Background and objectives: In CHRONOPHARMACOLOGY the biological rhythm variations caused by drug administration is assessed. Evaluation of the time of drug administration and the qualitative and quantitative effects of reactions to drugs is called chronopharmacodynamics. In this study, we assessed the chronopharmacodynamics of intrathecal co-administration of sufentanyl and bupivacaine in surgical operations of lower extremities.Methods: In 2006, patients aged 20-50 with ASA physical status of I and II, who underwent surgical operation of lower extremities were entered into this prospective study. The patients received a slow intrathecal injection of 10mg sufentanyl and 15 mg bupivacaine into subarachnoid of third and fourth lumbar spaces in 30 seconds. After the operation, the time of first pain sensation and the visual analogue scale (VAS) score, as the measure of severity of pain, were recorded.Results: 115 patients were studied in this project. The pain-free interval was considered as the time between injection and patient’s demand for pain relief. This interval was 746 (± 322) minutes. The average score of pain severity on VAS at the time of demand for pain relief was 24.7 (± 9.3). The average pain-free duration in patients injected about noon or at midnight was significantly longer than the pain-free interval of other patients.Conclusion: The results show that intrathecal co-administration of sufentanyl and bupivacaine at noon or midnight (conforming to the circadian rhythm) causes better pain-relief with longer duration in comparison with other times of the day or night.

To investigate the chronopharmacological effects of growth hormone on executive function and the oxidative stress response in rats. Materials and Methods: Fifty male Wistar rats (36-40 weeks old) had ad libitum access to water and food and were separated into four groups: diurnal control, nocturnal control, diurnal GH-treated, and nocturnal GH-treated animals. Levels of Cu, Zn superoxide dismutase (Cu, Zn-SOD), and superoxide release by spleen macrophages were evaluated. For memory testing, adaptation and walking in an open field platform was used. GH-treated animals demonstrated better performance in exploratory and spatial open-field tests. Results: The latency time in both GH-treated groups was significantly lower compared with the latency time of the control groups. The diurnal GH treatment did not stimulate superoxide release but increased the CuZn-SOD enzyme levels. The nocturnal GH treatment did not influence the superoxide release and CuZn-SOD concentration. GH treatment also resulted in heart atrophy and lung hypertrophy. Conclusion: Growth hormone treatment improved the performance of executive functions at the cost of oxidative stress triggering, and this effect was dependent on the circadian period of hormone administration. However, GH treatment caused damaging effects such as lung hypertrophy and heart atrophy.

Background: Knowledge of CHRONOPHARMACOLOGY and disease rhythms may provide additional therapeutic options for diabetic complications. The present research investigates the effect of chronomodulated alpha-lipoic acid/ nifedipine/ glimepiride combination in oxidative stress-mediated testicular toxicity in diabetic rats. A total of seven rat groups were used for the following study. Methods: A group of non-diabetic rats and a group of diabetic rats were treated with 1 mL/kg of water to serve as normal and diabetic controls respectively. All other groups were diabetic and received 10 mg/kg glimepiride at 20: 00h. Additionally, groups four to seven were treated with 20 mg/kg nifedipine at 08: 00h while groups five to seven received additional treatments with alpha-lipoic acid (ALA) at 08: 00h, 14: 00h and 20: 00h respectively. Rats were euthanized after four weeks of oral treatment and the epididymis and testis were excised for assessment of fertility markers. Serum testosterone and relative testes weights were measured. The right testes were preserved in phosphate buffer for cholesterol and antioxidant assay while the left testes were fixed in formalin for histological studies. Results: All rat groups treated with ALA showed significantly (p ≤,0. 01) better prognostic values for all markers assessed compared to the diabetic control group. Those treated with ALA at 20: 00h showed better prognosis (p ≤,0. 05) than treatment at other time points, showing values similar to the normal. Conclusion: Time-dependent triple therapy with alpha-lipoic acid, nifedipine and glimepiride mitigates oxidative stress-mediated testicular injury in diabetic rats and its clinical benefits may be explored using equivalent circadian timing in men.