The pharmacological activity of some new fluorescent small molecule histamine H2 receptor (H2-R) ligands, derived from aminopotentidine and squaramide, in the GTPase assay.

UNLABELLED: We characterized the pharmacological activity of some new fluorescent and nonfluorescent ligands derived from aminopotentidine and squaramide with respect to the interaction with human (h) and guinea pig (gp) H2R species isoforms on Spodoptera frugiperda (Sf9) cell membranes expressing H2R-Gsalpha fusion proteins. MATERIAL AND METHOD: The pharmacological studies were performed in a radioactivity-based GTPase assay. Non-linear curve ?tting was performed using the computer program Prism 4.0 (GraphPad-Prism). RESULTS: Interestingly is that the aminopotentidine ligands labeled with S0536 dye showed a higher activity than the squaramide ligands labeled with the same fluorophor. Moreover, for some cases, the bulky fluorescent groups can even substantially increase ligand affinity. CONCLUSION: The study of comparative antagonist activity of new H2R ligands derived from aminopotentidine and squaramide in the GTPase assay suggests that there is no common, lock' for all, keys' at the H2R.

The expanded pharmacological profile of histamine H2 receptor (H2R) species isoforms with respect to the interaction with new squaramide H2R ligands, in the GTP-ASE assay.

UNLABELLED: We comprehensively characterized the human (h), guinea pig (gp), canine (c) and rat (r) H2R species isoforms on Spodoptera frugiperda (Sf9) cell membranes expressing H2R-G(Salpha) with respect to the interaction with new ligands derived from squaramide. MATERIAL AND METHOD: Antagonist potencies were determined in the GTPase assay. Non-linear curve fitting was performed using the computer program Prism 4.0 (GraphPad-Prism). RESULTS: An interesting result was obtained for the squaratepentylamine compound in comparison with famotidine. Furthemore, the analysis of the new squaramide ligands, under the same experimental conditions, at the four H2R species isoforms, indicates that the rH2R exhibits increased constitutive activity, compared with hH2R, gpH2R and cH2R. CONCLUSION: The present study validates the notion that quantitative comparison of species isoforms of GPCRs provides unique insights into the molecular mechanisms of GPCR activation.

[Community pharmacy counseling. An important role in reducing and optimizing self-medication]. / Consilierea in farmacia comunitara. Rol important in reducerea si optimizarea automedicatiei.

UNLABELLED: The study was directed towards the evaluation of the use of analgesic drugs, non-steroidal anti-inflammatory and their combinations with other substances in a community pharmacy, with regard to the role of the pharmacist in patient counseling for the optimization of self-medication. MATERIAL AND METHOD: A group of 108 subjects, which repeatedly use drugs from the above-mentioned groups and have multiple pharmacy visitations, was divided into separate groups, according to the annual call frequencies and they received questionnaires with multiple questions, tailored according to the necessities of the study. RESULTS: The results demonstrated statistically significant differences between the patients that have medical prescriptions and those that employ self-medication (p < 0.05, ANOVA). From the group using initial self-medication, 75% were receptive to the counseling by the pharmacists and subsequently consulted a physician and 25% were non-compliant. For the assessment of the annual drug consumption (CM50), a quantal model for the quantitative evaluation was designed. The data were subjected to regression analysis, and it has been observed that a percentage of 10.7% from the general population uses repeatedly and regularly drugs from the groups taken in study.

Withania somnifera, a plant with a great therapeutical future.

Withania somnifera Dun is a plant which drew the interest of many researchers in several countries, either for its active principles or for the extremely important pharmacodynamic or pharmacotherapeutic properties it has and first of all for the content in withanolides, substances with a sterol structure.

[General research modalities with traditional remedies of plant origin with a view to their introduction into pharmacotherapy]. / Modalitati generale de cercetare a unor remedii traditionale de origine vegetala în vederea introducerii în farmacoterapie.

The literature had suggested some schemes of tests and procedures to be employed in the scientific investigations and pharmaceutical evaluation of the traditional plant remedies. The present paper is intended to be a critical review.

[The synthesis of oximes and O-acetyl derivatives with biological activity]. / Sinteza unor oxime si derivati O-acetilati cu activitate biologica.

Data about synthesis of some oximes and their O-acetyl derivates are shown here. This item also emphasize the results of testing the antimicrobial, antifungal, antilevural and anti-inflammatory action of the synthesized oximes.

[The experimental evaluation regarding analgesic activity of some extracts isolated from Achillea collina J. Becker ex Reichenb]. / Evaluarea experimentala privind activitatea analgezica a unor extracte izolate din specia Achillea collina J. Becker ex Reichenb.

In the present investigation we have evaluated the potential existence of analgesic activity of the residue of tincture and of the crude lipophilic (AC 2, AC 4) and hydrophilic portions (AC 1, AC 3) of infusion and decoction obtained from flower heads of Achillea collina J. Becker ex Reichenb. Acid acetic induced writhing and vascular permeability test was performed by the method of Whittle. Comparison was made with indomethacin, morphine and rutin, as references drugs. The mice were dosed orally with samples. AC 2 induced a potent inhibition (47.23%; p < 0.05) of the nociceptive response after oral administration of 250 mg/kg--a dose ten folds higher than the dose of indomethacin. AC 3, at a dose of 5000 mg/kg (p.o.) inhibited with 47.6% (p < 0.001) and 19.8% (p < 0.05) the increase in peritoneal vascular permeability caused by 0.5% acetic acid. Relative unexpected, morphine (1.14 mg/kg, p.o.), an opioid analgesic, also produced a significant reduction of the leakage (41.2%, p < 0.01). This finding is consistent with the reports in which the role of the endogenous opiate system in the physiological response to injury/inflammation, mainly controlling fluid leakage into the interstitial space, is sustained.

Histological aspects of the pulmonary territory as seen in an experimentally ovalbumin induced inflammation in guinea pigs.

The microscopic morphology of the respiratory territory was investigated on sections of pulmonary tissue and bronchioalveolar lavage liquid (BAL) that were stained with Giemsa, PAS and trichrome solutions. As a result of the induced pathological conditions, the following histological images were encountered: normal histological aspect of the bronchoalveolar territory was seen in the groups nebulized with 0.9% NaCl or sensitized after i.p. administration of ovalbumin (OA); macrophage cells influx in both tissue samples and BAL in animals nebulized with OA; after sensitization with OA followed by nebulization with OA, the same sequence of events as in atopical asthma was reproduced, including loss of epithelial structure and the appearance of mast cells and basophils in the alveolar territory. Hydrocortisone hemisuccinate, used to treat asthma attacks, causes a similar histological aspect as in the untreated group. Cells with intact basophilic granules were seen in the hypersensitized group under ketotiphen protection.

[Pyridazinilides (XIV). The action of p-phenyl-phenacyl bromide on 3-phenyl-pyridazine]. / Piridaziniu-ilide (XIV). Actiunea bromurii de p-fenil-fenacil asupra 3-fenil-piridazinei.

This time the synthesis of some new derivatives obtained by the quaternary substitution of one of the heterocyclic nitrogen atoms and by reactions of dipolar cycloaddition is presented. The results of the tests on their antimicrobial and antiinflammatory actions are discussed.

[Synthesis of new mandelic acid derivatives with preservative action. Synthesis and acute toxicity study]. / Sinteza unor noi derivati ai acidului mandelic cu actiune conservanta. Sinteza si studiul toxicitatii acute.

Starting from the antiseptic action of DL mandelic acid, there were synthesized a series of esters of the mandelic acid, esters which could have preservative action. This study present the synthesis, structure validation and the acute toxicity study, for the new synthesized compounds. The esters were obtained by acylating 4-hydroxybenzoic acid propyl, ethyl, methyl esters and salicylic acid with the DL mandelic chloride (that was protected initially by the hydroxylic group). The structure of the synthesized compounds was confirmed by quantitative elemental analysis and RMN 1H spectral measurements. The acute toxicity was determined for two of the esters, who proved to had a preservative action (previously studied) and indicated that these esters have a small toxicity.

[The reaction of 3-(R-phenyl)-6-hydrazine pyridazine with 5-methylisatin and 1-morpholinomethyl-5-methylisatin]. / La réaction de la 3-(R-phényle)-6-hydrazino-pyridazine avec la 5-méthyl-isatine et la 1-morpholinométhyl-5-méthyl-isatine.

This paper presents the synthesis of six hydrazones obtained by treating 5-methyl-isatin or 1-morpholino methyl-5-methyl-isatin with 3-(R-phenyl)-6-hydrazino-pyridazine (R = OCH3, Cl, Br) and two complex combination with copper, derived from 3-(p-anisyl-pyridazinyl)-hydrazone-5-methyl-indoline-2- one. The structure of the new compounds was confirmed by the results of the quantitative elementary and IR, UV-VIS spectral analysis. The biological tests point out that product VI, in which a copper atom binds two molecules of 3-(p-anisyl-pyridazinyl)-hydrazono-5-methyl-indoline-2-one, has a considerable antiinflammatory activity, giving a inflammation inhibition of 39, 6%. All the synthetized compounds have a moderate antimicrobial activity against Candida albicans.

[Studies reagarding the bioavailability of oxacillin from preconditioned powders]. / Cercetari privind biodisponibilitatea oxacilinei din pulberi prieconditionate.

Previous studies have pointed out a good antimicrobial activity of two oxacillin salts--DBED--oxacillin and calcic oxacillin--which were conditioned as "preconditioned powders" for oral suspensions. The above mentioned preparations were followed up by administration to animals, and similar seric concentrations in DBED oxacillin and sodic oxacillin (with the difference that insoluble salts present a long-time activity) were pointed out.

[The synthesis and anti-inflammatory properties of 7-theophyllineacetic acid derivatives]. / Cercetari privind sinteza si proprietatile antiinflamatoare ale unor derivati ai acidului 7-teofilinilacetic.

Some esters of 7-theophyllinylacetic acid were synthetized, characterized physicochemically and tested for their anti-inflammatory properties. As compared to indomethacin, reference anti-inflammatory drug, all synthetized compounds were less toxic. The anti-inflammatory properties are influenced by the nature of the ester group radicals, the more active having ramified alchils.

Hydrazones and formazans with possible biological activity.

This paper presents a synthesis about some hydrazones, formazans and copper's complexes combinations. The structure of the new compounds was confirmed by the results of the quantitative elementary and IR spectral analysis. The antimicrobial and antiinflammatory activities were investigated.

New derivatives of m-nitrobenzoyl-asparagic acid and m-nitrobenzoyl-asparagine with anti-inflammatory action.

In order to obtain new biologically active compounds some derivatives of 1-[N-(m-nitrobenzoyl)-alpha-D,L-asparaginyl]-2-benzyl-benzimidazole have been synthesized by ring opening reactions of 2-(m-nitrophenyl)-4-(beta-amidomethyl)-delta 2-oxazolin-5-one and 2-(m-nitrophenyl)-4-(beta-carboxymethyl)-delta 2-oxazolin-5-one with 2-benzylbenzimidazole (dibazole).

[The reaction of 3-(R-phenyl)-6-hydrazine pyridazines with substituted isatins (II)]. / La réaction de certaines 3-(R-phényle)-6-hydrazino-pyridazines avec des isatines substituées (II).

This paper presents the synthesis of six hydrazones from isatin and 1-morpholinomethyl-isatin and also of their six cooper's complex salts. Their structure was confirmed by the results of the quantitative elemental analysis and by IR, UV-VIS spectral analysis. The biological tests point out that cooper's complex salt of 3-(3'-phenyl-pyridazinylhydrazono)-5-methyl-indoline-2-one (1:2) (VI a) has the smallest toxicity (DMT over 800 mg/kg.w. p.o.), a remarkable anti-inflammatory activity (inhibition 57.1%, IAR 1.1) and also a gastroprotector coefficient of 43.3%. In the mean time, the cooper's complex salt of 3-(3'-p-anisyl-pyridazinyl-hydrazono)-5-methyl-ind oline-2-one (1:2) (VI b) has a gastroprotector coefficient of 76.3% and a lower anti-inflammatory activity than the first derivative (inhibition 36.9%).

[New isatin-derived hydrazones and Mannich bases with possible biological activity]. / Noi hidrazone si baze Mannich derivate de la isatina, cu eventuala activitate biologica.

The paper presents a synthesis of six new Mannich bases, five hydrazones derived from 1-piperidino-methyl-5-R-isatin and three copper complex compounds of 3-(3'-R-phenyl-pyridazinil-hydrazone)-indoline-2-ones (R=H, CH3, OCH3). The structure of the new compounds was confirmed by the results of the elementary and spectral analysis. Pharmacodynamic studies indicated that copper complex compounds present effective biological properties. Thus, it can be seen that the experimental carrageenan-induced inflammatory oedema was 58.3% inhibited by the complex V (R=CH3) after oral administration. Antimicrobial tests revealed that only compound V (R=OCH3) shows a moderate antimicrobial activity against the gram-positive and gram-negative bacteria, used in the test.

[Adhesive cutaneous pharmaceutical forms]. / Studiul unor forme farmaceutice adezive cutanate.

The adhesive cutaneous pharmaceutical forms aimed to local action release the drug substance in view of a dermatological, traumatological, antirheumatic, cosmetic action. Two such preparations were obtained and their stability, consistency and pH were determined. The "in vitro" tests of their bioavailability revealed the dynamics of calcium ions release according to the associations of each preparation. The bioavailability determined by evaluating the pharmacological response demonstrated the antiinflammatory action obtained by the association of calcium ions with the components extracted from poplar muds. The therapeutical efficiency of the studied preparations has proved in the treatment of some sport injuries.