Testicular cancer is the most common form of cancer in young men of reproductive age and its incidence is increasing globally. With the currently successful treatment and 95% survival rate, there is a need for deeper understanding of testicular cancer-related infertility. Most patients with testicular cancer experience semen abnormalities prior to cancer therapy. However, the exact mechanism of the effect of testicular cancer on sperm anomalies is not known. Mitochondria are organelles that play a crucial role in both tumorigenesis and spermatogenesis and their malfunction may be an important factor resulting in sperm abnormalities in testicular cancer patients. Within the scope of this review, we will discuss current knowledge of testicular cancer-related alterations in the ATP production pathway, a possible pathophysiological switch from oxidative phosphorylation (OXPHOS) to glycolysis, as well as the role of oxidative stress promoting sperm dysfunction. In this regard, the review provides a summary of the impact of testicular cancer on sperm quality as a possible consequence of impaired mitochondrial function including the energy metabolic pathways that are known to be altered in the sperm of testicular cancer patients.
Prevalence of non-alcoholic fatty liver disease (NAFLD) increases in line with obesity and type 2 diabetes, and there is no approved drug therapy. Polyunsaturated fatty acids of n-3 series (omega-3) are known for their hypolipidaemic and anti-inflammatory effects. Existing clinical trials suggest varying effectiveness of triacylglycerol- or ethyl ester-bound omega-3 in the treatment of NAFLD, without affecting advanced stages such as non-alcoholic steatohepatitis. Preclinical studies suggest that the lipid class used to supplement omega-3 may determine the extent and nature of their effects on metabolism. Phospholipids of marine origin represent an alternative source of omega-3. The aim of this review is to summarise the available evidence on the use of omega-3 phospholipids, primarily in obesity-related NAFLD, and to outline perspectives of their use in the prevention/treatment of NAFLD. A PubMed literature search was conducted in May 2021. In total, 1088 articles were identified, but based on selection criteria, 38 original papers were included in the review. Selected articles describing the potential mechanisms of action of omega-3 phospholipids have also been included. Preclinical evidence clearly indicates that omega-3 phospholipids have strong antisteatotic effects in the liver, which are stronger compared to omega-3 administered as triacylglycerols. Multiple mechanisms are likely involved in the overall antisteatotic effects, involving not only the liver but also adipose tissue and the gut. Robust preclinical evidence for strong antisteatotic effects of omega-3 phospholipids in the liver should be confirmed in clinical trials. Further research is needed on the possible effects of omega-3 phospholipids on advanced NAFLD.
- MeSH
- fosfolipidy MeSH
- kyseliny mastné omega-3 terapeutické užití MeSH
- lidé MeSH
- nealkoholová steatóza jater farmakoterapie etiologie MeSH
- obezita komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
High doses of corticosteroids in combination with rituximab remain an alternative in the treatment in relapsed or refractory chronic lymphocytic leukaemia (CLL) in the current era of targeted therapies. This study retrospectively evaluates the efficacy of an RCD (rituximab, cyclophosphamide and dexamethasone) regimen in the treatment of 51 patients with relapsed CLL (median age, 72 years). Unfavourable prognostic features, such as Rai stage III/IV, unmutated IGHV, del11q, TP53 mutation/deletion, complex karyotype and bulky lymphadenopathy, were frequent. The overall response or complete remission was of 57% and 7%, respectively, and the median progression-free survival (PFS) was of 12.3 months, median time to next treatment 23.1 months and median overall survival 39.2 months. Significant independent predictors of shorter PFS were TP53 deletion/mutation, advanced Rai stage and ≥2 previous lines of treatment. The incidence of neutropenia grade ≥ 3 was of 13%. Serious (CTCAE grade 3-5) infections were found in 20% of patients. Steroid-induced diabetes or diabetes decompensation occurred in 20% patients. Treatment-related adverse events resulted in RCD dose reduction in 35% of patients. In comparison with a historical R-Dex patient group, the treatment response and/or toxicity in our group was largely similar. However, the substantial differences in the baseline clinical characteristics of the groups may affect this comparison. In conclusion, the RCD regimen is an active, time-limited therapeutic strategy for elderly patients with relapsed CLL. Further, the results of our analysis indicate that the addition of cyclophosphamide to the R-Dex regimen maintains a similar efficacy, even after 50% reduction in the dexamethasone dose.
- MeSH
- chronická lymfatická leukemie farmakoterapie genetika patologie MeSH
- cyklofosfamid aplikace a dávkování MeSH
- dexamethason aplikace a dávkování MeSH
- diabetes mellitus chemicky indukované epidemiologie MeSH
- doba přežití bez progrese choroby MeSH
- indukce remise MeSH
- infekce epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie genetika patologie MeSH
- míra přežití MeSH
- nádorový supresorový protein p53 genetika MeSH
- neutropenie chemicky indukované epidemiologie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- retrospektivní studie MeSH
- rituximab aplikace a dávkování MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- vysazování léků MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Antibodies of non-human mammals are glycosylated with carbohydrate antigens, such as galactose-α-1-3-galactose (α-Gal) and N-glycolylneuraminic acid (Neu5Gc). These non-human carbohydrate antigens are highly immunogenic in humans due to loss-of-function mutations of the key genes involved in their synthesis. Such immunogenic carbohydrates are expressed on therapeutic polyclonal rabbit anti-human T-cell IgGs (anti-thymocyte globulin; ATG), the most popular induction treatment in allograft recipients. To decipher the quantitative and qualitative response against these antigens in immunosuppressed patients, particularly against Neu5Gc, which may induce endothelial inflammation in both the graft and the host. We report a prospective study of the antibody response against α-Gal and Neu5Gc-containing glycans following rabbit ATG induction compared to controls. We show a drop in the overall levels of anti-Neu5Gc antibodies at 6 and 12 months post-graft compared to the pre-existing levels due to the major early immunosuppression. However, in contrast, in a cross-sectional study there was a highly significant increase in anti-Neu5Gc IgGs levels at 6 months post-graft in the ATG-treated compared to non-treated patients(P = 0.007), with a clear hierarchy favouring anti-Neu5Gc over anti-Gal response. A sialoglycan microarray analysis revealed that the increased anti-Neu5Gc IgG response was still highly diverse against multiple different Neu5Gc-containing glycans. Furthermore, some of the ATG-treated patients developed a shift in their anti-Neu5Gc IgG repertoire compared with the baseline, recognizing different patterns of Neu5Gc-glycans. In contrast to Gal, Neu5Gc epitopes remain antigenic in severely immunosuppressed patients, who also develop an anti-Neu5Gc repertoire shift. The clinical implications of these observations are discussed.
- MeSH
- buněčná imunita fyziologie MeSH
- dospělí MeSH
- homologní transplantace MeSH
- imunoglobulin G farmakologie MeSH
- imunologické faktory farmakologie MeSH
- kyseliny neuraminové imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- protilátky imunologie metabolismus MeSH
- průřezové studie MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- thymocyty imunologie MeSH
- transplantace ledvin metody MeSH
- transplantační imunologie fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: New treatments in coeliac disease are being vigorously pursued to either replace or facilitate the difficult-tofollow gluten-free diet. DESIGN: The present review intends to summarise the challenges in gluten-free diet adherence during the transitional period, as reflected in the last Prague consensus, published in 2016. RESULTS: The honourable panel members recommended that dietary adherence and the consequences of nonadherence represent key components for discussion in the transitional period setting. CONCLUSIONS: There are numerous difficulties in adhering to gluten withdrawal, but the transition period from adolescence to young adulthood is considered a fragile and high-risk period for intentional and unintentional gluten intake.
- MeSH
- adherence pacienta * MeSH
- bezlepková dieta * MeSH
- celiakie dietoterapie MeSH
- konsensus MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Pheochromocytomas are tumours arising from chromaffin tissue located in the adrenal medulla associated with typical symptoms and signs which may occasionally develop metastases, which are defined as the presence of tumour cells at sites where these cells are not found. This retrospective analysis was focused on clinical, genetic and histopathologic characteristics of primary metastatic versus primary benign pheochromocytomas. MATERIALS AND METHODS: We identified 41 subjects with metastatic pheochromocytoma and 108 subjects with apparently benign pheochromocytoma. We assessed dimension and biochemical profile of the primary tumour, age at presentation and time to develop metastases. RESULTS: Subjects with metastatic pheochromocytoma presented at a significantly younger age (41·4 ± 14·7 vs. 50·2 ± 13·7 years; P < 0·001) with larger primary tumours (8·38 ± 3·27 vs. 6·18 ± 2·75 cm; P < 0·001) and secreted more frequently norepinephrine (95·1% vs. 83·3%; P = 0·046) compared to subjects with apparently benign pheochromocytomas. No significant differences were found in the incidence of genetic mutations in both groups of subjects (25·7% in the metastatic group and 14·7% in the benign group; P = 0·13). From available histopathologic markers of potential malignancy, only necrosis occurred more frequently in subjects with metastatic pheochromocytoma (27·6% vs. 0%; P < 0·001). The median time to develop metastases was 3·6 years with the longest interval 24 years. CONCLUSIONS: In conclusion, regardless of a genetic background, the size of a primary pheochromocytoma and age of its first presentation are two independent risk factors associated with the development of metastatic disease.
- MeSH
- adrenalin sekrece MeSH
- časové faktory MeSH
- dospělí MeSH
- feochromocytom genetika metabolismus patologie MeSH
- hodnocení rizik MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- nádory nadledvin genetika metabolismus patologie MeSH
- noradrenalin sekrece MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- tumor burden MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Intramural MeSH
BACKGROUND: The aim of our study was to assess the impact of increased iron stores on the presence of asymptomatic atherosclerosis in a cohort of healthy men. We anticipated that higher iron stores would be associated with higher soluble cluster of differentiation 163 (sCD163) concentrations, elevated markers of oxidative stress, inflammation and higher common carotid intima-media thickness, independently of traditional risk factors of atherosclerosis. METHODS: In this cross-sectional study that included 72 healthy men, we measured the ultrasonography of common carotid intima-media thickness (IACC), the ratio of plasma-circulating transferrin receptors concentration to plasma ferritin concentration, certain inflammatory and oxidative stress markers, insulin sensitivity, plasma lipids and markers of endothelial dysfunction. RESULTS: The plasma-circulating transferrin receptor concentration to plasma ferritin concentration ratio (TfR/F) showed significant association with IACC (r=-0·310, P=0·008 vs. r=0·295, P=0·012). Multivariate analysis confirmed that the correlation of TfR/F with IACC is independent of traditional risk factors of atherosclerosis. The TfR/F ratio correlated with other indicators of atherosclerotic process fibrinogen (r=-0·292, P=0·013), von Willebrand factor (vWf; r=0·284, P=0·017), sCD163 (r=0·239, P=0·043) and IL-8 (r=0·233, P=0·049). In multivariate analysis, TfR/F independently correlated with haemoglobin (β=-0·220, P=0·047), fibrinogen (β=-0·290, P=0·009), IL-8 (β=0·227, P=0·039) and sCD163 (β=0·244, P=0·025); however, when vWf was added, significant independent correlation was seen only with fibrinogen (β=-0·301, P=0·007) and IL-8 (β=0·219, P=0·047). In addition, we demonstrated the independent correlation of sCD163 with vWf (β=0·240, P=0·040). CONCLUSIONS: Our study showed a clear association of body iron stores expressed by the TfR/F ratio with asymptomatic carotid atherosclerosis. TfR/F further exhibited an independent positive correlation with fibrinogen and a negative correlation with sCD163 and IL-8.
- MeSH
- biologické markery metabolismus MeSH
- cévní endotel ultrasonografie MeSH
- dospělí MeSH
- ferritin krev MeSH
- fibrinogen metabolismus MeSH
- interleukin-8 krev MeSH
- intimomediální šíře tepenné stěny MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- multivariační analýza MeSH
- nemoci arterie carotis krev MeSH
- oxidační stres fyziologie MeSH
- průřezové studie MeSH
- receptory transferinu krev MeSH
- rizikové faktory MeSH
- von Willebrandův faktor metabolismus MeSH
- železo metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Background: A novel adipokine, visfatin, was found to be related to adiposity in humans and regulated by a number of hormonal signals. The aim of this study was to investigate the relationships of visfatin expression in adipose tissue with potential regulatory factors such as insulin, testosterone and tumor necrosis factor-alpha (TNF-alpha) and to elucidate the effect of a diet induced weight reduction on adipose tissue mRNA expression and plasma levels of visfatin. MATERIALS AND METHODS: Biopsies of subcutaneous abdominal adipose tissue (SCAAT) and plasma samples were obtained at the beginning of the study from 47 pre-menopausal women (age 38.7 +/- 1.7 years, body mass index (BMI) 27.9 +/- 1.4 kg m(-2)), consisting of 15 lean, 16 overweight and 16 obese subjects. The subgroup of 32 overweight/obese women (age 42.1 +/- 1.9 years, BMI 31.2 +/- 0.9 kg m(-2)) underwent a 12 week hypocaloric weight reducing diet and samples were obtained at the end of the diet. Biopsy samples were analysed for visfatin and TNF-alpha mRNA levels and plasma was analysed for relevant metabolites and hormones. RESULTS: In the group of 47 subjects visfatin mRNA expression in SCAAT was negatively correlated with plasma free testosterone (r = -0. 363, P < 0.05) and BMI (r = -0.558, P < 0.01) and positively associated with adipose tissue TNF-alpha mRNA expression (r = 0.688, P < 0.01). The diet resulted in the reduction of body weight and in the decrease of plasma insulin, free testosterone and TNF-alpha levels. In the group of overweight/obese subjects visfatin mRNA in SCAAT increased after the diet and the diet induced increase was positively correlated with the magnitude of body weight loss. CONCLUSION: Visfatin mRNA expression in SCAAT is associated with TNF-alpha expression, plasma free testosterone and BMI in pre-menopausal women. A weight reducing hypocaloric diet results in the increase of visfatin mRNA in SCAAT.
- MeSH
- distribuce tělesného tuku MeSH
- dospělí MeSH
- financování organizované MeSH
- hmotnostní úbytek fyziologie MeSH
- hormony krev metabolismus MeSH
- index tělesné hmotnosti MeSH
- lidé středního věku MeSH
- lidé MeSH
- nikotinamidfosforibosyltransferasa krev metabolismus MeSH
- podkožní tuk metabolismus MeSH
- statistika jako téma MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
BACKGROUND: Adipocyte-fatty acid binding protein (A-FABP) is a circulating protein expressed in adipocytes and macrophages. Several recent studies demonstrated that A-FABP might be involved in the pathogenesis of metabolic syndrome, particularly in dyslipidaemia, insulin resistance and atherosclerosis. The aim of this study was to investigate the influence of atorvastatin treatment (20 mg day(-1) for 3 months) on serum A-FABP value in subjects with hyperlipidaemia. MATERIALS AND METHODS: Anthropometric and serum analyses were performed for body mass index, A-FABP, triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), high sensitive C-reactive protein (hs-CRP), creatine kinase (CK) and glucose on 26 subjects (BMI 30.3 +/- 6.0, mean age 62 +/- 10 years) with hyperlipidaemia who met the criteria: total cholesterol > 5.2 mmol L(-1), LDL cholesterol > 3.3 mmol L(-1) and triglycerides < 3 mmol L(-1). RESULTS: After the 3-month therapy, a significant reduction in total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), glucose (P < 0.001), A-FABP (from 44.6 +/- 26.2 to 38.6 +/- 19.3 g L(-1), P < 0.01), uric acid (P < 0.05), AST (P < 0.05) and triglycerides (P < 0.05) values was observed. No difference was found in BMI, CK, ALT, hs-CRP, or HDL cholesterol values. A significant difference in the serum A-FABP value before and after the therapy remains after the correction for total cholesterol value (P < 0.001). A positive correlation between serum A-FABP and glucose was found (P < 0.05). CONCLUSIONS: In conclusion, our study confirmed in vivo that atorvastatin reduces serum A-FABP by a pleiotropic mechanism and supports the hypothesis that A-FABP is involved in atherosclerotic actions.
- MeSH
- anticholesteremika terapeutické užití MeSH
- cholesterol krev MeSH
- hyperlipidemie farmakoterapie MeSH
- index tělesné hmotnosti MeSH
- kyseliny heptylové terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom farmakoterapie MeSH
- prospektivní studie MeSH
- proteiny vázající mastné kyseliny účinky léků MeSH
- pyrroly terapeutické užití MeSH
- senioři MeSH
- tukové buňky účinky léků MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
