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Biomedical subjects

R Cirillo

Publications and source records attributed to R Cirillo.

At least 91 records · Page 5Linked to original sources

The effect of altered thyroid function on serum fructosamine concentrations.

The effect of altered thyroid function on serum fructosamine concentrations was investigated in 31 untreated hyperthyroid patients, 18 short-term hypothyroid patients (i.e., 20 days after withdrawal of thyroid hormone suppressive therapy for thyroid cancer), 7 untreated long-term hypothyroid patients, and 25 age-matched normal controls. No differences in serum fructosamine concentrations were observed between hyperthyroid patients and normal controls; conversely, serum fructosamine concentrations were significantly higher both in short-term and in long-term hypothyroid patients than those found in normal controls. Furthermore, long-term hypothyroid patients showed significantly higher serum fructosamine concentrations than short-term hypothyroid patients. L-Thyroxine (L-T4), replacement therapy in two hypothyroid patients, resulted in a marked decrease in serum fructosamine concentrations. In seven hyperthyroid patients, the restoration of euthyroidism with antithyroid drug therapy was associated with no significant changes in serum fructosamine concentrations. The results of the present study indicate that hypothyroidism is associated with a marked increase in serum fructosamine concentrations. This alteration does not appear to be the consequence of gross abnormalities in plasma protein or glucose metabolism. The duration of hypothyroidism seems to be an important factor, even though the mechanism underlying this alteration remains at present unexplained. These results also suggest that caution must be used in the interpretation of elevated serum fructosamine concentrations as an index of the metabolic control of diabetes mellitus in the presence of hypothyroidism.

Adolescent↗

Effect of teomorfolin [N-(7'-theophylline acetyl)morpholine], a new drug, on dislipidaemic conditions induced in the rat.

A study of a new compound with an original structure, teomorfolin [N-(7'-theophylline acetyl)morpholine], was performed in the rat to investigate interaction with experimentally induced dislipidaemic disturbance related to atherosclerotic disorders. The drug succeeded in normalizing the cholesterol and triglyceride serum levels in acute as well as in chronic hyperlipaemia, and, in this connection, it provoked a significant increase of serum alpha-lipoproteins and a decrease of serum beta-lipoproteins, with a consequent improvement of the beta/alpha ratio. In addition, it significantly limited the lipolytic effect produced by adrenaline. Moreover, the drug demonstrated in vitro and in vivo platelet anti-aggregant activity and was able to increase erythrocyte flexibility. Finally, the drug inhibited prostacyclin biosynthesis; this action could explain the anti-aggregant activity demonstrated by teomorfolin. In conclusion, the chemical under investigation showed a wide spectrum of biological properties that interfere with metabolic disturbances involved in atherosclerotic conditions.

Adenosine Diphosphate↗

Cytoprotective activity of deboxamet: a possible interference with prostaglandin and prostacyclin metabolism in rat gastric mucosa.

Deboxamet (5-methoxy-2-methyl-3-indolyl-acetohydroxamic acid) is a new synthetic drug with anti-ulcer and anti-secretory activity. The authors evaluated the ability of deboxamet to protect the rat gastric mucosa against the intensive necroses induced experimentally by absolute ethanol, NaCl (25%), HCl (0.6 N), acetylsalicylic acid plus HCl, and sodium taurocholate plus HCl. Deboxamet, as compared with pirenzepine, sulglycotide and PGE2, displayed a cytoprotective activity against these necrotizing agents. The involvement of deboxamet with prostacyclin metabolism was also investigated. In order to assess the presence of PGI2-like substances, extracts of mucosa from rats treated orally with deboxamet and sulglycotide were assayed i) on isolated rabbit mesenteric artery, ii) for hypotensive effect in anaesthetized rat, and iii) for anti-platelet activity. Deboxamet, like sulglycotide, was able to raise the availability of prostacyclins in the rat gastric mucosa, which is an important action in maintaining its cellular integrity. However, our results cannot determine whether this activity is due to an enhanced biosynthesis or a decreased degradation of prostacyclins.

Animals↗

Doxofylline and theophylline are xanthines with partly different mechanisms of action in animals.

Doxofylline is a new antibronchospastic drug, recently introduced in therapy, with pharmacological properties like theophylline, a potent adenosine receptor antagonist. The authors have investigated the occurrence, after doxofylline administration, of the typical side-effects displayed by methylxanthines in general. The EC50 values of doxofylline in inhibiting the adenosine-induced relaxation of tracheal smooth muscle and the negative inotropic effect induced by adenosine on isolated guinea-pig atria were about 15 and 10 times greater respectively than those of aminophylline. Again, doxofylline increased diuresis only slightly (+15.8) with 20 mg/kg os, and did not increase sodium excretion; aminophylline, on the contrary, produced a dose-dependent increase in urine volume and natriuresis. In mice, aminophylline (6-24 mg/kg given intraperitoneally) dose-dependently increased locomotor activity, while doxofylline (6-24 mg/kg, i.p.) had no effect on behaviour. In anaesthetized guinea-pigs, doxofylline, in continuous intravenous infusion (0.5 ml/min) at 10 and 30 mg/ml, demonstrated fewer toxic effects than those induced by aminophylline: the effect on diastolic blood pressure, on threshold-dose for convulsions, on death-time and on lethal dose came later than with aminophylline. Finally, doxofylline did not affect gastric acid secretion, either in vitro or in vivo, unlike theophylline. The lack of side-effects with doxofylline indicates that this drug can be used safely and effectively in the treatment of obstructive lung disease.

Adenosine↗

Inhibition of IgE-mediated release of histamine and peptide leukotriene from human basophils and mast cells by forskolin.

Forskolin, a diterpene compound isolated from the roots of Coleus forskohlii, activates adenylate cyclase in membranes from a variety of mammalian tissues. We found that forskolin (10(-7) to 3 X 10(-5) M) caused a concentration-related inhibition of IgE-mediated release of histamine and peptide leukotriene C4 (LTC4) from human basophils and lung mast cells. There was a significant linear correlation between the per cent inhibition of histamine and LTC4 release from both cell types. However, in both systems forskolin exerted a significantly greater inhibitory effect on LTC4 release than on histamine release. The concentration-response inhibition curve was paralleled by a forskolin-induced rise in cAMP levels in human leukocyte and mast cell preparations. The relationship between the effect of forskolin and the cAMP concentration was supported by the finding that forskolin inhibited the "first stage" of antigen-induced histamine release, but not the release caused by the Ca2+ ionophore, A23187. Propranolol, a competitive beta-receptor antagonist, did not block the inhibition of mediator release or the cAMP accumulation caused by forskolin. These data suggest that forskolin modulates the release of mediators of immediate hypersensitivity reactions via the activation of adenylate cyclase in human basophils and mast cells.

Adenylyl Cyclases↗

Physiological concentrations of zinc inhibit the release of histamine from human basophils and lung mast cells.

We have previously shown that physiological concentrations of zinc (congruent to 7 X 10(-6) M) inhibit the release of histamine from human basophil leukocytes (Marone et al., J. Pharmacol. Exp. Ther. 217: 292, 1981). In these experiments we compared the effect of zinc chloride on the release of chemical mediators from human basophils and mast cells isolated from human lung. Preincubation (5 min, 37 degrees C) of human basophils and lung mast cells with zinc chloride (10(-6)-3 X 10(-5) M) caused dose-related inhibition of histamine and peptide leukotriene C4 (LTC4) release induced by anti-IgE. Increase Ca2+ concentrations (0.3 to 6 mM) in the extracellular medium completely reversed the inhibitory effect of zinc on anti-IgE-mediated histamine secretion. Zinc chloride was a competitive antagonist of the action of Ca2+ in histamine secretion induced by anti-IgE with a dissociation constant (Kd) of about 10(-5) M in both the basophil and mast cell systems. Thus physiological concentrations of zinc inhibit the release of histamine from human basophils and lung mast cells, presumably by blocking Ca2+ uptake induced by anti-IgE activation.

Basophils↗

IgE-mediated activation of human heart in vitro.

We used human cardiac tissue from the right atrial appendages of patients undergoing corrective heart surgery to study content and de novo synthesis of mediators in the human heart. Human heart tissue contained 1.7 +/- 0.1 micrograms/g wet weight of histamine (mean +/- S.E.M.) and spontaneously produced 6-keto-PGF1 alpha (38.4 ng/g wet weight/min), PGF1 alpha (1.9 ng/g wet weight/min), PGE (1.7 ng/g wet weight/min) and thromboxane B2 (TxB2) (1.7 ng/g wet weight/min). Spontaneous release of PGD2, leukotriene C4 and histamine was negligible. Rabbit anti-human IgE (1-10 micrograms/ml) dose-dependently induced the release of histamine (5 to 15% of the total histamine content) and of PGD2 (5 to 100 ng/g of wet tissue). The effect of anti-IgE was dose-related and reached a maximum after 30-45 min of incubation. A significant linear correlation (rs = 0.90; p less than 0.001) was found between de novo synthesis of PGD2 and the secretion of histamine induced by anti-IgE challenge of human heart. These results support the concept that PGI2 is the main, but not the sole, product of arachidonic acid metabolism synthesized by human heart in vitro. Additionally, anti-IgE challenge of human heart in vitro induces the release of histamine and PGD2. The local concentrations of these mediators appear high enough to play some role in the modulation of several cardiac functions in vivo.

Animals↗

Complement cleavage products in the phototoxic reaction of porphyria cutanea tarda.

We have measured C3, C4, CH50 and complement cleavage products C3a and C5a in in sera and plasma from PCT patients and normal controls 10 min and 1, 4 and 24 h after UVA irradiation. We found elevated C3a concentrations in PCT patients immediately after UVA irradiation and 24 h later. The same was true for CH50, whereas C3, C4 and C5a did not change significantly. No such changes occurred in normal controls. Our data suggest that activation of the complement cleavage product C3a by porphyrin and UV light triggers a series of events that cause tissue damage.

Adult↗

The influence of experimental hypo- and hyperthyroid states on acute and chronic inflammatory reactions: modified response to non-steroidal anti-inflammatory agents.

Hyperthyroid and hypothyroid states were induced in rats by administration of triiodothyronine or surgical thyroparathyroidectomy. The anti-inflammatory activity of Indomethacin, Oxametacine and Phenylbutazone was evaluated in these animals using paw oedema provoked by carrageenan granulomas induced by cotton pellets and polyarthritis induced by Freund complete adjuvant. Our results indicate that the hyperthyroid state leads to a significant inhibition of the acute inflammatory response to carrageenan, while hypothyroidism has no effect. There was a marked increase in the anti-inflammatory activity of Indomethacin and Phenylbutazone in hyperthyroid rats. By contrast, in thyroparathyroidectomised animals the anti-inflammatory effect of these drugs appeared less than in euthyroid rats. The hyperthyroid state slightly inhibited the development of the cotton pellet-induced granuloma, while hypothyroidism enhanced it. Treatment of hypothyroid animals with the anti-inflammatory drugs resulted in a significant decrease in the size of the granuloma. In the hyperthyroid state, the activity of the compounds appeared similar to that detected in euthyroid rats. Neither hyperthyroidism, nor hypothyroidism affected the inflammatory response to mycobacterial adjuvant, or the effect of anti-inflammatory drugs on the response. These results suggest that thyroid hormones may influence, to various degrees the development of acute inflammation due to carrageenan, and chronic inflammation due to implanted cotton pellets. Our results indicate also that hyper- and hypothyroid states can modify the response of the rat to some non-steroidal anti-inflammatory drugs.

Animals↗

[Influence of propyl-gallate and 2-mercaptopropionylglycine on the development of acute inflammatory reactions and on biosynthesis of PGE2].

Anti-inflammatory activity of Propyl Gallate and 2.mercaptopropionylglycine, administered intraperitoneally to the rat, was evaluated against paw edema induced by Carrageenan, Bradykinin, Serotonin and Dextran. In addition, the influence of these chemicals on PGE2 formation from added arachidonic acid to spleen microsomal fraction incubated "in vitro" was assayed. Our results indicate Propyl Gallate and 2.mercaptopropionylglycine depress significantly the development of acute inflammatory reactions provoked by the above mentioned phlogogens and are able to limit the biosynthesis of PGE2. The last inhibitory activity appears to be less potent than that exerted by some non-steroidal anti-inflammatory agents, namely Indomethacin and Oxametacine, which act primarily by interfering with cyclo-oxigenase activity. In our opinion, the anti-inflammatory effect of Propyl Gallate and 2.mercaptopropionylglycine might be dependent on both the scavenger properties of the two compounds against some final products of lipid peroxides (aldehydes) originated at the inflammation site and the partial inhibition of the formation of PGE2 by acting on the cyclo-oxigenase system.

Amino Acids, Sulfur↗

Effect of a new anti-inflammatory drug (oxametacine) on the prostaglandin biosynthesis.

The influence of oxametacine, 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indoyl]acetohydroxamic acid, a new non-steroidal anti-inflammatory drug, on prostaglandin-synthetase was studied in vitro on rat spleen tissue. The drug exerts an inhibitory effect on prostaglandin biosynthesis which closely mimics that of indomethacin. On the other hand, oxametacine proves more active than other non-steroidal anti-inflammatory agents, namely ketoprofen, flufenamic acid, phenylbutazone and acetylsalicylic acid.

Animals↗

Animal and human arteries' "in vitro" response to serum of migraineurs.

"In vitro" experiments carried out by us and partially published have resulted in significant data concerning the contracting activity of migraineurs sera on extracranial animal arteries. In the present study, human and animal arteries (superficial temporal) were tested by means of blood samples taken under identical conditions. No contracting activity from sera taken both in the headache-free period and during the migraine crisis was observed in animal arteries. By contrast, sera obtained in the pre-attack and post-onset stages showed a synergistic effect not only on the action of serotonin and histamine but also on that of norepinephrine. This synergism increases with the worsening of the migraine attack while it decreases as soon as the attack wears off. Other experiments on human specimens provided data which cannot be evaluated yet. There is evidence that, on the occasion of the migraine attack, vasoactive substances which enable isolated organs to contract "in vitro" are released or activated. Moreover, an activity raises in sera which interferes with the other mediators on extracranial arteries.

Adolescent↗

Selective endoscopic contrastography (S.E.C.): an original association of radiology and endoscopy of the small and large intestine.

A more complete diagnostic information can be obtained by "carrying" the contrast medium through the fibercoloscope to those sites of the bowel where neither radiology alone nor endoscopy alone succeed in solving the diagnostic problem. The indications for a selective perendoscopic contrast study during coloscopy are few, but well defined and certainly not negligible:--demonstration and assessment of stenoses (unclarified by radiology and endoscopy);--accurate evaluation of the last ileal loop;--diagnostic study of ileo-colic surgical anastomoses;--fistulous tracts. Seventy-six patients were examined, without complications. The method proved useful in 42% of cases, conclusive in 33%, useless or inconclusive in 17%, unsuccessful in 8% (technical difficulties). On this basis, selective endoscopic contrastography is considered of use whenever its specific indications apply.

Constriction, Pathologic↗