Trichostatin A,an Inhibitor of Histone Deacetylase,Inhibits the Viability and Invasiveness of Hypoxic Rheumatoid Arthritis Fibroblast‐Like Synoviocytes via PI3K/Akt Signaling

This study was undertaken to explore the effects of trichostatin A (TSA), an inhibitor of histone deacetylase, on the viability, apoptosis, and invasiveness of hypoxic rheumatoid arthritis fibroblast‐like synoviocytes (RA FLSs). RA FLSs were exposed to hypoxia for 24 h in the presence or absence of 2 μM TSA and tested for cell viability, apoptosis, invasion, and gene expression. The involvement of the phosphatidylinositol‐3‐kinase (PI3K)/Akt pathway was checked. TSA significantly inhibited the viability and induced apoptosis of hypoxic RA FLSs, compared to vehicle control. TSA blocked hypoxia‐induced invasion of RA FLSs during Matrigel invasion assays and reduced the expression of matrix metalloproteinases (MMP‐2 and MMP‐9) and PI3K and phosphorylation of Akt. Overexpression of constitutively active Akt reversed TSA‐mediated suppression of invasiveness and downregulation of MMP‐2 and MMP‐9. Our results indicate the antisurvival and antiinvasive activities of TSA in hypoxic RA FLSs, which is associated with inactivation of PI3K/Akt signaling.     

Nitric Oxide in Arthritis

Nitric oxide’s (NO) involvement in arthritis was first demonstrated when levels of nitrite, a stable endproduct of NO metabolism, were shown to be elevated in serum and synovial fluid samples of rheumatoid and osteoarthritis patients. NO production by chondrocytes, its involvement in various biochemical events of cartilage metabolism, and the in vivo suppression of experimental arthritis by NO synthase inhibitors further implicated NO in arthritis. However, a conclusive role for NO in the pathogenesis of arthritis remains to be defined, in contrast to the NO-cGMP signal transduction pathway of endothelium-mediated vasodilation. It appears that NO has limited modulating effects in cartilage metabolism, with evidence for both protective and deleterious effects. Recent developments that contribute to our understanding of NO’s role in arthritis are discussed.     

Localization of viable bacteria and bacterial antigens in arthritic joints of Erysipelothrix rhusiopathiae-infected pigs

Abstract Chronic polyarthritis was induced in pigs by infection with Erysipelothrix rhusiopathiae (serovar 2, strain T28). Viable bacteria could be reisolated as long as 5 months post-infection from synovial fluid, synovial tissue and from isolated chondrocytes. The number of viable bacteria could be increased by hypotonic shock of the chondrocytes indicating a substantial intracellular amount of bacteria. Bacterial antigens were shown by immunohistochemistry to be present on the surface of both chondrocytes and synovial cells in arthritic joints. Neither viable bacteria nor bacterial antigen were detected in unaffected joints.     

The association of trace elements with arthritis in US adults: NHANES 2013–2016

BackgroundArthritis is a common chronic disease, and is a major cause of disability and chronic pain in adults. Considering inflammatory responses is closely related with trace elements (TEs), the role of TEs in arthritis has attracted much attention. This study aimed to assess the association between TEs and arthritis.MethodsConcentrations of TEs in whole blood [cadmium (Cd), lead (Pb), mercury (Hg), selenium (Se), and manganese (Mn)] and serum [copper (Cu) and zinc (Zn)] were measured in adults who participated in the US National Health and Nutrition Examination Survey. Logistic regression model and Bayesian kernel machine regression model were used to explore the association between TEs and arthritis.ResultsThe levels of five TEs (Pb, Hg, Cd, Se, and Cu) in the arthritis group changed significantly. Three TEs were found to be associated with an increased risk of arthritis: Pb [OR (95% CI): 2.96 (2.18, 4.03), p-value for trend (P-t) < 0.001], Cd [OR (95% CI): 2.28 (1.68, 3.11), P-t < 0.001], Cu [OR (95% CI): 2.05 (1.53, 2.76), P-t < 0.001]. The Relative Excess Risk of Interaction was 0.35 (95% CI: 0.06–0.65) and 0.38 (95% CI: 0.11–0.64), respectively, suggesting that Hg ions and Se ions have positive additional interactions with alcohol consumption, which reduced the risk of arthritis. Subgroup analysis showed that Pb ions and Cd ions were significantly correlated with osteoarthritis and rheumatoid arthritis.ConclusionElevated concentrations of Pb, Cd, and Cu were associated with increased risk of arthritis. Drinking with high levels of Hg or Se may be a protective factor for arthritis. Future studies are warranted to validate these findings in prospective studies.     

Seronegative spondyloarthropathies and diffuse idiopathic skeletal hyperostosis in ancient northern Chile

Bioarchaeological research of ancient Amerindians was undertaken to test the hypothesis that seronegative spondyloarthropathies (SNS) and diffuse idiopathic skeletal hyperostosis (DISH) existed in prehistoric South Americans. An osteological-radiographic model was developed from clinical literature and systematically applied to 504 archaeological human remains housed at the Universidad de Tarapacá in Arica, Chile, to search for evidence of these arthritides. The results showed that SNS existed with an average frequency of 7% for the adult sample and DISH averaged 4% in individuals over 40 years old. It was found that the antiquity of SNS date back at least 5,000 years in both New World and Old World populations. In contrast, the antiquity of DISH in the Americas is not clear because no previous studies have dealt with this subject; however, this research finds mild DISH cases dating back 4,000 years in northern Chile. It was also found that SNS and DISH exhibit a trend of increasing incidence with the advent of agro-pastoral activities and village formation. © 1993 Wiley-Liss, Inc.     

The physical and chemical properties of a chicken egg white glycoprotein purified by nondenaturing methodology

The oxidation of ethanol by the liver produces acetaldehyde, which is a highly reactive compound. Low concentrations of acetaldehyde inhibited mitochondrial respiration with glutamate, β-hydroxybutyrate, or α-ketoglutarate as substrates, but not with succinate or ascorbate. High concentrations led to respiratory inhibition with all substrates. Inhibition of succinate- and ascorbate-linked oxidation by acetaldehyde correlates with the inhibition of the activities of succinic dehydrogenase and cytochrome oxidase. A site more sensitive to acetaldehyde appears to be localized prior to the NADH-ubiquinone oxidoreductase segment of the respiratory chain. Acetaldehyde inhibits energy production by the mitochondria, as evidenced by its inhibition of respiratory control, oxidative phosphorylation, the rate of phosphorylation, and the ATP-³²P exchange reaction. Energy utilization is also inhibited, in view of the decrease in both substrate- and ATP-supported Ca²⁺ uptake, and the reduction in Ca²⁺-stimulated oxygen uptake and ATPase activity. The malate-aspartate, α-glycerophosphate, and fatty acid shuttles for the transfer of reducing equivalents, and oxidation by mitochondria, were highly sensitive to acetaldehyde. Acetaldehyde also inhibited the uptake of anions which participate in the shuttles. The inhibition of the shuttles is apparently caused by interference with NAD⁺-dependent state 3 respiration and anion entry and efflux. Ethanol (6–80 mm) had no significant effect on oxygen consumption, anion uptake, or mitochondrial energy production and utilization. The data suggest that acetaldehyde may be implicated in some of the toxic effects caused by chronic ethanol consumption.     

缓解性血清阴性对称性滑膜炎伴凹陷性水肿22例临床回顾

目的:总结缓解性血清阴性对称性滑膜炎伴凹陷性水肿(RS3PE)的临床特点及转归,为该病的诊治提供更多的参考依据。方法:回顾性分析我院2004年1月至2016年2月的22例我院收治的RS3PE住院病例的临床数据和随访资料,总结该病的特点。结果:本研究纳入男性13例(59.1%),女性9例(40.9%),平均发病年龄(65.6±10.0)岁(40.0～79.0岁),发病至确诊时间12天至2年,均为急性起病,并伴有不同程度的对称性多关节炎及肢端水肿。发热6例(27.3%)。主要实验室指标:血红蛋白(109.1±16.0)g·L~(-1),血小板计数(277.0±91.8)×109·L~(-1),血清白蛋白(36.1±5.0)g·L~(-1),C反应蛋白(62.5±67.4)mg·L~(-1),血沉(58.1±33.9)mm/h。测血清铁蛋白的6例中有5例(83.3%)升高,测肿瘤标记的10例均正常。18例(81.8%)行关节影像学检查,均未见骨破坏。5例行唇腺粘膜活检、2例行骨髓穿刺活检均无异常。住院期间治疗后症状均明显好转,4例(18.2%)单用糖皮质激素,18例(81.8%)在激素基础上联用慢作用药物。电话随访4.0月～8.0年(中位随访时间5.0年),有5例(22.7%)关节症状和肢端水肿持续缓解,4例(18.2%)症状减轻,1例(4.5%)反复,3例(13.6%)发展为类风湿关节炎,9例(40.9%)失访,确诊淋巴瘤1例(4.5%)。老年组RS3PE患者红细胞计数、血红蛋白、血清总蛋白及白蛋白低于非老年组。结论:RS3PE多为老年患者,急性起病,为对称性多关节炎伴肢端水肿,常伴贫血及低蛋白血症,对糖皮质激素敏感,有时可伴肿瘤,关于RS3PE的随访观察病例数迄今仍不足。     

T-cell receptor Vbeta deletion and Valpha polymorphism are responsible for the resistance of SWR mouse to arthritis induction

 Collagen type II-induced arthritis (CIA) develops in susceptible mouse strains after intradermal injections of type II collagen (CII) in complete Freund's adjuvant (CFA). Susceptibility to CIA in mice is linked to genes of the major histocompatibility complex (MHC). Although the SWR mouse has a susceptible MHC haplotype (H2 ^q ), it is resistant to CIA. SWR exhibits at least two known immunological defects: (1) it contains a germline deletion of about 50% of T-cell receptor (TCR) Vβ-chain gene segments, and (2) SWR is deficient in complement component C5. It has been shown that T cells that express TCRVα11.1 and TCRVβ8.2 play a substantial role in the pathogenesis of arthritis in the DBA/1 mouse (H2 ^q ). We generated SWR transgenic (tg) mice to determine whether the expression of pathogenic Vα11.1 and/or Vβ8.2 transgenes would confer arthritis susceptibility. Arthritis was induced in the SWR TCRαβ tg mice, but not in SWR TCRβ tg mice. To address the role of Vα11.1 in arthritis susceptibility, we examined the allelic polymorphisms of the Tcra-V11-gene subfamily members between the arthritis susceptible DBA/1 mouse and the arthritis-resistant SWR mouse strain. The amino acid sequences of the Vα11.1 alleles differ at two positions (codons 18 and 68). Accordingly, these two amino acid changes are sufficient to allow the production of pathogenic T cells in SWR mice. This is the first demonstration of the association of a particular Tcra-V allele and arthritis susceptibility in mice. Received: 20 November 1998 / Revised: 15 February 1999     

The ribonuclease inhibitors from porcine thyroid and liver are slow, tight-binding inhibitors of bovine pancreatic ribonuclease A

Ribonuclease inhibitors were purified from the latent ribonuclease fractions of porcine thyroid and liver and used to test the hypothesis that their inhibition of bovine pancreatic ribonuclease A is correctly described by tight-binding rather than Michaelis-Menton kinetics. Both proteins were found to act as slow, tight-binding inhibitors of the enzyme. These steady-state velocities also showed that both the thyroid and liver inhibitors were competitive inhibitors of bovine pancreatic ribonuclease A with Ki's of 0.1 and 0.4 nM, respectively. In contrast to interpretations based on Michaelis-Menton assumptions that show non-competitive inhibition, these results suggest that an enzyme:inhibitor:substrate complex does not exist.