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Biomedical subjects

D P Mikhailidis

Publications and source records attributed to D P Mikhailidis.

At least 19 recordsLinked to original sources
PubMed1995

Effects of papaverine and vasointestinal polypeptide on penile and vascular cAMP and cGMP in control and diabetic animals: an in vitro study.

Adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) mediate penile erection. We have previously established that adenylate and guanylate cyclase activity is elevated in the diabetic rat penis and aorta. This study investigates the action of papaverine and vasoactive intestinal polypeptide (VIP) on these cyclases. The aortae and penes of Sprague Dawley rats (n = 7) were stimulated with VIP and papaverine. Diabetes mellitus (DM) was induced in Sprague Dawley rats (n = 7) with streptozotocin and the penile and aortic tissues were treated with VIP. The penes, aortae and carotid arteries of New Zealand White rabbits were similarly processed. cAMP and cGMP generation was measured by radioimmunoassay. In all tissues: VIP stimulated cAMP synthesis; VIP did not increase cGMP levels; papaverine was without effect on either cAMP or cGMP synthesis. VIP-stimulated cAMP was significantly enhanced in the diabetic rat penis and aorta; there was also a significant elevation in the basal levels of cGMP in these tissues. These data: (1) consolidate that cAMP is a mediator of penile erection, (2) indicate that papaverine and VIP elicit erection by different mechanisms, (3) suggest that an enhanced penile capacity to generate cAMP in DM may constitute an adaptive response to counteract the previously reported reduction in VIP content and VIP receptors, and (4) indicate that the penile and vascular tissues of the rabbit respond in a similar manner to VIP and papaverine.

Animals↗
PubMed1994

Naftidrofuryl inhibits the release of 5-hydroxytryptamine and platelet-derived growth factor from human platelets.

Angioplasty and bypass-grafting are associated with restenosis which limits their efficacy. Platelet-rich thrombus formation is the predominant cause of acute occlusion whereas platelet release products with proliferating properties, e.g. 5-hydroxytryptamine (5-HT) and platelet-derived growth factor (PDGF), may contribute to late restenosis. Naftidrofuryl (NAF), a drug for the treatment of peripheral vascular disease, was shown previously to inhibit platelet shape change and aggregation. This study establishes whether NAF inhibits the release of 5-HT and PDGF from platelets obtained from healthy subjects. Platelets stimulated with agonists aggregated less and released less 5-HT/PDGF when pre-incubated with NAF. Indomethacin (INDO), a cyclooxygenase inhibitor, alone inhibited aggregation and PDGF/5-HT release; NAF enhanced the inhibitory effects of INDO. The effect of NAF, on its own or in combination with a cyclooxygenase inhibitor, may therefore confer protection against graft occlusion.

Adenosine Diphosphate↗
PubMed1994

Altered prostacyclin synthesis by aortae from hepatic portal vein-constricted rats: evidence for effects on protein kinase C and calcium.

To investigate the mechanisms causing reduced systemic vascular reactivity to vasoconstrictor agents in portal hypertension, we studied receptor- and signal-transduction-linked PGI2 (a vasodilator) synthesis (measured as 6-oxo-PGF1 alpha by radioimmunoassay) in the aorta (ex vivo) of portal vein-constricted rats. PGI2 synthesis was stimulated by adrenaline (via heterogeneous alpha-adrenoceptors), phorbol ester dibutyrate (a protein kinase C activator), arachidonic acid (the substrate for PGI2 synthesis) and the Ca2+ ionophore A23187 (A23187) and thapsigargin (both of which elevate intracellular Ca2+, which in turn elicits the release of arachidonic acid). The release of PGI2 by the aortae of rats with portal hypertension in comparison to sham-operated controls was: 1) enhanced in response to adrenaline, 2) reduced in response to phorbol ester dibutyrate, A23187 and thapsigargin and 3) unchanged in response to arichidonic acid. These data indicate that in aortae from rats with experimental portal hypertension: i) there are no changes in the enzymes involved in PGI2 synthesis (cyclooxygenase, PGI2 synthase), ii) there is a specific increase in adrenoceptor-linked PGI2 synthesis in aortae which may contribute to arterial vasodilation in this experimental model and 3) the diminished response of PGI2 synthesis to A23187, phorbol ester dibutyrate and thapsigargin indicates that there is a generalised attenuation of protein kinase C activator activity and of Ca2+. Since Ca2+ is a key component of excitation-contraction coupling and protein kinase C activator has been implicated in mediating this event, attenuation of these systems may also explain, at least in part, the known reduced vasoactivity of aortae from rats with portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Improvement of ketoacidosis in the diabetic rat after the administration of the oral antilipolytic agent GR 79236.

1. We assessed the effect of a novel oral antilipolytic agent, N-[(1S, trans)-2-hydroxycyclopentyl]adenosine (GR 79236), in experimental diabetic ketoacidosis. Ketotic rats were gavaged with GR 79236 (1 mg/kg) or water (vehicle) and their blood/plasma/serum biochemistry and haematological profile was determined. 2. We found that GR 79236 reduced the plasma non-esterified fatty acid concentration. This effect was associated with the correction of blood/plasma/serum biochemical variables (beta-hydroxybutyrate, acetoacetate, triacylglycerol) directly related to diabetic ketoacidosis, and of others (cholesterol, creatinine, creatine kinase and aspartate transaminase) which are not directly related to this metabolic abnormality. 3. There was, however, no evidence of GR 79236 lowering blood glucose in this model. One possible explanation for this observation is that GR 79236 stimulated gastric emptying leading to enhanced absorption of stomach contents when compared with untreated animals.

Adenosine↗
PubMed1994

Adenylate and guanylate cyclase activity in the penis and aorta of the diabetic rat: an in vitro study.

OBJECTIVE: To investigate the role of adenylate and guanylate cyclases in the mediation of erection in diabetic rats. MATERIALS AND METHODS: Hyperglycaemic diabetes mellitus was induced in 35 rats using streptozotocin. Two months later the penises and aortae of these rats were excised and cut into rings or segments before being treated with varying concentrations of acetylcholine (Ach), sodium nitroprusside (NaNP), prostaglandin E1 (PGE1) and adrenaline (AD). The levels of adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) so generated were measured by radioimmunoassay and the results compared with those from seven age-matched control rats that had not been given streptozotocin. RESULTS: Ach-stimulated cGMP synthesis was impaired in the aortae in diabetic rats. Ach-stimulated cGMP synthesis was undetectable in the penis. NaNP-stimulated cGMP and PGE1-stimulated cAMP synthesis was enhanced in both the penises and aortae in diabetic rats compared with controls. AD-stimulated cAMP synthesis was enhanced in the aorta in diabetic rats compared with controls, but AD had no effect on cAMP synthesis in the penis. CONCLUSION: Ach-stimulated nitric oxide (NO) synthesis is impaired in the vasculature of diabetic rats and an Ach-NO axis may not be present in the penis of the rat. The enhanced capacity of the penis and vasculature to generate cAMP and cGMP may constitute an adaptive response to counteract the reduction in receptor-linked NO release. Impaired adenylate or guanylate cyclase activity does not contribute to erectile dysfunction in diabetic rats.

Adenylyl Cyclases↗
PubMed1994

Unified European higher medical degrees.

Unequal access to higher medical degrees, which are important for career advancement, is a problem that is likely to plague UK medicine as integration within Europe proceeds. This paper analyses the characteristics of M.D.s at the Royal Free Hospital School of Medicine and proposes a solution of creating a common European doctorate.

Academic Dissertations as Topic↗
PubMed1994

Adrenoceptor-linked [45Ca2+] uptake in platelets from diabetic rats: a model for human platelets.

Adrenoceptor-linked 45 calcium uptake was investigated in platelet from diabetic rats (hyperglycaemic, streptozotocin-induced, of 60 days duration). Basal uptake was markedly enhanced in platelets from diabetic rats compared with controls. However, whereas adrenaline-stimulated uptake was unchanged, isoprenaline-stimulated uptake was significantly reduced and noradrenaline-stimulated uptake significantly increased. These latter data indicate that there are differential alterations of adrenoceptor subtypes in diabetes (i.e. an increase in alpha- but decrease in beta-adrenoceptors). These changes in calcium uptake and in adrenoceptor activity may relate to altered platelet function known to occur in experimental diabetes. Furthermore, the similarity of the rat platelet with that of the human (in terms of absolute calcium uptake, responses to agonists and changes in diabetes), renders the rat platelet an appropriate model for studying calcium dynamics and linked adrenoceptors in diabetes.

Animals↗
PubMed1994

Diminished platelet yield and enhanced platelet aggregability in platelet-rich plasma of peripheral vascular disease patients.

Centrifugation of citrated whole blood (cit-WB) for platelet rich plasma (PRP) preparation resulted in a significantly diminished platelet yield compared to when blood was collected in citrate + aspirin (acetylsalicylic acid; ASA) or EDTA anticoagulants in both apparently healthy young subjects and peripheral vascular disease (PVD) patients. The loss in platelets was significantly greater in PVD patients than in young apparently healthy subjects when using cit-WB. Median platelet volume (MePV) of PRP preparations was not different between PVD patients and apparently healthy subjects. The MePV of EDTA-PRP preparations was significantly bigger than cit-PRP and cit + ASA-PRP in both PVD patients and apparently healthy subjects. Citrate and citrate + ASA-PRP of patients was significantly more aggregable to adrenaline. In EDTA-PRP, adrenaline-induced aggregation did not occur. These findings indicate that platelet hyperactivity occurs in PVD even in the presence of ASA. Furthermore, studies involving the use of PRP may not be representative in PVD due to the significant loss of platelets during centrifugation. The methodology described here can be used by those who do not have facilities designed specifically for platelet research.

Aged↗