BACKGROUND: Female carriers of dystrophin gene mutations (DMD-FC) were previously considered non-manifesting, but in recent decades, cardiomyopathy associated with muscular dystrophy and myocardial fibrosis has been described. Our study aimed to assess prospectively myocardial fibrosis in asymptomatic DMD-FC compared to a sex-matched control group (CG) with similar age distribution using native T1 mapping and extracellular volume (ECV) quantification by cardiovascular magnetic resonance (CMR) imaging. MATERIALS AND METHODS: 38 DMD-FC with verified genetic mutation and 22 healthy volunteers were included. Using CMR, native T1 relaxation time and ECV quantification were determined in each group. Late gadolinium enhancement (LGE) was assessed in all cases. RESULTS: There were 38 DMD-FC (mean age 39.1 ± 8.8 years) and 22 healthy volunteers (mean age 39.9 ± 12.6 years) imagined by CMR. The mean global native T1 relaxation time was similar for DMD-FC and CG (1005.1 ± 26.3 ms vs. 1003.5 ± 25.0 ms; p-value = 0.81). Likewise, the mean global ECV value was also similar between the groups (27.92 ± 2.02% vs. 27.10 ± 2.89%; p-value = 0.20). The segmental analysis of mean ECV values according to the American Heart Association classification did not show any differences between DMD-FC and CG. There was a non-significant trend towards higher mean ECV values of DMD-FC in the inferior and inferolateral segments of the myocardium (p-value = 0.075 and 0.070 respectively). CONCLUSION: There were no statistically significant differences in the mean global and segmental native T1 relaxation times and the mean global or segmental ECV values. There was a trend towards higher segmental mean ECV values of DMD-FC in the inferior and inferolateral walls of the myocardium.

• Klíčová slova
• Cardiac magnetic resonance, Duchenne muscular dystrophy, Extracellular volume quantification, Late gadolinium enhancement, Native T1 mapping,
• MeSH
• dospělí MeSH
• Duchennova muskulární dystrofie * genetika   MeSH
• gadolinium MeSH
• kontrastní látky MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• myokard MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Spojené státy americké MeSH
• Názvy látek
• gadolinium MeSH
• kontrastní látky MeSH

BACKGROUND: In terms of cardiovascular magnetic resonance are haematocrit values required for calculation of extracellular volume fraction (ECV). Previously published studies have hypothesized that haematocrit could be calculated from T1 blood pool relaxation time, however only native T1 relaxation time values have been used and the resulting formulae had been both in reciprocal and linear proportion. The aim of the study was to generate a synthetic haematocrit formula from only native relaxation time values first, calculate whether linear or reciprocal model is more precise in haematocrit estimation and then determine whether adding post-contrast values further improve its precision. METHODS: One hundred thirty-nine subjects underwent CMR examination. Haematocrit was measured using standard laboratory methods. Afterwards T1 relaxation times before and after the application of a contrast agent were measured and a statistical relationship between these values was calculated. RESULTS: Different linear and reciprocal models were created to estimate the value of synthetic haematocrit and ECV. The highest coefficient of determination was observed in the combined reciprocal model "- 0.047 + (779/ blood native) - (11.36/ blood post-contrast)". CONCLUSIONS: This study provides more evidence that assessing synthetic haematocrit and synthetic ECV is feasible and statistically most accurate model to use is reciprocal. Adding post-contrast values to the calculation was proved to improve the precision of the formula statistically significantly.

• Klíčová slova
• CMR, Cardiovascular magnetic resonance, ECV, Extracellular volume, Synthetic haematocrit,
• MeSH
• hematokrit * MeSH
• kontrastní látky * MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• myokard patologie   MeSH
• nemoci srdce krev   diagnostické zobrazování   MeSH
• organokovové sloučeniny * MeSH
• prediktivní hodnota testů MeSH
• retrospektivní studie MeSH
• studie proveditelnosti MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• gadobutrol MeSH Prohlížeč
• kontrastní látky * MeSH
• organokovové sloučeniny * MeSH

• Publikační typ
• tisková chyba MeSH

Energy depletion during ischemia leads to disturbed ionic homeostasis and accumulation of neuroactive substances in the extracellular space, subsequently leading to volume changes in astrocytes. Confocal microscopy combined with 3D reconstruction was used to quantify ischemia-induced astrocyte volume changes in cortical slices of GFAP/EGFP transgenic mice. Twenty-minutes of oxygen-glucose deprivation (OGD) or oxygen-glucose deprivation combined with acidification (OGD(pH 6.8)) revealed the presence of two distinct astrocytic populations, the first showing a large volume increase (HR astrocytes) and the second displaying a small volume increase (LR astrocytes). In addition, changes in resting membrane potential (V(m)), measured by the patch-clamp technique, supported the existence of two astrocytic populations responding differently to ischemia. Although one group markedly depolarized during OGD or OGD(pH 6.8), only small changes in V(m) toward more negative values were observed in the second group. Conversely, acidification (ACF(pH 6.8)) led to a uniform volume decrease in all astrocytes, accompanied by only a small depolarization. Interestingly, two differently responding populations were not detected during acidification. Differences in the expression of inwardly rectifying potassium channels (Kir4.1), glial fibrillary acidic protein (GFAP), and taurine levels in cortical astrocytes were detected using immunohistochemical methods. We conclude that two distinct populations of astrocytes are present in the cortex of GFAP/EGFP mice, based on volume and V(m) changes during exposure to OGD or OGD(pH 6.8). Immunohistochemical analysis suggests that the diverse expression of Kir4.1 channels and GFAP as well as differences in the accumulation of taurine might contribute to the distinct ability of astrocytes to regulate their volume.

• MeSH
• astrocyty klasifikace   patologie   fyziologie   MeSH
• draslíkové kanály dovnitř usměrňující metabolismus   MeSH
• elektrická stimulace MeSH
• gliový fibrilární kyselý protein genetika   MeSH
• glukosa nedostatek   MeSH
• hypoxie MeSH
• ischemie patologie   MeSH
• kanál KCNJ10 MeSH
• koncentrace vodíkových iontů MeSH
• konfokální mikroskopie MeSH
• membránové potenciály fyziologie   MeSH
• metoda terčíkového zámku MeSH
• modely nemocí na zvířatech MeSH
• mozková kůra patologie   MeSH
• myši transgenní MeSH
• myši MeSH
• proteiny nervové tkáně metabolismus   MeSH
• taurin metabolismus   MeSH
• techniky in vitro MeSH
• velikost buňky * MeSH
• zelené fluorescenční proteiny genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• draslíkové kanály dovnitř usměrňující MeSH
• gliový fibrilární kyselý protein MeSH
• glukosa MeSH
• kanál KCNJ10 MeSH
• proteiny nervové tkáně MeSH
• taurin MeSH
• zelené fluorescenční proteiny MeSH

Valvular heart disease leads to ventricular pressure and/or volume overload. Pressure overload leads to fibrosis, which might regress with its resolution, but the limits and details of this reverse remodeling are not known. To gain more insight into the extent and nature of cardiac fibrosis in valve disease, we analyzed needle biopsies taken from the interventricular septum of patients undergoing surgery for valve replacement focusing on the expression and distribution of major extracellular matrix protein involved in this process. Proteomic analysis performed using mass spectrometry revealed an excellent correlation between the expression of collagen type I and III, but there was little correlation with the immunohistochemical staining performed on sister sections, which included antibodies against collagen I, III, fibronectin, sarcomeric actin, and histochemistry for wheat germ agglutinin. Surprisingly, the immunofluorescence intensity did not correlate significantly with the gold standard for fibrosis quantification, which was performed using Picrosirius Red (PSR) staining, unless multiplexed on the same tissue section. There was also little correlation between the immunohistochemical markers and pressure gradient severity. It appears that at least in humans, the immunohistochemical pattern of fibrosis is not clearly correlated with standard Picrosirius Red staining on sister sections or quantitative proteomic data, possibly due to tissue heterogeneity at microscale, comorbidities, or other patient-specific factors. For precise correlation of different types of staining, multiplexing on the same section is the best approach.

• Klíčová slova
• Collagen, Fibronectin, Fibrosis, Pressure overload, Valvular heart disease,
• MeSH
• aortální insuficience metabolismus   patologie   chirurgie   MeSH
• aortální stenóza * metabolismus   patologie   chirurgie   MeSH
• extracelulární matrix - proteiny * metabolismus   analýza   MeSH
• fibróza * metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezikomorová přepážka patologie   metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• extracelulární matrix - proteiny * MeSH

In this study, we focused on age-related changes in astrocyte functioning, predominantly on the ability of astrocytes to regulate their volume in response to a pathological stimulus, namely extracellular 50 mM K+ concentration. The aim of our project was to identify changes in the expression and function of transport proteins in the astrocytic membrane and properties of the extracellular space, triggered by aging. We used three-dimensional confocal morphometry, gene expression profiling, immunohistochemical analysis, and diffusion measurement in the hippocampal slices from 3-, 9-, 12-, and 18-month-old mice, in which astrocytes are visualized by enhanced green fluorescent protein under the control of the promoter for human glial fibrillary acidic protein. Combining a pharmacological approach and the quantification of astrocyte volume changes evoked by hyperkalemia, we found that marked diversity in the extent of astrocyte swelling in the hippocampus during aging is due to the gradually declining participation of Na+-K+-Cl- transporters, glutamate transporters (glutamate aspartate transporter and glutamate transporter 1), and volume-regulated anion channels. Interestingly, there was a redistribution of Na+-K+-Cl- cotransporter and glutamate transporters from astrocytic soma to processes. In addition, immunohistochemical analysis confirmed an age-dependent decrease in the content of Na+-K+-Cl- cotransporter in astrocytes. The overall extracellular volume changes revealed a similar age-dependent diversity during hyperkalemia as observed in astrocytes. In addition, the recovery of the extracellular space was markedly impaired in aged animals.

• Klíčová slova
• Aging, Astrocyte, Hippocampus, Potassium/glutamate uptake, Volume regulation,
• MeSH
• astrocyty účinky léků   metabolismus   patologie   fyziologie   MeSH
• draslík farmakologie   MeSH
• gliový fibrilární kyselý protein MeSH
• hipokampus cytologie   MeSH
• myši transgenní MeSH
• stárnutí patologie   fyziologie   MeSH
• velikost buňky * MeSH
• zelené fluorescenční proteiny MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• draslík MeSH
• gliový fibrilární kyselý protein MeSH
• zelené fluorescenční proteiny MeSH

OBJECTIVES: Systemic scleroderma (SSc) is a rare connective tissue disease presenting with fibrosis affecting skin and internal organs. Cardiovascular magnetic resonance (CMR) with quantification of extracellular volume (ECV) and T1 mapping might help to detect heart involvement. We aimed to evaluate whether myocardial involvement correlates with functional and laboratory parameters. METHODS: Thirty-three asymptomatic SSc patients (29 women, aged 56.6±12.2years) and 20 controls (10 women, 53.7±13.1years) were examined using CMR, echocardiography, functional pulmonary test and laboratory assessment. RESULTS: SSc patients had higher ECV (27.5±2.8 vs. 22.8±1.9%, P<0.0001) and native T1 values (1258.9±51.2 vs. 1192.2±32.6, P<0.0001) compared to controls. Plasma level of growth differentiation factor 15 (GDF-15) and galectin-3 correlated with ECV (r=0.35; P=0.0076 and r=0.38; P=0.0081) and native T1 (r=0.31; P=0.023 and r=0.35; P=0.012). GDF-15 was also negatively correlated with diffusing capacity of the lung for carbon monoxide (r=-0.58; P=0.0004) and positively correlated with modified Rodnan skin score (r=0.59; P=0.0003). Conventional echocardiography parameters were similar in SSc patients and controls. However, the global longitudinal peak systolic strain (GLPS) was lower in SSc patients compared to controls (18.6±1.6 vs. 21.1±1.2%; P<0.0001). GLPS also negatively correlated with native T1 (r=-0.35; P=0.0097), ECV (r=-0.33; P=0.014), GDF 15 (r=-0.31; P=0.022), and galectin-3 (r=-0.37; P=0.0076). CONCLUSIONS: Asymptomatic heart involvement is common in SSc patients and includes focal and diffuse myocardial fibrosis. GDF-15 and galectin-3 were positively correlated with myocardial fibrosis parameters. Future outcome studies must show whether measurement of GDF-15 and galectin-3 in SSC patients might be may be useful in clinical practice.

• Klíčová slova
• Cardiovascular magnetic resonance, Extracellular volume estimation, Galectin-3, Growth differentiation factor 15, Systemic sclerosis, T1 mapping,
• MeSH
• biologické markery krev   MeSH
• dopplerovská echokardiografie metody   MeSH
• dospělí MeSH
• fibróza MeSH
• kardiomyopatie krev   diagnostické zobrazování   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonance kinematografická metody   MeSH
• mediátory zánětu krev   MeSH
• prospektivní studie MeSH
• senioři MeSH
• systémová sklerodermie krev   diagnostické zobrazování   epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• mediátory zánětu MeSH

Glial fibrillary acidic protein (GFAP) is the main component of intermediate filaments in astrocytes. To assess its function in astrocyte swelling, we compared astrocyte membrane properties and swelling in spinal cord slices of 8- to 10-day-old wild-type control (GFAP(+/+)) and GFAP-knockout (GFAP(-/-)) mice. Membrane currents and K(+) accumulation around astrocytes after a depolarizing pulse were studied using the whole-cell patch-clamp technique. In vivo cell swelling was studied in the cortex during spreading depression (SD) in 3 to 6-month-old animals. Swelling-induced changes of the extracellular space (ECS) diffusion parameters, i.e., volume fraction alpha and tortuosity lambda, were studied by the real-time iontophoretic tetramethylammonium (TMA(+)) method using TMA(+)-selective microelectrodes. Morphological analysis using confocal microscopy and quantification of xy intensity profiles in a confocal plane revealed a lower density of processes in GFAP(-/-) astrocytes than in GFAP(+/+) astrocytes. K(+) accumulation evoked by membrane depolarization was lower in the vicinity of GFAP(-/-) astrocytes than GFAP(+/+) astrocytes, suggesting the presence of a larger ECS around GFAP(-/-) astrocytes. Astrocyte swelling evoked by application of 50 mM K(+) or by hypotonic solution (HS) produced a larger increase in [K(+)](e) around GFAP(+/+) astrocytes than around GFAP(-/-) astrocytes. No differences in alpha and lambda in the spinal cord or cortex of GFAP(+/+) and GFAP(-/-) mice were found; however, the application of either 50 mM K(+) or HS in spinal cord, or SD in cortex, evoked a large decrease in alpha and an increase in lambda in GFAP(+/+) mice only. Slower swelling in GFAP(-/-) astrocytes indicates that GFAP and intermediate filaments play an important role in cell swelling during pathological states.

• MeSH
• astrocyty účinky léků   metabolismus   patologie   MeSH
• buněčná membrána účinky léků   metabolismus   MeSH
• difuze účinky léků   MeSH
• draslík metabolismus   farmakologie   MeSH
• extracelulární prostor účinky léků   metabolismus   MeSH
• fluorescenční barviva farmakokinetika   MeSH
• gliový fibrilární kyselý protein nedostatek   genetika   MeSH
• intermediární filamenta účinky léků   metabolismus   patologie   MeSH
• isochinoliny farmakokinetika   MeSH
• membránové potenciály účinky léků   fyziologie   MeSH
• metoda terčíkového zámku MeSH
• mícha účinky léků   metabolismus   patologie   MeSH
• myši knockoutované anatomie a histologie   metabolismus   MeSH
• myši MeSH
• osmotický tlak účinky léků   MeSH
• permeabilita buněčné membrány účinky léků   fyziologie   MeSH
• šířící se kortikální deprese účinky léků   fyziologie   MeSH
• somatosenzorické korové centrum metabolismus   patofyziologie   MeSH
• velikost buňky účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• draslík MeSH
• fluorescenční barviva MeSH
• gliový fibrilární kyselý protein MeSH
• isochinoliny MeSH
• lucifer yellow MeSH Prohlížeč

BACKGROUND/AIMS: Chronic heart failure (HF) disrupts normal kidney function and leads to cardiorenal syndrome that further promotes HF progression. To identify potential participants in HF-related injury, we analyzed kidney proteome in an established HF model. METHODS: HF was induced by chronic volume overload in male HanSD rats using aorto-caval fistula. After 21 weeks, cardiac and renal functions (in-situ kidney study) and renal proteomics were studied in sham-operated (controls) and HF rats, using iTRAQ labeling and LC-MS with Orbitrap Fusion, leading to identification and quantification of almost 4000 proteins. RESULTS: Compared to controls, HF rats had cardiac hypertrophy, systemic and pulmonary congestion. Kidneys of HF rats had reduced renal blood flow, sodium excretion and urine production. While glomerular filtration rate, serum cystatin C and creatinine were still normal compared to controls, HF kidneys showed albuminuria and markedly increased tissue angiotensin-II levels (5-fold). HF kidneys (versus controls) displayed differential expression (˃1.5-fold) of 67 proteins. The most upregulated were angiotensin-converting enzyme (ACE, ˃20-fold), advanced glycosylation product-specific receptor (RAGE, 14-fold), periostin (6.8-fold), caveolin-1 (4.5-fold) and other proteins implicated in endothelial function (vWF, cavins 1-3, T-kininogen 2), proinflammatory ECM activation (MFAP4, collagen-VI, galectin-3, FHL-1, calponin) and proteins involved in glomerular filtration membrane integrity (CLIC5, ZO-1). Carboxylesterase-1D (CES1D), an enzyme that converts ACE inhibitors or sacubitril into active drugs, was also upregulated in HF kidneys. CONCLUSION: Chronic HF leads to latent kidney injury, associated with deep changes in kidney protein composition. These alterations may act in concert with intrarenal renin-angiotensin system activation and may serve as markers and/or targets to tackle cardiorenal syndrome.

• Klíčová slova
• Angiotensin-II, Cardiorenal syndrome, Heart failure, Kidney function, Proteomics,
• MeSH
• albuminurie etiologie   MeSH
• angiotensin konvertující enzym metabolismus   MeSH
• endotel metabolismus   MeSH
• extracelulární matrix - proteiny metabolismus   MeSH
• kardiomegalie patofyziologie   MeSH
• kardiorenální syndrom etiologie   metabolismus   MeSH
• krysa rodu Rattus MeSH
• ledviny chemie   zranění   patofyziologie   MeSH
• proteom analýza   metabolismus   MeSH
• proteomika metody   MeSH
• receptor pro konečné produkty pokročilé glykace metabolismus   MeSH
• renin-angiotensin systém MeSH
• srdeční selhání komplikace   MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Ager protein, rat MeSH Prohlížeč
• angiotensin konvertující enzym MeSH
• extracelulární matrix - proteiny MeSH
• proteom MeSH
• receptor pro konečné produkty pokročilé glykace MeSH

On the basis of direct quantification of hemodialysis (HD), the kinetics of phenols (Ph) were followed in 13 patients on regular HD treatment. The average plasma levels of Ph before and after HD were 627 +/- 109 mumol/L and 416 +/- 81 mumol/L, respectively. The total amount of Ph removed during 5-h HD was 7,481 +/- 1,894 mumol. For calculation of the generation rate (G), a new formula has been derived not requiring knowledge of the corresponding volume of distribution. The G of Ph was 2.9 +/- 0.7 mumol/min on average. The mean dialysis clearance (K) of Ph was 48.2 +/- 10.2 ml/min.

• MeSH
• biologické modely MeSH
• dialýza ledvin * MeSH
• dieta s nízkým obsahem soli MeSH
• dietní proteiny aplikace a dávkování   MeSH
• dospělí MeSH
• draslík dietní aplikace a dávkování   MeSH
• extracelulární prostor chemie   metabolismus   MeSH
• fenoly krev   farmakokinetika   MeSH
• hemoglobiny analýza   metabolismus   MeSH
• kompartmenty tělních tekutin fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• uremie krev   terapie   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• dietní proteiny MeSH
• draslík dietní MeSH
• fenoly MeSH
• hemoglobiny MeSH