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Biomedical subjects

I Rahman

Publications and source records attributed to I Rahman.

At least 55 records · Page 3Linked to original sources
PubMed1999

Epithelial permeability, inflammation, and oxidant stress in the air spaces of smokers.

The mechanism responsible for the increased air-space permeability in cigarette smokers is unknown. The aim of this study was to assess the acute and chronic effects of cigarette smoking on epithelial permeability, inflammation, and oxidant stress in the air spaces of smokers. Fourteen cigarette smokers underwent 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA) lung scans after abstaining from smoking for 12 h (chronic smoking) and 1 h after smoking two cigarettes (acute smoking). Each smoker also underwent bronchoscopy and bronchoalveolar lavage (BAL) after either chronic (n = 8) or acute smoking (n = 7). Seven nonsmokers also underwent bronchoscopy and BAL. The time to 50% clearance of 99mTc-DTPA (t50) after chronic smoking was 16.7 +/- 1. 3 min (mean +/- SE), and was further reduced after acute smoking to 14.8 +/- 1.0 min (p < 0.01). Neutrophil numbers were increased in bronchoalveolar lavage fluid (BALF) in the acute smoking group as compared with the nonsmokers (p < 0.05). Superoxide release from mixed BAL leukocytes was increased after chronic (p < 0.01) and acute (p < 0.001) smoking, as were thiobarbituric acid-reactive species (TBARS), providing evidence of lipid peroxidation in plasma (chronic, p < 0.05; acute, p < 0.05). Trolox equivalent antioxidant capacity (TEAC) was reduced in plasma (p < 0.001) and increased in BALF (p < 0.05) in both smoking groups. The study therefore showed an acute increase in epithelial permeability and an increase in the number of neutrophils in the air spaces of cigarette smokers concomitant with evidence of increased oxidant stress.

Adult↗
PubMed1999

Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease.

There is now increasing evidence that an oxidant/antioxidant imbalance, in favor of oxidants, occurs in chronic obstructive pulmonary disease (COPD). Evidence is also accumulating that oxidative stress is a critical event in the pathogenesis of this condition. A large number of studies have demonstrated an increased oxidant burden and consequently increased markers of oxidative stress in the airspaces, breath, blood, and urine of smokers and of patients with COPD. There are several events related to oxidative stress, which are important in the pathogenesis of COPD. These include oxidative inactivation of antiproteinases, airspace epithelial injury, increased sequestration of neutrophils in the pulmonary microvasculature, and gene expression of proinflammatory mediators. Oxidative processes have a fundamental role in the inflammation of smokers and patients with COPD, through redox-sensitive transcription factors such as NF-kappaB and AP-1, which regulate the genes for proinflammatory mediators and protective mechanisms, such as antioxidant gene expression. In addition to the oxidative stress produced by cigarette smoking, dietary deficiency in antioxidants is related to the development of airflow limitation, and hence dietary supplementation may be a beneficial therapeutic intervention in this condition. The use of antioxidants with good bioavailability or molecules that have antioxidant enzyme activity may be treatments that not only protect against the direct injurious effects of oxidants, but may fundamentally alter the inflammatory events that are thought to play an important part in the pathogenesis of COPD. MacNee W, Rahman I. Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease.

Animals↗
PubMed1998

Studies on pulmonary and systemic Aspergillus fumigatus-specific IgE and IgG antibodies in horses affected with chronic obstructive pulmonary disease (COPD).

Inhalant exposure to Aspergillus fumigatus (Asp. f.) antigens induces marked inflammatory and immunological alterations in the lungs of horses affected with chronic obstructive pulmonary disease (COPD). In this study we investigated the role of specific allergen(s) present in Asp. f. on systemic and pulmonary IgE and IgG responses in control and COPD-affected horses, using an enzyme-linked immunosorbent assay (ELISA) and immunoblotting techniques. Compared with controls, horses affected with COPD had significantly higher levels of BALF IgE and IgG to somatic Asp. f. antigens as well as to the allergen 1/a (Asp. f. 1/a). Serum levels of IgE and IgG against these antigens did not differ between control and COPD-affected horses. Antigen specific IgE and IgG levels did not correlate between BALF and serum. Scanning of Asp. f. and IgE and IgG blots revealed bands that are recognised by both IgE- and IgG-specific antibodies. Additionally, all horses responded with BALF IgE- and IgG-specific for 93, 35, 31 and 23 kDa allergens, suggesting that these antigens are involved in the induction of airway IgE and IgG responses. These allergens may have the potential to be used as biomarkers for the diagnosis of Asp. f. related exacerbations of equine COPD.

Animals↗
PubMed1998

Human circulating eosinophils secrete macrophage migration inhibitory factor (MIF). Potential role in asthma.

Macrophage migration inhibitory factor (MIF) is a potent proinflammatory mediator that has been shown to potentiate lethal endotoxemia and to play a potentially important regulatory role in human acute respiratory distress syndrome (ARDS). We have investigated whether eosinophils are an important source of MIF and whether MIF may be involved in the pathophysiology of asthma. Unstimulated human circulating eosinophils were found to contain preformed MIF. Stimulation of human eosinophils with phorbol myristate acetate in vitro yielded significant release of MIF protein. For example, eosinophils stimulated with phorbol myristate acetate (100 nM, 8 h, 37 degreesC) released 1,539+/-435 pg/10(6) cells of MIF, whereas unstimulated cells released barely detectable levels (< 142 pg/10(6) cells, mean+/-SEM, n = 8). This stimulated release was shown to be (a) concentration- and time-dependent, (b) partially blocked by the protein synthesis inhibitor cycloheximide, and (c) significantly inhibited by the protein kinase C inhibitor Ro-31,8220. In addition, we show that the physiological stimuli C5a and IL-5 also cause significant MIF release. Furthermore, bronchoalveolar lavage fluid obtained from asthmatic patients contains significantly elevated levels of MIF as compared to nonatopic normal volunteers (asthmatic, 797.5+/-92 pg/ml; controls, 274+/-91 pg/ml). These results highlight the potential importance of MIF in asthma and other eosinophil-dependent inflammatory disorders.

Asthma↗
PubMed1998

Characterisation of gamma-glutamylcysteine synthetase-heavy subunit promoter: a critical role for AP-1.

The 5'-flanking region of human gamma-glutamylcysteine synthetase-heavy subunit (gamma-GCS-HS) was characterised by creating a series of chloramphenicol acetyl transferase (CAT) reporter deletion constructs. Analysis of various deleted CAT constructs revealed that a putative AP-1 consensus sequence is required to direct the constitutive and oxidant-mediated promoter activity. Gel mobility shift and mutation analysis of the sequence (-269 to -263 bp), showed binding of AP-1 is involved in the oxidant-mediated regulation of gamma-GCS-HS promoter activity.

Cells, Cultured↗
PubMed1998

Antifungal activity of Indian plant extracts.

In vitro studies of water extracts of plants such as Terminalia chebula, Punica granatum, Delonix regia and Emblica officinalis were found to be detrimental to test dermatophytes.

Antifungal Agents↗
PubMed1998

Differential regulation of glutathione by oxidants and dexamethasone in alveolar epithelial cells.

We studied the regulation of GSH and the enzymes involved in GSH regulation, gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyl transpeptidase (gamma-GT), in response to the oxidants menadione, xanthine/xanthine oxidase, hyperoxia, and cigarette smoke condensate in human alveolar epithelial cells (A549). Menadione (100 microM), xanthine/xanthine oxidase (50 microM/10 mU), and cigarette smoke condensate (10%) exposure produced increased GSH levels (240 +/- 6, 202 +/- 12, and 191 +/- 2 nmol/mg protein, respectively; P < 0.001) compared with the control level (132 +/- 8 nmol/mg protein), which were associated with a significant increase in gamma-GCS activity (0.18 +/- 0.006, 0.16 +/- 0.01, and 0.17 +/- 0. 008 U/mg protein, respectively; P < 0.01) compared with the control level (0.08 +/- 0.001 U/mg protein) at 24 h. Exposure to hyperoxia (95% O2) resulted in a time-dependent increase in GSH levels. gamma-GCS activity increased significantly at 4 h (P < 0.001), returning to control values after 12 h of exposure. Dexamethasone (3 microM) exposure produced a significant time-dependent decrease in the levels of GSH and gamma-GCS activity at 24-96 h. The activity of gamma-GT did not change after oxidant treatment; however, it was decreased significantly by dexamethasone at 24-96 h. Thus oxidants and dexamethasone modulate GSH levels and activities of gamma-GT and gamma-GCS by different mechanisms. We suggest that the increase in gamma-GCS activity but not in gamma-GT activity may be required for the increase in intracellular GSH under oxidative stress in alveolar epithelial cells.

Cell Line↗
PubMed1998

Hydrogen peroxide-induced epithelial injury: the protective role of intracellular nonprotein thiols (NPSH).

Injury to the alveolar region is a hallmark of the adult respiratory distress syndrome (ARDS) whereas injury to the epithelium of the conducting airways is a characteristic of asthma. Reactive oxygen species have been implicated as mediators of lung injury in both of these conditions. We have investigated the relationship between intracellular nonprotein thiols (NPSH), and the release of the cytosolic enzyme lactate dehydrogenase (LDH), as an index of cell injury, following treatment of the human alveolar type II-like epithelial cell line (A549 cells) or the human bronchial epithelial cell line (16HBE140-) with hydrogen peroxide (H2O2). We have also assessed the protective effects of pre-incubation of both of these cells lines with H2O2 or enhancement of intracellular NPSH against H2O2-induced cell injury. Exposure of A549 and 16HBE140- cells to H2O2 (0.1 mM and 1 mM respectively for 16 h) produced the release of 40% of the total cellular LDH. H2O2 exposure produced an initial dose-dependent decrease in NPSH in A549 cells, with a subsequent increase to above control values. 16HBE140- cells also showed a dose-dependent decrease in NPSH following exposure to H2O2. Pretreatment of A549 cells with 0.1 mM H2O2 followed by subsequent exposure to H2O2 did not protect against H2O2-induced LDH release in this epithelial cell line. Pre-incubation with 2 mM N-acetylcysteine (NAC) increased NPSH but not intracellular reduced glutathione and resulted in total inhibition of H2O2-induced LDH release in both cell types. Pretreatment with reduced glutathione protected both cell types against the injurious effects of H2O2, whereas glutathione monethyl ester (GSHMEE) only partially protected A549 cells and had no effect in 16HBE140- cells. Intracellular cysteine levels were increased in both cell lines following NAC exposure but not sufficiently to account for the increase in NPSH levels. These observations raise the possibility that a critical concentration of nonprotein thiols may be necessary to protect pulmonary epithelial cells against hydrogen peroxide-induced injury.

Acetylcysteine↗
PubMed1997

Effect of aerosolization on culturability and viability of gram-negative bacteria.

Estimations of the bacterial content of air can be more easily made now than a decade ago, with colony formation the method of choice for enumeration of airborne bacteria. However, plate counts are subject to error because bacteria exposed to the air may remain viable yet lose the ability to form colonies, i.e., they become viable but nonculturable. If airborne bacteria exhibit this phenomenon, colony formation data will significantly underestimate the bacterial populations in air samples. The objective of the study reported here was to determine the effect of aerosolization on viability and colony-forming ability of Serratia marcescens, Klebsiella planticola, and Cytophaga allerginae. A collision nebulizer was used to spray bacterial suspensions into an aerosol chamber, after which duplicate samples were collected in all-glass impingers over a 4-h period. Humidity was maintained at ca. 20 to 25%, and temperature was maintained at 20 to 22 degrees C for each of two replicate trials per microorganism. Viability was determined by using a modified direct viable count method, employing nalidixic acid or aztreonam and p-iodonitrotetrazolium violet (INT). Cells were stained with acridine orange and observed by epifluorescence microscopy to enumerate total and viable cells. Viable cells were defined as those elongating in the presence of antibiotic and/or reducing INT. CFU were determined by plating on tryptic soy agar and R2A agar. It was found that culture techniques did not provide an adequate description of the bacterial burdens of indoor air (i.e., less than 10% of the aerosolized bacteria were capable of forming visible colonies). It is concluded that total cell count procedures provide a better approximation of the number of bacterial cells in air and that procedures other than plate counting are needed to enumerate bacteria in aerosol samples, especially if the public health quality of indoor air is to be estimated.

Aerosols↗
PubMed1997

Attenuation of oxidant/antioxidant imbalance during treatment of exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: An oxidant/antioxidant imbalance is thought to occur in patients with chronic obstructive pulmonary disease (COPD). It has recently been shown that during exacerbations of COPD the antioxidant capacity and protein sulfhydryls of plasma are lower and the levels of products of lipid peroxidation are higher than in age matched healthy subjects. The aims of this study were to confirm these data and to measure the time course of these changes. METHODS: The plasma Trolox equivalent antioxidant capacity (TEAC), protein sulfhydryls, and products of lipid peroxidation were measured throughout the course of treatment in 13 patients who presented with an acute exacerbation of COPD. RESULTS: TEAC values (mmol/l) were low on admission (mean 0.67, 95% confidence interval (CI) 0.32 to 0.88; p < 0.05) and had increased by discharge (0.98, 95% CI 0.88 to 1.2; p < 0.05) but still remained lower than in healthy subjects (1.33, 95% CI 1.11 to 1.65). There was also restoration of plasma protein sulfhydryl levels (mmol/l) from admission (0.32, 95% CI 0.20 to 0.43) to discharge (0.49, 95% CI 0.42 to 0.62, p < 0.001) to levels similar to those in healthy subjects (0.52, 95% CI 0.43 to 0.65). Products of lipid peroxidation, measured as thiobarbituric acid-malondialdehyde adducts (mumol/l), were significantly higher (2.08, 95% CI 1.8 to 2.5) than in control subjects (1.3, 95% CI 0.85 to 1.32; p < 0.01) and returned to normal values by the time of discharge (1.2, 95% CI 0.88 to 1.29). CONCLUSIONS: These data confirm the presence of a profound oxidant/antioxidant imbalance in the blood of patients with acute exacerbations of COPD which returns towards normal values during the course of treatment.

Adrenergic beta-Agonists↗
PubMed1997

Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors.

We studied asbestos, vitreous fiber (MMVF10), and refractory ceramic fiber (RCF1) from the Thermal Insulation Manufacturers' Association fiber repository regarding the following: free radical damage to plasmid DNA, iron release, ability to deplete glutathione (GSH), and activate redox-sensitive transcription factors in macrophages. Asbestos had much more free radical activity than any of the man-made vitreous fibers. More Fe3+ was released than Fe2+ and more of both was released at pH 4.5 than at pH 7.2. Release of iron from the different fibers was generally not a good correlate of ability to cause free radical injury to the plasmid DNA. All fiber types caused some degree of oxidative stress, as revealed by depletion of intracellular GSH. Amosite asbestos upregulated nuclear binding of activator protein 1 transcription factor to a greater level than MMVF10 and RCF1; long-fiber amosite was the only fiber to enhance activation of the transcription factor nuclear factor kappa B (NF kappa B). The use of cysteine methyl ester and buthionine sulfoximine to modulate GSH suggested that GSH homeostasis was important in leading to activation of transcription factors. We conclude that the intrinsic free radical activity is the major determinant of transcription factor activation and therefore gene expression in alveolar macrophages. Although this was not related to iron release or ability to deplete macrophage GSH at 4 hr, GSH does play a role in activation of NF kappa B.

Animals↗
PubMed1996

Transcriptional regulation of gamma-glutamylcysteine synthetase-heavy subunit by oxidants in human alveolar epithelial cells.

We studied the regulation of glutathione (GSH) synthesis and characterised the 5'-promoter region of the gamma-glutamylcysteine synthetase-heavy subunit (gammaGCS-HS) gene in human alveolar type II cells (A549) following exposure to menadione (MQ) and hydrogen peroxide (H2O2). Both MQ (100 microM) and H2O2 (100 microM) exposure increased intracellular GSH levels associated with increased gammaGCS activity. This was concomitant with enhanced expression of gammaGCS-HS mRNA. Transfection of deletion constructs of the gammaGCS-HS promoter (-1050 to +82 bp) in a chloramphenicol acetyl transferase (CAT) reporter system revealed that an human antioxidant response element (hARE), present within the proximal region of the promoter (-1050 to -818 bp), is not required for oxidant-mediated gene induction. We conclude that oxidant stress-induced gammaGCS-HS mRNA expression is associated with AP-1 or AP-1 like responsive elements (-817 to +45 bp).

Cells, Cultured↗
PubMed1996

Induction of gamma-glutamylcysteine synthetase by cigarette smoke is associated with AP-1 in human alveolar epithelial cells.

Increased levels of glutathione (GSH) occur in the epithelial lining fluid (ELF) of chronic cigarette smokers. Therefore we investigated the effect of cigarette smoke condensate solution (CSC) on GSH synthesis and the regulation of gamma-glutamylcysteine synthetase (gammaGCS) in human type II alveolar epithelial cells (A549). CSC exposure increased GSH levels, gammaGCS activity and gammaGCS heavy subunit (HS) mRNA, as well as increasing DNA binding of the activator protein-1 (AP-1) and the human antioxidant response element (hARE). Transfection of deletion constructs of the gammaGCS-HS promoter in a chloramphenicol acetyl transferase (CAT) reporter system revealed that an hARE, present within promoter, is not required for the CSC mediated induction. We conclude that CSC induction of gammaGCS-HS expression is associated with AP-1/AP-1-like responsive elements.

Antioxidants↗
PubMed1996

Role of oxidants/antioxidants in smoking-induced lung diseases.

An imbalance between oxidants and antioxidants has been considered in the pathogenesis of smoking-induced lung diseases, such as chronic obstructive pulmonary disease (COPD), particularly emphysema. Recent evidence indicates that increased neutrophil sequestration and activation occurs in the pulmonary microvasculature in smokers and in patients with COPD, with the potential to release reactive oxygen species (ROS). ROS generated by airspace phagocytes or inhaled directly from the environment also increase the oxidant burden and may contribute to the epithelial damage. Although much research has focused on the protease/antiprotease theory of the pathogenesis of emphysema, less attention has been paid to the role of ROS in this condition. The injurious effects of the increased oxidant burden in smokers and in patients with COPD are opposed by the lung antioxidant defences. Hence, determining the mechanisms regulating the antioxidant responses is critical to our understanding of the role of oxidants in the pathogenesis of smoking-induced lung disease and to devising future strategies for antioxidant therapy. In this article we have reviewed the evidence for the presence of an oxidant/antioxidant imbalance in smoking-induced lung disease and its relevance to therapy in these conditions.

Antioxidants↗
PubMed1996

Potential virulence of viable but nonculturable Shigella dysenteriae type 1.

We examined a virulent strain of Shigella dysenteriae type 1 after induction into the viable but nonculturable (VBNC) state for its ability to (i) maintain the Shiga toxin (stx) gene; (ii) maintain biologically active Shiga toxin (ShT); and (iii) adhere to intestinal epithelial cells (Henle 407 cell line). PCR was used to amplify the stx gene from VBNC cells of S. dysenteriae type 1, thereby establishing its presence even when cells are in the VBNC state. VBNC S. dysenteriae type 1 ShT was monitored by the enzyme-linked immunosorbent assay with mouse monoclonal antibodies against the B subunit of ShT and affinity-purified rabbit polyclonal antibodies against ShT. We used the Henle 407 cell line to study the adhesive property of VBNC S. dysenteriae type 1 cells in a series of tissue culture experiments. Results showed that VBNC S. dysenteriae type 1 not only maintained the stx gene and biologically active ShT but also remained capable of adhering to Henle 407 cells. However, S. dysenteriae type 1 cells lost the ability to invade Henle 407 cells after entering the VBNC state. From results of the study, we conclude that VBNC cells of S. dysenteriae type 1 retain several virulence factors and remain potentially virulent, posing a public health problem.

Animals↗