BACKGROUND: Free light chains, type kappa (FLC-K), in cerebrospinal fluid (CSF) were compared to oligoclonal IgG in many studies for sensitive detection of immune reactions in brain. The missing consensus about CSF data interpretation prevents reliable conclusions. This can be overcome by a theory-based hyperbolic reference range in CSF/serum quotient diagrams. METHODS: Mean Quotients for FLC-K, QKappa, and albumin, QAlb, of grouped, biochemically defined controls (N = 433) are fitted with the hyperbolic function QKappa(mean) = a/b (QAlb2 + b2)0.5 - c by a generally applicable procedure excluding outliers. RESULTS: With QKappa(mean), the coefficient of variation CV (22.5%) and the reference range (QKappa(mean) ± 3 CV) we got the discrimination line QKappa(lim) = (3.27(QAlb2 + 33)0.5-8.2) ×10-3 in a FLC-K Reibergram. Intrathecal FLC-K was found in 8% of another control group without OCB (N = 388) but was missed in 7% of patients with definite Multiple sclerosis (N = 95). In MS the mean intrathecal fraction was threefold larger for FLC-K (95%) compared to total IgG (36%). Similar mean quantities of intrathecal FLC-K contradict an immunological conversion between a Clinically isolated syndrome and MS. DISCUSSION: The hyperbolic reference range is superior to linear FLC-K Index (10 to 15% false negatives) and exponential curves (30% false positive interpretations for controls) in the analytical range of MS data, with excellent data fit for up to ten-fold larger QAlb values. Dynamics of the small molecule FLC-K contribute to the understanding of molecular size dependent barrier functions.

• MeSH
• Albumins analysis   standards   MeSH
• Immunoglobulin kappa-Chains analysis   MeSH
• Humans MeSH
• Cerebrospinal Fluid chemistry   MeSH
• Reference Values MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Advanced glycation end products (AGEs) accumulate in patients with decreased renal function and exert various toxic effects through the receptor for AGEs (RAGE). Soluble RAGE (sRAGE) is a naturally occurring inhibitor of AGE-RAGE action. The aim of the study is to describe the relationship of sRAGE to renal function and dialysis modalities. METHODS: The studied group consisted of 81 patients: 25 patients with various degrees of decreased renal function, 20 long-term hemodialysis (HD) patients, 15 peritoneal dialysis (PD) patients, and 21 healthy age-matched subjects. sRAGE was assessed immunochemically (enzyme-linked immunosorbent assay), and routine biochemical parameters were measured by means of certified methods. RESULTS: sRAGE level correlates positively with serum creatinine concentration (r = 0.50; P < 0.05), and its relationship to creatinine clearance is hyperbolic. sRAGE levels are elevated significantly, mainly in patients with end-stage renal disease (3,119.0 +/- 968.4 pg/mL in HD patients and 3,652.7 +/- 1,677.7 pg/mL in PD patients versus 1,405.1 +/- 426.1 pg/mL in controls; both P < 0.001 versus controls). In PD patients, sRAGE is detectable in spent dialysate (median, 75.8 pg/mL), correlates with its serum levels (r = 0.67; P < 0.05), and is related to protein losses in dialysate. In HD patients, sRAGE levels increase by 50% (P < 0.001) from 0 to 15 minutes during both HD and hemodiafiltration, and then decrease until the end of the session. CONCLUSION: Serum sRAGE levels increase in patients with decreased renal function, mainly patients with end-stage renal disease. It remains to be elucidated whether the increase is caused just by decreased renal function or whether sRAGE is upregulated to protect against toxic effects of AGEs.

• MeSH
• Kidney Failure, Chronic blood   physiopathology   therapy   MeSH
• Renal Dialysis MeSH
• Financing, Organized MeSH
• Middle Aged MeSH
• Humans MeSH
• Receptors, Immunologic blood   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH

Úvod: V denní praxi změnu renální funkce posuzujeme nejčastěji na podkladě změn sérové koncentrace kreatininu (SKr). V této práci jsme se snažili zjistit, zda a jak dalece pouze na podkladě změn SKr můžeme posoudit změny renální clearance kreatininu (CKr), glomerulární filtrace (GFR) odhadnuté na podkladě MDRD (Modification of Diet in Renal Disease) formule a přesně změřené na podkladě renální clearance inulinu (Cin). Metodika: U 32 jedinců s chronickým renálním onemocněním, jejichž průměrná SKr činila 202 (60–564) µmol/l, byla opakovaně vyšetřena Cin a na podkladě SKr a potřebných parametrů kalkulována GFR podle MDRD formule. Byly hodnoceny vztahy mezi diferencí či poměrem SKr zjištěné na začátku sledování (SKr)0 a jeho konci (SKr)t a příslušnými hodnotami Cin a MDRD. Při statistickém zpracování byla užita regresní analýza a hodnocení dle Blanda a Altmana. Závěry: Diference sérových koncentrací kreatininu (SKr)t - (SKr)0 umožňuje posoudit, zda dochází ke zhoršení nebo zlepšení renální funkce, nikoli však posoudit změnu renální funkce kvantitativně. Poměr (SKr)t/(SKr)0 umožňuje posoudit kvantitativně změnu CKr, avšak toto hodnocení není jednoduché, protože mezi (SKr)0/(SKr)t a (CKr)t/(CKr)0 je vztah hyperbolický. Jednodušším postupem je hodnocení reciproké hodnoty (SKr)0/(SKr)t, tj. poměru (SKr)0/(SKr)t, protože mezi touto veličinou a odhadnutou i změřenou GFR je vztah lineární. Tento postup umožňuje posoudit úbytek renální funkce v procentech výchozí hodnoty. Výsledky měření: Mezi hodnotami (SKr)0/(SKr)t a (MDRD)t/(MDRD)0 byla zjištěna vysoce významná lineární závislost (r=0,968; p<0,000). Hodnocení změn odhadnuté GFR na podkladě poměru (SKr)0/(SKr)t poskytuje rovnocenné informace jako hodnocení poměru (MDRD)t/(MDRD)0. mezi hodnotami (SKr)0/(SKr)t a (Cin)t/(Cin)0 byla zjištěna významná lineární závislost, avšak hodnota korelačního koeficientu je významně nižší (r=0,474; p<0,000). Na podkladě (SKr)0/(SKr)t lze posoudit jen větší změny Cin.

Introduction: In daily practice, changes of renal function are most commonly evaluated in the basis of serum creatinine (SCr) concentration. In this study, we tried to investigate if and how accurately SCr changes can be used to evaluate changes in renal creatinine clearance (CCr), and glomerular filtration rate (GFR) estimated on the basis of MDRD (Modification of Diet in Renal Disease) formula and accurately measured by renal inulin clearance (Cin). Methods: In 32 patients suffering from chronic renal disease, with average SCr 202 (60–564) µmol/l, Cin was repeatedly measured and GFR was calculated on the basis of SCr and other parameters needed according to the MDRD formula. Relationships between a difference or SCr ratio found in the beginning (SCr)0 and the end of the study (SCr)t with appropriate values of Cin a MDRD were investigated. Regression analysis and the Bland-Altman analysis were used as a statistical tool. Results: A highly significant linear relationship between values of (SCr)0/(SCr)t and (MDRD)t/(MDRD)0 was found (r=0,968; p<0,000). Evaluation of changes of GFR on the basis of (SCr)0/(SCr)t ratio yields equivalent information as evaluation of (MDRD)t/(MDRD)0 ratio. A significant linear dependence between values of (SCr)0/(SCr)t and (Cin)t/(Cin)0 were found, however the value of the correlation coefficient is substantially lower (r=0,474; p<0,000). Only greater changes of Cin can be evaluated on the basis of (SCr)0/(SCr)t. Conclusions: A difference in creatinine serum concentrations (SKr)t - (SKr)0 allows us to evaluate deterioration or amelioration of renal function, however a quantitative change of renal function cannot be determined. The (SCr)t/(SCr)0 ratio enables a quantitative change of CCr, however such an evaluation is not easy, while the relationship between (SCr)t/(SCr)0 and (CCr)t/(CCr)0 is hyperbolic. Evaluation of the reciprocal value of (SCr)t/(SCr)0, i.e. (SCr)0/(SCr)t ratio is simpler, because the relationship between this value and both estimated and measured GFR is linear. This method enables the evaluation of renal function decrease as a percentage of initial value.

• MeSH
• Biomarkers analysis   blood   metabolism   MeSH
• Kidney Failure, Chronic diagnosis   blood   MeSH
• Adult MeSH
• Financing, Organized MeSH
• Glomerular Filtration Rate physiology   MeSH
• Inulin analysis   diagnostic use   blood   MeSH
• Creatinine analysis   diagnostic use   blood   MeSH
• Humans MeSH
• Renal Circulation physiology   immunology   MeSH
• Severity of Illness Index MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH

• MeSH
• Mathematics MeSH
• Software MeSH
• Publication type
• Textbook MeSH

• Conspectus
• Matematika
• Programování. Software

The modification of biomaterial surfaces has become increasingly relevant in the context of ongoing advancements in tissue engineering applications and the development of tissue-mimicking polymer materials. In this study, we investigated the layer-by-layer (LbL) deposition of polyelectrolyte multilayer protein reservoirs consisting of poly-l-lysine (PLL) and hyaluronic acid (HA) on the hydrophobic surface of poly(glycerol sebacate) (PGS) elastomer. Using the methods of isothermal titration calorimetry and surface plasmon resonance, we systematically investigated the interactions between the polyelectrolytes and evaluated the deposition process in real time, providing insight into the phenomena associated with film assembly. PLL/HA LbL films deposited on PGS showed an exceptional ability to incorporate bone morphogenetic protein-2 (BMP-2) compared to other growth factors tested, thus highlighting the potential of PLL/HA LbL films for osteoregenerative applications. The concentration of HA solution used for film assembly did not affect the thickness and topography of the (PLL/HA)10 films, but had a notable impact on the hydrophilicity of the PGS surface and the BMP-2 release kinetics. The release kinetics were successfully described using the Weibull model and hyperbolic tangent function, underscoring the potential of these less frequently used models to compare the protein release from LbL protein reservoirs.

• MeSH
• Hyaluronic Acid * chemistry   MeSH
• Layer-by-Layer Nanoparticles MeSH
• Polyelectrolytes MeSH
• Polylysine * chemistry   MeSH
• Polymers MeSH
• Publication type
• Journal Article MeSH

Increased ATP/ADP ratio resulting from enhanced glycolysis and oxidative phosphorylation represents a plausible mechanism controlling the glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Although specific bioenergetics might be involved, parallel studies of cell respiration and mitochondrial membrane potential (DeltaPsi(m)) during GSIS are lacking. Using high resolution respirometry and parallel DeltaPsi(m) monitoring by two distinct fluorescence probes we have quantified bioenergetics in rat insulinoma INS-1E cells representing a suitable model to study in vitro insulin secretion. Upon glucose addition to glucose-depleted cells we demonstrated a simultaneous increase in respiration and DeltaPsi(m) during GSIS and showed that the endogenous state 3/state 4 respiratory ratio hyperbolically increased with glucose, approaching the maximum oxidative phosphorylation rate at maximum GSIS. Attempting to assess the basis of the "toxic" effect of fatty acids on insulin secretion, GSIS was studied after linoleic acid addition, which diminished respiration increase, DeltaPsi(m) jump, and magnitude of insulin release, and reduced state 3/state 4 dependencies on glucose. Its effects were due to protonophoric function, i.e. uncoupling, since without glucose, linoleic acid accelerated both state 3 and state 4 respiration by similar extent. In turn, state 3 respiration increased marginally with linoleic acid at 10-20mM glucose. We conclude that upon glucose addition in physiological range, the INS-1E cells are able to regulate the oxidative phosphorylation rate from nearly zero to maximum and that the impairment of GSIS by linoleic acid is caused by mitochondrial uncoupling. These findings may be relevant to the pathogenesis of type 2 diabetes.

• MeSH
• Adenosine Diphosphate metabolism   MeSH
• Adenosine Triphosphate metabolism   MeSH
• Financing, Organized MeSH
• Glucose pharmacology   MeSH
• Insulinoma secretion   MeSH
• Rats MeSH
• Linoleic Acid pharmacology   MeSH
• Islets of Langerhans secretion   drug effects   MeSH
• Membrane Potential, Mitochondrial drug effects   MeSH
• Mitochondria metabolism   drug effects   MeSH
• Tumor Cells, Cultured MeSH
• Pancreatic Neoplasms secretion   MeSH
• Rats, Wistar MeSH
• Oxygen Consumption drug effects   MeSH
• Microscopy, Electron, Transmission MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH