Apert's syndrome: differential in vitro production of matrix macromolecules and its regulation by interleukins

During embryonic development, variations in the composition of the extracellular matrix (ECM) macromolecules influence bone tissue differentiation. We present novel findings on the in vitro phenotypic expression of periosteal fibroblasts obtained from patients affected by Apert's syndrome, a rare craniofacial malformation, and the effects that interleukins (ILs) induce on the phenotype. Apert fibroblasts synthesized greater quantities of glycosaminoglycans (GAGs) and intracellular type I collagen, and also produced more type III collagen and fibronectin. The amount of hyaluronic acid (HA) secreted by Apert fibroblasts was much higher than that secreted by normal fibroblasts, but, as the absolute values of heparan sulphate (HS), chondroitin sulphate (CS) and dermatan sulphate (DS) also rose in Apert media, the HA–sulphated GAG ratio was similar in the media obtained from both populations. Both ILs triggered elevations of HA in normal cells, although relative percentage secretion remained unaltered, but significantly reduced HA secretion by Apert cells. IL-1 significantly increased CS in normal and Apert media, whereas IL-6 enhanced HS and DS in media of both populations. HA–sulphated GAG ratio decreased in Apert media after IL treatment. Both ILs boosted fibronectin production by Apert fibroblasts, whereas IL-1 increased type III but not type I collagen. Taken together, these data demonstrate that the synthesis and secretion of ECM macromolecules are markedly altered in Apert fibroblasts. The fact that treatment with ILs further modifies the Apert phenotype suggests that ILs may be implicated in the pathophysiology of the malformations during skull morphogenesis.     

严重烧伤患者血液单核细胞体外产生白细胞介素-1量的变化及临床意义

目的：检测严重烧伤患者伤后血液单核细胞体外产生白细胞介素１（ＩＬ１）量的变化，并结合内脏功能损害、多器官衰竭（ＭＯＦ）和严重全身感染的发生情况探讨其意义。方法：采用生物法检测２４例严重烧伤患者伤后不同时间单个器官功能损害患者、ＭＯＦ患者、局部感染患者和严重全身感染患者及３０例正常人单核细胞体外产生ＩＬＬ的量。结果：烧伤患者伤后单核细胞产生ＩＬ１的量减少，且病情越重，减少越多，在ＭＯＦ患者尤为明显；ＩＬ１产生量的变化与患者心、肝酶呈明显负相关。结论：ＩＬ１在严重烧伤患者内脏功能损害及ＭＯＦ的发生发展中起着重要作用。     

TH17细胞及IL-17在原发性抗磷脂综合征中的表达及临床意义

目的观察T_H17细胞及相关细胞因子IL-17在原发性抗磷脂综合征(PAPS)中的表达水平,并初步探讨其临床意义。方法收集32例PAPS患者及33例健康对照者静脉血标本,分离外周血单个核细胞(PBMC),流式细胞术检测T_H17细胞百分率,ELISA法检测血浆IL-17的表达水平,并分析IL-17水平与PAPS患者临床病理特征及实验室指标[抗心凝脂抗体(a CL)、抗β2糖蛋白Ⅰ(β2GPⅠ)和狼疮抗凝物(LA)]的关系。结果 PAPS患者外周血T_H17细胞百分率为(1.98±0.78)%,血浆IL-17水平为(60.72±18.71)pg/m L,均显著高于健康人对照组(P均0.01),且T_H17细胞百分率与血浆IL-17水平呈正相关(r=0.586,P0.01)。PAPS患者血浆IL-17水平与患者a CL、抗β2GPⅠ抗体和LA均无明显相关性(P均0.05)。与近期(≥3月)无相关临床事件发生的PAPS患者相比,新近(≤1月)发生动脉血栓事件的患者血浆IL-17水平差异无统计学意义(P=0.074),静脉血栓和血小板减少的PAPS患者IL-17蛋白水平显著升高(P0.01)。结论 T_H17细胞及IL-17与PAPS血栓形成和血小板减少密切相关,提示T_H17细胞及IL-17参与了PAPS脉管症状的发病机制。     

L-DOPA,a treatment for Parkinson's disease,and its enantiomer D-DOPA inhibit severe fever with thrombocytopenia syndrome virus infection in vitro

Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever. Patients mainly develop fever, thrombocytopenia, and leukopenia. A high case fatality rate of 16.2–47% has been reported. Vaccines and antivirals that are effective against SFTS virus (SFTSV) are not yet available in clinical practice. We previously showed that o-dihydroxybenzene is the important chemical core structure for anti-SFTSV activity. In this study, we evaluated the anti-SFTSV efficacy of 3-Hydroxy-L-tyrosine (L-DOPA), a treatment for Parkinson's disease and its enantiomer, 3-hydroxy-D-tyrosine (D-DOPA), both of which have an o-dihydroxybenzene backbone. SFTSV was preincubated with L- or D-DOPA and then inhibition of viral infection as well as viral attachment to host cells were evaluated by viral quantification. Both L- and D-DOPA inhibited SFTSV infection in a dose-dependent manner, mainly by blocking viral attachment to host cells. The half-maximal inhibitory concentration (IC₅₀) of L-DOPA was 4.46–5.09 μM. IC₅₀ of D-DOPA was 4.23–6.72 μM. IC₅₀ of L-DOPA is very close to its maximum blood concentration after oral administration as a therapy for Parkinson's disease. D-DOPA, which IC₅₀ was almost the same as that of L-DOPA, might not cause side effect. Thus, our present study demonstrated that L- and D-DOPA are potentially useful candidates for anti-SFTSV drugs.     

Metabolic syndrome in rheumatoid arthritis patients: Relationship among its clinical components

BackgroundMetabolic syndrome (MetS) prevalence in rheumatoid arthritis (RA) patients is known to vary considerably across the world. This study aimed to determine the prevalence of MetS in RA patients from western Mexico and to analyze the interrelation of the MetS components with the clinical variables of RA.MethodsThis case‐control study included 216 RA patients and 260 control subjects (CS). MetS prevalence was determined according to the NCEP/ATP III and the Latin American Consensus of the Latin American Diabetes Association (ALAD) criteria.ResultsMetS was observed in 30.6% RA patients and 33.3% of controls (p > 0.05) according to NCEP/ATP III and 28.7% in RA patients and 31.1% for controls using ALAD criteria. Total cholesterol, LDL‐C, and Castelli''s I‐II indexes were lower in RA (p < 0.001) than in CS. The RA patients with MetS had more swollen joints than those without MetS (p = 0.018). In RA patients with MetS, DAS‐28 score correlated with smoking index (rho = 0.4601, p = 0.0004) and VLDL‐C (rho = 0.3108, p = 0.0056); similarly, rheumatoid factor (RF) correlated with age (rho = 0.2031, p = 0.0027), smoking index (rho = 0.3404, p < 0.0001), triglycerides (rho = 0.1958, p = 0.0039), and VLDL‐C (rho = 0.1761, p = 0.0162).ConclusionsThe MetS prevalence in RA patients from western Mexico is not higher than controls; however, in RA patients with MetS, some inflammatory markers are associated with MetS components; thus, the control of MetS in RA could be beneficial to regulate disease activity.     

唾液腺超声诊断干燥综合征的研究进展

干燥综合征是一种慢性复杂异质性疾病,以干燥性口角炎及干燥性角膜结膜炎为特征性表现,多年来超声因其操作简便、无创、可重复性高等优点受到重视,并且越来越多的研究表明唾液腺超声在患者监测中具有潜在作用,本文分别就其对SS的诊断及监测价值进行综述。     

肾衰宁灌肠液对体外培养的人肾小球系膜细胞增殖及产生纤维连接蛋白的影响

目的 :观察肾衰宁 (SSN)灌肠液对体外培养的人肾小球系膜细胞增殖及产生纤维连接蛋白 (FN)的影响 ,以便从细胞生物学水平探讨肾衰宁防治慢性肾功能衰竭 (CRF)的作用机制。方法 :采用 4甲基偶氮唑盐(MTT)比色法和双抗夹心酶联免疫吸附 (EL ISA)法 ,观察 SSN大鼠血清对体外培养的人肾小球系膜细胞增殖和 FN生成的影响。结果 :SSN大鼠血清可抑制体外培养的人肾小球系膜细胞增殖和产生 FN,其抑制程度与药物浓度有一定的量效关系 :即随药物浓度的增加 ,对系膜细胞增殖和产生 FN的抑制率也相应增加。结论 :SSN对体外培养的人肾小球系膜细胞增殖和产生 FN有明显的抑制作用 ;SSN灌肠液抑制肾小球系膜细胞增殖和 FN产生是预防肾小球硬化发生发展的重要机制之一。     

Challenges in corticosteroid dose regulation in a patient with autoimmune thyroid disease and neuropsychiatric syndrome: A running commentary

In the following, we report a therapeutic challenge faced by reduction in corticosteroid therapeutic dosage in a patient diagnosed with Hashimoto''s encephalopathy (HE), which is equivalent to corticosteroid‐responsive encephalopathy related to autoimmune thyroiditis and often misdiagnosed as neuropsychiatric status. The patient developed psychiatric symptoms.     

微重力旋转培养法体外模拟维甲酸综合征及其与CXCR4/SDF-1α表达的关系

目的 探讨维甲酸综合征(RAS)发生的分子机制及防治方法.方法 用微重力旋转培养系统进行维甲酸诱导分化的急性早幼粒细胞白血病患者白血病(APL-ATRA)细胞浸润人肺组织的体外实验,用地塞米松(Dex)、阿糖胞苷(Ara-C)和柔红霉素(DNR)对APL-ATRA细胞的黏附、迁移和浸润能力进行干预,用逆转录-聚合酶链反应(RT-PCR)检测人肺组织基质细胞衍生因子1α(SDF-1α)mRNA的表达,用流式细胞术检测APL-ATRA细胞CXCR4蛋白的表达.结果 APL-ATRA细胞可明显浸润正常人肺组织,APL-ATRA细胞表面CXCR4表达水平(MFI为30.6±1.8)明显高于诱导前的APL细胞(9.8±4.2).检测的6份人肺组织SDF-1α mRNA表达均阳性.与对照组比较,Dex组可明显抑制APL-ATRA细胞的黏附和迁移能力[(46.0±3.0)%对(27.2±2.6)%;(48.2±3.0)%对(28.1±4.0)%];Ara-C组和DNR组均可明显抑制APL-ATRA细胞的黏附、迁移和浸润能力[(46.0±3.0)%对(28.1±3.0)%、(30.2±3.2)%,(48.2±3.0)%对(29.0±4.0)%、(23.0±5.2)%,(43.6±5.0)%对(16.8±7.6)%、(17.1±6.0)%].结论 APL-ATRA细胞有浸润人肺组织的能力;CXCR4和SDF-1α的高表达可能是APL-ATRA细胞引起人肺组织浸润的分子机制之一;Dex、Ara-C和DNR可抑制APL-ATRA细胞的黏附、迁移和浸润.     

Bart's syndrome associated with a disorder of sexual differentiation: An atypical presentation in a Cameroonian newborn

Bart''s syndrome consists of congenital aplasia of the skin affecting only the lower limbs, associated with bullae over the skin and/or mucous membranes, as well as a nail anomaly. It is an extremely rare genetic disorder, which can be associated with other birth defects. We report the case of a newborn baby admitted at day 0 of life in the neonatal department, for multifocal skin detachment predominantly at the lower limbs. In addition, examination of the external genitalia revealed a clitoridomegaly genital bud measuring 14 mm, scrotalized and unfused genital bulges with the presence of 2 orifices. No gonad was palpated. The clinical diagnosis of Bart''s syndrome associated with a disorder of sexual differentiation was retained. We hereby report the first case of Bart''s syndrome described in Cameroon in association with a disorder of sexual differentiation.     

First report of rheumatoid arthritis and secondary Sjögren's syndrome complicated with heart failure

A 70‐year‐old woman with rheumatoid arthritis for 45 years developed secondary Sjögren''s syndrome. She had a long‐term low‐salt and low‐fat diet and did not adhere to long‐term hormone and rheumatic immunotherapy, which led to heart failure.     

Novel presentation of autoimmune polyglandular syndrome II in a child with simultaneous Addison's disease,type 1 diabetes,and Hashimoto's thyroiditis: A case report

Providers should remain vigilant of autoimmune polyglandular syndrome type II in the context of persistent low blood sugar in type I diabetes. Correction of adrenal insufficiency is key for regulation of blood sugar and thyroid function.     

Delayed presentation of congenital rectal stenosis associated with Down's syndrome and hypothyroidism: Case report

Rectal stenosis is a rare variety of rectal atresia. A membrane separates the rectum from the anal canal in the presence of a normal anus. We report a case of rectal stenosis associated with Down''s syndrome and hypothyroidism in whom rectal stenosis was diagnosed at the age of 17 years.     

Cytokine profiles and clinical characteristics in primary Sjögren´s syndrome patient groups

BackgroundPrimary Sjögren''s syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups.MethodsNinety‐nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K‐mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal‐Wallis test and the Bonferroni test.ResultsHigher IFN‐γ, IL‐17F, IL‐21, IL‐23, IL‐4, and IL‐31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity.ConclusionCluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach.     

Dissociation between vascular and metabolic effects of nicotinic acid in Gilbert's syndrome

Summary. The relationship between the vasodilating and the hyperbilirubinaemic effect of low and high doses (50 and 300 mg i.v.) of nicotinic acid was studied in baseline conditions and after indomethacin pretreatment in healthy controls and patients with Gilbert's syndrome (a condition characterized by fluctuating, nonhaemolytic unconjugated hyperbilirubinaemia). The hyperbilirubinaemic effect of nicotinic acid was confirmed to be more pronounced in Gilbert's syndrome patients than in controls. The magnitude of hyperbilirubinaemia in the two groups was not dependent on the dose of nicotinic acid or indomethacin pretreatment. A dose-dependent vasodilation which was inhibited by indomethacin could be demonstrated in both controls and Gilbert's syndrome subjects. Vasodilating properties of nicotinic acid were therefore found to be dissociated from the effect on bilirubin.     

The combination of levodopa with levodopa-metabolizing enzyme inhibitors prevents severe fever with thrombocytopenia syndrome virus infection in vitro more effectively than single levodopa

Severe fever with thrombocytopenia syndrome is a hemorrhagic fever caused by a tick-borne infection. The causative agent, Dabie bandavirus, is also called the severe fever with thrombocytopenia syndrome virus (SFTSV). Ogawa et al. (2022) reported that levodopa, an antiparkinsonian drug with an o-dihydroxybenzene backbone, which is important for anti-SFTSV activity, inhibited SFTSV infection. Levodopa is metabolized by dopa decarboxylase (DDC) and catechol-O-methyltransferase (COMT) in vivo. We evaluated the anti-SFTSV efficacy of two DDC inhibitors, benserazide hydrochloride and carbidopa, and two COMT inhibitors, entacapone and nitecapone, which also have an o-dihydroxybenzene backbone. Only DDC inhibitors inhibited SFTSV infection with pretreatment of the virus (half-maximal inhibitory concentration [IC₅₀]: 9.0–23.6 μM), whereas all the drugs inhibited SFTSV infection when infected cells were treated (IC₅₀: 21.3–94.2 μM). Levodopa combined with carbidopa and/or entacapone inhibited SFTSV infection in both conditions: pretreatment of the virus (IC₅₀: 2.9–5.8 μM) and treatment of infected cells (IC₅₀: 10.7–15.4 μM). The IC₅₀ of levodopa in the above-mentioned study for pretreatment of the virus and treatment of infected cells were 4.5 and 21.4 μM, respectively. This suggests that a synergistic effect was observed, especially for treatment of infected cells, although the effect is unclear for pretreatment of the virus. This study demonstrates the anti-SFTSV efficacy of levodopa-metabolizing enzyme inhibitors in vitro. These drugs may increase the time for which the levodopa concentration is maintained in vivo. The combination of levodopa and levodopa-metabolizing enzyme inhibitors might be a candidate for drug repurposing.