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Biomedical subjects

Sheikh Arshad Saeed

Publications and source records attributed to Sheikh Arshad Saeed.

11 recordsLinked to original sources
PubMed2006

Role of cyclooxygenase-2 in myocardial infarction and ischaemia.

OBJECTIVE: To determine the role of cyclooxygenase-2 (COX-2), on coronary perfusion rate (CPR) in a rabbit heart model showing ischaemic damage and reperfusion injury to the myocardium. DESIGN: An experimental study. PLACE AND DURATION OF STUDY: The animal unit of the Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCS, University of Karachi during July 2004 to June 2005. MATERIALS AND METHODS: Rabbits were divided into three groups of six animals each. Group I had normal rabbits, group II consisted of infarcted rabbits (infarction induced by 65 mg /kg isoproterenol (ISP) and group III consisted of infarcted rabbits that received nimesulide, a COX-2 inhibitor (25 mg/kg). MI was induced in rabbits by ISP, a beta-agonist drug given by the intraperitoneal route. In this model, the acute phases of myocardial necrosis and repair mimicked those which occurred in humans. Induction of MI was confirmed by measuring changes in serum creatinine phosphokinase (CPK) and troponin I (TPI) levels, electrophysiological (ECG) changes and histochemical changes in the left ventricle before and after ISP injection. Coronary perfusion rate (CPR) was monitored using Langendorff isolated heart preparation at day 2, 4, 8 and 16 of post-infarction. RESULTS: CPR of infarcted and nimesulide treated rabbits displayed significant improvement on each corresponding day post-infarction as compared to the infarcted and control rabbits (p <0.01). CONCLUSION: Using this model, it was found that nimesulide, a COX-2 inhibitor, exerted a cardioprotective effects in MI.

Animals↗
PubMed2005

Myocardial ischaemia and reperfusion injury: reactive oxygen species and the role of neutrophil.

A growing body of evidence suggests that oxygen radicals can mediate myocardial tissue injury during ischaemia and, in particular, during reperfusion. This review focuses on the role of neutrophil as a mediator of myocardial damage. Upon reperfusion, neutrophils accumulate and produce an inflammatory response in the myocardium that is responsible, in part, for the extension of tissue injury associated with reperfusion. It has shown that the inhibition of neutrophil accumulation and adhesion is associated with decreased infarct size. This strongly suggests that myocardial cells at risk region undergo irreversible changes upon reperfusion and accumulation of neutrophils. Several pharmacological agents (ibuprofen, allopurinol, prostacyclin, and prostaglandin E analogues) protect the myocardium from reperfusion injury. In addition, the mechanisms by which these agents act and directions of research that may lead to therapeutically useful approaches are also discussed in this review.

Allopurinol↗
PubMed2005

Latest approaches to the diagnosis and management of food allergies in children.

Adverse food reactions are a challenge for physicians. As the prevalence of this condition rises, it is important that paediatricians and other health care professionals adeptly diagnose this condition. We begin by discussing the relevant points in history and physical examination, then we discuss the recent effective diagnostic tests and techniques available for doctors and patients, along with several management options. Over the last decade, there have been major advancements in this field and novel mechanisms have been proposed which efficiently modulate immune mechanisms involved. Although results are only preliminary, they do however, indicate a promising future for patients with food allergies.

Anti-Allergic Agents↗
PubMed2004

Involvement of thromboxane A2 and tyrosine kinase in the synergistic interaction of platelet activating factor and calcium ionophore A23187 in human platelet aggregation.

The present study was carried out to examine the mechanisms of the synergistic interaction of PAF and A23187 mediated platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of PAF (5 nM) and A23187 (1 mM) was inhibited by PAF receptor blocker (WEB 2086, IC50 = 0.65 mM) and calcium channel blockers, diltiazem (IC50 = 13 mM) and verapamil (IC50 = 18 mM). Pretreatment of platelets with PAF and A23187 induced rise in intracellular calcium and this effect was also blocked by verapamil. While examining the role of the down stream signaling pathways, we found that platelet aggregation induced by the co-addition of PAF and A23187 was also inhibited by low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50 = 10 mM), a cyclooxygenase inhibitor (indomethacin; IC50 = 0.2 mM) and inhibitor of TLCK, herbimycin A with IC50 value of 5 mM. The effect was also inhibited by a specific TXA2 receptor antagonist, SQ 29548 with very low IC50 value of 0.05 mM. However, the inhibitors of MAP kinase, PD98059 and protein kinase C, chelerythrine had no effect on PAF and A23187-induced platelet aggregation. These data suggest that the synergism between PAF and A23187 in platelet aggregation involves activation of thromboxane and tyrosine kinase pathways.

Benzoquinones↗
PubMed2004

A closer look at food allergy and intolerance.

Food allergy is a condition prevalent in over 2 percent of the world's population. The topic has been subject to research from ancient Greek times and continues to attract modern scientific and medical communities. In susceptible individuals certain foods produce a wide spectrum of unwanted effects like eczema, asthma, and urticaria. The management of food allergy and intolerance chiefly involves elimination diets, accurate diagnosis and detecting the causative mechanism providing us with ample food for thought. In this article, we have attempted to summarize and simplify the research on the various aspects of food allergy and intolerance, and discuss the natural history, manifestations, mechanisms, diagnosis, and management of this condition affecting countless worldwide.

Diet Therapy↗
PubMed2004

Signaling mechanisms mediated by G-protein coupled receptors in human platelets.

AIM: The present study deals with the investigation of mechanisms involved in the synergistic interaction between epinephrine and arachidonic acid (AA). METHODS: Venous blood was taken from healthy human volunteers reported to be free of medications for one week. Platelet aggregation was monitored at 37 degree using Dual-channel Lumi-aggregometer. The resulting aggregation was recorded for 5 min by the measurement of light transmission as a function of time. RESULTS: The data show that a synergism in platelet aggregation mediated by subthreshold concentrations of epinephrine (1 micromol/L) and AA (0.2 micromol/L) was inhibited by the alpha2-receptor antagonist (yohimbine, IC50)=0.6 micromol/L) and an inhibitor of AA-cyclooxygenase (COX), indomethacin (IC50=0.25 micromol/L). In examining receptor influence on intraplatelet signalling pathways, it was found that the synergistic effect was inhibited by calcium channel blockers, verapamil (IC50=0.4 micromol/L) and diltiazem (IC50=2.5 micromol/L), as well as by low concentrations of inhibitors of phospholipase C (PLC) (U73122; IC50=0.2 micromol/L) and mitogens activated protein kinase (MAPK) (PD 98059; IC50=3.8 micromol/L). Herbimycin A, a specific inhibitor of tyrosine light chain kinase (TLCK), showed inhibition at IC50 value of 15 micromol/L, whereas chelerythrine, a protein kinase C (PKC) inhibitor, had no effect up to 20 micromol/L. CONCLUSION: These data suggest that synergism between epinephrine and AA in platelet aggregation is triggered through receptors coupled to G-protein, which in turn, activate PLC, COX, and MAP kinase-signaling pathways.

Adrenergic Agonists↗
PubMed2003

Calcium-dependent synergistic interaction of platelet activating factor and epinephrine in human platelet aggregation.

AIM: To investigate the mechanism (s) involved in the synergistic interaction of platelet activating factor (PAF) and epinephrine. METHODS: Blood was obtained from healthy human subjects reported to be free of medications for at least two weeks before sampling. Aggregation was monitored at 37 oC using Dual-channel Lumi-aggregometer. The resulting aggregation was recorded for 5 min by the measurement of light transmission as a function of time. RESULTS: Platelet aggregation mediated by subthreshold concentrations of PAF (5-8 nmol/L) plus epinephrine (0.5-2 micromol/L) was inhibited by ?2-receptor blocker, yohimbine, and PAF receptor antagonist WEB 2086. This synergism was inhibited by calcium channel blockers, verapamil and diltiazem. In addition, platelet aggregation by co-addition of PAF and epinephrine was also inhibited by very low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50=0.2 micromol/L), the MAP kinase inhibitor, PD 98059 (IC50=3 micromol/L), and cyclooxygenase (COX-1) inhibitors including indomethacin (IC50=0.25 micromol/L), flurbiprofen (IC50=0.7 micromol/L), and piroxicam (IC50=7 micromol/L). However, COX-2 inhibitors, nimesulide (IC50=26 micromol/L), NS-398 (IC50=7 micromol/L), and etodolac (IC50=15 micromol/L) were also effective in inhibiting the aggregation. The inhibitors of protein kinase C (chelerythrine) and tyrosine kinase (genistien), and phosphatidylinositol 3-kinase inhibitor (wortmannin) had no significant effect on platelet aggregation induced by PAF and epinephrine. CONCLUSION: The synergistic effect of PAF and epinephrine on human platelet aggregation is receptor-mediated and involves the activation of PLC/Ca2+, COX and MAP kinase signalling pathways.

Adrenergic alpha-Agonists↗
PubMed2003

Synergism interaction between arachidonic acid by 5-hydroxytryptamine in human platelet aggregation is mediated through multiple signalling pathways.

AIM: To examine the signalling mechanisms involved in the synergistic interaction of 5-hydroxytryptamine (5-HT) and arachidonic acid (AA) in human platelet aggregation. METHODS: Blood was obtained from healthy human subjects, mixed with 3.8 % sodium citrate (9:1), and centrifuged to prepare platelet rich plasma (PRP). Aggregation was monitored using a Dual-channel Lumi-aggregometer. The agonist-induced influx of Ca2+ was measured using Fura-2 AM. TXA2 formation was studied using radiochemical method. RESULTS: Subthreshold concentration of 5-HT (2 micromol/L) potentiated the effect of low dose of AA (0.2 mmol/L) in human platelets. This synergistic effect was blocked by 5-HT2 receptor antagonist (methysergide IC(50)=5.2 nmol/L; cyproheptadine IC(50)=0.6 nmol/L), and thromboxane A2 receptor antagonist (SQ 29 548; IC(50)=30 nmol/L), showing that the effect is receptor-mediated. To examine the down-stream signalling pathways, we found that such an interaction was inhibited by calcium channel blockers (diltiazem; IC(50)=3 micromol/L and verapamil; IC(50)=5 micromol/L), phospholipase C (PLC) inhibitor (U73122; IC50=4 micromol/L), cyclooxygenase inhibitor, (indomethacin; IC(50)=0.2 micromol/L) and mitogen-activated protein (MAP) kinase inhibitor (PD98059; IC(50)=3 micromol/L). The effect was also inhibited by a specific tyrosine light chain kinase (TLCK) inhibitor, herbimycin A with IC(50) value of 5 micromol/L. Pretreatment of platelet with 5-HT and AA induced rise in intracellular calcium and this effect was blocked by verapamil. CONCLUSION: The synergism between 5-HT and AA in platelet aggregation involves activation of PLC/Ca2+, COX, and MAP kinase pathways.

Arachidonic Acid↗
PubMedDate not supplied

Synergistic interaction of epinephrine and calcium ionophore in platelet aggregation.

BACKGROUND: Platelets play a key role in haemostasis. Human Platelets contain alpha2 adrenergic receptors, which are coupled with guanine nucleotide proteins (G proteins). The platelet activation involves a number of receptors for agonists. It has also been shown that most of the agonists act in synergy and potentiate the effects of each other. The present experimental study was designed to study the potentiation of epinephrine on human platelets by calcium ionophore A23187 and the possible role of calcium in platelet aggregation as a second messenger. METHODS: Study was carried out at Department of Biological Sciences Aga Khan University, Karachi. Blood samples from healthy volunteers were collected; Platelet aggregation was measured using Dual channel Lumi Aggregometer. The chemicals used include epinephrine, calcium ionophore A23187, yohimbine, diltiazem, verapamil and S Nitrosoacetylpenicillamin (SNAP). RESULTS: Epinephrine at low concentrations (0.01-0.2 microM) and/or A23187 (0.1-0.5 microM) itself did not produce platelet aggregation. However, when added together, a marked potentiation of platelet aggregation was observed. This synergistic effect was inhibited by alpha2-receptor blocker yohimbine; (IC50 = 0.05 microM) showing that the response is receptor mediated. To find out the molecular basis of this potentiation, we used SNAP, a nitric oxide donor and Ca++ channel blockers, i.e. diltiazem and verapamil. The SNAP, diltiazem and verapamil inhibited the platelet aggregation induced by A23187 and epinephrine with IC50 value of 0.5 microM, 50 microM and 22 microM respectively. CONCLUSION: The results of the study suggest that epinephrine and calcium ionophore act synergistically and Ca++ plays an important role in this synergistic interaction. While calcium channels blocking drugs diltiazem and verapamil inhibit this synergism.

Calcium↗