Non-steroidal anti-inflammatory drugs occupy a leading position in the pharmaceutical market, but their class-specific side effect (ulcerogenic action) significantly limits their widespread use. The N-(4-methoxybenzyl)-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide derivative (compound NI-9) showed a pronounced analgesic effect in various models of pain syndromes. The aim of the study was to determine the effect of a new original derivative of 4-methyl-2.2-dixo-1H-2λ6,1-benzothiazine-3-carboxylic acid on the macroscopic state and biochemical parameters of the gastric mucosa of rats. The study was performed on 51 male Wistar rats. Compound NI-9 and the reference drug meloxicam were administered intragastrically once daily for 28 days at doses of 3 and 5 mg/kg, corresponding to their ED50 analgesic activity. Macroscopic indicators of GM damage, glycosaminoglycan content, phospholipid profile, level of MDA and CGP, as well as nitrates and nitrites and H2S were determined. The results were processed in the program STATISTICA 10.0 using non-parametric methods. The results showed that the carboxamide derivative was safer for the stomach because the ulcer index of compound NI-9 was 1.73 times lower than that of meloxicam. The damaging effect of the compound was more pronounced at the pre-epithelial and epithelial levels of GM protection, while the post-epithelial level (production of vasodilating molecules NO and H2S) was practically unaffected by this derivative, unlike meloxicam, which caused damage at all levels of protection. The obtained data supplement the data on the pharmacodynamics of the 4-methyl-2.2-dixo-1H-2λ6,1-benzothiazine-3-carboxylic acid derivative and determine the expediency of its further studies as a potential non-opioid analgesic.
Annotation. Sarcopenia is a typical complication of liver cirrhosis (LC) and is associated with a poor prognosis. The skeletal muscle index is the most studied radiological marker of sarcopenia, but it’s using requires the qualification of a radiologist, specialized software, time reserve. The aim of the study: to investigate the relationship between different radiological markers of skeletal muscle mass, to determine their reference ranges for Ukrainian population and to assess their diagnostic and prognostic value in patients with LC. The study involved 216 healthy people and 147 patients with LC. During 18 months of follow-up 45 patients died from LC complications. Skeletal muscles were assessed by computed tomography. Skeletal muscle index (SMI), psoas muscle index (PMI), and transverse psoas muscle thickness (TPMT) at L3 were determined. Statistical data processing was performed in SPSS22. Diagnostic and prognostic value of SMI, PMI, TPMT were studied in ROC analysis. It was found that in Ukrainian population the reference ranges of SMI are >52.2 / 39.3 cm2/m2, PMI>6. 44 / 3.49 cm2/m2, TPMT>11.1 / 7.42 mm/m, in men / women, respectively. Sarcopenia was diagnosed in 54.9% and 86.3% of LC class B and C patients. PMI and TPMT had a high diagnostic value in sarcopenia detection (SMI≤52.2 and ≤39.3 cm2/m2) in male and female LC patients (AUC PMI 0.899 and 0.955, p˂0.001, AUC TPMT 0.884 and 0.942, p˂0.001). SMI, PMI and TPMT predicted one-and-a-half-year mortality in male and female LC patients (AUC SMI 0.815 and 0.786, p<0.001; AUC PMI 0.745 and 0.804, p<0.001; AUC TPMT 0.752 and 0.871, p<0.001). The optimal cut-off values for predicting death in male and female are: SMI≤49.1 and ≤38.4 cm2/m2; PMI≤5.99 and ≤3.30 cm2/m2; TPMT≤11.0 and ≤6.70 mm/m. Thus, routine assessment of PMI and TPMT in LC can identify patients with sarcopenia and high risk of complications.
Вінницький національний медичний університет імені М.І. Пирогова Резюме. Метою даного огляду є ознайомлення широкого кола лікарів загальної практики, гастроентерологів, хірургів, реаніматологів із найбільш важливими досягненнями у вивченні етіології, патогенезу, особливостей клінічної картини, діагностики, лікування та профілактики інфекцій, які ускладнюють цироз печінки. Бактеріальні інфекції зумовлюють високу смертність серед хворих на цироз печінки. Ця категорія пацієнтів частіше за інших госпіталізованих хворих схильна до виникнення інфекцій. У пацієнтів із цирозом пе-чінки інфекційні ускладнення можуть призводити як до декомпенсації цирозу, так і до розвитку печінкової та/ або позапечінкової органної недостатності. Рання діагностика і своєчасний початок адекватної антибактеріальної терапії є основними принципами лікування хворих на цироз печінки з бактеріальними інфекціями.Ключові слова: бактеріальні інфекції, цироз печінки, діагностика, лікування, профілактика.
Loss of skeletal muscle mass or sarcopenia is associated with the development of complications and mortality in patients with liver cirrhosis (LC). Skeletal muscle index (SMI) is the most validated parameter of sarcopenia in clinical studies, but its evaluation is difficult in routine clinical practice. The purpose of the study was to assess the diagnostic concordance between different radiologic skeletal muscle parameters and their relationship with a short-term survival of LC patients. The study involved 147 LC patients, including 90 males and 57 females (55.51±0.97). LC Class A according to Child-Turcotte-Pugh (CTP) was diagnosed in 23 patients, class B in 51 patients, and class C in 73 patients. 50 patients died from LC complications during the follow-up period (489 (306 – 637) days). Skeletal muscle index (SMI), psoas muscle mass index (PMI), and transversal psoas muscle thickness (TPMT) were calculated using the computed tomography at L3 level. The statistical data was processed using the SPSS22 software (© SPSS Inc.). PMI and TPMT were found to be objective parameters of sarcopenia in LC patients having stable diagnostic concordance with SMI (r Spearman’s 0.734, 0.649, p˂0.001; k Cohen’s 0.727, 0.643, p˂0.001, respectively). The use of all three parameters allowed to reveal more patients with a reduced skeletal muscle mass. Sarcopenia was diagnosed in 54.9 % of CTP B patients, 86.3 % of CTP C patients, and was associated with an elevated incidence of ascites, hydrothorax, hepatic encephalopathy, and hypoalbuminemia. Sarcopenic patients were found more likely to have an alcohol-related etiology than viral one (HBV, HCV). The overall survival of patients with low SMI, PMI and TPMT was significantly lower according to Kaplan-Meier analysis. SMI, PMI, and TPMT were independent predictors of LC-associated mortality (HR 2.66, 2.19, 2.21, respectively, p˂0.05) in Cox proportional hazards regression. At least one of the three decreased radiologic skeletal muscle mass parameters was associated with the highest risk of fatal LC complications (HR 3.65, p=0.021). Therefore, the psoas muscle dimensions were considered a reliable tool for detection of sarcopenia and prediction of short-term survival in LC.
Annotation. Paraoxonase is a high-density lipoprotein-associated pleiotropic enzyme able to detoxify proatherogenic compounds such as oxi-low-density-lipoproteins and homocysteine-thiolactone. Low paraoxonase activity is likely to be involved in the development of cardiovascular diseases. The aim of the study – to investigate the relationship between paraoxonase activity, structural and functional markers of the heart and blood vessels, cardio-metabolic risk factors in women with hypertension of different reproductive age. The study included 193 women aged 32-70 years (55.4±0.68 years) with essential stage II hypertension. The control group consisted of 46 healthy women. The arylesterase activity of paraoxonase (EC 3.1.1.2) in blood serum was determined by spectrophotometric method. Statistical processing of the obtained results was performed in the application package SPSS22 (© SPSS Inc.). The mean and standard error of the mean (M ± m) were calculated. Student's t-test was used. Pearson correlation analysis was performed at p <0.05. It was found that in women with hypertension there was a significant decrease (16%) in serum paraoxonase activity, compared with healthy women. Low paraoxonase activity was registered in 33.3% of premenopausal patients and 56.7% of postmenopausal patients (p˂0.05) and was associated with serum estradiol levels (r=0.33, 0.41, p<0.05). Low paraoxonase activity was associated with aberrant levels of lipids, homocysteine, obesity, metabolic syndrome, increased left ventricular mass index and carotid intima-media thickness, decreased brachial artery endothelium-dependent vasodilation. Thus, the decrease in serum paraoxonase activity in women with hypertension is related with the reproductive age of patients and the development of unfavorable metabolic, structural and functional changes in the heart and blood vessels.
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