Aspirin does not inhibit adenosine diphosphate-induced platelet alpha- granule release

The involvement of metabolites of arachidonic acid in platelet-dense granule secretion and secondary platelet-platelet interactions is well characterized. However, their role in heterotypic interactions dependent on alpha-granule secretion is less well understood. Using platelet-surface expression of P-selectin as a marker of alpha-granule secretion, we have shown that: (1) aspirin treatment of platelets at doses that block dense granule secretion does not inhibit alpha-granule secretion to adenosine diphosphate (ADP); (2) synergism between epinephrine and ADP in the induction of P-selectin expression is similarly unaffected by aspirin; and (3) the ability of P-selectin to mediate adhesion of activated platelets to monocytes and polymorphonuclear lymphocytes in whole blood is also unchanged by aspirin treatment. To further explore the mechanisms responsible for platelet alpha-granule secretion, we have shown that inhibition of Na+/H+ exchange by either acidification of the extracellular medium or amiloride treatment blocked ADP-induced P-selectin expression. In contrast, incubation with the platelet lipoxygenase inhibitor 5,8,11- eicosatrynoic acid, by itself and with aspirin, did not decrease ADP- induced P-selectin expression. We conclude that platelet alpha-granule secretion in response to ADP is dependent on intact Na+/H+ exchange but is independent of the lipoxygenase- and cyclooxygenase-dependent metabolites of arachidonic acid.     

Expression of apoptosis regulatory proteins p53 and Bcl-2 in skin of patients with chronic renal failure on maintenance haemodialysis

BACKGROUND: Chronic renal failure results in multi-organ system derangement including cardiovascular, gastrointestinal, neurological, endocrinal, blood and dermatological abnormalities. Maintenance of skin homeostasis requires a delicate balance between proliferation, differentiation and apoptosis. p53 and Bcl-2 proteins play a central role in the regulation of apoptosis. OBJECTIVE: Evaluation of the expression of apoptosis regulatory proteins p53 and Bcl-2 in apparently normal skin of patients, with chronic renal failure on maintenance haemodialysis, with respect to their role in the apoptotic process. METHODS: Biopsy specimens were obtained from 10 patients with chronic renal failure on maintenance haemodialysis, as well as seven age-matched control subjects. Computer-assisted image analysis was employed to measure epidermal thickness in H&E-stained sections. Immunoperoxidase technique was also used to demonstrate p53 and Bcl-2 proteins and the TUNEL technique for detection of apoptotic cells in these specimens. RESULTS: The mean epidermal thickness was significantly higher (P < 0.0001) in patients than controls. Meanwhile, no apoptotic cells were detected in the epidermis of patients. On the other hand, a statistically significant difference was observed in both p53 (P = 0.0001) and Bcl-2 expression (P = 0.0003) when comparing patients and controls. Expression of p53 (2.74 +/- 0.84) and Bcl-2 (3.45 +/- 1.35) proteins was higher in skin samples obtained from patients with chronic renal failure and on maintenance haemodialysis than those from control cases (0.5 +/- 0.96 and 0.8 +/- 0.6, respectively). Moreover, Bcl-2 expression in patients was observed in basal as well as squamous cell layers of skin, whereas in control subjects it was confined to the basal cell layer only. CONCLUSION: These findings suggest that an alteration in the proliferation/apoptosis balance may be present in the skin of such patients.     

Patient controlled analgesia (PCA) in paediatric surgery: a prospective study following laparoscopic and open appendicectomy

Patient controlled analgesia (PCA) has not yet gained universal acceptance for the management of postoperative pain in paediatric surgery. In a prospective study we evaluated feasibility and complications of PCA following 90 cases of laparoscopic or open appendicectomy. PCA proved to be a safe and feasible method with few complications (2% of medical complications, no abort of application, 17 technical checks in a total running time of 4125 h). Acceptance by patients was high and children of all age groups worked the system properly. Assessment of application protocols showed, that the consumption of analgesics was significantly reduced following laparoscopic appendicectomy (P < 0.05). PCA is a safe and feasible method for the management of postoperative pain in children and PCA recording provides an excellent insight into the consumptional behaviour of patients, enabling staff to evaluate postoperative pain for various procedures.     

The neuroendocrine challenge paradigm in headache research

The neuroendocrine challenge paradigm provides a "window" on central neurotransmitter function in vivo. This strategy is based on the premise that the sensitivity of certain central receptors can be inferred from the magnitude of the hormonal response to specific pharmacologic probes. For example, the serotonin (5HT) receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin and induces migraine-like headaches. We have previously reported that the headache and cortisol responses to m-CPP are highly correlated, which may implicate a disturbance in central serotonergic neurotransmission in the pathogenesis of migraine. As pharmacologic probes with greater specificity for 5HT receptor subtypes become available, we may be able to elucidate these mechanisms with greater precision. The neuroendocrine challenge methodology is also applicable to the study of other neurotransmitter systems and other headache disorders.