Eight Weeks of Vitamin C Supplementation Restores the Lost Correlation between Serum Leptin and C-reactive Protein (CRP) in Patients with Type 2 Diabetes; A Randomized, Double-blind, Parallel-group, Placebo-controlled Clinical Trial.

OBJECTIVE: Inflammation is a well-described factor in the pathophysiology of type 2 diabetes mellitus (DM), which has been a suspect in the alteration of correlations between CRP and leptin in patients with type 2 DM. AIM: This study aimed to show the effect of vitamin C as an antioxidant on the correlation of the serum levels of C-reactive protein (CRP) and leptin in patients with type 2 DM. METHODS: We recruited 70 patients with longstanding T2DM and randomly assigned them into two groups; one received 500 mg/day of vitamin C, and the other received a placebo for eight weeks. Both groups were matched regarding baseline characteristics such as age, gender, weight, and diabetic medications. RESULTS: Out of 70 individuals, 57 participants were left in the study. After eight weeks of follow-up, leptin level was significantly increased in the Vitamin C group (MD = 3.48 change = 24%, p-value = 0.001) but did not change in the placebo group. Other markers such as Fasting plasma glucose, HbA1c, Creatinine, uric acid, Urea, cholesterol, HDL, LDL, TG, AST, ALT, insulin, and CRP did not significantly change in both groups (p value > 0.05). The significant changes in the leptin level among the vitamin C group also remained after controlling for age, BMI, Blood pressure (BP), Triglyceride (TG), and cholesterol. Also, the correlation between serum CRP and leptin became significant in the vitamin C group after eight weeks of follow-up but not in the placebo group. (rs = 0.730, p < 0.001 vs. rs = 0.286, p-value = 0.266 in placebo group). CONCLUSION: This study shows vitamin C can restore CRP-leptin correlation in patients with type 2 diabetes and increase serum leptin levels. More studies are needed to clarify the mechanism of this restoration. CLINICAL TRIAL REGISTRATION NUMBER: IRCT20160811029306N1.

l-carnitine adjunct to risperidone for treatment of autism spectrum disorder-associated behaviors: a randomized, double-blind clinical trial.

Present study was designed to evaluate the efficacy and safety of l-carnitine as an adjuvant agent to risperidone in the treatment of autism spectrum disorder (ASD)-associated behaviors. In this study, 68 children with confirmed ASD were randomly allocated to receive either l-carnitine (150 mg/day) or matched placebo in addition to risperidone. We utilized the Aberrant Behavior Checklist-Community Edition scale (ABC-C) and a checklist of potential adverse effects to assess changes in behavioral status and safety profile at weeks 0, 5 and 10 of the trial. The primary outcome was defined as a change in the irritability subscale score. Sixty patients with similar baseline characteristics completed the trial period. Although scores of ABC-C subscales significantly decreased in both groups over the trial period, the combination of l-carnitine and risperidone resulted in more reduction on the irritability and hyperactivity subscales compared to the combination of risperidone and placebo (P = 0.033 and P < 0.001, respectively). However, changes in lethargy, stereotypic behavior and inappropriate speech subscales were similar between groups. In conclusion, l-carnitine adjuvant to risperidone could improve irritability and hyperactivity features in children with ASD. Results of this study should be considered preliminary and further clinical trials with larger sample sizes and longer follow-up periods are warranted.

Inhibition of phosphodiesterase IV enzyme improves locomotor and sensory complications of spinal cord injury via altering microglial activity: Introduction of Roflumilast as an alternative therapy.

Despite the great search for an effective approach to minimize secondary injury in spinal cord injury (SCI) setting, there have been limited advances. Roflumilast is a selective inhibitor of phosphodiesterase 4 with potent anti-inflammatory properties. Here, we sought to explore Roflumilast efficacy in the improvement of locomotor and sensory deficits of SCI. In an animal setting, 50 male rats were randomly assigned to five groups: an SCI group receiving Placebo, three SCI groups receiving Roflumilast at the doses of 0.25, 0.5, and 1 mg/kg prior to T9 vertebra laminectomy, and a sham-operated group. Locomotor, mechanical, and thermal activities were evaluated for 28 days. At the end of the study, spinal cord samples were taken to assess the relative ratio of microglial subtypes, including M1 and M2, histopathological changes, levels of pro-inflammatory (TNF-α and IL-1ß) and anti-inflammatory (IL-10) biomarkers, and cAMP level. Repeated measure analysis revealed significant effect for time-treatment interaction on locomotion [F (24, 270) = 280.7, p < 0.001], thermal sensitivity [F (16, 180) = 4.35, p < 0.001], and mechanical sensitivity [F (16, 180) = 7.96, p < 0.001]. As expected, Roflumilast significantly increased the expression of spinal cAMP. H&E staining exhibited lesser histopathological disruptions in Roflumilast-treated rodents. We also observed a significant reduction in the M1/M2 ratio (p values < 0.001) as well as in pro-inflammatory biomarkers following the administration of Roflumilast to the injured rats. Furthermore, IL-10 level was increased in rodents receiving 1 mg/kg of the reagent. In conclusion, the increased spinal cAMP following Roflumilast therapy might attenuate neuroinflammation via altering microglial activity; therefore, it could be considered as an alternative therapeutic agent for SCI complications.

Efficacy and safety of tipepidine as adjunctive therapy in children with attention-deficit/hyperactivity disorder: Randomized, double-blind, placebo-controlled clinical trial.

AIM: This study evaluated the efficacy and safety of tipepidine as an add-on to methylphenidate in the drug treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: This study was an 8-week, randomized, parallel group, double-blind, placebo-controlled trial recruiting 53 ADHD-diagnosed children. Patients were randomly divided to receive methylphenidate + tipepidine or methylphenidate + placebo for 8 weeks. Participants were assessed using the parent version of ADHD Rating Scale-IV and the Clinical Global Impression scale at baseline, at week 4, and at the end of the trial. Moreover, the safety and tolerability of the treatment strategies were compared. RESULTS: On general linear model repeated measures analysis a significant effect was seen for time × treatment interaction on the total and hyperactivity-impulsivity subscales of the Parent ADHD Rating Scale-IV during the trial period (Greenhouse-Geisser corrected: F = 3.45, d.f. = 1.52, P = 0.049, and F = 5.17, d.f. = 1.52, P = 0.014, respectively). The effect for time × treatment interaction, however, was not significant on Clinical Global Impression-Severity scale (Greenhouse-Geisser corrected: F = 1.79, d.f. = 1.43, P = 0.182). The frequencies of adverse events were similar between the two groups. CONCLUSION: Eight weeks of treatment with tipepidine, as a supplementary medication, resulted in satisfactory efficacy and safety of the adjuvant therapy in management of patients with ADHD. Rigorous investigations, however, involving larger sample sizes, more extended treatment periods, and dose responses should be considered.