Dibenzocyclooctadiene lignans overcome drug resistance in lung cancer cells--study of structure-activity relationship.

A panel of nine dibenzo[a,c]cyclooctadiene lignans, schizandrin, gomisin A, gomisin N, gomisin J, angeloylgomisin H, tigloylgomisin P, deoxyschizandrin, gamma-schizandrin and wuweizisu C was examined for their effect on multidrug resistance, as well as their anti-proliferative activities. COR-L23/R, a multidrug resistant sub-line, which has been reported to over-express multidrug resistance-associated protein (MRP1), was used for the experiments together with its parent cell line COR-L23 (human lung cell carcinoma). We found that lignans deoxyschizandrin and gamma-schizandrin at relatively non-toxic concentrations restored the cytotoxic action of doxorubicin to COR-L23/R cells. Deoxyschizandrin and gamma-schizandrin also significantly enhanced the accumulation of doxorubicin in drug resistant cells. Both lignans alone had no effect on the cell cycle; however, when combined with sub-toxic doses of doxorubicin, they induced cell cycle arrest in the G2/M phase, which is typical for toxic doses of doxorubicin. Our results suggest that deoxyschizandrin and gamma-schizandrin potentiate the cytotoxic effect of doxorubicin in doxorubicin resistant lung cancer cells COR-L23/R by increasing the accumulation of doxorubicin inside the cells. The common structural feature of both active lignans is the R-biaryl configuration and the absence of a hydroxy group at C-8. Unlike the reversal effect, the cytotoxicity of lignans with the R-biaryl configuration was similar to that observed for lignans with the S-biaryl configuration.

Klion in the prevention of early complications following appendectomy.

The authors observations with prophylactic administration of metronidazole manufactured by the Gedeon Richter Company, Hungary (trade mark Klion) in children with phlegmonous appendicitis are reported. The drug was administered in three doses to 51 children. Results of bacteriology could be assessed in 42 children. The results of prophylactic administration of Klion in phlegmonous appendicitis were excellent. In our group there were no inflammatory wounds and/or intraperitoneal complications. For comparison, in a cohort of 1.008 children with phlegmonous appendicitis, without prophylaxis the rate of inflammatory complications was 3.62%. Klion has minimal side effects and is well tolerated and seems to be a superb drug for prophylaxis.

[Eikenella corrodens as part of the polymicrobial flora in infectious endocarditis]. / Eikenella corrodens jako soucást polymikrobiální flóry pri infekcní endokarditide.

The authors describe a case of polymicrobial endocarditis in a 24-year-old patient with immunodeficiency and a damaged heart (mitral valve affection, septal defect). Among the mixed flora, comprising Streptococcus intermedius and two types of the genus Bacteroides, in the haemoculture also a microaerophil potentially pathogenic type Eikenella corrodens was cultivated. The authors describe the properties of Eikenella corrodens, its occurrence in man and its ability to produce an infectious process in primarily damaged organs (in particular the endocardium) in weakened subjects and drug addicts. The authors mention the diagnostic criteria for assessment of Eikenella corrodens and how to cultivate it from infectious material.

[Prophylactic administration of Klion in acute appendicitis]. / Profylaktické podání Klionu u akutní apendicitidy.

The authors present their experience with the prophylactic administration of metronidazole of Richter Co. Hungary (trade name Klion) in children with phlegmonous appendicitis. The preparation was administered in three doses to 51 children. The bacteriological results were evaluated in 42 children. The results of Klion administration in phlegmonous appendicitis were excellent. In the investigated group there were no wound inflammatory nor intraabdominal complications. For comparison the authors mention a group of 1008 children with phlegmonous appendicitis without prophylactic provisions where the number of inflammatory wound complications was 3.62%. Klion has minimal side-effects, was well tolerated and proved excellent for prophylactic administration.

Eikenella corrodens infection of the oral cavity as a cause of bacterial endocarditis.

The authors describe the case of a 24-year-old woman with valve disease. After a bout of respiratory tract infection, she was diagnosed to have bacterial endocarditis associated with mitral valve disease. The causative agents isolated included Eikenella corrodens, Streptococcus intermedius, Bacteroides oralis and Bacteroides bivius. At the same time, the patient was found to have developed IgA immunodeficiency. A complication accompanying the cardiac disease was spontaneous pneumothorax. Since antibiotic therapy had failed, the mitral valve was replaced by a prosthetic one. After the procedure, the patient had her teeth examined. The examination revealed complete destruction of tooth 36, thick layers of calculus and chronic gingivitis. E. corrodens was isolated also after microbiological examination of the patient's oral cavity. The reason for reporting on what we regard as an interesting case is that bacterial endocarditis with E. corrodens implicated as the causative agent is relatively rare; to date, polymicrobial endocarditis due to E. corrodens and other microorganisms has been described in intravenous drug addicts only.

Sensitivity of Bacteroides species to modern antimicrobial preparations.

Strains of Bacteroides fragilis group isolated from peritoneal pus were tested for susceptibility to cefalotin, cefamandole, cefoxitin, clindamycin and metronidazole. Clindamycin and metronidazole were found to display the lowest MIC and MBC values. The median serum level of these antimicrobials was 2-4 times as high as the MIC effective against 100% of strains. The most active cephalosporin was the cephamycin derivative cefoxitin that inhibited 98% of strains at 16 mg/l which corresponds with the usual median serum level achieved at commonly recommended treatment regimens. The MICs of 16 mg/l to cefalotin and cefamandole were found in 9.8% and 3.7% of strains, respectively. These findings are consistent with data reported in the literature. Attention is also centered on the mode of antimicrobial action, principles of bacterial resistance and on factors which are co-responsible for the therapeutic effectiveness of the antimicrobials studied.