Ersin Yaris

Protective effect of melatonin against fractionated irradiation-induced epiphyseal injury in a weanling rat model

Abstract: The effects of melatonin, a free‐radical scavenger and a general antioxidant, on radiation‐induced growth plate injury have not been studied previously. The purpose of this study was to determine the potential benefits of sparing longitudinal bone growth by fractionated radiotherapy alone compared with pretreatment with melatonin that provides differential radioprotection of normal cells. Weanling 4‐wk‐old (75–100 g) male Sprague–Dawley rats were randomly assigned to one of three groups: Group R received fractionated radiation alone (n = 8); groups M5 (n = 8) and M15 (n = 7) received 5 or 15 mg/kg melatonin prior to fractionated radiation, respectively. The distal femur and proximal tibia in the right leg of each animal were exposed to a therapeutic X‐irradiation dose (25 Gy total in three fractions) with the contralateral left leg as the non‐irradiated control. Melatonin was administered intraperitoneally to the animals 30 min before radiation exposure. Six weeks after treatment, the rats were killed and the lower limbs disarticulated, skeletonized, radiographed, and bone growth was calculated based on measurement of the bone lengths. Fractionated radiation resulted in a mean percent overall limb growth loss of 41.2 ± 9.5 and a mean percent overall limb discrepancy of 11.2 ± 2.2. The administration of 5 or 15 mg/kg melatonin before each of the three fractions of radiotherapy reduced the mean percent overall limb growth loss to 33.9 ± 5.8 and 32.2 ± 4.5, respectively, and the mean percent overall limb discrepancy to 9.4 ± 1.6 and 8.9 ± 1.1, respectively; these values were significantly different compared with irradiation alone (range: P = 0.01–0.04). When compared with Group R, the growth arrest recovered by 5 or 15 mg/kg melatonin was 19.7 and 24.1% for the tibia, 7 and 18.6% for the femur, and 17.7 and 21.8% for the total limb, respectively. These results support further investigation of melatonin in combination with fractionation for potential use in growing children requiring radiotherapy to the extremity for malignant tumors.

Effect of gender on antinociceptive effect of paroxetine in hot plate test in mice.

PURPOSE Many studies have reported both a gender difference in the rates of depression and its treatment by using any of the widely used antidepressant drug groups. Some studies suggest that females respond more poorly to tricyclic antidepressants than males and appear to respond better to selective serotonin reuptake inhibitors (SSRI). There is no study investigating the analgesic/antinociceptive effects of antidepressant drugs on the basis of gender difference. In this study, we aimed to investigate the antinociceptive effect of paroxetine on the basis of gender difference. METHODS The antinociceptive effect of paroxetine was tested using hot plate test in Balb/c mice (30-40 g). The animals were divided into eight groups on the basis of gender. FINDINGS While paroxetine did not induce an antinociceptive effect in both sex at a dose of 1 mg kg(-1), it showed significant antinociceptive effects in both sex at a dose of 5 or 10 mg kg(-1). None of the doses of paroxetine revealed a gender difference in its antinociceptive action. CONCLUSION There are several studies showing positive or negative evidence on the gender difference of paroxetines antidepressant effect, but in the literature there is no study about the gender difference of paroxetines or any other SSRI drugs antinociceptive effect. In conclusion, our results do not show any gender difference in antinociceptive effect of paroxetine that may be important especially when it would be used as an adjuvant agent in some painful conditions.

Psychotropic drugs in pregnancy: a case-control study

Psychotropic drug exposure during pregnancy is a common problem. Among the 601 cases exposed to drugs during pregnancy, who were followed by our Toxicology Information and Follow-up Service, 124 cases had used psychotropic drugs for depression, anxiety, or psychotic disorders. As the control group, 248 women, who did not use any drugs were selected. Of the 124 cases, 80 (64.5%) had healthy babies, and 17 (13.7%) decided to terminate the pregnancy. Spontaneous abortions, intrauterine death (in the 38th week) and premature deliveries were observed in the 9 (7.3%), 1 (0.8%) and 3 (2.4%) cases, respectively, in the drug exposure group. Pregnancies of the 14 (11.3%) cases were continuing during the preparation of this manuscript. Of the 248 controls, 151 (60.9%) had healthy babies, 9 (3.6%) experienced spontaneous abortion and 3 (1.2%) decided to terminate their pregnancies, 3 (1.2%) had premature deliveries, and we observed one (0.4%) congenital abnormality, 81 (32.7%) cases were still pregnant. Odds Ratio (95% confidence interval) for spontaneous abortion was found to be 1.35 (1.27-11.82) in the cases exposed to psychotropic drugs (P=0.02). No developmental problems were observed in the babies followed for 12 months. These data may give information about the early- but not the late-term effects of psychotropic drugs used in pregnant women.

Paroxetine inhibited the relaxations induced by EFS in mice corpus cavernosum: is it a NOS inhibition?

Selective serotonin reuptake inhibitors are used in the treatment of psychiatric disorders but are associated with high incidence of sexual dysfunction such as ejaculation disorders by sertraline and fluoxetine, erection disorders by paroxetine. The aim of this study is to evaluate the effects of paroxetine, sertraline and fluoxetine on relaxation of smooth muscle of corpus cavernosum on the basis of nitric oxide (NO). Male mice were killed by cervical dislocation and their penile tissues were immediately removed. The tissues were incubated in organ baths containing Krebs solution at 37°C and bubbled with 95% O2 and 5% CO2. The corpus cavernosum strips were contracted with 10−5 m phenylephrine (PHE) and relaxed with either paroxetine, sertraline, fluoxetine (10−8–10−4 m) or electrical field stimulation (EFS). The effects of paroxetine, sertraline and fluoxetine were examined on EFS‐induced relaxations. While paroxetine did not show any effect on the corpus cavernosum strips precontracted with PHE, sertraline and fluoxetine caused a relaxation at concentrations of 3 × 10−5–10−4 m. The relaxations induced by sertraline and fluoxetine were completely abolished by l‐NAME, but not d‐NAME. The relaxations induced by EFS could be inhibited by l‐NAME but not d‐NAME. Paroxetine inhibited the relaxations at high concentrations. l‐Arginine potentiated the relaxations induced by EFS; however in the presence of paroxetine these relaxations were not observed. In contrast, sertraline (10−8–10−5 m) and fluoxetine (10−8–10−5m) increased the relaxations induced by EFS. Sertraline and fluoxetine seem to be releasing some relaxing factor(s) and this factor may be NO. Paroxetine probably has a NOS inhibitory activity either on nNOS or eNOS, in contrast to sertraline and fluoxetine.

Story of benzene and leukemia: epidemiologic approach of Muzaffer Aksoy.

Story of Benzene and Leukemia: Epidemiologic Approach of Muzaffer Aksoy: Fusun Yaris, et al. Karadeniz Technical University, School of Medicine, Department of Family Medicine, Turkey—In 1974, Professor Muzaffer Aksoy established a link to leukemia in humans as a result of occupational exposure to benzene. The aim of this study is to evaluate his epidemiological approach for his investigation on the effects of benzene and to bring attention to the benzene problem in Turkey. Dr. Aksoy observed that a large group of leukemic patients were shoemakers, or they worked in leather manufacturing. In the 1960s, benzene was a popular solvent in the leather industry. Dr. Aksoy conducted a field investigation in Gedikpasa‐ Istanbul, where the shoemakers worked so that he could draw his key observations from actual environmental conditions. With a gas detector, he found the concentration of benzene in these work places to be 150–210 ppm and up to 650 ppm on rare occasions. He performed an epidemiological study and health education among 28,500 shoe, slipper and handbag workers during the period from 1967 to 1974. He published these data, establishing an association between benzene and leukemia. The incidence of leukemia among the shoe workers was decreased by screening, health education, and legislative actions in Turkey, but it began to increase again because of lack of an occupational health policy and underestimation of the problem. These results suggest the importance of primary prevention of occupational cancers. Dr. Aksoys epidemiologic approach may highlight the necessity for detailed investigations of the occupational status of patients who need medical aid in order to diagnose the real underlying factor.