Endocrinology, diabetes and metabolism journal最新文献_第6页

A Polyherbal Indian System of Medicine (Ayush) Preparation for Optimization of Glycemic Control in Newly Diagnosed Type 2 Diabetes and Prediabetes; A Multicenter, Randomised, Double-Blind, Placebo- Controlled Trial 一种用于优化新诊断的2型糖尿病和糖尿病前期血糖控制的印度多草药药物体系（Ayush）制剂；多中心随机双盲安慰剂对照试验

Endocrinology, diabetes and metabolism journal

Pub Date : 2019-02-09 DOI: 10.31038/edmj.2019322

A. Sigamani, Sanjaya Chauhan, G. Vikneswaran, Anju Joseph, Arun Kumar, KG Padma, Sandeep Kumar, Gupta, S. Tiwari, S. Kannan, Haleh Roohi, Leva Samimi, Prathipati Philip, C. Pidathala

Background: Current therapeutics do not provide optimized care in early stage type 2 diabetes and there is no established treatment for prediabetes. We did a randomised trial to assess the efficacy and safety of a popular Ayush product, Sugar Balance ® (sugar balance) in patients with newly diagnosed type 2 diabetes and prediabetes. Methods: In this multicentre, double blind placebo-controlled trial, we randomly assigned (1: 1) eligible participants, 30 years of age or older, of either gender and diagnosed with type 2 diabetes (HbA1c ≥ 6.5%) or prediabetes (FPG ≥ 5.6 mmol/L). We used computer-generated ramdomisation, stratified by type of diagnosis (prediabetes or diabetes). Active recipients were to receive 250 mg capsules containing 3 Organic certified whole herbs : Coccinia indica, Bougainvillea spectabilis and Madagascar periwinkle (sadabahar). The recommended dose was 2 capsules twice daily. The primary outcome was ≥0.5% reduction in HbA 1c for type 2 diabetes subjects and an increased incidence of normalization in impaired fasting blood glucose for prediabetes subjects at 6 months after randomization. The primary analysis included all subjects who received the allocated intervention and had 1 follow up visit after randomisation. All subjects received standard life style recommendations for diet and exercise. Type 2 diabetes subjects were allowed to be on biguanides (metformin) of their choice. This trial is registered with ClinicalTrials.gov, number NCT02866539 and clinical trials registry of India, number CTRI/2016/11/007435, and is completed. Findings: Between December 14 th 2016 and 28 th August 2017, 122 subjects were randomly assigned to active sugar balance (n=61) or matching placebo (n=61), of whom one subject (assigned to placebo) did not receive the allocated intervention. All follow up was completed on 16 th December 2017. At 6 months type 2 diabetes subjects allocated to active arm had a mean reduction of HbA 1c of -0.52% versus -0.43% among placebo arm (difference of -0.09% 95% CI -0.1705 - -0.0095). 13 (52%) versus 4 (15.4%) prediabetes subjects receiving the polyherbal achieved normalization of impaired fasting glycaemia (<100 mg/dl) (difference of 36.6% 95% CI 10.683 - 56.805). None of the study participants experienced significant hypoglycemia or significant changes in their safety clinical biochemistry parameters on therapy. Conclusions: Sugar Balance promises to be effective and safe supplement for type 2 diabetes subjects to achieve a better optimization of HbA 1c when taken along with standard dose of metformin and for prediabetes subjects to achieve their target fasting blood sugars with diet and exercise.

背景：目前的治疗方法并不能为早期2型糖尿病提供最佳的护理，也没有针对糖尿病前期的既定治疗方法。我们进行了一项随机试验，以评估流行的Ayush产品Sugar Balance®（糖平衡）对新诊断的2型糖尿病和糖尿病前期患者的疗效和安全性。方法：在这项多中心、双盲安慰剂对照试验中，我们随机分配（1:1）符合条件的参与者，年龄在30岁或以上，无论性别，都被诊断为2型糖尿病（HbA1c≥6.5%）或糖尿病前期（FPG≥5.6 mmol/L）。我们使用计算机生成的随机分组法，根据诊断类型（糖尿病前期或糖尿病）进行分层。受试者将接受250 mg胶囊，胶囊中含有3种有机认证的全草药：印度Coccinia indica、三角梅和马达加斯加长春花（sadabahar）。推荐剂量为2粒，每日两次。随机化后6个月，2型糖尿病受试者的主要结果是HbA1c降低≥0.5%，糖尿病前期受试者空腹血糖受损正常化的发生率增加。主要分析包括所有接受分配干预并在随机分组后进行1次随访的受试者。所有受试者都接受了关于饮食和锻炼的标准生活方式建议。2型糖尿病受试者可以自行选择服用双胍（二甲双胍）。该试验在ClinicalTrials.gov注册，编号NCT02866539，在印度临床试验注册中心注册，编号CTRI/2016/11/007435，并已完成。研究结果：在2016年12月14日至2017年8月28日期间，122名受试者被随机分配到活性糖平衡组（n=61）或匹配的安慰剂组（n=六十一），其中一名受试人员（分配到安慰剂组）没有接受分配的干预。所有随访于2017年12月16日完成。在6个月时，被分配到活动组的2型糖尿病受试者的HbA1c平均降低了-0.52%，而安慰剂组的HbA1C平均降低了-0.43%（差异为-0.09%95%置信区间-0.1705--0.0095）。13名（52%）和4名（15.4%）接受多糖治疗的糖尿病前期受试者实现了受损空腹血糖（<100 mg/dl）的正常化（差异为36.6%95%置信区间10.683-56.805）。没有一名研究参与者在治疗中经历了显著的低血糖或其安全性临床生物化学参数的显著变化。结论：糖平衡有望成为2型糖尿病受试者的有效和安全的补充剂，当与标准剂量的二甲双胍一起服用时，可更好地优化HbA1c，糖尿病前期受试者可通过饮食和运动达到其目标空腹血糖。

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引用次数: 0

Dalteparin Induced Skin Necrosis in a Patient Following Pelvic Floor Repair Surgery 盆底修复手术后达特帕林诱发的皮肤坏死

Endocrinology, diabetes and metabolism journal

Pub Date : 2019-02-09 DOI: 10.31038/edmj.2019321

引用次数: 0

Endothelial Cell Growth Promoting Activity in Graves' Disease Sera is Neutralized by Anti-Basic Fibroblast Growth Factor Antibodies in Patients with Fat Expansive but Not Infiltrative Orbitopathy. 在脂肪扩张性而非浸润性眼病患者中，抗碱性成纤维细胞生长因子抗体可中和Graves病血清中内皮细胞生长促进活性

Endocrinology, diabetes and metabolism journal

Pub Date : 2019-02-01 Epub Date: 2019-01-08

Mark B Zimering, John J Shin, Jennifer D Zaitz, Elkin A Nunez, Andrew G Gianoukakis

Purpose: To report a case of orbital fat expansion leading to globe prolapse in a Graves' disease patient undergoing high-dose glucocorticoid therapy. To evaluate the growth factor receptor specificities of plasma autoantibodies in Graves' disease patients who exhibited contrasting subtypes of thyroid-associated ophthalmopathy, i.e. orbital fat expansion-type vs. infiltrative.

Methods: Sera from Graves' orbitopathy and control patients with or without Graves' disease were subjected to protein-A affinity chromatography to obtain immunoglobulin G. A (1/50^th to 1/1600^th) range in dilutions of the protein-A eluate fraction was incubated for four days at 37 degrees C with bovine pulmonary artery endothelial cells to test for endothelial cell inhibition or stimulation. Growth stimulatory autoantibodies were co-incubated with specific neutralizing anti-insulin like growth factor 1 receptor antibodies or anti-basic fibroblast growth factor antibodies to assess autoantibody specificity in contrasting Graves' orbitopathy subtypes.

Results: We observed increased mean endothelial cell growth promoting activity in the protein-A eluates of serum from eighteen patients with active Graves' disease (117 ± 28%, n = 18) compared to mean endothelial cell activity (89 ± 10%, n = 13, P = 0.003) in thirteen adults without Graves' disease. The protein-A eluate fraction in acute infiltrative-type Graves' orbitopathy contained a high titer (> 1:1000) of endothelial cell stimulatory activity which was significantly neutralized by specific monoclonal anti-human insulin-like growth factor 1 receptor antibodies. The protein-A eluate fraction in fat expansion-type Graves' orbitopathy contained endothelial cell inhibitory activity (at low titers) and stimulatory activity (at high titers), and the latter stimulatory activity was completely neutralized by specific anti-basic fibroblast growth factor antibodies.

Conclusion: Graves' disease suffering globe prolapse secondary to marked orbital fat-expansion had coexisting plasma fibroblast growth factor-inhibitory and -stimulatory autoantibodies. The latter was completely neutralized by anti-basic fibroblast growth factor antibodies.

目的:报告一例接受大剂量糖皮质激素治疗的Graves病患者因眼眶脂肪扩张导致眼球脱垂。评估甲状腺相关眼病不同亚型(即眼眶脂肪扩张型与浸润型)Graves病患者血浆自身抗体的生长因子受体特异性。方法:用蛋白A亲和层析获得免疫球蛋白G. A(1/50 ~ 1/1600)，与牛肺动脉内皮细胞在37℃下孵养4天，检测内皮细胞的抑制或刺激作用。生长刺激自身抗体与特异性中和抗胰岛素样生长因子1受体抗体或抗碱性成纤维细胞生长因子抗体共孵育，以评估自身抗体在对比Graves眼病亚型中的特异性。结果:我们观察到18例活动性Graves病患者血清中促进内皮细胞生长的蛋白- a洗脱物的平均活性(117±28%，n = 18)高于13例非Graves病患者的平均内皮细胞活性(89±10%，n = 13, P = 0.003)。急性浸润型Graves眼病的蛋白a洗脱液部分含有高滴度(> 1:1000)的内皮细胞刺激活性，这种活性被特异性单克隆抗人胰岛素样生长因子1受体抗体显著中和。脂肪扩张型Graves眼病的蛋白a洗脱液部分含有内皮细胞抑制活性(低滴度)和刺激活性(高滴度)，后者的刺激活性被特异性抗碱性成纤维细胞生长因子抗体完全中和。结论:Graves病继发于眼眶脂肪明显扩张的球脱垂患者存在血浆成纤维细胞生长因子抑制和刺激自身抗体。后者被抗碱性成纤维细胞生长因子抗体完全中和。

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引用次数: 0

Validation of an Automated Extraction Procedure for Amino Acids and Acylcarnitines for Use with Tandem Mass Spectrometry for Newborn Screening 串联质谱法用于新生儿筛查的氨基酸和酰基肉毒碱自动提取程序的验证

Endocrinology, diabetes and metabolism journal

Pub Date : 2019-01-30 DOI: 10.31038/edmj.2019314

Stefan Gaugler, Jana Rykl, V. Cebolla

A certified reagent kit for newborn screening was transferred on a fully automated dried blood spot platform. The dried blood spot cards are directly eluted and the extract is online guided to tandem mass spectrometry instrument, where the amino acid and acyl carnitine panel is detected. The method takes 2 minutes per sample and requires no human interaction for up to 500 samples. The method is fully standardized through the automation and the usage of only certified consumables and reference material. The manual reagent kit was first modified to fit the automated platform, secondly validated and third, successfully transferred into a routine newborn screening laboratory.

将经认证的新生儿筛查试剂盒转移到全自动干血点平台上。干燥的血点卡被直接洗脱，提取物被在线引导到串联质谱仪，在那里检测氨基酸和酰基肉碱组。该方法每个样本需要2分钟，最多500个样本不需要人工交互。该方法通过自动化和仅使用经认证的耗材和参考材料而完全标准化。手动试剂盒首先进行了修改，以适应自动化平台，其次进行了验证，第三次成功转移到常规新生儿筛查实验室。

引用次数: 3

Endothelial Cell Growth Promoting Activity in Graves' Disease Sera is Neutralized by Anti-Basic Fibroblast Growth Factor Antibodies in Patients with Fat Expansive but Not Infiltrative Orbitopathy. Graves病血清中的内皮细胞生长促进活性被脂肪膨胀但非浸润性眼眶病患者的抗碱性成纤维细胞生长因子抗体中和。

Endocrinology, diabetes and metabolism journal

Pub Date : 2019-01-08 DOI: 10.31038/edmj.2019313

M. Zimering, John J. Shin, Jennifer D Zaitz, E. A. Nunez, A. Gianoukakis

PurposeTo report a case of orbital fat expansion leading to globe prolapse in a Graves' disease patient undergoing high-dose glucocorticoid therapy. To evaluate the growth factor receptor specificities of plasma autoantibodies in Graves' disease patients who exhibited contrasting subtypes of thyroid-associated ophthalmopathy, i.e. orbital fat expansion-type vs. infiltrative.MethodsSera from Graves' orbitopathy and control patients with or without Graves' disease were subjected to protein-A affinity chromatography to obtain immunoglobulin G. A (1/50th to 1/1600th) range in dilutions of the protein-A eluate fraction was incubated for four days at 37 degrees C with bovine pulmonary artery endothelial cells to test for endothelial cell inhibition or stimulation. Growth stimulatory autoantibodies were co-incubated with specific neutralizing anti-insulin like growth factor 1 receptor antibodies or anti-basic fibroblast growth factor antibodies to assess autoantibody specificity in contrasting Graves' orbitopathy subtypes.ResultsWe observed increased mean endothelial cell growth promoting activity in the protein-A eluates of serum from eighteen patients with active Graves' disease (117 ± 28%, n = 18) compared to mean endothelial cell activity (89 ± 10%, n = 13, P = 0.003) in thirteen adults without Graves' disease. The protein-A eluate fraction in acute infiltrative-type Graves' orbitopathy contained a high titer (> 1:1000) of endothelial cell stimulatory activity which was significantly neutralized by specific monoclonal anti-human insulin-like growth factor 1 receptor antibodies. The protein-A eluate fraction in fat expansion-type Graves' orbitopathy contained endothelial cell inhibitory activity (at low titers) and stimulatory activity (at high titers), and the latter stimulatory activity was completely neutralized by specific anti-basic fibroblast growth factor antibodies.ConclusionGraves' disease suffering globe prolapse secondary to marked orbital fat-expansion had coexisting plasma fibroblast growth factor-inhibitory and -stimulatory autoantibodies. The latter was completely neutralized by anti-basic fibroblast growth factor antibodies.

目的报告一例接受大剂量糖皮质激素治疗的Graves病患者眼窝脂肪扩张导致眼球脱垂。评估甲状腺相关眼病不同亚型(即眼眶脂肪扩张型与浸润型)Graves病患者血浆自身抗体的生长因子受体特异性。方法用蛋白A亲和层析获得免疫球蛋白G. A(1/50 ~ 1/1600)，与牛肺动脉内皮细胞在37℃下孵养4天，检测内皮细胞的抑制或刺激作用。生长刺激自身抗体与特异性中和抗胰岛素样生长因子1受体抗体或抗碱性成纤维细胞生长因子抗体共孵育，以评估自身抗体在对比Graves眼病亚型中的特异性。结果18例活动性Graves病患者(117±28%，n = 18)血清中促内皮细胞生长蛋白a洗脱物的平均活性高于13例非Graves病患者(89±10%，n = 13, P = 0.003)。急性浸润型Graves眼病的蛋白a洗脱液部分含有高滴度(> 1:1000)的内皮细胞刺激活性，这种活性被特异性单克隆抗人胰岛素样生长因子1受体抗体显著中和。脂肪扩张型Graves眼病的蛋白a洗脱液部分含有内皮细胞抑制活性(低滴度)和刺激活性(高滴度)，后者的刺激活性被特异性抗碱性成纤维细胞生长因子抗体完全中和。结论graves病眼球脱垂继发于眼眶脂肪明显扩张，血浆中存在成纤维细胞生长因子抑制和刺激自身抗体。后者被抗碱性成纤维细胞生长因子抗体完全中和。

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引用次数: 1

Oral Glucose Tolerance Test with Cooked Rhizomes of Zingiber Officinale (Ginger) 生姜根茎炮制后口服葡萄糖耐量试验

Endocrinology, diabetes and metabolism journal

Pub Date : 2019-01-02 DOI: 10.31038/edmj.2019311

M. A. Mannan, K. Jannat, M. Rahmatullah

Rhizomes of Zingiber officinale (ginger) are used as a spice in many culinary dishes of Bangladesh. Since a number of scientific reports are present on the beneficial effects of raw ginger in Type 2 diabetes mellitus, it was of interest to determine the anti-hyperglycemic efficacy of cooked (boiled) ginger through oral glucose tolerance test (OGTT) in mice. The OGTT results showed that when administered at doses of 50, 100, 200 and 400 mg per kg body weight, methanolic extract of cooked ginger (MEZOC) reduced blood glucose in glucose-loaded mice by 8.0, 20.3, 29.2, and 32.0%, respectively. By comparison, a standard antihyperglycemic drug, glibenclamide, when administered at a dose of 10 mg per kg, reduced blood glucose levels by 48.8%. The results suggest that cooked ginger retains efficiency in lowering blood glucose. Since cooking causes ginger to be less pungent, partaking of ginger in such a manner may prove to be more acceptable to diabetic patients and help control their blood glucose concentrations.

生姜的根茎在孟加拉国的许多烹饪菜肴中被用作香料。由于已有许多关于生姜对2型糖尿病有益作用的科学报道，因此通过小鼠口服葡萄糖耐量试验(OGTT)来确定煮熟(煮熟)姜的抗高血糖功效是一项有趣的研究。OGTT结果显示，每公斤体重50、100、200和400 mg剂量的熟姜甲醇提取物(MEZOC)分别使葡萄糖负荷小鼠的血糖降低8.0、20.3%、29.2%和32.0%。相比之下，标准的抗高血糖药物格列本脲每公斤10毫克的剂量可使血糖水平降低48.8%。研究结果表明，煮熟的生姜仍有降低血糖的功效。由于烹饪使姜不那么刺鼻，以这种方式吃姜可能更容易被糖尿病患者接受，并有助于控制他们的血糖浓度。

引用次数: 0

Zinc Supplements – Any Benefit in Diabetes? 锌补充剂对糖尿病有好处吗?

Endocrinology, diabetes and metabolism journal

Pub Date : 2019-01-01 DOI: 10.31038/edmj.2019342

I. Télessy

Zinc is a divalent cation mainly present intracellularly and exerts several indispensible effect therefore maintaining zinc homeostasis is essential. Zinc has a pivotal role in the insulin production, storage and pathways and in carbohydrate metabolism. Plays also an important function in the development of diabetes mellitus and diabetic complications as well. Based on preclinical and clinical studies here we present the most important contributions of zinc to diabetic state and briefly demonstrate why zinc supplementation is beneficial for diabetic patients.

锌是一种主要存在于细胞内的二价阳离子，具有多种不可缺少的作用，因此维持锌的稳态至关重要。锌在胰岛素的产生、储存和途径以及碳水化合物代谢中起着关键作用。在糖尿病和糖尿病并发症的发生中也起着重要的作用。基于临床前和临床研究，本文介绍了锌对糖尿病状态的最重要贡献，并简要说明了为什么锌补充剂对糖尿病患者有益。

引用次数: 0

Comparison of Inositol, Metformin and Oral Contraceptives in Polycystic Ovary Syndrome 肌醇、二甲双胍和口服避孕药治疗多囊卵巢综合征的比较

Endocrinology, diabetes and metabolism journal

Pub Date : 2019-01-01 DOI: 10.31038/edmj.2019352

Andreea Borlea, L. Cotoi, L. Deharde, D. Stoian

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder that affects women in reproductive age and associates variable degrees of hyperandrogenism, anovulation and/or Polycystic Ovary Morphology (PCOM), generating different phenotypes. Due to its heterogenic etiology, there is no general treatment, but rather an individual approach for each case. The aim of this study is to detect possible variations in clinical and biochemical outcome in PCOS cases, after treatment with combined oral contraceptive pills, metformin or inositols. This prospective study presents 56 patients in fertile age (18–36 years old), diagnosed with PCOS, which received treatment with oral contraceptives (30mg Etinylestradiol+Dienogest), metformin (2x500mg) or inositols (2g Myoinositol). Patients were evaluated clinically and biochemically at baseline, at 3 and 6 months. In patients treated with contraceptive pills, LH levels decreased by 77.71% after 3 months, and LH:FSH ratio with 54.01% (p=0.0005) after 6 months. There was a 52% improvement in PCOM at ultrasound examination from 3 months treatment on (p<0.0001), but no significant decrease in menstrual cycle length. Metformin proved superior in decreasing abdominal circumference and HbA1c. The inositol group had the most significant improvement after 3 months, all parameters being significantly improved apart from Ferriman-Gallwey score; menstrual cycle pattern improved significantly after 3 months of treatment (54.7%, p=0.0008). There were significant differences in outcomes for clinical and biochemical parameters between the different treatments, yet none of them turned out superior in all main signs and symptoms, (hyperandrogenism, ovarian dysfunction and polycystic morphology). Treatment in PCOS patients should be individualised to patient’s symptoms and needs.

多囊卵巢综合征(Polycystic ovarian Syndrome, PCOS)是一种常见于育龄期女性的内分泌疾病，伴有不同程度的高雄激素、无排卵和/或多囊卵巢形态(Polycystic Ovary Morphology, PCOM)，产生不同的表型。由于其异质性的病因，没有一般的治疗方法，而是针对每个病例采取单独的治疗方法。本研究的目的是检测多囊卵巢综合征患者在口服避孕药、二甲双胍或肌醇联合治疗后临床和生化结果的可能变化。本前瞻性研究纳入56例育龄(18-36岁)诊断为PCOS的患者，接受口服避孕药(30mg炔雌雌二醇+Dienogest)、二甲双胍(2x500mg)或肌醇(2g肌醇)治疗。在基线、3个月和6个月时对患者进行临床和生化评估。服用避孕药后3个月LH水平下降77.71%，6个月LH:FSH比值下降54.01% (p=0.0005)。与治疗3个月相比，超声检查PCOM改善52% (p<0.0001)，但月经周期长度无明显减少。二甲双胍在降低腹围和HbA1c方面表现优异。肌醇组在3个月后改善最为显著，除Ferriman-Gallwey评分外，其他指标均有显著改善;治疗3个月后月经周期明显改善(54.7%，p=0.0008)。不同的治疗方法在临床和生化参数的结果上存在显著差异，但在所有主要体征和症状(雄激素分泌亢进、卵巢功能障碍和多囊形态)上都没有表现出优势。多囊卵巢综合征患者的治疗应根据患者的症状和需要进行个体化治疗。

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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“偏倚激动作用”:代谢性谷氨酸2/3受体激动作用正调节神经毒性

Endocrinology, diabetes and metabolism journal

Pub Date : 2019-01-01 Epub Date: 2019-08-14

Mark B Zimering, Shree G Nadkarni

Aims: To 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.

Methods: Plasma 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.

Results: Chronic 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.

Conclusion: Schizophrenia 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神经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;以及通过代谢2/3受体激动剂LY379268调节血清素能信号。方法:对5例老年慢性精神分裂症患者和8例年龄匹配的其他神经精神、免疫或代谢疾病患者的血浆进行蛋白- a亲和层析，获得IgG自身抗体。在Gq/11/PLC/IP3R信号通路、gi偶联、β -arrestin2导向通路或LY379268的特异性拮抗剂存在或不存在的情况下，用自身抗体孵育小鼠N2A神经母细胞瘤细胞，测定平均神经突缩回(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可完全预防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神经突退缩。LY379268促进自身抗体诱导的神经突收缩，导致剂量-反应曲线向左偏移。RhoA/Rho激酶和Gq/11/PLC/IP3R信号通路的拮抗剂可阻断自身抗体介导的神经突收缩。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:精神分裂症血浆自身抗体激活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细胞神经突缩回。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激酶依赖的机制促进了N2A细胞存活的增加(部分)。LY379268对5-HT2AR介导的神经突收缩的正向调节表明，自身抗体可能(部分地)靶向5-HT2AR/mGlu2R异构体。

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引用次数: 0

Comparative Treatment between Sitagliptin vs. Metformin, Alone or In Combination, In Patients with Polycystic Ovarian Syndrome. A Clinical Entity with a High Risk of Developing Diabetes Mellitus and Gestational Diabetes 西格列汀与二甲双胍单独或联合治疗多囊卵巢综合征患者的比较治疗糖尿病及妊娠期糖尿病高危人群的临床研究

Endocrinology, diabetes and metabolism journal

Pub Date : 2019-01-01 DOI: 10.31038/edmj.2019341

J. C. P. Palma, C. Velázquez, Mario Alberto Huesca Rodriguez, L. B. Macedo, Dra., C. P. Palma, E. Hernández, Beatriz Irene Sanchez Trampe, DanielLópez Hernández, Georgina, G. Zarate, M. R. Bonilla

Juan Carlos Paredes Palma1*, Carlos Ramirez Velázquez2, Mario Alberto Huesca Rodriguez3, Lorena Balladares Macedo4, Dra Claudia N Paredes Palma4, Erik Osvaldo Sanchez Hernández5, Beatriz Irene Sanchez Trampe6, Daniel López Hernandez7, Georgina González Zárate7, Maria De Rocío Thompson Bonilla8 1Head of Teaching and Research Delegation South Area of the ISSSTE, Mexico City, Mexico 2Research Coordinator in the Delegation South Area of the ISSSTE, Mexico City, Mexico 3Medical Delegate of the South Area of ISSSTE, Mexico City, Mexico 4Specialist in Gynecology and Obstetrics Addressed To the Churubusco ISSSTE Clinic of Specialties, Mexico City, Mexico 5Head of Teaching and Research of the Churubusco ISSSTE Clinic of Specialties ISSSTE, Mexico City, Mexico 6Coordinator of Teaching and Research of the “Dr. Dario Fernandez Fierro” Hospital of the ISSSTE, Mexico City, Mexico 7Clinical Researcher of the Medical Subdelegation of the South Area of the ISSSTE, Mexico City, Mexico 8Biomolecular Research of the “1 DE OCTUBRE”Hospital of the ISSSTE, Mexico City, Mexico

Juan Carlos Paredes Palma1*， Carlos Ramirez Velázquez2, Mario Alberto Huesca rodriguez, Lorena Balladares Macedo4, Dra Claudia N Paredes Palma4, Erik Osvaldo Sanchez Hernández5, Beatriz Irene Sanchez Trampe6, Daniel López Hernandez7, Georgina González Zárate7, Maria De Rocío Thompson Bonilla8 1墨西哥墨西哥城国家科学技术援助协会南部地区教学和研究代表团负责人2墨西哥墨西哥城国家科学技术援助协会南部地区研究协调员，墨西哥3墨西哥墨西哥城ISSSTE南区医学代表4墨西哥墨西哥城Churubusco ISSSTE专科诊所妇产科专家5墨西哥墨西哥城ISSSTE Churubusco ISSSTE专科诊所教研组组长6墨西哥墨西哥城ISSSTE“Dr. Dario Fernandez Fierro”医院教研组协调员7 ISSSTE南区医学分团临床研究员墨西哥，墨西哥城8墨西哥国家科学院“10月1日”医院生物分子研究，墨西哥城

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引用次数: 1