Антицитрулінові антитіла в діагностиці артритів у дітей

Віходячи з проведеного дослідження, описаного в роботі, можна дійти висновку, що серед дітей із різними формами артритів тільки 4,8% пацієнтів були серопозитивними за РФ, та 23,8% дітей – за рівнем АЦЦП. Прогнастичне значення підвищеного рівня АЦЦП у дітей із РеА полягає в високій вірогідності розвитку ЮРА, що обумовлює більш ретельне їх спостереження із застосуванням індивідуальних схем профілактичного лікування. При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/1128

Salsalate activates brown adipose tissue in mice

Salsalate improves glucose intolerance and dyslipidemia in type 2 diabetes patients, but the mechanism is still unknown. The aim of the current study was to unravel the molecular mechanisms involved in these beneficial metabolic effects of salsalate by treating mice with salsalate during and after development of high-fat diet-induced obesity. We found that salsalate attenuated and reversed high-fat diet-induced weight gain, in particular fat mass accumulation, improved glucose tolerance, and lowered plasma triglyceride levels. Mechanistically, salsalate selectively promoted the uptake of fatty acids from glycerol tri[(3)H]oleate-labeled lipoprotein-like emulsion particles by brown adipose tissue (BAT), decreased the intracellular lipid content in BAT, and increased rectal temperature, all pointing to more active BAT. The treatment of differentiated T37i brown adipocytes with salsalate increased uncoupled respiration. Moreover, salsalate upregulated Ucp1 expression and enhanced glycerol release, a dual effect that was abolished by the inhibition of cAMP-dependent protein kinase (PKA). In conclusion, salsalate activates BAT, presumably by directly activating brown adipocytes via the PKA pathway, suggesting a novel mechanism that may explain its beneficial metabolic effects in type 2 diabetes patient

Niacin Reduces Atherosclerosis Development in APOE*3Leiden.CETP Mice Mainly by Reducing NonHDL-Cholesterol

<div><p>Objective</p><p>Niacin potently lowers triglycerides, mildly decreases LDL-cholesterol, and largely increases HDL-cholesterol. Despite evidence for an atheroprotective effect of niacin from previous small clinical studies, the large outcome trials, AIM-HIGH and HPS2-THRIVE did not reveal additional beneficial effects of niacin (alone or in combination with laropiprant) on top of statin treatment. We aimed to address this apparent discrepancy by investigating the effects of niacin without and with simvastatin on atherosclerosis development and determine the underlying mechanisms, in APOE*3Leiden.CETP mice, a model for familial dysbetalipoproteinemia (FD).</p><p>Approach and Results</p><p>Mice were fed a western-type diet containing cholesterol without or with niacin (120 mg/kg/day), simvastatin (36 mg/kg/day) or their combination for 18 weeks. Similarly as in FD patients, niacin reduced total cholesterol by -39% and triglycerides by −50%, (both P<0.001). Simvastatin and the combination reduced total cholesterol (−30%; −55%, P<0.001) where the combination revealed a greater reduction compared to simvastatin (−36%, P<0.001). Niacin decreased total cholesterol and triglycerides primarily by increasing VLDL clearance. Niacin increased HDL-cholesterol (+28%, P<0.01) and mildly increased reverse cholesterol transport. All treatments reduced monocyte adhesion to the endothelium (−46%; −47%, P<0.01; −53%, P<0.001), atherosclerotic lesion area (−78%; −49%, P<0.01; −87%, P<0.001) and severity. Compared to simvastatin, the combination increased plaque stability index [(SMC+collagen)/macrophages] (3-fold, P<0.01). Niacin and the combination reduced T cells in the aortic root (−71%, P<0.01; −81%, P<0.001). Lesion area was strongly predicted by nonHDL-cholesterol (R² = 0.69, P<0.001) and to a much lesser extent by HDL-cholesterol (R² = 0.20, P<0.001).</p><p>Conclusion</p><p>Niacin decreases atherosclerosis development mainly by reducing nonHDL-cholesterol with modest HDL-cholesterol-raising and additional anti-inflammatory effects. The additive effect of niacin on top of simvastatin is mostly dependent on its nonHDL-cholesterol-lowering capacities. These data suggest that clinical beneficial effects of niacin are largely dependent on its ability to lower LDL-cholesterol on top of concomitant lipid-lowering therapy.</p></div

Reanalysis of mGWAS results and in vitro validation show that lactate dehydrogenase interacts with branched-chain amino acid metabolism

Diabetes mellitus: pathophysiological changes and therap

Effect of niacin on VLDL production and clearance.

<p>To determine VLDL production, mice were injected with Trans³⁵S label and tyloxapol and the accumulation of TG in plasma (A) and the production rate of VLDL-TG and apoB, as well as VLDL lipidation, defined as the ratio of VLDL-TG/apoB, were determined (B). To determine VLDL clearance, mice were injected with glycerol tri[³H]oleate- and [¹⁴C]cholesteryl oleate-labeled VLDL-like emulsion particles. Plasma ³H-activity was determined as percentage of the initial dose (C), and uptake of ³H-activity by various organs was determined as percentage of the injected dose per gram wet tissue (D). (BAT, brown adipose tissue; gonWAT, gonadal white adipose tissue; subWAT, subcutaneous white adipose tissue; visWAT, visceral white adipose tissue; values are means ± SD; n = 6 per group for VLDL production and n = 3–5 per group for VLDL clearance; *P<0.05 as compared to control).</p

Effect of niacin, simvastatin and their combination on lesion composition.

<p>Macrophage area (A) and SMC area (B) were determined for all lesions and calculated per cross section. To correct for lesion size, macrophage content (C), SMC content (D), as well as plaque stability index (ratio of collagen and SMC content to macrophage content) (E) were also calculated as a percentage of lesion area, specifically in severe lesions (Type IV–V). (Simva, simvastatin; SMC, smooth muscle cells; values are means ± SD; n = 15 per group; *P<0.05, **P<0.01 and ***P<0.001 as compared to control; ^#P<0.05, and ^###P<0.001 as compared to niacin+simvastatin).</p

Effect of niacin, simvastatin and their combination on monocyte adhesion and T cell number.

<p>The number of monocytes adhering to the endothelium (A) and the number of T cells in the aortic root area (B) were determined per cross section. (Simva, simvastatin; values are means ± SD; n = 15 per group; **P<0.01; ***P<0.001 as compared to control; ^###P<0.001 as compared to niacin+simvastatin).</p