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Folate/Vitamin b Alleviates Hyperhomocysteinemia-Induced Alzheimer-Like Pathologies in Rat Retina

Neuroscience bulletin 2019年第2期35卷 325-335页

作者： Jing Guo Shaozhou Ni Qihang Li Jian-Zhi Wang Ying Yang Department of Pathophysiology School of Basic Medicine and Collaborative Innovation Center for Brain Science Key Laboratory for Neurological Disorders of the Ministry of Education of China Tongji Medical College Huazhong University of Science and Technology Emergency Department Zhongnan Hospital of Wuhan University School of Optometry and Ophthalmology and Eye Hospital Wenzhou Medical College Co-innovation Center of Neuroregeneration Nantong University

Hyperhomocysteinemia(Hhcy) is an independent risk factor for Alzheimer's disease(AD). Visual dysfunction is commonly found and is positively correlated with the severity of cognitive defects in AD patients. Our previous study demonstrated that Hhcy induces memory deficits with AD-like tau and amyloid-b(Ab) pathologies in the hippocampus, and supplementation with folate and vitamin b12(Fb) prevents the Hhcy-induced AD-like pathologies in the hippocampus. Here, we investigated whether Hhcy also induces AD-like pathologies in the retina and the effects of Fb. An Hhcy rat model was produced by vena caudalis injection of homocysteine for14 days, and the effects of Fb were assessed by simultaneous supplementation with Fb in drinking water. We found that Hhcy induced vessel damage with Ab and taupathologies in the retina, while simultaneous supplementation with Fb remarkably attenuated the Hhcy-induced tau hyperphosphorylation at multiple AD-related sites and Ab accumulation in the retina. The mechanisms involved downregulation of amyloid precursor protein(APP), presenilin-1, beta-site APP-cleaving enzyme 1, and protein phosphatase-2 A. Our data suggest that the retina may serve as a window for evaluating the effects of Fb on hyperhomocysteinemia-induced Alzheimer-like pathologies.

关键词： Hyperhomocysteinemia Alzheimer’s disease Retina Folate Vitamin b12

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Correlation between serum vitamin b12 level and peripheral neuropathy in atrophic gastritis

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World Journal of Gastroenterology 2018年第12期24卷 1343-1352页

作者： Guo-Tao Yang Hong-Ying Zhao Yu Kong Ning-Ning Sun Ai-Qin Dong Department of Third Neurology Cangzhou Central Hospital Cangzhou Clinical Medical School of Hebei Medical University Department of Elderly Internal Medicine Cangzhou Central Hospital Cangzhou Clinical Medical School of Hebei Medical University Department of Second Digestion Cangzhou Central Hospital Cangzhou Clinical Medical School of Hebei Medical University Department of First Digestion Cangzhou Central Hospital Cangzhou Clinical Medical School of Hebei Medical University

AIM To explore the correlation between serum vitamin b12 level and peripheral neuropathy in patients with chronic atrophic gastritis(CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination fromSeptember 2013 to September 2016 were selected for this study. The age of these patients ranged within 18-to 75-years-old. blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori(H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin b12 deficiency risk factors, and to analyze the relationship between vitamin b12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin b12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin b9 and vitamin b12 were risk factors for the occurrence of peripheral nerve degeneration.Furthermore,CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin b12 deficiency. Serum vitamin b12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve(R = 0.463). After vitamin b12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin b12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin b12 deficiency and peripheral neuropathy. When treating CAG, vitamin b12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin b12 deficiency may be considered

关键词： Chronic gastritis Chronic atrophic gastritis Vitamin b12 Peripheral neuropathy

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High incidence of maternal vitamin b12 deficiency detected by newborn screening: first results from a study for the evaluation of 26 additional target disorders for the German newborn screening panel

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World Journal of Pediatrics 2018年第5期14卷 470-481页

作者： Gwendolyn Gramer Junmin Fang-Hoffmann Patrik Feyh Glynis Klinke Peter Monostori Jürgen G.Okun Georg F.Hoffmann Division of Neuropediatric and Metabolic Medicine Department of General PediatricsCenter for Pediatric and Adolescent MedicineUniversity Hospital HeidelbergIm Neuenheimer Feld 43069120 HeidelbergGermany

background Newborn screening (NbS) in Germany currently includes 15 target disorders. Recent diagnostic improvements suggest an extension of the screening panel. Methods Since August 2016, a prospective study evaluating 26 additional target disorders (25 metabolic disorders and vitamin b12-deficiency) in addition to the German screening panel is performed at the Newborn Screening Center Heidel-berg. First-tier results from tandem-MS screening are complemented by second-tier strategies for 15 of the additional target disorders. NbS results of seven patients diagnosed symptomatically with one of the additional target disorders by selective screening since August 2016 are retrospectively evaluated. Results Over a 13-month period, 68,418 children participated in the study. Second-tier analyses were performed in 5.4%of samples. Only 59 (0.1%) of study participants had abnormal screening results for one of the additional target disorders. Target disorders from the study panel were confirmed in 12 children: 13-hydroxy-3-methylglutaryl coenzyme A (CoA)-lyase deficiency, 1 citrullinemia type I, 1 multiple acyl-CoA dehydrogenase-deficiency, 1 methylenetetrahydrofolate reductase-deficiency, and 8 children with maternal vitamin b12-deficiency. In addition, six of seven patients diagnosed symptomatically outside the study with one of the target disorders would have been identified by the study strategy in their NbS sample. Conclusions Within 13 months, the study 'Newborn Screening 2020' identified additional 12 children with treatable con-ditions while only marginally increasing the recall rate by 0.1%. Maternal vitamin b12-deficiency was the most frequent finding. Even more children could benefit from screening for the additional target disorders by extending the NbS panel for Germany and/or other countries.

关键词： Metabolic disorders Newborn screening Second-tier Vitamin b12 deficiency

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Ataxic gait following total gastrectomy for gastric cancer

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World Journal of Gastroenterology 2016年第37期22卷 8435-8438页

作者： Chang Ho Hwang Dong Jin Park Gyu Yeol Kim Department of Physical Medicine and Rehabilitation Medicine Ulsan University Hospital University of Ulsan College of Medicine Department of Surgery Ulsan University Hospital University of Ulsan College of Medicine

A 58-year-old woman, who had undergone total gastrectomy for early gastric cancer 9 years previously, visited the outpatient clinic complaining of progressive difficulty in walking for 15 d. Laboratory examinations showed macrocytic anemia and a decreased serum vitamin b12 concentration and increased serum concentrations of folate, vitamin E and copper. Magnetic resonance imaging showed multifocal high signal intensities along the posterior column of the cervical and thoracic spinal cord. Treatment consisted of intramuscular injections of vitamin b12 for 7 d, which increased her serum level of vitamin b12 to normal. This was followed by weekly intramuscular injections of vitamin b12 for another 2 wk and oral administration of vitamin b12 three times per day. After comprehensive rehabilitation for 4 wk, she showed sufficient improvements in strength and ataxic gait, enabling her to return to her normal daily activities.

关键词： Subacute combined degeneration Vitamin b12 deficiency Total gastrectomy Gastric cancer

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High Prevalence and Factors Contributing to Hyperhomocysteinemia, Folate Deficiency, and Vitamin b_(12) Deficiency among Healthy Adults in Shanghai, China

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biomedical and Environmental Sciences 2019年第1期32卷 63-67页

作者： WANG Yu Heng YAN Qing Hua XU Ji Ying LI Xin Jian CHENG Min Na Shanghai Municipal Center for Disease Control and Prevention

Elevated plasma or serum total homocysteine (tHcy) level has been established as a risk factor for cardiovascular disease[1], as well as dementia and cognitive decline[2]. Plasma or serum folate and vitamin b12 influence homocysteine (Hcy) metabolism as a co-substrate and cofactor respectively, so that low concentrations of folate and vitamin b12 are also associated with high Hcy levels[1]. However, not much information is available describing serum tHcy, folate, and vitamin b12 status in Shanghai adults, especially in a healthy population. Therefore, we hypothesize that low serum folate and vitamin b12 is associated with high Hcy in healthy adults in Shanghai. The aim of this study was to determine the status of serum tHcy, folate, and vitamin b12, and the prevalence and factors contributing to HHcy, folate deficiency, and vitamin b12 deficiency among healthy adults in Shanghai, China.

关键词： Cardiovascular disease Serum total homocysteine (tHcy) Vitamin b12

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Redox active ionic liquid as efficient mediator and solvent for visible light-driven b_(12) catalytic reactions

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Green Energy & Environment 2019年第2期4卷 116-120页

作者： Hisashi Shimakoshi Noriyuki Houfuku Li Chen Yoshio Hisaeda Department of Chemistry and biochemistry Graduate School of Engineering Kyushu University

The redox active ionic liquid, 1-ethyl-4-(methoxycarbonyl)pyridinium bis(trifluoromethanesulfonyl)amide(RIL), was synthesized from its iodide form by an anion exchange reaction of Li(NTf_2) with viscos liquid(η= 122 cP at 25C) and characterized by NMR, IR, and elemental analysis. The compound showed reversible redox couples at -0.65 V and -1.48 V vs. Ag/AgCl and worked as an electron mediator in the b_(12) complex/[Ru(bpy)_3]Cl_2 photosensitizer catalytic system under visible light irradiation. The catalytic efficiency in the RIL was higher than those in DMF, MeOH, and the redox inactive ionic liquid, 1-butyl-3-methyl imidazolium bis(trifluoromethylsulfonyl)amide.

关键词： Ionic liquid Photosensitizer Redox active Visible light Vitamin b12

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Newborn screening for remethylation disorders and vitamin deficiency-evaluation of new strategies in cohorts from Qatar and Germany

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World Journal of Pediatrics 2017年第2期13卷 136-143页

作者： Gwendolyn Gramer Ghassan Abdoh Tawfeg ben-Omran Noora Shahbeck Rehab Ali Laila Mahmoud Junmin Fang-Hoffmann Georg F.Hoffmann Hilal Al Rifai Jürgen G.Okun University Hospital Heidelberg Center for Pediatric and Adolescent MedicineDivision of Neuropediatrics and Metabolic MedicineHeidelbergGermany Department of Pediatrics Hamad Medical CorporationDohaQatar

background:Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine-β-synthase deficiency).Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from Qatar.Methods:A new optimized newborn screening strategy for remethylation disorders and homocystinuria was developed and evaluated for newborns from Qatar using total homocysteine measurement as first-tier and methionine,methionine-phenylalanine-ratio and propionylcarnitine as second-tiers.Proposed cnt-offs were also retrospectively evaluated in newborn screening samples of 12 patients with remethylation disorders and vitamin b12 deficiency from Qatar and Germany.Results:Over a 12 months period,the proposed strategy led to a decrease in the recall rate in homocysteine screening for Qatar from 1.09% to 0.68%,while allowing for additional systematic inclusion of remethylation disorders and vitamin b12 deficiency into the screening panel for Qatar.In the evaluated period the applied strategy would have detected all patients with classical homocystinuria identified by the previous strategy and in addition 5 children with maternal nutritional vitamin b12 deficiency and one patient with an isolated remethylation disorder.Additional retrospective evaluation of newborn screening samples of 12 patients from Germany and Qatar with remethlyation disorders or vitamin b12 deficiency showed that all of these patients would have been detected by the cutoffs used in the proposed new strategy.In addition,an adapted strategy for Germany using methionine,methionine-phenylalanine-ratio and propionylcarnitine as first-tier,and homocysteine as a second-tier test was also positively evaluated retrospectively.Conclusions:The proposed strategy for samples from Qatar allows inclusion of remethylation disorders and vitamin b12 deficiency in the screening panel,while lowering the recal

关键词： classical homocystinuria newborn screening remethylation disorders second-tier vitamin b12 deficiency

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Study on the Electrosynthesis of Coenzyme b_12 Model Compound by Spectroelectrochemistry

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Chinese Science bulletin 1994年第20期39卷 1692-1696页

作者：高德郑国栋高赛俞汝勤

A lot of relevant work has been done on the important role of coenzyme b12 in various metabolism proceeding in biobody.because the Co—C bond of coenzyme b12 and its models is instable, there are some difficulties in ... 详细信息

A lot of relevant work has been done on the important role of coenzyme bb>12b> in various metabolism proceeding in biobody.because the Co—C bond of coenzyme bb>12b> and its models is instable, there are some difficulties in further studying

关键词： coenzyme b12 model compound electrosynthesis spectroelectrochemistry.

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Study of Coenzyme b_(12) Model Compounds——CNDO/2 Calculation of C_2H_5Co (Sb) and RCo (salen) L Complexes

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Chinese Science bulletin 1994年第12期39卷 1007-1010页

作者：韩德艳陈慧兰缪强俞马宏倪浩唐雯霞 Department of Chemistry State Key Laboratory of Coordination Chemistry Nanjing University Nanjing 210008 PRC Department of ChemistryHubei Normal UniversityHuangshi 435002PRC Department of Chemistry State Key Laboratory of Coordination Chemistry Nanjing University Nanjing 210008 PRC Department of Chemistry State Key Laboratory of Coordination Chemistry Nanjing University Nanjing 210008 PRC Department of ChemistryNanjing University of Science and TechnolgyNanjing 210014PRC

To synthesize and study the relation between structure and characteristics of Co-Cbond of coenzym b12 model compounds, it is an effective way to understand the fac-tors which can influence the stabilities of Co-C bond... 详细信息

To synthesize and study the relation between structure and characteristics of Co-Cbond of coenzym bb>12b> model compounds, it is an effective way to understand the fac-tors which can influence the stabilities of Co-C bond and the mechanism of mutasecatalyzed substrate rearrangement. Unfortunately knowledge about micro reaction mecha-nism of the model compounds is limited. W. N. Lipscomb calculated the

关键词： coenzyme b12 model compound Co - C bond bond order CNDO/2.

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神经科住院老年患者维生素b12缺乏的调查(英文)

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Neuroscience bulletin 2009年第4期25卷 209-215页

作者：王宇卉严芳张文波叶刚郑赟赟张旭花邵福源上海市浦南医院神经内科上海200125 第二军医大学长征医院神经科上海200003

目的调查神经科老年住院患者维生素(Vit)b12缺乏的状况。方法对本院神经内科2007年3月—2008年7月间连续住院的、年龄≥60岁的患者进行血清叶酸、Vitb12、同型半胱氨酸(Hcy)等指标的检测,筛查Vitb12缺乏者。共827例患者入组,平均年龄77.... 详细信息

目的调查神经科老年住院患者维生素(Vit)b12缺乏的状况。方法对本院神经内科2007年3月—2008年7月间连续住院的、年龄≥60岁的患者进行血清叶酸、Vitb12、同型半胱氨酸(Hcy)等指标的检测,筛查Vitb12缺乏者。共827例患者入组,平均年龄77.1±7.5岁。所有患者均无严重肝肾功能障碍,且近3个月内未补充Vitb12。对Vitb12正常患者和缺乏患者的神经系统症状、体征及神经电生理检查结果进行比较和分析。结果Vitb12缺乏者有163例(占所有患者总数的19.71%),神经电生理检查多有异常,患病率女性高于男性,并随年龄增长有增加的趋势。Vitb12缺乏者中伴有胃肠道疾病的比率较高,巨红细胞贫血仅为9.82%。Vitb12缺乏患者更易出现行走不稳及振动觉减退等症状,更多还伴有脑梗死、高血压、冠心病等慢性疾病。结论神经科住院老年患者常伴有Vitb12缺乏症,症状表现多样,神经系统表现较之巨红细胞贫血更常见。

关键词：衰老住院老年患者神经科维生素 b12 缺乏

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