RESUMEN
Fazio-Londe disease and Brown-Vialetto-Van Laere syndrome are rare related neurological disorders. Although SLC52A3 and SLC52A2 that encode riboflavin transporters are their only known causative genes, many patients without mutations in these genes have been reported. Clinical and genetic data of a patient with features suggestive of Fazio-Londe disease are presented. Neurological examination revealed significant involvement of cranial nerves and weakness in the lower extremities. Pontobulbar presentations were prominent. EDX study suggested motor neuronopathy. Hearing was normal. She was diagnosed with FL disease. Response to riboflavin supplementation was not favorable. The patient's pedigree suggested recessive inheritance. SLC52A3 and SLC52A2 were screened and mutations were not observed. Results of exome sequencing and segregation analysis suggested that a mutation in TNRC18 is a candidate cause of disease in the patient. The three dimensional structure of the TNRC18 protein was predicted and it was noted that its two conserved domains (BAH and Tudor) interact and that the valine residue affected by the mutation is positioned close to both domains. A mutation in TNRC18 is cautiously reported as the possible cause of FL disease in the patient. The finding warrants further inquiries on TNRC18 about which little is presently known.
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The objective of present study was to assess the safety and efficacy of nanocurcumin as an anti-inflammatory and antioxidant agent in adults with amyotrophic lateral sclerosis (ALS). We conducted a 12-month, double-blind, randomized, placebo-controlled trial at a neurological referral center in Iran. Eligible patients with a definite or probable ALS diagnosis were randomly assigned to receive either nanocurcumin (80 mg daily) or placebo in a 1:1 ratio. A computerized random number generator was used to prepare the randomization list. All patients and research investigators were blinded to treatment allocation. The primary outcome was survival, and event was defined to be death or mechanical ventilation dependency. Analysis was by intention-to-treat and included all patients who received at least one dose of study drug. A total of 54 patients were randomized to receive either nanocurcumin (n = 27) or placebo (n = 27). After 12 months, events occurred in 1 patient (3.7%) in the nanocurcumin group and in 6 patients (22.2%) in the placebo group. Kaplan-Meier analysis revealed a significant difference between the study groups regarding their survival curves (p = 0.036). No significant between-group differences were observed for any other outcome measures. No serious adverse events or treatment-related deaths were detected. No patients withdrew as a result of drug adverse events. The results suggest that nanocurcumin is safe and might improve the probability of survival as an add-on treatment in patients with ALS, especially in those with existing bulbar symptoms. Future studies with larger sample sizes and of longer duration are needed to confirm these findings.
Asunto(s)
Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Curcumina/uso terapéutico , Riluzol/uso terapéutico , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoRESUMEN
BACKGROUND: Accumulating evidences from experimental, epidemiologic and clinical studies support the potential linkage between poor vitamin D status and the risk of developing Multiple Sclerosis (MS), as well as, an adverse disease course. However, the results of the trials on the clinical outcomes of vitamin D supplementation in MS patients are less consistent which brought many discrepancies in routine practice. In this article we presented a summary of a symposium on vitamin D and MS. In this symposium we aim to review the current data about the relationship between vitamin D and MS, and suggest management guides for practicing neurologists. DISCUSSION: Generally, supplementation seems to be reasonable for all MS and clinically isolated syndrome (Rinaldi et al., Toxins 7:129-37, 2015) patients with serum 25(OH)D level below 40 ng/ml. In patients with vitamin D insufficiency or deficiency, a large replacing dose (e.g. 50,000 IU capsules of D per week for 8-12 week) is recommended. Panel also suggested: the checking of the serum vitamin D, and calcium level, as well as, patients' compliance after the initial phase; a maintenance treatment of 1500-2000 IU daily or equivalent intermittent (weekly, biweekly or monthly) Dose, considering the patient's compliance; routine check of serum vitamin D level at least two times a year especially at the beginning of spring and autumn; Serum vitamin D evaluation for first degree relatives of MS patients at high risk age and supplementation in case of insufficiency (25(OH)D less than 40 ng/ml); correction of vitamin D deficiency and insufficiency before pregnancy, as well as, a daily dose of 1500-2000 IU or equivalent biweekly intake in 2nd and 3rd trimesters; stopping supplementation if 25(OH)D serum level exceeds 100 ng/ml. Although the results of high power studies are not available, correcting vitamin D status seems plausible in all MS and CIS patients. Maintaining the serum 25(OH)D level between 40 and 100 ng/ml is not known to exert adverse effect. More ever, it might be associated with lower disease activity.
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Consenso , Esclerosis Múltiple/tratamiento farmacológico , Vitamina D/uso terapéutico , Femenino , Humanos , Irán , Esclerosis Múltiple/complicaciones , Embarazo , Vitamina D/sangreRESUMEN
Decreasing the population and activation of inflammatory T helper cells in multiple sclerosis (MS) patients using vitamin A derivatives (retinoic acids) has been well documented. The present study determined the effect of vitamin A supplementation on psychiatric signs in MS patients. The subjects were 101 relapsing-remitting MS patients enrolled in a placebo-controlled randomized clinical trial. The treatment group was administered 25000 IU/d retinyl palmitate (RP) for 6 months followed by 10000 IU/d RP for another 6 months. The results for baseline characteristics, modified fatigue impact scale and Beck Depression Inventory-II were recorded at the beginning and end of the one-year study. The non-normal distribution data was compared between groups using a nonparametric test and normal distribution data was analyzed using a parametric test. (ClinicalTrials.gov Identifiers: NCT01417273). The results showed significant improvement in the treatment group for fatigue (p=0.004) and depression (p=0.01). Vitamin A supplementation helped during interferon therapy in the treatment process and improved psychiatric outcomes for anti-inflammatory mechanisms.
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Depresión/tratamiento farmacológico , Suplementos Dietéticos , Fatiga/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Vitamina A/análogos & derivados , Adulto , Depresión/diagnóstico , Suplementos Dietéticos/efectos adversos , Evaluación de la Discapacidad , Diterpenos , Método Doble Ciego , Fatiga/diagnóstico , Fatiga/etiología , Femenino , Humanos , Irán , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Escalas de Valoración Psiquiátrica , Ésteres de Retinilo , Factores de Tiempo , Resultado del Tratamiento , Vitamina A/efectos adversos , Vitamina A/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Many studies have shown that active vitamin A derivatives suppress the formation of pathogenic T cells in multiple sclerosis (MS) patients. The aim of the present study is to determine the impact of vitamin A on disease progression in MS patients. METHODS: A total of 101 relapsing-remitting MS (RRMS) patients were enrolled in a 1-year placebo-controlled randomized clinical trial. The treated group received 25000 IU/d retinyl palmitate for six month followed by 10000 IU/d retinyl palmitate for another six month. The results of the expanded disability status scale (EDSS) and multiple sclerosis functional composite (MSFC) were recorded at the beginning and the end of the study. The relapse rate was recorded during the intervention. Patients underwent baseline and follow up brain MRIs. RESULTS: The results showed "Mean ± SD" of MSFC changes in the treated group was (-0.14 ± 0.20) and in the placebo group was (-0.31 ± 0.19). MSFC was improved significantly (P < 0.001) in the treatment group. There were no significant differences between the "Mean ± SD" of EDSS changes in the treated (0.07 ± 0.23) and placebo (0.08 ± 0.23) groups (P = 0.73). There were also no significant differences between the "Mean ± SD" of annualized relapse rate in the treated group (-0.36 ± 0.56) and placebo (-0.53 ± 0.55) groups (P = 0.20). The "Mean ± SD" of enhanced lesions in the treatment (0.4 ± 1.0) and in the placebo (0.2 ± 0.6) groups were not significantly different (P = 0.26). Volume of T2 hyperintense lesions "Mean ± SD" was not significantly different between treatment (45 ± 137) and placebo (23 ± 112) groups after intervention (P = 0.23). CONCLUSION: Vitamin A improved total MSFC score in RRMS patients, but it did not change EDSS, relapse rate and brain active lesions.
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Progresión de la Enfermedad , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Vitamina A/análogos & derivados , Adulto , Evaluación de la Discapacidad , Diterpenos , Método Doble Ciego , Femenino , Humanos , Irán , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Ésteres de Retinilo , Resultado del Tratamiento , Vitamina A/administración & dosificación , Adulto JovenRESUMEN
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.
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Suplementos Dietéticos , Esclerosis Múltiple/metabolismo , Receptores de Ácido Retinoico/genética , Vitamina A/farmacología , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Receptores de Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico , Transcripción Genética/efectos de los fármacos , Vitamina A/administración & dosificación , Receptor de Ácido Retinoico gammaRESUMEN
Neuroblastoma is the most common solid tumor in children. Current therapy modalities have resulted in little amelioration in the cure rate of neuroblsatoma and therefore, outlining biologically based therapies for neuroblastoma remains of main priority. This study was carried out to appraise the impeding effects of silibinin, a potent anti-cancer agent, on two different neuroblastoma cell lines, stromal SK-N-MC and neuroblastic SK-N-BE(2) cells. The microculture tetrazolium assay, gelatin zymography, colony formation assay, cell cycle distribution survey, apoptosis assay, and quantitative real-time reverse transcription-PCR were applied to evaluate the effects of silibinin on metabolic activity, gelatinolytic activity of MMP-2 and MMP-9, surviving potential, cell cycle, apoptosis, and expression pattern of the genes involved in cell survival and invasion of the two neuroblastoma cell lines. Treatment for 48 h inhibited metabolic activity and clonogenic potential of SK-N-MC cells in a dose-dependent manner. Silibinin also inhibited transcriptional levels of MMP-2, MMP-9, and uPAR, as markers of cell invasion, in SK-N-MC cells. Higher concentration of silibinin (75, 100 µM) suppressed enzymatic activity of MMP-2 in this cell line. No change in apoptosis and cell cycle was observed in neither of the cells after treatment with silibinin. On the other hand, silibinin highly decreased mRNA expression of Akt, and NF-κB1 and its regulators, IKK1 and IKK2 in SK-N-MC cell line. Comparison of transcriptional expression of Akt, and NF-κB1 in untreated stromal and neuroblastic cell lines shows that their basal transcriptional levels are much higher in SK-N-BE(2) cell line than that in SK-N-MC cells. It seems that SK-N-BE(2) cell line probably resists to silibinin through higher expression of Akt and probably NF-κB1. Collectively, our results demonstrated that silibinin highly inhibits the proliferative potentials of SK-N-MC cell line, whilst it had less inhibitory effect on SK-N-BE(2) cell line. Our results suggest that suppression of SK-N-MC cell line by silibinin may be through inhibition of Akt-mediated NF-κB1.