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The Landscape of Androgens in Cushing's Syndrome. 库欣综合征中雄激素的作用。
Hanna F Nowotny, Leah Braun, Nicole Reisch

Hyperandrogenemia in patients with Cushing's syndrome (CS) presents a diagnostic pitfall due to its rare occurrence and overlapping symptoms with more common conditions like polycystic ovary syndrome (PCOS). This review explores the significance of androgen dysregulation in CS, focusing on both classical and 11-oxygenated androgens. While classical androgens contribute to hyperandrogenism in CS, their levels alone do not fully account for clinical symptoms. Recent research highlights the overlooked role of 11oxC19 androgens, particularly 11OHA4 and 11KT, in driving hyperandrogenic manifestations across all CS subtypes. These adrenal-specific and highly potent androgens offer stable expression throughout the lifespan of a woman, serving as valuable diagnostic biomarkers. Understanding their prominence not only aids in subtype differentiation but also provides insights into the complex nature of androgen dysregulation in CS. Recognizing the diagnostic potential of 11oxC19 androgens promises to refine diagnostic approaches and improve clinical management strategies for patients with CS.

库欣综合征(Cushing's Syndrome,CS)患者的高雄激素血症是一个诊断陷阱,因为它很少发生,而且症状与多囊卵巢综合征(Polycystic ovary Syndrome,PCOS)等更常见的疾病重叠。本综述探讨了雄激素失调在库欣综合征中的意义,重点关注经典雄激素和 11 氧代雄激素。虽然传统雄激素会导致 CS 中的雄激素过多,但仅凭其水平并不能完全解释临床症状。最近的研究强调了 11oxC19 雄激素(尤其是 11OHA4 和 11KT)在所有 CS 亚型的高雄激素表现中被忽视的作用。这些肾上腺特异性强的雄激素在女性的整个生命周期中都有稳定的表达,是有价值的诊断生物标志物。了解它们的重要性不仅有助于亚型的区分,还能深入了解 CS 中雄激素失调的复杂性。认识到 11oxC19 雄激素的诊断潜力有望完善 CS 患者的诊断方法并改进临床管理策略。
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引用次数: 0
Evaluating the Diagnostic Role of ACR-TIRADS and Bethesda Classifications in Thyroid Nodules Highlighted by Cyto-Histopathological Studies. 评估 ACR-TIRADS 和 Bethesda 分类在甲状腺结节细胞组织病理学研究中的诊断作用。
Marwa S Eissa, Rania M Sabry, Mona S Abdellateif

Objective: To evaluate the accuracy of thyroid imaging reporting and data system (ACR-TIRADS) and the Bethesda system for reporting cytopathology (TBSRCP) classifications for identifying or ruling out thyroid malignancy in relation to the gold standard (post-surgical pathology).

Methods: This cross-sectional study included 573 patients with single or multiple thyroid nodules. Patients were evaluated using the TIRADS and the TBSRCP classification. The data from a cohort of patients who underwent surgery (77/573, 13.4%) were correlated with post-operative pathology and the relevant clinical features of the patients.

Results: Of 573 patients, 545 (95.1%) were euthyroid, 24 (4.1%) were hypothyroid, and 4 (0.8%) were hyperthyroid; 419 (73.1%) had benign nodules (Bethesda II), 115 (20.1%) had intermediate (Bethesda III, IV), and 39 (6.8%) had Bethesda V and VI nodules. Four-hundred twenty (73.3%) patients were categorized as TIRADS 2,3, and 153 (26.7%) were categorized as TIRADS 4,5. The Bethesda and TIRADS classifications concorded significantly in thyroid nodule diagnosis (K=14.9%, P<0.001).Thyroid malignancy was significantly associated with microcalcification and interrupted halo, while benign nodules were significantly associated with macrocalcification and complete halo type (P=0.041, P=0.005, respectively). The TBSRCP could significantly detect malignant thyroid nodules with a sensitivity, specificity, PPV, and NPV of 64.1%, 98.1%, 85.0%, and 94.1%, respectively (K=88.2%, P<0.001), while the respective values for the TIRADS classification were 63.5%, 76.0%, 84.6%, and 50.0% (K=34.8%, P=0.001).

Conclusion: The TIRADS and TBSRCP are essential primary steps for evaluating thyroid nodules and both are complimentary. Hence, each patient with thyroid nodules should be evaluated by both approaches before opting for surgery. Highly suspicious TIRADS categories TR4 and TR5 need further evaluation by fine needle aspiration cytology.

目的评估甲状腺成像报告和数据系统(ACR-TIRADS)和贝塞斯达细胞病理学报告系统(TBSRCP)分类在确定或排除甲状腺恶性肿瘤方面与金标准(手术后病理学)相比的准确性:这是一项横断面研究,共纳入了573例单发或多发甲状腺结节患者。采用TIRADS和TBSRCP分类法对患者进行评估。研究数据与接受手术的 77/573 例患者(13.4%)的术后病理结果以及患者的相关临床特征相关联:545例(95.1%)患者甲状腺功能正常,24例(4.1%)患者甲状腺功能减退,只有4例(0.8%)患者甲状腺功能亢进。419名(73.1%)患者有良性结节(贝塞斯达II),115名(20.1%)患者有中等结节(贝塞斯达III、IV),39名(6.8%)患者有贝塞斯达V、VI。有 420 名(73.3%)患者为 TIRADS 2、3 级,153 名(26.7%)患者为 TIRADS 4、5 级。在甲状腺结节的诊断中,贝塞斯达和 TIRADS 有明显的一致性(K=14.9%,PC 结论:TIRADS和TBSRCP是评估甲状腺结节的基本步骤,两者互为补充。因此,建议每位甲状腺结节患者在匆忙进行手术前都要同时进行这两个步骤。高度可疑的TIRADS分类TR4和TR5需要通过细针穿刺细胞学(FNAC)进行进一步评估。
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引用次数: 0
Dihydromyricetin Improves High Glucose-Induced Dopaminergic Neuronal Damage by Activating AMPK-Autophagy Signaling Pathway. 二氢杨梅素通过激活AMPK-自噬信号通路改善高糖诱导的多巴胺能神经元损伤。
Qi Li, Zhenjiang Song, Liting Peng, Shuidong Feng, Kebin Zhan, Hongyan Ling

Introduction: In recent years, a growing number of clinical and biological studies have shown that patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing Parkinson's disease (PD). Prolonged exposure to hyperglycemia results in abnormal glucose metabolism, which in turn causes pathological changes similar to PD, leading to selective loss of dopaminergic neurons in the compact part of the substantia nigra. Dihydromyricetin (DHM) is a naturally occurring flavonoid with various biological activities including antioxidant and hepatoprotective properties. In this study, the effect of DHM on high glucose-induced dopaminergic neuronal damage was investigated.

Methods: The potential modulatory effects of DHM on high glucose-induced dopaminergic neuronal damage and its mechanism were studied.

Results: DHM ameliorated high glucose-induced dopaminergic neuronal damage and autophagy injury. Inhibition of autophagy by 3-methyladenine abrogated the beneficial effects of DHM on high glucose-induced dopaminergic neuronal damage. In addition, DHM increased levels of p-AMP-activated protein kinase (AMPK) and phosphorylated UNC51-like kinase 1. The AMPK inhibitor compound C eliminated DHM-induced autophagy and subsequently inhibited the ameliorative effects of DHM on high glucose-induced dopaminergic neuronal damage.

Discussion: DHM ameliorates high glucose-induced dopaminergic neuronal damage by activating the AMPK-autophagy pathway.

近年来,越来越多的临床和生物学研究表明,2型糖尿病(T2DM)患者患帕金森病(PD)的风险增加。长期处于高血糖状态会导致糖代谢异常,进而引起类似帕金森病的病理变化,导致黑质紧密部位多巴胺能神经元的选择性丧失。二氢杨梅素(DHM)是一种天然类黄酮,具有多种生物活性,包括抗氧化和保肝特性。本研究旨在探讨 DHM 是否能调节高糖诱导的多巴胺能神经元损伤及其机制。我们发现,DHM 可改善高糖诱导的多巴胺能神经元损伤和自噬损伤。用3-甲基腺嘌呤(3-MA)抑制自噬会减弱DHM对高糖诱导的多巴胺能神经元损伤的有益作用。此外,DHM 还增加了 p-AMPK 和 p-ULK1 的水平。AMPK 抑制剂化合物 C(CC)消除了 DHM 诱导的自噬,随后抑制了 DHM 对高葡萄糖诱导的多巴胺能神经元损伤的改善作用。综上所述,DHM通过激活AMPK-自噬通路来改善高糖诱导的多巴胺能神经元损伤。
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引用次数: 0
Efficacy of Thyroid Hormone Replacement Therapy in Nasopharyngeal Carcinoma Patients with Radiation-Induced Subclinical Hypothyroidism. 甲状腺激素替代疗法对因辐射导致亚临床甲状腺功能减退的鼻咽癌患者的疗效。
Chen-Lu Lian, Gui-Ping Chen, Rui Zhou, Yi-Feng Yu, Ping Zhou, Qin Lin, San-Gang Wu

Aims: Hypothyroidism is a common side effect of radiotherapy for nasopharyngeal carcinoma. However, the impact of thyroid hormone replacement therapy on patients with radiation-induced subclinical hypothyroidism has not been extensively explored. This study aimed to analyze the efficacy of thyroid hormone replacement therapy in nasopharyngeal carcinoma patients with subclinical hypothyroidism.

Methods: Patients diagnosed with nasopharyngeal carcinoma who developed subclinical hypothyroidism after definitive radiotherapy between September 2019 and December 2020 were selected for inclusion in this study. Prior to thyroid hormone replacement therapy and after maintaining euthyroidism for 6-12 months through thyroid hormone replacement therapy, assessments using the SF36 Brief Health Status Scale and the Hypothyroidism-related Symptom Questionnaire were conducted via trained questionnaires. Lipid profiles were assessed at baseline and after 6-12 months of thyroid hormone replacement therapy. Statistical analyses were performed using matched samples T-test or Mann-Whitney U test.

Results: The median follow-up period was 14.5 months. The median score of hypothyroid symptoms was 5.5 out of 19 points, with the most common symptoms being chills (65.0%), fatigue (50.0%), weight gain (45.0%), and limb numbness (40.0%). Thyroid hormone replacement therapy did not significantly improve the quality of life, hypothyroidism-related symptoms, or blood lipid profile in patients. However, there was an observed downward trend in serum cholesterol levels following treatment (P=0.052).

Conclusion: Thyroid hormone replacement therapy did not have a significant impact on alleviating hypothyroid symptoms, improving quality of life, or enhancing lipid profiles in patients with radiation-induced subclinical hypothyroidism. Nevertheless, a potential decrease in serum cholesterol levels was noted after thyroid hormone replacement therapy.

鼻咽癌的甲状腺激素替代疗法。
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引用次数: 0
Diabetes Mellitus and its Association with Work Patterns and Characteristics: A Narrative Review. 糖尿病及其与工作模式和特点的关系:叙述性综述。
Anna Eleftheriou, Aikaterini Rokou, Evangelia Nena, Nikolaos Papanas

Diabetes mellitus is a leading cause of disability with adverse effects on the quality of life. It also affects occupational health by impacting several work-related parameters. This review discusses the relationship between diabetes and absenteeism, presenteeism, work impairment and unemployment. The association between work and diabetic complications such as neuropathic pain, diabetic foot, psychological issues and hypoglycemia due to treatment is also examined. Evidence points to a relationship between diabetes and absenteeism, reduced work productivity, and, thus, overall work impairment. A stronger negative impact on work performance is mediated by painful diabetic neuropathy and diabetic foot. In addition, psychological distress has been positively correlated with total workdays lost and frequency of absence. Depression in the diabetic population has also been linked with increased absenteeism, presenteeism, and work disability. Moreover, hypoglycaemia induced by antidiabetic medication may affect work attendance and performance. Finally, diabetes has been associated with inequality in the work environment, lower job satisfaction and higher unemployment rates, mainly because of its complications.

糖尿病是导致残疾的主要原因之一,对生活质量有不利影响。它还会影响多个工作参数,从而影响职业健康。本综述旨在讨论糖尿病与缺勤、旷工、工作损伤和失业之间的关系。此外,还探讨了工作与糖尿病并发症(如神经性疼痛、糖尿病足、心理问题和因治疗导致的低血糖)之间的关系。有证据表明,糖尿病与旷工、工作效率降低以及整体工作受损有关。疼痛性糖尿病神经病变和糖尿病足对工作表现的负面影响更大。此外,心理困扰与总工作日损失和缺勤频率呈正相关。糖尿病患者的抑郁情绪也与缺勤、旷工和工作残疾的增加有关。此外,抗糖尿病药物引起的低血糖可能会影响出勤率和工作表现。最后,糖尿病与工作环境不平等、工作满意度较低和失业率较高有关,这主要是由于其并发症所致。
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引用次数: 0
A Single Sauna Session Does Not Improve Postprandial Blood Glucose Handling in Individuals with Type 2 Diabetes Mellitus: A Cross-Over, Randomized, Controlled Trial. 单次桑拿不会改善 2 型糖尿病患者的餐后血糖控制:一项交叉、随机对照试验。
Laura Schenaarts, Floris K Hendriks, Cas J Fuchs, Wendy Em Sluijsmans, Tim Snijders, Luc Jc van Loon

Introduction: Passive heat treatment has been suggested to improve glycemic control in individuals with type 2 diabetes mellitus (T2DM). Previous studies have focused predominantly on hot water immersion and traditional sauna bathing, as opposed to the more novel method of infrared-based sauna bathing. Here, the impact of a single infrared sauna session on post-prandial glycemic control was assessed in older individuals with T2DM.

Methods: In this randomized controlled crossover trial, 12 participants with T2DM (male/female: 10/2, age: 69±7 y, BMI: 27.5±2.9 kg/m2) rested in an infrared sauna twice: once in a heated (60°C) and once in a thermoneutral (21°C) condition for 40 min, immediately followed by a 2-h oral glucose tolerance test (OGTT). Venous blood samples were obtained to assess plasma glucose and insulin concentrations and to determine the whole-body composite insulin sensitivity index.

Results: Body core and leg skin temperature were higher following the heated condition compared to the thermoneutral condition (38.0±0.3 vs. 36.6±0.2°C and 39.4±0.8 vs. 31.3±0.8°C, respectively; P<0.001 for both). The incremental area under the curve (iAUC) of plasma glucose concentrations during the OGTT was higher after the heated condition compared to the thermoneutral condition (17.7±3.1 vs. 14.8±2.8 mmol/L/120 min; P<0.001). No differences were observed in plasma insulin concentrations (heated: 380±194 vs. thermoneutral: 376±210 pmol/L/120 min; P=0.93) or whole-body composite insulin sensitivity indexes (4.5±2.8 vs. 4.5±2.1; P=0.67).

Conclusions: A single infrared sauna session does not improve postprandial blood glucose handling in individuals with T2DM. Future studies should assess the effect of more prolonged application of infrared sauna bathing on daily glycemic control.

介绍:被动热疗被认为可以改善 2 型糖尿病患者的血糖控制。以前的研究主要集中在热水浸泡和传统桑拿浴,而不是更新颖的红外线桑拿浴方法。在此,我们评估了一次红外线桑拿浴对老年 2 型糖尿病患者餐后血糖控制的影响:在这项随机对照交叉试验中,12 名 2 型糖尿病患者(男/女:10/2,年龄:69±7 岁,体重指数:27.5±2.9 kg/m2)在红外线桑拿浴中休息了两次:一次在加热条件下(60°C),一次在中温条件下(21°C),共 40 分钟,随后立即进行了 2 小时的口服葡萄糖耐量试验(OGTT)。采集静脉血样本以评估血浆葡萄糖和胰岛素浓度,并测定全身胰岛素敏感性综合指数:结果:与恒温状态相比,加热状态下的体温和腿部皮肤温度更高(分别为 38.0±0.3 vs 36.6±0.2°C 和 39.4±0.8 vs 31.3±0.8°C;PPP=0.93),全身综合胰岛素敏感指数也更高(4.5±2.8 vs 4.5±2.1;P=0.67)。结论 单次红外线桑拿并不能改善 2 型糖尿病患者餐后血糖的处理。未来的研究应评估更长时间的红外桑拿浴对日常血糖控制的影响。
{"title":"A Single Sauna Session Does Not Improve Postprandial Blood Glucose Handling in Individuals with Type 2 Diabetes Mellitus: A Cross-Over, Randomized, Controlled Trial.","authors":"Laura Schenaarts, Floris K Hendriks, Cas J Fuchs, Wendy Em Sluijsmans, Tim Snijders, Luc Jc van Loon","doi":"10.1055/a-2406-4491","DOIUrl":"10.1055/a-2406-4491","url":null,"abstract":"<p><strong>Introduction: </strong>Passive heat treatment has been suggested to improve glycemic control in individuals with type 2 diabetes mellitus (T2DM). Previous studies have focused predominantly on hot water immersion and traditional sauna bathing, as opposed to the more novel method of infrared-based sauna bathing. Here, the impact of a single infrared sauna session on post-prandial glycemic control was assessed in older individuals with T2DM.</p><p><strong>Methods: </strong>In this randomized controlled crossover trial, 12 participants with T2DM (male/female: 10/2, age: 69±7 y, BMI: 27.5±2.9 kg/m<sup>2</sup>) rested in an infrared sauna twice: once in a heated (60°C) and once in a thermoneutral (21°C) condition for 40 min, immediately followed by a 2-h oral glucose tolerance test (OGTT). Venous blood samples were obtained to assess plasma glucose and insulin concentrations and to determine the whole-body composite insulin sensitivity index.</p><p><strong>Results: </strong>Body core and leg skin temperature were higher following the heated condition compared to the thermoneutral condition (38.0±0.3 vs. 36.6±0.2°C and 39.4±0.8 vs. 31.3±0.8°C, respectively; P<0.001 for both). The incremental area under the curve (iAUC) of plasma glucose concentrations during the OGTT was higher after the heated condition compared to the thermoneutral condition (17.7±3.1 vs. 14.8±2.8 mmol/L/120 min; P<0.001). No differences were observed in plasma insulin concentrations (heated: 380±194 vs. thermoneutral: 376±210 pmol/L/120 min; P=0.93) or whole-body composite insulin sensitivity indexes (4.5±2.8 vs. 4.5±2.1; P=0.67).</p><p><strong>Conclusions: </strong>A single infrared sauna session does not improve postprandial blood glucose handling in individuals with T2DM. Future studies should assess the effect of more prolonged application of infrared sauna bathing on daily glycemic control.</p>","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":" ","pages":"622-630"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From Nelson's Syndrome to Corticotroph Tumor Progression Speed: An Update. 从纳尔逊综合征到皮质营养肿瘤进展速度:最新进展。
Laura Bessiène, Chiara Villa, Xavier Bertagna, Bertrand Baussart, Guillaume Assié

Since the first description of Nelson syndrome 60 years ago, the way to consider corticotroph pituitary neuroendocrine tumors (PitNETs) after bilateral adrenalectomy has evolved. Today, it is globally acknowledged that only a subset of corticotroph PitNETs is aggressive.After adrenalectomy, corticotroph tumor progression (CTP) occurs in about 30 to 40% of patients during a median follow-up of 10 years. When CTP occurs, various CTP speeds (CTPS) can be observed. Using simple metrics in patients with CTP, CTPS was reported to vary from a few millimeters to up to 40 mm per year. Rapid CTPS/ Nelson's syndrome was associated with more severe Cushing's disease, higher adrenocorticotropic hormone (ACTH) in the year following adrenalectomy, and higher Ki67 on pituitary pathology. Complications such as apoplexy, cavernous syndrome, and visual defects were associated with higher CTPS. During follow-up, early morning ACTH, absolute variations properly reflected CTPS. Finally, CTPS was not higher after than before adrenalectomy, suggesting that cortisol deprivation after adrenalectomy does not impact CTPS in a majority of patients.Taken together, rapid CTPS/ Nelson's syndrome probably reflects the intrinsic aggressiveness of some corticotroph PitNETs. The precise molecular mechanisms related to corticotroph PitNET aggressiveness remain to be deciphered. Regular MRIs combined with intermediate morning ACTH measurements probably provide a reliable way to detect early and manage fast-growing tumors and, therefore, limit the complications.

自 60 年前首次描述纳尔逊综合征以来,考虑双侧肾上腺切除术后皮质垂体神经内分泌肿瘤 (PitNET) 的方法不断演变。如今,全球公认只有一部分皮质垂体神经内分泌肿瘤具有侵袭性。肾上腺切除术后,在 10 年的中位随访期间,约有 30% 至 40% 的患者会出现皮质营养肿瘤进展(CTP)。当 CTP 发生时,可以观察到各种 CTP(CTPS)速度。据报道,通过对 CTP 患者进行简单的度量,CTPS 的变化范围从每年几毫米到每年高达 40 毫米。快速 CTPS/Nelson's 综合征与更严重的库欣、肾上腺切除术后一年内更高的促肾上腺皮质激素和更高的垂体病理学 Ki67 有关。并发症,如脑溢血、海绵体综合征和视觉缺陷与较高的 CTPS 有关。在随访期间,清晨促肾上腺皮质激素的绝对值变化正确地反映了CTPS。最后,肾上腺切除术后的 CTPS 并不高于肾上腺切除术前,这表明肾上腺切除术后的皮质醇剥夺不会影响大多数患者的 CTPS。综上所述,快速 CTPS/Nelson's 综合征可能反映了某些皮质营养型 PitNET 的内在侵袭性。与皮质营养型PitNET侵袭性有关的确切分子机制仍有待破解。定期进行核磁共振成像和中间晨间促肾上腺皮质激素(ACTH)测量可能是早期发现和控制快速生长肿瘤的可靠方法,因此可以限制并发症的发生。
{"title":"From Nelson's Syndrome to Corticotroph Tumor Progression Speed: An Update.","authors":"Laura Bessiène, Chiara Villa, Xavier Bertagna, Bertrand Baussart, Guillaume Assié","doi":"10.1055/a-2359-8649","DOIUrl":"10.1055/a-2359-8649","url":null,"abstract":"<p><p>Since the first description of Nelson syndrome 60 years ago, the way to consider corticotroph pituitary neuroendocrine tumors (PitNETs) after bilateral adrenalectomy has evolved. Today, it is globally acknowledged that only a subset of corticotroph PitNETs is aggressive.After adrenalectomy, corticotroph tumor progression (CTP) occurs in about 30 to 40% of patients during a median follow-up of 10 years. When CTP occurs, various CTP speeds (CTPS) can be observed. Using simple metrics in patients with CTP, CTPS was reported to vary from a few millimeters to up to 40 mm per year. Rapid CTPS/ Nelson's syndrome was associated with more severe Cushing's disease, higher adrenocorticotropic hormone (ACTH) in the year following adrenalectomy, and higher Ki67 on pituitary pathology. Complications such as apoplexy, cavernous syndrome, and visual defects were associated with higher CTPS. During follow-up, early morning ACTH, absolute variations properly reflected CTPS. Finally, CTPS was not higher after than before adrenalectomy, suggesting that cortisol deprivation after adrenalectomy does not impact CTPS in a majority of patients.Taken together, rapid CTPS/ Nelson's syndrome probably reflects the intrinsic aggressiveness of some corticotroph PitNETs. The precise molecular mechanisms related to corticotroph PitNET aggressiveness remain to be deciphered. Regular MRIs combined with intermediate morning ACTH measurements probably provide a reliable way to detect early and manage fast-growing tumors and, therefore, limit the complications.</p>","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":" ","pages":"581-590"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Skeletal Effects of a Prolonged Oral Metformin Treatment in Adult Wistar Rats. 成年 Wistar 大鼠长期口服二甲双胍对骨骼的影响
Nahuel E Wanionok, María S Molinuevo, Juan M Fernández, Besada Lucas, Ana M Cortizo, Evelyn J Castillo, Jessica M Jiron, Sedlinsky Claudia, Schurman Leon, José I Aguirre, Antonio D McCarthy

Introduction: We previously showed that a 3-week oral metformin (MET) treatment enhances the osteogenic potential of bone marrow stromal cells (BMSCs) and improves several bone histomorphometric parameters in Wistar rats with metabolic syndrome (MetS). However, the skeletal effects of extended periods of MET need to be completely elucidated. Hence, in this study, the impact of a prolonged (3-month) MET treatment was investigated on bone architecture, histomorphometric and biomechanics variables, and osteogenic potential of BMSCs in Wistar rats with or without MetS.

Materials and methods: Young male Wistar rats (n=36) were randomized into four groups (n=9) that received either 20% fructose (F), MET (MET), F plus MET treatments (FMET), or drinking water alone (Veh). Rats were euthanized, blood was collected, and bones were dissected and processed for peripheral quantitative computed tomography (pQCT) analysis, static and dynamic histomorphometry, and bone biomechanics. In addition, BMSCs were isolated to determine their osteogenic potential.

Results: MET affected trabecular and cortical bone, altering bone architecture and biomechanics. Furthermore, MET increased the pro-resorptive profile of BMSCs. In addition, fructose-induced MetS practically did not affect the the structural or mechanical variables of the skeleton.

Conclusion: A 3-month treatment with MET (with or without MetS) affects bone architecture and biomechanical variables in Wistar rats.

简介:我们以前的研究表明,在患有代谢综合征(MetS)的Wistar大鼠中,口服三周二甲双胍(MET)可增强骨髓基质细胞(BMSCs)的成骨潜能,并改善骨骼组织形态学的一些参数。然而,长期服用 MET 对骨骼的影响仍未完全阐明。因此,我们研究了长期(3 个月)MET 处理对有或没有 MetS 的 Wistar 大鼠骨结构、组织形态计量学和生物力学变量以及 BMSCs 成骨潜能的影响。材料和方法:36 只年轻雄性 Wistar 大鼠被随机分为四组(n=9),分别接受 20% 果糖(F)、MET(MET)、F 加 MET 处理(FMET)或单独饮用水(Veh)。对大鼠实施安乐死,收集血液,解剖并处理骨骼,进行 pQCT 分析、静态和动态组织形态测量以及骨生物力学分析。此外,还分离了 BMSCs,以确定其成骨细胞的潜力:结果:MET影响了骨小梁和皮质骨,改变了骨结构和生物力学。此外,MET 增加了 BMSCs 的促骨吸收特性。此外,果糖诱导的 MetS 实际上并不影响骨骼的结构或机械变量:结论:为期 3 个月的 MET 治疗(无论是否存在 MetS)都会影响 Wistar 大鼠的骨骼结构和生物力学变量。
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引用次数: 0
Oridonin Attenuates Diabetes‑induced Renal Fibrosis via the Inhibition of TXNIP/NLRP3 and NF‑κB Pathways by Activating PPARγ in Rats. 奥利多宁通过激活 PPARγ 抑制 TXNIP/NLRP3 和 NF-κB 通路,减轻糖尿病诱发的大鼠肾脏纤维化。
Gengzhen Huang, Yaodan Zhang, Yingying Zhang, Xiaotao Zhou, Yuan Xu, Huiting Wei, Xian Chen, Yuerong Ma

Introduction: Oridonin possesses remarkable anti-inflammatory, immunoregulatory properties. However, the renoprotective effects of oridonin and the underlying molecular mechanisms in diabetic nephropathy (DN). We hypothesized that oridonin could ameliorate diabetes‑induced renal fibrosis.

Methods: Streptozocin (STZ)-induced diabetic rats were provided with a high-fat diet to establish a type 2 diabetes mellitus (T2DM) animal model, and then treated with Oridonin (10, 20 mg/kg/day) for two weeks. Kidney function and renal fibrosis were assessed. High glucose-induced human renal proximal tubule epithelial cells (HK-2) were also treated with oridonin. The expression of inflammatory factors and fibrotic markers were analyzed.

Results: Oridonin treatment preserved kidney function and markedly limited the renal fibrosis size in diabetic rats. The renal fibrotic markers were inhibited in the oridonin 10 mg/kg/day and 20 mg/kg/day groups compared to the T2DM group. The expression of thioredoxin-interacting proteins/ nod-like receptor protein-3 (TXNIP/NLRP3) and nuclear factor (NF)‑κB pathway decreased, while that of peroxisome proliferator-activated receptor-gamma (PPARγ) increased in the oridonin treatment group compared to the non-treated group. In vitro, PPARγ intervention could significantly regulate the effect of oridonin on the high glucose-induced inflammatory changes in HK-2 cells.

Conclusion: Oridonin reduces renal fibrosis and preserves kidney function via the inhibition of TXNIP/NLRP3 and NF‑κB pathways by activating PPARγ in rat T2DM model, which indicates potential effect of oridonin in the treatment of DN.

简介奥利多宁具有显著的抗炎和免疫调节特性。然而,奥利多宁对糖尿病肾病(DN)的肾脏保护作用及其潜在的分子机制尚未得到研究。我们假设奥利多宁能改善糖尿病引起的肾脏纤维化:方法:用链脲佐辛(STZ)诱导的糖尿病大鼠联合高脂饮食建立 2 型糖尿病(T2DM)动物模型,然后用奥利多宁(10、20 毫克/千克/天)治疗两周。对肾功能和肾纤维化进行了评估。我们还用奥利多宁处理了高糖诱导的人肾近曲小管上皮细胞(HK-2)。此外,我们还分析了炎症因子和纤维化标志物的表达:结果:奥利多宁治疗可保护糖尿病大鼠的肾功能,并显著限制其肾脏纤维化的程度。与 T2DM 组相比,10 毫克/千克/天组和 20 毫克/千克/天组的肾纤维化标志物均受到抑制。此外,与未治疗组相比,奥利多宁治疗组 TXNIP/NLRP3 和 NF-κB 通路的表达水平降低,PPARγ 水平升高。在体外,PPARγ的干预可显著调节奥利多宁对高糖诱导的HK-2炎症变化的影响:结论:在T2DM大鼠模型中,奥利多宁通过激活PPARγ抑制TXNIP/NLRP3和NF-κB通路,减轻肾脏纤维化并保护肾功能,这表明奥利多宁对DN具有潜在的治疗作用。
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引用次数: 0
Role of Medical and Surgical Treatment in Management of the Patients With Prolactinoma: A Single-Center Experience. 药物和手术治疗在催乳素瘤患者管理中的作用;单中心经验。
Guldana Zulfaliyeva, Ahmet Numan Demir, Semih Can Cetintas, Dilan Ozaydin, Necmettin Tanriover, Pinar Kadioglu

Background: Current guidelines recommend dopamine agonists (DA) as the primary therapeutic approach for prolactinomas; however, emerging evidence suggests that surgical intervention can also yield favorable outcomes.

Objective: To comprehensively evaluate prolactinoma patients undergoing surgical and medical treatments at our pituitary center.

Methods: Retrospective review of mMedical records from prolactinoma patients treated between 2015 and 2022 was performedwere retrospectively reviewed. The study focused on treatment outcomes and remission rates while investigating factors influencing the success of both treatment modalities in achieving remission.

Results: A total of 301 prolactinoma patients were included, of whom 199 were women. Among them, 235 were managed medically, while 66 underwent surgical intervention. The overall remission rates of patients treated with medical and surgery were similar at the final examination (Respectively respectively 82.9% and 81.8%, p=0.114). Factors associated with remission in both treatment modalities included female sex, low initial prolactin levels, small adenoma size, and absence of cavernous invasion. Compared to DA treatment, Ssurgical treatment demonstrated a higher rate of drug-free remission compared to DA treatment for microadenomas, and macroadenomas without cavernous invasion. In cases with cavernous invasion, standalone surgical treatment yielded a low rate of drug-free remission (7.7%); however, when combined with DA therapy post-surgery, remission rates increased to 66.7%.

Conclusion: Medical treatment with DAs remains the preferred option for macroadenomas with cavernous sinus invasion, and giant adenomas, with surgery reserved for selected cases to address complications. Conversely, surgery emerges as the most effective modality for achieving remission in patients with microadenomas, and macroadenomas confined to the sella. The recommendation of DAs as first-line therapy for all patients has been withdrawn in the current guidelines, and individual treatment approaches based on tumor characteristics are emphasized. Our results support this approach.

背景:目前的指南推荐多巴胺受体激动剂(DA)作为催乳素瘤的主要治疗方法:目前的指南建议将多巴胺激动剂(DA)作为催乳素瘤的主要治疗方法;然而,新出现的证据表明,手术干预也能产生良好的疗效:全面评估本垂体中心接受手术和药物治疗的泌乳素瘤患者:对2015年至2022年间接受治疗的泌乳素瘤患者的病历进行回顾性审查。研究重点是治疗结果和缓解率,同时调查影响两种治疗方式成功实现缓解的因素:共纳入 301 名泌乳素瘤患者,其中 199 人为女性。其中 235 人接受了药物治疗,66 人接受了手术治疗。最终检查结果显示,药物治疗和手术治疗患者的总体缓解率相似(分别为 82.9% 和 81.8%,P=0.114)。两种治疗方式的缓解率相关因素包括女性、初始催乳素水平低、腺瘤体积小以及无海绵体侵犯。对于微腺瘤和无海绵体侵犯的大腺瘤,手术治疗的无药缓解率高于DA治疗。在有海绵体侵犯的病例中,独立手术治疗的无药缓解率较低(7.7%);然而,如果术后结合DA治疗,缓解率则增至66.7%:结论:对于有海绵窦侵犯的大腺瘤和巨大腺瘤,使用DAs进行药物治疗仍是首选方案,而手术则保留给特定病例以解决并发症。相反,对于微腺瘤和局限于椎间盘的大腺瘤患者,手术则是获得缓解的最有效方式。目前的指南已不再建议将 DAs 作为所有患者的一线治疗方法,而是强调根据肿瘤特征采取个性化的治疗方法。我们的研究结果支持这一观点。
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Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
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