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Biomedical subjects

I Rahman

Publications and source records attributed to I Rahman.

At least 19 recordsLinked to original sources
PubMed2006

Oxidative stress and redox regulation of lung inflammation in COPD.

Reactive oxygen species, either directly or via the formation of lipid peroxidation products, may play a role in enhancing inflammation through the activation of stress kinases (c-Jun activated kinase, extracellular signal-regulated kinase, p38) and redox-sensitive transcription factors, such as nuclear factor (NF)-kappaB and activator protein-1. This results in increased expression of a battery of distinct pro-inflammatory mediators. Oxidative stress activates NF-kappaB-mediated transcription of pro-inflammatory mediators either through activation of its activating inhibitor of kappaB-alpha kinase or the enhanced recruitment and activation of transcriptional co-activators. Enhanced NF-kappaB-co-activator complex formation results in targeted increases in histone modifications, such as acetylation leading to inflammatory gene expression. Emerging evidence suggests the glutathione redox couple may entail dynamic regulation of protein function by reversible disulphide bond formation on kinases, phosphatases and transcription factors. Oxidative stress also inhibits histone deacetylase activity and in doing so further enhances inflammatory gene expression and may attenuate glucocorticoid sensitivity. The antioxidant/anti-inflammatory effects of thiol molecules (glutathione, N-acetyl-L-cysteine and N-acystelyn, erdosteine), dietary polyphenols (curcumin-diferuloylmethane, cathechins/quercetin and reserveratol), specific spin traps, such as alpha-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (extracellular superoxide dismutase (SOD) mimetic, SOD mimetic M40419 and SOD, and catalase manganic salen compound, eukarion-8), porphyrins (AEOL 10150 and AEOL 10113) and theophylline have all been shown to play a role in either controlling NF-kappaB activation or affecting histone modifications with subsequent effects on inflammatory gene expression in lung epithelial cells. Thus, oxidative stress regulates both key signal transduction pathways and histone modifications involved in lung inflammation. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in chronic obstructive pulmonary disease are also discussed.

Antioxidants↗
PubMed2005

Open globe injuries: factors predictive of poor outcome.

OBJECTIVE: Despite advances in ocular and orbital imaging, instrumentation, materials, and surgical procedures, the management of open globe injuries continues to pose difficult management dilemmas. In this retrospective study, we identify clinical characteristics and outcome of a series of open globe injuries presenting to a major UK centre. METHOD: Operating department records were reviewed to identify all patients who had undergone repair of an open globe injury from 1 January 1998 to 1 January 2003 at the Manchester Royal Eye Hospital. Case notes were examined to determine demographic data, mechanisms of injury, influence of alcohol/drugs, and location of injury. The Snellen visual acuity on presentation and initial clinical signs were recorded. RESULTS: In total, 115 cases of open globe injury were identified of which 107 cases notes were available for review. Injury to the eye with a sharp object accounted for 71/107 (66%) cases and blunt mechanisms for 30/107 (28%) cases. In six (6%) cases the cause of injury was unknown. The rate of secondary enucleation in our series of 107 open globe injuries was 13/107 (12%). Significant risk factors on presentation associated with eventual enucleation included relative afferent pupillary defect (P<0.001), absence of a red reflex (P<0.001), presence of a lid laceration (P<0.02), a blunt mechanism of injury (P<0.02), and an initial VA worse than 6/60 (P=0.03). CONCLUSION: From this retrospective study, we have identified several factors that may aid the clinician in deciding on the prognostic value of primary repair. Blunt injuries associated with adnexal trauma, with poor initial visual acuity, the presence of an RAPD or retinal detachment, and the absence of a red reflex are associated with a significantly higher rate of subsequent enucleation.

Accidents↗
PubMed2005

Long-term results of cataract extraction with intraocular lens implantation in patients with uveitis.

OBJECTIVE: To investigate the long-term visual results after cataract extraction in patients with uveitis, and to demonstrate the long-term viability of intraocular lenses. DESIGN: In all, 61 patients (72 eyes), with update clinical examination, were retrospectively evaluated. Comparison of preoperative, postoperative, and latest visual function including best-corrected Snellen visual acuity, progression of uveitis and its complications, need for postoperative medical or surgical interventions. RESULTS: After a minimum follow-up of 5 years (mean 7 years 7 months), 82% of eyes maintained a visual improvement of two Snellen lines, 74% maintained 6/9 or better, and 14% had 6/18 or worse. The mode acuity was better than 6/6. The prevalence of macular oedema or scarring was 24%, of posterior capsule opacification 96%, and of glaucoma drainage, 15%. CONCLUSIONS: We report the long-term follow-up of cataract extraction and intraocular lens (IOL) implantation performed by a single surgeon on patients with uveitis attending a regional tertiary referral uveitis clinic. Using stringent perioperative and postoperative control of inflammation, patients with uveitis usually maintain high visual acuity over long-term follow-up. The incidence of sight-threatening postoperative complications is low and no ongoing complication has been attributed to IOL implantation.

Adolescent↗
PubMed2005

Orbital exenteration: a 13 year Manchester experience.

BACKGROUND/AIMS: Orbital exenteration is a psychologically and anatomically disfiguring procedure reserved for the treatment of potentially life threatening malignancies or relentlessly progressive conditions unresponsive to other treatments. In this study the authors aimed to review their experience with exenteration, including indications, outcomes, and reasons for the increased rate of exenterations over the past 15 months. METHOD: This retrospective study reviewed operating department records via a computerised database to identify all patients who had undergone exenteration of the orbit from 1 January 1991 to 1 April 2004 inclusive, at the Manchester Royal Eye Hospital. Where case records were unavailable, attempts were made to obtain patient data from general practitioners, local health authorities, and referring hospitals. RESULTS: 69 orbits of 68 patients were identified. The mean age of the cohort was 68.2 years, with 33 males and 35 females having undergone exenterations. In total, 31 patients had previously undergone treatments undertaken by the referring specialty with a mean time from the primary procedure to exenteration of 115 months. 14 different tumours were encountered, of which basal cell carcinoma (28), melanoma (10), sebaceous cell carcinoma (nine), and squamous cell carcinoma (six) were the most common. An increasing incidence was observed in cases of BCCs requiring exenteration. 30 patients received orbital prosthesis within an 11 month period post-exenteration. CONCLUSION: Exenteration is a procedure performed with increasing frequency in this unit over the past 15 months, the majority the result of BCCs. A large proportion of these exenterations had undergone previous treatments under a variety of non-ophthalmic specialties in other units. Exenterations are disfiguring procedures that may, therefore, be reduced in incidence by aggressive removal at the time of primary removal. Once performed, the cosmetic rehabilitation is long, with multiple postoperative visits, independent of the method used to close the orbital defect.

Adolescent↗
PubMed2005

Mortality following exenteration for malignant tumours of the orbit.

BACKGROUND: Orbital exenteration is a rare, but disfiguring procedure reserved for the treatment of locally invasive malignancy or potentially life threatening orbital neoplasms, when less destructive techniques are inadequate. The authors report their experience and analyses of 64 cases of orbital exenteration performed over a 13 year period, looking specifically at key factors affecting mortality associated with such a destructive surgical procedure. METHODS: Records were reviewed retrospectively of all patients who had undergone exenteration of the orbit from 1 January 1991 to 1 April 2004 inclusive, at the Manchester Royal Eye Hospital. In all cases of deceased individuals, the cause of death was determined by liaison with the general practitioner and local health authority. Duplicate death certificates were requested for all deceased patients from the Registrar for Births, Deaths, and Marriages, Southport, UK. Kaplan-Meier analysis was used to estimate survival following exenteration. RESULTS: Overall, 1 year survival post-exenteration was high at 93%. After 3 years this had fallen to 67%, followed by 57% after 5 years, and 37% at 10 years. 13 patients died as a direct result of the orbital tumour. A further nine died of unrelated medical conditions, and two patients succumbed to malignant processes originating elsewhere in the body. There was no difference in survival rate at 3 years (p=0.99) and 5 years (p=0.454) between those with clear resection margins and those without. CONCLUSION: In this study it was found that there was an overall mortality rate of 38% over 12 years. The presence of clear surgical margins, although reassuring for the surgeon, should not be regarded as an indication of cure. However, an overall 1 year survival of 93% and a 10 year survival of 37% are reassuring in that a proportion of individuals achieve surgical cure following exenteration. 38% of patients died as a result of other medical causes over the 12 year follow up.

Adolescent↗
PubMed2005

Toxicological study of plant extracts on termite and laboratory animals.

Toxic activity of leaf extracts of Polygonum hydropiper L. and Pogostemon parviflorus Benth. were tested in the laboratory against tea termite, Odontotermes assamensis Holm. Both the tested extracts caused mortality of the termite. The highest toxic activity (100%) was found in the 2.0% chloroform extracts of P. hydropiper. The chloroform extract of P. hydropiper was explored for possible mammalian toxicological effects. The LD50 was 758.58 mg/kg in male albino mice. Subcutaneous injection of sub-lethal dose of extract into male mice once a week for 6 weeks failed to express any significant influence on WBC, RBC count and blood cholesterol.

Animals↗
PubMed2003

Annexin A1 processing is associated with caspase-dependent apoptosis in BZR cells.

Annexins are widely distributed and have been described in lung as well as in other cells and tissues. Annexin I (ANX AI) is a member of the calcium-dependent phospholipid binding protein family. Besides its anti-inflammatory function, ANX AI has been involved in several mechanisms such as the Erk repression pathway or apoptosis. To investigate the role of ANX AI on apoptosis in broncho-alveolar cells, we have constructed a plasmid containing the ANX AI full length cDNA. Transfected BZR cells displayed a higher level of both forms of ANX AI (37 and 33 kDa) as well as a decrease in cell viability (two-fold versus cells transfected with an empty vector). In order to analyse the endogenous ANX AI processing during stimulus-induced apoptosis, BZR cells were treated with a commonly used inducer, i.e. C2 ceramides. In these conditions, microscopic analysis revealed chromatin condensation in dying cells and the Bcl-2, Bcl-x(L)/Bax mRNA balance was altered. Caspase-3 is one of the key executioners of apoptosis, being responsible for the cleavage of many proteins such as the nuclear enzyme poly(ADP-ribose) polymerase (PARP). We demonstrate that caspase-3 was activated after 4 h treatment in the presence of ceramide leading to the cleavage of PARP. Dose-response experiments revealed that cell morphology and viability modifications following ceramide treatment were accompanied by an increase in endogenous ANX AI processing. Interestingly, in both ceramide and transfection experiments, the ANX AI cleaved form was enhanced whereas pre-treatment with the caspase inhibitor Z-VAD-fmk abolished ANX AI cleavage. In conclusion, this study demonstrates a complex regulatory role of caspase-dependent apoptosis where ANX AI is processed at the N-terminal region which could give susceptibility to apoptosis upon ceramide treatment.

Annexin A1↗
PubMed2002

PM(10)-exposed macrophages stimulate a proinflammatory response in lung epithelial cells via TNF-alpha.

There is now considerable evidence for an association between the levels of particulate air pollution [particulate matter <10 microm in aerodynamic diameter (PM(10))] and various adverse health endpoints. The release of proinflammatory mediators from PM(10)-exposed macrophages may be important in stimulating cytokine release from lung epithelial cells, thus amplifying the inflammatory response. A549 cells were treated with conditioned media from monocyte-derived macrophages stimulated with PM(10), titanium dioxide (TiO(2)), or ultrafine TiO(2). We demonstrate that only conditioned media from PM(10)-stimulated macrophages significantly increased nuclear factor-kappaB and activator protein-1 DNA binding, enhanced interleukin-8 (IL-8) mRNA levels as assessed by RT-PCR, and augmented IL-8 protein levels, over untreated controls. Furthermore, PM(10)-conditioned media also caused transactivation of IL-8 as determined by an IL-8-chloramphenicol acetyl transferase reporter. Analysis of these conditioned media revealed marked increases in tumor necrosis factor-alpha (TNF-alpha) and protein levels and enhanced chemotactic activity for neutrophils. Preincubation of conditioned media with TNF-alpha-neutralizing antibodies significantly reduced IL-8 production. These data suggest that PM(10)-activated macrophages may amplify the inflammatory response by enhancing IL-8 release from lung epithelial cells, in part, via elaboration of TNF-alpha.

Air Pollutants↗
PubMed2001

Oxidant-mediated lung epithelial cell tolerance: the role of intracellular glutathione and nuclear factor-kappaB.

The airway epithelium is injured by oxidants inhaled as atmospheric pollutants or produced during inflammatory responses. We studied the effect of modulating the antioxidant intracellular glutathione, both using thiol compounds and by the adaptive effect of hyperoxia, on oxidant-induced injury and activation of the nuclear factor-kappaB (NF-kappaB) in two cell lines: the human bronchial (16HBE) and type II alveolar epithelial cells (A549). The thiol antioxidants glutathione (GSH) and glutathione monoethyl ester (GSH-MEE) [2 mM] increased GSH levels (nmol/mg protein) in A549 cells (GSH 383 +/- 26 and GSH-MEE 336 +/- 23 vs control 171 +/- 13, P < 0.001) and in 16HBE cells (GSH 405 +/- 33, GSH-MEE 362 +/- 37 vs control 198 +/- 12, P < 0.001, N = 3). Treatment of hyperoxia (95% oxygen) also increased GSH levels between 4 and 24 hr exposure compared with control (P < 0.01). Hydrogen peroxide (H(2)O(2)) (0.01 mM) induced NF-kappaB activation, whereas hyperoxia exposure did not affect NF-kappaB activation in either cell line. Pretreatment with dl-buthionine (SR)-sulfoximine, which decreased intracellular glutathione, increased NF-kappaB binding induced by H(2)O(2) and increased lactate dehydrogenase (LDH) release (P < 0.001). Pretreatment with the thiol compounds and hyperoxia totally inhibited H(2)O(2)-induced NF-kappaB binding and cell injury as measured by LDH release. These data indicate the importance of intracellular glutathione and inhibition of NF-kappaB in both protection/tolerance against oxidant-induced epithelial cell injury, and NF-kappaB activation in response to oxidative stress which may be important in lung inflammation. Thus, increasing intracellular glutathione may be of therapeutic relevance if able to modulate NF-kappaB activation and hence attenuate inflammation.

Adaptation, Biological↗