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H Trachtman

Publications and source records attributed to H Trachtman.

At least 19 recordsLinked to original sources
PubMed2001

Cytoprotective effect of curcumin in human proximal tubule epithelial cells exposed to shiga toxin.

We conducted the following experiments to determine whether curcumin, an antioxidant compound extracted from the spice tumeric, inhibits cell death induced by Shiga toxin (Stx) 1 and 2 in HK-2 cells, a human proximal tubule cell line. Cells were incubated for 24-48 h with Stx1 or Stx2, 0-100 ng/ml. Test media contained either no further additives or 10-50 microM curcumin. Exposure to Stx1 and Stx2, 100 ng/ml, reduced cell viability to approximately 25% of control values after 24 h and 20 microM curcumin restored viability to nearly 75% of control. Cell staining confirmed that Stx1 and Stx2-induced damage in HK-2 cells involved a combination of apoptosis and necrosis. Thus, Stx1 caused apoptosis and necrosis in 12.2 +/- 2.2 and 12.7 +/- 0.9% of HK-2 cells, respectively. Similarly, Stx2 caused apoptosis and necrosis in 13.4 +/- 2.1 and 9.0 +/- 0.5% of HK-2 cells, respectively. Addition of 20 microM curcumin decreased the extent of apoptosis and necrosis to 2.9 +/- 2.0 and 3.8 +/- 0.2%, respectively in the presence of Stx1 and to 3.0 +/- 2.1 and 3.9 +/- 0.3%, respectively, for Stx2 (P < 0.01). Stx-induced apoptosis and its inhibition by curcumin were confirmed by DNA gel electrophoresis and by an assay for fragmentation. The protective effect of curcumin against Stx1 and Stx2-induced injury to HK-2 was not related to its antioxidant properties. Instead, curcumin enhanced expression of heat shock protein 70 (HSP70) in HK-2 cells under control conditions and after exposure to Stx1 or Stx2. No injury was detectable after incubation of LLC-PK(1) or OK cells, non-human proximal tubule cell lines, with Stx1 or Stx2. Thus, curcumin inhibits Stx-induced apoptosis and necrosis in HK-2 cells in vitro. The cytoprotective effect of curcumin against Stx-induced injury in cultured human proximal tubule epithelial cells may be a consequence of increased expression of HSP70.

Animals↗
PubMed2001

HUS or not HUS?

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed2001

mRNA expression for insulin-like growth factor 1, receptors of growth hormone and IGF-1 and transforming growth factor-beta in the kidney and liver of Zucker rats.

Kidney dysfunction and mesangial enlargement are consequences of obesity found in Zucker rats. This study examines some of the early mechanisms by which the kidneys of Zucker rats undergo these changes. Our study shows that the glomerular planar area in the genetically obese Zucker rat undergo enlargement as early as 12 weeks of life, compared to the lean controls. This suggests mesangial proliferation is already occurring at this time, earlier than previously shown. The mRNA expression for IGF-I, and GHR in the kidney and liver of the obese Zucker rats were significantly reduced compared to the lean controls. However, the mRNA of the IGF-IR was significantly elevated in the kidney of the obese Zucker rats. The increase in kidney IGF-1R mRNA in the obese Zucker rat may suggest an increase in IGF-1 binding leading to the kidney hypertrophy observed in these rats.

Journal Article↗
PubMed2000

Yield of renal arteriography in the evaluation of pediatric hypertension.

The prevalence of renovascular disease is estimated to be 3%-5% in pediatric patients with hypertension. The utility of non-invasive imaging tests has not been evaluated in children, and renal arteriography remains the diagnostic test of choice. However, there are no established guidelines for the application of this test and information is not available about the likelihood of detecting an abnormality if an arteriogram is performed in children with hypertension. Therefore, we reviewed the yield of renal arteriography in pediatric patients if the test was performed based on the following two criteria: (1) severe hypertension exceeding the 99th percentile for age and sex or (2) failure to control high blood pressure with one antihypertensive drug. During the period 1983-1998, 28 children (mean age 11.7 years) who satisfied one of the above criteria underwent renal arteriography to investigate hypertension. None of the patients were renal transplant recipients. The average duration of hypertension was 11 months and the peak blood pressure was 168/107 mmHg. The renal arteriogram was abnormal in 12 patients (43%). Unilateral renal artery stenosis was the most-common abnormality. When the patients were divided into two groups - those with an abnormal or normal test result - they did not differ in age, sex, or racial distribution. The peak systolic blood pressure was higher in children with an abnormal renal arteriogram (P<0.05). Among those undergoing the arteriogram on the basis of the first criterion, i.e., severe hypertension, 11 of 23 (48%) studies were abnormal. Five children had an arteriogram based on the second criterion--failure to control the blood pressure with one medication--and in 1 patient (20%) the test was abnormal. We conclude that the prevalence of renovascular disease in a population of hypertensive children subjected to renal arteriography is around 40%. Two clinical criteria--namely severe hypertension or failure to control hypertension effectively with one drug--are useful to guide the application of renal arteriography in children with hypertension.

Adolescent↗
PubMed2000

Pediatric biopsy of a single native kidney.

Technological improvements have reduced the frequency of complications in children receiving a percutaneous renal biopsy. No study has systematically compared the safety of open and percutaneous kidney biopsy. Yet many nephrologists consider a single native kidney an absolute contraindication to percutaneous biopsy. We have established an international registry of single native kidney biopsies in children and we now report our early results. Eight biopsies are included. Seven patients had percutaneous biopsies and one an open biopsy. None of the patients had major complications, and adequate tissue was obtained from all. Our limited experience indicates that the presence of a single native kidney is not an absolute indication for an open approach. We encourage our colleagues to report to the international registry in order to further document the safety of percutaneous biopsy of the single native kidney in children.

Acute Kidney Injury↗
PubMed2000

Bartter syndrome and focal segmental glomerulosclerosis: a possible link between two diseases.

We describe a patient with signs and symptoms of classic Bartter syndrome. The patient tested negative for all known genetic abnormalities associated with this tubular disorder. Proteinuria was found within 1 year after the diagnosis of Bartter syndrome. A renal biopsy performed 6 months later, when her kidney function was normal, revealed focal segmental glomerulosclerosis (FSGS). We propose a link between stimulation of the renin-angiotensin system and sclerotic changes in the glomerulus. This lesion may explain previous reports of kidney failure in patients with Bartter syndrome.

Adolescent↗
PubMed2000

Anti-apoptotic effect of L-arginine in cultured rat mesangial cells.

Nitric oxide has been shown to be an important factor in the regulation of apoptosis in mesangial cells. The following studies were conducted to determine whether L-arginine, the metabolic precursor of nitric oxide synthesis, directly modulates programmed cell death in response to a variety of stimuli. Cultured rat mesangial cells were exposed for 24-48 h to one of the following four experimental conditions known to induce apoptosis: i) a cytokine combination consisting of interferon-gamma (50 U/ml), interleukin-1 (5 ng/ml), and LPS (10 microg/ml); ii) 0.75 mM hydrogen peroxide; iii) etoposide, 150 microg/ml; and iv) cis-platinum, 100 microg/ml. Addition of L-arginine resulted in a dose-dependent decrease in apoptosis in cytokine-treated RMC. This effect was demonstrable by gel electrophoresis, diphenylamine assay of DNA fragmentation, and an ELISA to detect DNA oligonucleosomes. The effect was not related to increased osmolality of the test media and was not reproduced by the addition of equimolar D-arginine. L-Arginine also reduced apoptosis and necrosis in RMC that were incubated with etoposide and cis-platinum. In contrast, the amino acid had no beneficial effect on RMC survival following exposure to hydrogen peroxide. These findings indicate that several components of the nitric oxide biosynthetic pathway including the precursor and the enzymatic product independently exert direct effects on apoptosis in cultured rat mesangial cells.

Animals↗
PubMed2000

The role of nitric oxide in obstructive nephropathy.

PURPOSE: Ureteral obstruction leads to tubulointerstitial fibrosis and loss of renal function. Nitric oxide production ameliorates fibrosis due to obstructive uropathy. However, nitric oxide is produced by 3 isoforms of the enzyme, nitric oxide synthase. We evaluated the role of inducible nitric oxide synthase in obstructive uropathy using nitric oxide synthase knockout mice, and determined whether the administration of L-arginine to promote nitric oxide synthesis by alternative nitric oxide synthase isoforms modulates renal fibrosis in these animals. MATERIALS AND METHODS: Complete unilateral ureteral obstruction was created in wild-type C57 and inducible nitric oxide synthase knockout mice. Control animals of each strain underwent sham surgery. Throughout the experiment mice had free access to untreated tap water or water supplemented with 10 gm./l. L-arginine. Animals were sacrificed 1 and 2 weeks, respectively, after creation of unilateral ureteral obstruction. We obtained serum as well as bladder and obstructed renal pelvic urine, and determined the nitrite level in each fluid. Renal cortical thickness was measured in the normal and obstructed kidneys. The degree of tubulointerstitial fibrosis was evaluated by trichrome staining and type I collagen deposition in kidney tissue specimens. RESULTS: Nitrite was significantly decreased in the serum, bladder and renal pelvic urine of inducible nitric oxide synthase knockout mice with unilateral ureteral obstruction compared with that in wild-type C57 mice at 1 and 2 weeks (p<0.05). In knockout mice with unilateral ureteral obstruction 1 week in duration that drank tap or L-arginine supplemented water nitrite in serum and each urine sample was higher than in sham operated knockout controls. The level returned to baseline after 2 weeks of obstruction (p<0.05). After 2 weeks of obstruction there was significantly greater cortical thinning in knockout than in C57 mice (p<0.05). Moreover, knockout mice given L-arginine supplemented water for 2 weeks had even greater cortical thinning than after 1 week or than mice given tap water for 1 to 2 weeks (p<0.05). Decreased renal cortical thickness in knockout mice after 2 weeks of obstruction was associated with less intense trichrome staining and a virtual absence of type I collagen deposition compared with findings in the wild-type C57 strain. CONCLUSIONS: Inducible nitric oxide synthase knockout mice with unilateral ureteral obstruction have significantly lower nitrite in serum and urine than wild-type C57 mice. Knockout mice also have more severe renal cortical thinning than C57 animals after creation of unilateral ureteral obstruction. Providing L-arginine supplemented water to inducible nitric oxide synthase knockout mice exacerbates the loss of cortical thickness. Alterations in cortical thinning that we observed in knockout mice were associated with decreased tubulointerstitial fibrosis and a decreased net renal extracellular matrix accumulation. These data indicate that endothelial or neuronal nitric oxide synthase may be more important than inducible nitric oxide synthase for modulating renal fibrosis in obstructive uropathy.

Animals↗
PubMed1999

Influence of alpha-tocopherol over the time course of experimental IgA nephropathy.

The present study investigated the pathogenesis and the time course of kidney injury in experimental IgA nephropathy. In order to determine an appropriate period in the course of experimental IgA nephropathy to study renal injury and repair, we examined proteinuria and IgA deposition in the renal mesangium after 4, 8, and 16 weeks of mucosal challenge by bovine gamma globulins (BGG) provided in the drinking water. The hallmark of IgA deposition in the mesangium was present after 4 weeks and 8 weeks of BGG inoculation, but by 16 weeks, the mesangial IgA deposition had resolved. In addition, we confirmed our previous report on the beneficial effects of alpha-tocopherol in reducing proteinuria in IgA nephropathy at 8 weeks, and extended this observation to investigate the effects of dietary supplementation of alpha-tocopherol at both 4 weeks and 16 weeks. Proteinuria resolved spontaneously at 16 weeks. There is oxidative stress, as suggested by the elevation in plasma and renal malondialdehyde content, and increased fibrogenic cytokine message, as suggested by elevated transforming growth factor beta1 mRNA. These increases were clearly blunted by alpha-tocopherol at both 4 weeks and 8 weeks. Treatment with alpha-tocopherol was associated with a significant reduction in the severity of proteinuria. Thus, our data suggest that the period between 4 and 8 weeks of BGG vaccination could be relevant in designing an appropriate model to study the molecular biology of the pathogenesis of renal injury and the effects of treatment. The 16-week model may be useful in exploring gene expression involved with spontaneous resolution.

Animals↗
PubMed1999

Vitamin E treatment of focal segmental glomerulosclerosis: results of an open-label study.

Experimental data indicate that excessive production of reactive oxygen molecules contributes to progressive renal injury and that treatment with antioxidants attenuates this damage. Therefore, we investigated whether vitamin E supplementation could ameliorate renal disease and reduce proteinuria in children with a variety of kidney disorders. Vitamin E, 200 IU twice daily, was administered orally to 11 children with focal segmental glomerulosclerosis (FSGS) (group A) and 9 patients with miscellaneous kidney diseases (group B) [Henoch-Schönlein purpura nephritis (n=3), urinary tract anomalies (n=2), non-specific immune complex glomerulonephritis (n=2), IgA nephropathy (n=1), and reflux nephropathy (n=1)]. The duration of vitamin E treatment, when no other therapy was introduced, was 2.9+/-0.4 months. Proteinuria was determined by measuring the protein:creatinine ratio (mg/mg) in an early morning urine specimen. In children with FSGS, administration of vitamin E lowered the protein:creatinine ratio in 10 of 11 patients from 9. 7+/-5.1 to 4.1+/-1.1 (P<0.005). In contrast, among children with miscellaneous renal diseases, vitamin E had no beneficial impact on urinary protein excretion-protein:creatinine ratio 2.5+/-1.0 pre versus 2.4+/-1.2 post antioxidant. Vitamin E supplementation had no effect on glomerular filtration rate, serum albumin, or cholesterol concentration in either group of patients. These findings suggest that reactive oxygen molecules may play a more-prominent role in causing renal injury in patients with FSGS than in other kidney disorders. Antioxidant therapy may be a useful adjunct in the treatment of children with FSGS and proteinuria that is refractory to standard medical management.

Adolescent↗
PubMed1999

Pathogenesis, treatment, and therapeutic trials in hemolytic uremic syndrome.

Diarrhea-associated hemolytic uremic syndrome is one of the most common causes of acute renal failure in childhood. Nearly all cases are the result of an antecedent infection by Shiga toxin--producing strains of Escherichia coli, especially the O157:H7 serotype. Most cases occur after ingestion of contaminated meat; however, new food sources such as leaf lettuce, alfalfa sprouts, and goat's milk have been identified, and diarrhea-associated hemolytic uremic syndrome can occur after exposure to contaminated water in recreational swimming sites. Diarrhea-associated hemolytic uremic syndrome is a systemic disease with activation of a variety of inflammatory cytokines. Kidney injury may result from direct effects of the Shiga toxin on renal tubular epithelial cells as well as endothelial cells. Early diagnosis of diarrhea-associated hemolytic uremic syndrome may be expedited by the introduction of new techniques to rapidly detect toxin and microorganism in stool samples. Optimal therapy of diarrhea-associated hemolytic uremic syndrome includes intensive management of the renal failure and serious extrarenal complications that may occur during the course of disease. The role of antibiotics in prevention and amelioration of diarrhea-associated hemolytic uremic syndrome remains controversial. Experimental therapies that are undergoing evaluation in clinical trials include SYNSORB Pk (SYNSORB Biotech, Inc., Calgary, Alberta, Canada), a drug designed to bind Shiga toxin in the lumen of gastrointestinal tract. Immunization strategies are also being developed and tested. It is hoped that with continued progress in this field the incidence of diarrhea-associated hemolytic uremic syndrome in children will be substantially reduced in the coming years.

Adult↗
PubMed1999

Pharmacological treatment of nephrotic syndrome.

In the "minimal change" nephrotic syndrome (MCNS), steroids induce remissions in most cases (93% in children and 81% in adults). Response occurs in an average time of 11 days in children but may take up to 16 weeks in adults. The dose of prednisone is 60 mg/m(2)/day (maximum 80 mg/day) given usually for 4 weeks and then reduced to 40 mg/m(2) on alternate days for a few weeks. The medication may be discontinued abruptly at the end of the course of treatment. Children who do not respond to prednisone should be biopsied. Those whose biopsy shows minimal changes may have a remission with more prolonged alternate day treatment, or may need cyclophosphamide or cyclosporine. Relapses of nephrotic syndrome are common and usually respond to steroids given daily until remission, then on alternate days for 4 weeks. In adults prednisone on alternate days for 1 year after the presenting attack decreases the risk of relapse. Toxicity is a problem only in steroid-dependent patients who may require other drugs. Cyclophosphamide (2-3 mg/kg/day) and chlorambucil (0.15 mg/kg/day) for 8-12 weeks induce long-term remissions in 25-70% of children and are also beneficial in adults. The effectiveness of cyclophosphamide in steroid-resistant MCNS is limited to bringing about a faster remission. In children with MCNS who are initially steroid-responsive and later become resistant, cyclophosphamide usually induces a remission and restores steroid responsiveness. The toxicity of cyclophosphamide and chlorambucil in MCNS has generally been mild and reversible. It includes bone marrow depression, hemorrhagic cystitis, some hair loss, infertility and, extremely rarely, oncogenesis. The risk of gonadal toxicity is minimized with total doses below 200 mg/kg for cyclophosphamide and 7-10 mg/kg for chlorambucil. Seizures have been reported in 8% of children treated with chlorambucil. Cyclosporine (6 mg/kg/day initially) produces complete remissions in 85% of children and 79% of adults with steroid dependence and in 67% of children and 61% of adults with steroid resistance. Levamisole may be helpful in steroid-dependent cases, but data about its efficacy are conflicting. Cyclosporine and levamisole usually do not induce permanent remissions.

Journal Article↗
PubMed1999

Growth of rat mesangial cells on oxidized extracellular matrix increases inducible nitric oxide synthase activity.

Biochemical modification of extracellular matrix (ECM) proteins can alter the function in overlying cells. We tested the hypothesis that metal-catalyzed oxidation of native ECM and individual matrix proteins modulates the activity of inducible nitric oxide synthase (iNOS) in cultured rat mesangial cells (RMC). Oxidized modification of native ECM resulted in a 32% increase in iNOS activity (P<0.01) without influencing the response to supplemental L-arginine or to the addition of the iNOS inhibitor, L-NAME. Immunoblot analysis indicated that enhanced iNOS activity was not associated with a parallel rise in the cytosolic content of iNOS. Synthesis of type IV collagen was unaffected by growth of RMC on oxidized native ECM. Oxidation of three normal constituents of the mesangial matrix - type IV collagen, laminin, and fibronectin - also stimulated iNOS activity in overlying RMC by 18-32% (P<0.05). Growth of RMC on oxidized type I collagen or Vitrogel had no effect on NO production. We conclude that oxidized modification of the mesangial matrix promotes increased iNOS activity and NO production by mesangial cells. Further work is required to determine whether this response limits glomerular injury or promotes damage to the mesangium in oxygen free radical-mediated diseases such as chronic renal failure, atherosclerosis and diabetes.

Animals↗
PubMed1999

Circulating factor in patients with recurrent focal segmental glomerulosclerosis postrenal transplantation inhibits expression of inducible nitric oxide synthase and nitric oxide production by cultured rat mesangial cells.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) recurs in nearly 30% of patients who progress to end-stage renal disease and then receive a kidney transplant. A circulating plasma factor has been isolated from these patients that increases glomerular permeability to albumin in vitro. Because of the pivotal role of the mesangial cell in the accumulation of extracellular matrix (ECM) material within the glomerulus and the modulation of matrix protein synthesis by nitric oxide (NO), we examined the effect of the FSGS factor on inducible nitric oxide synthase (iNOS) expression and NO production by cultured rat mesangial cells (RMC). METHODS: RMC were incubated with the supernatant following 70% ammonium sulfate precipitation of serum from patients with recurrent FSGS. RESULTS: Addition of the FSGS factor to cultured RMC led to a significant inhibition of nitrite accumulation, an index of NO synthesis. There was a parallel decline in iNOS gene and protein expression. Sera obtained from control patients or those with minimal change nephrotic syndrome or diabetic nephropathy that was processed in the same manner as FSGS samples had no effect NO synthesis or iNOS activity. The inhibitory effect of the FSGS factor on NO production persisted despite addition of indomethacin (0.1-1 mumol/L) or cyclosporine (25 micrograms/mL) to test media. CONCLUSIONS: These data indicate that the FSGS factor independently alters two aspects of glomerular function--permselectivity and matrix protein synthesis--by distinct mechanisms. FSGS factor-induced disturbances in iNOS gene and protein expression and NO production by mesangial cells may antagonize the antifibrotic effect of NO within the mesangium and contribute to progressive glomerulosclerosis in patients with primary FSGS.

Animals↗
PubMed1998

Effect of vascular endothelial growth factor on nitric oxide production by cultured rat mesangial cells.

Vascular endothelial growth factor (VEGF) stimulates nitric oxide (NO) production by endothelial cells in vitro and in vivo. However, the impact of VEGF on inducible nitric oxide synthase (iNOS) activity and NO synthesis in cultured mesangial cells is not known. Therefore, we measured nitrite accumulation in cytokine-stimulated, rat mesangial cells (RMC) in response to graded concentrations of VEGF. Addition of VEGF (10-50 ng/ml) did not alter RMC viability or NO production in either normal (5.6 mM) or high (33.3 mM) glucose conditions. Exposure of RMC to VEGF did not modify the effects of L-arginine (20 mM) or L-NAME (1 mM) on nitrite accumulation in normal or high glucose media. The steady state abundance of iNOS mRNA and the cytosolic content of iNOS protein were unaffected by addition of VEGF. Cultured RMC expressed the high-affinity tyrosine kinase VEGF receptors, flt and flk/KDR, and the levels were not modulated by incubation in normal or high glucose media. We conclude that VEGF does not regulate proliferation or NO production in cultured RMC. These findings suggest that disturbances in the normal interaction between VEGF and NO are not involved in the pathogenesis of abnormal mesangial cell structure or function in diabetic nephropathy.

Animals↗