The Possible Antidiabetic Effect of Ficus carica L. Tablet on lloxan-Induced Diabetes Model in Rats

BACKGROUND: Fig leaves are reported to have an effect on reducing blood glucose levels. However, the use of fresh leaves makes the effects obtained is not measurable and efficient. AIM: The purpose of this research was to determine the antidiabetic potential of ethanol extract of fig leaves and to optimize tablet dosage formulations. METHODS: Four tablet formulas were made using the wet granulation method. Formula I (FI), Formula I (FII), and Formula III (FIII) groups to give a tablet of ethanol extract of fig leaves with a dose of 40 mg, 60 mg, and 80 mg and placebo treatment group. There were eight groups of male rats strain Wistar treated as follows: Normal control, negative control, positive control (metformin tablets), basis group, placebo treatment group, F1, F2, and F3 groups. The antidiabetic activity was evaluated from a decrease in rat blood glucose levels. Previously, rats were induced first using alloxan 150 mg/kg intraperitoneally to damage β-pancreatic cells so that the rats could experience increased blood glucose levels. After giving treatment to each group for 14 days, a rat blood sample was then taken on days 9 and 14, which were then analyzed by the GOD PAP method with readings carried out using a spectrophotometer with a wavelength of 500 nm. RESULTS: The average weight (mg) of FI tablets (617.8 ± 3.21%), FII (629.35 ± 8.16%), and FIII (643.6 ± 6.21%), and placebo tablet (666.45 ± 4.36%). As for the uniformity of size, all formulas have a diameter of 0.9 ± 0.0 (cm). For the hardness values of FI (5.7 kg), FII (1.31 kg), and FIII (3.09 kg), placebo tablet (2.98%). The value of friability FI (1.42%), FII (11.8%), and FIII (0.84%), placebo tablet (1.16%). While the disintegration time of FI (11.02 min), FII (10.10 min), and FIII (17.00 min), placebo tablet (12.23%). As for the uniformity of size, all formulas have a diameter of 0.9 ± 0.0 (cm). Whereas the dissolution rate (DE45) of each formulation decreased with increasing dose of extract, FI (73.73%), FII (74.80%), and FIII (69.80%). The treatment group of the ethanol extract of fig leaves at a dose of 40 mg, ethanol extract of fig leaves at a dose of 60 mg, and ethanol extract of fig leaves at a dose of 80 mg could reduce rats’ blood glucose levels with statistically significant results (p < 0.05) compared to negative group. When it was compared to the positive group, it had significant results with a statistical value (p < 0.05). CONCLUSION: Ethanol extract of fig leaf tablets had a significant effect on lowering rats’ blood glucose levels.

493 Weight Loss With FT218, a Once-Nightly Sodium Oxybate Formulation for the Treatment of Narcolepsy: Post Hoc Analysis From REST-ON

Introduction Patients with narcolepsy are more likely to be obese compared with healthy controls. FT218 is an investigational once-nightly sodium oxybate formulation for the treatment of narcolepsy. Here, we report on changes in weight-related clinical values with FT218 treatment in patients with narcolepsy. Methods This was a randomized, double-blind, placebo-controlled multicenter study in patients with narcolepsy ≥16 years old. Patients were not excluded based on baseline weight or body mass index (BMI). Patients were randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Weight and BMI were measured at baseline and study end. LS mean difference in BMI between FT218 and placebo was analyzed using analysis of covariance. Results A total of 107 patients received FT218 and 105 patients received placebo. At baseline, mean (SD) weight was 81.2 (20.8) kg in the FT218 treatment group and 82.1 (22.5) kg in the placebo treatment group. At end of study (week 13), mean (SD) weight was 80.9 (21.9) kg in the FT218 treatment group and 82.25 (21.6) in the placebo treatment group. At week 13, mean (SD) change in weight from baseline was –1.29 (3.6) kg for FT218 and 0.19 (2.6) kg for placebo; 17.5% of patients receiving FT218 vs 3.8% of patients receiving placebo had ≥5% weight loss. At baseline, mean (SD) BMI was 28.1 (7.8) kg/m2 in the FT218 treatment group and 28.2 (6.6) kg/m2 in the placebo treatment group. At study end (week 13), LS mean (SE) change from baseline in BMI was ‒0.51 (0.13) kg/m2 for patients receiving FT218 and 0.08 (0.13) kg/m2 for patients receiving placebo (LS mean difference [95% CI], ‒0.59 [‒0.95 to ‒0.23]; P=0.001). FT218 was generally well tolerated. Conclusion Patients receiving FT218 experienced a significantly greater decrease in weight and BMI vs placebo. These results suggest that treatment with once-nightly FT218 may provide weight-related benefit for patients with narcolepsy and comorbid weight gain. Support (if any) Avadel Pharmaceuticals

Oxygen Hyperbaric Exposure Induces GLUT4 Expression Reduction and No Folliculogenesis Alterations in Rat PCOS with Insulin Resistance Model

Objectives: To know effect of hyperbaric oxygen therapy to GLUT4 expression and folliculogenesis in rat PCOS with insulin resistent model.Materials and Methods: this is an analytic experimental study used 30 rats induced by testosterone propionate injection 1 mg/100 g body weight daily for 28 consecutive days as a PCOS with insulin resistent model. Animal models divided into 3 groups. Negative control was not given treatment, positive control was given placebo. Treatment group was given hyperbaric oxygen 2.4 ATA 90 minutes 2x5 days. GLUT4 expression determined by immunohystochemistry to m. Gastrocnemius. Hematoxylin Eosin staining to rat ovaries were performed to know differentiation in folliculogenesis. The results were then compared.Results: There were significant decrease of GLUT4 expression in treatment group (mean0,84+0,47)compared to negative and positive control (mean3,96+3,16and3,36+2,17). There were no different folliculogenesis in these groups.Conclusion: Hyperbaric oxygen 2.4 ATA 90 minutes 2x5 days induce decrease of GLUT4 expression and no alterations in folliculogenesis in rat PCOS with insulin resistent model, therefore can not yet be used as alternative therapy in PCOS.

Abstract 3656: Estradiol Improves Neural Functional Recovery After Nerve Injury by Reducing Inhibition of the Hedgehog-signaling Pathway

Background: Prior data indicate that estradiol (E2) favorably affects neovascularization in injured tissue, and that Sonic Hedgehog (Shh)-induced neovascularization is critical for nerve regeneration; however, little is known about the relationship between E2 and Shh signaling. We tested the hypothesis that E2 potentiates nerve regeneration via Shh-activated neoangiogen-esis. Methods and Results: Ovariectomized mice were subjected to unilateral sciatic nerve crush injury and treated with either E2 (via locally administered biodegradable polymer) or placebo (polymer alone). E2 treatment resulted in greater functional recovery of the nerve as evaluated by both exercise duration (P<0.05) and motor nerve conduction velocity (P<0.05), and intraneural vascularity was significantly higher in E2-treated animals than in the placebo-treatment group (P<0.05). Analyses of mRNA expression in the injured nerves of placebo-treated mice showed that the Shh pathway was activated immediately after injury, but Shh expression declined substantially within 7 days. Shh activation persisted in the E2-treatment group; Shh expression on day 7 was greater in E2-treated animals than in the placebo-treatment group (P<0.05). The expression of Hedgehog-interacting protein (HIP), an endogenous Shh inactivator, was significantly downregulated 24 hours after E2 treatment, and HIP downregulation was attenuated by the E2-receptor blocker ICI, suggesting that E2 augments Shh signaling both my enhancing Shh expression and by inhibiting HIP. Inhibition of HIP expression by E2 was also observed in vitro in Schwann cells and endothelial cells. The expression of Ptc1 (Shh receptor) and Gli1 (a downstream target of Shh) was evaluated in Ptc1-LacZ and Gli1-LacZ mice after nerve-crush injury. X-gal staining demonstrated that E2 treatment upregulated both Ptc1 and Gli1 expression within 3 days of surgery. Conclusions: E2 accelerates the functional recovery of injured nerves by enhancing angiogenesis. We propose that these effects occur in part through the inhibition of the Shh inactivator HIP, thereby preserving Shh activity after nerve injury. These findings may have identified a novel regulatory mechanism for nerve repair via E2-enhaced, Shh-mediated angiogenesis.

Phase II, Randomized, Double-Blind, Placebo-Controlled Studies of Ruprintrivir Nasal Spray 2-Percent Suspension for Prevention and Treatment of Experimentally Induced Rhinovirus Colds in Healthy Volunteers

ABSTRACT Human rhinovirus (HRV) infections are usually self-limited but may be associated with serious consequences, particularly in those with asthma and chronic respiratory disease. Effective antiviral agents are needed for preventing and treating HRV illnesses. Ruprintrivir (Agouron Pharmaceuticals, Inc., San Diego, Calif.) selectively inhibits HRV 3C protease and shows potent, broad-spectrum anti-HRV activity in vitro. We conducted three double-blind, placebo-controlled clinical trials in 202 healthy volunteers to assess the activity of ruprintrivir in experimental HRV infection. Subjects were randomized to receive intranasal ruprintrivir (8 mg) or placebo sprays as prophylaxis (two or five times daily [2×/day or 5×/day] for 5 days) starting 6 h before infection or as treatment (5×/day for 4 days) starting 24 h after infection. Ruprintrivir prophylaxis reduced the proportion of subjects with positive viral cultures (for 5×/day dosing groups, 44% for ruprintrivir treatment group versus 70% for placebo treatment group [P = 0.03]; for 2×/day dosing groups, 60% for ruprintrivir group versus 92% for placebo group [P = 0.004]) and viral titers but did not decrease the frequency of colds. Ruprintrivir treatment reduced the mean total daily symptom score (2.2 for ruprintrivir treatment group and 3.3 for the placebo treatment group [P = 0.014]) by 33%. Secondary endpoints, including viral titers, individual symptom scores, and nasal discharge weights, were also reduced by ruprintrivir treatment. Overall, ruprintrivir was well tolerated; blood-tinged mucus and nasal passage irritation were the most common adverse effects reported. Pharmacokinetic analysis of plasma and nasal ruprintrivir concentrations revealed intranasal drug residence with minimal systemic absorption. Results from these studies in experimental rhinoviral infection support continued investigation of intranasal ruprintrivir in the setting of natural HRV infection.

Fluoxetine: Efficacy Against Placebo and by Dose-An Overview

The most unequivocal demonstration of efficacy with putative or reference antidepressants is normally obtained from placebo-controlled studies; heavy reliance is therefore placed on such investigations, particularly in the early stages of development of any new therapeutic agent. However, many clinicians are understandably reluctant to allow some patients to be treated with placebo, which may lead to a sampling bias. It is equally understandable that doctors taking part in such studies are anxious about clinical deterioration or lack of response, and this in turn may result in a higher drop-out rate than would be seen in studies using reference antidepressants without a placebo treatment group. However, in spite of these and other drawbacks, it is still generally accepted that the efficacy of potential antidepressants is established in a more scientific and unequivocal way using placebo-controlled methodology. Fluoxetine has been the subject of a number of such investigations (Table I); their findings are reviewed in this paper.