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Publications (7) View all
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Article: Prevalence of microalbuminuria with relation to glycemic control in type-2 diabetic patients in Karachi
Journal of Ayub Medical College, Abbottabad: JAMC 01/2009; J Ayub Med Coll Abottabad Jul - Sep 2009;21(3):83-6. -
Article: Anti-inflammatory role of methotrexate in adjuvant arthritis: effect on substance p and calcitonin gene-related Peptide in thymus and spleen.
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ABSTRACT: Objective: To investigate the anti-inflammatory effect of methotrexate (MTX) in rats with adjuvant arthritis through its influence on the expression of proinflammatory neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) in immune organs, thymus and spleen. Design: Phase-I pre-clinical trial. Place and Duration of Study: The Aga Khan University, Karachi, from July to December 2003. Materials and Method: Adjuvant arthritis was induced in rats by inoculation with heat-killed mycobacteria. One group of arthritic rats (n=6) was treated with MTX (0.2 mg/kg body weight, subcutaneously) on every 4th day for a period of 18 weeks, while another group of arthritic rats (n=6) was treated with physiological saline served as control. At the end of experiment, animals were sacrificed and thymus and spleen were dissected and prepared for immunohistochemical analysis. The neuronal density of SP and CGRP immunoreactivity in thymus and spleen was assessed by semi-quantitative analysis. Results: There was a marked reduction in hind paw swelling and inflammation in the MTX-treated rats after 18 weeks of treatment. Restoration of joint spaces (tibiotalar and subtalar) was seen after 9 weeks of MTX treatment. CGRP-positive nerve fibres were significantly reduced (p=0.0001) in thymus of rats treated with MTX compared to control rats. SP-positive nerve fibers were also found to be decreased in thymus of rats treated with MTX compared to controls, however, the decrease was not statistically significant. The neuronal density of SP and CGRP-immunoreactivity in spleen was not significantly different in MTX-treated and placebo-treated rats. Conclusion: In arthritic rats, MTX significantly reduced CGRP expression in thymus. Suppression of pro-inflammatory neuropeptides, such as CGRP and probably SP could be another mechanism by which MTX produces its anti-inflammatory effect in adjuvant arthritis.Journal of the College of Physicians and Surgeons--Pakistan: JCPSP 09/2007; 17(8):490-4. · 0.34 Impact Factor -
Article: Polymorphism of HLA-DR and HLA-DQ in rheumatoid arthritis patients and clinical response to methotrexate--a hospital-based study.
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ABSTRACT: To investigate the frequency and distribution of DRB1 and DQB1 alleles in Patients with rheumatoid arthritis (RA) and analyze the relationship between clinical response to methotrexate (MTX) and the HLA-DR and HLA-DQ genotypes in these patients. In this case-control study, the HLA-DRB1 and HLA-DQB1 polymorphism in 91 RA patients and 91 healthy controls was done using polymerase chain reaction and sequence specific primers. There was no statistical difference in frequencies of HLA-DRB1*03, DRB1*04, DRB1*07, DRB1*10, DRB1*11, DRB1*12, DRB1*13, DRB1*14, DRB1*15 and DRB1*16 genotypes between patients and controls. However, DRB1*01 was found to be significantly more common (p=0.015) in RA patients compared to controls. HLA-DRB1*15 was more common in patients (43.5%) compared to controls (30.8%) but results were not significant. HLA-DRB1*08 and DRB1*09 were present in negligible number in patients as well as controls while HLA-DRB1*12 was conspicuously absent in controls. Similarly, DQB1*06 was also significantly more common (p = 0.01) among the patients compared to healthy control subjects, while there was no statistical difference in the frequencies of DQB1*02, DQB1*03, DQB1*04 and DQB1*05 among the cases and the controls. RA susceptibility in most patients appeared to be associated with the HLA-DRB1*01/DQB1 *06 genotype. Regarding association between HLA-DR or HLA-DQ genotype and clinical response to methotrexate (MTX), the data showed that with the exception of HLA-DRB1*03, there appears to be no association between the particular subtypes of HLA-DR and HLA-DQ. HLA-DRB1*03 was significantly-more common among non-responders to MTX alluding to the possibility that another genes responsible for MTX metabolism, might be in linkage disequilibrium with HLA-DRB1*03 in the Pakistani population, thereby making such individuals non-responsive to MTX-therapy. RA susceptibility in most Pakistani patients is associated with the HLA-DRB1*01/DQB1*06 genotype. HLA-DRB1*03 was found to be significantly more common among non-responders to MTX treatment suggesting that Pakistani patients with this genotype are less likely to benefit from MTX.Journal of the Pakistan Medical Association 11/2006; 56(10):452-6. -
Article: The effects of non-steroidal anti-inflammatory drugs on the disposition of methotrexate in patients with rheumatoid arthritis.
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ABSTRACT: We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently taking the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, diclofenac, naproxen, indomethacin, and ibuprofen. The area under the curve, the total systemic clearance, the distribution volume, and the half-life of methotrexate in patients receiving concurrent NSAID therapy did not change significantly (at p < 0.05). Concurrent treatment with NSAIDs resulted in increased inter-patient variability of methotrexate concentration, possibly as a result of biochemical interactions; however, it does not appear clinically relevant. The data suggest that the NSAIDs do not significantly affect the disposition of methotrexate, contrary to some of the earlier reports.Biopharmaceutics & Drug Disposition 04/1998; 19(3):163-7. · 2.07 Impact Factor -
Article: ROLE OF METHOTREXATE IN RHEUMATOID ARTHRITIS
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ABSTRACT: Rheumatiod arthritis is a chronic, autoimmune, inflammatory disorder in which the joints are primarily affected with synovitis causing the articular destruction. About 1% of the world population and 0.1-0.2% of Pakistani population is affected with RA. It is hypothesized that the genetically susceptible individuals, after exposure to arthritogenic antigen, under go for inflammatory reaction leading to joint destruction The etiology of RA is unknown, therefore, the curative treatment is not yet established. However, the current treatment is to suppress the inflammatory response to ameliorate the symptoms thereby preventing the damage to articular structure. To achieve these goals several therapies have been used The disease modifying antiheumatic drugs (DMARD) with non-steroidal antinflammatory drugs (NSAIDs) are being extensively used to provide the best possible relief to RA patients Among the DMARDs, the methotrexate (MTX), is being extensively used in low doses (7.5 mg ÃÂâÃÂÃÂÃÂà15 mg/day) in the treatment of RA. Its popular use in RA is due to its reasonably rapid ant inflammatory action with minimum side effects and low cost. In spite of its extensive use in RA, the mechanism of ant inflammatory action of MTX still not known Since RA is quite common in Pakistan, we embarked on investigating the role of MTX in patients with RA in Pakistani population The study had following four objectives: i). To observe the effectiveness and tolerability of MTX in our RA population. ii). To observe the effects of commonly used NSAIDs on disposition of MTX in our RA patients. iii). To observe the frequency distribution of HKLA-DRBI and HLA-DQB1 alleles and to see if there is any relationship between clinical response to MTX and HLA-DR and HLA-DQ genotypes in these RA patients. iv). To investigation whether the ant inflammatory effect of MTX in RA is through suppression of pro-inflammatory neuropeptides (substance P and calcitonin gene related peptide). The important findings of the study are: MTX despite its adverse effects in some patients, was found to be a very effective (83% of the patients showing good to excellent response after one year treatment) in RA. There was no significant pharmacokinetic interaction between MTX and various NSAID (naproxen, diclofenac, ibuprofen, aspirin, and indomethacin), indicating that MTX can be safely given along with above mentioned NSAIDs. The susceptibility to develop RA, in most of the Pakistani population, appeared to be associated with HLA-DRBI*15/DQ1*16 genotype. However, there was a lack of association between HLA-DRB1? DQB1 genotypes and clinical response to MTX. MTX suppresses the expression of pro-inflammatory neuropeptides (SP and OGRP) at the site of inflammation and at the level of lymphoid organs. Therefore pro-inflammatory neuropeptides do appear to have a role in RA and one of the mechanisms of anti-inflammatory action of MTX could be due to suppression of these neuropeptides.
