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Ameliorative effects of gallic acid on tebuconazole-induced adverse effects in the cerebellum of adult albino rats: histopathological and immunohistochemical evidence. 没食子酸对戊唑醇诱导的成年白化大鼠小脑不良反应的改善作用:组织病理学和免疫组化证据。
IF 1.1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-09-02 Epub Date: 2024-08-06 DOI: 10.1080/01913123.2024.2387685
Omnia I Ismail, Hala Mohamed Hassanin

Tebuconazole (TEB) is a common triazole sterol demethylation inhibitor fungicide utilized to manage a variety of diseases in crops like cereals, fruits, and vegetables. The aim of this work was to assess the effects of TEB on the structure of the cerebellum in adult albino rats and possible protective impact of co-administration of Gallic acid (GA). Four groups of forty adult male albino rats were randomly selected, and the rats in group I received corn oil through daily gavage for 4 weeks. Group II received GA dissolved in the normal saline at a dose of 100 mg/kg through daily gavage for 4 weeks, group III administered with TEB dissolved in corn oil at its acceptable daily intake dose (0.02 mg/kg body weight) through daily gavage for 4 weeks, group IV rats received both TEB and GA. For light microscopic, ultrastructural, and immunohistochemical investigations, cerebellar specimens were prepared. TEB exposure led to neuronal damage in the form of degenerated Purkinje cells with vacuolated cytoplasm, areas of lost Purkinje cells, the basket cells appeared vacuolated with degenerated neuropil, the granule cells clumped with congested areas between them, dilated cerebellar islands, weak positive bcl2 immunoreactions in the Purkinje cells, and numerous GFAP-positive astrocytes. GA mitigated TEB-mediated histological changes in the cerebellar cortex. We concluded that TEB caused Purkinje neurons in the rat cerebellar cortex to degenerate and undergo apoptosis. GA had a neuroprotective benefit against TEB toxicity in the rat cerebellar cortex.

戊唑醇(TEB)是一种常见的三唑类甾醇脱甲基化抑制剂杀菌剂,用于防治谷物、水果和蔬菜等作物的多种病害。这项研究的目的是评估 TEB 对成年白化大鼠小脑结构的影响,以及同时服用没食子酸(GA)可能产生的保护作用。随机选取四组四十只成年雄性白化大鼠,第一组每天灌胃玉米油,持续四周。第二组大鼠每天灌胃 100 毫克/千克剂量溶于生理盐水的 GA,连续 4 周;第三组大鼠每天灌胃 0.02 毫克/千克体重剂量溶于玉米油的 TEB,连续 4 周;第四组大鼠同时灌胃 TEB 和 GA。为了进行光学显微镜、超微结构和免疫组化研究,制备了小脑标本。暴露于 TEB 会导致神经元损伤,表现为具有空泡化胞质的浦肯野细胞变性、浦肯野细胞消失区域、篮状细胞出现空泡化并伴有神经髓变性、颗粒细胞聚集并在它们之间出现充血区域、小脑岛扩张、浦肯野细胞中出现弱阳性 bcl2 免疫反应以及大量 GFAP 阳性星形胶质细胞。GA减轻了TEB介导的小脑皮质组织学变化。我们的结论是,TEB 会导致大鼠小脑皮质中的浦肯野神经元退化和凋亡。GA对大鼠小脑皮质的TEB毒性具有神经保护作用。
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引用次数: 0
Excessive lipid production shapes glioma tumor microenvironment. 过多的脂质生成塑造了胶质瘤的肿瘤微环境。
IF 1.1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-09-02 Epub Date: 2024-08-19 DOI: 10.1080/01913123.2024.2392728
Haitham H Maraqah, John Paul Aboubechara, Mones S Abu-Asab, Han Sung Lee, Orwa Aboud

Disrupted lipid metabolism is a characteristic of gliomas. This study utilizes an ultrastructural approach to characterize the prevalence and distribution of lipids within gliomas. This study made use of tissue from IDH1 wild type (IDH1-wt) glioblastoma (n = 18) and IDH1 mutant (IDH1-mt) astrocytoma (n = 12) tumors. We uncover a prevalent and intriguing surplus of lipids. The bulk of the lipids manifested as sizable cytoplasmic inclusions and extracellular deposits in the tumor microenvironment (TME); in some tumors the lipids were stored in the classical membraneless spheroidal lipid droplets (LDs). Frequently, lipids accumulated inside mitochondria, suggesting possible dysfunction of the beta-oxidation pathway. Additionally, the tumor vasculature have lipid deposits in their lumen and vessel walls; this lipid could have shifted in from the tumor microenvironment or have been produced by the vessel-invading tumor cells. Lipid excess in gliomas stems from disrupted beta-oxidation and dysfunctional oxidative phosphorylation pathways. The implications of this lipid-driven environment include structural support for the tumor cells and protection against immune responses, non-lipophilic drugs, and free radicals.

脂质代谢紊乱是胶质瘤的一个特征。本研究利用超微结构方法来描述胶质瘤中脂质的流行和分布情况。本研究使用了来自IDH1野生型(IDH1-wt)胶质母细胞瘤(n = 18)和IDH1突变型(IDH1-mt)星形细胞瘤(n = 12)肿瘤的组织。我们发现了一种普遍存在且耐人寻味的脂质过剩现象。大部分脂质表现为肿瘤微环境(TME)中的大量细胞质包涵体和胞外沉积物;在一些肿瘤中,脂质储存在经典的无膜球形脂滴(LDs)中。脂质经常积聚在线粒体内,这表明β-氧化途径可能出现了功能障碍。此外,肿瘤血管腔内和血管壁上也有脂质沉积;这些脂质可能是从肿瘤微环境中转移进来的,也可能是血管中的肿瘤细胞产生的。胶质瘤中的脂质过剩源于β-氧化紊乱和氧化磷酸化途径功能失调。这种脂质驱动环境的影响包括为肿瘤细胞提供结构支持,保护其免受免疫反应、非亲脂药物和自由基的伤害。
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引用次数: 0
Features that characterize monoclonal light chain ("myeloma") cast nephropathy with immunofluorescence challenges and emphasis on electron microscopy. 单克隆轻链("骨髓瘤")铸型肾病的特征与免疫荧光挑战,重点是电子显微镜。
IF 1.1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-09-02 Epub Date: 2024-08-21 DOI: 10.1080/01913123.2024.2390892
Guillermo A Herrera, Luan D Truong, Sadhna Dhingra, Elba A Turbat-Herrera

Renal disease is a common cause of morbidity and mortality in patients with plasma cell dyscrasias. The serum-free light chain assay is used in patients, mostly older, with unexplained acute kidney injury to screen for potential myeloma cast nephropathy. This study consists of a systematic review of diagnostic features in myeloma cast nephropathy. The morphological features of tubular casts in patients with multiple myeloma have not been systematically analyzed. This study focuses on the morphology of these casts, emphasizing ultrastructural features, in a series of 23 patients with light chain ("myeloma") cast nephropathy and compared them with casts in 10 patients with various diseases. The immunofluorescence data were correlated with morphological findings to provide diagnostic assessments and practice guidelines. The ultrastructural features identified as diagnostic of casts associated with myeloma included: amyloid and crystals in the casts, multiple well-defined fracture planes forming a complex jigsaw puzzle arrangement of cast contents, indicative of the fragility of the immunoglobulin light chains involved, and reactive tubular cells lining the tubules with the casts. These features were seen in 95.2% of MCN cases and none of the casts in other renal conditions. Myeloma casts exhibited light chain monoclonality in a significant percentage of the MCN cases and often no staining for IgA or IgM. In contrast, the majority of non-myeloma casts stained for both kappa and lambda light chains, lgA, and lgM, and showed ultrastructurally a rather uniform finely to coarsely granular electron density occasionally admixed with cellular debris.

肾脏疾病是浆细胞异常患者发病和死亡的常见原因。无血清轻链测定可用于不明原因的急性肾损伤患者(多为老年人),以筛查潜在的骨髓瘤铸型肾病。本研究对骨髓瘤铸型肾病的诊断特征进行了系统回顾。目前尚未对多发性骨髓瘤患者肾小管铸型的形态特征进行系统分析。本研究重点研究了一系列 23 例轻链("骨髓瘤")铸型肾病患者的这些铸型的形态,强调了超微结构特征,并将其与 10 例不同疾病患者的铸型进行了比较。免疫荧光数据与形态学结果相互关联,从而提供诊断评估和实践指南。经鉴定,可诊断骨髓瘤相关铸型肾病的超微结构特征包括:铸型中的淀粉样蛋白和结晶、多个界限清晰的断裂面形成铸型内容物的复杂拼图排列(表明相关免疫球蛋白轻链的脆性),以及反应性小管细胞与铸型肾病患者的肾小管相衬。在 95.2% 的 MCN 病例中出现了这些特征,而在其他肾脏疾病中却没有出现这些铸型。在相当大比例的 MCN 病例中,骨髓瘤铸型表现出轻链单克隆性,而且通常没有 IgA 或 IgM 染色。与此相反,大多数非骨髓瘤铸型都对 kappa 和 lambda 轻链、lgA 和 lgM 进行了染色,并在超微结构上显示出相当均匀的细粒至粗粒电子密度,偶尔会混有细胞碎片。
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引用次数: 0
Emperipolesis in pleural fluid mesothelial cells. A phenomenon not associated with Rosai-Dorfman disease, report of a case. 胸腔积液间皮细胞中的包膜。一个与罗赛-多夫曼病无关的现象,一个病例的报告。
IF 1.1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-09-02 Epub Date: 2024-07-30 DOI: 10.1080/01913123.2024.2382987
Diana Sofía Vargas-Lías, Mónica Lizette Serrano-Arévalo, Lara-Torres César, Corredor-Alonso Guillermo Ernesto, Hugo R Dominguez-Malagon

Emperipolesis is a cell-within-cell phenomenon distinct from phagocytosis more often described in Rosai-Dorfman disease, where usually lymphocytes or other bone marrow cells (plasma cells, erythroblasts or neutrophils) are entirely surrounded but not engulfed by macrophages as the host cell, but occasionally megakaryocytes and neoplastic could be. Mesothelial cell has been described in a couple of cases of lymphomas affecting serous membranes, but never described in pleuritis. In the present work, the first case of emperipolesis by mesothelial cells in a patient with self-limited pleural effusion was demonstrated by immunohistochemistry and Electron Microscopy studies.

通常淋巴细胞或其他骨髓细胞(浆细胞、红细胞或中性粒细胞)会完全被巨噬细胞包围,但不会像宿主细胞那样被巨噬细胞吞噬,偶尔巨核细胞和肿瘤细胞也会被吞噬。在几例影响浆膜的淋巴瘤病例中曾描述过间皮细胞,但从未在胸膜炎中描述过。在本研究中,通过免疫组化和电子显微镜研究,首次在一名自限性胸腔积液患者中证实了间皮细胞引起的胸膜炎。
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引用次数: 0
Can the analysis of chromatin texture and nuclear fractal dimensions serve as effective means to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features from other malignancies with follicular pattern in the thyroid?: a study. 染色质纹理和核分形尺寸分析能否作为有效手段,将具有乳头状核特征的非侵袭性甲状腺滤泡性肿瘤与其他具有甲状腺滤泡形态的恶性肿瘤区分开来?
IF 1.1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-07-03 Epub Date: 2024-06-03 DOI: 10.1080/01913123.2024.2362758
Geet Bhuyan, Anjumoni Rabha

Objective: Thyroid carcinoma ranks as the 9th most prevalent global cancer, accounting for 586,202 cases and 43,636 deaths in 2020. Computerized image analysis, utilizing artificial intelligence algorithms, emerges as a potential tool for tumor evaluation.

Aim: This study aims to assess and compare chromatin textural characteristics and nuclear dimensions in follicular neoplasms through gray-level co-occurrence matrix (GLCM), fractal, and morphometric analysis.

Method: A retrospective cross-sectional study involving 115 thyroid malignancies, specifically 49 papillary thyroid carcinomas with follicular morphology, was conducted from July 2021 to July 2023. Ethical approval was obtained, and histopathological examination, along with image analysis, was performed using ImageJ software.

Results: A statistically significant difference was observed in contrast (2.426 (1.774-3.412) vs 2.664 (1.963-3.610), p = .002), correlation (1.202 (1.071-1.298) vs 0.892 (0.833-0.946), p = .01), and ASM (0.071 (0.090-0.131) vs 0.044 (0.019-0.102), p = .036) between NIFTP and IFVPTC. However, morphometric parameters did not yield statistically significant differences among histological variants.

Conclusion: Computerized image analysis, though promising in subtype discrimination, requires further refinement and integration with traditional diagnostic parameters. The study suggests potential applications in scenarios where conventional histopathological assessment faces limitations due to limited tissue availability. Despite limitations such as a small sample size and a retrospective design, the findings contribute to understanding thyroid carcinoma characteristics and underscore the need for comprehensive evaluations integrating various diagnostic modalities.

目的:甲状腺癌在全球癌症发病率中排名第九,2020 年将有 586 202 例发病,43 636 例死亡。目的:本研究旨在通过灰度级共现矩阵(GLCM)、分形和形态计量分析,评估和比较滤泡性肿瘤的染色质纹理特征和核尺寸:方法:2021 年 7 月至 2023 年 7 月进行了一项回顾性横断面研究,涉及 115 例甲状腺恶性肿瘤,特别是 49 例具有滤泡形态的甲状腺乳头状癌。研究获得了伦理批准,并使用 ImageJ 软件进行了组织病理学检查和图像分析:结果:NIFTP 和 IFVPTC 的对比度(2.426 (1.774-3.412) vs 2.664 (1.963-3.610),p = .002)、相关度(1.202 (1.071-1.298) vs 0.892 (0.833-0.946),p = .01)和 ASM(0.071 (0.090-0.131) vs 0.044 (0.019-0.102),p = .036)差异有统计学意义。然而,形态计量参数在组织学变异之间并没有产生统计学意义上的显著差异:结论:计算机图像分析虽然在亚型鉴别方面很有前景,但还需要进一步完善并与传统诊断参数相结合。这项研究表明,在传统组织病理学评估因组织可用性有限而面临限制的情况下,计算机图像分析具有潜在的应用价值。尽管存在样本量小和回顾性设计等局限性,但研究结果有助于了解甲状腺癌的特征,并强调了综合各种诊断方式进行全面评估的必要性。
{"title":"Can the analysis of chromatin texture and nuclear fractal dimensions serve as effective means to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features from other malignancies with follicular pattern in the thyroid?: a study.","authors":"Geet Bhuyan, Anjumoni Rabha","doi":"10.1080/01913123.2024.2362758","DOIUrl":"10.1080/01913123.2024.2362758","url":null,"abstract":"<p><strong>Objective: </strong>Thyroid carcinoma ranks as the 9th most prevalent global cancer, accounting for 586,202 cases and 43,636 deaths in 2020. Computerized image analysis, utilizing artificial intelligence algorithms, emerges as a potential tool for tumor evaluation.</p><p><strong>Aim: </strong>This study aims to assess and compare chromatin textural characteristics and nuclear dimensions in follicular neoplasms through gray-level co-occurrence matrix (GLCM), fractal, and morphometric analysis.</p><p><strong>Method: </strong>A retrospective cross-sectional study involving 115 thyroid malignancies, specifically 49 papillary thyroid carcinomas with follicular morphology, was conducted from July 2021 to July 2023. Ethical approval was obtained, and histopathological examination, along with image analysis, was performed using ImageJ software.</p><p><strong>Results: </strong>A statistically significant difference was observed in contrast (2.426 (1.774-3.412) vs 2.664 (1.963-3.610), <i>p</i> = .002), correlation (1.202 (1.071-1.298) vs 0.892 (0.833-0.946), <i>p</i> = .01), and ASM (0.071 (0.090-0.131) vs 0.044 (0.019-0.102), <i>p</i> = .036) between NIFTP and IFVPTC. However, morphometric parameters did not yield statistically significant differences among histological variants.</p><p><strong>Conclusion: </strong>Computerized image analysis, though promising in subtype discrimination, requires further refinement and integration with traditional diagnostic parameters. The study suggests potential applications in scenarios where conventional histopathological assessment faces limitations due to limited tissue availability. Despite limitations such as a small sample size and a retrospective design, the findings contribute to understanding thyroid carcinoma characteristics and underscore the need for comprehensive evaluations integrating various diagnostic modalities.</p>","PeriodicalId":23430,"journal":{"name":"Ultrastructural Pathology","volume":" ","pages":"310-316"},"PeriodicalIF":1.1,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Morphological and histopathological changes of maternal levetiracetam on the cerebellar cortex of the offspring of albino rat. 母体左乙拉西坦对白化大鼠后代小脑皮层的形态学和组织病理学变化
IF 1.1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-07-03 Epub Date: 2024-06-08 DOI: 10.1080/01913123.2024.2353064
Safaa M Hanafy

Levetiracetam (LEV) is being used by women with reproductive-age epilepsy at a significantly higher rate. The purpose of the study was to assess how levetiracetam treatment during pregnancy affected the offspring's weight and cerebellum. Forty pregnant rats were divided into two groups (I, II). Two smaller groups (A, B) were created from each group. The rats in group I were gavaged with approximately 1.5 mL/day of distilled water either continuously during pregnancy (for subgroup IA) or continuously during pregnancy and 14 days postpartum (for subgroup IB). The rats in group II were gavaged with about 1.5 mL/day of distilled water (containing 36 mg levetiracetam) either continuously during pregnancy (for subgroup IA) or continuously during pregnancy and 14 days postpartum (for subgroup IB). After the work was completed, the body weight of the pups in each group was recorded, and their cerebella were analyzed histologically and morphometrically. Following levetiracetam treatment, the offspring showed decreased body weight and their cerebella displayed delayed development and pathological alterations. These alterations manifested as, differences in the thicknesses of the layers of cerebellar cortex as compared to the control groups; additionally, their cells displayed cytoplasmic vacuolation, nuclear alterations, fragmented rough endoplasmic reticulum and lost mitochondrial cristae. Giving levetiracetam to pregnant and lactating female rats had a negative impact on the body weight and cerebella of the offspring. Levetiracetam should be given with caution during pregnancy and lactation.

育龄女性癫痫患者使用左乙拉西坦(LEV)的比例明显增加。这项研究的目的是评估怀孕期间服用左乙拉西坦对后代体重和小脑的影响。40 只怀孕大鼠被分为两组(I、II)。每组再分成两个小组(A、B)。I 组大鼠在怀孕期间(IA 亚组)或在怀孕期间和产后 14 天(IB 亚组)连续每天灌胃约 1.5 毫升蒸馏水。第二组大鼠在怀孕期间(IA 亚组)或怀孕期间和产后 14 天(IB 亚组)连续每天灌胃约 1.5 毫升蒸馏水(含 36 毫克左乙拉西坦)。工作结束后,记录各组幼崽的体重,并对其大脑进行组织学和形态学分析。在接受左乙拉西坦治疗后,后代的体重下降,大脑发育迟缓并出现病理改变。与对照组相比,这些改变表现为小脑皮质各层厚度的差异;此外,它们的细胞还表现出细胞质空泡化、核改变、粗面内质网破碎和线粒体嵴消失。给怀孕和哺乳期雌性大鼠服用左乙拉西坦对后代的体重和小脑有负面影响。妊娠期和哺乳期应慎用左乙拉西坦。
{"title":"Morphological and histopathological changes of maternal levetiracetam on the cerebellar cortex of the offspring of albino rat.","authors":"Safaa M Hanafy","doi":"10.1080/01913123.2024.2353064","DOIUrl":"10.1080/01913123.2024.2353064","url":null,"abstract":"<p><p>Levetiracetam (LEV) is being used by women with reproductive-age epilepsy at a significantly higher rate. The purpose of the study was to assess how levetiracetam treatment during pregnancy affected the offspring's weight and cerebellum. Forty pregnant rats were divided into two groups (I, II). Two smaller groups (A, B) were created from each group. The rats in group I were gavaged with approximately 1.5 mL/day of distilled water either continuously during pregnancy (for subgroup IA) or continuously during pregnancy and 14 days postpartum (for subgroup IB). The rats in group II were gavaged with about 1.5 mL/day of distilled water (containing 36 mg levetiracetam) either continuously during pregnancy (for subgroup IA) or continuously during pregnancy and 14 days postpartum (for subgroup IB). After the work was completed, the body weight of the pups in each group was recorded, and their cerebella were analyzed histologically and morphometrically. Following levetiracetam treatment, the offspring showed decreased body weight and their cerebella displayed delayed development and pathological alterations. These alterations manifested as, differences in the thicknesses of the layers of cerebellar cortex as compared to the control groups; additionally, their cells displayed cytoplasmic vacuolation, nuclear alterations, fragmented rough endoplasmic reticulum and lost mitochondrial cristae. Giving levetiracetam to pregnant and lactating female rats had a negative impact on the body weight and cerebella of the offspring. Levetiracetam should be given with caution during pregnancy and lactation.</p>","PeriodicalId":23430,"journal":{"name":"Ultrastructural Pathology","volume":" ","pages":"247-260"},"PeriodicalIF":1.1,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Infection as a trigger of acute, transient glomerular deposition of clonal immunoglobulins. 感染是克隆免疫球蛋白急性、一过性肾小球沉积的诱因。
IF 1.1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-07-03 Epub Date: 2024-05-16 DOI: 10.1080/01913123.2024.2356112
Bangchen Wang, Micah Schub, Derrick L Robinson, David N Howell

Glomerular deposition of monoclonal IgM, frequently in the form of intracapillary pseudothrombi, can be seen in Waldenström macroglobulinemia (WM) and type I cryoglobulinemia (CG). They are typically associated with plasma cell or B-lymphoid neoplasms, particularly lymphoplasmacytic lymphoma (LPL). While infection is a frequent trigger of mixed (type II and III) CG, its association with type I CG is uncommon. We report two cases in which striking lambda-chain-restricted IgM deposits and acute kidney injury (AKI) occurred in the setting of known or suspected systemic infections, with prompt resolution on treatment of the infection.

在瓦尔登斯特伦巨球蛋白血症(WM)和Ⅰ型低温球蛋白血症(CG)中可见到单克隆 IgM 在肾小球沉积,经常表现为毛细血管内假血栓。它们通常与浆细胞或 B 淋巴肿瘤有关,尤其是淋巴浆细胞性淋巴瘤(LPL)。虽然感染是混合型(II 型和 III 型)CG 的常见诱因,但感染与 I 型 CG 的关联并不常见。我们报告了两个病例,这两个病例在已知或疑似全身感染的情况下出现了惊人的λ-链限制性 IgM 沉积和急性肾损伤(AKI),并在治疗感染后迅速缓解。
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引用次数: 0
Hydralazine use can be associated with IgM-dominated immune complex-mediated glomerulonephritis. 使用氯丙嗪可能与 IgM 主导的免疫复合物介导的肾小球肾炎有关。
IF 1.1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-07-03 Epub Date: 2024-04-29 DOI: 10.1080/01913123.2024.2346660
Ping L Zhang, Brandon D Metcalf, Sarang Khan, Jamal Abukhaled, Khalid Zafar, Wei Li, Hassan D Kanaan

Context: IgM-dominant immune complex-mediated glomerulonephritis (IgM-dominant ICMGN) is a rare renal entity, characterized by a membranoproliferative pattern by light microscopy, dominant IgM staining by immunofluorescent staining, and subendothelial deposits by electron microscopy. This study was to investigate if some of IgM-ICMGN were associated with autoimmune disorders induced by hydralazine.

Design: Seven IgM-dominant ICMGN cases were identified over 8 years. Their pathologic phenotypes and clinical scenarios were analyzed in detail.

Results: Patients' ages ranged from 47 to 87 years old with 5 women and two men. Six of seven patients had drug-induced autoimmune phenomenon (hydralazine-induced positive ANCA and ANA). All of them had renal dysfunction and some proteinuria. Most pathologic features showed a membranoproliferative pattern of glomerulonephritis with dominant IgM deposits at subendothelial spaces. IgM nephropathy (a variant of focal segmental glomerulosclerosis), chronic thrombotic microangiopathy, and cryoglobulinemic glomerulopathy were ruled out in the cases.

Conclusion: The hydralazine-induced autoimmune phenomenon can be seen in IgM-dominant ICMGN, which should be classified as a subtype of membranoproliferative glomerulonephritis.

背景:IgM显性免疫复合物介导的肾小球肾炎(IgM-dominant ICMGN)是一种罕见的肾脏疾病,其特点是光镜下为膜增生型,免疫荧光染色为显性IgM染色,电镜下为内皮下沉积。本研究旨在探讨某些 IgM-ICMGN 是否与水拉嗪诱发的自身免疫性疾病有关:设计:历时 8 年,共发现 7 例 IgM-ICMGN 病例。详细分析了他们的病理表型和临床表现:患者年龄从 47 岁到 87 岁不等,其中女性 5 人,男性 2 人。七名患者中有六名出现了药物诱导的自身免疫现象(水拉嗪诱导的 ANCA 和 ANA 阳性)。所有患者都有肾功能障碍和一些蛋白尿。大多数病理特征显示肾小球肾炎呈膜增生型,内皮下间隙有明显的 IgM 沉积。这些病例排除了 IgM 肾病(局灶节段性肾小球硬化症的一种变异)、慢性血栓性微血管病和冷球蛋白血症肾小球病的可能性:结论:氢氯嗪诱导的自身免疫现象可见于 IgM 主导型 ICMGN,应将其归类为膜增生性肾小球肾炎的一种亚型。
{"title":"Hydralazine use can be associated with IgM-dominated immune complex-mediated glomerulonephritis.","authors":"Ping L Zhang, Brandon D Metcalf, Sarang Khan, Jamal Abukhaled, Khalid Zafar, Wei Li, Hassan D Kanaan","doi":"10.1080/01913123.2024.2346660","DOIUrl":"10.1080/01913123.2024.2346660","url":null,"abstract":"<p><strong>Context: </strong>IgM-dominant immune complex-mediated glomerulonephritis (IgM-dominant ICMGN) is a rare renal entity, characterized by a membranoproliferative pattern by light microscopy, dominant IgM staining by immunofluorescent staining, and subendothelial deposits by electron microscopy. This study was to investigate if some of IgM-ICMGN were associated with autoimmune disorders induced by hydralazine.</p><p><strong>Design: </strong>Seven IgM-dominant ICMGN cases were identified over 8 years. Their pathologic phenotypes and clinical scenarios were analyzed in detail.</p><p><strong>Results: </strong>Patients' ages ranged from 47 to 87 years old with 5 women and two men. Six of seven patients had drug-induced autoimmune phenomenon (hydralazine-induced positive ANCA and ANA). All of them had renal dysfunction and some proteinuria. Most pathologic features showed a membranoproliferative pattern of glomerulonephritis with dominant IgM deposits at subendothelial spaces. IgM nephropathy (a variant of focal segmental glomerulosclerosis), chronic thrombotic microangiopathy, and cryoglobulinemic glomerulopathy were ruled out in the cases.</p><p><strong>Conclusion: </strong>The hydralazine-induced autoimmune phenomenon can be seen in IgM-dominant ICMGN, which should be classified as a subtype of membranoproliferative glomerulonephritis.</p>","PeriodicalId":23430,"journal":{"name":"Ultrastructural Pathology","volume":" ","pages":"317-322"},"PeriodicalIF":1.1,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chronic liver fibrosis induction in aging causes significant ultra-structural deterioration in liver and alteration on immune response gene expressions in liver-spleen axis. 衰老诱导的慢性肝纤维化会导致肝脏超结构显著恶化,并改变肝脾轴心的免疫反应基因表达。
IF 1.1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-07-03 Epub Date: 2024-06-06 DOI: 10.1080/01913123.2024.2360447
Zeynal Mete Karaca, Gamze Karaca, Başak Kayhan, Mehmet Gül, Veysel Ersan, Harika Gözükara Bağ, Elif Yeşilada

The relationship between damage to the liver and spleen by aging and the immune response status in these two organs, which are anatomically and immunologically interconnected, is unknown. The authors investigated the histopathological, ultrastructural, and immunological effects of aging in young and aged fibrotic mice by using an experimental model. Four groups were planned, with 10 mice in each experimental group. The levels of fibrosis and ultrastructural destruction in the liver were determined by α-SMA staining and TEM analysis. Expression levels of immunity genes (Il2, Il4, Il6, Il10, Il12, Il17, Tnf, Ifng, Tgfb1, Gata3, Rorc, Tbx21, Foxp3, Ccl2, Ccr2, Cxcr3, Pf4, Cxcl10) were carried out by qRT-PCR. While structural disorders were detected in the mitochondria of aged healthy group, cellular destruction in the fibrosis-induced elderly group was at a dramatic level. Fibrosis induction in aged mice caused an elevation in the expression of chemokines (CCl2, CXCL10, CCR2) and cytokine (IL-17a) genes that induce autoinflammatory response in the liver. Unlike the cellular pathology and genes activated in fibrosis in youth and the natural occurrence of fibrosis with aging, induction of fibrosis during aging causes deterioration in the liver and expression of genes responsible for autoimmunity in both the liver and spleen.

肝脏和脾脏在解剖学和免疫学上相互关联,而衰老对肝脏和脾脏的损伤与这两个器官的免疫反应状态之间的关系尚不清楚。作者通过实验模型研究了衰老对年轻和老年纤维化小鼠的组织病理学、超微结构和免疫学影响。实验计划分为四组,每组 10 只小鼠。通过α-SMA染色和TEM分析确定肝脏纤维化和超微结构破坏的程度。免疫基因(Il2、Il4、Il6、Il10、Il12、Il17、Tnf、Ifng、Tgfb1、Gata3、Rorc、Tbx21、Foxp3、Ccl2、Ccr2、Cxcr3、Pf4、Cxcl10)的表达水平通过 qRT-PCR 进行检测。虽然在健康老年组的线粒体中检测到了结构紊乱,但在纤维化诱导的老年组中,细胞破坏却达到了惊人的程度。诱导老年小鼠纤维化会导致趋化因子(CCl2、CXCL10、CCR2)和细胞因子(IL-17a)基因的表达升高,从而诱发肝脏的自身炎症反应。与年轻时纤维化的细胞病理学和激活的基因以及随着年龄增长而自然发生的纤维化不同,衰老过程中纤维化的诱导会导致肝脏恶化以及肝脏和脾脏中负责自身免疫的基因的表达。
{"title":"Chronic liver fibrosis induction in aging causes significant ultra-structural deterioration in liver and alteration on immune response gene expressions in liver-spleen axis.","authors":"Zeynal Mete Karaca, Gamze Karaca, Başak Kayhan, Mehmet Gül, Veysel Ersan, Harika Gözükara Bağ, Elif Yeşilada","doi":"10.1080/01913123.2024.2360447","DOIUrl":"10.1080/01913123.2024.2360447","url":null,"abstract":"<p><p>The relationship between damage to the liver and spleen by aging and the immune response status in these two organs, which are anatomically and immunologically interconnected, is unknown. The authors investigated the histopathological, ultrastructural, and immunological effects of aging in young and aged fibrotic mice by using an experimental model. Four groups were planned, with 10 mice in each experimental group. The levels of fibrosis and ultrastructural destruction in the liver were determined by α-SMA staining and TEM analysis. Expression levels of immunity genes (<i>Il2, Il4, Il6, Il10, Il12, Il17, Tnf</i>, <i>Ifng</i>, <i>Tgfb1, Gata3, Rorc, Tbx21, Foxp3, Ccl2, Ccr2, Cxcr3, Pf4, Cxcl10</i>) were carried out by qRT-PCR. While structural disorders were detected in the mitochondria of aged healthy group, cellular destruction in the fibrosis-induced elderly group was at a dramatic level. Fibrosis induction in aged mice caused an elevation in the expression of chemokines (CCl2, CXCL10, CCR2) and cytokine (IL-17a) genes that induce autoinflammatory response in the liver. Unlike the cellular pathology and genes activated in fibrosis in youth and the natural occurrence of fibrosis with aging, induction of fibrosis during aging causes deterioration in the liver and expression of genes responsible for autoimmunity in both the liver and spleen.</p>","PeriodicalId":23430,"journal":{"name":"Ultrastructural Pathology","volume":" ","pages":"261-273"},"PeriodicalIF":1.1,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The potential therapeutic effects of exosomes derived from bone marrow mesenchymal stem cells on ileum injury of a rat sepsis model (histological and immunohistochemical study). 骨髓间充质干细胞外泌体对败血症模型大鼠回肠损伤的潜在治疗作用(组织学和免疫组化研究)。
IF 1.1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-07-03 Epub Date: 2024-07-01 DOI: 10.1080/01913123.2024.2368011
Heba M Elnegris, Abeer A Abdelrahman, Eman S El-Roghy

Sepsis denotes a serious high mortality concern. The study was designed to evaluate the effect of mesenchymal stem cell exosomes (MSC-exosomes) on the evolution of the animal model of sepsis. In this study, 36 rats were distributed into three groups, (I) controls, (II) LPS-treated, and (III) LPS+MSC-EVs. Sepsis was simulated by administering E. coli-LPS to the laboratory animals. Group III was given MSC-exosomes four hours after the LPS injection. Forty-eight hours later rats were sacrificed. Ileum samples were excised, and processed for the histological assessment, immunohistochemical identification of CD44, and inducible nitric oxide synthase (iNOS). Ileum homogenate was used to estimate tumor necrosis factor α (TNF α) besides Cyclooxygenase-2 (COX 2). PCR was used for the detection of interleukin 1α (IL‑1α), and interleukin 17 (IL‑17). Statistical and morphometrical analysis was done. The LPS-treated group showed increased TNF-α, IL‑1α, IL‑17, and decreased COX 2. LPS administration led to cytoplasmic vacuolization of enterocytes, an increase in the vasculature, and cellular infiltrations invaded the lamina propria. There was a significant rise in goblet cells and the proportion of collagen fibers. Ultrastructurally, the enterocytes displayed nuclear irregularity, rough endoplasmic reticulum (rER) dilatation, and increased mitochondria number. Sepsis induces a significant increase in iNOS and a decrease in CD44 immune expressions. LPS+MSC-EVs group restored normal ileum structure and revealed a significant elevation in CD44 and a reduction in iNOS immunoreactions. LPS-sepsis induced an obvious ileum inflammatory deterioration ameliorated by MSC-exosomes, mostly through their antioxidant, anti-inflammatory, and anti-apoptotic properties.

败血症是一种严重的高死亡率疾病。本研究旨在评估间充质干细胞外泌体(MSC-exosomes)对败血症动物模型演变的影响。在这项研究中,36只大鼠被分为三组,(I) 对照组,(II) LPS处理组,(III) LPS+间充质干细胞外泌体组。通过给实验动物注射大肠杆菌-LPS来模拟败血症。在注射 LPS 四小时后,给第三组大鼠注射间充质干细胞外泌体。48 小时后,大鼠被处死。切除回肠样本并进行组织学评估、CD44和诱导型一氧化氮合酶(iNOS)的免疫组化鉴定。回肠匀浆用于评估肿瘤坏死因子α(TNF α)和环氧化酶-2(COX 2)。白细胞介素 1α(IL-1α)和白细胞介素 17(IL-17)的检测采用 PCR 技术。进行了统计和形态学分析。LPS 处理组显示 TNF-α、IL-1α、IL-17 增加,COX 2 减少。给予 LPS 会导致肠细胞胞浆空泡化,血管增加,细胞浸润侵入固有层。鹅口疮细胞和胶原纤维的比例明显上升。从超微结构上看,肠细胞核不规则,粗面内质网(rER)扩张,线粒体数量增加。败血症会诱导 iNOS 的显著增加和 CD44 免疫表达的减少。LPS+MSC-EVs 组恢复了正常的回肠结构,并显示出 CD44 的显著升高和 iNOS 免疫反应的降低。间充质干细胞外泌体主要通过其抗氧化、抗炎和抗凋亡特性改善了LPS败血症引起的回肠炎症恶化。
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Ultrastructural Pathology
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