Fibroblast Growth Factor 23 and Klotho Are Associated With Trabecular Bone Score but Not Bone Mineral Density in the Early Stages of Chronic Kidney Disease: Results of the Cross-Sectional Study.

This study evaluates bone mineral density (BMD) and trabecular bone score (TBS) in relationship with new markers of chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23), and klotho. The patients in this cross-sectional study were divided as follows: group A -patients in stages G1-3; group B -patients in stages G4 - 5 according to KDIGO. Plasma levels of soluble klotho and FGF23 were determined by ELISA. Bone mineral density (BMD) and trabecular bone score (TBS) were measured. 74 patients with CKD (mean age 68.8 years) were included in the study. Higher levels of FGF23 were observed in group B (N=15) compared to group A (N=59; p=0.001) were observed. FGF23 was higher in group A compared to group B. Significant difference in TBS within the first 3 stages of CKD was observed (mean TBS in G1=1.375 vs. G2=1.340 vs. G3a=1.24; p<0.05) and negative correlation of FGF23 and TBS (R=-0.33; p=0.05) and positive correlation between klotho and TBS (R=0.419; p=0.04) was observed. This study confirmed that FGF23 and klotho are associated with TBS, but TBS reflects a decrease in kidney function only in the first 3 stages of CKD. Thus, FGF23 and klotho together with TBS are promising markers of early trabecular bone impairment in CKD.

3D Echocardiography - A Useful Method for Cardiovascular Risk Assessment in End-Stage Renal Disease Patients.

Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI). We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD.

Fibroblast Growth Factor 23 and Klotho Are Associated With Trabecular Bone Score but Not Bone Mineral Density in the Early Stages of Chronic Kidney Disease: Results of the Cross-Sectional Study.

This study evaluates bone mineral density (BMD) and trabecular bone score (TBS) in relationship with new markers of chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23), and klotho. The patients in this cross-sectional study were divided as follows: group A -patients in stages G1-3; group B -patients in stages G4 - 5 according to KDIGO. Plasma levels of soluble klotho and FGF23 were determined by ELISA. Bone mineral density (BMD) and trabecular bone score (TBS) were measured. 74 patients with CKD (mean age 68.8 years) were included in the study. Higher levels of FGF23 were observed in group B (N=15) compared to group A (N=59; p=0.001) were observed. FGF23 was higher in group A compared to group B. Significant difference in TBS within the first 3 stages of CKD was observed (mean TBS in G1=1.375 vs. G2=1.340 vs. G3a=1.24; p<0.05) and negative correlation of FGF23 and TBS (R=-0.33; p=0.05) and positive correlation between klotho and TBS (R=0.419; p=0.04) was observed. This study confirmed that FGF23 and klotho are associated with TBS, but TBS reflects a decrease in kidney function only in the first 3 stages of CKD. Thus, FGF23 and klotho together with TBS are promising markers of early trabecular bone impairment in CKD.

3D Echocardiography - A Useful Method for Cardiovascular Risk Assessment in End-Stage Renal Disease Patients.

Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI). We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD.

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor.

Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the functional role of ORs in the human heart is still unclear. Here, we firstly report the functional characterization of an OR in the human heart. Initial next-generation sequencing analysis revealed the OR expression pattern in the adult and fetal human heart and identified the fatty acid-sensing OR51E1 as the most highly expressed OR in both cardiac development stages. An extensive characterization of the OR51E1 ligand profile by luciferase reporter gene activation assay identified 2-ethylhexanoic acid as a receptor antagonist and various structurally related fatty acids as novel OR51E1 ligands, some of which were detected at receptor-activating concentrations in plasma and epicardial adipose tissue. Functional investigation of the endogenous receptor was carried out by Ca2+ imaging of human stem cell-derived cardiomyocytes. Application of OR51E1 ligands induced negative chronotropic effects that depended on activation of the OR. OR51E1 activation also provoked a negative inotropic action in cardiac trabeculae and slice preparations of human explanted ventricles. These findings indicate that OR51E1 may play a role as metabolic regulator of cardiac function.

Unique populations of lung mast cells are required for antigen-mediated bronchoconstriction.

BACKGROUND: Studies in both human and mouse indicate that mediators released by mast cells can lead to bronchoconstriction, and thus these are important effector cells in lifethreatening anaphylaxis. Much of our understanding of the various functions of mast cells emanates from the study of mice lacking these cells, particularly mice carrying mutations in the tyrosine kinase gene Kit. Definitive evidence for the role of mast cells in the altered immune response requires the demonstration that this response can be normalized by reconstitution of the mice with cultured bone marrow-derived mast cells (BMMCs). While many mast cell niches can be restored with BMMCs, this has not been demonstrated for mast cells present in the airways of the lung, cells poised to mediate bronchoconstriction during allergic responses. OBJECTIVE: To determine if mast cell-deficient Kit(Wsh/Wsh) reconstituted lines are an appropriate model for the study of the role of these cells in bronchoconstriction associated with allergic responses. METHODS: Kit(Wsh/Wsh) mice were reconstituted with either whole bone marrow (WBM) or BMMCs and responses to IgE-mediated mast cell activation were determined; including systemic hypothermia, mediator release, and bronchoconstriction in anaesthetized, mechanically ventilated animals. RESULTS: Engraftment of Kit(Wsh/Wsh) mice with WBM and BMMCs results in reconstitution of the central airways with mast cells. While the treatment of the two groups of animals resulted in systemic changes when challenged with IgE/Ag in a model of passive anaphylaxis, bronchoconstriction was observed only in kit(Wsh/Wsh) animals, which had received a bone marrow transplant. CONCLUSIONS: While BMMCs can populate the lung, they cannot restore IgE/Ag-mediated bronchoconstriction to mast cell-deficient animals. This suggests that the mast cell population, which mediates this function, may be unique, and to fill this niche in the lung cells must undergo a specific developmental programme, one that is no longer available to cultured mast cells.

[Loneliness in the elderly as a social and medical problem]. / Osamelost starých lidí jako sociální a medicínský problém.

The proportion of elderly people in the Czech population is increasing. Old age is often associated with loneliness, which significantly leads to a medical institutionalization. In addition to that, depression, dementia, and alcohol abuse may occur as a result and cause of further deterioration. We describe a case of a woman who has spent substantial part of the last five years of her life being hospitalized at departments of psychiatry, neurology, and internal medicine respectively. Social factors played an important role in this development. The vicious circle of loneliness, depression, and institutionalization of elderly people may be overcome in several ways, e.g. by an adequate physical, mental, and social activity, self-education, psychotherapy, outpatients nursing care, and an early diagnostics and treatment of depression.

[Reliability and validition of the Slovak modified version of the Stanford Health Assessment Questionnaire using the functional disability index in patients with rheumatoid arthritis]. / Reliabilita a validita slovenskej verzie a modifikácia Stanfordského dotazníka hodnotiaceho zdravie pomocou indexu disability (HAQ) u pacientov s reumatoidnou artritídou.

BACKGROUND: Functional disability is one of the most important consequences of RA in the patient's daily life. The HAQ has been widely used in its self administered form for the assessment of disability. A sensitive and valid instrument is needed for a Slovak population with RA. OBJECTIVE: To evaluate reliability and validity of the Slovak version of the HAQ in patients with RA and to explore relationships between HAQ score and disease activity and to provide information concerning utilization of this instrument in clinical practice. METHODS: In preparing the Slovak version of the HAQ careful attention has been paid to the translation, in terms of linguistic and conceptual equivalence, in order to preserve the original purpose of the instrument. The wording of some items required adaptation to the current activities of daily living and Slovak lifestyle. The sample consisted of 160 RA-patients, out of which 135 were women and 25 were men. The inclusion criteria were the following: age from 20 to 70 years at the onset of the study, diagnosis of RA according to the ARA criteria. The exclusion criteria were the presence of another serious disease or very disabling RA (stage IV of the Steinbrocker's classification). To analyze the data t-test, correlations, one-way analysis of variance (ANOVA), and principal component analysis (PCA) available in the SPSS/PC+ statistical package were used. RESULTS: The Cronbach's coefficient of reliability alpha for the HAQ total scale was 0.94. The results of PCA showed that the 20 HAQ items loaded on four components for which the eigen values were greater than 1, accounting for 70% of overall interpersonal variability. Orthogonal varimax rotation of the principal components provided factor loadings reflecting the eight dimensions within the HAQ. Validity of the HAQ was examined further by means of known-groups technique. The HAQ was found to be sensitive to differentiate between the Steinbrocker's functional capacity groups, as well as between males and females. Moreover, significant correlations (p < or = 0.01) were found between the HAQ and the C-reactive protein, the ESR, the NHP-pain, the Ritchie articular index, the Steinbrocker's functional capacity (r = 0.31-0.62) and disease duration (p < or = 0.05, r = 0.17). CONCLUSION: The results of the current investigation provide support for reliability and construct validity of the Slovak version of the HAQ in patients with RA. The HAQ has sufficient discriminant ability. The index disability can be used as an criterion of severity of RA, as a criterion of effectiveness in therapeutical trials for patient stratification of the Slovak population with RA.

Bodily characteristics and lifestyle of Czech children aged 7.00 to 10.99 years, incidence of childhood obesity.

In 1991-2000 in the Czech Republic a survey of the prevalence of obesity was made. The assessment was made by the transversal method in elementary schools in all regions of the Czech Republic. Children aged 7.00 to 10.99 years were investigated. The survey comprised a total of 3362 children (1668 girls and 1694 boys). A total of 12 anthropometric dimensions were recorded and questionnaires addressed to the children and parents were analyzed. From the results ensued that the ratio of obese children of both sexes in the CR (i.e. children with BMI values about the 97th percentile of the reference population) increased. This zone comprised 6.0% boys and 5.6% girls of the investigated group. An important finding was also the increase of mean values of the abdominal circumference of the children in all age groups in both sexes. The ratio of obese children in different communities is related unequivocally to the size of the community., In smaller communities there are more obese children (according to our data 6.9%) and in large towns the ratio of obese children is 2.3%. In large towns there is also a greater proportion of thin children - 12.1%, in small communities 8.6%. It was found that there is a higher percentage of obese children in families where the mother has elementary education as compared with children of mothers with secondary and university education. Mothers with elementary education have 9.6% obese children while university educated mothers have only 3.6% obese children. Analysis of the dietary questionnaires revealed that only 62.9% children in large towns eat breakfast, the position in villages is similar - 63.9%. In the group of children with excessive body weight fewer children have breakfast (only 54.1%), in the group of children with a low body weigh the majority eat breakfast (75.3%). The majority of children have a mid-morning snack at school which they bring from home. As regards school lunch the majority of children from large towns replied that they have lunch at school. the number of rural children who had school lunch was smaller. An afternoon snack is taken by less than half the children in different groups.

Structure-function analysis of Lyn kinase association with lipid rafts and initiation of early signaling events after Fcepsilon receptor I aggregation.

The first step in immunoreceptor signaling is represented by ligand-dependent receptor aggregation, followed by receptor phosphorylation mediated by tyrosine kinases of the Src family. Recently, sphingolipid- and cholesterol-rich plasma membrane microdomains, called lipid rafts, have been identified and proposed to function as platforms where signal transduction molecules may interact with the aggregated immunoreceptors. Here we show that aggregation of the receptors with high affinity for immunoglobulin E (FcepsilonRI) in mast cells is accompanied by a co-redistribution of the Src family kinase Lyn. The co-redistribution requires Lyn dual fatty acylation, Src homology 2 (SH2) and/or SH3 domains, and Lyn kinase activity, in cis or in trans. Palmitoylation site-mutated Lyn, which is anchored to the plasma membrane but exhibits reduced sublocalization into lipid rafts, initiates the tyrosine phosphorylation of FcepsilonRI subunits, Syk protein tyrosine kinase, and the linker for activation of T cells, along with an increase in the concentration of intracellular Ca(2+). However, Lyn mutated in both the palmitoylation and myristoylation sites does not anchor to the plasma membrane and is incapable of initiating FcepsilonRI phosphorylation and early signaling events. These data, together with our finding that a constitutively tyrosine-phosphorylated FcepsilonRI does not exhibit an increased association with lipid rafts, suggest that FcepsilonRI phosphorylation and early activation events can be initiated outside of lipid rafts.

Self-reported health problems of Slovak adolescents.

This paper describes self-reported health problems among 2616 Slovak adolescents (52.4% boys, 47.6% girls). Adolescents consider their health as very good in general. They often feel 'vital', and rarely feel depressed or irritated. However, the psychological health of more than 20% of the boys and 40% of the girls was unsatisfactory. Furthermore, a sizeable number suffered from separate physical complaints, chronic diseases or used medical services. Findings are more unfavourable for girls in comparison with boys. Our findings indicate that adolescence is not such a healthy period in human life as is often considered. The Slovak Republic, a Central European country, does not differ in this respect from Western European countries.

Differential sensitivity to acute cholesterol lowering of activation mediated via the high-affinity IgE receptor and Thy-1 glycoprotein.

Lateral cross-linking of transmembrane high-affinity IgE receptors (FcepsilonRI) or glycosylphosphatidylinositol-anchored Thy-1 glycoproteins on the surface of rat mast cells and rat basophilic leukemia (RBL) cells triggers the signaling pathways that lead to the release of allergy mediators. Although both of these pathways are initiated by an increased activity of Lyn kinase, the exact mechanism by which Lyn kinase interacts with aggregated FcepsilonRI and Thy-1 is not completely understood. Here we demonstrate that pretreatment of RBL cells with methyl-beta-cyclodextrin (MBCD) resulted in a dose- and time-dependent decrease in cellular cholesterol, increased detergent solubilization of Thy-1 and Lyn kinase, and a transient increase in tyrosine phosphorylation of several proteins. Acute lowering of cholesterol suppressed the activation through Thy-1, as determined by tyrosine phosphorylation of Syk kinase and some other proteins, and modulation of free cytoplasmic calcium. In contrast, the FcepsilonRI-mediated activation events were more resistant. Thy-1 and FcepsilonRI in MBCD-pretreated cells also differed in the extent of aggregation after cross-linking: Thy-1 formed large caps, whereas FcepsilonRI accumulated in small patches. MBCD treatment induced an increased release of secretory components in both Thy-1- and FcepsilonRI-activated cells. The combined data indicate that cholesterol depletion does not merely block receptor signaling but has more complex consequences.

New specificity and yield enhancer of polymerase chain reactions.

Tetramethylammonium (TMA) chloride, dimethyl sulfoxide and formamide are known to increase, under certain conditions, the specificity and efficiency of the polymerase chain reaction (PCR). We compared the ability of several TMA derivatives and some other reagents to increase the specificity of PCR and to improve the yield of amplification. A novel combination of the enhancer TMA and oxalate as anion is demonstrated to be a powerful enhancer of PCR. Addition of 2 mM TMA oxalate to the PCR mixture decreases the formation of non-specific DNA fragments and increases the yield of specific PCR products.

[Pain and rheumatoid arthritis]. / Bolest a reumatoidná artritída.

OBJECTIVE: Chronic pain is an important part of the clinical picture in patients with RA and therefore the authors attempted to assess the relationship of pain of patients with RA to the inflammatory process, articular damage and to predict the variance of pain in relation to psychosocial, demographic factors and functional disability. METHOD: Pain was examined using the Nottingham Health Profile (NHP), psychological health by means of the General Health Questionnaire (GHQ) and disability was assessed by the Health Assessment Questionnaire (HAQ). RESULTS: The authors examined 160 patients with RA with a mean age of 48.34 +/- 12.13 years and persistence of the disease for 21.32 +/- 15.61 months. Pain was significantly related to clinical manifestations of inflammation and articular damage. The relationship between pain and laboratory manifestations of inflammation (CRP, FW) was not very close. The relationship between age and pain and between persistence of the disease and pain was not statistically significant. Pain correlated significantly with functional disability (HAQ) (r = -0.54) and the articular index (RAI) (r = 0.58). Pain did not correlate with manifestations of depression (r = -0.15), but correlated significantly with anxiety (r = -0.35) and social dysfunction (r = -0.36). Among the investigated parameters (demographic factors, GHQ and HAQ) the most marked variation of pain was caused by HAQ (32%), GHQ (8%). Almost unrelated were demographic parameters (0.6%) (age, persistence of disease, education lifestyle, and gender).

[The Groningen Activity Restriction Scale (GARS) in the evaluation of severity of rheumatoid arthritis]. / Groningenská mierka obmedzenia cinností (GARS) pri posúdení závaznosti reumatoidnej artritídy.

BACKGROUND: The functional ability of the patient in chronic diseases reflects the severity of the pathological process and the success of treatment. OBJECTIVE: Evaluation of the functional ability of patients with RA and assessment of the influence of the pathological process on the performance of simple everyday tasks. METHODS: Physical capacity and functional ability were examined using the Groningen activity restriction scale (GARS) and Health Assessment Quesionnaire (HAQ). RESULTS: The authors examined 160 patients with RA (135 women and 25 men), mean age 48.3 +/- 12.13 years and a duration of the disease of 21.32 +/- 15.61 months. The mean value of the functional ability according to GARS was 32.67 +/- 11.61. Women had a poorer score (33.36 +/- 11.91) than men (28.96 +/- 9.44), the difference was however not statistically significant. The mean value of functional ability according to HAQ/FDI of the patients was 1.079 +/- 0.65. Women had a poorer score (1.156 +/- 0.625) than men (0.722 +/- 0.936), the difference being significant (P < 0.01). The authors found a significant correlation (P < 0.001) between HAQ and GARS as well as a significant relationship with parameters assessing the inflammatory activity. In GARS a relationship with the duration of the disease was found (P < 0.05), but not with HAQ. There was no significant relationship between GARS or HAQ with the patients age. In investigations of the restriction of functional ability during common everyday activities it was revealed that the greatest problem of patients is care of feet and nails, climbing stairs and personal hygiene. As to household activities the highest score was recorded for "strenuous house work" (scrubbing floors, cleaning windows and vacuum cleaning), shopping ironing and bedmaking. CONCLUSION: GARS is a reliable practical and simple scale of functional ability of patients with RA which can be used for the accurate description of the severity and for evaluation of the degree of functional ability.

[Computer evaluation of respiratory changes during acute hypoxia in an experimental model]. / Pocítacové hodnotenie zmien dýchania pocas akútnej hypoxie v modelovom pokuse.

Experiences are presented concerning the use of a computer system in analyzing the dynamics of respiratory changes during reversible respiratory failure induced by inhalation of nitrogen in anesthetized cats. The main focus is on semiautomatic evaluation of the air flow signal during experimentally induced hypoxia in model experiment. On the basis of experience with computer aided evaluation of respiratory changes in over 40 animals and regarding the analysis of actual data obtained from 29 hypoxic episodes leading to reversible respiratory failure in 9 cats, advantages and pitfalls of evaluating respiration parameters by the breath-by-breath method are highlighted. Besides demonstrating the applied computer processing of data, the paper evaluates the most important of the 30 respiratory parameters studied, i.e. tidal volume (VT), minute ventilation (VE), inspiratory time (TI), and the ratios VI/TI and TI/TTOT. The results allow to quantify well the dynamics of development of changes of the respiratory model particularly during the first phase of acute hypoxic hypoxia. (Tab. 1, Fig. 5, Ref. 21).

Interrelation of coronary and cerebral arteriosclerosis.

In our investigation the histories of 323 patients diagnosed as MI and CVA were examined. After a detailed examination of our set it has been proved that there is a relation between the CNS and heart arterial systems, by which the existence of this syndrome (SACC) has been proved.

Hathayogic exercise jalandharabandha in its effect on cardiovascular response to apnoea.

Jalandharabandha (JB) is the important constituent of apnoea (kumbhaka) in hathayogic breathing exercises. It is performed by pressing the chin into the jugular notch and creating thus the positive pressure on the neck region. The influence of JB on the heart rate and vasomotor response was studied in relationship to different lung volumes. The course of R-R intervals is highly significantly different according to the type of apnoea. JB leads to the diminution of bradycardia, but does not change the position of the maximum and minimum in comparison to the apnoea without JB. Application of JB increases the number of vasodilatations and shortens the latencies of vasodilatations, duration and amplitude of reactions. JB during breath holding decreases the vagal reflex changes and may thus work as a stabilizing component in yogic breathing exercises.