The evaluation of analgesic effects of milnacipran and sertraline in tail-flick test.

INTRODUCTION: Antidepressant drugs are used in the treatment of pain as an adjuvant or alone. It has been shown that antidepressant drugs have analgesic effects in various diseases (diabetic neuropathy, low back pain, cancer pain etc.) Sertraline is a potent serotonin re-uptake inhibitor. Some antidepressant drugs inhibited both of the reuptake of serotonin and of noradrenaline. These drugs are called serotonin-noradrenaline re-uptake inhibitors (SNRIs). Milnacipran is a serotonin-noradrenaline re-uptake inhibitor. We have studied the analgesic effects of sertraline and milnacipran after acute and chronic application in tail-flick test in mice. METHODS: The analgesic effects of milnacipran (10, 30, 50 mg/kg) and sertraline (10, 20, 50 mg/kg) were measured after acute and chronic application in tail flick test. The analgesic effects of milnacipran (30 mg/kg) or sertraline (50 mg/kg) were evaluated after the application of L-NAME (10 mg/kg), naloxone (5 mg/kg), prazosin (1 mg/kg), ondansetron (0.1 mg/kg) in tail flick test. RESULTS: Milnacipran (30 mg/kg) and sertraline (50 mg/kg) produced statistically significant analgesic effect compared to their control values after acute and chronic application in tail-flick test. The analgesic effects of both milnacipran (30 mg/kg) and sertraline (50 mg/kg) in the presence of L-NAME (10 mg/kg), naloxone (5 mg/kg), ondansetron (0.1 mg/kg) and prazosin (1 mg/kg) were inhibited in tail-flick test. CONCLUSION: These results indicate that the analgesic effects of milnacipran and sertraline are related to nitrergic, opioidergic, serotonergic and adrenergic system (Fig. 8, Ref. 23).

Hormonal and histological changes in the ovaries with high-doses of methylprednisolone administration for acute spinal cord injury: an experimental study.

This study was conducted to investigate the hormonal and histological changes in the ovaries with high doses of methylprednisolone administration for acute spinal cord injury (SCI). Group I (trauma group, eight rats) were subjected to laminectomy and SCI but received no treatment. Group II (steroid group, eight rats) were subjected to SCI and received methylprednisolone (30 mg/kg, intraperitoneally). Group III (control group, six rats) underwent a sham operation without trauma and treatment. Malondialdehyde (MDA) levels were significantly decreased in Group II (p < 0.05). The scores of histopathological damage of the ovaries in the three groups were found to be statistically comparable (p > 0.05). Serum anti-Müllerian hormone (AMH) levels in the steroid group was significantly lower compared with the control group (p < 0.05). High-dose methylprednisolone administration may effect ovarian reserve with reversible ovarian damage and can resolve lipid peroxidation in rats with spinal cord injury.

The evaluation of analgesic effects of simvastatin, pravastatin and atorvastatin in hot plate test.

OBJECTIVES: Simvastatin, pravastatin and atorvastatin have been evaluated whether to have analgesic effects in mice in hot plate test. MATERIALS AND METHODS: Simvastatin (5, 10, 30 mg/kg), pravastatin (5, 10, 30 mg/kg) and atorvastatin (5, 10, 30 mg/kg) were administered acute and chronically by oral gavage in mice. Control (pretreatment value) and posttreatment (after drugs application) values in 60th and 120th minutes were measured in hot-plate test. RESULTS: All three drugs at 10, 30 mg/kg doses produced analgesic effects compared with their control values in 60th and 120th minutes on acute and chronic application in mice. The analgesic effects of drugs were evaluated after the application of L-nitro arginine methyl ester (L-NAME) (10 mg/kg) or naloxone (0.5 mg/kg). L-NAME (10 mg/kg) has no effect compared to the control value on both minutes. The analgesic effects of both atorvastatin (30 mg/kg) and simvastatin (30 mg/kg) in the presence of L-NAME (10 mg/kg) were not inhibited. However, the analgesic effect of pravastatin (30 mg/kg) in the presence of L-NAME (10 mg/kg) was inhibited significantly on both minutes (p < 0.05). Naloxone (0.5 mg/kg) has no effect compared to the control value on both minutes. The analgesic effect of atorvastatin (30 mg/kg) in the presence of naloxone (0.5 mg/kg) was partially (43%) but significantly inhibited only on 60th minute (p < 0.05). The analgesic effect of pravastatin (30 mg/kg) in the presence of naloxone (0.5 mg/kg) was partially (48-40%) but significantly inhibited on both minutes (p < 0.05). However, the analgesic effect of simvastatin (30 mg/kg) in the presence of naloxone (0.5 mg/kg) was inhibited significantly on both minutes (p < 0.05). CONCLUSIONS: These finding indicated that the analgesic effect of pravastatin was related to nitrergic systems and partially opioidergic system; analgesic effect of simvastatin was related to opiodergic system in hot plate test. However, the analgesic effect of atorvastatin was not directly related to both system.

The Effect of High Dose Methylprednisolone on Experimental Ovarian Torsion/Reperfusion Injury in Rats.

Purpose: Aim of the study was to evaluate the effects of high dose methylprednisolone on experimental ovarian torsion-detorsion injury in rats. Materials and Methods: Twenty-two Sprague-Dawley rats were randomly divided into three groups. Group 1 (ischemia group, 8 rats) were subjected to left adnexal torsion for 2 h but received no treatment. Group 2 (methylprednisolone group, 8 rats) were subjected to left adnexal torsion for 2 h and received methylprednisolone (30 mg/kg, administered intraperitoneally) at the end of a 2-hour ischemic period followed by 24-hour reperfusion. Group 3 (control group, 6 rats) underwent a sham operation with no adnexal torsion and no treatment. Results: Serum malondialdehyde (MDA), ischemia-modified albumin (IMA), total oxidant status (TOS) and tissue MDA levels were increased in Group 1 rats; total antioxidant status (TAS) levels and oxidative stress index (OSI) were significantly decreased compared with rats in Groups 2 and 3 (p < 0.05). MDA, IMA, TOS and tissue MDA levels were lower and TAS levels and OSI were higher in Group 3 compared to Group 2. Ovarian damage scores in Group 1 were significantly higher compared with Groups 2 and 3 (p < 0.05). Conclusion: This study demonstrated that high dose methylprednisolone reduces ovarian ischemia/reperfusion injury.

Long-term effects of the levonorgestrel-releasing intrauterine system on serum lipids and the endometrium in breast cancer patients taking tamoxifen.

OBJECTIVE: To investigate the long-term effects of a levonorgestrel-releasing intrauterine system on the endometrium and lipid profile of breast cancer patients taking tamoxifen. STUDY DESIGN: A total of 142 postmenopausal women taking tamoxifen were included in the study. A levonorgestrel-releasing intrauterine system was fitted to 70 women in the study group; a further 72 women acted as the control group. All women were followed for 36 months. Serum lipids were measured at the beginning and at the end of 36 months. Endometrial biopsies were obtained by hysteroscopy at the beginning and at the end of the 36th month in both groups. RESULTS: After 36 months, there were minor changes in serum lipids, fewer endometrial polyps and no endometrial hyperplasia in the study group compared to the control group. CONCLUSION: The levonorgestrel-releasing intrauterine system does not affect serum lipid levels significantly and may prevent the increased risk of endometrial polyps and hyperplasia associated with the use of tamoxifen in women with breast cancer. This may reduce the need for investigation of side-effects in women taking tamoxifen and also reduce patient discomfort while improving treatment adherence.

Nitric oxide in postmenopausal women taking three different HRT regimens.

OBJECTIVE: To search and compare the effects of three different HRT regimens on nitric oxide levels of postmenopausal women. METHODS: Four groups of postmenopausal women were included in this prospective, randomised, placebo controlled study. 34 women used 0.625 mg conjugated estrogen continuously combined with 5 mg medroxyprogesterone acetate, 32 women used 2.5 mg tibolone, 26 women used 50 mcg transdermal estrogen alone continuously and 32 women used placebo for 12 months. Before the treatment and after 1 year, serum NO (nitrate/nitrite) and some other biochemical parameters were evaluated. RESULTS: All HRT using groups had increased serum nitric oxide levels significantly compared to placebo group and also there was not any difference among three HRT using groups concerning to increases in nitric oxide levels. CONCLUSION: Both conjugated estrogen combined with continuous progestin and transdermal estrogen alone and also tibolone increases serum nitric oxide levels of postmenopausal women equally for 12-months of treatment.

Urinary tract infections in unplanned pregnancies and fetal outcome.

AIM: Many pregnant women are exposed to antibiotics for urinary tract infections during pregnancy. Our aim is to bring attention to antibiotherapy in unplanned pregnancies. METHOD: Among the 511 cases followed by our 'Toxicology Information and Follow-up Service' for drug exposure during pregnancy, 101 cases, unaware of their pregnancy, had been prescribed antibiotics and urinary antiseptic drugs in the first trimester of their unplanned pregnancies. The data on the outcome of these pregnancies and the babies were evaluated in this study. RESULTS: Of the 511 cases, 101 pregnant women were exposed to nine kinds of drugs. Seventy-five cases had healthy babies; two had babies with major malformations; one had a baby with congenital hypothyroidism; five had spontaneous abortions; and eight cases underwent induced abortions. The outcomes of eight pregnancies are unknown. Two pregnancies are still continuing without any problem. One baby had a fetal renal anomaly; however, the physical examination did not reveal any other malformations. The baby died 4 hours after delivery. Another baby had atrial septal defect, a major malformation, and one baby had congenital hypothyroidism. CONCLUSION: Urinary tract infection is one of the most frequently seen complications of pregnancy. Our study indicated that the possibility of pregnancy should be considered when prescribing antibiotics for urinary tract infections in women of reproductive age.

Intracystic application of mebendazole solution in the treatment of liver hydatid disease. Preliminary report of two cases.

Mebendazole, a derivate of benzimidazole, is commonly used for the treatment of hydatid disease in patients at high operative risk and/or to prevent secondary hydatidosis. In this study, 2 cases of liver hydatid disease, in which mebendazole was used both orally and for intracystic application are presented. These cases have been treated by percutaneous drainage and videolaparoscopic methods. Mebendazole solution at a concentration of 2.4 micrograms/ml was injected into the cyst. For a period of 6 months 50 mg/kg/day oral treatment was given. At the end of a 6- to 9-month period, the total recovery was observed. This is the first report of mebendazole pair-treatment in the literature.