[Action of methoxybutropate in chronic bronchitis. Comparison with guacetisal].
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Biomedical subjects
Publications and source records attributed to P Conti.
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Peritoneal rat macrophages incubated with human recombinant tumour necrosis factor (hrTNF alpha) released 2-3 times more thromboxane (TxB2) than untreated macrophage controls, a result similar to that obtained by incubating them with endotoxin (ET) or calcium ionophore A23187.
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The effects of pulsed extremely low frequency electromagnetic fields on human peripheral blood lymphocyte mitogenesis induced by phytohaemoagglutinin, concanavalin A or calcium ionophore A23187 were studied. The dependence of the field effect on mitogen concentrations was investigated. Field exposure produced strong inhibition of DNA synthesis when optimal doses of mitogens were used, confirming our previous findings. Opposite effects were observed at suboptimal concentration of mitogens. Experiments performed by exposing cell cultures to the field for short periods indicated that a field application of at least 6 h is needed to influence irreversibly lymphocyte blastogenesis.
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Human peripheral blood polymorphonuclear leukocytes (PMNs) and murine peritoneal macrophages (M phi) were stimulated to generate thromboxane upon treatment with highly purified human interleukin 1/leukocytic pyrogen (IL1/LP) at various concentrations. Thromboxane B2 was measured by radioimmunoassay in the cell-free supernatants of cell suspensions after 1 hour incubation at 37 degrees C. Thromboxane B2 amounts increased in a way which depended on the dose of IL1 added to the cell cultures.
Macrophages (M phi) and polymorphonuclear leukocytes (PMNs) are cell types that interact with bacterial endotoxin and play key roles in mediating the inflammatory reaction. We examined the ability of rat peritoneal macrophages and human PMNs to synthesize thromboxane A2 (detected as TxB2) in response to human recombinant interleukin 1 (hrIL1). TxB2 levels were measured by radioimmunoassay in the cell-free supernatant of cell suspensions after 1 hr incubation at 37 degrees C. TxB2 release by both PMNs and M phis was increased in a dose-dependent manner by hrIL1.
Endogenous opioid peptides, by modulating the release of sympathetic transmitters, may play a role in the pathogenesis of migraine and related headaches which are considered hypernociceptive syndromes. Hypoendorphinaemia has been demonstrated in migraine attack. Captopril, a drug able to potentiate morphine analgesia in rats and inhibit enkephalinase in animals and in man, improves the clinical course of migraine. In the present research the cerebrospinal fluid and plasma beta-endorphin (beta-EP) levels have been evaluated following a single oral dose of captopril. The drug increased plasma beta-EP levels in migraine sufferers, and these data may be relevant in the mechanism of action of this drug in migraine and related headaches.
The authors compare the effect of indomethacin and proglumetacin on the production of prostacyclin in the rat gastric mucosa, and investigate the potential ulcerogenic effect elicited by the two drugs. The results show that indomethacin and proglumetacin, at doses giving similar inhibition of gastric-protacyclin synthesis, drastically differ in their gastric ulcerogenic effects.
The DNA synthesis of lymphocytes triggered by phytohemagglutinin or phorbol-myristate-acetate is strongly reduced by the externally applied electromagnetic field (ELF). Ca2+ uptake by stimulated lymphocytes is also reduced by ELF. The effect appears to be synergistic with that of the well-known calcium blocker agent, verapamil.
The present study involves the determination of the effect of supernatants obtained from mitogen-induced lymphocytes of human tonsils and containing lymphotoxins on human peripheral blood polymorphonuclear leukocytes (PMNs). PMNs treated with supernatants from phytohemagglutinin-stimulated lymphocytes were found to increase the release of thromboxane B2, compared to normal control levels. This increase was blocked by the preincubation of PMNs with indomethacin. The production or increase in production of thromboxanes may be induced by lymphotoxins since these substances have been reported to activate phospholipase A2 in target cell membranes, which may result in release of the thromboxane precursor, arachidonic acid.
PMN's were cultivated in vitro and treated with supernatants obtained from mitogenic-induced lymphocytes of human tonsil. Cytoplasmic vacuolization increased with time and there was a lower number of neutrophilic clumps in the culture treated with a supernatant containing lymphotoxin. In addition, the PMN's released more thromboxane B2 which was inhibited by indomethacin. We conclude that the action of lymphotoxin on the target PMN's is not mediated by the production of thromboxane B2.
Polymorphonuclear leukocytes (PMN) are capable to produce prostaglandins in vivo and in vitro, and thromboxane B2 (TXB2) which is the main metabolite of arachidonic acid in these cells. In the present work we studied, with radioimmunoassay method, the effect of calcium ionophore A23187 on PMN. This substance is capable to stimulate TXB2 release by PMN and its effect is inhibited by indomethacin.
Blastogenesis of human peripheral blood lymphocytes stimulated in vitro by non-specific mitogens (PHA, ConA, PWM) upon exposure to extremely low frequency EMF has been studied. Different frequencies of square waveforms have been used. PHA-stimulation resulted in strong inhibitions as measured by [3H]thymidine incorporation. A frequency window (3-50 Hz) within which ConA-induced blastogenesis was significantly inhibited has been individuated. The mitogenic effect of PWM was significantly affected only at 3 Hz.
High concentrations of the non-steroid anti-inflammatory drugs, alone and in association, reduce the blastogenesis of human lymphocytes in vitro. This effect is probably due to the toxicity of these agents and not to the inhibition of prostaglandin (PG) prosuction. Therefore drugs, such as, salicylates and associations of salicylates with other non-steroid anti-inflammatory drugs, which have a weak action on PG-synthesis, also inhibit proliferation of lymphocytes.
Prostaglandin (PG) E1, PGD2 and the unstable PGI2 are inhibitors of human platelet aggregation and increase the concentration on cAMP in human platelets, presumably by stimulation of the adenylate cyclase. Methylxanthines exert their antiaggregatory effect by inhibiting the platelet cAMP phosphodiesterase. We examined whether caffeine-indomethacin is able to block PGI2 release from gastric mucosa less than the administration of indomethacin alone. PGI2 production was determined on aliquots of incubated mucosal strips, tested for ADP-induced aggregation of human platelet rich plasma. The obtained data indicate that the PGI2 production found in rats treated with the association was higher than that observed in rats treated with indomethacin alone. The present preliminary findings suggest that caffeine when given together with indomethacin reduces the indomethacin-induced inhibition of PGI2 release from the gastric mucosa.
In the present work it has been tested if associations of indomethacin or aspirin with diflunisal or sodium salicylate block PGI2 release from gastric mucosa less than the administration of the compounds alone. PGI2 production was determined on aliquots of incubated mucosal strips, tested for ADP-induced aggregation of human platelet rich plasma. The obtained data indicate that PGI2 generation found in rats treated with indomethacin or aspirin associated with diflunisal or sodium salicylate was higher than that found in rats treated with indomethacin or aspirin alone. This effect may be likely explained by competition between salicylates and other non steroidal anti-inflammatory drugs for binding sites on PG-synthetase and plasma proteins.
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