Oral Coenzyme Q10 supplementation leads to better preservation of kidney function in steroid-resistant nephrotic syndrome due to primary Coenzyme Q10 deficiency.

Primary Coenzyme Q10 (CoQ10) deficiency is an ultra-rare disorder caused by defects in genes involved in CoQ10 biosynthesis leading to multidrug-resistant nephrotic syndrome as the hallmark kidney manifestation. Promising early results have been reported anecdotally with oral CoQ10 supplementation. However, the long-term efficacy and optimal prescription remain to be established. In a global effort, we collected and analyzed information from 116 patients who received CoQ10 supplements for primary CoQ10 deficiency due to biallelic pathogenic variants in either the COQ2, COQ6 or COQ8B genes. Median duration of follow up on treatment was two years. The effect of treatment on proteinuria was assessed, and kidney survival was analyzed in 41 patients younger than 18 years with chronic kidney disease stage 1-4 at the start of treatment compared with that of an untreated cohort matched by genotype, age, kidney function, and proteinuria. CoQ10 supplementation was associated with a substantial and significant sustained reduction of proteinuria by 88% at 12 months. Complete remission of proteinuria was more frequently observed in COQ6 disease. CoQ10 supplementation led to significantly better preservation of kidney function (5-year kidney failure-free survival 62% vs. 19%) with an improvement in general condition and neurological manifestations. Side effects of treatment were uncommon and mild. Thus, our findings indicate that all patients diagnosed with primary CoQ10 deficiency should receive early and life-long CoQ10 supplementation to decelerate the progression of kidney disease and prevent further damage to other organs.

A novel metabolic disorder in the degradation pathway of endogenous methanol due to a mutation in the gene of alcohol dehydrogenase.

BACKGROUND: A small amount of methanol is produced endogenously in the human body but it is efficiently metabolized by alcohol dehydrogenase (ADH) and other enzymes, and the products eliminated without harm. In this study, we present a new entity of inborn error of methanol metabolism due to a mutation in the ADH1C gene coding for the γ subunit that is part of several ADH isoenzymes. RESULTS: This disorder was discovered in an 11.58-year-old boy. During one 9-month hospital admission, he had periods of 1-4 days during which he was comatose, and between these periods he was sometimes verbose and euphoric, and had ataxia, dysarthria. Following hemodialysis treatments, he became conscious and appeared healthy. Organ evaluations and his laboratory tests were normal. Toxicological evaluation of his blood showed a high methanol level [12.2 mg/dL (3.8 mmol/L), normal range up to 3.5 mg/dL (1.09 mmol/L) while the formaldehyde level was undetectable. The finding of liver function tests that were within normal limits, coupled with a normal eye examination and size of the liver, elevated blood methanol levels and an undetectable formaldehyde level, suggested ADH insufficiency. Adding zinc to the drug regimen 15 mg/daily dramatically reduced the patient's methanol level and alleviated the abnormal symptoms. When zinc supplementation was discontinued, the patient relapsed into a coma and hemodialysis was once again required. A homozygous mutation in ADH1C gene located at exon 3 was found, and both parents were heterozygous for this mutation. CONCLUSION: Accumulation of methanol due to mutation in ADH1C gene may result in drunkenness and ataxia, and leads to coma. This condition can be successfully treated with zinc supplementation as the cofactor of ADH.

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.

Osteogenic differentiation of stem cells derived from menstrual blood versus bone marrow in the presence of human platelet releasate.

In recent decades, stem cell therapy has been introduced as a novel therapeutic approach for patients suffering from bone disorders. Recently, menstrual blood has been identified as an easily accessible and recycled stem cell source. However, the osteogenic differentiation capacity of menstrual blood-derived stem cells (MenSCs) compared with other adult stem cells remained unsolved. The aim of this study was to investigate the osteogenic differentiation capacity of MenSCs compared to bone marrow-derived mesenchymal stem cells (BMSCs) in the presence of human platelet releasate (HPR). Our results showed that MenSCs were strongly positive for mesenchymal and negative for hematopoietic stem cell markers in a similar manner to BMSCs. In contrary to BMSCs, MenSCs exhibited marked expression of OCT-4 and a significantly higher proliferative capacity. Mineralization, as judged by alizarin red staining, was more pronounced in differentiated BMSCs than in differentiated MenSCs in an osteogenic medium fortified with fetal bovine serum (FBS). However, FBS substitution with HPR in a differentiation medium resulted in typical impact on intensity of MenSC mineralization. The results of semiquantitative reverse transcription-polymerase chain reaction showed comparable levels of parathyroid hormone receptor and osteocalcin transcripts in both types of differentiated stem cells in an HPR medium supplemented with osteogenic inducers. However, the upregulation level of alkaline phosphatase was relatively lower in differentiated MenSCs than that in differentiated BMSCs. We concluded that despite lower osteogenic differentiation capacity of MenSCs compared to BMSCs, substitution of FBS with HPR could equalize the osteogenic differentiation of MenSCs. Therefore, by taking advantage of osteogenic driving potential of HPR, MenSCs could be introduced as an apt and safe alternative to BMSCs for bone tissue-engineering purposes.