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Biomedical subjects

I Rahman

Publications and source records attributed to I Rahman.

At least 73 records · Page 4Linked to original sources
PubMed1996

Mechanisms of cigarette smoke induced increased airspace permeability.

BACKGROUND: Increased epithelial permeability of the airspaces occurs commonly in the lungs of cigarette smokers. It is likely to be important in augmenting the inflammatory response in the airspaces and hence may have a role in the pathogenesis of emphysema. It has previously been shown that intratracheal instillation of cigarette smoke condensate induces increased epithelial permeability in vivo in rats and in vitro in epithelial cell monolayers, associated with a disturbance in the lung antioxidant, glutathione (GSH). The aim of this study was to assess the role of neutrophils, GSH, and tumour necrosis factor (TNF) in the increased epithelial permeability following intratracheal instillation of cigarette smoke condensate. METHODS: Epithelial permeability of the airspaces was measured in rat lungs as the passage of intratracheally instilled 125-iodine labelled bovine serum albumin (BSA) into the blood. The permeability of a monolayer of human type II alveolar epithelial cells to 125I-BSA was also measured. RESULTS: Cigarette smoke condensate produced a 59.7% increase in epithelial permeability over control values peaking six hours after instillation and returning to control values by 24 hours. Depletion of neutrophils and, to a lesser extent, macrophages by an intraperitoneal injection of antineutrophil antibody did not influence the increased epithelial permeability induced by cigarette smoke condensate. Although instillation of human recombinant TNF alpha produced an increase in epithelial permeability in the rat lung from 0.62 (0.61)% to 1.27 (0.08)%, only a trivial amount of TNF alpha was detected in bronchoalveolar lavage (BAL) fluid in vivo or in culture medium from BAL leucocytes obtained from animals treated with cigarette smoke condensate (94.9 (28.8) units/ml). Furthermore, antiTNF antibody did not abolish the increased epithelial permeability produced by cigarette smoke condensate. The role of GSH was assessed by measuring the changes in both the reduced (GSH) and oxidised form (GSSG) in lung tissue and in BAL fluid. One hour after instillation of cigarette smoke condensate there was a marked fall in the GSH content in the lung (from 809.8 (31.8) to 501.7 (40.5) nmol/g) in association with increased GSSG levels (from 89.8 (2.7) to 148.7 (48.8) nmol/g). This was followed by a return of GSH levels to control values, with a concomitant decrease in GSSG levels six hours after instillation. GSH levels in BAL fluid fell dramatically following cigarette smoke condensate (from 2.56 (0.30) to 0.31 (0.21) nmol/ml) and this fall was sustained up to six hours after instillation of cigarette smoke condensate. CONCLUSIONS: These studies suggest that neutrophils and TNF do not have a major role in the increased epithelial permeability induced by cigarette smoke condensate. However, the data support a role for the depletion of the antioxidant glutathione in the increased epithelial permeability caused by cigarette smoke condensate.

Animals↗
PubMed1996

Systemic oxidative stress in asthma, COPD, and smokers.

An imbalance between oxidants and antioxidants is proposed in smokers and in patients with airways diseases. We tested this hypothesis by measuring the Trolox equivalent antioxidant capacity (TEAC) of plasma and the levels of products of lipid peroxidation as indices of overall oxidative stress. The plasma TEAC was markedly reduced (0.66 +/- 0.07 mmol/L; mean +/- SEM; n = 11), with increased levels of lipid peroxidation products, in healthy chronic smokers as compared with healthy nonsmokers (1.31 +/- 0.10 mmol/L, n = 14, p < 0.001), an effect that was exaggerated in those who had smoked 1 h before the study. Plasma TEAC was also low in patients presenting with acute exacerbations of chronic obstructive pulmonary disease (COPD) (0.46 +/- 0.10 mmol/L, n = 20, p < 0.001) or asthma (0.61 +/- 0.05 mmol/L, n = 9, p < 0.01) with increases in plasma lipid peroxidation products. There was a negative correlation between superoxide anion release by stimulated neutrophils and plasma antioxidant capacity (r = -0.73, p < 0.001) in patients with acute exacerbations of COPD. The profound decrease in TEAC was associated with a decreased plasma protein sulfhydryl concentrations in acute exacerbations of COPD but not in smokers or in asthmatic subjects. Therefore smoking, acute exacerbations of COPD, and asthma are associated with a marked oxidant/antioxidant imbalance in the blood, associated with evidence of increased oxidative stress. The decreased antioxidant capacity in plasma may result from different mechanisms in these conditions.

Adult↗
PubMed1995

Hypoxia prolongs neutrophil survival in vitro.

Neutrophil apoptosis represents a major mechanism involved in the resolution of inflammation. Since hypoxia induces apoptosis in several cell lines and is of particular relevance in many disease states, we studied the effect of oxygen concentration on neutrophil survival in vitro. Hypoxia caused a dramatic decrease in neutrophil apoptosis (% apoptosis 20 h: 78.7 +/- 2.2% in 21% O2, 61.4 +/- 6.5% in 2.5% O2, 23.1 +/- 3.2% in 0% O2, n = 5). This was additive to the effect of GM-CSF (50 U/ml), not associated with induction of bcl-2 expression, and was not mimicked by methionine (5 mM), superoxide dismutase (200 micrograms/ml) or Trolox (10 mM) but was mimicked by catalase (250 micrograms/ml). Hence, hypoxia has a bcl-2-independent effect on neutrophil apoptosis that may adversely affect the clearance of these cells from an inflammatory focus.

Cell Hypoxia↗
PubMed1995

Glutathione homeostasis in alveolar epithelial cells in vitro and lung in vivo under oxidative stress.

We studied the acute effects of cigarette smoke condensate (CSC), H2O2, and tumor necrosis factor (TNF)-alpha on the glutathione (GSH) redox system in a human type II epithelial cell line (A549) in vitro. CSC, in vitro and in vivo after intratracheal instillation of CSC in the rat, produced a depletion of intracellular soluble GSH, concomitant with GSH-conjugate formation, without significant elevation of oxidized GSH (GSSG), protein-GSH mixed disulfides (PrSSG), nor any GSH efflux from the cells. By contrast, H2O2 (500 microM) after 5-min exposure to A549 cells caused significant depletion of intracellular GSH associated with an efflux of GSSG and a significant increase in the formation of PrSSG. TNF-alpha, in concentrations of 100 U/ml and 1,000 U/ml, produced a significant depletion of GSH in A549 cells after 4- and 24-h exposure, with an associated elevation of GSSG. The activities of glutathione peroxidase, gamma-glutamylcysteine synthetase, and glucose-6-phosphate dehydrogenase were significantly decreased in epithelial cells and in rat lungs after CSC exposure, without change in glutathione S-transferase and glutathione reductase activities. By contrast, H2O2 and TNF-alpha did not alter these enzyme activities in epithelial cells. Thus GSH depletion and alteration in enzyme activities in alveolar epithelial cells by CSC, H2O2, and TNF-alpha occur by different mechanisms.

Animals↗
PubMed1994

Methionine uptake and cytopathogenicity of viable but nonculturable Shigella dysenteriae type 1.

A pathogenic strain of Shigella dysenteriae type 1 was selected for study to elucidate the physiology and potential pathogenicity of organisms in the viable but nonculturable (VBNC) state in the environment. Studies in our laboratory have shown that S. dysenteriae type 1 survives in laboratory microcosms in the VBNC state for long periods of time, i.e., more than 6 months. VBNC cells of S. dysenteriae type 1 were found to retain cytopathogenicity for cultured HeLa cells. To determine whether VBNC S. dysenteriae type 1 expressed protein after loss of culturability, 35S-labelled methionine was added to suspensions of VBNC cells. Total cellular proteins were extracted and examined by autoradiography. Results indicate that VBNC S. dysenteriae type 1 is capable of both active uptake of methionine and incorporation of methionine into protein. Amino acid uptake and protein synthesis substantiate the viability of cells of S. dysenteriae type 1 in the VBNC state, i.e., although the cells are unable to be cultured on laboratory media by standard bacteriological methods, the cells remain metabolically active. Furthermore, VBNC cells of S. dysenteriae type 1 may pose a potential public health hazard that has not yet been recognized.

Biological Transport, Active↗
PubMed1994

An investigation of the role of glutathione in increased epithelial permeability induced by cigarette smoke in vivo and in vitro.

Airspace epithelial permeability is known to increase in cigarette smokers. To study the role of the antioxidant reduced glutathione (GSH) in this phenomenon, we used an in vitro model of the epithelial permeability of a monolayer of human type II alveolar epithelial cells (A549 cell line). Both whole (WSC) and vapor (VSC) smoke condensates induced a recoverable, concentration-dependent increase in epithelial permeability to 125iodine-labeled bovine serum albumin (125IBSA), associated with a profound fall in intracellular GSH. Buthionine sulfoximine (BSO), a GSH synthesis inhibitor, decreased GSH levels in A549 epithelial cells, significantly increased A549 epithelial cell permeability, and enhanced both WSC and VSC-induced A549 epithelial cell permeability. Co-culturing epithelial cells and GSH (500 microM) reduced WSC-induced, but not VSC-induced A549 epithelial cell permeability. Increasing intracellular GSH also ameliorated the smoke-induced increased epithelial permeability. Concentrations of cigarette smoke condensate of < 20% increased A549 epithelial cell permeability without associated cell detachment and lysis, which was also the case with BSO-induced increased epithelial permeability. WSC and VSC, instilled intratracheally, significantly increased rat lung epithelial permeability to 125IBSA, 6 h postinstillation, associated with a significant recruitment of neutrophils into the airspaces. This was associated with a small increase in GSH in the lung tissue of VSC-treated rats. However, both WSC and VSC markedly reduced GSH in bronchoalveolar lavage (BAL) fluid. Reduction in lung GSH to 95% but not to 68% of control values by BSO increased lung epithelial permeability in vivo. However, there was no additive effect on epithelial permeability of WSC and BSO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Endotoxin treatment protects rats against ozone-induced lung edema: with evidence for the role of manganese superoxide dismutase.

Ozone is a strong oxidizing agent that can cause lung damage and edema. There is evidence that it does so by causing peroxidation of membrane lipids. However, the elevation in lung activity of copper, zinc superoxide dismutase (Cu, ZnSOD), and manganese superoxide dismutase (MnSOD) during exposure to ozone suggests that increased production of superoxide could contribute to lung edema caused by ozone. This latter observation, and preliminary evidence that treatment of rats with endotoxin elevates lung activity of MnSOD without elevation of the activity of Cu, ZnSOD, catalase (CAT), or glutathione peroxidase (GP), led to the present study. We treated rats with endotoxin, exposed them to different concentrations of ozone, measured lung wet weight to dry weight ratio, thiobarbituric acid-reactive material (TBAR), and assayed lung tissue for Cu, ZnSOD, MnSOD, CAT, and GP activity. Our major findings are, (1) a strongly edemogenic concentration of ozone-lowered MnSOD activity; (2) endotoxin treatment of air-breathing rats did not decrease lipid peroxidation as indicated by the lung concentration of TBAR; (3) induction of increased MnSOD activity in lung by treatment with endotoxin was associated with virtually complete protection against an otherwise edemogenic concentration of ozone, with less lipid peroxidation, and with less loss of weight; and (4) this protection occurred without elevated Cu, ZnSOD, CAT, or GP activity.

Animals↗
PubMed1992

Exposure of rats to ozone: evidence of damage to heart and brain.

Ozone is a strong oxidizing agent, and in many locations it is a major atmospheric pollutant. It is phytotoxic and an important cause of lung dysfunction in humans. Recently, a significant association has been established between total atmospheric oxidants, of which ozone is one, and daily cardiovascular mortality rates. In this article, we show that exposure of rats to ozone for 5 days, in a concentration found in major urban centers, results in an increased concentration of thiobarbituric acid-reactive material (an indicator of lipid peroxidation) in heart and brain tissue as well as elevated activity of catalase and glutathione peroxidase (enzymic scavengers of peroxides) in these tissues. We examined the heart anatomically and found evidence of extracellular and intracellular edema. These findings indicate that the heart and brain are damaged by a concentration of ozone present in major urban centers; they may have important implications for chronic illness and degenerative processes in humans.

Animals↗
PubMed1991

Rat lung antioxidant enzyme induction by ozone.

We exposed rats of different ages (weights approximately 45-300 g) to 0.7 ppm O3 for 1-5 days. At 5 days lungs of O3-exposed rats had higher activity of Cu,Zn superoxide dismutase (SOD), Mn SOD, catalase, and glutathione peroxidase than air-breathing rats; this greater activity was not due to blood-associated enzyme activity. The greater enzyme activity occurred with a higher concentration of the mRNA for each enzyme (Mn SOD not measured) without altered stability of these mRNAs. In adult rats the concentrations of these mRNAs were measured after 1, 3, and 5 days exposure to O3 and were elevated by day 3. The intergroup differences (air vs. O3) among antioxidant enzymes (AOEs) were unequal, and the intergroup differences in concentration of the specific AOE mRNA were greater than the differences in activity of their AOE. We conclude exposure to O3 led to greater expression of AOE genes; the increased expression was mediated pretranslationally probably at the level of transcription.

Animals↗
PubMed1990

Fetal macrosomia--maternal risks and fetal outcome.

Two hundred eighty-four macrosomic babies of 4000 g or over at birth were compared with an equal number of appropriate weight term infants, to identify maternal risk factors and fetal outcome. Maternal obesity, grand multiparity, diabetes mellitus and postmaturity were the major maternal risks. Prolonged labor, shoulder dystocia and injury to infant following instrumental delivery for mid-cavity arrest were the major fetal risks. A protocol for management of fetal macrosomia is proposed.

Adult↗
PubMed1975

Comparison of a semi-automated sphygmomanometer with the clinical sphygmomanometer.

A semi-automated sphygmomanometer Stanley B-200 has been compared with the clinical sphygmomanometer in 500 college boys by using a blind simultaneous method. Stanley B-200 has shown significantly higher systolic blood pressure (14.8 mmHg, P smaller than 0.05) and diastolic blood pressure (3.8 mmHg, P smaller than 0;05). This device also recorded 15 false positive systolic and 12 false negative diastolic results (P smaller than 0.05).

Adolescent↗