Background Cognitive impairment is the most important feature of schizophrenia leading to severe functional disability. To identify pathways that improve pathophysiological neurocognition in schizophrenia is a current challenge for the development of goal-directed clinical interventions. In the present study, we investigated the effects of raloxifene (a selective estrogen modulator) and isradipine (a voltage-gated L-type calcium channel blocker) on cognitive deficits in patients with schizophrenia. Method We designed a double-blind, randomized, parallel, placebo-controlled trial. We randomized 60 patients with schizophrenia into 3 groups including isradipine 5 mg, raloxifine 60 mg, and placebo for 6 consequent weeks, all in the same shape capsules, 2 times a day, along with treatment as usual. The initial and final results of blood tests, electrocardiograms, and cognitive tests in specific domains, such as attention, processing speed, executive function, and verbal memory were evaluated. Results Our findings revealed a remarkable association between adjunctive raloxifene treatment and the alleviation of verbal memory deficits. Isradipine treatment significantly improved the verbal memory and attention dysfunction in some variables of the Stroop test, compared with the placebo. However, no effect was observed in processing speed and executive function deficits. Conclusions To the best of our knowledge, this study provides the first evidence that isradipine is a novel therapy option improving verbal memory and attention, both related to its activity in the hippocampus and the cerebellum. Further investigations are necessary to elucidate the mechanisms of action for both drugs in schizophrenia.

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Introduction: Tissue regenerative medicine strategies, as a promising alternative has become of major interest to the reconstruction of critical size bone defects. This study evaluated the effects of the simultaneous application of polycaprolactone (PCL), amniotic fluid mesenchymal stem cells (AF-MSCs) and platelet-rich plasma (PRP) on the repair of rat cranial bone defects. Methods: The AF-MSCs were isolated at the end of the second week of pregnancy in rats. PRP obtained from rat blood and the random PCL fibrous scaffolds were prepared using the electrospinning method. Circular full thickness (5 mm) bone defects were developed on both sides of the parietal bones (animal number=24) and the scaffolds containing AF-MSCs and PRP were implanted in the right lesions. Thereafter, after eight weeks the histological and immunohistochemistry studies were performed to evaluate the bone formation and collagen type I expression. Results: The spindle-shaped mesenchymal stem cells were isolated and the electron microscope images indicated the preparation of a random PCL scaffold. Immunohistochemical findings showed that collagen type I was expressed by AF-MSCs cultured on the scaffold. The results of hematoxylin and eosin (H & E) staining indicated the formation of blood vessels in the presence of PRP. Additionally, immunofluorescence findings suggested that PRP had a positive effect on collagen type I expression. Conclusion: The simultaneous application of fibrous scaffold + AF-MSCs + PRP has positive effects on bone regeneration. This study showed that PRP can affect the formation of new blood vessels in the scaffold transplanted in the bone defect.

Background Depression is one of the most common mental health disorders, which affiliated more than four percent of world population. Several antidepressant agents, including citalopram were developed. High dose and long-term treatment with these agents along with their side effects decrease the treatment adherence. Using supplements such as acid folic is a way to increase these drug’s efficacy. The aim of this study was to assess the effect of acid folic supplement and increase in blood folate level of the intensity of depression symptoms.Methods This was a randomized-controlled clinical trial. Twenty-four patients with major depression were randomly assigned to two groups. Both groups received citalopram as their standard treatment. The intervention group received acid folic supplement (1mg/daily). The folate levels of blood, Beck's depression inventory and Hamilton depression scale scores were measured. The measurements were conducted before intervention, and in 45 and 90 days follow ups. Data were analyzed using Mann-Whitney U and Friedman tests.Results The blood level of folate was increased for the intervention group. The Hamilton depression scale and Beck Depression Inventory Scores were reduced significantly in both groups after 90 days follow up. There were no significant differences between two groups in the reduction of depression scores. In the intervention group, the decrease of Hamilton's depression scale score was negatively correlated to the increase of blood folate level.Conclusions The increase in blood folate level may be correlate with the decrease in depression symptoms. The use of 1mg/d supplement of acid folic was not effective in the reduction of depression symptoms in patients with major depression.Registered in Iranian Registry of Clinical Trials (IRCT20180115038373N1)