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

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

Involvement of throm box aneA2 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 micrometer) was inhibited by PAF receptor blocker (WEB 2086, IC50=0.65 micrometer) and calcium channel blockers, diltiazem (IC50=13 micrometer) and verapamil (IC50=18 micrometer). 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 micrometer), a cyclooxygenase inhibitor (indomethacin; IC50=0.2 micrometer) and inhibitor of TLCK, herbimycin A with IC50 value of 5 micrometer. The effect was also inhibited by a specific TXA2 receptor antagonist, SQ 29548 with very low IC50 value of 0.05 micrometer. 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.

closer look at food allergy and intolerance

Food allergy is a condition prevalent in over 2% 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

Role of phosphatidylinositol 3-kinase in epinephrine and calcium ionophore, A 23187 induced platelet aggregation

Human platelets contain a2-adrenergic receptors, which are coupled with guanine nucleotide proteins [G Proteins]. Stimulation of a2 adrenergic receptors leads to the activation of Gi adenylyl cyclase cascade in platelets. Recent evidence suggests the role of cross regulation between adenylyl cyclase and phospholipase signaling pathways. Calcium ionophore, A23187 is thought to activate cellular phospholipases. In the present study, we have investigated the mechanism involved in the action of epinephrine on platelet aggregation induced by A23187. The results show that epinephrine at low concentrations [0.01 - 0.2 pM] and/or A23187 [0.1-0.5 micro M] itself did not produce platelet aggregation. However, when added together, a marked potentiation of platelet aggregation was observed. This synergistic effect was inhibited by a2-receptor blocker [yohimbine; IC50 = 0.05 micro M] showing that the response is receptor mediated. To find out the molecular basis of this potentiation, we used Wortmannin, selective inhibitor of phosphatidylinositol 3. kinase [P13K]. Wortmannin inhibited the platelet aggregation induced by A23187 and epinephrine with IC50 value of 0.35 pM. The data suggest that epinephrine and calcium influx act synergistically and P13K plays an important role in platelet aggregation