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Biomedical subjects

M Brezis

Publications and source records attributed to M Brezis.

At least 109 records · Page 6Linked to original sources
PubMed1989

Protective role of furosemide and saline in radiocontrast-induced acute renal failure in the rat.

Acute renal failure (ARF) can be produced in rats by a combination of insults which augment transport activity and blunt regulatory mechanisms designed to maintain medullary oxygen sufficiency. This type of ARF is characterized by necrosis of medullary thick ascending limbs (mTALs). Uninephrectomized, salt-depleted rats injected with indomethacin (10 mg/kg) develop ARF following the administration of the radiocontrast agent, iothalamate. Furosemide (20 mg/kg, intravenous), administered immediately before the contrast material, attenuated the severity of ARF and reduced mTAL necrosis. Treatment with furosemide and/or normal saline prevented both the decline in renal function and mTAL injury. It is concluded that furosemide and normal saline may ameliorate the course of ARF if administered before radiocontrast.

Acute Kidney Injury↗
PubMed1989

Renal medullary Na-K-ATPase and hypoxic injury in perfused rat kidneys.

We wished to see if chronic alterations in Na-K-ATPase activity in the medullary thick ascending limb would modify the susceptibility of its cells to the hypoxic injury produced by perfusion of the isolated kidney. Rats were fed a diet high (64%) or low (8%) in protein for three weeks. Renal medullary Na-K-ATPase was 75 +/- 12 U/mg protein/hr (mean +/- SE) in the high protein group and 44 +/- 3 in rats given low protein. After 90 minutes of perfusion, the kidneys of rats fed a high protein diet showed almost all mTAL cells near the inner medulla with severe damage (93 +/- 4.8%), whereas the same zone in perfused kidneys of rats on a low protein diet showed only 47 +/- 7.7% injury. In a similar fashion, damage to mTAL cells seen in perfused kidneys was greatly augmented by compensatory renal hypertrophy produced by removal of the contralateral kidney two weeks earlier, and by a diet high in potassium given for two weeks, procedures which also increased the activity of medullary Na-K-ATPase. The results suggest that the level of transport work of medullary cells mediated by Na-K-ATPase is a determinant of the vulnerability of mTAL cells to hypoxic injury.

Animals↗
PubMed1989

Improvement of immune-complex nephritis associated with hepatitis B surface antigen excess.

A case of hypocomplementemic membranoproliferative glomerulonephritis was studied during remission of nephrosis induced by high doses of corticosteroids. Hepatitis B surface antigen (HBsAg) and immune complexes were detected in serum and glomeruli. Anti-hepatitis-B surface antibody, undetectable in serum by conventional radioimmunoassays was identified in circulating immune complexes (CIC). On two occasions, improvement in renal function coincided paradoxically with an extreme increase in serum HBsAg levels as well as with marked elevation of CIC. We suggest that, as previously observed in animal models of glomerulonephritis, extreme antigen excess may inhibit glomerular deposition of immune complexes.

Antigen-Antibody Complex↗
PubMed1988

Hypoxic injury to medullary thick ascending limbs in perfused rat kidneys: reversible and irreversible phases.

The tubular epithelial cells located in the renal medulla are normally working in a hypoxic milieu. In isolated rat kidneys perfused with a cell-free medium, the medullary thick ascending limbs of Henle's loop are selectively and reproducibly injured by the imbalance between oxygen demand and supply in this area. Hypoxic lesions rapidly progress from reversible to irreversible forms of cell damage. Reversible injury consists of chromatin margination and mitochondrial swelling, which can disappear upon restoration of an adequate balance of oxygenation. Irreversible injury consists of nuclear pyknosis and cytoplasmic fragmentation, lesions which persist after re-oxygenation or even progress to cell death. Reversible and irreversible phases of hypoxic injury in this distal tubule segment are comparable to, but different from, those previously defined for the proximal tubule.

Animals↗
PubMed1988

Calcium and hypoxic injury in the renal medulla of the perfused rat kidney.

To study the interaction between calcium and the medullary hypoxic lesions found in isolated perfused rat kidneys, the acute effects of high extracellular calcium upon renal function and morphology were evaluated in kidneys perfused with cell-free medium at a total calcium concentration of 8 to 9 mg/dl (controls), 13 to 14 and 19 to 20 mg/dl (high Ca++). High Ca++ increased hypoxic damage to medullary thick ascending limbs from 58.2 +/- 4.0% of tubules in controls to 80.2 +/- 4.0% (P less than 0.005) in the deepest area of the outer medulla. Morphological changes in the cortex were minimal. The increase in damage to medullary thick limbs induced by high Ca++ was prevented by the calcium channel blocker verapamil. Addition of the calcium ionophore A23187 to controls reproduced the effects of high Ca++ with an increase in the proportion of damaged thick limbs to 92.1 +/- 4.1% (P less than 0.001 vs. controls). Addition of equimolar amounts of magnesium chloride did not reproduce the effect of high calcium perfusions. When transport activity was reduced with ouabain, high calcium perfusions were no longer associated with structural damage. In kidneys perfused with a medium enriched with amino acids, the proportion of tubules with severe, irreversible damage increased from 12 +/- 3 to 43 +/- 10% (P less than 0.01) after high calcium perfusion, and to 75 +/- 12% (P less than 0.001) after perfusion with the calcium ionophore. High extracellular and intracellular calcium appear to act in concert with hypoxia to increase the susceptibility of the renal medulla to injury by mechanisms potentially operative in hypercalcemic and ischemic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1988

Familial medullary sponge kidney in association with congenital absence of teeth (anodontia).

Medullary sponge kidney was found in association with congenital absence of teeth (anodontia) in 3 siblings of a single family. Anodontia occurs in the rare familial syndrome of ectodermal dysplasia, but its association with a renal (mesodermal) anomaly is not known. The present report lends further support to a possible hereditary etiology for medullary sponge kidney.

Adult↗
PubMed1988

Acute renal failure with selective medullary injury in the rat.

Since human acute renal failure (ARF) is frequently the result of multiple rather than single insults, we used a combination of treatments to induce ARF in rats. Uninephrectomized, salt-depleted rats injected with indomethacin developed ARF after administration of radiocontrast. After 24 h, the plasma creatine rose from 103 +/- 3 to 211 +/- 22 mumol/liter (mean +/- SE) and the creatinine clearance dropped from 0.7 +/- 0.1 to 0.2 +/- 0.04 ml/min (P less than 0.001). Severe injury was confined to the outer medulla and comprised necrosis of medullary thick ascending limbs (mTALs), tubular collapse, and casts. Other nephron segments were free of damage except for the proximal convoluted tubules which showed vacuole formation originating from lateral limiting membranes that resembled changes reported in human contrast nephropathy. Cell damage to mTALs included mitochondrial swelling, nuclear pyknosis, and cytoplasmic disruption with superimposed calcification; these changes were most severe in the deepest areas of the outer medulla, away from vasa recta in zones remote from oxygen supply. The fraction of mTALs with severe damage was 30 +/- 7% (range 2-68) and the extent of injury was correlated with a rise in plasma creatinine (r = 0.8, P less than 0.001). Thus, the nature of mTAL injury was similar to the selective lesions observed in isolated kidneys perfused with cell-free medium and was shown to derive from an imbalance between high oxygen demand by actively transporting mTALs and the meager oxygen supply to the renal medulla. Combined multiple renal insults in the rat produce ARF that resembles the clinical syndrome of contrast nephropathy and is characterized by selective mTAL injury conditioned by medullary hypoxia.

Acute Kidney Injury↗
PubMed1987

Physiological and clinical implications of medullary hypoxia.

Because of countercurrent capillary flow, the renal medulla of mammalian kidneys is perpetually hypoxic, the ambient oxygen tension hovering close to the critical Po2 that limits respiration. Within this environment, the mitochondria-rich cells of the medullary thick ascending limb (mTAL) require large amounts of energy to accomplish the work of ion transport. These cells are therefore uniquely vulnerable to anoxic damage, as is demonstrated by morphological changes in isolated perfused rat kidneys. The lesions of hypoxia in mTAL cells of perfused kidneys can be greatly exaggerated by maneuvers that increase the work of transport and practically eliminated by inhibitors of active transport, like ouabain or furosemide, or by interrupting glomerular filtration. The close dependence of experimental ischemic injury on active transport suggests that endogenous inhibitors of transport may play an important physiological role in modulating the susceptibility of the medulla to anoxic injury in health and disease. Candidates for this role include adenosine and locally formed derivatives of arachidonic acid that have been shown to influence metabolism and transport.

Acute Kidney Injury↗
PubMed1986

Mitochondrial activity: a possible determinant of anoxic injury in renal medulla.

In brain, heart and kidney, cell work in the absence of oxygen has been thought to precipitate anoxic damage by increasing the rate of depletion of cellular energy stores. In the medullary thick ascending limb of isolated perfused rat kidneys, however, reduction of ATP synthesis by a variety of mitochondrial or metabolic inhibitors caused ATP depletion comparable to that produced by oxygen deprivation but did not reproduce the lesions of anoxia. In these cells, unrestrained mitochondrial activity may be an important source of anoxic injury.

Adenosine Triphosphate↗
PubMed1986

Second degree type II and complete atrioventricular block due to hyperkalemia.

An 83-year-old woman was hospitalized with complete atrioventricular block and a pulse of 20/min. Three days earlier an electrocardiogram had revealed right bundle branch block with classic type II second degree atrioventricular block. Admission potassium was 7.8 meq/L; within 24 hours the potassium was lowered to 4.9 meq/L and the atrioventricular block disappeared. The patient was followed for nineteen months and remained normokalemic without recurrence of atrioventricular block, although the right bundle branch block persisted. She was then readmitted with bradycardia due to complete atrioventricular block despite normokalemia. We conclude that hyperkalemia can produce the classic picture of progressive bilateral bundle branch disease leading to high degree atrioventricular block, although this seems to occur in patients with extensive intrinsic disease of the conduction system.

Aged↗
PubMed1986

Differential responsiveness of proximal tubule segments to metabolic inhibitors in the isolated perfused rat kidney.

Rat kidneys were perfused for 90 minutes with cyanide, rotenone, antimycin, 2-deoxyglucose, or combinations of rotenone or antimycin with 2-deoxyglucose in oxygenated Krebs-albumin medium. Following perfusion, proximal tubule injury was evaluated by light microscopy. The types of lesions seen were similar to those previously reported after hypoxic perfusion and included brush border clubbing/mitochondrial swelling in S1 and S2 and cytoplasmic edema or cell fragmentation in S3. This finding supports the contention that these lesions represent characteristic responses of these segment types and that the S3 response differs from that in S1 and S2. S1 appeared most vulnerable to low dose cyanide or inhibition of mitochondrial electron transport (rotenone, antimycin). Inhibition of glycolysis (2-deoxyglucose) only produced injury in S2 tubules. With high dose cyanide or a combination of 2-deoxyglucose with either rotenone or antimycin, there was diffuse proximal tubule damage. Thus S3 appeared more resistant than the convoluted tubular segments to both inhibition of glycolysis and to inhibition of mitochondrial electron transport. This finding stands in contrast to the selective vulnerability of the S3 segment in ischemic renal injury.

Animals↗
PubMed1986

Hypoxic injury in the proximal tubule of the isolated perfused rat kidney.

The effect of hypoxia on the morphology of the proximal tubule was examined in isolated rat kidneys perfused with Krebs-albumin medium, gassed with 95% N2/5% CO2 for 45, 90 and 190 min. The major findings were heterogeneity of types of cell injury and definable topographical zones of protection from damage. The characteristic injury in S1 and S2 was that of mitochondrial swelling and brush border alterations that progressed to complete disorganization of this zone. S3 manifested two distinct lesions, one characterized by cell swelling and the other by tubular epithelial fragmentation. Protection from these injuries was seen in tubules located in periarterial zones, apparently due to gradients of oxygenation. The same types of injury but without zones of protection were seen after perfusion with cyanide (10 mM) in oxygenated medium. A "reflow" period of oxygenated perfusion did not alter the fundamental character of these lesions but affected tubules showed progression of damage while there was preservation of tubules in periarterial areas. Thus the responses of the proximal tubule to hypoxic injury depends both on segment type (S1, S2 versus S3) and on tubular location in relation to O2 availability. Additional factors appear to determine the type of response in S3 tubules.

Animals↗
PubMed1986

Transport-dependent cell injury in the S3 segment of the proximal tubule.

Two distinct types of injury, cytoplasmic edema and cell fragmentation occur in the S3 segment of the proximal tubule in isolated hypoxic perfused rat kidneys (Krebs-albumin medium gassed without O2). The proportion of S3 tubules with fragmentation strongly correlated with the GFR and urine output during the perfusion, and approached 100% when the GFR was increased by high perfusion pressure. Conversely, the fragmentation lesion was absent and the edema lesion extensive when tubular transport was inhibited by perfusion with hyperoncotic medium to prevent glomerular filtration or by addition of ouabain (10(-2) M) to the perfusate. Polyene antibiotics increase membrane permeability and thus the work of active electrolyte transport. Perfusion with amphotericin (3 X 10(-5) M) or nystatin (200 U/mliter) in oxygenated medium also produced fragmentation in S3. The lesion was prevented in the non-filtering kidney. Ouabain completely eliminated the cell fragmentation due to nystatin and significantly reduced that due to amphotericin. These results suggest that the injury of cell fragmentation is enhanced by transport activity and diminished when transport is inhibited. The edema lesion appears fundamentally different and more akin to lesions described in ischemia where tubular flow is absent, active transport is diminished, and the morphologic changes appear related to loss of cell volume regulation. The type of hypoxic damage exhibited by proximal tubular S3 segments may therefore be conditioned by active ion transport of tubular cells.

Amphotericin B↗
PubMed1986

Primary hyperparathyroidism presenting as cervical myelopathy.

Quadriplegia as a presenting syndrome in a case of primary hyperparathyroidism is reported. The clinical picture was misdiagnosed as a space-occupying lesion in the cervical spinal canal, for which an unnecessary laminectomy was performed. The neurologic deficits disappeared following the removal of a parathyroid adenoma. The neurologic presentations of hyperparathyroidism are reviewed and discussed.

Adenoma↗
PubMed1986

Laetrile intoxication and hepatic necrosis: a possible association.

A 65-year-old woman with cirrhosis and hepatoma lapsed into deep coma, hypotension, and acidosis after ingestion of 3 gm of Laetrile, a cyanogenetic glucoside. After initial treatment, the patient regained consciousness, but massive hepatic damage led to her death. We suggested a possible relationship between Laetrile poisoning and massive hepatic necrosis.

Aged↗
PubMed1986

Substrates induce hypoxic injury to medullary thick limbs of isolated rat kidneys.

Under certain conditions, excess of substrates may be detrimental to the kidney. In isolated rat kidneys perfused with cell-free medium, oxidative metabolism to support reabsorptive transport in the presence of a limited oxygen supply results in hypoxic injury to medullary thick ascending limbs (mTAL). Since inhibitors of mitochondrial respiration markedly reduced this injury, we evaluated the effects of altering the availability of substrate for oxidative metabolism in the mTAL. Inhibition of glucose utilization with 2-deoxyglucose (50 mM) and simultaneous inhibition of long-chain fatty acid metabolism with 2-tetradecylglycidic acid (10(-4) M) in the absence of exogenous substrates consistently reduced hypoxic cell injury to mTAL. Similarly, the direct inhibition of substrate oxidation by the citric acid cycle with monofluoroacetate (5 mM) also reduced the extent of damage to this nephron segment. Bypassing these metabolic blockades with L-lactate, pyruvate, or alpha-ketoglutarate stimulated renal oxidative metabolism and increased hypoxic damage to mTAL. Enhanced renal metabolism and function (higher renal oxygen consumption, tubular reabsorption of sodium, and glomerular filtration rate) were paradoxically associated with greater damage to mTAL. Thus, when oxygen supply is limited, substrate-supported aerobic metabolic activity for tubular transport may induce hypoxic injury in the renal medulla.

Animals↗