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Time for New Recommendation of Upper Limit of Serum Vitamin D in Humans 人类血清维生素D上限的新推荐时间
Pub Date : 2019-09-27 DOI: 10.31038/edmj.2019353
P. Schwarz
There is a continued debate and exchange of knowledge with respect to serum 25- hydroxyvitamin D (25(OH)D) cut-off levels. Based on our current knowledge it is time to reconsider our recommendations of the optimal level of serum 25(OH)D in the clinical setting and not only focus on low levels but also recommend an upper serum limit of around 125 nmol/L (40–50 ng/mL) among healthy and diseased.
关于血清25-羟基维生素D (25(OH)D)的截止水平一直存在争论和知识交流。根据我们目前的知识,是时候重新考虑我们在临床环境中对血清25(OH)D最佳水平的建议,不仅关注低水平,而且建议在健康和患病人群中,血清上限约为125 nmol/L (40-50 ng/mL)。
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引用次数: 0
Schizophrenia Plasma Autoantibodies Promote 'Biased Agonism' at the 5-Hydroxytryptamine 2A Receptor: Neurotoxicity is Positively Modulated by Metabotropic Glutamate 2/3 Receptor Agonism. 精神分裂症血浆自身抗体促进5-羟色胺2A受体的“偏向性激动”:代谢型谷氨酸2/3受体激动对神经毒性有积极调节作用。
Pub Date : 2019-08-14 DOI: 10.31038/edmj.2019344
M. Zimering, S. Nadkarni
AimsTo test whether neurite-inhibitory plasma autoantibodies in chronic schizophrenia activate Gq/11- and Gi- coupled signaling pathways downstream of 5-hydroxytryptamine 2A receptor activation; and for modulation of serotonergic signaling by the metabotropic 2/3 receptor agonist LY379268.MethodsPlasma from five older adults with chronic schizophrenia and eight age-matched patients having another neuropsychiatric, immune or metabolic disorder was subjected to Protein-A affinity chromatography to obtain IgG autoantibodies. Mean neurite retraction (5 minutes) or cell survival (24 hours) was determined in mouse N2A neuroblastoma cells incubated with autoantibodies in the presence or absence of specific antagonists of the Gq/11/PLC/IP3R signaling pathway, Gi-coupled, beta-arrestin2-directed pathways, or LY379268.ResultsChronic schizophrenia plasma autoantibodies- mediated dose- and time-dependent acute N2A neurite retraction was completely prevented by M100907, a selective 5-hydroxytryptamine 2A receptor antagonist. LY379268 promoted autoantibody-induced neurite retraction causing a shift-to-the-left in the dose-response curve. Antagonists of the RhoA/Rho kinase and Gq/11/PLC/IP3R signaling pathways blocked autoantibody-mediated neurite retraction. Chronic schizophrenia plasma autoantibodies mediated increased N2A cell survival which was blocked by LY379268, pertussis toxin, and antagonists of PI3-kinase- mediated survival signaling.ConclusionSchizophrenia plasma autoantibodies activate the 5-hydroxytryptamine 2A receptor positively coupled to Gq/11/PLC/IP3R pathway and RhoA/Rho kinase signaling activation in promoting acute N2A cell neurite retraction. Autoantibodies in a subset of patients experiencing hallucinations promoted increased N2A cell survival mediated (in part) via a pertussis-toxin sensitive, Gi-coupled, PI3-kinase-dependent mechanism. Positive modulation of 5-HT2AR-mediated neurite retraction by LY379268 suggests the autoantibodies may target (in part) the 5-HT2AR/mGlu2R heteromer.
目的检测慢性精神分裂症患者的轴突抑制性血浆自身抗体是否激活5-羟色胺2A受体激活下游的Gq/11和Gi偶联信号通路;以及代谢型2/3受体激动剂LY379268对5-羟色胺能信号的调节。方法对5名患有慢性精神分裂症的老年人和8名患有另一种神经精神、免疫或代谢障碍的年龄匹配患者的血浆进行蛋白-A亲和层析,以获得IgG自身抗体。在存在或不存在Gq/11/PLC/IP3R信号通路、Gi偶联的β-rrestin2-定向通路的特异性拮抗剂的情况下,在与自身抗体孵育的小鼠N2A神经母细胞瘤细胞中测定平均轴突回缩(5分钟)或细胞存活(24小时),结果选择性5-羟色胺2A受体拮抗剂M100907完全阻止了慢性精神分裂症血浆自身抗体介导的剂量和时间依赖性急性N2A轴突回缩。LY379268促进自身抗体诱导的轴突回缩,导致剂量-反应曲线向左移动。RhoA/Rho激酶和Gq/11/PLC/IP3R信号通路的拮抗剂阻断自身抗体介导的轴突回缩。慢性精神分裂症血浆自身抗体介导的N2A细胞存活增加,被LY379268、百日咳毒素和PI3激酶介导的存活信号拮抗剂阻断。结论精神分裂症患者血浆自身抗体激活与Gq/11/PLC/IP3R通路正偶联的5-羟色胺2A受体和RhoA/Rho激酶信号激活,促进急性N2A细胞突起回缩。在经历幻觉的患者亚群中,自身抗体通过百日咳毒素敏感、Gi偶联、PI3激酶依赖性机制(部分)促进了N2A细胞存活率的增加。LY379268对5-HT2AR-介导的轴突回缩的阳性调节表明自身抗体可能(部分)靶向5-HT2AR/mGlu2R异聚体。
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引用次数: 4
Autoantibodies in Type-2 Diabetes having Neurovascular Complications Bind to the Second Extracellular Loop of the 5-Hydroxytryptamine 2A Receptor. 具有神经血管并发症的2型糖尿病中的自身抗体与5-羟色胺2A受体的第二细胞外环结合。
Pub Date : 2019-08-01 DOI: 10.31038/edmj.2019345
M. Zimering
Diabetes is associated with a substantially increased risk of certain neurovascular and neurodegenerative complications, e.g. stroke, dementia, Parkinson’s disease, major depressive disorder [1], through complex and poorly-defined mechanisms. We previously reported the occurrence of activating 5-HT2A receptor IgG autoantibodies in plasma or serum from older adult diabetes suffering with major depressive disorder [2], Parkinson’s disease or dementia [3]. Acute neurite retraction and accelerated mouse neuroblastoma N2a cell death induced by the autoantibodies in cell culture was partially or completely prevented by co-incubation (of IgG autoantibodies) with selective antagonists of the 5-HT2A receptor [2,3].
糖尿病与某些神经血管和神经退行性并发症的风险显著增加有关,如中风、痴呆、帕金森病、严重抑郁障碍[1],其机制复杂且不明确。我们之前报道了患有严重抑郁障碍[2]、帕金森病或痴呆[3]的老年糖尿病患者的血浆或血清中激活5-HT2A受体IgG自身抗体的情况。通过与5-HT2A受体的选择性拮抗剂共同孵育(IgG自身抗体),部分或完全预防了细胞培养中自身抗体诱导的急性轴突回缩和加速小鼠神经母细胞瘤N2a细胞死亡[2,3]。
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引用次数: 7
Autoantibodies in Type-2 Diabetes having Neurovascular Complications Bind to the Second Extracellular Loop of the 5-Hydroxytryptamine 2A Receptor. 伴有神经血管并发症的2型糖尿病的自身抗体与5-羟色胺2A受体的第二细胞外环结合
Pub Date : 2019-08-01 Epub Date: 2019-08-14
Mark B Zimering
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引用次数: 0
Risk of Foot Ulcer Development in Diabetic Patients – Relation to Isokinetic Muscle Strength, Sensory Function, and Clinical Findings 糖尿病患者发生足溃疡的风险——与等速肌力、感觉功能和临床表现的关系
Pub Date : 2019-05-01 DOI: 10.31038/edmj.2019333
A. Pedersen, L. Havé, H. Andersen, N. Ejskjaer, C. Z. Swan
Aim : To investigate whether reduced muscle strength in the lower extremities in diabetic patients is associated to the development of Diabetic Foot Ulcer (DFU). Methods : We conducted a retrospective cohort study on 95 diabetic patients who participated in studies on Diabetic Polyneuropathy (DPN) and motor function 12–16 years earlier. Isokinetic muscle strength at the ankle and knee, Neurological Impairment Scores (NIS), vibration perception thresholds (VPT), and demographic data were obtained from the initial studies. Patient files were systematically reviewed, and information on DFU occurrence and Macrovascular Disease (MVD) acquired. Results : Twenty-six patients developed DFU. A temporal relationship was found for development of DFU among patients with reduced strength at both the ankle and knee (all P<0.05). Univariate analyses showed a relationship between DFU and reduced strength for ankle dorsal flexion (P<0.001), ankle plantar flexion (P<0.005), knee extension (P<0.001), and knee flexion (P<0.005). DFU was related to NIS (P<0.001) and MVD (P<0.05) in both univariate and multivariate regression analyses. After adjustment for MVD, all strength measures were related to DFU. When adjusting for NIS, a trend was only found for ankle dorsal flexion (P=0.08). Conclusions : In DPN, muscle weakness at the ankle and knee contributes to development of foot ulcers.
目的:探讨糖尿病患者下肢肌力下降是否与糖尿病足溃疡(DFU)的发生有关。方法:我们对95名糖尿病患者进行了回顾性队列研究,这些患者在12-16年前参与了糖尿病多神经病(DPN)和运动功能的研究。踝关节和膝关节等速肌力、神经损伤评分(NIS)、振动感知阈值(VPT)和人口统计数据均来自初始研究。系统地回顾了患者档案,并获得了DFU发生和大血管疾病(MVD)的信息。结果:26例患者出现DFU。在踝关节和膝关节强度降低的患者中,DFU的发展存在时间关系(均P<0.05)。单变量分析显示,DFU与踝关节背侧屈曲(P<0.001)、踝关节足底屈曲(P<0.005)、膝关节伸展(P<0.001,在单因素和多因素回归分析中,DFU与NIS(P<0.001)和MVD(P<0.05)相关。MVD调整后,所有强度测量均与DFU相关。当调整NIS时,只发现踝关节背屈有趋势(P=0.08)。结论:在DPN中,踝关节和膝关节的肌肉无力会导致足部溃疡的发展。
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引用次数: 0
Cardiovascular Changes in Normo and Hypogonadal Rats Treated with a High-Fructose Diet and Induced Hyperuricemia Condition 高果糖饮食和诱导高尿酸血症对正常和性腺功能低下大鼠心血管的影响
Pub Date : 2019-04-20 DOI: 10.31038/edmj.2019332
J. Soutelo, Y. Samaniego, MC Fornari, C. ReyesToso, Ponzo OJ Ph
Objective: to evaluate the presence and type of cardiovascular damage in normogonadic and hypogonadic male rats with a induced condition of mild hyperuricemia and exposed to a high-fructose diet. Methods: Fifty six (56) male adult Wistar rats were used in the present work. Animals were divided into two groups; normogonadic (NGN) and hypogonadic (HGN), and each group was divided into four subgroups according to their treatment: control with only water (C), Fructose (F), Oxonic acid (OA) and Fructose plus Oxonic acid (FOA). Cardiovascular changes were evaluated by measuring systolic blood pressure , myocyte volume, fibrosis and intima media of aorta. Results: The FOA group significantly increased blood pressure, myocyte volume (p<0.0001), the percentage of fibrosis was significant in the group receiving OA (p<0.001). When comparing NGN vs HGN, hypogonadic animals showed a less favorable lipid profile. Conclusion: Hypogonadic, hyperuricemic conditions and a high-fructose diet favor blood pressure increase , along with changes in the cardiac hypertrophy, fibrosis and thickness increase of the intima media.
目的:评估性腺正常和性腺功能低下的雄性大鼠在轻度高尿酸血症诱导条件下暴露于高果糖饮食时心血管损伤的存在和类型。方法:选用56只雄性成年Wistar大鼠。将动物分为两组;性腺正常(NGN)和性腺功能减退(HGN),每组根据治疗分为四个亚组:仅用水对照(C)、果糖对照(F)、草酸对照(OA)和果糖加草酸对照(FOA)。通过测量收缩压、心肌细胞体积、纤维化和主动脉内膜介质来评估心血管变化。结果:FOA组显著增加了血压、肌细胞体积(p<0.0001),OA组的纤维化百分比显著增加(p<0.001)。当比较NGN与HGN时,性腺功能减退的动物表现出不太好的脂质状况。结论:性腺功能低下、高尿酸血症和高果糖饮食有利于血压升高,同时伴有心脏肥大、纤维化和内膜中膜厚度增加的变化。
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引用次数: 0
The Need for Fixed Dose Combination (FDC) for the Management of Type 2 Diabetes in Mauritius 毛里求斯2型糖尿病管理需要固定剂量组合(FDC)
Pub Date : 2019-03-25 DOI: 10.31038/edmj.2019331
Mohammad Yaasir Ozeer, Jhoti Somanah Bhugowandeen
The State health services of Mauritius are provided free to all 1.27 million inhabitants of the island. Despite so, successive surveys by the Ministry of Health and Quality of Life have shown that diabetes remains a major public health threat to Mauritians. With 24% of the adult population affected by (type 2 diabetes) T2D, our island is ranked amongst those countries with highest diabetes-related mortality, which emphasizes the need for educating the population proper self-management of the disease. It is also evident that poor treatment adherence looms large. Patients with T2D under conventional treatment often require multiple medications to achieve glycaemic control. This induces a significant pill burden when coupled with co-morbid conditions associated to diabetes and deters adherence to treatment. Public health institutions in Mauritius support the usage of loose pills for diabetes treatment as opposed to private institutions who promote the adoption of Fixed Dose Combination (FDC) therapy as a means to improve treatment efficacy. A scaled-study was conducted to explore the efficiency and patients’ perspectives on FDC in the management of T2D. 65 patients from the Diabetes and Vascular Health Centre were grouped according to their treatment regimen: FDC from start; switched to FDC from loose pills; reverted to loose pills after trying FDC and loose pills treatment. Patients were interviewed and their clinical parameters recorded. Results showed that 67.7 % of patients were taking more than 7 pills a day to achieve glycaemic control, with only 30.8 % being made aware of possible FDC options by their healthcare practitioner. 96.3% patients who were on loose pills expressed their willingness to shift to FDC if made available in public institutions. Overall glycaemic control was better managed among the FDC group. Our findings concluded that the loose pill regime was indeed problematic for diabetics to achieve optimal glycaemic control. FDC could be pivotal in improving their health outcomes, barriers such as communication of treatment availabilities, financial constraints, shared decision-making and self-management training also need to be addressed.
毛里求斯向全岛127万居民免费提供国家保健服务。尽管如此,卫生和生活质量部的连续调查表明,糖尿病仍然是毛里求斯人面临的主要公共健康威胁。我国成年人口中有24%患有(2型糖尿病)T2D,是与糖尿病有关的死亡率最高的国家之一,这就强调有必要教育人民对这种疾病进行适当的自我管理。治疗依从性差的问题也很明显。常规治疗的T2D患者往往需要多种药物才能达到血糖控制。当与糖尿病相关的合并症相结合时,这就会导致严重的药物负担,并阻碍治疗的坚持。毛里求斯的公共卫生机构支持使用散装药片治疗糖尿病,而私营机构则提倡采用固定剂量联合疗法作为提高治疗效果的手段。我们进行了一项规模研究,以探讨FDC在T2D治疗中的效率和患者的观点。来自糖尿病和血管健康中心的65名患者根据他们的治疗方案进行分组:从开始的FDC;从散装药丸改为FDC;在尝试FDC和散丸治疗后又恢复服用散丸。对患者进行访谈并记录其临床参数。结果显示,67.7%的患者每天服用7片以上的药物来控制血糖,只有30.8%的患者被他们的保健医生告知可能的FDC选择。96.3%服用散装药片的患者表示,如果公共机构提供FDC,他们愿意转向FDC。FDC组总体血糖控制较好。我们的研究结果表明,对于糖尿病患者来说,松散的药丸疗法确实存在问题,无法达到最佳的血糖控制。FDC可在改善其健康结果方面发挥关键作用,但也需要解决诸如通报治疗情况、财政限制、共同决策和自我管理培训等障碍。
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引用次数: 0
Blood Pressure in Healthy Youngsters is modified by Vitamin-D Supplementation 补充维生素d可改善健康青少年的血压
Pub Date : 2019-03-12 DOI: 10.31038/edmj.2019325
Rune Tønnesen, Kristian Buch, P. Hovind, L. T. Jensen, P. Schwarz
Objective Our study aimed to investigate the effect of vitamin D supplementation on blood pressure in vitamin D insufficient young volunteers compared to an age matched control group with sufficient levels of vitamin D. Secondarily we aimed to evaluate the effect of vitamin D supplementation on the RAAS and sympathetic nervous system. Design Single centre, Randomised controlled Trial. of Range 2.4) mmHg (p = 0.009), diastolic BP (daytime) decreased -4.5 (2.1) mmHg (p = 0.03), norepinephrine decreased -0.80 (0.21) nmol/L, (p = 0.0002). There was no effect of vitamin D supplementation on night time systolic or diastolic BP, and no effect on angiotensinogen, renin, angiotensin (I+II), aldosterone or epinephrine. We observed that 180 days of vitamin D supplementation in normal youngsters with insufficient vitamin D significantly lowered systolic and diastolic BP during daytime. Vitamin D supplementation also significantly lowered circulating norepinephrine. Nothing happened in the control group with normal vitamin D. Hence, it is tempting to conclude that vitamin D acts on BP through SNS as no changes were observed in the RAAS.
目的我们的研究旨在调查与维生素D水平充足的年龄匹配对照组相比,维生素D缺乏的年轻志愿者补充维生素D对血压的影响。其次,我们旨在评估维生素D补充对RAAS和交感神经系统的影响。设计单中心随机对照试验。范围为2.4)mmHg(p=0.009),舒张压(白天)下降-4.5(2.1)mmHg,去甲肾上腺素下降-0.80(0.21)nmol/L,(p=0.0002)。补充维生素D对夜间收缩压或舒张压没有影响,对血管紧张素原、肾素、血管紧张素(I+II)、醛固酮或肾上腺素也没有影响。我们观察到,在维生素D不足的正常青少年中,180天的维生素D补充显著降低了白天的收缩压和舒张压。补充维生素D也能显著降低循环中的去甲肾上腺素。在维生素D正常的对照组中没有发生任何变化。因此,很容易得出结论,维生素D通过SNS对BP起作用,因为在RAAS中没有观察到变化。
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引用次数: 0
The Reg`Activ Cholesterol Positive Effects in Asymptomatic Volunteers with Borderline Values of Cardio-Metabolic Risk Factors are Sustainable in Long-Term Run 具有心脏代谢危险因素临界值的无症状志愿者的Reg`Activ胆固醇阳性作用在长期内是可持续的
Pub Date : 2019-02-22 DOI: 10.31038/edmj.2019324
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引用次数: 0
Effects of a New Combination of Cranberry Extracts, D-Mannose and GAGs for the Management of Uncomplicated Urinary Tract Infection 蔓越莓提取物、D-甘露糖和GAGs新组合治疗非复杂尿路感染的效果
Pub Date : 2019-02-09 DOI: 10.31038/edmj.2019315
De Lucio, Capretti Camilla, Scarcella Simone, Damiano
OBJECTIVE: Several studies have investigated the role of cranberry extract and D-mannose in the prevention of recurrent urinary tract infections (UTIs). The aim of this preliminary study was to test whether the use of a new dietary supplement (UROIAL TM sachets) containing cranberry extracts (S&R PACs), D-mannose, hyaluronic Acid and Glucosamine Chondroitin may reduce the incidence of episodes of cystitis and improve urinary symptoms. METHODS: In this prospective comparative study, 40 women with an acute diagnosis of cystitis received a single sachet of Fosfomycin Tromethamine (3gr). The subjects were then randomly assigned to two groups: Group A: 20 women were given UROIAL TM , 2 sachet per day during the first 7 days, then 1 sachet per day for two weeks; Group B: 20 women did not receive any treatment to serve as a control group. RESULTS: The results of the present study showed a complete remission of urinary symptoms in 37 women, a slight decrease in urinary symptoms was observed in 2 subjects, whereas 1 woman who stopped the treatment was considered a drop-out. Patients in Group A had a lower incidence of episodes of recurrent cystitis during treatment and follow-up; urine samples had significantly lower median bacterial load compared to baseline as well as a symptomatic relief was reported in treated subjects despite the control group. DISCUSSION: Several studies have investigated and demonstrated the role of cranberry extracts in the prevention of recurrent urinary tract infections (UTIs), on different selected subpopulations and even at increased risk of UTI. Even the use of D-mannose, a natural sugar has proven to have clinical benefit, although clinical data is limited. A randomized placebo-controlled non-blinded clinical trial has shown that a daily dose of 2 g d-mannose was superior to placebo in preventing UTI. Mannose receptors are found on uroepithelial cells lining the urinary tract they constitute the protective mucopolysaccharide layer of the bladder. The mechanism of action involves binding of the mannose receptors to E. coli pili, thus preventing both adhesion to and invasion of urothelial cells. The interaction between mannose molecules and E. coli bacteria can then be washed away with urine voiding. CONCLUSIONS: Our data indicate that the addition of GAGs (hyaluronic acid and chondroitin sulfate) to cranberry/D-Mannose containing products could represent a valid novel therapeutic approach for the treatment and/or prophylaxis of cystitis.
目的:几项研究探讨了蔓越莓提取物和D-甘露糖在预防复发性尿路感染(UTIs)中的作用。这项初步研究的目的是测试使用一种含有蔓越莓提取物(S&R PACs)、D-甘露糖、透明质酸和氨基葡萄糖软骨素的新膳食补充剂(UROIAL TM小袋)是否可以降低膀胱炎发作的发生率并改善尿路症状。方法:在这项前瞻性比较研究中,40名急性诊断为膀胱炎的女性接受了单袋磷霉素-乙胺(3gr)治疗。然后将受试者随机分为两组:A组:20名女性服用UROIAL TM,前7天每天2袋,然后两周每天1袋;B组:20名女性未接受任何治疗作为对照组。结果:本研究结果显示,37名女性的尿液症状完全缓解,2名受试者的尿液症状略有减轻,而1名停止治疗的女性被视为退出治疗。A组患者在治疗和随访期间复发性膀胱炎的发生率较低;与基线相比,尿液样本的中位细菌载量显著较低,尽管有对照组,但治疗受试者的症状也有所缓解。讨论:几项研究已经调查并证明了蔓越莓提取物在预防复发性尿路感染(UTI)、不同亚群甚至增加UTI风险方面的作用。即使使用D-甘露糖,一种天然糖,也被证明具有临床益处,尽管临床数据有限。一项随机安慰剂对照非盲法临床试验表明,每天2克d-甘露糖在预防尿路感染方面优于安慰剂。甘露糖受体存在于尿路上皮细胞上,它们构成膀胱的保护性粘多糖层。作用机制包括甘露糖受体与大肠杆菌菌毛的结合,从而防止粘附和侵袭尿路上皮细胞。甘露糖分子和大肠杆菌之间的相互作用可以通过尿液排泄被冲走。结论:我们的数据表明,在含有蔓越莓/D-甘露糖的产品中添加GAGs(透明质酸和硫酸软骨素)可能是治疗和/或预防膀胱炎的一种有效的新治疗方法。
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引用次数: 2
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Endocrinology, diabetes and metabolism journal
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