BACKGROUND: Skeletal muscle alterations are associated with higher mortality and morbidity in patients with liver cirrhosis. Assessing these changes seems to be a promising method for identifying patients at a high risk of poor outcomes following liver transplantation (LT). This is particularly important given the current global shortage of organ donors. However, evidence of the impact of these alterations on the prognosis of patients undergoing LT is inconclusive. The aim of our prospective study was to evaluate the impact of skeletal muscle changes, reflected in sarcopenia, myosteatosis and metabolic changes in the calf muscles, on perioperative outcomes and long-term survival after LT. We also sought to determine the posttransplant evolution of the resting muscle metabolism. METHODS: We examined 134 adult LT candidates. Of these, 105 underwent LT. Sarcopenia and myosteatosis were diagnosed by measuring the skeletal muscle index and mean psoas muscle radiation attenuation, respectively, which were obtained from computed tomography (CT) scans taken during pretransplant assessment. Additionally, patients underwent 31P MR spectroscopy (MRS) of the calf muscles at rest before LT and 6, 12 and 24 months thereafter. The median follow-up was 6 years. RESULTS: Patients with abnormal 31P MRS results and CT-diagnosed myosteatosis prior to LT had significantly worse long-term survival after LT (hazard ratio (HR), 3.36; 95% confidence interval (CI), 1.48-7.60; p = 0.0021 and HR, 2.58; 95% CI, 1.06-6.29; p = 0.03, respectively). Multivariable analysis showed that abnormal 31P MR spectra (HR, 3.40; 95% CI, 1.50-7.71; p = 0.003) were a better predictor of worse long-term survival after LT than myosteatosis (HR, 2.78; 95% CI, 1.14-6.78; p = 0.025). Patients with abnormal 31P MR spectra had higher blood loss during LT (p = 0.038), required a higher number of red blood cell transfusions (p = 0.006) and stayed longer in ICU (p = 0.041) and hospital (p = 0.007). Myosteatosis was associated with more revision surgeries following LT (p = 0.038) and a higher number of received red blood cell transfusion units (p = 0.002). Sarcopenia had no significant effect on posttransplant patient survival. An improvement in the resting metabolism of the calf muscles was observed at 12 and 24 months after LT. CONCLUSIONS: Abnormal 31P MRS results of calf muscles were superior to CT-based diagnosis of myosteatosis and sarcopenia in predicting perioperative complications and long-term survival after LT. Resting muscle metabolism normalized 1 year after LT in most recipients.

• MeSH
• dospělí MeSH
• kosterní svaly * diagnostické zobrazování   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie * metody   MeSH
• počítačová rentgenová tomografie * metody   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• sarkopenie etiologie   metabolismus   MeSH
• senioři MeSH
• transplantace jater * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Major depressive disorder (MDD) is a mental illness with a high worldwide prevalence and suboptimal pharmacological treatment, which necessitates the development of novel, more efficacious MDD medication. Nuclear magnetic resonance (NMR) can non-invasively provide insight into the neurochemical state of the brain using proton magnetic resonance spectroscopy (1H MRS), and an assessment of regional cerebral blood flow (rCBF) by perfusion imaging. These methods may provide valuable in vivo markers of the pathological processes underlying MDD. METHODS: This study examined the effects of the chronic antidepressant medication, citalopram, in a well-validated MDD model induced by bilateral olfactory bulbectomy (OB) in rats. 1H MRS was utilized to assess key metabolite ratios in the dorsal hippocampus and sensorimotor cortex bilaterally, and arterial spin labelling was employed to estimate rCBF in several additional brain regions. RESULTS: The 1H MRS data results suggest lower hippocampal Cho/tCr and lower cortical NAA/tCr levels as a characteristic of the OB phenotype. Spectroscopy revealed lower hippocampal Tau/tCr in citalopram-treated rats, indicating a potentially deleterious effect of the drug. However, the significant OB model-citalopram treatment interaction was observed using 1H MRS in hippocampal mI/tCr, Glx/tCr and Gln/tCr, indicating differential treatment effects in the OB and control groups. The perfusion data revealed higher rCBF in the whole brain, hippocampus and thalamus in the OB rats, while citalopram appeared to normalise it without affecting the control group. CONCLUSION: Collectively, 1H MRS and rCBF approaches demonstrated their capacity to capture an OB-induced phenotype and chronic antidepressant treatment effect in multiple brain regions.

• MeSH
• bulbus olfactorius metabolismus   chirurgie   účinky léků   MeSH
• citalopram * farmakologie   MeSH
• deprese farmakoterapie   metabolismus   MeSH
• depresivní porucha unipolární farmakoterapie   metabolismus   MeSH
• hipokampus metabolismus   účinky léků   MeSH
• krysa rodu rattus MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• modely nemocí na zvířatech * MeSH
• mozek * metabolismus   účinky léků   MeSH
• mozkový krevní oběh * účinky léků   MeSH
• potkani Sprague-Dawley MeSH
• protonová magnetická rezonanční spektroskopie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Changes in the protonation state of lyophilized proteins can impact structural integrity, chemical stability, and propensity to aggregate upon reconstitution. When a buffer is chosen, the freezing/drying process may result in dramatic changes in the protonation state of the protein due to ionization shift of the buffer. In order to determine whether protonation shifts are occurring, ionizable probes can be added to the formulation. Optical probes (dyes) have shown dramatic ionization changes in lyophilized products, but it is unclear whether the pH indicator is uniform throughout the matrix and whether the change in the pH indicator actually mirrors drug ionization changes. In solid-state NMR (SSNMR) spectroscopy, the chemical shift of the carbonyl carbon in carboxylic acids is very sensitive to the ionization state of the acid. Therefore, SSNMR can be used to measure ionization changes in a lyophilized matrix by employing a small quantity of an isotopically-labeled carboxylic acid species in the formulation. This paper compares the apparent pH of six trehalose-containing lyophilized buffer systems using SSNMR and UV-Vis diffuse reflectance spectroscopy (UVDRS). Both SSNMR and UVDRS results using two different ionization probes (butyric acid and bromocresol purple, respectively) showed little change in apparent acidity compared to the pre-lyophilized solution in a sodium citrate buffer, but a greater change was observed in potassium phosphate, sodium phosphate, and histidine buffers. While the trends between the two methods were similar, there were differences in the numerical values of equivalent pH (pHeq) observed between the two methods. The potential causes contributing to the differences are discussed.

• MeSH
• fosfáty * chemie   MeSH
• histidin * chemie   MeSH
• koncentrace vodíkových iontů MeSH
• kyselina citronová chemie   MeSH
• lyofilizace * metody   MeSH
• magnetická rezonanční spektroskopie * metody   MeSH
• pufry MeSH
• spektrofotometrie ultrafialová metody   MeSH
• trehalosa * chemie   MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Many patients with long COVID experience neurological and psychological symptoms. Signal abnormalities on MR images in the corpus callosum have been reported. Knowledge about the metabolic profile in the splenium of the corpus callosum (CCS) may contribute to a better understanding of the pathophysiology of long COVID. MATERIALS AND METHODS: Eighty-one subjects underwent proton MR spectroscopy examination. The metabolic concentrations of total N-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr), myo-inositol (mI), and NAA/Cho in the CCS were statistically compared in the group of patients containing 58 subjects with positive IgG COVID-19 antibodies or positive SARS-CoV-2 qPCR test at least two months before the MR and the group of healthy controls containing 23 subjects with negative IgG antibodies. RESULTS: An age-dependent effect of SARS-CoV-2 on Cho concentrations in the CCS has been observed. Considering the subjective threshold of age = 40 years, older patients showed significantly increased Cho concentrations in the CCS than older healthy controls (p = 0.02). NAA, Cr, and mI were unchanged. All metabolite concentrations in the CCS of younger post-COVID-19 patients remained unaffected by SARS-CoV-2. Cho did not show any difference between symptomatic and asymptomatic patients (p = 0.91). DISCUSSION: Our results suggest that SARS-CoV-2 disproportionately increases Cho concentration in the CCS among older post-COVID-19 patients compared to younger ones. The observed changes in Cho may be related to the microstructural reorganization in the CCS also reported in diffusion measurements rather than increased membrane turnover. These changes do not seem to be related to neuropsychological problems of the post-COVID-19 patients. Further metabolic studies are recommended to confirm these observations.

• MeSH
• cholin * metabolismus   MeSH
• corpus callosum * diagnostické zobrazování   metabolismus   MeSH
• COVID-19 * diagnostické zobrazování   metabolismus   MeSH
• dospělí MeSH
• inositol metabolismus   MeSH
• kreatin * metabolismus   MeSH
• kyselina aspartová * analogy a deriváty   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• protonová magnetická rezonanční spektroskopie * metody   MeSH
• SARS-CoV-2 * MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Combining proton and phosphorus magnetic resonance spectroscopy offers a unique opportunity to study the oxidative and glycolytic components of metabolism in working muscle. This paper presents a 7 T proton calf coil design that combines dipole and loop elements to achieve the high performance necessary for detecting metabolites with low abundance and restricted visibility, specifically lactate, while including the option of adding a phosphorus array. We investigated the transmit, receive, and parallel imaging performance of three transceiver dipoles with six pair-wise overlap-decoupled standard or twisted pair receive-only coils. With a higher SNR and more efficient transmission decoupling, standard loops outperformed twisted pair coils. The dipoles with standard loops provided a four-fold-higher image SNR than a multinuclear reference coil comprising two proton channels and 32% more than a commercially available 28-channel proton knee coil. The setup enabled up to three-fold acceleration in the right-left direction, with acceptable g-factors and no visible aliasing artefacts. Spectroscopic phantom measurements revealed a higher spectral SNR for lactate with the developed setup than with either reference coil and fewer restrictions in voxel placement due to improved transmit homogeneity. This paper presents a new use case for dipoles and highlights their advantages for the integration in multinuclear calf coils.

• MeSH
• fantomy radiodiagnostické * MeSH
• kosterní svaly * diagnostické zobrazování   chemie   MeSH
• kyselina mléčná chemie   metabolismus   MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• magnetická rezonanční tomografie * metody   MeSH
• poměr signál - šum MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

β-Lactamases (EC 3.5.2.6) confer resistance against β-lactam group-containing antibiotics in bacteria and higher eukaryotes, including humans. Pathogenic bacterial resistance against β-lactam antibiotics is a primary concern for potential therapeutic developments and drug targets. Here, we report putative β-lactamase activity, sulbactam binding (a β-lactam analogue) in the low μM affinity range, and site-specific interaction studies of a 14 kDa UV- and dark-inducible protein (abbreviated as UVI31+, a BolA homologue) from Chlamydomonas reinhartii. Intriguingly, the solution NMR structure of UVI31 + bears no resemblance to other known β-lactamases; however, the sulbactam binding is found at two sites rich in positively charged residues, mainly at the L2 loop regions and the N-terminus. Using NMR spectroscopy, ITC and MD simulations, we map the ligand binding sites in UVI31 + providing atomic-level insights into its β-lactamase activity. Current study is the first report on β-lactamase activity of UVI31+, a BolA analogue, from C. reinhartii. Furthermore, our mutation studies reveal that the active site serine-55 is crucial for β-lactamase activity.

• MeSH
• beta-laktamasy * chemie   metabolismus   MeSH
• Chlamydomonas reinhardtii * enzymologie   MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• nukleární magnetická rezonance biomolekulární metody   MeSH
• rostlinné proteiny chemie   metabolismus   MeSH
• sekvence aminokyselin MeSH
• simulace molekulární dynamiky MeSH
• sulbaktam chemie   farmakologie   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: To understand how macromolecular content varies in the human brain with age in a large cohort of healthy subjects. METHODS: In-vivo 1H-MR spectra were acquired using ultra-short TE STEAM at 7T in the posterior cingulate cortex. Macromolecular content was studied in 147 datasets from a cohort ranging in age from 19 to 89 y. Three fitting approaches were used to evaluate the macromolecular content: (1) a macromolecular resonances model developed for this study; (2) LCModel-simulated macromolecules; and (3) a combination of measured and LCModel-simulated macromolecules. The effect of age on the macromolecular content was investigated by considering age both as a continuous variable (i.e., linear regressions) and as a categorical variable (i.e., multiple comparisons among sub-groups obtained by stratifying data according to age by decade). RESULTS: While weak age-related effects were observed for macromolecular peaks at ̃0.9 (MM09), ̃1.2 (MM12), and ̃1.4 (MM14) ppm, moderate to strong effects were observed for peaks at ̃1.7 (MM17), and ̃2.0 (MM20) ppm. Significantly higher MM17 and MM20 content started from 30 to 40 y of age, while for MM09, MM12, and MM14, significantly higher content started from 60 to 70 y of age. CONCLUSIONS: Our findings provide insights into age-related differences in macromolecular contents and strengthen the necessity of using age-matched measured macromolecules during quantification.

• MeSH
• cingulární gyrus diagnostické zobrazování   chemie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• magnetická rezonanční tomografie metody   MeSH
• makromolekulární látky * chemie   MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stárnutí * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Článek podává přehled o možnostech zobrazovacích metod v neuroonkologii. Pojednává o nejdostupnějším vyšetření v podobě výpočetní tomografie až po dominantní metodu, a to multiparametrické zobrazení pomocí magnetické rezonance a jejích pokročilých způsobů zobrazení. Článek se věnuje i hybridním metodám, které umožňují spojení předností metabolického zobrazení s výhodami zobrazení magnetickou rezonancí.

The article provides an overview of the possibilities of imaging methods in neurooncology. Firstly the most accessible examination using computed tomography and secondly dominant magnetic resonance imaging and its multiparametric imaging thanks to its advanced submodalities. The article also shows potential and usage of hybrid methods that allow the combination of advantages of metabolic imaging with advantages of magnetic resonance imaging.

• MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• magnetická rezonanční tomografie metody   MeSH
• multiparametrická magnetická rezonance MeSH
• nádory centrálního nervového systému diagnostické zobrazování   MeSH
• neurozobrazování * metody   MeSH
• počítačová rentgenová tomografie metody   MeSH
• Check Tag
• lidé MeSH

In this study, we utilized proton magnetic resonance spectroscopy (MRS) to understand the role of glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) of OCD patients in the pregenual anterior cingulate cortex (pgACC). In total, 54 patients with OCD and 54 healthy controls (HC) matched for age and sex were included in the study. They underwent MRS in the pgACC region to calculate the concentrations of Glu, Gln, GABA, and Glu + Gln (Glx). After quality control of the MRS data, 21 OCD and 21 HC were statistically analyzed. The severity of symptoms were evaluated using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the statistical analysis, we compared differences between groups for the metabolites; in the OCD we analyzed the correlations with symptom severity, medication status, age, and duration of illness. A significant decrease in Glx, in Glu, and in Gln in the pgACC were observed in the OCD compared to HC. The correlation statistics showed a significant positive correlation between Glu levels and the YBOCS compulsions subscale. The results indicate that patients with OCD present a disturbance in glutamatergic metabolism in the pgACC. The results also demonstrate that these changes correlate with the severity of compulsions.

• MeSH
• cingulární gyrus * metabolismus   MeSH
• GABA metabolismus   MeSH
• glutamin metabolismus   MeSH
• kyselina glutamová metabolismus   MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• obsedantně kompulzivní porucha * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Pilot study validating the animal model of depression - the bilateral olfactory bulbectomy in rats - by two nuclear magnetic resonance methods, indirectly detecting the metabolic state of the brain. Furthermore, the study focussed on potential differences in brain laterality. METHODS: Arterial spin labelling assessed cerebral brain flow in prefrontal, sensorimotor, and piriform cortices, nucleus accumbens, hippocampus, thalamus, circle of Willis, and whole brain. Proton magnetic resonance spectroscopy provided information about relative metabolite concentrations in the cortex and hippocampus. RESULTS: Arterial spin labelling found no differences in cerebral perfusion in the group comparison but revealed lateralisation in the thalamus of the control group and the sensorimotor cortex of the bulbectomized rats. Lower Cho/tCr and Cho/NAA levels were found in the right hippocampus in bulbectomized rats. The differences in lateralisation were shown in the hippocampus: mI/tCr in the control group, Cho/NAA, NAA/tCr, Tau/tCr in the model group, and in the cortex: NAA/tCr, mI/tCr in the control group. CONCLUSION: Olfactory bulbectomy affects the neuronal and biochemical profile of the rat brain laterally and, as a model of depression, was validated by two nuclear magnetic resonance methods.

• MeSH
• cholin metabolismus   MeSH
• kreatin metabolismus   MeSH
• krysa rodu rattus MeSH
• kyselina aspartová metabolismus   MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• magnetická rezonanční tomografie * MeSH
• mozek * patologie   MeSH
• pilotní projekty MeSH
• receptory antigenů T-buněk metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH