In vitro and in vivo reversal of cancer cell multidrug resistance by the semi-synthetic antibiotic tiamulin

A large number of multidrug resistance (MDR) modulators, termed chemosensitizers, have been identified from a variety of chemicals, but most have been proven to be clinically toxic. Low concentrations of the pleuromutilin-derived semi-synthetic antibiotic tiamulin (0.1 to 10 microM) sensitized the three highly resistant P-glycoprotein (Pgp)-overexpressing tumor cell lines P388 (murine lymphoid leukemia), AS30-D (rat hepatoma), CEM (human lymphoblastic leukemia), and the barely resistant AS30-D/S cell lines to several MDR-related anticancer drugs. Flow cytometric analysis showed that tiamulin significantly increased the intracellular accumulation of daunomycin. When compared to reference modulating agents such as verapamil and cyclosporin A, tiamulin proved to be 1.1 to 8.3 times more efficient in sensitizing the resistant cell lines. Moreover, when given i.p. (1.6 microg/mg body weight), tiamulin increased the survival rate of adriamycin-treated mice bearing the P388/ADR25 tumor line by 29%. In the presence of an anticancer drug, tiamulin inhibited both ATPase and drug transport activities of Pgp in plasma membranes from tumor cells. Tiamulin is thus a potent chemosensitizer that antagonizes the Pgp-mediated chemoresistance in many tumor cell lines expressing the MDR phenotype at different levels and displays no toxic effects on contractile tissues at active doses, therefore providing the promise for potential clinical applications.     

Methods of financial analysis for the delivery of dental assistance with the obligatory health coverage

The authors offer a method for estimation of financing of dental care and differentiation of it by various sections. With detailed information at hand, it is possible to estimate the cost of a territorial program of obligatory medical insurance in dentistry by combining its various sections with consideration for the preset scope of dental care and the mean per capita standard of financing and the reserve fund.     

Effects of information processing load in abstinent and nonabstinent smokers' psychomotor task performance.

Recent evidence has indicated that nicotine, the active agent in tobacco, may affect mental abilities of smokers. To better understand the effects of nicotine on central processing, we used a basic chronometric approach to studying information processing. This chronometric approach allowed for the independent examination of nicotine's effects on two theoretically nonoverlapping information-processing stages, stimulus identification and response programming. Two stimulus intensity and four distance traversed conditions were used to affect the stimulus identification and response programming stages, respectively. The 11 subjects completed two experimental sessions (nicotinized and denicotinized), which were conducted 1 week apart. Each experimental session comprised two tests. The first test consisted of abstinent baseline measures, and the second test was administered after subjects smoked an investigator-supplied nicotinized or denicotinized cigarette. Data analysis revealed that the higher intensity stimulus elicited faster reaction times, as did the shorter movement distances, thus confirming successful manipulation of both the stimulus identification and response programming stages of the information-processing model. Furthermore, the significant improvement in reaction-time performance over baseline abstinent levels was consistent despite the manipulations made within the stimulus identification stage of processing, demonstrating that no interaction existed between stimulus intensity and the administration of nicotine. Interestingly, these data provide initial evidence that although nicotine may not affect the programming of very simple movements, it has a more pronounced effect on more complex movements. Although distance traversed had a reliable effect on movement time, nicotine had no observable effect.     

Comparative study of three antineoplastic alkylating agents on DNA

The influence of three alkylating anticancer preparations phosphamide, sarcolysine, cyclophosphane on content of the 5-methylcytosine and parameters of the melting DNA of the liver healthy animals and tumor sarcoma 45 was investigated. It was shown, that among the investigated preparations cyclophosphane has stronger anticancer influence and comparatively weaker side effect on DNA liver. We came to the conclusion that it is preferable to use this preparation.     

1H-magnetic resonance spectroscopy-determined cerebral lactate and poor neurological outcomes in children with central nervous system disease

By using proton magnetic resonance spectroscopy ((1)H-MRS), cerebral lactate has been shown to be elevated in a wide variety of pediatric and adult neurological diseases. In this study we compared 36 newborns, infants, and children with elevated lactate peaks on (1)H-MRS with 61 patients without an identifiable lactate signal. (1)H-MRS was acquired from the occipital gray and parietal white matter (8 cm3 volume, STEAM sequence with echo time = 20 msec, repetition time = 3.0 seconds) and data were expressed as ratios of different metabolite peak areas (N-acetylaspartate [NA]/creatine [Cr], NA/choline [Ch], and Ch/Cr) and the presence of a characteristic lactate doublet peak at 1.3 ppm. Outcomes (Pediatric Cerebral Performance Category Scale score; PCPCS) were assigned 6 to 12 months after injury. Patients with lactate peaks were more likely to have suffered a cardiac arrest, were more often hyperglycemic, and had lower Glasgow Coma Scale scores on admission. They were also more likely to have abnormal metabolite ratios when compared with age-matched controls or with patients without detectable lactate. Of prognostic importance, patients with increased lactate were more likely to be severely disabled (39% vs 10%), survive in a persistent vegetative state (13% vs 2%), or have died (39% vs 7%). In contrast, patients with similar conditions without increased lactate were more likely to have had a good outcome (23% vs 3%) or recovered to a mild (38% vs 6%) or moderate disability (20% vs 0%). Our data suggest that (1)H-MRS is useful in the prediction of long-term outcomes in children with neurological disorders. Patients with elevated cerebral lactate are more likely to die acutely or are at greater risk for serious long-term disability.