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Biomedical subjects

G Bartolini

Publications and source records attributed to G Bartolini.

At least 37 records · Page 2Linked to original sources
PubMed1987

Clinical trial with muzolimine in healthy and hypertensive subjects: new vistas on the drug action.

The mechanism of muzolimine (3-amino-1-[3,4-dichloro-alpha-methyl-benzyl]-2 pyrazolin-5-one) action is still not completely defined. The identified site of action is the Henle loop, similarly to furosemide which acts also by mediating renal prostaglandin synthesis. The aim of the present study was to evaluate the early effects of muzolimine (30 mg per os) on renal function and prostaglandin urinary excretion in healthy controls and hypertensive subjects. Urinary flow reached the peak values by the third hour after the drug and a diuretic effect not directly dependent on glomerular filtration was observed, especially in hypertensive patients. In these cases the diuresis increased also due to a low glomerular filtration rate and tubular phenomena were more evident than in controls: an increasing Na+ tubular excretion and a parallel decreasing % Na+ reabsorption. Blood pressure was not significantly influenced by muzolimine in healthy subjects, while it returned to normal values in the hypertensive group. A cyclooxigenase inhibitor, lysine acetylsalicylate (1 g i.m.) administered 10 minutes after muzolimine, was not able to modify the parameters under consideration. Therefore a mediation by prostaglandins on the diuretic and antihypertensive effects of the drug under study may probably be excluded.

Aged↗
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↗
PubMed1986

A multihormonal tumor of the pancreas producing neurotensin associated with the WDHA syndrome. Histology, histochemistry and origin.

A pancreatic tumor associated with severe WDHA syndrome has been studied histologically and immunohistochemically. Light microscopy revealed that the growth pattern of the tumor varied greatly from zone to zone but with prevailing solid arrangement of the tumoral cells. The majority of the endocrine cells showed numerous eosinophilic, PTAH-positive, and argyrophilic secretory granules, that were ultrastructurally similar to those of normal and tumoral neurotensin-containing cells. A minority of the endocrine cells had secretory granules ultrastructurally different from the aforementioned ones, but these were not diagnostic on purely morphological grounds. Inside the tumor, immunohistochemistry demonstrated a majority of neurotensin-immunoreactive cells, sparse and small clusters of VIP-immunoreactive cells and few, dispersed pancreatic polypeptide-immunoreactive cells. Some structural and ultrastructural aspects of the tumoral stroma have also been reported. Ducts and solid masses of duct-like cells were also found, and small clusters and singly dispersed duct-like cells were seen invading the endocrine tissue and undergoing mitoses. Such features suggest that the tumor originated from precursors located in the medium-sized and small pancreatic ducts. Because of the multihormonal nature of the tumor, the role of neurotensin and VIP in producing the patient's symptoms is discussed and a synergistic action of the two hormones is suggested in causing the particularly severe WDHA syndrome.

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↗
PubMed1984

A two-stage mouse skin carcinogenesis study of lyngbyatoxin A.

A strong skin irritant, lyngbyatoxin A, isolated from the marine blue-green alga Lyngbya majuscula is structurally related to teleocidin. Since lyngbyatoxin A satisfied our short-term screening tests for possible tumor promoters, viz. irritation of mouse ear, induction of ornithine decarboxylase (ODC) in mouse skin, and adhesion of human promyelocytic leukemia cells (HL-60), a two-stage carcinogenesis experiment was carried out. Tumor incidences in the groups treated with 7,12-dimethylbenz(a)anthracene (DMBA) plus lyngbyatoxin A and with DMBA plus 12-O-tetradecanoylphorbol-13-acetate (TPA) were 86.7% and 93.3% in week 30, respectively. The average number of tumors per mouse was 3.7 in the former group and 10.5 in the latter group. This paper reports for the first time the potent tumor-promoting activity of lyngbyatoxin A and also the histological examination of tumors.

9,10-Dimethyl-1,2-benzanthracene↗
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↗