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At least 523 records · Page 29Linked to original sources
PubMed2004

Advances in insulin sensitizers.

Insulin resistance is the major cause in Non Insulin Dependent Diabetes Mellitus (NIDDM). In this review insulin production from beta-cells and action of insulin is briefly described. Any intervention either in the production or action of insulin has been the leading cause of NIDDM. Therapeutic intervention to deal with the defective action of insulin at various receptor or target tissues has been outlined. Structure-activity relationship of a large number of thiazolidinediones, oxazolidinediones, isoxazolidinediones, biguanides, tetrazole derivatives, pyrazoles and pyrazolones, oxathiadiazole oxide, hydroxyurea and carboxylic acid derivatives have been described. The probable mechanism of action of these novel compounds through Peroxisome Proliferator-Activated Receptors that ameliorate the insulin resistance, has been described. Finally the clinical candidates at various stages of clinical evaluation have been compiled.

Animals↗
PubMed2001

Recent developments in the combinatorial synthesis of nitrogen heterocycles using solid phase technology.

Recognizing the potential of combinatorial chemistry to accelerate drug discovery and development, most pharmaceutical and related industries are seriously looking toward combinatorial synthesis of compounds in order to facilitate the identification of 'lead' molecules. In particular, solid phase synthesis is the core technology for combinatorial chemistry and is widely used for generating libraries of structurally related compounds. Since many drugs contain the nitrogen heterocyclic component and since heterocycles possess a high order of structural diversity, a precise overview of recent progress in the combinatorial synthesis of nitrogen heterocycles using solid phase methodology would be useful. Since the progress in solid phase synthesis of organic molecules has been reviewed regularly from 1992 to 1998, only the development of solid phase combinatorial synthetic approaches of small nitrogen heterocycles since 1999 will be reviewed here. This review describes the solid phase synthesis of azepanes, benzodiazepines, benzimidazoles, benzothiazepines, cinnolines, indolizines, beta lactams, oxazepins, oxazoles including benzisooxazoles, hydantoins, piperidines, pyrimidines, pyrazolones, quinolones, trizolopyridazines and thiazoles.

Combinatorial Chemistry Techniques↗
PubMed2001

Update on sensitivity to nonsteroidal antiinflammatory drugs.

Non steroidal antiinflammatory drugs (NSAIDs) are among the most frequently prescribed medications worldwide. These drugs are effective for the treatment of a wide spectrum of diseases: musculoskeletal disorders, headhache, fever, pain, and others. Their widespread use explains the very high incidence of intolerance; reactions range from asthma, rhinitis, to urticaria/angioedema, various skin eruptions and anaphylactic shock. The pathogenesis of intolerance is still unclear: immune-mediated reactions have been reported following the use of pyrazolone derivatives and, less commonly aspirin, anthranilic-acid derivatives and diclofenac. It has been suggested that NSAIDs may induce pseudoallergic reactions, while in case of bronchial asthma the inhibition of cyclooxigenase by NSAIDs has been proposed as a pathogenetic mechanism. The diagnosis of NSAIDs sensitivity can usually be established by history; in fact skin prick tests with NSAIDs have not been successful and no reliable in vitro tests are available. The only definitive diagnostic test is oral test dosing. To identify an alternative NSAIDs in a sensitive patient a tolerance test is performed. Here we review the current state of knowledge concerning NSAIDs sensitivity, including personal data to increase awareness on this issue.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Tolerability of imidazole salycilate in aspirin-sensitive patients.

Over the last few years, many studies have been carried out in order to individualize which nonsteroidal anti-inflammatory drug (NSAID) can be tolerated in aspirin sensitivity. Imidazole salicylate (IS) is a new NSAID that inhibits Tromboxane A2 synthesis, without interferring with cyclo-oxygenase pathway, whose inhibition was demonstrated to cause asthma and/or urticaria/angioedema in aspirin-sensitive patients. We enrolled 67 subjects with documented intolerance to aspirin, pyrazolones or NSAIDs, clinically manifested as urticaria/angioedema (68%), asthma, and/or rhinitis (32%). A challenge with IS was carried out in every patient in single-blind fashion, reaching a cumulative dosage of 1000 mg in the fourth session. No appearance of urticaria or bronchospastic reactions was registered in any subject, confirming the safe use of IS in aspirin-sensitive patients.

Adolescent↗
PubMed1996

Carbohydrate composition of stereociliary glycocalyx of the utricle of guinea pig inner ear.

The carbohydrate composition of the stereociliary glycocalyx of the utricle was analysed quantitatively. The utricular sensory epithelium was collected from adult albino guinea pigs, and its apical surface structure was blotted onto a PVDF membrane, which was then subjected to acid hydrolysis. The hydrolysate was treated with 1-phenyl-3-methyl-5-pyrazolone for labelling and analysed by reversed-phase HPLC coupled with detection of UV absorbance at 245 nm. Man, GlcN, GaIN, Glc, Gal and Fuc were detected and estimated to be 211, 219, 46, 1,270, 266 and 36 pmoles per 10 utricular maculae, respectively. The presence of Man indicates the presence of N-linked glycoconjugates, and the considerable amounts of GLcN and Gal suggest the presence of complex-type N-glycosides, poly-lactosamine and/or keratan sulfate. The relatively low GaIN content indicates that O-glycosides, chondroitin sulfates and GaINAc-containing glycosphingolipids, i.e. gangliosides and globosides, are minor components. Electronmicroscopic and confocal laser scanning microscopic observations revealed that the blotted apical surface structure constituted mostly the ciliary bundle. Consequently, the observed carbohydrate composition is probably that of the stereociliary glycocalyx of the utricular sensory epithelium.

Animals↗
PubMed1999

Retrospective study of adverse reactions to non steroid anti-inflammatory drugs (NSAIDs): predictive value of controlled challenge with alternative drugs.

Acetylsalicylic acid (ASA) and NSAIDs, which inhibit the cyclo-oxygenase enzyme (C-O), are responsible, when administered at therapeutic doses, for adverse reactions mainly involving the skin and respiratory tract. The prevalence of intolerance to ASA and NSAIDs, assessed by the Section of Allergic and Immunological Diseases at the University of Bari on a population of 15,800 patients referred for allergic diseases over a period of 7 years, was found to be 11.4%. The adverse reactions to NSAIDs observed were in most cases skin complaints (88.9%), followed by respiratory symptoms (asthma +/- rhinitis, rhinitis) and general symptoms (shock, hypotension, lipothymia). The most common types of NSAIDs taken were pyrazolones, salicylics, arylpropionics, paracetamol. Controlled oral challenges with alternative NSAIDs (especially nimesulide) confirm the predictive power of this test: in fact, among patients who showed tolerance to the challenge drug, only 10.6% manifested unexpected reactions during the course of one year's follow-up.

Adolescent↗
PubMed1975

Tartrazine: solid-phase radioimmunoassay studies of an azo dye implicated in allergic reactions (azo dyes and allergy).

A solid-phase radioimmunoassay procedure was adapted for the haptenic study of tartrazine, an azo dye implicated in various forms of allergy. Further, the haptenic relationship of tartrazine and aspirin was investigated, since sensitivity of individuals to the two substances is often clinically associated. The specificity of antibody to tartrazine was directed strongly toward a pyrazolone intermediate of the molecule, 1-(4-sulfophenyl)-3-carboxy-5-hydroxy-pyrazole. Aspirin did not cross-react with anti-tartrazine, suggesting that the clinical association of aspirin and tartrazine sensitivity in patients is a nonimmunological phenomenon.

Antigens↗
PubMed2004

Volume-sensitive chloride channels do not mediate activation-induced chloride efflux in human neutrophils.

Many agents that activate neutrophils, enabling them to adhere to venular walls at sites of inflammation, cause a rapid Cl(-) efflux. This Cl(-) efflux and the increase in the number and affinity of beta(2) integrin surface adhesion molecules (up-regulation) are all inhibited by ethacrynic acid and certain aminomethyl phenols. The effectiveness of the latter compounds correlates with their inhibition of swelling-activated Cl(-) channels (I(Clvol)), suggesting that I(Clvol) mediates the activator-induced Cl(-) efflux. To test this hypothesis, we used whole-cell patch clamp in hypotonic media to examine the effects of inhibitors of up-regulation on I(Clvol) in neutrophils and promyelocytic leukemic HL-60 cells. Both the channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid and [3-methyl-1-p-sulfophenyl-5-pyrazolone-(4)]-[1,3-dibutylbarbituric acid]-pentamethine oxonol (WW781), a nonpenetrating oxonol, inhibited I(Clvol) at concentrations similar to those that inhibit beta(2) integrin up-regulation. However, ethacrynic acid, at the same concentration that inhibits activator-induced Cl(-) efflux and up-regulation, had no effect on I(Clvol) and swelling-activated Cl(-) efflux, providing evidence against the involvement of I(Clvol) in the activator-induced Cl(-) efflux.

Benzenesulfonates↗
PubMed1992

Familial occurrence of fixed drug eruptions.

Fixed drug eruptions following the use of pyrazolone derivatives occurred in 4 members of the same family: a 12-year-old girl, her grandmother, and two of her great aunts. Although the pathophysiologic events leading to this type of reaction are unknown, these cases of familial occurrence suggest that genetic predisposition might be an important causal factor.

Child↗
PubMed1992

Drug-triggered pemphigus in a predisposed woman.

A 31-year-old woman with three pemphigus-prone antigens in her HLA haplotype (B7, DR4, DQw7) developed the disease soon after taking a pyrazolone derivative, viz. feprazone. The pemphigus lesions persisted despite withdrawal of the drug and worsened appreciably when she used ceftriaxone (a new cephalosporin with three sulphur atoms) for a bout of acute pharyngitis. Thiol groups formed from the metabolic breakdown of ceftriaxone are thought to have promoted acantholysis via a biochemical route. Genetic predisposition alone ('the soil') may be essential, though not per se sufficient for outbreak of pemphigus; the intervention of exogenous, heterogeneous factors ('the seed') often seems decisive in triggering full-blown disease.

Adult↗
PubMed1976

Analysis of drug decomposition products. Part 34. Gas chromatography method for quantitative determination of METET in the presence of its sulfoxide.

Gas chromatographic method for the determination of METET in the presence of its oxydation product sulfoxide was worked out. The gas chromatographic conditions were: gas chromatograph--Chrom4CSSR,FID,N2-flow20--30cm3/min glass, column 100 cm, phi 0-2 cm, 10% SE-30 on Chromosorb W 100/120 mesh, temp. 180--200 degrees C. The determination was carried by means of internal standard (phenylbutazone--PhB--1,2-diphenyl 4n-butyl pyrazolidino-3,5-dione or aminophenazone--APh--1-phenyl-2,3-dimethyl-4-dimethylamino-pyrazolone-5) and the calibration curve was prepared. The ratio of peak heights for the determined comound and the standard was considered. The error of the METET determination expressed as standard percentage deviation was sr = 2--3% at n = 10.

Chromatography, Gas↗
PubMed1976

[The relative therapeutic value of drugs in international comparison: differences between Switzerland and Canada].

In Switzerland the relative therapeutic value of various drugs (e.g. pyrazolone analgesics, phenacetin, clindamycine, clioquinol) is placed demonstrably higher than in Canada. In Canada, rare but possibly dangerous complications of drug therapy are considered to be of greater importance. Two factors might be responsible for these differences: 1. Compared with similar publications in Canada, drug advertisements in Swiss medical journals contain fewer warnings of untoward effects. This can be interpreted as an "information lag". 2. Since the link between an untoward effect and a drug is very difficult to establish with absolute certainty, it may be concluded that the drug is relatively inoffensive. This conclusion is drawn more often in Switzerland than in Canada. Uniformization of the way in which the physician is presented with information concerning untoward drug effects would be an important step towards the establishment of internationally accepted standards of drug therapeutic value.

Analgesics↗
PubMed1976

[Serum complement level (C'H5O) during treatment of rheumatoid arthritis patients].

Decreased total complement serum level (C'H50) was established in 72 per cent of the 78 patients examined, associated most likely with the developing processes of antigen-antibody reaction and the severe course of the illness. The applied treatment with different antirheumatic remedies, according to their mechanism of action, determined the respective changes in the complement level. Indomethacinum and chinoline derivatives induce complement values elevation, whereas the corticosteroids, salicylate and pyrazolone preparations lead to the complement values normalization.

Adrenal Cortex Hormones↗
PubMed1976

[Influence of an antispastic, analgesic combination on blood pressure, dynamics and contractility of the left ventricle in the dog].

The following cardiovascular parameters were continuously measured in 12 dogs anaesthetized with sodium pentobarbital following i.v. application of Baralgin, a combination of 1-beta- piperidino-ethoxycarbmethoxy-benzophenone-hydrochloride with diphenylpiperidino-ethyl-acetamide-bromomethylate and 2.3-dimethyl-4-methylamino-1-phenyl-5-pyrazolone-N-methanesulfonic acid: Mean arterial blood pressure, left ventricular pressure, dp/dt-value in the left ventricle, the parameter (see article), told peripheral resistance, cardiac work, heart rate, cardiac output and stroke volume, flow rate in the A. femoralis and the repiration volume. In this experimental series dosages of 0.1, 0.25, 0.625 and 1.56 ml Baralgin/kg i.v. were tested and the subsequent cardiovascular activity was recorded for a period of 90 min following application. 1. The mean arterial blood pressure remained practically unaltered following low doses of Baralgin (0.1 and 0.25 ml/kg i.v.), whereas higher doses (0.625 and 1.56 ml/kg) led to an initial drop in blood pressure corresponding to the fall in total resistance. 2. The cardiac output rose slightly in correlation with rise in stroke volume. In the dosage range of 0.25 ml Baralgin/kg i.v. the rise in cardiac output was accentuated by an increase in heart rate. 3. The cardiac work remained relatively stable following small Baralgin doses, however, a slight diminution in cardiac work due to the fall in blood pressure and decrease in cardiac output, resulted from application of 1.56 mg/kg i.v. 4. A slight positive inotropic stimulation of the heart became apparent in the initial period following small doses of Baralgin (0.1 and 0.25 ml/kg i.v.), higher i.v. dosages caused a marginal reduction in cardiac contractility.

Aminopyrine↗
PubMed1998

[Determination of cyanide in whole blood by completely differential spectrophotometry].

This paper introduced a method for the determination of cyanide in whole blood by completely differential spectrophotometry with pyridine-pyrazolone method after stabilization by addition of silver sulfate and separation by distillation. The analytical results showed a precision 5.4% (n = 6) for the determination of 0.068 microgram.ml-1 CN- in whole blood. The average recovery was 97.4%. This method was successfully used for the determination of cyanide in whole blood of non-smokers and smokers.

Cyanides↗
PubMed2000

Somatic and skeleton development of rat foetuses following in-utero exposure to isopropylantipyrine (propyphenazone) during the second trimester of gestation.

Isopropylantipyrine (IPA, propyphenazone) is a pyrazolone derivative, widely used as an antipyretic and analgesic drug. The aim of the study was to evaluate the influence of propyphenazone on rat development. IPA was administered to pregnant rats from day 8 to day 14 of pregnancy once a day, orally by a stomach tube at doses of 2.10 (R1), 21.0 (R2), and 210.0 mg/kg/day (R3). The dams were sacrificed on day 21 of gestation and corpora luteum, implants, resorptions, and live foetuses were counted. The weight of foetuses and placentas, the length of foetuses and their tails were checked. The foetuses were fixed in alcohol and skeletons were stained with alizarin. There was a statistical difference in body length in R1, R2 and numbers of subcutaneous ecchymose in R1. External and skeletal examination of the foetuses revealed no evidence of teratogenesis. It can be concluded that IPA has no harmful effects on the prenatal development of the rat offspring at doses used in the present study.

Animals↗
PubMedDate not supplied

NSAID facial angioedema in a selected pediatric atopic population.

Epidemiological data for drug reactions in pediatric medical literature as well as in specialized periodicals are scarce. A relationship between nonsteroidal antiinflammatory drugs (NSAIDs), facial angioedema and atopic status has been described in adults. A 10-year retrospective random review of 1,007 charts of atopic children (60.9% male) attending an allergy clinic for management of asthma and/or rhinitis was carried out. Careful attention was given to the written history of NSAID facial angioedema reactions (41 out of 1007, 4.07%) and atopy was confirmed if the patient had a family history and at least one positive skin prick test (>3 mm wheal compared to glycerosaline control) to aeroallergens. Telephone recall was performed when available. Patients were classified into four age groups as follows: a) 0-5 years old; b) 6-10 years old; c) 11-15 years old; and d) 16-21 years old. NSAID facial angioedema rates were as follows: group a 10/493 (2.0%), group b 14/361 (3.8%), group c 10/121 (8.2%), and group d 7/32 (21.8%). Aspirin was the most commonly reported NSAID, and less common were pyrazolones and ibuprofen. Of the 41 patient with chart-reported reactions, 27 (66%) could be contacted by telephone. Of these, 17 patients confirmed the facial angioedema NSAID reaction occurring once or more due to inadvertent exposure. No reactions were reported in the remaining 10 patients since no other NSAID, except acetaminophen, had been used for fever or pain. In conclusion, our data show the age dependency of these reactions and its rather frequent occurrence in such selected pediatric atopic populations. Since NSAIDs are used more frequently in younger children, exposure would not be a plausible explanation for these observations.

Adolescent↗
PubMedDate not supplied

Synthesis and antimicrobial activity of novel pyrazole, pyrazoline, pyrazolinone and pyrazolidinedione derivatives of benzimidazole.

Four novel series of pyrazolylbenzimidazole derivatives have been prepared, namely 2-[(1-substituted phenyl-3,5-dimethyl-4-pyrazolyl)methyl]benzimidazole 5a-d 2-[(1-substituted phenyl-3-methyl-5-oxo-4,5-dihydro-4-pyrazolyl-4-yl)methyl]benzimidazoles 6a-d; 2-[(1-substituted phenyl-3,5-dioxopyrazolidin-4-yl)methyl]benzimidazoles 7a-d and 2-[(4-(1-phenyl-5-aryl-4,5-dihydro-3-pyrazolyl)phenylaminoacetyl]thio- methyl)-benzimidazoles 12a-e. The antimicrobial testing of the prepared compounds was performed using Escherichia Coli (NCTC 5933) as Gram-negative bacteria, Staphylococcus aureus (NCTC 4163) as gram-positive bacteria and Candida albicans (NCTC 5310) as yeast like fungi. The most potent compound was the pyrazolone 6a which exhibits interesting antibacterial activity against the gram-negative bacteria E. coli.

Anti-Bacterial Agents↗