Kinetics of cisplatin binding to cellular DNA and modulations by thiol-blocking agents and thiol drugs.

DNA platination by cisplatin (CDDP) was investigated in peripheral blood mononuclear cells and ovarian cancer cells using atomic absorption spectroscopy. Plots showing the amount of platinum (Pt) bound to DNA versus the molar concentration of cisplatin in the incubation medium ([CDDP]) were nonlinear. For [CDDP] < about 5 microM, the amount of Pt bound to DNA increased slowly with added drug. However, for larger [CDDP], the slope of the plot increased significantly. To study the role of thiols in affecting cisplatin binding to DNA, cells were treated with N-ethylmaleimide, which modifies thiol groups, rendering them incapable of binding cisplatin. Analysis using high-pressure liquid chromatography showed that approximately 99% of cellular glutathione was modified by N-ethylmaleimide. A plot of the amount of Pt bound to DNA versus [CDDP] for thiol-blocked cells is linear, with a slope similar to that of unblocked cells at high [CDDP]. Neither S-2-(3 aminopropylamino)ethanethiol (WR-1065) nor mesna, when added at clinically achievable concentrations (i.e., < approximately 300 microM), affected DNA platination. However, DNA platination was totally abolished by millimolar concentrations of the drug thiols (approximately 1.25 mM WR-1065 or approximately 5 mM mesna). Thus, the data show that endogenous thiols intercept cellular cisplatin, but this mechanism is less important at high [CDDP]. Moreover, therapeutic concentrations of drug thiols do not significantly affect DNA platination. A simple model that reproduces the experimental results of the amount of cisplatin binding to DNA as a function of [CDDP], time, and thiol content is proposed. The model takes into account passage of cisplatin and thiols through the cell membrane, binding of cisplatin to cellular thiols, and platination of DNA.     

In vitro effects of some anesthetic drugs on enzymatic activity of human red blood cell glucose 6-phosphate dehydrogenase

The study investigated in vitro effects of halothane, isoflurane, ketamine, sevoflurane, prilocaine, diazepam, and midazolam on enzymatic activity of human red blood cell glucose-6-phosphate dehydrogenase (G6PD; E.C. 1.1.1.49). G6PD was purified from human red blood cells by 2',5'-ADP-sepharose 4B affinity gel. Enzymatic activity was spectrophotometrically measured at 340 nm according to the method of Beutler. I50 values were determined from drug activity (%) - drug concentration curves. I50 values were as follows: 0.72 mM for isoflurane, 1.82 mM for sevoflurane, 0.38 mM for diazepam, and 0.0019 mM for midazolam. But halothane, ketamine and prilocaine had no inhibitory effect on the G6PD activity in in vitro.     

The seroprevalence of varicella zoster antibodies in Behçet's and other skin diseases

The purpose of this study was to investigate the association of the varicella zoster virus (VZV) IgG, and IgM antibodies with Behçet's and other skin diseases (group 1: recurrent aphthos stomatitis, fungal infections, psoriasis; group 2: vitiligo, lichen planus). Twenty eight patients with Behçet's disease (BD), and 117 patients with dermatological disorders other than BD were evaluated for specific VZV IgG and IgM antibodies by using a third generation enzyme-linked immunosorbent assay (ELISA). The Mantel Heizshel ² method was used to adjust the confounding of age and sex of the patients. The serological positivity for VZV IgG and IgM antibodies in BD was not statistically different from other skin diseases. When we considered the age of the patients, ² = 2.64, CI (0.27–1.65), odds ratio (1, 1.25, 2.21) (p = 0.10) and when we considered the sex of the patients, ² = 0.31, CI (0.81–1.28), odds ratio (1, 1.45, 1.41), (p = 0.57).     

In vitro effects of dantrolene sodium and verapamil on noradrenaline-induced contractions of rabbit aorta and their interactions

The effects of dantrolene sodium (0.1 to 10 microM) and verapamil (0.01 to 1 microM) administered alone or together (1 microM verapamil, 0.1 to 10 microM dantrolene sodium) were investigated in isolated rabbit thoracic aorta precontracted with 0.1 microM noradrenaline (NA). Verapamil plus dantrolene sodium produced a dose-dependent inhibition of aortic strips contractions evoked by NA, and all concentrations of dantrolene sodium significantly decreased the inhibitory effect of 1 microM verapamil (p < 0.001, ANOVA). In conclusion, dantrolene sodium and verapamil inhibited 0.1 microM noradrenaline-evoked aorta contractions, and all doses of dantrolene sodium decreased the inhibitory effect of 1 microM verapamil in a dose-dependent manner.     

Anthrax in eastern Turkey, 1992-2004

We investigated animal and human anthrax cases during a 13-year period in eastern Turkey. From 1992 to 2004, a total of 464 animal and 503 human anthrax cases were detected. Most cases occurred in summer. Anthrax remains a health problem in eastern Turkey, and preventive measures should be taken.     

Chemical and Biological Characteristics of Propolis from Apis Mellifera Caucasica from the Ardahan and Erzurum Provinces of Turkey: A Comparative Study

The aim of this study was to compare the biological activities of ethanolic propolis extracts of Apis mellifera caucasica obtained from Ardahan and Erzurum provinces of Turkey. Samples were tested for antioxidant, anticytotoxic, anticarcinogenic, antibacterial, and antifungal potentials using different techniques. Propolis samples from the two provinces had different mineral and organic compositions related to their geographical origin. The ferric reducing antioxidant power (FRAP) test showed superiority of Ardahan propolis over the Erzurum. Regardless of origin and the presence of mitomycin C in the culture medium, propolis enhanced human peripheral lymphocyte viability, which depended on the duration and propolis concentration. Antiperoxidative activity on MCF-7 breast cancer cells was concentration-dependent. Erzurum propolis showed the highest anticarcinogenic activity at the concentrations of 62.5 μg/mL and 125 μg/ mL, which dropped at higher concentrations. All propolis samples also showed antibacterial activity against the tested human pathogens similar to ampicillin and penicillin controls, except for Pseudomonas aeruginosa. However, they did not exert any antifungal activity against Candida albicans and Yarrowia lipolytica. In conclusion, propolis samples from both provinces showed promising biological activities, but further research should focus on finding the right concentrations for optimal effect and include the cell necrosis pathway to get a better idea of the anticarcinogenic effects.Key words: anticarcinogen, antimicrobial, biological activity, mineral, mitomycin C, organic composition     

The contracting and relaxing responses of human internal mammary artery grafts harvested by two different methods

Perioperative spasm of internal mammary artery is a common experience in coronary artery bypass grafting. Many techniques were described of harvesting the internal mammary artery to prevent vasospasm. We investigated the comparison of the contracting and relaxing responses of human internal mammary artery grafts harvested by two different methods. Patients were divided into two groups depending on the harvesting technique. In the first and second groups arteries were harvested by classical and carbon dioxide insufflation techniques, respectively. In both groups, endothelial function of arteries was assessed by precontracting the rings with phenylephrine (10(-5)M) and dilatating them by cumulative acetylcholine (10(-8) to 10(-5)M) concentrations. Cumulative concentration-response curves for phenylephrine (10(-8) to 10(-4)M), noradrenaline (10(-9) to 10(-4)M), and 5-hydroxytryptamine (10(-9) to 10(-4)M) were obtained in all groups. Endothelial integrity of arteries were histopathologically evaluated. In both groups, acetylcholine caused concentration-dependent relaxations in rings precontracted with phenylephrine (10(-5)M). In arteries harvested by carbon dioxide insufflation technique, acetylcholine caused significantly higher relaxations compared to the rings obtained by classical technique (p<0.05). In all rings of study groups, phenylephrine, noradrenaline and 5-hydroxytryptamine caused concentration-dependent contractions. There was not any significant difference in concentration-dependent responses of these contracting pharmacological agents between the groups. Histopathological evaluation revealed no major arterial damage in both groups. Carbon dioxide insufflation technique does seem not only to protect the integrity of the endothelium and the whole vessel, but also prevent the possible vasospasm of the internal mammary artery segments.     

The emergence of tics during escitalopram and sertraline treatment

The selective serotonin reuptake inhibitors (SSRIs) have well-established antidepressant activity and have also demonstrated efficacy in a number of anxiety disorders, including panic disorder. The SSRIs, escitalopram and sertraline, are well-tolerated and movement disorders are rarely associated with their use. We present a case of the emergence of tics associated with escitalopram and sertraline treatment, which might be due to an imbalance in the dopaminergic neurotransmitter system.     

The genotoxic and antigenotoxic effects of tannic acid in human lymphocytes

The genotoxicity of tannic acid (TA, tannin) were investigated using chromosome aberration (CA), sister chromatid exchange (SCE), and micronucleus (MN) test systems in human peripheral lymphocytes. Also, the antigenotoxicity of TA against known mutagen EMS was also examined. The lymphocytes were treated with 1.74?×?10(-5), 3.49?×?10(-5), and 6.98?×?10(-5) μM of TA for 24- and 48-hour treatment periods. For the antigenotoxicity of TA, the lymphocytes were treated with three different concentrations of TA and 2.71 μM of EMS. TA synergically induced the CA alone and with the mixture of EMS. However, TA did not induce the SCE alone, whereas TA and EMS as a mixture also synergically induced SCE. TA alone showed no clear effect on micronucleus formation, and it did not induce the MN when used with EMS as a mixture. In addition, TA showed a synergistic cytotoxic effect by decreasing the mitotic and nuclear division indices. The replication index was decreased at all concentrations for 48 hours of treatment time by TA and EMS as a mixture.