Artificial Neural Networks: A Financial Tool As Applied in the Australian Market

Aim. In the elderly subjects metabolic syndrome (MetS) seems to be associated with low levels of circulating protective soluble receptor for advanced glycation end products (sRAGE). This secondary study aimed to answer whether this phenomenon is manifested from early childhood. Methods. 73 mothers and their 77 infants (4-to-12-months of age) were included in the study. Mothers were classified according to the presence of MetS components as negative (n = 32), those with pre-MetS (insulin resistance + 1 sign of MetS, n = 27) and overt MetS (n = 14). sRAGE and carboxymethyllysine (CML) were determined in the mothers and the infants. Results. Mothers with pre- and overt MetS displayed lower sRAGE levels, while in their children only a trend towards decline was observed. sRAGE levels significantly and inversely correlated with insulin sensitivity and BMI/body weight. No difference in CML levels across the groups was observed. Conclusions. Metabolic syndrome is associated with decreased levels of sRAGE in the mothers and a tendency towards decline of sRAGE in their offspring. Infants of mothers with MetS maintain normoglycemia on the account of higher insulin levels. Keywords: metabolic syndrome, mother-child pairs, QUICKI, sRAGE, insulin resistance, CML.Мета. У пацієнтів похилого віку розвиток метаболічного синдрому (МетС) асоційований з низьким рівнем циркулюючого розчинного рецептора для кінцевих продуктів повного глікозилювання (sRAGE). Мета цієї роботи полягала у пошуку відповіді на питання, чи проявляється таке явище у ранньому дитинстві? Методи. Досліджено 73 матері і 77 дітей віком від чотирьох до 12 місяців. Залежно від присутності компонентів МетС матерів розділили на три групи: негативна (n = 32) – без компонентів МетС; з початковою стадією МетС (резистентність до інсуліну + одна ознака МетС, n = 27) та з явно вираженим МетС (n = 14). У матерів і дітей визначали рівень концентрації sRAGE і карбоксиметиллізину (КМЛ). Результати. У матерів з початковою та явно вираженою стадіями МетС встановлено нижчий рівень sRAGE порівняно з їхніми дітьми, у яких спостерігали лише тенденцію до його падіння. Кількість sRAGE корелює з чутливістю до інсуліну та показником BM (індекс маси тіла) I /маса тіла. Різниці в концентрації КМЛ по групах не знайдено. Висновки. Метаболічний синдром пов'язаний із зниженням рівня sRAGE у матерів. Показано тенденцию до зменшення кількості sRAGE у їхніх дітей. Нормоглікемія у дітей, у матерів яких визначено МетС, підтримується вищим рівнем інсуліну. Ключові слова: метаболічний синдром, пара мати–дитина, QUICKI, sRAGE, резистентність до інсуліну, карбоксиметиллізин.Цель. У пациентов пожилого возраста развитие метаболического синдрома (МетС) ассоциировано с низким уровнем циркулирующего растворимого рецептора для конечных продуктов полного гликозилирования (sRAGE). Цель этой работы состояла в поиске ответа на вопрос, проявляется ли данное явление в раннем детстве? Методы. Исследованы 73 матери и 77 детей в возрасте от четырех до 12 месяцев. В зависимости от присутствия компонентов МетС матерей разделили на три группы: отрицательная (n = 32) – без компонентов МетС; с начальной стадией МетС (резистентность к инсулину + один признак МетС, n = 27) и с явно выраженным МетС (n = 14). У матерей и детей определяли уровень концентрации sRAGE и карбоксиметиллизина (КМЛ). Результаты. У матерей с начальной и явно выраженной стадиями МетС выявлен более низкий уровень sRAGE, в то время как у их детей наблюдалась лишь тенденция к его снижению. Количество sRAGEкоррелирует с чувствительностью к инсулину и показателем BM (индекс массы тела) I/масса тела. Разницы в концентрации КМЛ по группам не установлено. Выводы. Метаболический синдром связан со снижением уровня sRAGE у матерей. Показана тенденция к уменьшению количества sRAGE у их детей. Нормогликемия у детей, у матерей которых обнаружен МетС, поддерживается более высоким уровнем инсулина. Ключевые слова: метаболический синдром, пара мать–ребенок, QUICKI, sRAGE, резистентность к инсулину, карбоксиметиллизин

Is vitamin D deficiency related to accumulation of advanced glycation end products, markers of inflammation, and oxidative stress in diabetic subjects?

Objectives. In diabetes accumulated advanced glycation end products (AGEs) are involved in the striking cardiovascular morbidity/mortality. We asked whether a hypovitaminosis D associates with an increased formation and toxicity of AGEs in diabetes. Methods. In 276 diabetics (160M/116 F, age: 65.0 ± 13.4; 43 type 1,T1DM, and 233 type 2 patients, T2DM) and 121 nondiabetic controls (60 M/61 F; age: 58.6 ± 15.5 years) routine biochemistry, levels of 25-hydroxyvitamin D$_{3}$ (25-(OH)D), skin autofluorescence (SAF), plasma AGE-associated fluorescence (AGE-FL), N$^{ε}$ -(carboxymethyl) lysine (CML), soluble receptor for AGEs (sRAGE), soluble vascular adhesion protein-1 (sVAP-1), high sensitive C-reactive protein (hs-CRP), and renal function (eGFR) were determined. Results. In the diabetics SAF and AGE-Fl were higher than those of the controls and correlated with age, duration of diabetes, and degree of renal impairment. In T2DM patients but not in T1DM the age-dependent rise of SAF directly correlated with hs-CRP and sVAP-1. 25-(OH)D levels in diabetics and nondiabetics were lowered to a similar degree averaging 22.5 ng/mL. No relationship between 25-(OH)D and studied markers except for sVAP-1 was observed in the diabetics. Conclusion. In diabetics hypovitaminosis D does not augment accumulation of AGEs and studied markers of microinflammation and oxidative stress except for sVAP-1

Oxidative status in plasma, urine and saliva of girls with anorexia nervosa and healthy controls: a cross-sectional study

2-s2.0-85104635276Background: Anorexia nervosa (AN) is a serious psychosomatic disorder with unclear pathomechanisms. Metabolic dysregulation is associated with disruption of redox homeostasis that might play a pivotal role in the development of AN. The aim of our study was to assess oxidative status and carbonyl stress in plasma, urine and saliva of patients with AN and healthy controls. Methods: Plasma, spot urine, and saliva were collected from 111 girls with AN (aged from 10 to 18 years) and from 29 age-matched controls. Markers of oxidative stress and antioxidant status were measured using spectrophotometric and fluorometric methods. Results: Plasma advanced oxidation protein products (AOPP) and advanced glycation end products (AGEs) were significantly higher in patients with AN than in healthy controls (by 96, and 82%, respectively). Accordingly, urinary concentrations of AOPP and fructosamines and salivary concentrations of AGEs were higher in girls with AN compared with controls (by 250, and 41% in urine; by 92% in saliva, respectively). Concentrations of thiobarbituric acid reactive substances (TBARS) in saliva were 3-times higher in the patients with AN than in the controls. Overall antioxidants were lower in plasma of girls with AN compared to the controls, as shown by total antioxidant capacity and ratio of reduced and oxidized glutathione (by 43, and 31%, respectively). Conclusions: This is the first study assessing wide range of markers of oxidative status in plasma, urine and saliva of the patients with AN. We showed that both, higher levels of markers of oxidative stress and lower antioxidants play a role in redox disruption. Restoration of redox homeostasis might be of the clinical relevance © 2021, The Author(s).2018/36-LFUK-10 Ministerstvo školstva, vedy, v?skumu a športu Slovenskej republiky: 1/0613/17This study was supported by the Grant of Ministry of Health of the Slovak republic 2018/36-LFUK-10 and by the Grant Agency of Ministry of Education, Science, Research and Sport of the Slovak Republic VEGA 1/0613/17

The peroxisome proliferator-activated receptor-α agonist, BAY PP1, attenuates renal fibrosis in rats

Recent studies have shown renoprotective effects of the peroxisome proliferator-activated receptor-α (PPAR-α), but its role in kidney fibrosis is unknown. In order to gain insight into this, we examined the effect of a novel PPAR-α agonist, BAY PP1, in two rat models of renal fibrosis: unilateral ureteral obstruction and the 5/6 nephrectomy. In healthy animals, PPAR-α was expressed in tubular but not in interstitial cells. Upon induction of fibrosis, PPAR-α was significantly downregulated, and treatment with BAY PP1 significantly restored its expression. During ureteral obstruction, treatment with BAY PP1 significantly reduced tubulointerstitial fibrosis, proliferation of interstitial fibroblasts, and TGF-β(1) expression. Treatment with a less potent PPAR-α agonist, fenofibrate, had no effects. Treatment with BAY PP1, initiated in established disease in the 5/6 nephrectomy, halted the decline of renal function and significantly ameliorated renal fibrosis. In vitro, BAY PP1 had no direct effect on renal fibroblasts but reduced collagen, fibronectin, and TGF-β(1) expression in tubular cells. Conditioned media of BAY PP1-treated tubular cells reduced fibroblast proliferation. Thus, renal fibrosis is characterized by a reduction of PPAR-α expression, and treatment with BAY PP1 restores PPAR-α expression and ameliorates renal fibrosis by modulating the cross-talk between tubular cells and fibroblasts. Hence, potent PPAR-α agonists might be useful in the treatment of renal fibrosi

Paradox of circulating advanced glycation end product concentrations in patients with congestive heart failure and after heart transplantation

Objectives: To analyse circulating concentrations of advanced glycation end products (AGEs) in patients with severe congestive heart failure (CHF) and after heart transplantation; to identify the potential contribution of kidney function to plasma AGE concentrations; and to determine whether AGE concentrations and parameters of oxidative stress are interrelated. Methods and results: Circulating N(ɛ)-(carboxymethyl)lysine (CML) and AGE associated fluorescence (AGE-Fl), lipid peroxidation, and glomerular filtration rate (GFR) were measured in a cross sectional study of 22 patients with advanced CHF, 30 heart transplant recipients, and 20 healthy controls. Compared with the controls, the CHF patients had decreased CML (mean (SEM) 467.8 (20.0) ng/ml v 369.3 (22.3) ng/ml, p < 0.01), AGE-Fl (mean (SEM) 302.2 (13.3) arbitrary units v 204.9 (15.7) arbitrary units, p < 0.01), and GFR (p < 0.01). CML was positively related to decreased total protein and serum albumin and negatively to body mass index (p < 0.01). In contrast, in the heart transplant group, impaired GFR was associated with a notable rise of both CML (mean (SEM) 876.1 (53.1) ng/ml, p < 0.01) and AGE-Fl (mean (SEM) 385.6 (26.1) arbitrary units, p < 0.01). A positive relation between CML and serum albumin (r  =  0.394, p < 0.05) and lipofuscin (r  = 0.651, p < 0.01) was found. Conclusions: The contrasting concentration of CML and AGE-Fl between patients with CHF and after heart transplantation in the presence of decreased GFR and oxidative stress are explained by lowered plasma proteins in CHF and higher concentrations in heart transplant recipients. In heart transplant recipients, in addition to myocardial inflammatory processes, immunosuppression may be important for enhanced formation of AGEs

Development of methodology for alternative testing strategies for the assessment of the toxicological profile of nanoparticles used in medical diagnostics. NanoTEST – EC FP7 project

Nanoparticles (NPs) have unique, potentially beneficial properties, but their possible impact on human health is still not known. The area of nanomedicine brings humans into direct contact with NPs and it is essential for both public confidence and the nanotech companies that appropriate risk assessments are undertaken in relation to health and safety. There is a pressing need to understand how engineered NPs can interact with the human body following exposure. The FP7 project NanoTEST (www.nanotest-fp7.eu) addresses these requirements in relation to the toxicological profile of NPs used in medical diagnostics