotic medium. Restoration of GFR by increasing perfusion pressure in the presence of hyperoncotic medium reestablished amino acid-induced vasodilatation and increases QO2. Furosemide did not block the vasodilatory response. Inhibition of mitochondrial respiration by antimycin blocked both vasodilatation and increases QO2, but rotenone blockade could be bypassed by succinate or glutamine. Amino acids have a direct vasodilating action on isolated kidneys probably related to their role as metabolic substrates and linked to an increase in renal O2 consumption.

Amino Acids↗
PubMed1984

Selective vulnerability of the medullary thick ascending limb to anoxia in the isolated perfused rat kidney.

A specific anatomical lesion sharply localized to the cells of the medullary thick ascending limbs (mTAL) and characterized by mitochondrial swelling progressing to nuclear pyknosis and cell death is elicited reproducibly in isolated rat kidneys perfused for 15 or 90 min with cell-free albumin-Ringer's medium gassed with 5% CO2, 95% O2 (O2 content, 1.5 vol/100 ml). The lesion, involving about half of mTALs, appears first in mTALs removed from vascular bundles and near the inner medulla, areas most likely to be anoxic. Hypoxic perfusion (O2 content 0.12 vol/100 ml) exaggerates the lesion, wiping out gradations of damage and extending it to all mTALs. O2-enriched perfusions using rat erythrocytes (O2 content 7.1 vol/100 ml) completely eliminates the lesion (unless gassed with carbon monoxide). Similarly, supplementation of the perfusion medium with a purified hemoglobin (O2 content 5.8 vol/100 ml) prevents mTAL injury. Perfusion with a fluorinated hydrocarbon blood substitute, Oxypherol (O2 content 4.3 vol/100 ml) also attenuates the lesion. These findings suggest that the mTAL is exquisitely susceptible to anoxic damage because of low O2 supply imposed by the medullary vascular system and the high rate of metabolism mandated by active reabsorption of sodium chloride. The vulnerability of the mTAL to anoxic injury could play a key role in the pathogenesis of ischemic renal injury.

Animals↗
PubMed1984

Transport-dependent anoxic cell injury in the isolated perfused rat kidney.

The hypothesis that decrease in energy demand may prevent anoxic cell damage has been examined in the medullary thick ascending limb of isolated perfused rat kidneys exposed to oxygen deprivation. The effects of decreasing active reabsorptive transport in the medullary thick ascending limb were observed on the extensive damage regularly induced by hypoxic perfusion (gassed with no oxygen) or potassium cyanide. Anoxic injury was consistently attenuated or abolished if reabsorptive transport was decreased with ouabain or furosemide or by halting the glomerular filtration rate with the use of a hyperoncotic medium (nonfiltering kidney). Comparison of the injury generated by warm ischemia for identical time periods showed that complete ischemia does not reproduce the severe lesions seen during hypoxic perfusion. These results suggest that transport activity is a determining factor of anoxic cell death in the thick ascending limb of Henle's loop.

Animals↗
PubMed1983

Blockade of the renal tubular effects of vitamin D by cycloheximide in the rat.

To further characterize the mechanisms by which 25(OH) vitamin D3 (25(OH)D3) and 1.25(OH)2 vitamin D3 (1,25(OH)2D3) suppress the phosphaturic action of parathyroid hormone (PTH) we have studied the effects of cycloheximide (cyclohex), a protein synthesis inhibitor, on the interaction between PTH and vitamin D metabolites in parathyroidectomized (PTX) rats, both in vivo and in vitro experiments. In clearance studies PTX PTH-infused rats were pretreated with cyclohex 2 h before the administration of vitamin D. In control, PTX PTH-infused rats not pretreated with cyclohex, the administration of 25(OH)D3 and 1,25(OH)2D3 was associated with a fall in fractional excretion of phosphate (CP/CIN) from 0.30 +/- 0.05 to 0.16 +/- 0.02 and from 0.31 +/- 0.05 to 0.13 +/- 0.01 (P less than 0.005) respectively. Cyclohex-pretreated PTX PTH-infused rats failed to respond to both 25(OH)D3 and 1,25(OH)2D3, and CP/CIN, which rose after PTH, remained 0.32 +/- 0.05 and 0.29 +/- 0.03 respectively. In vitro, both 25(OH)D3 and 1,25(OH)2D3 inhibited the PTH-induced activation of adenylate cyclase in the renal isolated membrane fractions. Pretreatment with cyclohex abolished this effect of vitamin D metabolites. These results show that cyclohex blocks the antiphosphaturic effects of both 25(OH)D3 and 1,25(OH)2D3 but does not alter the response to PTH. These findings are consistent with the possibility that the acute renal action of vitamin D depends on de novo synthesis of protein.

Adenylyl Cyclases↗
PubMed1983

Selective glutathione depletion on function and structure of the isolated perfused rat kidney.

The role of glutathione (GSH) in the preservation of renal function and the pathogenesis of renal injury has been investigated using the isolated perfused rat kidney as a model. In kidneys perfused for 80 min with 5 mM glucose as the only exogenous substrate, tissue GSH becomes depleted, renal function deteriorates, and a degenerative change appears, restricted to the medullary thick ascending limb. These abnormalities can be ameliorated by providing amino acid supplements or by adding GSH itself to the perfusion. To distinguish between the effects of amino acid supplementation and GSH depletion per se, selective depletion of GSH was accomplished in several different ways. Synthesis of GSH was inhibited by the addition of dl-buthionine-SR-sulfoximine, a specific inhibitor of gamma-glutamyl cysteine synthetase. GSH depletion was also produced by 2-cyclohexene-1-one and diethylmaleate, both known to diminish the concentration of GSH selectively without affecting protein thiols. Perfused kidneys selectively depleted of GSH showed significant impairment of concentrating ability, and less marked decreases in tubular reabsorption of sodium. The degenerative changes in the medullary thick ascending limb, on the other hand, were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗