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Biomedical subjects

Y Wolman

Publications and source records attributed to Y Wolman.

17 recordsLinked to original sources

Effect of montelukast pretreatment on inducible nitric oxide synthase mRNA expression in the lungs of antigen-challenged allergic mice.

BACKGROUND: Growing evidence suggests that inducible nitric oxide synthase (iNOS) is the main source of the high output of exhaled nitric oxide (NO) in asthma. Treatment of asthmatic patients with glucocorticoids reduces high levels of exhaled NO mainly by inhibiting the transcription of iNOS. A similar reduction in exhaled NO was recently observed in patients treated with the leukotriene receptor antagonists, but the exact interaction between these drugs and iNOS remains obscure. OBJECTIVE: The purpose of this study was to evaluate the effect of a leukotriene receptor antagonist, montelukast, on the expression and activity of iNOS in a murine model of allergic asthma. METHODS: Twenty-four BALB/c mice were sensitized to OVA and were equally divided into 3 groups (Groups 1-3). Eight additional mice were sham sensitized and served as a negative control group (Group 4). Group 1 received montelukast 1 mg/kg/day in their drinking water, Group 2 received dexamethasone 1 mg/kg/day in their drinking water and Groups 3 and 4 received plain tap water. After 1 week, the animals were challenged by inhalation of OVA and, 3 h later, they were killed and their lung cells were isolated by enzymatic tissue digestion. NO generation was measured by a Griess assay, and iNOS mRNA was studied by RT-PCR. RESULTS: A significant increase in iNOS mRNA expression and in NO generation was evident after allergen challenge compared with the controls. Pretreatment with montelukast mildly decreased NO production without producing a concomitant significant decrease in iNOS mRNA expression. CONCLUSION: Unlike pretreatment with glucocorticoids, we failed to find compelling evidence for a major role for montelukast treatment in the modulation of iNOS mRNA in a murine model of acute asthma.

Acetates↗

Time course of lipopolysaccharide-induced nitric oxide synthase mRNA expression in rat glomeruli.

The decrease in glomerular filtration rate that is characteristic of sepsis has been shown to result from the local glomerular inhibition of endothelial nitric oxide synthase (NOS) by nitric oxide (NO) generated from the inducible isoform of NOS (iNOS). iNOS activation depends on de novo synthesis of both RNA and protein. Therefore it is assumed that several hours are required for its full activation. Yet the renal hemodynamic response in sepsis has been documented as early as 60 minutes after lipopolysaccharide (LPS) administration. Experiments were designed to determine the time course of LPS-induced glomerular iNOS mRNA expression and activity in rats. Rats were treated with LPS (2 mg/kg body weight IP). Kidneys were removed after 1,2, 4, 6, and 16 hours. Glomeruli were isolated and incubated. Nitric oxide generation was measured with a Griess assay, and iNOS mRNA was studied by reverse transcriptase-polymerase chain reaction. Similar time course experiments were repeated in glomeruli isolated from normal rats and exposed to LPS in vitro. A significant increase in iNOS mRNA expression was evident as early as 60 minutes after both in vivo and in vitro administration of LPS. The quantity of iNOS mRNA reached its peak between 2 to 4 hours after administration and declined to baseline levels after 16 hours. Immunohistochemical studies were remarkable for a significant increase in the staining for iNOS in glomeruli 2 hours after the in vivo administration of LPS. Plasma nitric oxide concentration after the in vivo administration of LPS increased from a baseline level of 11.25 +/- 0.8 micromol/L to a peak level of 62.9 +/- 3.8 micromol/L (P < .05 vs baseline) at 4 hours and then decreased to 17.5 +/-1.9 micromol/L at 16 hours. Similar results were obtained when the glomerular generation of nitric oxide after in vivo administration of LPS was measured (2.6 +/- 0.8 pmol/h/microg tissue, 17.2 +/- 2.1 pmol/h/microg tissue (P < .05 vs baseline), and 0.4 +/- 0.65 pmol/h/microg tissue, respectively). These results provide evidence of the rapid activation of glomerular iNOS after in vivo and ex vivo administration of LPS and thus support the role of nitric oxide in the early renal hemodynamic response to LPS.

Animals↗

Prenatal diagnosis of interrupted inferior vena cava as an isolated finding: a benign vascular malformation.

We report two cases of interrupted inferior vena cava with azygous continuation diagnosed as an isolated finding during routine prenatal scans. Visualization of the venous vasculature of the abdomen and thorax in the mid-sagittal plane failed to visualize the segment of the inferior vena cava between the kidneys and the liver. A vessel with venous flow was observed parallel, adjacent and posterior to the aorta between the kidney and the right atrium. This blood vessel connected with the superior vena cava. Axial planes of the thorax confirmed the presence of two vessels running paravertebrally. A detailed ultrasound examination of the fetal anatomy failed to demonstrate other anomalies. The neonatal course of both fetuses was uneventful. Isolated interruption of the inferior uena cava can be a vascular malformation without known pathological consequences.

Adult↗

Serial serum MCA measurements in the follow-up of breast cancer patients.

Mucin-like carcinoma-associated antigen (MCA) was serially assayed in 58 women with histologically proven breast cancer after their treatment for primary disease. MCA sensitivity and specificity were 87.5% and 76.9%, respectively, and the positive predictive value 82.4%. 10 patients had elevated MCA and no evidence of disease (NED) during their follow-up, of whom 4 finally developed overt metastases. The 4 had a mean (S.D.) MCA value of 46.48 (18.26) U/ml during the lead time, versus 18.76 (2.69) U/ml in the other 6, who are still at high risk for developing overt metastases. Raised levels of MCA in patients with NED create a dilemma of "treat" versus "wait and see". Early treatment of patients with serially uprising MCA levels should be evaluated in a prospective randomised study to assess its ability to prevent or delay the development of overt metastatic disease and influence survival.

Adult↗

Protein intake and kidney function in humans: its effect on 'normal aging'.

The effect of dietary protein on kidney function expressed by creatinine clearance was studied in healthy subjects following a "normal" unrestricted protein diet and compared with a group of vegetarians maintained on a long-term low-protein diet. Both groups had similar kidney function and displayed the same rate of progressive deterioration in renal function with age. These results suggest that, in contrast with the important therapeutic effect of low-protein intake on the progressive deterioration of kidney function in diseased kidneys, such a diet does not significantly affect kidney function with "normal aging" in healthy subjects.

Adult↗

Alkaline phosphatase activity in fresh intestinal mucosa and cultured mucosal explants.

Alkaline phosphatase (AP) activity is an accepted marker of epithelial cell differentiation and integrity in intestinal mucosal explant systems. In experiments involving AP it is usually expressed as activity per unit protein in tissue culture. It has been previously demonstrated that during organ culture a considerable amount of protein and nucleic acid (NA) may leave the cell and enter the surrounding medium. It may therefore not be appropriate to measure enzyme synthesis in relation to total tissue protein. In this study we attempted to gather additional information on enzyme dynamics and tissue integrity during organ culture of intestinal mucosal explants from children with celiac disease (CD) on a normal diet (ND) (n = 21), children with CD on a gluten-free diet (GFD) (n = 12), and patients with gastrointestinal disorders other than CD (controls) (n = 17). We confirmed the leakage of protein, NA, and AP from the tissue explant into the medium, and normalized the AP data by expressing AP as total AP in tissue plus medium per total NA in tissue plus medium. In patients with CD on a ND, the AP level at time 0 was 9.58 (+/- 12.2) mIU/micrograms NA and after 24 h culture rose to 21.9 (+/- 15.7) mIU/micrograms NA. In patients with CD on a GFD the baseline AP level was 24.9 (+/- 34.8) mIU/micrograms NA, and this value rose after culture to 28.6 (+/- 17.9) mIU/micrograms NA. In the controls the initial AP activity was 17.2 (+/- 15.7) mIU/micrograms NA, and the increase was to 38 (+/- 27.6) mIU/micrograms NA.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

Prebiotic synthesis of hydrophobic and protein amino acids.

The formation of amino acids by the action of electric discharges on a mixture of methane, nitrogen, and water with traces of ammonia was studied in detail. The presence of glycine, alanine, alpha-amino-n-butyric acid, alpha-aminoisobutyric acid, valine, norvaline, isovaline, leucine, isoleucine, alloisoleucine, norleucine, proline, aspartic acid, glutamic acid, serine, threonine, allothreonine, alpha-hydroxy-gamma-aminobutyric acid, and alpha,gamma-diaminobutyric acid was confirmed by ion-exchange chromatography and gas chromatography-mass spectrometry. All of the primary alpha-amino acids found in the Murchison Meteorite have been synthesized by this electric discharge experiment.

Alanine↗

Nonprotein amino acids from spark discharges and their comparison with the murchison meteorite amino acids.

All the nonprotein amino acids found in the Murchison meteorite are products of the action of electric discharge on a mixture of methane, nitrogen, and water with traces of ammonia. These amino acids include alpha-amino-n-butyric acid, alpha-aminoisobutyric acid, norvaline, isovaline, pipecolic acid, beta-alanine, beta-amino-n-butyric acid, beta-aminoisobutyric acid, gamma-aminobutyric acid, sarcosine, N-ethylglycine, and N-methylalanine. In addition, norleucine, alloisoleucine, N-propylglycine, N-isopropylglycine, N-methyl-beta-alanine, N-ethyl-beta-alanine alpha,beta-diaminopropionic acid, isoserine, alpha,gamma-diaminobutyric acid, and alpha-hydroxy-gamma-aminobutyric acid are produced by the electric discharge, but have not been found in the meteorite.

Journal Article↗

Use of esters of N-hydroxysuccinimide in the synthesis of N-acylamino acids.

Several crystalline N-hydroxysuccinimide esters of short- and long-chain fatty acids have been synthesized. These compounds react with free amino acids to form preferentially N-acylamino acids. The reaction of the N-hydroxysuccinimide esters with hydroxylamine and the behavior of the N-acylamino acids on thin-layer chromatography are described.

Amino Acids↗

The outcome of non-selective vs selective nitric oxide synthase inhibition in lipopolysaccharide treated rats.

UNLABELLED: Nitric oxide (NO), generated by inducible nitric oxide synthase (NOS) following lipopolysaccharide (LPS) administration, produces renal failure through autoinhibition of glomerular endothelial NOS activity. Preadministration of selective iNOS inhibitors abolishes this effect. Although nonselective NOS inhibitors further decrease GFR, current clinical trials investigate the effect of nonselective NOS inhibition in septic patients. The goals of our study were to determine whether treatment with selective NOS inhibitors can reverse the decrease in GFR in LPS treated rats with already established renal failure and to define the outcome of LPS treated rats following nonselective NOS inhibition. Four hours following the administration of LPS (4 mg/kg), we measured creatinine clearance (CrCl) before and after the administration of either L-NIL (selective iNOS inhibitor, 3 mg every 20 minutes) or saline. Selective iNOS inhibition attenuated the decrease in blood pressure [ CONTROLS: 105 +/- 6 to 98 +/- 5, LPS: 92 +/- 5* to 83 +/- 4*, LPS + L-NIL: 88 +/- 6* to 94 +/- 6 mm Hg; *p < 0.05, vs controls (n = 6)], and reversed the decrease in GFR after LPS [ CONTROLS: 2.21 +/- 0.13 to 2.07 +/- 0.11, LPS: 0.82 +/- 0.18* to 0.66 +/- 0.22*, LPS + L-NIL: 0.76 +/- 0.15* to 1.86 +/- 0.15 ml/min; *p < 0.05 vs controls (n = 6)]. We next studied the effect of complete non-selective NOS inhibition (L-NAME 200 mg, 2 hours after LPS) on LPS treated rats. All (6/6) animals treated with both LPS and L-NAME died within 2 hours following LPS, while rats treated with either LPS, L-NAME, or LPS + L-NIL survived. Histologic studies performed in all experimental groups were unremarkable. Overnight mortality was studied using smaller doses of L-NAME. All LPS + L-NAME (10/10) and 1/10 LPS treated rats died. L-NAME, control, and LPS + L-NIL animals survived. The characteristic histologic findings in LPS + L-NAME rats were diffuse ischemic changes, most importantly acute myocardial infarction. IN CONCLUSION: Selective iN-OS inhibition might prove to have clinical application as it prevents the decrease in GFR following LPS, even after renal failure is established. Treatment with a non selective NOS inhibitor in septic patients should be reconsidered.

Analysis of Variance↗