Saffron in the treatment of patients with mild to moderate Alzheimer’s disease: a 16‐week,randomized and placebo‐controlled trial

What is known: Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response. Crocus sativus (saffron) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer’s disease (AD). Objective: The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD. Methods: Forty‐six patients with probable AD were screened for a 16‐week, double‐blind study of parallel groups of patients with mild to moderate AD. The psychometric measures, which included AD assessment scale‐cognitive subscale (ADAS‐cog), and clinical dementia rating scale‐sums of boxes, were performed to monitor the global cognitive and clinical profiles of the patients. Patients were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice per day) (Group A) or capsule placebo (two capsules per day) for a 16‐week study. Results: After 16 weeks, saffron produced a significantly better outcome on cognitive function than placebo (ADAS‐cog: F = 4·12, d.f. = 1, P = 0·04; CDR: F = 4·12, d.f. = 1, P = 0·04). There were no significant differences in the two groups in terms of observed adverse events. What is new and conclusion: This double‐blind, placebo‐controlled study suggests that at least in the short‐term, saffron is both safe and effective in mild to moderate AD. Larger confirmatory randomized controlled trials are called for.     

The effects and side effects of laquinimod for the treatment of multiple sclerosis patients: a systematic review and meta-analysis of clinical trials

European Journal of Clinical Pharmacology - Although studies have shown the efficacy of laquinimod (LAQ) on disease progression in patients with multiple sclerosis (MS), there is some controversy...     

Safety of cranial fixation in endoscopic brow lifts

Introduction

The endoscopic brow lift technique relies on brow mobilization and often soft fixation to the underlying calvarium. While the endoscopic brow lift has been used safely, there are anecdotal reports of cerebrospinal fluid leak. We sought to measure calvarial thickness to improve the safety of cranial fixation.

Methods

A retrospective review was performed of T2 weighted MRIs of the face of 28 patients. Calvarial thickness was measured on 10 coronal planes, from 3 centimeters (cm) anterior to 6 cm posterior to coronal suture. Fifteen points were measured on each coronal plane, starting in the midline and extending laterally for 7 cm. There were a total of 150 calvarial measurements per patient, covering the surface area used in endoscopic brow lifts. Statistical comparison was performed using analysis of variance.

Results

Cranial thickness ranged from 1.1 to 13.6 mm, with a mean of 6.1 mm. The skull was thickest 2–4 cm posterior to the coronal suture, and thinnest 1 cm anterior to the coronal suture. The cranium thins as it extends laterally, with an average thickness of 5.0 mm at seven centimeters from midline. Average skull thickness for males was 5.96 versus 6.16 in females. There was no relationship between age and skull thickness.

Conclusion

Cranial thickness increases medially and posteriorly, and is larger for females compared with their male counterparts. Given the risk of CSF leak, surgeons need to be aware of how cranial thickness varies by location along the skull.     

Serum and CSF PDGF‐AA and FGF‐2 in relapsing‐remitting multiple sclerosis: a case–control study

Background and purpose: Fibroblast growth factor‐2 (FGF‐2) and platelet‐derived growth factor‐A (PDGF‐AA) are potent modulators of oligodendrocytes, the main responsible cells for myelin regeneration. We measured FGF‐2 and PDGF‐AA in the sera and cerebrospinal fluid (CSF) of patients with relapsing‐remitting multiple sclerosis (RR‐MS) and compared these values with control subjects. Methods: Twenty‐three patients with RR‐MS and 23 subjects without inflammatory and demyelinating diseases were included. Serum samples of the patients were collected in both relapse and remission phases and were analyzed with ELISA method. CSF was drawn during the relapse period. Blood and CSF were drawn from control subjects for comparison. Wilcoxon and Mann–Whitney U‐test and Spearman’s rank correlation were used for analysis. P values of <0.05 were considered significant. Results: Age and sex distribution were similar in both groups. Serum values of FGF‐2 were higher in relapse phase compared with remission phase, with a trend toward significance (P = 0.052). CSF PDGF‐AA showed significant negative correlation with disease duration (correlation coefficient = ?0.58, P = 0.004). Serum levels of PDGF did not differ between two phases significantly. There was no difference in serum and CSF values of these factors between patients and controls. When we compared patients with prolonged disease with controls, a significant difference between the CSF levels of PDGF‐AA was observed (mean ± SEM 2.78 ± 0.8 in controls vs. 0.55 ± 0.29 in patients with MS ≥ 2 years, P < 0.05). Conclusion: Our study was the first to show that CSF PDGF‐AA is related to disease duration. Supporting previous findings we showed that serum and CSF levels of these factors are weak indicators of disease severity.     

Impact of Vitamin A Supplementation on RAR Gene Expression in Multiple Sclerosis Patients

Vitamin A and its derivatives have been shown to modulate the immune system via retinoic acid receptor (RAR). This study explored the impact of retinyl palmitate supplementation on RAR subtype gene expression in peripheral blood mononuclear cells (PBMCs) in multiple sclerosis (MS) patients. The study designed as a double-blind randomized clinical trial in which relapsing remitting multiple sclerosis patients were evaluated. Both groups received one capsule 50,000 IU vitamin D3 per 2 weeks and one intramuscular injection interferon beta-1a per week. The intervention group received one 25,000 IU retinyl palmitate capsule daily for 6 months and the placebo group received one placebo capsule daily. The PBMCs were isolated from participants and the expression level changes of RAR-α and RAR-γ genes were determined by real-time PCR. After supplementation, in the intervention group, the RAR-α gene expression level was significantly decreased compared to the placebo group (p?=?0.03); however, the expression of RAR-γ gene did not significantly change (p?=?0.10). These results show that vitamin A supplementation can significantly downregulate the expression of RAR-α gene in PBMCs of MS patients that suggest the presence of in vivo regulatory mechanisms for the action of vitamin A on the immune system.     

The Effect of Vitamin A Supplementation on Retinoic Acid-Related Orphan Receptor γt (RORγt) and Interleukin-17 (IL-17) Gene Expression in Avonex-Treated Multiple Sclerotic Patients

The aim of this study was to investigate the role of vitamin A on RORγt and IL-17 gene expression in multiple sclerotic patients. Patients in the vitamin A group received 25,000 IU retinyl palmitate per day, while patients in the placebo group took one capsule of placebo per day for 6 months. Gene expression was measured by real-time PCR at the first and end of the study. The results of this study show that vitamin A downregulates IL-17 and RORγt gene expression. No changes in gene expression occurred in the placebo group.     

The application of high density microarray for analysis of mitogenic signaling and cell-cycle in the adrenal

Angiotensin II (AII) binds to specific G-protein coupled receptors and is mitogenic in adrenal, liver epithelial, and vascular smooth muscle cells. The H295R human adrenocortical cell line, which expresses AII receptors predominantly of the AT1 subclass, proliferates in response to treatment with AII. The induction and maintenance of cellular proliferation involves a precisely coordinated induction of a variety of genes. As the human genome sequencing projects near completion a variety of high throughput technologies have been developed in order to create dynamic displays of genomic responses. One high throughput method, the gridded cDNA microarray has been developed in which immobilised DNA samples are hybridized on glass slides for the identification of global genomic responses. For this purpose high precision robotic microarrayers have been developed at AECOM. The cyclin D1 gene, which encodes the regulatory subunit of the cyclin D1-dependent kinase (CD1K) required for phosphorylation of the retinoblastoma protein (pRB), was induced by AII in H295R cells. Abundance of the cyclin D1 gene is rate-limiting in G1 phase progression of the cell-cycle in a variety of cell types. AII induced cyclin D1 promoter activity through a c-Fos and c-Jun binding sequence at -954 bp. Theabundance of c-Fos within this complex was increased by AII treatment. Analysis of AII signaling in adrenal cells by cDNA microarray demonstrated an induction of the human homologue of Xenopus XPMC2 (HXPMC2). The cDNA for XPMC2 was previously shown to rescue mitotic catastrophe in mutant S. Pombe defective in cdc2 kinase function. Further studies are required to determine the requirement for cyclin D1 and XPMC2H in AII-induced cell-cycle progression and cellular proliferation in the adrenal.     

A case of choreoacanthocytosis with marked weight loss: impact of orolingual dyskinesia

Choreoacanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder characterized by progressive onset of hyperkinetic movements and red cell acanthocytosis. The most striking clinical feature is that of the orofacial and lingual movement abnormalities leading to severe feeding difficulties. Maintenance of proper nutrition in ChAc is a challenge. We report on a case of ChAc in a 32-year-old male in whom dramatic weight loss due to orolingual dyskinesia was the major consequence of the disease. This case report warrants more attention to the impact of orolingual dyskinesia on nutritional status in patients with ChAc.     

Differential Expression of Klotho in the Brain and Spinal Cord is Associated with Total Antioxidant Capacity in Mice with Experimental Autoimmune Encephalomyelitis

Recently, we reported a positive correlation between Klotho, as an anti-aging protein, and the total antioxidant capacity (TAC) in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. However, there is no information about the Klotho and TAC changes within the central nervous system (CNS). Thus, the current study aimed to employ an experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice using MOG_35–55 peptide to examine the relationship between Klotho and TAC within the CNS. To this end, the brain and spinal cord were obtained at the onset and peak stages of EAE as well as non-EAE mice (sham/control groups). The Klotho expression was assessed in the brain and spinal cord of different experimental groups at mRNA (qPCR) and protein (ELISA) levels. Also, TAC level was determined in the tissues of different experimental groups. The results showed that Klotho expression in the brain at the onset and peak stages of EAE were significantly lower than that in non-EAE mice. Conversely, Klotho expression in the spinal cord at the onset of EAE was significantly higher than that of non-EAE mice, while Klotho was comparable at the peak stage of EAE and non-EAE mice. The pattern of TAC alteration in the brain and spinal cord of EAE mice was similar to that of Klotho expression. In conclusion, for the first time, this study demonstrated a significant positive correlation between Klotho and TAC changes during the pathogenesis of EAE. It is suggested that Klotho may have neuroprotective activity through the regulation of redox system.