IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism

Interleukin (IL)-19, a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. Nonalcoholic steatohepatitis (NASH) is a disease that has progressed from nonalcoholic fatty liver disease (NAFLD) and is characterized by inflammation and fibrosis. We evaluated the functions of IL-19 in a NAFLD/NASH mouse model using a 60% high fat diet with 0.1% methionine, without choline, and with 2% cholesterol (CDAHFD). Wild-type (WT) and IL-19 gene-deficient (KO) mice were fed a CDAHFD or standard diet for 9 weeks. Liver injury, inflammation, and fibrosis induced by CDAHFD were significantly worse in IL-19 KO mice than in WT mice. IL-6, TNF-α, and TGF-β were significantly higher in IL-19 KO mice than in WT mice. As a mechanism using an in vitro experiment, palmitate-induced triglyceride and cholesterol contents were decreased by the addition of IL-19 in HepG2 cells. Furthermore, addition of IL-19 decreased the expression of fatty acid synthesis-related enzymes and increased ATP content in HepG2 cells. The action of IL-19 in vitro suppressed lipid metabolism. In conclusion, IL-19 may play an important role in the development of steatosis and fibrosis by directly regulating liver metabolism and may be a potential target for the treatment of liver diseases

Early detection of septic arthritis caused by Streptococcus dysgalactiae subspecies equisimilis in a dog – a case report

In this report, a seven-year-old English Pointer male with Streptococcus dysgalactiae subsp. equisimilis arthritis joint infection is presented. The dog was referred to the Internal Medicine Department Policlinics with the symptoms of anorexia, weakness, swollen joints and ulcerative wounds on testes. On physical examination, the dog was depressed and manifesting discomfort during manipulation of the fore and hind legs’ joints. There were palpable effusions of the right carpal, elbow, and tibiotarsal joints. Haematological and serum biochemical analyses showed mild anaemia, moderate thrombocytopaenia, and elevated alanine aminotransferase. As soon as the synovial fluid aspirates were obtained aseptically from the right elbow, radiocarpal, and tibiotarsal joints, they were sent to bacteriological examination. Symptomatic and supportive treatment was initiated immediately. Empirical enrofloxacin therapy was initially started. Bacteria which were cultivated from the synovial fluid aspirates specimen were identified as S. equisimilis. The isolate was found to be resistant to enrofloxacin and susceptible to amoxycillin/clavulanic acid. According to the results of the antimicrobial susceptibility tests, enrofloxacin therapy was terminated and amoxycillin/clavulanic acid therapy was immediately started lasting for four weeks. The dog was treated successfully. To our knowledge, Streptococcus dysgalactiae subsp. equisimilis was isolated from the synovial fluid from a dog for the first time in Turkey, as it is rarely seen in dogs

The effects of resistive exercise with low intensity-high frequency on essential mild hypertension in men

高血圧症は心筋梗塞, 脳卒中, 動脈硬化の独立した危険因子になっている。日本人30歳以上の成人男子の約48%が軽症を含めた高血圧症とされている。高血圧関連疾患や死亡の予防として軽症高血圧症時の血圧コントロールは重要な関心点である。薬物による高血圧治療は著しい効果をあげているが, 好ましくない副作用の発現も見逃せない。薬物療法に対して運動療法が近年広く処方されるようになってきた。これまでに多くの研究が有酸素運動の降圧効果を報告しているが, レジスタンス運動による降圧効果については異なる知見が出されている。そこで本研究においては, 有酸素運動の様式に似た低強度-高頻度レジスタンス運動を用いて中年軽症高血圧男子に対する降圧効果を検索した。方法。42歳-56歳 (平均48.3) の男子10名が被検者として参加し, 内5名がレジスタンス運動群 (RE) に他の5名がウオーキング群 (AE) に区分された。RE群は10種目のウエイト運動を最大筋力の40-50%強度, 20-25レペテイションで2-3セット, 週3回の形で12週間行った。一方のAE群は同様に予測最大心拍数の60-75%強度の30分速歩を週3回, 12週間行った。結果。安静時血圧においてRE群はAE群より程度は低いものの有意な (P値2.3ml/kg/min=6.9%) と身体組成の改善 (体脂肪1.5kg=8.8%減) が見られ, その改善率はAE群に比べて小さいがいずれも有意であった (AE群 : 6ml/kg/min=17%, 3.1kg=18.9%)。また, 体重もしくは体脂肪の減少量と降圧値との間には有意差が得られなかったが相関傾向が見られた。しかし, AE群と異なり, RE群では血清総コレステロール, 高比重リポ蛋白コレステロール, 低比重リポ蛋白コレステロール, トリグリセライド (中性脂肪) の血清脂質・リポ蛋白濃度の有意な改善は見られなかった。結語。これまで血圧や身体組成もしくは有酸素性体力の改善, 向上に対するレジスタンス運動の効果については意見の一致をみていない。考えられる要因の一つに運動の処方の違いが挙げられる。血圧や身体組成の改善に対しては低強度・高頻度による運動量負荷 (Volume loading) の処方が好ましく, 高強度による過重負荷 (Over-weight loading) は至適処方とは言えないであろう。今回の研究においてレジスタンス運動による血清脂質の有意な改善が見られなかったのは総運動量が十分な刺激とならなかったものと考えられる。本研究は低強度高頻度のレジスタンス運動の習慣化が軽症高血圧患者の健康改善に効果的であることを示唆するものである。Five sedentary middle-aged men with mild hypertension were studied to determine the effects of a low-to moderate-intensity resistive exercise program (RE group) on resting systolic and diastolic blood pressures. Another group of five mild hypertensive men was also examined to determine the effects of a moderate aerobic exercise program (AE group) on the resting blood pressures. Besides blood pressures, effects of respective training programs were studied on aerobic capacity, muscle strengths, and serum lipid and lipoprotein concentrations. Resistive exercise consisted of 10 stations of weight training machines for 12 weeks. Workloads were set at 40-50% maximum and the subjects performed 10 repetitions for each station with 2-3 sets, 3 times per week. The subjects in the aerobic exercise group performed 30-min brisk waking or jogging with intensities of 60-75% their predicted maximum heart rates. The following changes occurred in the resistive exercise group : (1) resting systolic blood pressure dropped significantly (from 150 to 143mm Hg) after training and diastolic blood pressure dropped significantly (from 91 to 88mm Hg) after training ; (2) VO_ significantly increased 2.3 ml/kg/min or 6.9% (from 33.3 to 35.6 ml/kg/min) after training ; (3) increases of muscle strengths were profound, 17.9% and 23% in lower and upper body strengths, respectively ; (4) body weight and body fat decreased 2.6% (P) as well as body composition. Serum lipid lipoproteins included total cholesterol (TC), high-density cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Significant (P<0.01) increase was noted for HDL-C while significant decreases were seen in TC, LDL-C, and TG

Kinetic and Thermodynamic Control of Nitrile Dissociation in the Complexes (RFe,RC)/(SFe,RC)-[CpFe(Prophos)NCR]X (X = I, PF6) by the Inductive Effect

The chiral-at-metal complexes (R-Fe,R-C )/(S-Fe,R-C )-[CpFe(Prophos)NCR]X (X = I, PF6 ; R = Et, Ph, p-substituted Ph) were prepared, and the diastereomers were separated by fractional crystallization. Eight diastereomerically pure complexes (S-Fe,R-C)-[CpFe(Prophos)NCR]X could be characterized by X-ray crystallography. The kinetics of epimerization with respect to the labile Fe-configuration in CDCl3 at ambient temperatures was measured for the EtCN, PhCN, and (p-C6H4NMe2 ) complexes. The half-lives of 162 and 760 min of the 40 first-order reactions of (S-Fe,R-C)-[CpFe(Prophos)NCPh]PF6 and (S-Fe,R-C)-[CpFe(Prophos)NC(p-C6H4NMe2)]PF6 at 293 K demonstrate the importance of the inductive effect in the rate-determining cleavage of the Fe-NCR bond. The diastereomer ratios of 5:95 to 10:90 at equilibrium under thermodynamic control were strongly in favor of the (S-Fe,R-C )-[CpFe(Prophos)NCR]X diastereomers. In ligand exchange reaction reactions, (R-Fe,R-C)/(S-Fe,R-C ) diastereomer ratios of up to 35:65 were observed under kinetic control

16- and 17-Electron Intermediates in the MeCN/RNC Exchange in Chiral-at-Metal [CpFe(Prophos)NCMe]X (X = I, PF₆)

The compounds (<i>R</i>_Fe,<i>R</i>_C)-/(<i>S</i>_Fe,<i>R</i>_C)-[CpFe­(Prophos)­NCMe]­X (X = I, PF₆), configurationally labile at the metal center, were used in the MeCN/ligand exchange reactions with cyclohexyl isocyanide (CyNC) and <i>tert</i>-butyl isocyanide (^<i>t</i>BuNC). Kinetic measurements showed that the MeCN/CyNC exchange in diastereomerically pure (<i>S</i>_Fe,<i>R</i>_C)-[CpFe­(Prophos)­NCMe]­X proceeded via the slow S_N1-type dissociation of the Fe–NCMe bond, already observed in the MeCN/phosphite exchange reactions. The product (<i>R</i>_Fe,<i>R</i>_C)-/(<i>S</i>_Fe,<i>R</i>_C)-[CpFe­(Prophos)­CNCy]­X (X = I, PF₆) was formed in diastereomer ratios between 40:60 and 60:40. However, specific for the MeCN/CyNC exchange in (<i>S</i>_Fe,<i>R</i>_C)-[CpFe­(Prophos)­NCMe]­PF₆, in some of the samples a fast initial reaction interfered, initiated by traces of oxygen, which oxidized the cation in (<i>S</i>_Fe,<i>R</i>_C)-[CpFe­(Prophos)­NCMe]­PF₆ to (<i>S</i>_Fe,<i>R</i>_C)-[CpFe­(Prophos)­NCMe]²⁺. This dipositive cation started an electrocatalytic chain reaction, producing (<i>R</i>_Fe,<i>R</i>_C)-/(<i>S</i>_Fe,<i>R</i>_C)-[CpFe­(Prophos)­CNCy]­PF₆ with a high stereoselectivity of 2:98 in favor of (<i>S</i>_Fe,<i>R</i>_C)-[CpFe­(Prophos)­CNCy]­PF₆. Deactivation processes terminated the chain reaction, depending on the varying amounts of (<i>S</i>_Fe,<i>R</i>_C)-[CpFe­(Prophos)­NCMe]²⁺ present in the system. Larger amounts of oxygen or oxidants, such as I₂ and AgPF₆, caused immediate complete conversion to (<i>R</i>_Fe,<i>R</i>_C)/(<i>S</i>_Fe,<i>R</i>_C)-[CpFe­(Prophos)­CNR]­PF₆ in a diastereomer ratio of 2:98. In contrast to the hexafluorophosphate salt, addition of a crystal of iodine did not initiate the chain reaction in the iodide salt [CpFe­(Prophos)­NCMe]­I, because I₂ added to I^– to form I₃^–, which did not oxidize the cation of [CpFe­(Prophos)­NCMe]­I. Instead, there was slow conversion according to the dissociative pathway. The correlation between the configuration of (<i>R</i>_Fe,<i>R</i>_C)- and (<i>S</i>_Fe,<i>R</i>_C)-[CpFe­(Prophos)­CNCy]­X and the conformation of the Fe-Prophos chelate ring on the one hand and the correlation with the P–P coupling constants of the Prophos ligand on the other hand was corroborated

Associations between microalbuminuria and parameters of flow-mediated vasodilatation obtained by continuous measurement approaches

The associations between microalbuminuria and various parameters of flow-mediated vasodilatation (FMD) are not completely understood. We retrospectively analyzed 265 consecutive patients who underwent coronary angiography and in whom we could measure FMD and the urine albumin-creatinine ratio (UACR). Using 15 continuous measurement approaches, we measured FMD as the magnitude of the percentage change in the brachial artery diameter from baseline to peak (bFMD), the maximum FMD rate calculated as the maximal slope of dilation (FMD-MDR), and the integrated FMD response calculated as the area under the dilation curve during the 60- and 120-s dilation periods (FMD-AUC60 and FMD-AUC120). We divided the patients into two groups according to UACR: normoalbuminuria (NOR, n = 211) and microalbuminuria (MIC, n = 54). The MIC group showed a significantly higher percentage of coronary artery disease than the NOR group. FMD-AUC60 and FMD-AUC120, but not FMD-MDR, in the MIC group were significantly lower than those in the NOR group. On the other hand, bFMD in the MIC group tended to be lower than that in the NOR group, but this difference was not significant. A multiple regression analysis indicated that FMD-AUC120 and diabetes mellitus were predictors of MIC. Finally, we defined the cut-off value of FMD-AUC120 for the presence of MIC in all patients as 8.4 mm x second (sensitivity 0.640, specificity 0.588) by a receiver-operating characteristic curve analysis. In conclusion, this study provides more definitive evidence for the association of microalbuminuria with endothelial dysfunction. FMD-AUC120 may be a superior marker for MIC