Objective(s): The purpose of this study was to investigate the change in plasma anandamide (AEA) levels throughout the normal menstrual cycle, and to analyze the relationship among AEA, sex steroids and gonadotrophins. Materials and Methods: The patients were fertile women with normal menstrual cycle, proposed to get in vitro fertilization (IVF) treatment due to oviduct obstruction or male infertility. Patients were divided into two groups, cross-sectional (n=79) and longitudinal (n=10). The plasma AEA levels were examined by the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) system. The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P) were measured by chemiluminescence. Results: The AEA levels in the late follicular phase were slightly higher than those in the early follicular phase. Subsequently, the AEA levels peaked at the time of ovulation in both two cohorts. Finally, the lowest AEA levels were measured in the luteal phase. Moreover, there were highly significant positive correlations between the plasma AEA concentration and the serum levels of FSH, LH and E2, whereas the AEA level was not correlated with P during the normal menstrual cycle. Conclusion: Our observations reveal a dynamic change in the plasma AEA level, which is closely associated with the levels of gonadotrophin and sex steroid hormones, suggesting that the hormones may be involved in the regulation of AEA levels during the menstrual cycle. Our studies help to design new strategies to improve implantation and treatments for reproductive diseases.

Introduction: Anandamide (AEA) has shown a wide spectrum of pharmacological activities including the effects against the peptic ulcer, meanwhile, the poor solubility or short half-life may negatively affect the effectiveness of this valuable cannabinoid. Based on the superior properties of carbon nanotubes (CNTs) for controlled drug delivery, we aimed to prepare AEA-CNTs complex and evaluate its therapeutic potential in an experimental model of gastric ulcer. Methods: Amino-functionalized multi-walled CNTs-AEA (MWCNTs-AEA) complex was prepared using COOH-MWCNTs and then characterized by Fourier transform infrared spectroscopy and transmission electron microscopy. Gastric ulcer was induced by water immersion and restrain stress (WRS) for 3. 5 and 6 h in rats and the gastric lesion and oxidative stress were evaluated. Results: AEA at higher doses reduced the gastric ulcer area and malondialdehyde content and elevated glutathione level and superoxide dismutase and catalase activities after 3. 5-h WRS but it was ineffective after 6-h WRS. MWCNTs-AEA complex showed therapeutic effects after both 3. 5-and 6-h WRS. Conclusion: Aminated MWCNTs are suitable carriers for AEA as they provide longer lasting effects for this cannabinoid. The antioxidant mechanism may be involved in the gastroprotective effects of MWCNTs-AEA complex.

Introduction: The therapeutic potential of anandamide (AEA) for the neurological disorders may be negatively affected by its short half-life or poor solubility. The superior properties of carbon nanotubes (CNTs) for controlled drug delivery, prompted us to design AEA-CNTs complex and assess its effect in in vitro model of ischemic stroke.Methods: In this experimental study, a multi-walled CNTs (MWCNTs) -AEA complex was prepared using amino-functionalized COOH-MWCNTs and characterized by Fourier transform infrared spectroscopy and transmission electron microscopy. PC12 cells in the presence of AEA (0.5, 1, 2 mg/ml), acid- or amine-modified MWCNTs, or MWCNTs-AEA complex (2, 5, 8 mg/ml) were exposed to 1 and 3 h oxygen-glucose deprivation (OGD) followed by 24 h re-oxygenation. In vitro cytotoxicity and oxidative stress were evaluated using three-way ANOVA.Results: AEA immobilization on the aminated MWCNTs was confirmed. OGD significantly reduced cell viability (P<0.001). After 3 h of OGD induction, COOHMWCNTs showed higher cytotoxicity than other MWCNTs (P<0.05, P<0.01, P<0.001) and MWCNTs-AEA was more protective than AEA alone (P<0.05, P<0.01). OGD increased malondialdehyde (MDA) and decreased glutathione (GSH) and superoxide dismutase (SOD) (P<0.001). Following 1-h OGD, AEA dose-dependently reduced MDA (P<0.001), and elevated GSH (P<0.05, P<0.01) and SOD (P<0.05, P<0.01), but AEA was ineffective following 3-h OGD (P>0.05). MWCNTs-AEA complex was effective at both time points (MDA and GSH: P<0.01, P<0.001, SOD: P<0.05, P<0.01, P<0.001). This nanostructure was more effective than AEA following longer exposure periods to OGD insult (P<0.05, P<0.01, P<0.001).Conclusion: Aminated MWCNTs are suitable carriers for AEA and provide longer -lasting effects against OGD insult.

Background: Aerobic exercise, ozone therapy and cell therapy have each been independently proposed as treatments for osteoarthritis. Therefore, the present study aimed to investigate the effect of aerobic exercise with ozone and cell therapy on serum levels of anandamide concentration in osteoarthritis rats. Materials and Methods: Forty-five male rats were randomly divided into 9 groups, including 1 group: healthy control, 2-patient control, 3-exercise, 4-ozone therapy, 5-cell therapy, 6-exercise+ozone therapy, 7-exercise+cell therapy, 8-ozone+cell therapy and 9-ozone+cell therapy+exercise. Cell groups alone and combination cell therapy received 1×106cells/kg, and ozone groups alone and ozone combination therapies received 20μ, g/ml of ozone in 3 replications before exercise. The training program consisted of running on a treadmill at a speed of 16 meters per minute for 8 weeks. Forty-eight hours after the last exercise session, serum levels of anandamide were measured by Elisa. Results: Findings showed that the serum level of anandamide in the osteoarthritis patient group was significantly reduced compared to the healthy group that exercise and ozone therapy led to a significant increase in the serum anandamide level,but cell therapy could not have a significant effect on increasing serum levels of anandamide. The peak of this increase was seen in ozone+cell therapy and the interaction of all three interventions simultaneously. Conclusion: Although aerobic exercise and ozone therapy each independently have a positive effect on anandamide in people with osteoarthritis, but the interaction of all three interventions simultaneously with ozone+cell therapy is more effective.