Ischemic diseases are characterized by reduced blood supply to a tissue or an organ due to obstruction of blood vessels. The most serious and most common ischemic diseases include ischemic heart disease, ischemic stroke, and critical limb ischemia. Revascularization is the first choice of therapy, but the cell therapy is being introduced as a possible way of treatment for no-option patients. One of the possibilities of cell therapy is the use of mesenchymal stem cells (MSCs). MSCs are easily isolated from bone marrow and can be defined as non-hematopoietic multipotent adult stem cells population with a defined capacity for self-renewal and differentiation into cell types of all three germ layers depending on their origin. Since 1974, when Friedenstein and coworkers (Friedenstein et al. 1974) first time isolated and characterized MSCs, MSC-based therapy has been shown to be safe and effective. Nevertheless, many scientists and clinical researchers want to improve the success of MSCs in regenerative therapy. The secret of successful cell therapy may lie, along with the homing, in secretion of biologically active molecules including cytokines, growth factors, and chemokines known as MSCs secretome. One of the intracellular signalling mechanism includes the activity of phosphatidylinositol-3-kinase (phosphoinositide 3-kinase) (PI3K) - protein kinase B (serine-threonine protein kinase Akt) (Akt) pathway. This PI3K/Akt pathway plays key roles in many cell types in regulating cell proliferation, differentiation, apoptosis, and migration. Pre-conditioning of MSCs could improve efficacy of signalling mechanism.

• MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• fyziologická neovaskularizace MeSH
• ischemie metabolismus   terapie   MeSH
• kinázy asociované s rho metabolismus   MeSH
• lidé MeSH
• mezenchymální kmenové buňky metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Cholelithiasis is more common in patients with Crohn's disease (CD) than in the healthy population. The aim here was to examine risk factors for cholelithiasis in a cohort of CD patients and to compare the prevalence of cholelithiasis in a cohort of CD patients with that in a control group. This was a single-center retrospective case-control study. The cohort comprised all consecutive CD patients who underwent abdominal ultrasound from January 2007 to January 2018. The control group comprised age- and gender-matched non-CD patients referred for upper gastrointestinal tract dyspepsia. The study included 238 CD patients and 238 controls. The prevalence of cholelithiasis in the CD and control groups was 12.6 % and 9.2 %, respectively (risk ratio (RR), 1.36; p=0.24). Univariate analysis revealed that cholelithiasis was associated with multiple risk factors. Multivariate analysis identified age (OR, 1.077; 95 % CI, 1.043-1.112; p<0.001) and receipt of parenteral nutrition (OR, 1.812; 95 % CI, 1.131-2.903; p=0.013) as independent risk factors for cholelithiasis in CD patients. The prevalence of cholelithiasis in CD patients was higher than that in the control group; however, the difference was not statistically significant. Age and receipt of parenteral nutrition were independent risk factors for cholelithiasis in CD patients.

• MeSH
• cholelitiáza epidemiologie   etiologie   MeSH
• Crohnova nemoc komplikace   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• prevalence MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH

Patients with diabetes mellitus are at an increased risk of bone fractures. Several groups of effective antidiabetic drugs are available, which are very often given in combination. The effects of these medications on bone metabolism and fracture risk must not be neglected. Commonly used antidiabetic drugs might have a positive, neutral or negative impact on skeletal health. Increased risk of fracture has been identified with use of thiazolidinediones, most definitively in women. Also treatment with sulfonylureas can have adverse effects on bone. One consequence of these findings has been greater attention to fracture outcomes in trails of new diabetes medication (incretins and SGLT-2 inhibitors). The effect of insulin on bone is discussed and the risk of fractures in patients using insulin seems to be unrelated to insulin as itself. The aim of the review is to summarize effects of antidiabetic treatment on bone - bone mineral density, fractures and bone turnover markers. The authors also try to recommend a strategy how to treat patients with diabetes mellitus regarding the risk of osteoporotic fractures. In this review the problem of how to treat osteoporosis in patient with diabetes is also discussed.

• MeSH
• diabetes mellitus 2. typu komplikace   farmakoterapie   MeSH
• hypoglykemika škodlivé účinky   MeSH
• inhibitory kostní resorpce terapeutické užití   MeSH
• inkretiny farmakologie   MeSH
• inzulin farmakologie   MeSH
• kosti a kostní tkáň účinky léků   MeSH
• lidé MeSH
• metformin farmakologie   MeSH
• osteoporóza komplikace   diagnóza   farmakoterapie   MeSH
• sulfonylmočovinové sloučeniny škodlivé účinky   MeSH
• thiazolidindiony škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

It is well known that smoking is the risk factor in the development and clinical course of Crohn s disease (CD), but on the other hand, smoking is a protective factor against ulcerative colitis (UC). The pathways that are influenced by smoking in CD and UC are poorly understood. The aim of our study was to analyse the influence of smoking on the mRNA expression of cytokines in mucosa in patients with CD and UC. We performed a cross-sectional study. The cohort consisted of 86 IBD patients (48 CD patients and 38 UC patients) and took place at the IBD Centre at the University Hospital Bratislava-Ružinov. We took the demographic and clinical data of each patient, including information about their smoking habits. We performed a colonoscopy on each patient and took biopsies from both inflamed and non-inflamed sigma (CD, UC) and terminal ileum (CD). mRNA was extracted from mucosal biopsy samples for each cytokine and was normalized to a housekeeping gene (GAPDH). Finally, we compared the mRNA expression of target cytokines in the mucosa of smokers and non-smokers in IBD patients. Smokers with Crohn s disease have a significantly higher mRNA expression of pro-inflammatory cytokine TNF ? (p=0.003) in inflamed mucosa in sigma compared with non-smokers. In smokers with ulcerative colitis, we observed significantly higher mRNA expression of anti-inflammatory cytokine IL 10 (p=0.022) in non-inflamed mucosa of sigma. Similarly, smokers with UC have a significantly decreased mRNA expression of cytokine TLR 2 (p=0.024) and CCR1 (p=0.049) in non-inflamed mucosa of sigma. Based on our results, smoking has a positive influence on cessation and the clinical course of UC due to the stimulation of anti-inflammatory cytokine IL 10 in mucosa. On the other hand, smokers with CD have a higher expression of pro-inflammatory cytokine TNF ?, which could be associated with a worsening of the disease and response to therapy.

• MeSH
• Crohnova nemoc metabolismus   MeSH
• cytokiny metabolismus   MeSH
• dospělí MeSH
• kouření tabáku metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• mladý dospělý MeSH
• průřezové studie MeSH
• senioři MeSH
• střevní sliznice metabolismus   MeSH
• ulcerózní kolitida metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Store-operated calcium entry (SOCE) is one of regulatory mechanisms which regulates Ca2+ cycling in the heart. SOCE alterations in pathological conditions contribute to progression of heart failure and cardiac hypertrophy by multiple signaling pathways such as Cn/NFAT and CaMKII/MEF2. Several components mediating SOCE have been identified, such as STIM and Orai. Different isoforms of both Orai and STIM have been detected in animal studies, exhibiting distinct functional properties. This study is focused on the analysis of STIM and Orai isoforms expression in the end-stage human failing myocardium. Left ventricle samples isolated from 43 explanted hearts from patients undergoing heart transplant and from 5 healthy donor hearts were used to determine the mRNA levels of Orai1, Orai2 and Orai3, STIM1, STIM2 and STIM2.1 by qRT-PCR. The expression was further analyzed for connection with gender, related co-morbidities, pathoetiology, clinical data and biochemical parameters. We show that Orai1 expression is decreased by 30 % in failing myocardium, even though we detected no significant changes in expression of Orai2 or Orai3. Interestingly, this decrease in Orai1 was gender-specific and was present only in men, with no change in women. The ratio Orai1/Orai3 was significantly lower in males as well. The novel STIM2.1 isoform was detected both in healthy and failing human myocardium. In the end-stage heart failure, the expression of STIM2.1 was significantly decreased. The lower ratio of STIM2.1/STIM2 in failing hearts indicates a switch from SOCE-inhibiting STIM2.1 isoform to stimulatory STIM2.2. STIM1 mRNA levels were not significantly changed. These observed alterations in Orai and STIM expression were independent of functional heart parameters, clinical or biochemical patient characteristics. These results provide detailed insight into the alterations of SOCE regulation in human failing myocardium. Gender-specific change in Orai1 expression might represent a possible mechanism of cardioprotective effects of estrogens. The switch from STIM2.1 to STIM2.2 indicates an amplification of SOCE and could contribute to the hypertrophy development in the filing heart.

• MeSH
• dospělí MeSH
• kanály aktivované uvolněním vápníku metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myokard metabolismus   MeSH
• pohlavní dimorfismus MeSH
• protein - isoformy metabolismus   MeSH
• proteiny STIM metabolismus   MeSH
• remodelace komor MeSH
• srdeční selhání metabolismus   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Osteoporosis is an increasingly widespread disease, as well as diabetes mellitus. It is now accepted that osteoporotic fractures are a serious co-morbidity and complication of diabetes. Despite of good bone mineral density in Type 2 Diabetes (T2DM) patients is the fracture risk elevated. It is due to reduced bone quality. To determine the effect of glycemic compensation on bone density and trabecular bone score (TBS) in T2DM. We analyzed a cohort of 105 postmenopausal women with T2DM. For all patients, central bone density (spinal and lumbar spine) was tested by DXA methodology, glycemic control parameters were assessed, and anthropometric parameters were measured. Bone quality was analyzed using TBS software. The results were statistically processed. Good glycemic compensation with glycated hemoglobin (A1c) value <7.0 % DCCT did not lead to BMD changes in patients with T2DM. However, patients with HbA1c <7 % DCCT had significantly better TBS (1.254±0.148 vs. 1.166±0.094, p=0.01). There was a negative correlation between TBS and glycated hemoglobin (r= -0,112, p<0.05) with glycemic fasting (r= -0.117, p<0.05). The optimal effect on TBS is achieved when all three markers of glycemic compensation (glycated hemoglobin, fasting plasma glucose and postprandial glycemia) are in optimal range. By using ROC curves glycated hemoglobin has the most significant effect on TBS. Optimal glycemic compensation, evaluated by glycated hemoglobin, does not lead to changes in BMD but has a beneficial effect on TBS in T2DM. Good glycemic control is required also for reduction of the risk of osteoporosis and osteoporotic fractures.

• MeSH
• diabetes mellitus 2. typu krev   farmakoterapie   patologie   MeSH
• glykovaný hemoglobin metabolismus   MeSH
• hypoglykemika farmakologie   terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• kostní denzita * MeSH
• lidé středního věku MeSH
• lidé MeSH
• metformin farmakologie   terapeutické užití   MeSH
• postmenopauza MeSH
• průřezové studie MeSH
• sitagliptin fosfát farmakologie   terapeutické užití   MeSH
• trabekulární kostní tkáň účinky léků   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The randomized trials showed that the addition of training resistance program to androgen-deprivation therapy (ADT) had many beneficial effects for prostate cancer (PC) patients (significant protective effect on the volume of muscle mass) and the studies have revealed a panel of miRNAs, which are deregulate in PC and may serve as promising biomarkers of PC risk. The primary aim of our present study was to investigate the effect of exercise training to changes in body composition (muscle strength) and the secondary endpoint was to investigate the impact of an exercise training program on plasma levels of selected myogenic microRNAs (miRNAs) (miRNA-1, miRNA-29b, and miRNA-133) in PC patients undergoing the ADT. Effect of ADT and exercise intervention showed significant increase (experimental group vs. control group) the changes in body composition, free testosterone levels, IL-6 and plasma levels of myogenic miRNAs and significant reduced insulin serum levels. In conclusion, resistance training with ADT in the treatment of PC significantly changed the physical and metabolic function and the plasma levels of specific myogenic miRNAs. Our data support with the other publicized results.

• MeSH
• antagonisté androgenů terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA krev   MeSH
• nádory prostaty krev   terapie   MeSH
• odporový trénink * MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

This article is focused on endocrine-mediated osteoporosis caused by growth hormone (GH) disorders; adult GH deficiency and acromegaly. GH and insulin like growth factor-1 (IGF-1) stimulate linear bone growth through complex hormonal interactions and activates epiphyseal prechondrocytes. GH, via receptor activator of nuclear factor-kappaB (RANK), its ligand (RANK-L), and the osteoprotegerin system, stimulates production of osteoprotegerin and its accumulation in bone matrix. Malfunction of this mechanism, could lead to specific bone impairment. However, the primary problem of bone disease in GH secretion disorders is the primary prevention of osteoporotic fractures, so it is important to determine bone quality that better reflects the patient's actual predisposition to fracture. A method estimating bone quality from lumbar spine dual X-ray absorptiometry (DXA) scans is trabecular bone score (TBS). TBS in addition to bone mineral density (BMD) is a promising predictor of the osteoporotic fracture risk in women with postmenopausal osteopenia. In acromegaly TBS better defines risk of fracture because BMD is normal or even increased. TBS helps to monitor the effect of growth hormone therapy. Despite these findings, TBS should not be used alone, but a comprehensive consideration of all fracture risk factors, BMD and bone turnover markers is necessary.

• MeSH
• endokrinní nemoci kostí patologie   MeSH
• lidé MeSH
• růstový hormon nedostatek   MeSH
• trabekulární kostní tkáň patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Drug-induced liver injury (DILI) is a common event in patients with rheumatic diseases (RD) on biological therapy (BT). We aimed at evaluating the prevalence and pattern of DILI. Consecutive RD patients treated with BT were followed for 6 months. ALT and ALP >the upper limit normal (ULN) and 3xULN injury Grade 2. 582 liver function tests (LFTs) in 199 patients were evaluated, median age 53y, 59.3 % females, RA in 108, AS 49, and PsA 42 patients. ALT Grade 1 elevation was observed in 25.6 %, transient in 18.6 %, persisting in 7 %, Grade 2 in 1.5 %, ALP Grade 1 in 3.5 %, transient in 2 %, persisting in 1.5 %. We report no case of ALP Grade 2 or Hy ́s law (ALT>3xULN, bilirubin>2xULN). Patients with persisting ALT elevation had higher BMI (28.23 vs. 25.74, p=0.016), lower DAS28 (2.22 vs. 5.28, p=0.046). ALT Grade 1 injury was more frequent with solo tocilizumab compared with other agents (27.5 % vs. 13.6 %, p=0.01). DILI was frequent, in 18.6 % transient, in 7 % persisting, Grade 2 in 1.5 %, led to treatment alteration in 0.5 %, with higher prevalence on solo tocilizumab therapy. We report no new safety signals for BT in RD.

• MeSH
• biologická terapie škodlivé účinky   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky škodlivé účinky   MeSH
• kohortové studie MeSH
• lékové postižení jater epidemiologie   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• prevalence MeSH
• revmatické nemoci terapie   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH