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Biomedical subjects

C De Vos

Publications and source records attributed to C De Vos.

32 records · Page 2Linked to original sources

Antihistamines and allergic asthma.

Subjects with asthma demonstrate hyperresponsive airways to histamine and require only small quantities of this mediator to demonstrate changes in their pulmonary functions. The discovery of drugs that could compete with and antagonize the target-tissue effects of histamine has provided a method of testing whether histamine contributes as a mediator of asthma. Now, there are potent and selective anti-H, drugs which are relatively non sedating. Some of them inhibit the bronchoconstrictions induced either by allergen or exercise (e.g. terfenadine, astemizole, azelastine); some others, moreover, inhibit mast cell degranulation (e.g. azelastine). Finally, some others (e.g. cetirizine, ketotifen) display some inhibitory actions on eosinophil functions, an important cell in allergic cellular recruitment and inflammation. Some studies with H1 antihistamines in asthma have demonstrated some therapeutic benefits. However, additional carefully controlled studies are required to confirm their efficacy in asthma.

Asthma↗

Inhibition of human eosinophil chemotaxis and of the IgE-dependent stimulation of human blood platelets by cetirizine.

Cetirizine is a new anti-allergic compound with a potent, long-acting, and specific antihistaminic property. Strongly active in the therapy of urticaria and seasonal or perennial rhinitis, it has been shown to inhibit the in vivo eosinophil attraction at skin sites challenged with allergen in atopic patients. In the present work, we confirmed that, at a therapeutical concentration, this molecule had a potent inhibitory action in vitro on eosinophil chemotaxis induced either by N-formyl-Met-Leu-Phe or platelet-activating factor and also on the IgE-dependent stimulation of platelets. These observations appear in favour of a possible role for cetirizine in the modulation of inflammatory cell interactions in allergic processes.

Blood Platelets↗

Inhibitory effect of oral cetirizine on in vivo antigen-induced histamine and PAF-acether release and eosinophil recruitment in human skin.

The use of a noninvasive skin chamber technique in vivo in pollen-sensitive patients allowed us to quantify the time-course release of histamine and the recruitment of inflammatory cells (i.e., neutrophils, monocytes, and eosinophils) in skin sites challenged with pollen, histamine, and compound 48/80. The new H1-receptor antagonist, cetirizine 2 HCl, orally administered with 10 mg once a day to pollen-sensitive patients in a double-blind, crossover study versus placebo, induced a significant decrease in the wheal-and-flare cutaneous reaction induced by intradermal injection of pollen, histamine, and compound 48/80. It also significantly inhibited the immediate histamine release occurring in skin chambers after pollen introduction, whereas it did not significantly inhibit the late release. In patients receiving placebo, we detected platelet-activating factor-acether in media collected at the sixth hour from chambers filled with pollen. With cetirizine 2 HCl treatment, platelet-activating factor-acether was not detected in chamber media. Interestingly, cetirizine 2 HCl significantly reduced the eosinophil recruitment observed on the superficial dermis 24 hours after pollen challenge.

Administration, Oral↗

Inhibition of eosinophil chemotaxis by a new antiallergic compound (cetirizine).

The in vivo inhibitory effect of a new antiallergic, anti-H1 drug, cetirizine, on eosinophil attraction at skin sites challenged with various stimuli has been recently suggested. In the present work, we confirmed that this molecule, at therapeutical concentration, has a potent inhibitory action on eosinophil response to different chemoattractant mediators such as platelet-activating factor (PAF acether) and N-formyl methionyl leucyl phenyl alanyl in vitro. Another anti-H1 drug, polaramine, did not show this effect at the same concentration. These findings suggest that cetirizine in addition to its antihistaminic effect could also play a direct inhibitory effect on eosinophil recruitment. Moreover, cetirizine was not toxic for eosinophils and did not induce degranulation, as shown by the absence of peroxidase release. Comparison between cetirizine and a PAF acether antagonist (BN 52021) suggested that cetirizine did not act by a PAF receptor-blocking activity.

Cell Survival↗

Inhibition of histamine and allergen skin wheal by cetirizine in four animal species.

Histamine-induced skin reactions were studied in four animal species. Cetirizine displayed very potent oral antihistaminic activity in this model. In rats, the dose that reduced the reaction by 50% in comparison to controls was 4.2 mumol/kg and between 0.1 and 0.4 mumol/kg for the other species (mice, guinea pigs, and dogs). Cetirizine also inhibited the immediate hypersensitivity reaction induced by Ascaris extract in dogs. By the oral route, cetirizine had a more potent and longer acting activity than mepyramine, clemastine, terfenadine, astemizole, and hydroxyzine.

Allergens↗

A simple rapid method for detection of IL-2 in a physiological medium.

The Con A-activated proliferation of C57BL/6 mice thymus cell suspension is completely blocked by a low concentration of hydrocortisone. This inhibition is reversed by the addition of a 24 h Con A-activated splenic cell supernatant to the thymic cell culture. The restoring activity is completely destroyed by heating. Restoration is not obtained by addition of IL-1-rich supernatant from an LPS-activated peritoneal adherent cell population. The supernatant of a 24 h splenic cell culture activated by Con A in the presence of indomethacin not only restores hydrocortisone-blocked thymocyte reactivity but also enhances thymic cell stimulation. Addition of PGE to the splenic cell culture inhibits the restoring potency of the supernatant. These results are in accord with the proposition that IL-2 is responsible for the restoring phenomenon. These properties have been used to develop a semi-quantitative method for detection of IL-2 in a physiological medium.

Alprostadil↗

Nitrogen bridgehead compounds. 44. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. 4.

The weak antiallergic activity of 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carbox yli c acid (1) in the rat reaginic passive cutaneous anaphylaxis test was enhanced by the introduction of an (arylamino)methylene moiety into position 9 of the pyridopyrimidine ring. Compound 34, (+)-6(S)-methyl-9-[(m-methylphenyl)-hydrazono]-4-oxo-4H-pyrido[1,2 -a] pyrimidine-3-carboxylic acid, displayed about 10 000 times the activity of the starting compound 1. A structure-activity relationship study of 9-[(arylamino)methylene]tetrahydropyridopyrimidine-3-carb ox ylic acids resulted in conclusions similar to those found for the 9-(arylhydrazono)tetrahydro-and 9-(arylamino)dihydropyridopyrimidine series. Replacement of the 3-carboxy group of 9-(phenylhydrazono)-tetrahydropyridopyrimidin-4-ones with an acrylic acid moiety caused slight increases in potency. In the 6-methyl-substituted series, a high stereospecificity was observed between the enantiomers with 6S and 6R absolute configurations, the former being responsible for the antiallergic activity. The effects of some 9-[(arylamino)-methylene]tetrahydropyridopyrimidine-3-car box ylic acids on the rat passive peritoneal anaphylaxis test were also investigated.

Anaphylaxis↗

Pharmacology of a new orally active antiallergic: pyrido[1,2-a]pyrimidine, ucb L140 (CHINOIN 1045) in rats.

ucb L140 (CHINOIN 1045) has been tested in various rat anaphylaxis systems. In models of passive cutaneous anaphylaxis (PCA), passive peritoneal anaphylaxis (PPA) and anaphylactic bronchospasms, ucb L140 appears to be more potent than sodium cromoglycate (DSCG). Upon oral administration, ucb L140 exhibits a marked inhibition of these anaphylactic reactions. Sensitized rat mast cells in vitro display a decreased Nippostrongylus-induced histamine release when treated with a concentration of ucb L140 three times smaller than DSCG. In PCA testing after intravenous administration of ucb L140 a cross-tachyphylaxis with DSCG was observed. These results suggest that the action of ucb L140 is similar to that of DSCG in inhibiting the release of allergic mediators from mast cells and therefore may present antiallergic activity.

Administration, Oral↗

Determination of manganese in blood and urine by flameless atomic absorption spectrophotometry.

A method for the determination of manganese in blood and urine is described. A chelate fo manganese with cupferron is extracted with methylisobutylketone and determined by flameless atomic absorption spectrophotometry. The method is directly applicable to urine but the determination of manganese in blood required a preliminary digestion step. With the use of internal standards, this technique allows the determination of manganese concentrations of the order of 1 mug/1 of urine or 1 mug/100 ml whole blood.

Humans↗

Clinical evaluation of a peritoneal dialysis solution with 33 mmol/L bicarbonate.

OBJECTIVE: To evaluate the efficacy and safety of a new peritoneal dialysis solution with 33 mmol/L bicarbonate. DESIGN: In an acute, prospective, randomized cross-over study, 8 patients were randomized in two groups of 4. On the first study day, the first group performed two consecutive 4-hour exchanges with a dialysis solution containing 35 mmol/L lactate: the first exchange with 13.6 g/L and the second with 38.6 g/L dextrose. On the second study day, the same type of exchanges were performed with bicarbonate. The second group underwent the same treatment, but used bicarbonate solutions on the first day and control solutions on the second study day. Thirty-three patients participated in a 2-month prospective and randomized study. After a 4-week baseline period using solutions containing 40 mmol/L lactate, the patients were dialyzed with either 33 mmol/L bicarbonate solutions or 40 mmol/L lactate solutions. SETTING: Peritoneal dialysis units at the University Hospital of Brescia and the Niguarda Hospital of Milan, Italy. RESULTS: Acute study: Control and bicarbonate solutions had similar effects on blood chemistries and peritoneal transport. Chronic study: Mean venous bicarbonate concentrations remained unchanged in the control group (26.6-27.2 mmol/L), but decreased significantly in the bicarbonate group from 28.8 mmol/L at the start of the study to 23.0 mmol/L after 2 months of bicarbonate administration. Other biochemical parameters remained unchanged. CONCLUSION: A peritoneal dialysis solution with a bicarbonate level of 33 mmol/L does not adequately correct uremic acidosis.

Adult↗