The aim of this short review is to provoke focuses on the antioxidant-induced stress. Although there are studies documenting that supplementation with antioxidants appears to reduce lipid peroxidation and oxidative stress, it is still unknown exactly what amounts are needed to have a beneficial antioxidant effect and which dose reflects the safe and appropriate limit for use. Many of antioxidant vitamins and the other antioxidants can cause pathologic changes to the exposed tissues and to the organs of the bodies by initiating different mechanisms. These harmful and undesired effects are created by prooxidant, antioxidant or some other unknown ways. Although the most important point related to the use of antioxidants is not their dosages, the term hypervitaminosis is commonly used referring to the negative effects of the overdoses of the vitamin antioxidants. The question which level of the antioxidants may lead to stress is unanswered yet though this is vital in determining antioxidative stress. This article uses the term “antioxidative stress” for the first time for the negative effects of antioxidants. In our opinion, focusing on antioxidative stress is essential as it is on oxidative stress by the medical disciplines. For this purpose, close collaboration between the triad of molecular biochemist, physiologist and the pharmacologist is required to develop new, specific, and more effective antioxidants and therapy modulations. We believe that further studies are needed to elucidate the factors and ways creating the antioxidative stress, as well as its consequences together with an “insurance policy” containing appropriate measures against to it.

The class of calcium antagonists is constituted by pharmacological agents which inhibit the contraction evoked by extracellular calcium in depolarized smooth muscles. While the inhibiting action of calcium antagonists on the gastrointestinal motility is well documented, its action on the biliary tract has not been extensively studied, despite its potential clinical usefulness. Therefore we investigated the effect of a calcium channel blocker (verapamil) on fasting and postprandial gallbladder volume in normal subjects. Method: Twenty healthy volunteers participated in this study. The gallbladder volumes were measured using ultrasonography. After the baseline measurement was taken, the volunteers received 80 mg of verapamil (n:10) or a placebo (n:10) per oral in the morning one h before rescanning. The gallbladder was rescanned in 15 min intervals for 60 min. At the end of this period all the volunteers received a standard liquid test meal (Ensure), and then scans were performed again. Results: The administration of verapamil increased the fasting gallbladder volume to a maximum of 61.2% to 74.2% compared to the baseline (p<0.05) and of 49.1%- 62.6% compared to the placebo group (p<0.05). In the verapamil group significant changes in the postprandial gallbladder volumes were observed. The postprandial gallbladder volume increased to a maximum of 4.6%-61.2% compared to the baseline (p<0.05) in the first 30 min. Then it decreased to the baseline value. The gallbladder volume of the verapamil group was increased to a maximum of 86.8%-111.7% compared to the placebo group (p<0.05 and 0.01). Conclusion: These results demonstrated that verapamil significantly increased fasting and postprandial gallbladder volume.

Common bile duct (CBD) injuries cause sig- nificant morbidity and mortality. CBD injuries can be repaired by various approaches. In biliary tract recon- struction for CBD defect, we used a graft which we obtained from the posterior sheat of the rectus muscle. Method: This experimental study was carried out on eight street dogs. A tissue fragment was excised from the posterior sheat of the rectus muscle together with the fascia transversalis and peritoneum. A tube of fas- cia graft was wrapped around an FG G feeding tube. Results: Anastomotic insufficiency was determined in one dog who died on the thirteenth day. The fascial graft gained an appearance similar to bile duct in other dogs. Blood biochemical parameters were normal. Conclusion: We concluded that fascia graft can be used in repair of CBD defect as an alternative method.

Valproic acid is a commonly used antiepileptic drug for chronic therapy and may have adverse effects on gastrointestinal, hematologic and nervous system. Potential mutagenic effects of sodium valproate have been reported, but this effect of valproic acid has still not been clarified yet. Comet assay was performed in peripheral lymphocytes of 24 epileptic adolescent and adult female treated with valproic acid monotherapy for at least one year and in a control group including 16 adolescent and adult healthy, drug free females. The frequencies of comet scores in the valproic acid treated epileptic patients were significantly higher than that of the control group (p<0.05) indicating a detectable chromosome damaging effect of valproic acid monotherapy on human lymphocytes. No significant correlation was noted amongst age, drug dose, blood valproic acid levels, duration of valproic acid therapy and the comet scores. Although genotoxic effects of valproic acid was shown by means of sister chromatid exchange and chromosomal aberration assays in previous studies, we report here the first demonstration of genotoxic potential of valproic acid with comet assay. This data supports the conclusion that valproic acid is genotoxic.

To determine the efficacy and safety of midazolam given as a continuous infusion in the treat- ment of refractory generalized status epilepticus (RGSE). Method: Prospective, open study. Eleven patients with RGSE, who received intravenous doses of 0.3 mg/kg of diazepam (three times at 5 min intervals), 20 mg/kg of phenytoin, and 20 mg/kg of phenobarbital that failed to bring the episode under control were administered a bolus of midazolam (200 mg/kg iv) followed by a con- tinuous infusion at 1 mg/kg/min. The dose was in- creased every 15 min until the episode of seizure was brought under control. Time to control seizures, infu- sion rate, and side-effects were monitored. Results: The mean age of the patients was 22.8 yrs (range 16 yrs to 73 yrs; 5 females and 6 males). In ten of the patients, seizures were completely controlled in a mean time of 2.1 hrs (range 0.4 hrs to 4.5 hrs), with an infusion rate of 8.4 mg/kg/min (range 3 to 12). In one patient seizures did not stop. None of the patients had clinically important changes in blood pressure, heart rate, oxygen saturation or respiratory status at- tributable to the use of midazolam. The mean time to full consciousness for patients after stopping the in- fusion was 1.6 hrs (range 2 to 8.5). Conclusion: Midazolam is an effective and safe drug to control RGSE and may represent a substantial im- provement over current therapeutic approaches such as pentobarbital anesthesia.

Objective: We have confirmed by PCR-amplification of the DNA polymerase gene, three cases of Herpes Sim- plex encephalitis (HSE) with atypical clinical symp- toms. Methods: Cerebrospinal fluid (CSF) samples were col- lected by lumbar puncture during the course of test- ing from 23 patients suspected to have viral encepha- litis based on commonly encountered symptoms, cy- tochemical analysis and neurological testing. PCR was done on CSF using specific primers that amplify a 290 base pair sequence on the DNA polymerase gene com- mon to both HSV-1 and HSV-2 strains. Results: Only 3 of the 23 CSF samples collected showed the expected amplicon size on the target se- quence. One case had conventional symptoms of en- cephalitis and 2 cases showed atypical symptoms from the conventional ones. All 3 patients recovered after administration of acyclovir. Fourteen PCR-negative patients were shown to have non-HSE viral encephali- tis and the remaining 6 patients were shown later to have other neurological diseases. Conclusion: PCR was efficient in elucidating the atypi- cal cases of HSV encephalitis.