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.

Hepatoprotective effects of a self-micro emulsifying drug delivery system containing Silybum marianum native seed oil against experimentally induced liver injury.

The main purpose of this study was to certify the effect of native silymarin oil (SM-oil) formulated in a self-microemulsifying drug delivery system (SMEDDS). The optimal formulation was 25% of SM-oil, 33.3 % of Cremophor RH40, 20% of Transcutol HP, 16.6% of Labrasol and 5% of Capryol 90. In this novel formulation the SM-oil was the active substance and the lipid part. The in vivo study examined the preventive effects of SMEDDS containing SM native seeds oil against carbon tetrachloride (CC14) induced hepatotoxicity in mice. Determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels and also liver histology investigations have been done. The liver antioxidant status was determined with the concentrations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione (GSH) hepatic lipid peroxidation was examined and expressed in terms of malondialdehyde (MDA) content. The plasma levels of AST and ALT significantly diminished by pre-treatment with 500 mg/kg and 1000 mg/kg SMEDDS. The pre-treatment with 500 mg/kg and 1000 mg/kg SMEDDS increased GSH level by about 6% respectively 24% compared to the CC14 group. Due to preventive administration of 500 mg/kg and 1000 mg/kg of SMEDDS in the intoxicated animals, MDA levels were reduced by 22% respectively 58%. Also, an insignificant rise by almost 17% and 19% in the animals treated with the both doses of SMEDDS could be noticed. It can be concluded that hepatotoxicity may be avoided by the oral application of our formulation.

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.

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.

[Periapical surgery of the molars]. / Periapikalna hirurgija molara.

INTRODUCTION: If loss of a great number of teeth occurs, one molar in the lateral segment is of great importance. Contemporary techniques and materials provide extremely successful conservative treatment of pulpal diseases and apical periodontitis. In some cases, however, surgery is indicated. INDICATIONS: Indications for periapical surgery used to be a matter of double standards. If periapical surgery is indicated in incisors, it is performed without delay, but if it is indicated in molars, it is often exchanged for extraction. Surgical access in the region of upper and lower molars is specific in regard to much more frequently operated incisors due to anatomic structures at the surgical site. Canal filling techniques, implants, endodontic surgical procedures are of importance and can provide better healing. High quality canal filling is condition sine qua non in treatment of apical periodontitis. It is performed prior surgery, by conventional orthograde endodontic techniques, during surgery by orthograde technique and/or retrogradely. Implants provide better bone healing and are recommended in surgery of molar apex. Surgical packing has numerous advantages (better psychological and mechanical care). CONCLUSION: Good knowledge of anatomy and surgical techniques is a pre-requisite for molar apicoectomy. Careful establishment of indications and good relations with the patient provide good prognosis of this therapeutic method.

[Measurement of velocity waveforms in the median cerebral artery in cases of ventriculomegaly in mature fetuses]. / Az arteria cerebri media áramlásvizsgálata magzati ventriculomegalia esetén kiviselt terhességek során.

The authors give account of three pregnancies, where fetal ventriculomegaly was diagnosed. Their examinations were aimed to prove connection between the figures of velocity waveforms of cerebral arteries and the prognosis of ventriculomegaly. The study based on the results of the published cephalic neonatal and infant ultrasound examinations which consider the method useful. The authors consider on the basis of their examinations, that the measurement of the velocity of the fetal cerebral arteries is useful and maybe has prognostic values. Considering the low number of examined patients further investigations are necessary to statistically analyse the results.