Identification and functional analysis of combined oxidative phosphorylation deficiency 28 gene mutation / 中华内科杂志

Objective:To report a case of combined oxidative phosphorylation deficiency 28 (COXPD28) in China, identified the pathogenic mutation and explored the pathogenic mechanism preliminarily.Methods:The clinical characteristics of a patient with COXPD28 were retrospectively analyzed and the pathogenic mutations were identified by mitochondrial gene sequencing and whole exome sequencing. The wild-type and mutant plasmids of pathogenic genes were constructed, and effect of mutation on protein expression by quantitative real-time PCR (qPCR) and Western blot were evaluated. Statistical methods mainly used one-way ANOVA and LSD test.Results:A 21 year old female patient presented with lactic acid poisoning due to repeated chest distress and wheezing since childhood. The sequencing of the whole exon group gene found that solute carrier family 25 member 26 (SLC25A26) gene had a compound heterozygous mutation (c.34G>C, p.A12P; c.197C>A, p.A66E), which was the first report in China. In vitro function test showed that the expression levels of SLC25A26 mRNA and S-adenosylmethionine carrier (SAMC) protein in cells transfected with SLC25A26 mutant plasmid were significantly lower than those transfected with wild type plasmid. The p.A66E mutant plasmid reduced the expression level of SLC25A26 mRNA and SAMC protein to 6% and 26% of wild type plasmids respectively (both P<0.001), while p.A12P mutant plasmid decreased to 62% and 82% of wild type plasmids respectively ( P<0.001, P=0.044). When the double mutant (p.A66E+p.A12P) plasmids were co-transfected, the expression levels of SLC25A26 mRNA and SAMC protein decreased to 47% and 57% of the wild type plasmids, respectively ( P<0.001, P=0.001). Conclusion:The pathogenic mutation gene of this patient with COXPD28 is SLC25A26 gene mutation (p.A66E, p.A12P), which causes the decrease of SLC25A26 expression level, mitochondrial oxidative phosphorylation dysfunction, and induces COXPD28.

Compliance and tolerability evaluation of diacerein versus s-adenosyl methionine in osteoarthritis patients

Background: Diacerein and S-adenosyl methionine (SAMe) are symptomatic slow-acting drugs in osteoarthritis (SYSADOA). Diacerein is a semisynthetic, anthraquinone derivative, an interleukin 1beta inhibitor with anti-inflammatory, anti-catabolic and pro-anabolic properties on cartilage and synovial membrane. SAMe is a dietary supplement used in the management of OA. The objective of this study is to find out compliance and tolerability evaluation of Diacerein versus S-adenosyl methionine inpatients suffering from Osteoarthritis. Materials and methods: This was a prospective, randomized, interventional study conducted in Orthopedic OPD and ward in Rajah Muthiah Medical College and Hospital for a period of one year. A total of 80 patients were enrolled in this study as per the inclusion criteria. 40 patients in each group were randomly assigned to receive either diacerein 50mg BD or SAMe 200 mg TDS for12 weeks. The NSAID diclofenac 50 mg BD was administered orally for a short course of one week to both the groups to relieve acute symptoms. Efficacy of both the drugs was assessed using Lysholm knee scoring scale. The tolerability profile was evaluated during each clinical visit on weeks 1, 4 and 12. Gayathri C.R., Vanitha Samuel, Senthilnathan A, Nirmala P. Compliance and tolerability evaluation of diacerein versus sadenosyl methionine in osteoarthritis patients. IAIM, 2017; 4(11): 6-13. Page 7 Results: Diacerein and SAMe which were symptomatic slow-acting drugs show a profound reduction in pain starting from 4th to 12th week of treatment. Lower GI side effects like diarrheawere observed in the diacerein group and insomnia was reported in the SAMe group. Though the overall adverse effects were more in the diacerein group, compliance was better with regard to drug intake Conclusion: Both diacerein and SAMe were found to be effective in reducing the pain in Osteoarthritis patients. Diacerein with a good compliance factor was less tolerable because of the incidence of diarrhea. SAMe though better tolerated has a compliance score of fair to good.

Efficacy Observation of Ursodesoxycholic Acid Combined with S-Adenosyl Methionine in the Treatment of Mild ICP of Pregnancy / 中国药房

OBJECTIVE:To observe therapeutic efficacy of ursodeoxycholic acid(UDCA)combined with S-adenosyl methio-nine (SAMe) in the treatment of mild intrahepatic cholestasis (ICP) of pregnancy. METHODS:213 pregnant patients with mild ICP were selected and randomly divided into combination group (107 cases) and single drug group (106 cases). Combination group received UDCA combined with SAMe,and single drug group was given UDCA alone. Therapeutic efficacy and pregnancy outcome were compared between 2 groups. RESULTS:Compared to before treatment,TBA,CG,DBIL,ALT and AST of 2 groups were decreased after treatment,and the decrease of combination group was more significant than that of single drug group, with statistical significance(P0.05);the preterm birth rate of combination group was 11.22%,which was significantly lower than 20.75% of single drug group,with statistical significance(P<0.05). CONCLUSIONS:Compared to UD-CA alone,UDCA combined with SAMe in the treatment of patients with ICP can control the clinical symptoms timely,recovery laboratory index as soon as possible and obtain better therapeutic efficacy.