Plasma irisin and the brain-derived neurotrophic factor levels in sedentary subjects: effect of 8-weeks lifestyle intervention.

Objectives. Sedentary lifestyle increasingly observed in the population contributes to the incremental incidence of obesity, cardiovascular diseases, mental disorders, type 2 diabetes, hyper-tension, dyslipidemia, and others. Physical inactivity together with an imbalance in caloric intake and expenditure leads to a loss of muscle mass, reduced insulin sensitivity, and accumulation of the visceral fat. Organokines (adipokines, myokines, hepatokines, etc.) serve in the organism for inter-organ communication. However, human studies focused on the exercise-related changes in plasma levels of certain myokines have produced contradictory results. In the present study, we verified a hypothesis that myokine irisin, which is expected to increase in response to physical activity, induces brain-derived neurotrophic factor (BDNF) production and by this way mediates the beneficial effect of exercise on several brain functions. Subjects and Methods. Women (n=27) and men (n=10) aged 44.5±12.0 years, who were sedentary and overweight/obese (men ≥25%, women ≥28% body fat), participated in the study. The effect of an 8-week intensive lifestyle intervention (150 minutes of moderate physical activity per week, diet modification, and reduction of caloric intake) on the selected organokines (irisin, BDNF) in the context of an expected improvement in cardiometabolic status was examined. Results. The 8-week lifestyle intervention resulted in a significant (p<0.05) reduction in body mass index, body fat, blood pressure, insulin resistance, lipid and liver parameters, and irisin levels (p<0.001). However, BDNF increase in the whole group did not reach statistical significance. After the improvement of cardiometabolic parameters, a significant decrease in irisin and increase in BDNF levels were also observed in the subgroup with unsatisfactory (≤5%) body weight reduction. Neither relationship between irisin and BDNF levels, nor effect of age or sex on their levels was observed. Conclusions. We cannot confirm the hypothesis that exercise-induced irisin may increase the BDNF levels, whereas, the organokine levels in the periphery may not completely reflect the processes in the brain compartments. The observed decrease in irisin levels after 8-week intensive lifestyle intervention program, which was in contrary to its supposed mechanisms of action and dynamics, suggests the presence of several yet undiscovered impacts on the secretion of irisin.

Nutritional interventions for patients with alkaptonuria: A minireview.

Alkaptonuria (AKU, OMIM, No. 203500) is a rare, slow-progressing, irreversible, multisystemic disease resulting from a deficiency of the homogentisate 1,2-dioxygenase enzyme, which leads to the accumulation of homogentisic acid (HGA) and subsequent deposition as pigment in connective tissues called ochronosis. As a result, severe arthropathy of large joints and spondyloarthropathy with frequent fractures, ligament ruptures, and osteoporosis develops in AKU patients. Since 2020, the first-time treatment with nitisinone has become available in the European Union. Nitisinone significantly reduces HGA production and arrests ochronosis in AKU patients. However, blocking of the tyrosine metabolic pathway by the drug leads to tyrosine plasma and tissue concentrations increase. The nitisinone-induced hypertyrosinemia can lead to the development of corneal keratopathy, and once it develops, the treatment needs to be interrupted. A decrease in overall protein intake reduces the risk of the keratopathy during nitisinone-induced hypertyrosinemia in AKU patients. The low-protein diet is not only poorly tolerated by patients, but over longer periods, leads to a severe muscle loss and weight gain due to increased energy intake from carbohydrates and fats. Therefore, the development of novel nutritional approaches is required to prevent the adverse events due to nitisinone-induced hypertyrosinemia and the negative impact on skeletal muscle metabolism in AKU patients.

Endothelial Function in Patients with Multiple Sclerosis: The Role of GLP-1 Agonists, Lipoprotein Subfractions, and Redox Balance.

INTRODUCTION: Epidemiological studies have suggested an increased vascular risk in patients with multiple sclerosis (MS). There is increasing evidence of the beneficial effects of GLP-1 agonists (GLP-1a) in preventing vascular complications and slowing the progression of neurodegeneration. Our objective was to explore the changes in the endothelial function of MS patients after 12 months of GLP-1a therapy. We also explored the role of lipoprotein subfractions and the antioxidant capacity of plasma. METHODS: MS patients were enrolled in a prospective, unicentric study. GLP-1a (dulaglutide) was administered to 13 patients. The control population consisted of 12 subjects. Endothelial function was determined by peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI). Trolox equivalent antioxidant capacity (TEAC) was used to assess the total antioxidant capacity of the plasma. The levels of lipoprotein subfractions were evaluated. RESULTS: The GLP-1a group did not have a significant change in their RHIs after 12 months (2.1 ± 0.6 vs. 2.1 ± 0.7; p = 0.807). However, a significant increase in their TEACs was observed (4.1 ± 1.4 vs. 5.2 ± 0.5 mmol/L, p = 0.010). On the contrary, the subjects in the control group had a significant worsening of their RHIs (2.1 ± 0.5 vs. 1.8 ± 0.6; p = 0.030), without significant changes in their TEACs. Except for a significant decrease in very-low-density lipoprotein (VLDL) (30.8 ± 10.2 vs. 22.6 ± 8.3 mg/dL, p = 0.043), no other significant changes in the variables were observed in the control group. VLDL levels (beta = -0.637, p = 0.001), the use of GLP-1a therapy (beta = 0.560, p = 0.003), and small LDL (beta = 0.339, p = 0.043) were the only significant variables in the model that predicted the follow-up RHI. CONCLUSION: Our results suggest that the application of additional GLP-1a therapy may have atheroprotective and antioxidant effects in MS patients with high MS activity and thus may prospectively mitigate their vascular risk. However, the lipoprotein profile may also play an important role in the atherogenic risk of MS subjects.

Cardiac autonomic function in patients with early multiple sclerosis.

PURPOSE: Cardiac autonomic dysfunction has been reported in patients with long-standing multiple sclerosis (MS); however, data in early disease are limited. The present study was aimed at evaluating cardiac autonomic function in patients with early MS in the context of white matter metabolic status, which could potentially affect functions of the autonomic brain centers. METHODS: Cardiac sympathetic and baroreflex cardiovagal responses to the Valsalva maneuver, orthostatic test, and the Stroop test were evaluated in 16 early, treatment-naïve patients with relapsing-remitting MS, and in 14 healthy participants. Proton magnetic resonance spectroscopic imaging (MRSI) of the brain was performed in eight of these MS patients and in eight controls. RESULTS: Valsalva maneuver outcomes were comparable between patients and controls. At baseline, norepinephrine levels were lower (p = 0.027) in MS patients compared to controls. The patients had higher heart rate (p = 0.034) and lower stroke volume (p = 0.008), but similar blood pressure, cardiac output and norepinephrine increments from baseline to 2 min of the orthostatic test compared to controls. MS patients and controls did not differ in responses to the Stroop test. MRSI showed lower total N-acetylaspartate/total creatine (p = 0.038) and higher myo-inositol/total creatine (p = 0.013) in MS lesions compared to non-lesional white matter. CONCLUSION: Our results show normal cardiac sympathetic and baroreflex cardiovagal function in MS patients with relapsing-remitting MS with lesions at the post-acute/early resolving stage. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov under the Identifier: NCT03052595 and complies with the STROBE checklist for cohort, case-control, and cross-sectional studies.

Seroprevalence of SARS-CoV-2 IgG antibodies in the staff of the Slovak Academy of Sciences in response to COVID-19 and/or vaccination: situation in August 2021.

Cross-sectional seroprevalence study of SARS-CoV-2 IgG antibodies was accomplished in the Slovak Academy of Sciences to inform authorities of research institutions about the situation at their workplaces, to assess the risk of next exposure to SARS-CoV-2, and to guide decisions on institutional measures sustaining essential research in evolving epidemic situation. Study participants provided informed consent, anamnestic information, and self-collected dry blood spot samples that were analyzed by ELISA for SARS-CoV-2 S protein-specific IgG antibodies. Relative antibody levels detected in 1928 subjects showed seroprevalence of 84.13% and led to the following main findings consistent with the current knowledge: (1) mRNA-based vaccines induce better humoral response compared to adenovirus vaccines, (2) antibody levels reflect severity of COVID-19 symptoms, (3) post-COVID vaccination results in marked elevation of IgG levels particularly in asymptomatic and mild cases, (4) antibody levels decrease with increasing time elapsed from vaccination or COVID-19. In addition, data sorting to distinct research institutes and their clustering to three principal scientific sections of the Slovak Academy of Sciences revealed marked differences in seroprevalence, and allowed to identify workplaces with relatively high seropositivity and response rate that can potentially provide a safer working environment than those, where seroprevalence was low or unknown due to low participation. Thus, findings of this study can have direct implications on management decisions during the next pandemic development, with the necessity to keep in mind the phenomenon of time-dependent immunity waning and current spread of more contagious Delta variant of SARS-CoV-2. Keywords: SARS-CoV-2 coronavirus; COVID-19; spike protein; seroprevalence; antibodies; vaccination.

Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?

BACKGROUND: Inflammatory cytokines contribute to proatherogenic changes in lipid metabolism by reduction of HDL-cholesterol (HDL-C) levels, impairment of its antiinflammatory and antioxidant functions. Therefore, the protective actions of HDL-C can be limited in chronic inflammatory diseases such as multiple sclerosis (MS). The aim of this study was to assess the association between lipoprotein subfractions and inflammatory status in early stages of multiple sclerosis. METHODS: Polyacrylamide gel electrophoresis Lipoprint© System was used for lipoprotein profile analysis in 19 newly diagnosed MS patients, and in matched 19 healthy controls. Serum levels of interleukin (IL) 1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, interferon-γ and TNF-α were measured by multiplex bead assay. RESULTS: Concentrations of the measured cytokines and lipoprotein subclasses were comparable between MS patients and controls. Male, but not female MS patients had significantly higher total HDL-C and small HDL-C subfraction than healthy controls. Large HDL-C negatively correlated with all measured cytokines except IL-17 in MS but not in controls. Intermediate HDL-C subfractions correlated positively with all measured cytokines except G-CSF in MS females but not in MS males or controls. CONCLUSION: Our results of higher HDL-C and mainly its small HDL-C subfraction suggest that male MS patients are at higher risk of atherosclerosis and the subtle dyslipidemia is present in early stages of the disease. The correlations between specific HDL-C subfractions and the inflammatory cytokines demonstrate mutual links between systemic inflammation and lipid metabolism in MS. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03052595 Registered on Feb 14, 2017.

Autonomic Nervous System Response to Stressors in Newly Diagnosed Patients with Multiple Sclerosis.

Autonomic dysfunction is commonly detected in patients with multiple sclerosis (MS). However, data evaluating autonomic nervous system function in early MS are limited. Present study investigates response to two different stressors in newly diagnosed MS patients, looking for the signs of autonomic dysfunction at the beginning of the disease. We examined 19 MS patients and 19 age, sex, and body mass index matched healthy controls. MS patients were newly diagnosed, untreated, and with low expanded disability status scale (EDSS) values [median 1.0 (interquartile range 1.0-1.5)]. Two stressors were used to evaluate the response of autonomic nervous system: Stroop word-color interference mental stress test and orthostasis. Plasma levels of epinephrine and norepinephrine, blood pressure (BP), and heart rate variability (HRV) parameters were evaluated. At the end of Stroop test MS patients had lower systolic BP (121 ± 15 vs. 132 ± 17 mmHg, p = 0.044), lower heart rate (79 ± 9 vs. 88 ± 16 1/min, p = 0.041), and lower epinephrine increment (10 ± 22 vs. 30 ± 38 pg/ml; p = 0.049) compared to healthy controls. Norepinephrine response was unaffected in MS, however, with lower norepinephrine levels during the test (p = 0.036). HRV parameters were similar in both groups. No differences in BP, heart rate, catecholamines, and HRV parameters between groups during orthostatic testing were found. We found slightly diminished sympathetic response to mental stress test, but unchanged response to orthostasis, in newly diagnosed untreated MS patients. The results suggest that autonomic dysfunction in MS is connected with more developed disease.

Contribution of Genetic Factors to Lower DHEAS in Patients with Rheumatoid Arthritis.

OBJECTIVE: Lower production of adrenal androgens has been confirmed in females with rheumatoid arthritis (RA); however, the mechanisms of this finding are not completely understood. The aim of our study was to assess the contribution of genetic factors associated with variability of dehydroepiandrosterone sulfate (DHEAS) levels to lower DHEAS in female RA patients. METHODS: 448 RA and 648 healthy controls were genotyped for single-nucleotide polymorphisms (SNPs) in genes ZKSCAN5 (rs11761528), SULT2A1 (rs2637125), HHEX (rs2497306), and ARPC1A (rs740160). Serum DHEAS concentrations were measured in 112 RA patients and 91 healthy women. RESULTS: The allele frequencies in DHEAS-related loci were similar in RA and controls. RA patients had significantly lower serum DHEAS concentrations compared to healthy women. The cumulative number of alleles associated with lower DHEAS within genes ZKSCAN5, SULT2A1, HHEX, and ARPC1A present in each individual negatively correlated with DHEAS levels in RA patients, but not in controls. Linear regression analysis showed significant effect of polymorphisms in genes ZKSCAN5 and ARPC1A on serum DHEAS levels in female RA patients but not in the control group. CONCLUSION: Our findings suggest that complex interactions exist between genotype and adrenal androgen hypofunction in RA.

LDL and HDL lipoprotein subfractions in multiple sclerosis patients with decreased insulin sensitivity.

OBJECTIVES: Increased metabolic and cardiovascular morbidity has been reported in multiple sclerosis (MS) patients. Previously, we have found decreased insulin sensitivity and hyperinsulinemia in a group of newly diagnosed MS patients. We hypothesize that these features may be associated with an altered lipid profile and low, intermediate, or high density lipoprotein (LDL, IDL, HDL) subclasses accelerating atherosclerosis and thus contributing to the cardiovascular risk increase in these patients. SUBJECTS AND METHODS: In a group of 19 newly diagnosed untreated MS patients with previously found hyperinsulinemia and insulin resistance and a matched group of 19 healthy controls, the lipoprotein subclasses profile was determined. Polyacrylamide gel electrophoresis was used to separate and measure the LDL (large LDL and small dense LDL), HDL (large, intermediate and small), and IDL (A, B and C) subclasses with the Lipoprint© System (Quantimetrix Corporation, Redondo Beach, CA, USA). RESULTS: No difference was found either in the conventional lipid or lipoprotein subclasses profile between the MS patients and healthy controls. We found an inverse association between the level of IDL-B with fasting insulin (r=-0.504, p=0.032), the insulin resistance estimated by homeo-static model assessment - insulin resistance (HOMA-IR) (r=-0.498, p=0.035), insulin response expressed as area under the curve (AUC; r=-0.519, p=0.027), and area above the baseline (AAB; r=-0.476, p=0.045) and positive association with insulin sensitivity estimated by insulin sensitivity index (ISI) Matsuda (r=0.470, 0.048) in MS patients, but not in healthy controls suggesting the first signs in lipoprotein subclasses profile change. CONCLUSIONS: Our data indicate that changes in lipoprotein profile and subclasses are preceded by insulin resistance and hyperinsulinemia in patients with newly diagnosed MS.

Effects of short-term Pilates exercise on selected blood parameters.

The aim of our prospective, interventional, pre-post, single arm study was to supplement the lack of knowledge of the effect of short-term Pilates intervention on selected blood parameters of healthy women. Female volunteers were recruited for 2-weeks Pilates intervention. Blood has been collected and anthropometric parameters were measured before and after exercise period (EP). Plasma insulin, cortisol, and dehydroepiandrosterone sulphate levels, erythrocyte antioxidant activity, glutathione levels, NK cytotoxicity and plasma cytokines were analysed. We found a decrease in erythrocyte antioxidant enzymes SOD and GPx activity; GSH levels; in the pro-inflammatory chemokine MCP-1 and trend to reduction in MIP-1ß, PDGF and VEGF levels in plasma. NK cell cytotoxic activity increased after Pilates EP in the percentage of specific lysis at 25:1 effector: target (E:T) ratio and the same trend was observed at all E:T ratios as well as in the amount of lytic units per 107 cells. Our findings show that Pilates exercise may improve NK cell immune response and inflammatory milieu in plasma of healthy women.

Hypoxic conditions increases H2S-induced ER stress in A2870 cells.

Hypoxia - a state of lower oxygen demand-is responsible for a higher aggressiveness of tumors and therefore a worse prognosis. During hypoxia, several metabolic pathways are re-organized, e.g., energetic metabolism, modulation of pH, and calcium transport. Calcium is an important second messenger that regulates variety of processes in the cell. Thus, aim of this work was to compare H2S modulation of the intracellular calcium transport systems in hypoxia and in cells grown in standard culture conditions. For all experiments, we used ovarian cancer cell line (A2780). H2S is a novel gasotransmitter, known to be involved in a modulation of several calcium transport systems, thus resulting in altered calcium signaling. Two models of hypoxia were used in our study-chemical (induced by dimethyloxallyl glycine) and 2 % O2 hypoxia, both combined with a treatment using a slow H2S donor GYY4137. In hypoxia, we observed rapid changes in cytosolic and reticular calcium levels compared to cells grown in standard culture conditions, and these changes were even more exagerrated when combined with the GYY4137. Changes in a calcium homeostasis result from IP3 receptor´s up-regulation and down-regulation of the SERCA 2, which leads to a development of the endoplasmic reticulum stress. Based on our results, we propose a higher vulnerability of calcium transport systems to H2S regulation under hypoxia.

Hyperinsulinemia in newly diagnosed patients with multiple sclerosis.

There are limited data regarding glucose metabolism dysregulation in multiple sclerosis (MS). Present study investigates glucose and insulin response during oral glucose tolerance test (oGTT) in MS patients. We examined 19 MS patients and 19 age, sex and body mass index (BMI) matched healthy controls. MS patients were newly diagnosed, untreated and with low Expanded Disability Status Scale (EDSS) score (1.1 ± 0.7). Plasma glucose, lactate, insulin and GLP-1 during oGTT, and fasting adipokines, lipid and inflammatory parameters were analyzed. Insulin sensitivity indices (ISI) were calculated. MS patients had comparable fasting (5.2 ± 0.3 vs. 5.0 ± 0.4 mmol/l, p = 0.05) and post-load glucose concentrations as controls. Insulin response to oral glucose load in MS was increased (p = 0.022). Insulin sensitivity was lower in MS compared to controls [ISI(Matsuda) 6.95 ± 3.44 vs. 10.60 ± 4.81, p = 0.011 and ISI(Cederholm) 49.9 ± 15.3 vs. 61.3 ± 16.3, p = 0.032]. We did not find any difference in lactate, GLP-1, total, HDL and LDL cholesterol, triglycerides, interleukin 6, tumor necrosis factor, C-reactive protein, resistin, leptin, adiponectin levels between groups. We found decreased insulin sensitivity with postprandial hyperinsulinemia in MS patients, which seems not to be related to chronic inflammation or physical inactivity. The role of hyperinsulinemia in CNS function impairment should be further investigated.

Dynamic neuroendocrine changes in critically ill patients with polytrauma.

OBJECTIVE: Acute multiple-trauma induces activation of neuroendocrine system. Nonthyroidal illness syndrome (NTIS) is considered to be associated with adverse outcome in intensive care unit (ICU) patients. This study was aimed to assess dynamic changes of neuroendocrine hormones in patients with polytrauma and their association with the polytrauma score (PTS). METHODS: Blood samples from 24 critically ill patients with polytrauma were obtained on 1st, 2nd, 3rd and 7th day after admission to ICU for analysis of thyroid-stimulating hormone (TSH), total triiodothyronine (T3); free triiodothyronine (fT3), total thyroxine (T4), free thyroxine (fT4), growth hormone (GH), prolactin (PRL) and procalcitonin levels. RESULTS: Acute Physiology and Chronic Health Evaluation (APACHE) II score was 16±5 points on average at the admission to ICU. All patients had normal baseline TSH, T4, fT4, but low T3, and fT3 levels were found in 20% and 33% ICU patients, respectively. On the 7th day after admission to ICU TSH had tendency to increase (p=0.07) and fT4 significantly decreased (p=0.03). The PRL level significantly increased on the 3rd day after admission as compared to 1st day (p=0.04). PTS positively correlated with fT3 (r=0.582, p=0.004) and negatively with fT4 (r=-0.422, p=0.04) at the 1st day in ICU. CONCLUSION: Critical illness in patients with polytrauma leaded to trauma severity-dependent alterations of the thyroid axis response early after injury. Our findings suggest that detection of dynamic hormonal response is more appropriate than single measurement. However supplemental therapy for NTIS should be used after more detailed studies are completed.

Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies.

Irisin was identified as a myokine secreted by contracting skeletal muscle, possibly mediating some exercise health benefits via 'browning' of white adipose tissue. However, a controversy exists concerning irisin origin, regulation and function in humans. Thus, we have explored Fndc5 gene and irisin protein in two clinical studies: (i) a cross-sectional study (effects of type 2 diabetes (T2D) in drug-naive men) and (ii) an intervention study (exercise effects in sedentary, overweight/obese individuals). Glucose tolerance and insulin sensitivity were assessed. Maximal aerobic capacity and muscle strength were measured before and after training. Body composition (magnetic resonance imaging), muscle and liver fat content (1H-magnetic resonance spectroscopy (MRS)) and in vivo muscle metabolism (32P-MRS) were determined. Skeletal muscle and subcutaneous abdominal adipose tissue samples were taken in the fasted state and during euglycaemic hyperinsulinaemia (adipose tissue) and before/after exercise training (muscle). We found that muscle Fndc5 mRNA was increased in prediabetes but not T2D. Fndc5 in adipose tissue and irisin in plasma were reduced in T2D by 40% and 50%, respectively. In contrast, T2D-derived myotubes expressed/secreted the highest levels of Fndc5/irisin. Neither hyperinsulinaemia (adipose tissue/plasma) nor exercise (muscle/plasma) affected Fndc5/irisin in vivo. Circulating irisin was positively associated with muscle mass, strength and metabolism and negatively with fasting glycaemia. Glucose and palmitate decreased Fndc5 mRNA in myotubes in vitro. We conclude that distinct patterns of Fndc5/irisin in muscle, adipose tissue and circulation, and concordant in vivo down-regulation in T2D, indicate that irisin might distinguish metabolic health and disease. Moreover, Fndc5/irisin was discordantly regulated in diabetic muscle and myotubes in vitro, suggesting that whole body factors, such as glucose and fatty acids, might be important for irisin regulation. Exercise did not affect Fndc5/irisin. However, irisin was positively linked to muscle mass, strength and metabolism, pointing to common regulatory factors and/or the potential for irisin to modify muscle phenotype.

Disubstituted thiourea as a suitable sulfur source in the gram-scale synthesis of yellow- and red-emitting CdTeS/Cd x Zn1-x S core/shell quantum dots.

The key parameters of semiconductor quantum dots (QDs) that determine the suitability and efficiency for the design of most optoelectronic devices are the spectral positions of absorbance (ABS) and photoluminescence (PL) maxima, Stokes shift, photoluminescence quantum yield (PL QY) and photoluminescence lifetime (PL LT). All these parameters have been considered in the design of new ternary core CdTeS and core/shell CdTeS/Cd x Zn1-x S QDs. One-pot synthesis conducted in an organic medium at 160 °C using substituted thioureas as new, highly reactive sulfur sources allowed for the formation of a series of size- and emission-tunable CdTe0.05S0.95 QDs. Gram-scale synthesis of yellow-red emitting CdTe0.06S0.94 and CdTe0.12S0.88 cores was performed through the manipulation of their precursor ratio for the controllable formation of CdTeS/Cd x Zn1-x S (x = 0.1, 0.2, and 0.3) core/shell QDs. The development of the designed nanomaterials was carried out with a special emphasis on their optical properties, in particular a high PL QY up to 87% and extremely large Stokes shift, reaching ≈280 nm for core/shell QDs. Promisingly, for biolabeling and diagnostics, the synthesized core/shell QDs were transferred into water via surface ligand modification with the expected loss of photoluminescence efficiency. The results indicated that the availability of initial components, high yield of the desired product, stability in the organic phase, and high optical characteristics can scale up the synthesis of the developed nanomaterials from the laboratory level to industrial production.

5-Fluorouracil Induced Hypertriglyceridemia During the Colorectal Cancer Treatment in a Patient With Multifactorial Chylomicronemia Syndrome: A Case Report.

PURPOSE: The case of a 47-year-old female patient who underwent sigmoidectomy for metastatic colorectal cancer is reported. Treatment with capecitabine and 5-fluorouracil induced severe hypertriglyceridemia repeatedly. METHODS: Based on laboratory tests and clinical evaluations, treatment was suggested by specialists. FINDINGS: After treatment with capecitabine, the patient's triglycerides increased from 19.7 mmol/L to 42 mmol/L. It was proposed that the patient had multifactorial chylomicronemia syndrome triggered by secondary factors. Statins, fenofibrate, ezetimib, and metformin were added to the therapy. After metastases appeared, FOLFIRI (leucovorin calcium [folinic acid], 5-fluorouracil, and irinotecan hydrochloride) chemotherapy and biological treatment (cetuximab) followed and triglycerides increased to 55.3 mmol/L. IMPLICATIONS: Monitoring triglyceride levels before and during therapy is suggested.

Ultrasensitive impedimetric lectin biosensors with efficient antifouling properties applied in glycoprofiling of human serum samples.

Ultrasensitive impedimetric lectin biosensors recognizing different glycan entities on serum glycoproteins were constructed. Lectins were immobilized on a novel mixed self-assembled monolayer containing 11-mercaptoundecanoic acid for covalent immobilization of lectins and betaine terminated thiol to resist nonspecific interactions. Construction of biosensors based on Concanavalin A (Con A), Sambucus nigra agglutinin type I (SNA), and Ricinus communis agglutinin (RCA) on polycrystalline gold electrodes was optimized and characterized with a battery of tools including electrochemical impedance spectroscopy, various electrochemical techniques, quartz crystal microbalance (QCM), Fourier transform infrared (FT-IR) spectroscopy, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS) and compared with a protein/lectin microarray. The lectin biosensors were able to detect glycoproteins from 1 fM (Con A), 10 fM (Ricinus communis agglutinin (RCA), or 100 fM (SNA) with a linear range spanning 6 (SNA), 7 (RCA), or 8 (Con A) orders of magnitude. Furthermore, a detection limit for the Con A biosensor down to 1 aM was achieved in a sandwich configuration. A nonspecific binding of proteins for the Con A biosensor was only 6.1% (probed with an oxidized invertase) of the signal toward its analyte invertase and a negligible nonspecific interaction of the Con A biosensor was observed in diluted human sera (1000×), as well. The performance of the lectin biosensors was finally tested by glycoprofiling of human serum samples from healthy individuals and those having rheumatoid arthritis, which resulted in a distinct glycan pattern between these two groups.

Increased production of IL-6 and IL-17 in lipopolysaccharide-stimulated peripheral mononuclears from patients with rheumatoid arthritis.

TLR4-mediated inflammatory responses are important for innate immune functions, thus their alterations may participate in the pathogenesis of rheumatoid arthritis (RA). Cortisol is one of the most potent immunomodulatory hormones involved in control of inflammation. In this study, we analyzed TLR4-mediated responses and cortisol effects on the process in peripheral blood mononuclear cells (PBMC) from RA patients. Lipopolysaccharide-stimulated PBMC from 23 female patients and 15 healthy controls were cultured in the presence or absence of cortisol (1 µM) for 24 h. A panel of 17 inflammatory cytokines was analyzed in the cell culture supernatants. Higher (p < 0.05) concentrations of IL-6, IL-17 and MCP-1 were found in lipopolysaccharide-stimulated PBMC from RA patients compared to controls. After normalization of stimulated cytokine secretion to unstimulated cells, a significantly higher (p < 0.05) IL-6 and G-CSF production was found in RA PBMC. Cortisol induced stronger (p < 0.05) suppression of lipopolysaccharide-stimulated secretion of IL-1ß, IL-6, IL-17 and G-CSF in RA group compared to controls. The observed higher production of the key inflammatory cytokines by RA PBMC to lipopolysaccharide stimulation supports involvement of TLR4-mediated processes in RA pathogenesis. The higher sensitivity of LPS-stimulated RA PBMC to immunosuppressive effects of cortisol may reflect adaptive processes to chronic inflammation.

Solution processed multi-layered thin films of Ge20Sb5S75 and Ge20Sb5Se75 chalcogenide glasses.

Solution processed non-toxic Ge20Sb5Se75 chalcogenide glass thin films were deposited using spin-coating method from n-propylamine-methanol solvent mixture in specular optical quality. Optical properties, composition, structure, and chemical resistance were studied in dependence on the annealing temperature. Significant increase of refractive index and chemical resistance caused by thermoinduced structural polymerization and release of organic residua were observed. The high chemical resistance of hard-baked thin films allowed repeated direct depositions by spin-coating, increasing total thickness. Multilayered thin films of amorphous Ge20Sb5Se75 and Ge20Sb5S75 were also successfully prepared by direct deposition for the first time. Solution based deposition of non-toxic Ge20Sb5Se75 thin films in specular optical quality significantly widens the applicability of solution processed chalcogenide glass thin films. Moreover, solution based direct deposition of different glasses on hard-baked thin films opens the way to simple and cost-effective preparation of more sophisticated optical elements (e.g. beam splitters, photonic mirrors).

Autonomic nervous system function in rheumatoid arthritis.

The sympathoneural and the adrenomedullary systems are involved in regulation of immune processes. Their impairment has been suggested in patients with rheumatoid arthritis (RA). In this study, sympathetic response to orthostasis was evaluated in 22 RA females with <40 years of age and in 15 matched healthy controls. The testing consisted of stabilization period in supine position, legs-up position, 10 min of orthostasis and again supine position. In each of the body position blood samples were drawn, blood pressure and electrocardiogram was recorded. Plasma levels of epinephrine (EPI) and norepinephrine (NE) were measured and sympathoneural activity was evaluated by analysis of heart rate variability (HRV). During the testing, RA patients had similar EPI and NE concentrations compared to controls. Baseline diastolic blood pressure tended to be higher in RA patients compared to controls; however, blood pressure response to orthostasis was comparable between the groups. The RA and control groups did not differ in heart rate and HRV parameters. This study showed normal reactivity of the sympathoneural and the adrenomedullary systems during orthostatic challenge in RA patients younger than 40 years.