Biocompatibility investigation of different pharmaceutical excipients used in liquid dosage forms.

Aqueous pharmaceutical solutions provide prosperous living conditions for microbiological agents. In order to eliminate these microbes, we use preservatives which can harm human cells as well. Their cytotoxicity is concentration-dependent and the aim of our study was to find how other pharmaceutical excipients modify the cytotoxic attributes of preservatives. We tested the following compounds: methylparaben, benzalkonium chloride, polysorbate 20, Labrasol® and hydroxyethyl cellulose. The MTT tests indicated that surfactants increase the cytotoxicity while polymers may decrease it in some cases.

Assessment of the hemolytic activity and cytotoxicity of different PEG-based solubilizing agents.

The hemolytic activity and the cytotoxicity of PEG-based solubilizing agents on Caco-2 monolayer were investigated. In vitro tests can predict the irritancy potential and the delayed toxicity of the surfactants. There were significant concentration dependent differences between the result of the MTT (3-(4,5-dimethylthiazol-2-yl))-2,5-diphenyltetrazolium bromide) test and the data of the hemolytic activity test. Our investigations show that safer and more applicable tensides can be selected in order to form a more biocompatible medicament.

Evaluation of the cytotoxicity of beta-cyclodextrin derivatives: evidence for the role of cholesterol extraction.

Several beta-cyclodextrin (beta-CD) derivatives have been synthesized recently to improve the physicochemical properties and inclusion capacities of the parent molecule, however, there is limited information available about their cytotoxic effects. In this study we investigated the cytotoxic and hemolytic properties of various beta-CDs in correlation with their cholesterol-solubilizing capacities to expose the mechanism of toxicity. MTT cell viability test, performed on Caco-2 cells showed significant differences between the cytotoxicity of beta-CD derivatives. Cell toxicity of methylated-beta-CDs was the highest, while ionic derivatives proved to be less toxic than methylated ones. Most of the second generation beta-CD derivatives, having both ionic and methyl substituents showed less cytotoxicity than the parent compounds both on Caco-2 cells and human erythrocytes. Inclusion of cholesterol into the ring of randomly methylated-beta-CD and heptakis(2,6-di-O-methyl)-beta-CD abolished the cell toxicity indicating the role of cholesterol extraction in cytotoxicity. These data demonstrate the correlation between the cytotoxic effect, hemolytic activity and the cholesterol complexation attributes of beta-CD derivatives and we propose that cholesterol-solubilizing properties can be a predictive factor for beta-CD cell toxicity.

Cytotoxicity of different types of methylated beta-cyclodextrins and ionic derivatives.

Cyclodextrins (CDs) are widely used materials and still in the focus of drug development. In spite of the extensive studies, there is limited information about the cytotoxic effect of different derivatives. This study compares the cytotoxic effect of methylated beta-CDs and some ionic derivatives. The methylated CDs involved in this study differ in the number and position of the methyl substituents. Heptakis(2,6-di-O-methyl)-beta-CD (DIMEB) with a degree of substitution (DS) of 14 has two methyl groups in all of the seven glucose subunits mostly at O-2 and O-6 position, each OH group is methylated in heptakis(2,3,6-tri-O-methyl)-beta-CD (TRIMEB) (DS = 21), and an unsystematic substitution is realized in randomly methylated beta-CD (RAMEB). DS is defined as the number of substituents per cyclodextrin ring. Using the above definition, the DS for RAMEB is 12.6. To see the effect of the ionic groups an anionic and a cationic CD derivative were also investigated: (2-hydroxy-3-N,N,N-trimethylamino)propyl beta-CD (QABCD) (DS = 2) and carboxymethylated beta-CD (CMBCD) (DS = 3,5). The in vitro cell toxicity decreases in the order of DIMEB > TRIMEB > or = RAMEB > QABCD > CMBCD. Ionic beta-CDs were less toxic than the methylated derivatives.

The role of exogenous carbon monoxide in the recovery of post-ischemic cardiac function in buffer perfused isolated rat hearts.

Isolated rat hearts were perfused for 10 min with oxygenated buffer and equilibrated with carbon monoxide (CO) of 0.001% and 0.01% before the induction of 30 min global ischemia followed by 120 min of reperfusion. These concentrations of CO significantly improved the post-ischemic recovery of coronary flow (CF), aortic flow (AF), and left ventricular developed pressure (LVDP). The improvement in recovery reflected in the reduction of infarct size and the incidence of reperfusion-induced ventricular fibrillation (VF). Thus, hearts subjected to 0.001% and 0.01% of CO exposure via the perfusion buffer, infarct size was reduced from the CO-free control value of 39% +/- 5% to 21% +/- 3% (*p<0.05) and 18% +/- 4% (*p<0.05), respectively. In the presence of 0.001% and 0.01% CO, the incidence of VF was also reduced from its control value of 92% to 17% (*p<0.05) and 17% (*p<0.05), respectively. Increasing the CO exposure to 0.1% in the buffer, all hearts showed VF combined with ventricular tachycardia or bradycardia and various rhythm disturbances indicating the direct toxic effects of CO on the myocardium. The results show that cardioprotective concentrations (0.01% and 0.001%) of exogenous CO related to an increase in cGMP levels and guanylate cyclase activities.

[About the incidence of chronic airway diseases in infants and children (author's transl)]. / Zur Frage des Vorkommens chronischer Luftwegserkrankungen im Säuglings- und Kindesalter.

Based on the experiences with 1,500 infants and children, hospitalized during a five-year period, who had undergone clinical, routine laboratory, immunological bacteriological, allergological, X-ray, oto-rhino-laryngological, spirometrical and bronchological examinations performed by unchanging teams using the same methods and instruments, it was found that the cause of respiratory diseases in a comparatively high number of patients were developmental anomalies, that it is important to look for tracheal stenoses, that there is chronic bronchitis in infants and children, that sinusitis maxillaris or shortage of immunoglobulins are relatively rare, and that selective bacteriological cultures are not very often positive. These results emphasize the importance of carefully differentiating between the various forms of respiratory diseases in infants and children.

Studies on xylanase from Basidiomycetes. Selection of strains for the production of xylanase.

Formation of extracellular xylanase was studied in 10 strains of wood-destroying fungi belonging to Basidiomycetes during their submerged cultivation with willow sawdust. The highest enzyme activity was found in the fungus Trametes hirsuta (Wulf.) Pilát. The effect of sources of carbon and nitrogen, cultivation time and initial pH of the cultivation solution on the formation of xylanase by the fungus Trametes hirsuta was investigated. The highest production of the enzyme was reached during cultivation in the presence of willow sawdust, asparagine and at the initial pH of 5.0. The presence of xylanase, cellulase, mannanase and amylase as well as of beta-xylosidase, beta-glucosidase, beta-mannosidase and beta-galactosidase was demonstrated in the enzyme preparation obtained after a 10-day submerged cultivation of Trametes hirsuta under optimal conditions.