[The effect of low-frequency sinusoidal pulse electromagnetic fields on human lymphocytes stimulated with mitogenic lectins. Preliminary results].
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Biomedical subjects
Publications and source records attributed to M G Cifone.
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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.
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.
In the present work it was determined the ability of non-steroidal anti-inflammatory drugs (Diflunisal and Indomethacin) to inhibit formation of "granuloma pouch" exudate induced in rats. This study shows that the combined administration of Diflunisal and Indomethacin exerts similar anti-inflammatory activity as the single drugs. There does not seem to be additive anti-inflammatory effects of the drugs in combination but, if anything, a weak antagonism. The association of the two compounds produces a reduced harmful effect on the gastric mucus.
Cultures of lymphocytes from a patient with a suppressed immune-system were set up, and a low response was seen after treatment with mitogenic substances such as PHA and ConA. Other lymphocyte cultures from the same patient were treated with Levamisole, and after this it was noted that the percentage of T-cell rosettes with sheep erythrocytes was increased.
In this work, the authors are concerned with the study of the effects of non-steroidal antiinflammatory drugs in the gastric mucosa of the rat after induced chronic inflammation with potassium permanganate.
The effects of oral exposure for nearly 6 months to Cd (200 or 400 ppm) on rat natural killer (NK) activity were investigated. No significant differences in body and thymus weights were observed. Peripheral blood lymphocyte (PBL) number was consistently higher in treated rats throughout the treatment; the number of spleen cells decreased during the first 50 days, and then reached a level higher than in controls. NK activity, evaluated in a 4-h chromium release assay against YAC-1 target cells, was altered in treated rats: lower up to day 30, and then higher. In parallel, a reduction of the large granular lymphocytes (LGL) was found initially in the peripheral blood of Cd-treated rats, followed by a persistent marked increase. These changes were closely correlated with the altered distribution of CD8+ aGM1+ CD5- cells, which mostly consist of NK cells. Fluorescence-activated cell sorter (FACS) analysis revealed a decrease of cell subset with a typical NK phenotype during the first 30 days of treatment and a clear increase thereafter. Post-exposure observations indicated that all these effects disappeared with a return to control values 2 months after cessation of treatment. These findings suggest that in vivo administration of Cd induces both inhibitory and stimulatory effects on rat NK cell number and cytotoxic activity, depending on time of exposure.