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Biomedical subjects

P Boni

Publications and source records attributed to P Boni.

At least 37 records · Page 2Linked to original sources

Pharmacodynamic profile of the new potent antibronchospastic agent 7-[(2,2-dimethyl)propyl]-1-methyl xanthine.

The pharmacodynamic profile of a new xanthine derivative, 7-[(2,2-dimethyl)propyl]-1-methyl xanthine (CAS 155006-67-0, MX2/120), was investigated in comparison with theophylline. The compound reduces in vitro the bronchospastic tone induced by carbachol or histamine in guinea-pig bronchi, with a potency 11 and 5 fold greater than theophylline, respectively. MX2/120 is significantly more active and long-lasting than theophylline in in vivo experiments toward spasmogens such as acetylcholine (ED50 over 5 h = 15 mumol/kg p.o. vs 230 mumol/kg p.o.) or histamine (ED50 over 5 h = 122 mumol/kg p.o. vs 500 mumol/kg p.o.) while being almost equiactive to theophylline toward antigen and capsaicin induced cough strokes. MX2/120, if administered by i.p. route reduces hyperresponsiveness to histamine induced by PAF and extravasation of protein into bronchoalveolar lavage fluid induced by capsaicin. These anti-inflammatory effects of MX2/120 are of similar extent when compared to theophylline. Unlike theophylline, MX2/120 up to 275 mumol/kg p.o. possesses little or no CNS excitatory effects in mice in terms of reduction of sleeping time induced by chlordiazepoxide, increase in mortality and convulsions induced by pentetrazol and increase in locomotor activity. This reduced neuroexcitatory action is probably related to its lack of affinity to adenosine receptors that could also explain the absence of effect on basal gastric secretion. Chronotropic effects of MX2/120 in conscious rats are similar to those of theophylline while the effects of both drugs on blood pressure are of minor extent. The overall pharmacodynamic properties of MX2/120 are superior to those of theophylline in relation to its antibronchospastic activity and lack of excitatory effects on CNS.

Acetylcholine↗

A new class of antibronchospastic agents: 7-(2,2-dimethyl)propyl substituted xanthines.

A series of 7-(2,2-dimethyl)propyl substituted xanthines were synthesized and tested for their antibronchospastic activity in comparison with theophylline. In vitro, the inhibition of carbachol-induced increase in bronchial tone was determined. In vivo, the inhibition of antigen-induced bronchoconstriction in guinea pigs was determined 1, 3 and 5 h after oral administration. Central side effects were evaluated. In vitro, the majority of compounds were more effective than theophylline. In vivo, three compounds 2, 14 and 15 showed an effect comparable to theophylline but longer lasting. A mild sedative effect was generally observed. Compound 2, 7-(2,2-dimethyl)propyl-1-methyl xanthine, coded MX2/120, was selected for a deeper evaluation.

Animals↗

In vivo evidence for the activation of a septide-sensitive tachykinin receptor in guinea pig bronchoconstriction.

Intravenous administration of the undecapeptide [Sar9]substance P (SP) sulfone (1.5 nmol/kg) and the hexapeptide [Glp6,Pro9]SP(6-11) (septide; 0.4 nmol/kg) produced a comparable (about 30-40% of maximal effect) increase of insufflation pressure (bronchospasm) in anesthetized guinea-pigs. The non peptide NK-1 receptor antagonist, (+/-)CP 96,345 and the peptide NK-1 receptor antagonist, GR 82,334 antagonized dose-dependently the response to both agonists. Both antagonists were more potent against septide than against [Sar9]SP sulfone (9 and 4 fold difference in ED50 for (+/-)CP 96,345 and GR 82,334, respectively). These findings indicate that a 'septide-sensitive' mechanism mediates bronchoconstriction in vivo and it influences the estimate of the potency of NK-1 receptor antagonists.

Animals↗

Interleukin 1 beta (IL-1 beta) release from fresh and cultured colonic mucosa in patients with ulcerative colitis (UC).

Interleukin-1, a cytokine produced by macrophages and other tissue cells, has a major role in inflammatory and immunological responses. Increased levels of IL-1 activity have been reported in experimental colitis and in patients with active Crohn's disease (CD) and ulcerative colitis (UC). IL-1 beta release from fresh and cultured colonic biopsies and IL-1 beta plasma concentrations was determined in 15 patients with active UC, 16 with UC in remission and 10 normal control subjects. Biopsies, taken at colonoscopy were weighed, washed in 1 ml of 0.9% sodium chloride solution and then cultured for 24 h in 10% fetal calf serum/RPMI. IL-1 beta activity was determined by ELISA KIT (Cystron Biotechnology) in plasma samples, washing solution and the incubation medium. Very low levels of IL-1 beta were detected only in 3 plasma samples, all from active patients. Significantly more IL-1 beta was released from fresh and cultured colonic mucosa obtained from patients with UC in remission compared to normal mucosa (p less than 0.01). Furthermore, specimens from active UC released significantly more IL-1 beta than those from patients in remission (p less than 0.01). In conclusion, IL-1 may play an important role in mediating the inflammatory response in UC.

Adult↗

The effect of daily hassles on salivary IgA: experimental evidence.

The study aimed at evidencing the suppressive effect of daily hassles on salivary immunoglobulin A (S-IgA); in fact, previous research did not detect a clear relationship between the two variables. Twenty-four subjects were tested as to the hassles that had occurred in their recent life and to S-IgA; the tests were repeated three times, with an interval of four weeks between each. The results show that the variation of S-IgA values between times 2 and 3 is associated with the variation of hassles between times 1 and 2 (r = -.46, p < .01).

Adult↗

Resolution and pharmacological properties of the enantiomers of the potent alpha-adrenoceptor antagonist 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine.

Resolution of the optical isomers of the alpha-adrenoceptor antagonist IP-66 (1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine) and its intermediate IP-30 (1-[2-hydroxy-2-(3'-pyridyl)ethyl]-4- (2'-methoxy-phenyl)piperazine have been carried out. Optical purity was assayed by high-pressure liquid chromatography. The antagonistic potencies of racemic mixtures and stereoisomers toward phenylephrine- and norepinephrine-induced contraction in isolated rat aortic strips have been compared. (+)-IP-66 and (+)-IP-30 were resp. 363 and 170 times more potent than respective (-) isomers in eliciting competitive alpha 1-adrenoceptor blockade. Similarly IP-66 (+) or (+/-) were extremely more effective than the (-) isomer in antagonizing norepinephrine-induced pressor responses in pithed rat.

Adrenergic alpha-Antagonists↗

Thymopentin (TP-5) therapy during lymphadenopathy syndrome (LAS/ARC): preliminary report.

Persistent generalized lymphadenopathy during HIV infection is now a well classified syndrome featuring multiple chronic lymph node enlargement frequently associated with further symptoms (diarrhea, nocturnal sweating, loss of weight, fever): it is invariably accompanied by serious alterations of the cell-mediated immunity including lymphopenia, reduced number of helper lymphocytes in circulation, inversion of the helper/suppressor ratio, lower proliferative response in vitro and deficient delayed skin sensitivity tests. Minor opportunistic infections are also more frequent, the most widespread being chronic oral candidiasis. Whenever several of these signs are associated in a single patient, especially if the immunitary deficit is severe, an immunomodulating treatment is indicated to improve the lymphocyte functionality and finally to modify any evolutive tendency. The Authors give the preliminary results of a pilot study carried out on 12 patients with LAS/ARC treated with Thymopentin at a dosage of 50 mg by intra muscular injection on alternate days for cycles of 30 days. Compared with 14 untreated patients, the subjects receiving therapy showed a more stable immunological picture, and improvement in subjective symptoms and a better therapeutic response to minor opportunistic infections.

AIDS-Related Complex↗

Importance of laboratory parameters in the evaluation of Crohn's disease activity.

Some laboratory investigations are abnormal during the course of Crohn's disease (CD). We investigated the trend of some of these laboratory tests in a group of patients with CD to study the relationships between an activity index made up of such laboratory parameters only (LCDAI) and the usual Crohn's disease activity index (CDAI). One hundred thirty-one examinations of 63 patients were evaluated. At each investigation, besides calculation of the CDAI, 10 laboratory investigations were carried out. Three gastroenterologists independently gave an overall evaluation of the laboratory activity for each of the 131 examinations on the basis of the results of the blood tests alone. The sum of the evaluations was used as an independent variable on which a laboratory index was developed by multiple regression analysis. C reactive protein, red cell sedimentation rate, acid alpha 1-glycoprotein, alpha 1-antitrypsin, and white blood cells had an important share in the development of this laboratory index. The evaluation of the relationships existing between LCDAI and CDAI showed that in patients with moderate to severe clinical disease activity, LCDAI was constantly altered. The same happened in 55% of cases in clinical remission, which suggests an inflammatory activity that is not clinically evident. These results point to the advisability of supplementing a predominantly clinical index, such as CDAI, with a laboratory index such as LCDAI in the evaluation of CD.

Crohn Disease↗

Successful treatment of subacute cerebellar degeneration in ovarian carcinoma with plasmapheresis. A case report.

Subacute cerebellar degeneration is a rare complication of some neoplasms, and is generally resistant to therapy. A case of subacute cerebellar degeneration in a 50-year-old woman with a Stage II grade 3 serous ovarian adenocarcinoma is reported. The onset of the neurologic symptoms preceded the diagnosis of cancer and progressively worsened during and after four cycles of chemotherapy. A quick, partial improvement of the neurologic syndrome was documented after three weekly treatments with plasmapheresis. The contribution of circulating factors in inducing subacute cerebellar degeneration can be postulated. A trial using this new type of treatment should be performed in patients who have this therapeutically refractory clinical condition.

Acute Disease↗

In vitro comparison of pre- and postsynaptic effects of dihydroergotoxine mesylate and 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl) piperazine (IP-66).

The effects caused on the intestine mesenteric artery preparation by 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl) piperazine (IP-66), a compound having a prevailing alpha-blocking action, and by dihydroergotoxine mesylate (DHEM) were compared in normal conditions and in propranolol-induced beta-receptors block. The two drugs behaved in a completely different way both on vasoconstrictor response (delta p) and on noradrenaline (norepinephrine, NA) outflow induced by electrical stimulation of periarterial nerves. In fact IP-66 inhibited delta p much more than DHEM did but, unlike the latter, it increased NA outflow only at the lowest concentration (8.7 X 10(-9) mol/l) whereas it reduced it at the highest one (2.9 X 10(-7) mol/l). Moreover the effect of IP-6--but not that of DHEM--on NA outflow was completely abolished by propranolol. The hypothesis is put forward that IP-66 may show a strong antagonism towards postsynaptic alpha-receptors and a slight agonism towards presynaptic beta-receptors.

Adrenergic alpha-Antagonists↗

[Hepatitis B and hepatitis A markers in 33 cases of acute hepatitis B surface antigen-negative, hepatitis A virus antibody-positive viral hepatitis. Importance of immune complexes].

The authors have looked for the markers of HBV by R.I.A. method (HBsAg, anti HBsAg, HBeAg, anti HBeAg, anti HBcAg), of HAV (by measurement on two samples of HAVab or by measurement of HAVab IgM), the immune-complexes (I.C.C.) by C1q solid-phase binding assay method with E.L.I.S.A. with determination after division I.C.C. of HBsAg by R.I.A. method in 33 cases of HBsAg negative acute viral hepatitis. The 9% (3 cases) were HAV acute hepatitis, the 42,4% (14 cases) no A no B acute hepatitis, the 36,3% (12 case) were HBV acute hepatitis, in 9 anti HBcAg positive cases the I.C.C. with HBsAg positive after division resulted positive, the 12,3% (4 cases) had a positivity for HAVab by stereoconversion (2 cases) or HAVab IgM (2 cases) with HBsAg positivity after division I.C.C. This result puts a nosologic problem about the 4 cases of acute viral hepatitis, which, from epidemiological and clinical point of the view are HAV acute hepatitis.

Antibodies, Viral↗

The rat mesenteric artery-intestinal loop preparation. Noradrenaline outflow and vascular responses to nerve stimulation and drugs.

A new preparation, intestine-mesenteric blood vessels of the rat, was tested for simultaneous measure of noradrenaline (NA) overflow and vasoconstrictor response (delta p) induced by electric stimulations. Control experiments showed that this preparation could be used within a wide range of frequencies and repeatedly stimulated without any important decrease of response. The effects of phenoxybenzamine, dihydroergotoxine mesylate, imipramine and pargyline were investigated. All the drugs inhibited delta p and, except for dihydroergotoxine mesylate, increased NA outflow. The results were discussed in the light of the present knowledge. It is concluded that this preparation can be profitably used to study drug effects at pre- and post-synaptic level.

Adrenergic alpha-Antagonists↗