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Biomedical subjects

M Khullar

Publications and source records attributed to M Khullar.

At least 19 recordsLinked to original sources
PubMed2006

Oxidative status in stable renal transplantation.

Increased oxidative stress and hyperhomocysteinemia are frequently observed in patients with end-stage renal disease. The effects of kidney transplantation on oxidative state are incompletely understood. With an aim to evaluate the prevalence and severity of oxidative stress in living donor renal transplant recipients, we conducted a cross-sectional study. Thirty-five renal transplant recipients (mean age 34 years; body mass index 21.93 +/- 1.92) with normal renal function (mean serum creatinine 1.41 +/- 0.33 mg%) were enrolled in the study. All patients were on cyclosporine-based immunosuppression. We assessed serum nitric oxide (NO) levels, plasma total homocysteine levels (tHCy), and malonaldehyde (MDA) levels. We evaluated the antioxidant power ferric reducing ability of plasma (FRAP) assay. The mean duration to the first sampling was 9.23 months after transplantation. Fourteen age- and sex-matched normotensive people were used as controls. The mean tHCy was significantly higher among patients (15.29 +/- 0.66 mmol/L compared with controls (9.58 +/- 2.90 mmol/L; P < .05). The MDA levels in patients (6.405 +/- 2.05 nmol/mL) were comparable to controls (6.093 +/- 1.93 nmol/mL; P = .099). The status of antioxidative power as measured by FRAP showed a trend to higher antioxidative status (697.57 +/- 103.07 mmol/L) in patients compared with controls (518 +/- 120.99 mmol/L; P = NS). The mean NO levels in patients (545.01 +/- 281.49 mmol/mL) were significantly higher than controls (183.49 +/- 64.53 nmol/mL; P < .05). Stable renal transplant recipients display a pattern of increased oxidant stress that may be counterbalanced by an enhanced antioxidant mechanisms.

Adult↗
PubMed2005

Hyperhomocysteinemia as a risk factor for ischemic stroke: an Indian scenario.

BACKGROUND: Hyperhomocysteinemia has been proposed as an important risk factor for ischemic stroke worldwide, but data available from the Indian subcontinent is scarce. AIM: To study homocysteine levels in patients with ischemic stroke and compare it with age- and sex-matched controls. SETTINGS AND DESIGN: Case-control prospective study. MATERIALS AND METHODS: Fifty-seven patients with ischemic stroke and 30 controls were recruited for the study. They were subdivided into two subgroups (< 40 years and> 40 years of age) and plasma fasting total homocysteine (tHcy) levels were measured. STATISTICAL ANALYSIS USED: Student's 't' test and chi-square test. RESULTS: The tHcy were significantly high in patients with stroke, compared to controls (9.91 +/- 2.25 vs 8.00 +/- 2.74 micromol/l; P vs 8.45 +/- 2.72 micromol/l; P = 0.01) and female patients compared to controls (9.08 +/- 1.81 vs 6.79 +/- 2.60 micromol/l; P = 0.04). The tHcy levels were significantly high in patients with hypertension compared to normotensive patients (10.96 vs 9.49 micromol/l; P = 0.01) and smokers compared to nonsmokers (11.17 vs 9.33 micromol/l; P = 0.01). CONCLUSIONS: Hyperhomo-cysteinemia emerged as an important independent risk factor for ischemic stroke. A strong positive correlation was also observed between hypertension, smoking, and high-tHcy levels in the present study.

Adult↗
PubMed2001

Enalapril acts through release of nitric oxide in patients with essential hypertension.

BACKGROUND: Endothelial dysfunction has been proposed as an etiological agent in the pathogenesis of essential hypertension. Amongst the various antihypertensive drugs, angiotensin converting enzyme inhibitors (ACEI) have been implicated in modifying the vascular endothelium by the release of mediators that include bradykinin, nitric oxide, prostaglandins and thromboxane A2. MATERIALS AND METHODS: To study the mechanism of action of enalapril, an ACEI, serum reactive nitrite intermediates (RNI) and citrulline, by products of nitric oxide metabolism were measured before and after treatment with enalapril in 25 consecutive patients of essential hypertension. RESULTS: Following treatment serum RNI intermediate increased from a pretreatment value of 164.5 +/- 20.2 nmol/mL to a post treatment value of 266.9 +/- 47.3 nmol/mL (p < 0.05), however there was no significant change in the levels of citrulline (p > 0.1). There was no significant correlation between the severity of hypertension and serum RNI. Serum RNI levels were lower in the postmenopausal women but did not reach statistical significance. CONCLUSIONS: It is postulated that enalapril exhibits its antihypertensive property through release of nitric oxide.

Adolescent↗
PubMed2001

Serum and urine nitrite and citrulline levels among patients with systemic lupus erythematosus: a possible addition to activity parameters?

Nitric oxide (NO) plays a significant role in the inflammatory process and has been implicated in several autoimmune disorders. This study was carried out prospectively to estimate the levels of nitrite and citrulline in the serum and urine, as surrogate markers of NO production, among patients with systemic lupus erythematosus (SLE). Forty-seven patients and 44 age- and sex-matched, healthy volunteers were studied. Nitrite and citrulline were measured in serum and urine by spectrophotometry.Median serum nitrite and citrulline levels and urine citrulline levels were higher among patients as compared with controls (p < 0.05). Patients with skin involvement stood out and had higher median serum and urine citrulline levels (p < 0.05). Disease activity correlated with steroid dosage, serum nitrite levels, and serum and urine citrulline levels (p < 0.05). Steroid dosage correlated with serum citrulline level (p < 0.05). Serum and urine citrulline levels correlated with each other (p < 0.01). In the subset of 13 individuals with renal involvement, serum and urine citrulline levels correlated with each other (p < 0.01) as did urine nitrite and citrulline levels (p < 0.05).NO production is increased among patients with SLE, and this increase correlates with disease activity and dosage of steroids used. The addition of a urine test to measure NO production as a marker of disease activity using simple spectrophotometry can be a valuable adjunct to other tests, can obviate the need for drawing a blood sample for this purpose, and can be repeated as often as necessary.

Journal Article↗
PubMed2001

Calcium supplementation in pre-eclampsia.

OBJECTIVE: The objective of this prospective, open, randomised trial was to determine the role of calcium supplementation in preventing pre-eclampsia. METHODS: One hundred uncomplicated normotensive primigravidae were enrolled in the study before 20 weeks of pregnancy. Fifty each were randomised to receive either two gram elemental calcium daily from 20 weeks of gestation to delivery (study group) or no calcium supplementation (control group). Prior to 20 weeks of gestation each underwent a complete clinical and laboratory evaluation. Serum and urine calcium was measured first at 20 weeks of gestation and then at 24-28 weeks and at 32-36 weeks of pregnancy. RESULTS: Patient characteristics at the start of therapy were similar in the two groups. Blood pressure profile was similar throughout pregnancy in the groups. The incidence of pre-eclampsia was similar (18% in the study group and 16% in the control group), but severe pre-eclampsia was significantly less in the study group. There was no significant difference between the two groups with regards to intra- and postpartum characteristics, perinatal outcome and maternal or fetal side effects. Serum and urinary calcium levels did not differ between the two groups. CONCLUSION: While calcium supplementation did not lower the incidence of pre-eclampsia it did reduce its severity.

Blood Pressure↗
PubMed2000

Pentoxiphylline reduces nitric oxide production among patients with HIV infection.

Tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels are elevated among patients with human immunodeficiency virus (HIV) infection. TNF-alpha is known to lower NO production. In this study we used a TNF-alpha inhibitor, pentoxiphylline, to treat patients with HIV infection who were free of opportunistic infections and see if NO production was altered with this drug. NO production was determined by spectrophotometric analysis using nitrite and citrulline as surrogate markers and TNF-alpha levels were determined by ELISA before and after 4 weeks of the treatment. Nineteen patients (ten males, mean age 36.6+/-5.2 years) and 16 age and sex matched healthy controls were studied. Mean CD4 counts of patients were 206.5 mm(3). Nitrite level among patients at recruitment was 99.7+/-26.5 nmol/ml (range 50-167 nmol/ml) and was significantly higher than 46.4+/-16.2 nmol/ml; the value of healthy controls (P<0.05). Patient levels declined significantly to 44. 2+/-19.7 nmol/ml (range 10-106.6 nmol/ml) following 4 weeks of therapy (P<0.01). Citrulline level at recruitment was 810.8+/-425.8 nmol/ml (range 366.6-1888.7 nmol/ml), which was significantly higher than 488.6+/-224.5 nmol/ml, the level of controls (P<0.01). There was a statistically significant decrease in these levels among patients to 533.6+/-299.5 nmol/ml (range 250-163.4 nmol/ml) after 4 weeks of therapy (P<0.01). TNF-alpha levels showed a significant decline in the OD values from 0.34+/-0.22 at the start of therapy to 0.24+/-0.18 (P<0.05). We conclude that the use of pentoxiphylline is associated with decrease in TNF-alpha levels and NO production.

Adult↗
PubMed2000

Increased nitric oxide production in patients with systemic sclerosis.

Nitric oxide (NO, nitrogen monoxide) is a messenger molecule whose synthesis can be induced by proinflammatory cytokines. Increased production of NO has been reported in various inflammatory and autoimmune diseases. We studied serum nitrite and citrulline as surrogate markers for NO production in patients with systemic sclerosis (SSc) and looked for correlation with extent of disease, disease duration, age, and systemic involvement. Thirty-four patients were studied against 20 controls. The nitrite levels were significantly higher in the disease group (1588.4 +/- 998.2 nmol/ml compared to 327.8 +/- 137.7 nmol/ml; P < 0.001). The citrulline levels of the disease group were also significantly higher (5490.1 +/- 2518.3 nmol/ml compared to 3264.5 +/- 2509.7 nmol/ml in the controls; P = 0.005). There was no significant difference among limited and diffuse subgroups. There was no significant difference in patients with or without arthritis or interstitial lung disease or with other systemic involvement. On multivariate analysis there was a trend toward a rising level of nitrite with worsening lung functions (P = 0.07). Hence, there is evidence of increased NO production in patients with SSc. There is no difference between NO levels in disease subgroups or those with systemic involvement.

Biomarkers↗
PubMed2000

Elevated nitric oxide production in patients with primary Sjögren's syndrome.

Nitric oxide (NO) production is elevated in patients with inflammatory disorders. We have previously shown increased NO production in patients with rheumatoid arthritis and systemic lupus erythematosus. In this study we used nitrite and citrulline levels as surrogate markers of NO production in patients with primary Sjögren's syndrome (SS) and measured their levels by spectrophotometry. Fifteen patients and 15 age- and sex-matched controls were studied. Mean nitrite levels in patients were 582.3+/-208.3 nmol/ml, but those in controls were significantly lower, at 203.2-106.9 nmol/ml (p<0.001). Citrulline levels were 2820.4+/-933.9 nmol/ml in patients and were significantly higher than 217.4+/-144.8 nmol/ml, the levels in controls (p<0.0001). Mean levels of both nitrite and citrulline were significantly higher in patients with arthritis than in those who had no joint manifestations (p<0.05). There was no correlation between NO production and other variables, such as age, disease duration, drug therapy and antinuclear antibodies or rheumatoid factor positivity. Increased NO production may be partly a reflection of the presence of arthritis in five patients. It is concluded that there is increased NO production in patients with primary SS, especially if they have associated arthritis.

Adult↗
PubMed2000

Intestinal mucins: the binding sites for Salmonella typhimurium.

Mucus-bacterial interactions in the gastrointestinal tract and their impact on subsequent enteric infections are poorly delineated. In the present study, we have examined the binding of Salmonella typhimurium to rat intestinal mucus and characterized a mucus protein (Mucus-Rs) which specifically binds to S. typhimurium. Both virulent (1402/84), and avirulent (SF 1835) S. typhimurium were observed to bind to crude mucus, however, the virulent strain showed 6 fold more binding as compared to avirulent strain. Fractionation of crude mucus on sepharose CL-6B resolved it into three major peaks. Maximal bacterial binding was observed with a high mol. wt. glycoprotein corresponding to neutral mucin. SDS-PAGE of purified protein (termed Mucus-Rs) under non reducing conditions showed it to be a homogenous glycoprotein (mol. wt. 250 kDa), while under reducing conditions, three bands corresponding to mol. wt. of 118,75 and 60 kDa were observed. Pretreatment of Mucus-Rs with pronase, trypsin and sodium metaperiodate markedly inhibited bacterial binding. GLC analysis of Mucus-Rs showed it to contain Mannose, Glucose, Galactose, Glucosamine, Galactosamine and Sialic acid as main sugars. Competitive binding in the presence of various sugars and lectins indicated the involvement of mannose in the mucus-bacterial interactions. The Mucus-Rs binding was highly specific for S. typhimurium; no significant binding was seen with E. coli and V. cholerae. Thus, we conclude that S. typhimurium specifically binds to a 250 kDa neutral mucin of intestinal tract. This binding appears to occur via specific adhesin-receptor interactions involving bacterial pili and mannose of neutral mucin.

Animals↗
PubMed2000

Role of anaerobiosis in virulence of Salmonella typhimurium.

Intestinal pathogens are exposed to various stress conditions during their infectious cycle. Anaerobiosis, one of such hostile condition, is offered by the host within gut and intestinal lumen, where survival, multiplication and entry into intestinal epithelial cells is priority for the invading pathogen. In the present study, a virulent strain of S. typhimurium (1402/84) was grown under anaerobic conditions and its virulence characteristics such as host cell binding, penetration and intracellular survival were compared with aerobic S. typhimurium. Anaerobically grown S. typhimurium showed significantly higher binding to immobilized mice enterocytes and intestinal mucus as compared to bacteria grown aerobically. Anaerobic bacteria also showed an early penetration of mucus and subsequent binding to underlying immobilized enterocytes, in vitro. Anaerobic S. typhimurium exhibited increased intracellular survival within spleen macrophages of mice and caused significantly higher fluid accumulation in ligated rabbit ileal loops as compared to aerobic bacteria. LD50 of anaerobic S. typhimurium was also observed to be 2 fold lower when compared to aerobic bacteria. Cell surface hydrophobicity of anaerobic S. typhimurium was also found to be significantly higher than aerobic bacteria. Thus, it appears that exposure of S. typhimurium to anaerobiosis results in its enhanced virulence, adhesion and penetration of host cells.

Anaerobiosis↗
PubMed2000

Effect of oral magnesium supplementation on blood pressure, platelet aggregation and calcium handling in deoxycorticosterone acetate induced hypertension in rats.

OBJECTIVE: To study the effect of oral magnesium supplementation on blood pressure, platelet aggregation and platelet calcium handling in deoxycorticosterone acetate (DOCA)-induced hypertension in rats. DESIGN AND METHODS: Rats were divided into four groups of 20 each. Drug treatments were given for a 6-week period. Control rats were vehicle treated. In the second group, DOCA, 15 mg/kg, was injected subcutaneously twice weekly with 1% NaCl used instead of drinking water. The third group was given magnesium oxide (MgO), 1 g/kg daily, orally by gavage. The fourth group was given MgO along with DOCA and 1% NaCl. Blood pressure and heart rate were measured weekly. Platelet aggregation, intracellular calcium, calcium uptake and calcium efflux studies were performed at the end of sixth week. Serum magnesium concentration, plasma levels of reactive nitrogen intermediates (RNI) and citrulline were also measured RESULTS: There was a significant rise in blood pressure in the DOCA-treated rats. Magnesium prevented the gradual rise in blood pressure when given along with DOCA, but had no effect in normotensive rats. Heart rate did not show any significant change. Platelet aggregation was significantly reduced in all the treatment groups compared to the control group. DOCA treatment produced a significant increase in the intracellular calcium concentration as well as the calcium uptake compared to the control group. Magnesium supplementation inhibited the increased intracellular calcium concentration and calcium uptake in DOCA-treated rats. RNI and citrulline levels were elevated in all the treatment groups. Serum magnesium levels were significantly higher in the magnesium-treated and DOCA plus magnesium-treated rats. CONCLUSIONS: Magnesium supplementation prevents blood pressure elevation in DOCA hypertensive rats. These effects are associated with inhibition of platelet calcium uptake and decreased intracellular free calcium concentration.

Administration, Oral↗
PubMed1999

Nitric oxide production is increased in patients with inflammatory myositis.

Nitric oxide (NO) production is increased in several inflammatory disorders. We have previously demonstrated higher levels of NO production among patients with rheumatoid arthritis and systemic lupus erythematosus. In this study we measured serum levels of nitrite and citrulline using calorimetric methods as surrogate markers of NO production among patients with inflammatory myositis (IM). Twenty patients with IM and 19 age- and sex-matched controls were studied. Serum nitrite levels were significantly higher among patients than among controls (986.6 +/- 880 and 204.3 +/- 113.9 nmol/ml, respectively; P = 0.001). Serum citrulline levels, too, were significantly higher among patients than among controls (3755.7 +/- 1905.5 and 189 +/- 177.2 nmol/ml, respectively; P < 0.0001). There was a positive correlation between steroid dosage and serum citrulline levels (r = 0.51, P = 0.036) and a negative correlation between steroid dosage and disease duration (r = -0.54, P = 0.025). It was concluded that NO production is increased in patients with IM and those with more active disease, as indicated by higher steroid dosage, have higher serum citrulline levels.

Adolescent↗
PubMed1998

Nitric oxide synthesis is increased in patients with systemic lupus erythematosus.

Nitric oxide (NO) is believed to have a role in the inflammatory process. NO production was measured in 26 patients with systemic lupus erythematosus (SLE) and 20 healthy volunteers, using spectrophotometrically determined serum nitrite and citrulline as surrogate markers. Both nitrite and citrulline levels were significantly higher in patients with SLE than in controls (P < 0.001). Twelve and 10 patients, respectively, with SLE had nitrite and citrulline levels that were two standard deviations higher than the mean level of controls. These patients had a significantly higher measure of disease activity (SLE Disease Activity Index). These data show that there is increased NO production in SLE and that it may serve as a marker for disease activity.

Adolescent↗
PubMed1998

Can fingernail creatinine concentrations be used to predict duration of azotemia?

Clinical use of fingernail creatinine estimation to predict duration of azotemia is yet to be validated. We studied the fingernail creatinine concentrations in 48 subjects: seven controls, nine with acute renal failure, five with rapidly progressive glomerulonephritis, 12 with chronic renal failure and 15 with end-stage renal failure on maintenance hemodialysis. The creatinine concentration in aqueous eluates of powdered nail clippings was determined by the alkaline picrate reaction. The mean fingernail creatinine concentration was significantly higher in patients with chronic renal failure (93.7 +/- 83.7 micrograms/g) and end-stage renal disease on maintenance hemodialysis (118.4 +/- 46.8 micrograms/g) as compared to those with acute renal failure (36.6 +/- 23.7 micrograms/g) and rapidly progressive glomerulonephritis (35.8 +/- 20.6 micrograms/g). The creatinine concentrations did not differ significantly between normal subjects (27.2 +/- 28.7 micrograms/g) and those with acute renal failure and rapidly progressive glomerulonephritis. However because of large variability in the values of fingernail creatinine concentrations within each group, the test lacked specificity. Therefore, this investigation is an unreliable indicator of duration of azotemia in individual patients and is not likely to be of much clinical use.

Acute Kidney Injury↗
PubMed1996

Platelet calcium pump activity in essential hypertensives and their first-degree relatives.

Intracellular free Ca2+ concentration has been shown to be elevated in platelets of patients with essential hypertension. This study was designed to characterize Ca(2+)-pump activity of the platelet membranes (surface and intracellular) in these patients A double-blind study was carried out. Untreated and treated (on beta-blockers) essential hypertensives were studied in comparison with normotensive control subjects. First degree blood relatives of essential hypertensives were also studied. The Ca2+ activation kinetics of the enzyme showed a significant decrease in the Vmax (for the plasma- and intracellular membranes) and Km (for the intracellular membranes) in the essential hypertensive patients. Increased platelet membrane cholesterol content was observed in these patients. Lowered Ca2(+)-efflux by Ca2(+)-ATPase may lead to elevated intracellular free Ca2(+)-levels in platelet of essential hypertensives. A lowered Ca2(+) -ATPase activity may emerge as a marker for essential hypertension.

Adolescent↗
PubMed1995

Staphylococcal enterotoxin-B (SEB) alters [14C]-choline transport and phosphatidylcholine metabolism in cultured human kidney proximal tubular cells.

We studied the effects of SEB on [14C]-choline transport and metabolism of choline containing phospholipids in cultured human kidney proximal tubular (PT) cells. SEB increased the uptake of [14C]-choline in PT cells as a function of toxin concentration, incubation time, and pH. The maximum increase in uptake (3.5-5-fold compared to control) was observed at a toxin concentration of 10 micrograms/10(4) cells, at 4 h and at pH 7.4. Two toxins structurally related to SEB, Staphylococcal enterotoxin-A and toxic shock toxin (TST-1) failed to alter [14C]-choline uptake in PT cells, a finding which indicates that SEB-mediated alteration in choline uptake in PT cells has high specificity. We found that SEB markedly and significantly increased the incorporation of [14C]-choline into phosphatidylcholine, Iysophosphatidylcholine and sphingomyelin, but not into phosphatidylethanolamine. Maximum increase in the incorporation of [14C]-choline into phosphatidylcholine (3-fold compared to control) was observed at 4 h after incubation with toxin. In contrast, SEB did not alter the incorporation of [14C]-choline in phosphatidylethanolamine. The cellular level of phosphatidylcholine was also increased (2-fold compared to control) in PT cells incubated with SEB. This was accompanied by a 3-to-4-fold increase in CTP; phosphocholine, cytidyltransferase activity. In sum, SEB specifically stimulates phosphatidylcholine synthesis in PT cells by increasing choline uptake or by activating CTP: phosphocholine, cytidyltransferase, or both. We believe this is the first-ever report indicating that a toxin can increase phosphatidylcholine synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport, Active↗