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Biomedical subjects

R Cirillo

Publications and source records attributed to R Cirillo.

At least 73 records · Page 4Linked to original sources
PubMed1991

Heterogeneity of human mast cells and basophils in response to muscle relaxants.

The authors studied the effects of increasing concentrations 10(-5)-10(-3) M) of four muscle relaxants (succinylcholine, d-tubocurarine, vecuronium, and atracurium) on histamine release from peripheral blood basophils and mast cells isolated from human lung parenchyma, skin tissues, and heart fragments. Basophil granulocytes released less than 5% of their histamine content when incubated with any one of the muscle relaxants tested. In contrast, mast cells showed a significant heterogeneity in response to different muscle relaxants. Succinylcholine did not induce histamine release from any type of mast cell, and only high concentrations of d-tubocurarine (10(-3) M) caused histamine release from skin and lung mast cells. Vecuronium concentration-dependently induced histamine release from skin and lung--but not from heart mast cells--to a maximum of 7.2 +/- 2.1% and 4.9 +/- 1.4%, respectively. Atracurium concentration-dependently caused significant histamine release from skin and lung mast cells to a maximum of 46.2 +/- 15.1% and 30.6 +/- 6.0%, respectively. Atracurium (5 x 10(-5) - 2 x 10(-4) M) also induced histamine release from heart mast cells. The histamine release process from both lung and skin mast cells caused by atracurium and vecuronium was extremely rapid (t1/2 = less than 1 min). The releasing activity of atracurium and vecuronium on lung and skin mast cells was not reduced, and not abolished, by lowering the temperature of the incubation buffer to 22 degrees C and 4 degrees C. Extracellular calcium did not affect the capacity of atracurium and vecuronium to induce histamine release from lung and skin mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Basophils↗
PubMed1991

Pharmacological studies in animals of beta-hydroxyethyltheophylline, the major metabolite of doxofylline in humans.

beta-HET (beta-Hydroxyethyltheophylline), the major metabolite of the antibronchospastic, antiasthmatic drug doxofylline was studied in several in vitro and in vivo trials to characterize its pharmaco-toxicological profile. When compared to the parent compound, beta-HET was found to be significantly less active. It was also discovered to be a very weak inhibitor of phosphodiesterase activity. Its affinity for A1- and A2-adenosine receptors was even lower than that of doxofylline, which was quite low. The oral toxicity of beta-HET was about three times lower than that of doxofylline. The pharmacological activity of doxofylline is due to the drug in its original form and not to its major metabolite.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Doxofylline differs from methylxanthines in its movement of cytosolic calcium.

This paper contributes to the pharmacological profile of doxofylline (Ansimar), a new xanthine derivative with high antibronchospastic activity and no extrapulmonary or cardiac side-effects, clearly demonstrating its inability to mobilize intracellular calcium stores, unlike other xanthines. In vitro, doxofylline does not cause rabbit ear artery contraction under Ca(++)-free conditions. In vivo, doxofylline does not induce a decrease in the calcium concentration of rabbit washed blood platelets. In the same trials theophylline showed opposite results. Furthermore, doxofylline does not antagonize receptors of Ca-antagonists, and does not interfere with the influx of calcium into the cell. Doxofylline also has a very low affinity for adenosine receptors inhibiting cAMP-phosphodiesterase as does theophylline. The absence of typical methylxanthine side-effects is undoubtedly due to doxofylline's low affinity for adenosine receptors, although this does not explain the absence of cardiovascular effects. The present study presents clear evidence that the inability of doxofylline to cause positive inotropism can be linked to its inability to induce calcium movement from intracellular stores.

Aminophylline↗
PubMed1990

Cyclosporin A rapidly inhibits mediator release from human basophils presumably by interacting with cyclophilin.

We have examined the effects of cyclosporin A (CsA) and a series of CsA analogs that bind with decreasing affinity to cyclophilin, to evaluate the involvement of this protein in the release of preformed (histamine) and de novo synthesized (peptide leukotriene C4; LTC4) mediators of inflammatory reactions from human basophils. CsA (8 to 800 nM) concentration-dependently inhibited (5 to 60%) histamine release from peripheral blood basophils challenged with anti-IgE. CsA was more potent (92.6 +/- 1.8 vs 59.1 +/- 4.5%; p less than 0.001) and, at low concentrations, more effective when the channel-operated influx of Ca2+ was bypassed by the ionophore A23187 (IC40 = 24.1 +/- 3.9 vs 105.5 +/- 22.2 nM; p less than 0.05). CsA had no effect on the release of histamine caused by phorbol myristate and bryostatin 1 that activate different isoforms of protein kinase C. Inhibition of histamine release from basophils challenged with anti-IgE was not abolished by washing (three times) the cells before anti-IgE challenge. CsA also inhibited the de novo synthesis of LTC4 from basophils challenged with anti-IgE. The inhibitory effect of CsA was very rapid, and the drug, added from 1 to 10 min during the reaction, inhibited the ongoing release of histamine caused by anti-IgE and by A23187. The experiments with CsA analogs (CsG, CsC, CsD, and CsH) showed that CsH, which has an extremely low affinity for cyclophilin, has no effect on basophil mediator release. In addition, there is a significant correlation between the concentrations of CsA, G, C, and D that inhibited by 30% the histamine release induced by anti-IgE (r = 0.99; p less than 0.001) and by A23187 (r = 0.87; p less than 0.001) and their affinity for cyclophilin.

Antibodies, Anti-Idiotypic↗
PubMed1990

Is the imbalance between thrombin and plasmin activity in diabetes related to the behaviour of antiplasmin activity?

The aim of this study was to evaluate the balance between thrombin and plasmin activity in a group of 79 diabetic patients (IDDM and NIDDM). For this purpose we determined fibrinopeptide A (FPA) and B beta 15-42, specific products of thrombin and plasmin activity. Moreover we investigated the behaviour of antithrombin III and alpha 2 antiplasmin, important inhibitors of blood coagulation and fibrinolysis. Results show an increase both in FPA and B beta 15-42 in IDDM and NIDDM patients when compared to healthy controls. However the ratio between B beta 15-42 and FPA was lower than in controls indicating an imbalance between thrombin and plasmin activity. Antithrombin III levels were not different from the controls and no correlation was found with Hb A1c. alpha 2 antiplasmin was found to be higher in IDDM when compared both with NIDDM and controls. A non linear correlation was found between Hb A1c and alpha 2 AP in both diabetic groups. We conclude that the imbalance between thrombin and plasmin activity may have a role in determining fibrin deposition. These subclinical abnormalities, unrelated to vascular complications and duration of the disease, may progressively contribute to the development of the vascular complications in diabetes.

Adolescent↗
PubMed1990

Pharmacological and toxicological activities of a new methylxanthine derivative [7-(1,3-dithiolan-2-ylmethyl)1,3-dimethylxanthine] with antibronchospastic and mucoregulatory properties.

7-(1,3-Dithiolan-2-ylmethyl)-1,3-dimethylxanthine (ABC 99) has been studied in the animal to evaluate its pharmacological activity. This compound was found to have antibronchospastic activity in vitro and in vivo markedly greater than aminophylline. The new compound also had moderate antitussic properties and was an active mucoregulator. ABC 99 acts as an intestinal muscle relaxant, but it has no cardiovascular, urinary, or CNS side effects. The mechanism of ABC 99 could be explained by its inhibition of guinea-pig lung phosphodiesterases and affinity for adenosine receptors, particularly A2 receptors. ABC 99 had a low acute toxicity in animals, indicating it may be useful for treating asthma and chronic bronchitis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Doxofylline exerts a prophylactic effect against bronchoconstriction and pleurisy induced by PAF.

The effect of doxofylline, a new xanthine drug with a low incidence of side-effects in the central nervous, renal and gastroenteric system, on the actions of PAF-acether on bronchopulmonary functions was studied. Doxofylline inhibited: (1) PAF-induced bronchoconstriction in vitro, and the concomitant generation of TXA2-like activity in perfused guinea-pig lungs; (2) PAF-induced bronchoconstriction in vivo and the concomitant release of TXA2-like activity into the circulation; (3) PAF-acether-induced pleurisy and the liberation of type C4 leukotriene into the rat pleural cavity. The results suggest that doxofylline, like theophylline, is able to counteract the bronchoconstriction induced by PAF-acether and, in addition, displays anti-inflammatory properties. These pharmacological data support the notion that doxofylline exerts a prophylactic effect against the respiratory damage induced by mediators, such as PAF-acether, of lung bronchial hyperreactivity; its mechanism of action is unusual, it has slight antagonistic activity at A1- and A2-adenosine receptors.

Airway Resistance↗
PubMed1989

Human basophil/mast cell releasability. VII. Heterogeneity of the effect of adenosine on mediator secretion.

5'-N-ethylcarboxamideadenosine (NECA) greater than 2-chloroadenosine greater than adenosine greater than N6-(R-phenyl-isopropyl)-adenosine (R-PIA) inhibited in vitro anti-IgE-induced histamine and peptide leukotriene C4 (LTC4) release from human basophils in a concentration-dependent fashion. Micromolar concentrations of adenosine, NECA and R-PIA potentiated the anti-IgE-stimulated release of histamine and LTC4 from human lung parenchymal mast cells. Submillimolar concentrations of adenosine, NECA and R-PIA inhibited in a concentration dependent manner the release of histamine and prostaglandin D2 (PGD2) from skin mast cells challenged with anti-IgE. These results demonstrate marked heterogeneity of the modulatory effect exerted by adenosine on mediator release from human basophils and mast cells.

2-Chloroadenosine↗
PubMed1989

Pathophysiology of human basophils and mast cells in allergic disorders.

Basophil leukocytes and tissue mast cells are inflammatory cells that are found in virtually all human tissues. They appear to be involved in the pathogenesis of such allergic diseases as allergic rhinitis, bronchial asthma, anaphylaxis, atopic and contact dermatitis, chronic urticaria, and hypersensitivity pneumonitis. By releasing a variety of chemical mediators, they could also play a role in the pathophysiology of a wide range of inflammatory disorders of the joints, and of intestine, lung, coronary, and myocardial diseases. Although these two cell types are similar in several aspects, striking differences have also been observed. Moreover, human mast cells from different anatomical sites and within an individual tissue synthesize different mediators and have different release mechanisms. The recent advent of techniques that yield highly purified basophils and mast cells from diverse tissues will probably lead to major advancements in understanding the biochemical and pharmacological mechanisms that control the release process of these cells. The release of mediators from these cells is also controlled by a series of largely undefined biochemical steps that represent the basis of the concept of basophil and mast cell releasability. Alterations of basophil or mast cell releasability have already been detected in patients with allergic rhinitis, bronchial asthma, atopic dermatitis, and chronic urticaria. Taken together, these findings demonstrate that basophils, mast cells, and their chemical mediators play a pivotal role in several inflammatory disorders.

Animals↗
PubMed1989

Inhibition of histamine and prostaglandin D2 release from human lung mast cells by ciclosporin A.

Cyclosporin A (CsA) is now widely used in the prevention/treatment of graft rejection and in the treatment of some human inflammatory diseases. We studied the effect of CsA on the release of chemical mediators from human lung mast cells in vitro. CsA (0.03-3 micrograms/ml) inhibited the release of histamine and prostaglandin D2 induced by anti-IgE from lung mast cells. CsA-induced inhibition of mediator release was not abolished by washing the cells before stimulation and it was not affected by the degree of purity of mast cell preparations. Our results indicate that CsA, in pharmacological concentrations, is a rapid and irreversible inhibitor of the release of preformed and de novo synthesized mediators from human lung mast cells. These findings might explain, at least in part, some of the therapeutic actions of CsA in vivo.

Antibodies, Anti-Idiotypic↗
PubMed1989

[Celiac disease in insulin-dependent diabetes mellitus and insulin-independent diabetes mellitus].

The IgA antigliadin antibodies AGA title was detected in 37 patients with IDDM, mean age 32.59 +/- 14.71, where mean duration of disease was 8.76 +/- 9.62 years, and 29 patients with NIDDM, mean age 55.31 +/- 14.71, where disease lasted 11.5 +/- 5.55 years. A group of 51 normal pts. was employed as control. In IDDM group 2 cases on 37 showed high AGA title (case n. 1 and n. 2) but just the case n. 1 where IDDM lasted 16 years, showed an histologic picture of coeliac disease (partial villous atrophy), while in the case n. 2 where IDDM was at the onset, the histologic picture was normal. The increase of AGA title in the IDDM at the onset is rarely associated with coeliac disease, but it seems to be an aspecific response. Viceversa an increased AGA title is in IDDM for greater than 1 years often associated with coeliac disease. In NIDDM no high AGA title was found. The prevalence of coeliac disease in our patients with IDDM was 1:37 and we suggest that diabetics be screened routinely for antigliadin antibody.

Adolescent↗
PubMed1989

[Activity of the coagulation and fibrinolysis in non-insulin-dependent diabetes mellitus. In vivo study].

In vivo study of blood coagulation and fibrinolysis activities in non insulin dependent diabetes mellitus. The aim of the study was to investigate in vivo blood coagulation and fibrinolysis activities in a group of diabetic patients NIDDM with and without vascular complications. For this purpose we determined two sensitive indicators in vivo of blood coagulation and fibrinolytic activities such as fibrinopeptide A and B beta 15-42 respectively. Moreover, we computed the ratio between B beta 15-42 and fibrinopeptide A in order to investigate a possible imbalance in vivo between blood coagulation and fibrinolysis. Control groups were 15 healthy subjects and 28 non diabetic patients affected by atherosclerotic disease. Fibrinopeptide A and B beta values were significantly higher in the diabetic patients than controls but there was no difference between the former group and the atherosclerotic patients. Also, no correlation was found for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose levels. There was no difference in B beta, FPA and B beta/FPAr values for patients treated with insulin and for those treated with either hypoglycemic agents or diet. Our data indicate that in diabetic patients fibrinolysis activity is increased, but it cannot counterbalance thrombin activity which appears much more enhanced. Finally, the lack of correlation for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose suggests that blood coagulation and fibronolysis abnormalities are not related to the degree of blood glucose control.

Adult↗
PubMed1989

Doxofylline, an adenosine-nonblocking xanthine, does not induce cardiostimulant effects.

Doxofylline (ANSIMAR) is a new adenosine-nonblocking anti-asthmatic drug with potent bronchodilator activity that does not display the typical extrapulmonary side effects of theophylline--a potent adenosine antagonist. The cardiac activity of doxofilline and theophylline was investigated in guinea pig right and left atrial preparations and in anestetized cat. In spontaneously beating right atria doxofylline slightly increased the atrial rate only at 0.3 mM, while theophylline induced a concentration-dependent positive chronotropic effect starting at 0.03 mM. The contractile force of electrically stimulated left atria was affected by doxofylline starting at 0.3 mM. Theophylline induced the same effect already at 0.03 mM. In the anesthetized cat, doxofylline (1-30 mg/kg.i.v.) did not affect the diastolic blood pressure, but the heart rate increased slightly at a dose of 30 mg/kg i.v. On the contrary, theophylline induced a marked dose-dependent hypotensive and positive chronotropic effect. Doxofylline was 10 times less potent that theophylline is its ability to antagonize the cardiodepressant activity induced by adenosine in isolated guinea pig atria. The pharmacodynamic differences between doxofylline and theophylline may bring new insights to the understanding of the mechanisms underlying the positive chronotropic effects of xanthines, and the functional importance of endogenous adenosine. Additionally, the lack of cardiostimulant effects makes doxofylline highly suitable for the treatment of chronic obstructive lung disease particularly in combination with beta 2-adrenergic agonists.

Adenosine↗
PubMed1989

[Histologic evaluation of gastric tolerability in rats of ferritin compared with ferrous sulfate].

The gastric tolerance of ferritin has been studied in Wistar rats and compared with a conventional antianaemic product (ferrous sulphate). The oral administration of the same amount of elementary iron (10-50-100 mg/kg 3 times in 24 h) from each compound produces different anatomopathological results. The treatment with ferritin caused only a moderate gastritic process. In contrast, the administration of ferrous sulphate induced a dose-dependent progression from incipient gastritis to intense gastritis, focal haemorrhagic gastritis and focal necrotizing gastritis. Ferritin did not produce other secondary effects, and is well tolerated even at the highest dosages.

Animals↗