Search PubMed⌕ Search

Biomedical subjects

V Tomasi

Publications and source records attributed to V Tomasi.

At least 37 records · Page 2Linked to original sources
PubMed1986

Regulation of thromboxane A2 biosynthesis in platelet-free human monocytes and the possible role of polypeptide growth factor(s) in the induction of cyclooxygenase system.

It has previously been shown that platelet-free human monocytes, when properly incubated in the presence of animal and human sera, became capable of producing large amounts of thromboxane A2 and prostaglandin E2. The characteristics of these processes are reported here. Prostaglandin biosynthesis was time and cell concentration dependent; 24 h of incubation at 37 degrees C and 0.5 X 10(6) cells per ml medium were found to give the most reproducible results. Human monocytes produced thromboxane A2 and prostaglandin E2 in a typical ratio which ranged from 2.0 to 5.0 (28 experiments). Animal and human sera were similarly effective, while serum obtained from platelet-free blood was much less active. The activity of all sera tested was stable to heating (100 degrees C for 2-10 min) and extreme pH values (pH 2 and 11). It was unstable when the serum was heated at pH 11 and after 2-mercaptoethanol treatment. These observations prompted us to check the effect of polypeptide growth factors having properties similar to those reported above, such as platelet-derived growth factor, fibroblast growth factor, epidermal growth factor as well as insulin and transferrin. None of these, alone or in various combinations, was capable of eliciting a stimulation comparable with that of serum. Stimulation due to sera was, as expected, dose dependently inhibited by acetylsalicylic acid and more efficiently by indomethacin; unexpectedly it was also inhibited by protein synthesis inhibitors such as actinomycin D and cycloheximide in conditions under which no toxic effect of the drugs was evident. On the basis of these results we conclude that: (a) polypeptide growth factor(s) with a molecular weight at least 30 000 (as judged by Amicon ultrafiltration) is involved in the regulation of prostaglandin biosynthesis); (b) such a factor(s) acts by inducing rather than by activating the cyclooxygenase system.

ABO Blood-Group System↗
PubMed1986

Are the vascular complications of diabetes mellitus preceded by an altered thromboxane/prostacyclin plasmatic ratio?

Although many data regarding the biosynthesis of thromboxane A2 and prostacyclin in diabetes mellitus have recently appeared in the literature, it is not clear whether an imbalance between the generation of the two prostaglandins might be connected to the vascular complications of diabetes. In the present review we have tried to emphasize the most significant aspects of these studies and we have focused on alterations of platelet prostacyclin receptors and on the effects of circulating immune complexes on platelets of diabetics. It is likely that studies on the release of platelet derived growth factor as well as more precise definitions of its action on vessel wall cells leading to a massive release of prostacyclin, will permit us to ascertain whether an alteration in prostaglandin ratio is linked to the genesis of the vascular complications in diabetics.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Prostaglandin and thromboxane biosynthesis in resting and activated platelet-free monocytes from aged subjects.

The main cyclo-oxygenase-dependent arachidonic acid (AA) derivatives, i.e. prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), have been measured by radioimmunoassay in platelet-free cultures of human monocytes from young and old subjects, in presence and in absence of activating substances (10% fetal calf serum). No difference was found between cells from the two groups as far as the production of PGE2 and TXB2 (stable metabolite of TXA2) was concerned, at variance with reported data in young and old experimental animals. The addition to the cultures of exogenous AA caused a reorientation of cyclic endoperoxide metabolism resulting in a consistent decrease of the ratio TXB2/PGE2, but only in monocytes from young subjects. The data are discussed with respect to the claimed role of prostaglandins in the age-related immune derangement which is present in aged humans.

Adult↗
PubMed1985

Prostaglandin and thromboxane biosynthesis in isolated platelet-free human monocytes. I. A modified procedure for the characterization of the prostaglandin spectrum produced by resting and activated monocytes.

We have developed a technique to isolate monocytes from human peripheral blood. The technique takes special care of completely eliminating platelets which are usually present in other preparations. Monocytes obtained in good yields (2.5-5.0 X 10(5) cells/ml blood), were found to be 70-80% pure on the basis of morphological and histochemical criteria. Contamination was largely due to the presence of lymphocytes. Monocytes were incubated in the presence or absence of arachidonic acid and TXB2, PGE2 and 6-keto-PGF1 alpha were measured by specific and sensitive radio-immunoassays. It was found that when cells were incubated for up to 1 hr, the production of PGs was low or absent even in the presence of 10 microM arachidonic acid in the incubation medium. However, when incubations were carried out for 24 hrs in the presence of at least 1% fetal calf serum a dramatic increase in TXB2 production occurred, with levels as high as 150 ng X 10(6) cells. The ratio TXB2/PGE2 was around 3, while 6-keto-PGF1 alpha was produced at a much lower level. In the same conditions, when care was taken to evaluate PGs already present in fetal serum and/or cross reactivity due to media generally employed, purified human lymphocytes appeared unable to produce detectable levels of the three PGs tested.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Platelet aggregation and evaluation of the ratio thromboxane B2/6-keto-prostaglandin F1 alpha in the plasma of patients on long term cimetidine treatment.

It has been reported that a long term treatment with cimetidine may give rise to thrombotic complications and may cause reversible damage to blood cells. In 57 patients on long term cimetidine treatment, platelet aggregates, platelet aggregation in vitro, plasma 6-keto-PGF1 alpha/thromboxane B2 ratio and platelet cyclic AMP levels were assessed. In 52% of the patients, platelet aggregate ratios were abnormal and collagen and ADP-hypersensitive platelets were observed. Such alterations began occurring after the first month of therapy and were shown to worsen progressively during the administration. Four of these patients, who developed unexpected thrombotic compliances after about 7 months of therapy, showed higher than normal plasma thromboxane B2, lower plasma 6-keto-PGF1 alpha and two of them, lower platelet cyclic AMP concentrations. It is suggested that cimetidine, through an unknown mechanism which probably involves activation of endogenous cyclic AMP phosphodiesterase, may favour the action of platelet aggregating agents.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

[Is it useful to correct the immunological deficit in cancer patients? And with what modality?].

A certain degree of immunodepression appears to be present in some neoplastic patients. Many factors such as age and nutritional and hormonal state (particularly thymic factors and locally-acting hormones like prostaglandins of E series) are involved in this phenomenon. The literature shows that all these factors are very important in neoplastic processes and might strikingly contribute also to the extent of immunodepression observed in neoplastic patients. Moreover, the HLA genotype seems to effect the efficiency of the antineoplastic treatments. The authors think that immunodepression in neoplastic patients might be improved by immunomodulators such as zinc ions, thymic hormones and, possibly, inhibitors of prostaglandins of E series.

HLA Antigens↗
PubMed1983

Plasmatic TXB2 and 6-keto-PGF1 alpha levels during charcoal hemoperfusion in chronic renal failure patients.

6 patients with end-stage renal disease underwent hemoperfusion with charcoal columns, for 60 min. Blood samples anticoagulated with 2% EDTA/aspirin solution were obtained from arteriovenous fistulas in the basal condition, 5 min after a bolus injection of heparin (7,500 U), at the end of hemoperfusion, and 30 min after. The study was repeated few days later, in the same patients, two hours after 100 mg aspirin by mouth. TXB2 and 6-keto-PGF1 alpha were assayed with RIA in unextracted (U) and extracted (E) and chromatographed platelet poor plasma (PPP). Platelet counts before and after hemoperfusion were also performed. Low levels of the two prostaglandins were found in plasma; this could be related to the procedures for collection and processing of plasma samples; no significant differences were observed between extracted and unextracted samples: there were slightly higher levels of 6-keto-PGF1 alpha in unextracted samples. After charcoal hemoperfusion there was only a slight and not significant increase of TXB2 and 6-keto-PGF1 alpha; low dose aspirin did not modify significantly plasma levels of the two prostaglandins before hemoperfusion but it reduced TXB2 and 6-keto-PGF1 alpha levels after charcoal hemoperfusion. The platelet count fell (-22%) after charcoal hemoperfusion with heparin alone and in similar manner after low-dose aspirin pretreatment (-24%, 7%).

6-Ketoprostaglandin F1 alpha↗
PubMed1981

[Preliminary observations on in vitro biosynthesis of prostaglandins E in tumor cells and virus transformed cells].

Biosynthesis of prostaglandins of E series in BK virus-transformed rabbit-kidney cells (RKBK) and mouse hepatoma cells cultured in vitro with and without exogenous arachidonic acid was determined by radioimmunoassay. Elevated concentrations of prostaglandin E2 were observed in both cell types; moreover, tumor and transformed cells were capable to synthesize higher levels of prostaglandin E2 than normal cells. Mouse hepatoma cells produced more prostaglandins compared to RKBK cells; in addition they seemed less sensitive to inhibition by indomethacin. These data suggest that arachidonic acid metabolism may be another one of the intrinsic biochemical properties that differentiate tumor and virus transformed cells.

Animals↗
PubMed1980

Regulation of cyclic AMP levels in human lymphocytes and lymphoblasts by prostaglandins.

The sensitivity of human lymphocytes to prostaglandins was compared to that of two lines of cultured lymphoblasts. It was found that 25 nM PGE1 increased lymphocyte cyclic AMP levels twofold, but had no effect on lymphoblasts. At 2.8 micrometers PGE1 the increase of cyclic AMP in lymphocytes was 14 fold versus a 1-3 fold increase in lymphoblasts. Lymphoblasts maintained a response to 6-keto-PGE1, isoproterenol and histamine similar to that observed in lymphocytes. Thus, it appears that the rapidly proliferating lymphoblasts excape signals inhibiting proliferation by impairing the function of the PGE receptor.

Alprostadil↗
PubMed1980

The effect of 6-keto-prostaglandin E1 on human lymphocyte cAMP levels.

6-keto-PGE1 was capable of increasing cyclic AMP levels of peripheral human blood lymphocytes in a dose and time dependent fashion. The response was maximal after 30 min of incubation at 37 degrees C; 1 microgram per ml of 6-keto-PGE1 elevated cyclic AMP levels 5 fold which compares with a 10 fold increase due to PGE1. Thus 6-keto-PGE1 may play a role as a modulator of lymphocyte function.

Alprostadil↗
PubMed1980

Elevated levels of prostaglandin E2 in Yoshida hepatoma and the inhibition of tumour growth by non-steroidal anti-inflammatory drugs.

Prostaglandin (PG) E2 biosynthesis in Yoshida hepatoma (AH 130) was evaluated by radioimmunoassay. When hepatoma cells were incubated in vitro, the levels of PGE2 in the medium were similar to those found in hepatocytes for the first 2 h; this was followed by a rapid increase in PGE2 formation, and the 6h incubation levels were 4-fold higher than in hepatocytes. Addition of sodium arachidonate markedly and dose-dependently stimulated PGE2 synthesis; the increase was largely prevented by the addition of indomethacin (1 microM) or L 8027, a prostaglandin synthetase inhibitor. Experiments in vivo indicated that indomethacin treatment of tumour-bearing rats significantly reduced the tumour mass. When rats were injected with PGE2 after receiving the drug, the number of tumour cells was very similar to that of untreated animals. This, as well as the inhibition of tumour growth by acetylsalicylic acid, strongly suggests that the inhibition of PG biosynthesis by anti-inflammatory drugs and the inhibition of tumour proliferation may be closely associated events. It was also found that injections of indomethacin very significantly prolonged survival of hepatoma-bearing rats. Since PGE2 does not appear to affect the cyclic AMP levels of hepatoma cells, it is possible that hepatoma may use PGE2 to subvert the immune system. This could help to explain the effectiveness of anti-inflammatory drugs in the control of tumour growth.

Animals↗
PubMed1979

Is a slow reacting substance-like compound involved in rat platelet agglutination.

Endoperoxide analogs at doses 100-fold higher than those required to aggregate human platelet-rich plasma (PRP), were ineffective on rat PRP. Indomethacin (20 microM) and imidazole did not affect arachidonate-induced aggregation of rat PRP. On the other hand, prostaglandin (PG) E1 inhibited aggregation at doses similar to those effective on human PRP, while high doses of PGI2 failed to inhibit arachidonate aggregation in the rat. Eicosatetraynoic acid (10 microgram) blocked the second phase of aggregation; the Ca2+-ionophore A 23187 potentiated the arachidonate effect. Thus, it appears that endoperoxides or thromboxane A2 may not be involved in rat platelet aggregation and that the formation of aggregants from arachidonate shares many properties with the biosynthesis of slow reacting substance, a metabolite of arachidonic acid containing a sulphate group. To test this, rat PRP was incubated with labeled sulphate and aggregated with arachidonate. After column and thin layer chromatography a labeled lipid was identified having a mobility higher than phospholipids but lower than PGF2 alpha. Treatment with arylsulphatase decreased radioactivity by at least 70%.

Adenosine Diphosphate↗