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 asparagová * 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

AIM: Patients with multiple brain metastases (BM) benefit from hippocampal-avoiding whole brain radiotherapy (HA-WBRT), the challenging and less available form of WBRT. This study explores potential of pre-radiotherapy (pre-RT) hippocampal magnetic resonance spectroscopy (MRS) measuring hippocampal neuronal density as an imaging surrogate and predictive tool for assessing neurocognitive functions (NCF). METHODS: 43 BM patients underwent pre-RT hippocampal MRS. N-acetyl aspartate (NAA) concentration, a marker for neuronal density (weighted by creatine (Cr) and choline (Cho) concentrations), and neurocognitive function (NCF) tests (HVLT and BVMT) performed by certified psychologists were evaluated. Clinical variables and NAA concentrations were correlated with pre-RT NCFs. RESULTS: HVLT and BVMT subtests showed pre-RT deterioration except for BVMT recognition. Significantly better NCFs were observed in women in HVLT subsets. Significantly higher NAA/Cr + Cho was measured in women (median 0.63 vs. 0.55; P=0.048) in the left hippocampus (no difference in the right hippocampus). In men, a positive correlation (0.51, P=0.018) between total brain volume and HVLT-TR, between left hippocampal NAA/Cr + Cho and HVLT-R (0.45, P=0.063), and between right hippocampal NAA/Cr + Cho and BVMT-recognition (0.49, P=0.054) was observed. In women, a borderline significant negative correlation was observed between left hippocampal NAA/Cr + Cho and BVMT-TR (-0.43, P=0.076) and between right NAA/Cr + Cho and HVLT-DR (-0.42, P=0.051). CONCLUSION: Borderline statistically significant correlations were observed with speculative interpretation underlying the challenges of hippocampal MRS as a surrogate for neurocognitive impairment. Further studies need to be done to ascertain the opportunities for imaging predictors of benefit from memory sparing radiotherapy.

• MeSH
• cholin metabolismus   MeSH
• dospělí MeSH
• hipokampus * diagnostické zobrazování   patologie   MeSH
• kognitivní dysfunkce etiologie   MeSH
• kraniální ozáření škodlivé účinky   MeSH
• kreatin metabolismus   MeSH
• kyselina aspartová analogy a deriváty   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie * metody   MeSH
• nádory mozku * radioterapie   sekundární   MeSH
• neuropsychologické testy MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Degenerative cervical myelopathy (DCM) is a severe consequence of degenerative cervical spinal cord (CSC) compression. The non-myelopathic stage of compression (NMDC) is highly prevalent and often progresses to disabling DCM. This study aims to disclose markers of progressive neurochemical alterations in NMDC and DCM by utilizing an approach based on state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Proton-MRS data were prospectively acquired from 73 participants with CSC compression and 47 healthy controls (HCs). The MRS voxel was centered at the C2 level. Compression-affected participants were clinically categorized as NMDC and DCM, radiologically as mild (MC) or severe (SC) compression. CSC volumes and neurochemical concentrations were compared between cohorts (HC vs. NMDC vs. DCM and HC vs. MC vs. SC) with general linear models adjusted for age and height (pFWE < 0.05) and correlated to stenosis severity, electrophysiology, and myelopathy symptoms (p < 0.05). Whereas the ratio of total creatine (tCr) to total N-acetylaspartate (tNAA) increased in NMDC (+11%) and in DCM (+26%) and SC (+21%), myo-inositol/tNAA, glutamate + glutamine/tNAA, and volumes changed only in DCM (+20%, +73%, and -14%) and SC (+12%, +46%, and -8%, respectively) relative to HCs. Both tCr/tNAA and myo-inositol/tNAA correlated with compression severity and volume (-0.376 < r < -0.259). Myo-inositol/tNAA correlated with myelopathy symptoms (r = -0.670), whereas CSC volume did not. Short-echo 1H-MRS provided neurochemical signatures of CSC impairment that reflected compression severity and clinical significance. Whereas volumetry only reflected clinically manifest myelopathy (DCM), MRS detected neurochemical changes already before the onset of myelopathy symptoms.

• MeSH
• dospělí MeSH
• inositol metabolismus   MeSH
• komprese míchy metabolismus   patologie   MeSH
• krční mícha * MeSH
• krční obratle MeSH
• kreatin metabolismus   MeSH
• kyselina asparagová analogy a deriváty   metabolismus   MeSH
• kyselina glutamová metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie * MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVE: In multiple sclerosis (MS), deep grey matter (DGM) atrophy has been recognised as a crucial component of the disease that presents early and it has been associated with disability. Although the precise mechanism underlying grey matter atrophy is unknown, several hypotheses have been postulated. Our previous research pointed to correlations of hypothalamic metabolic alterations with clinical outcomes of MS, therefore we decided to further test the relationship of these alterations with DGM atrophy. METHODS: We used 1H-Magnetic Resonance spectroscopy (1H-MRS) of the hypothalamus to test its metabolites in 26 patients with RRMS and 22 healthy age-matched controls. DGM atrophy was evaluated by simple planimetry of third ventricular width on the hypothalamic level (3VW) in T1 weighted MRI pictures. Metabolite ratios of N-acetyl aspartate (NAA), choline (Cho), glutamate and glutamine (Glx), myo-inositol (mIns) and creatine (Cr) were correlated with Multiple Sclerosis Severity Scale (MSSS) and 3VW. RESULTS: Metabolite concentrations were compared between patients and controls using multiple regression models allowing for age, 3VW and metabolites. It revealed that the only relevant predictors of MSSS were 3VW and Glx/NAA. At a significance level of P<0.05, a unit increase of 3VW was associated with a 0.35 increase of MSSS, for a typical value of Glx/NAA; P value 0.0039. A unit increase of Glx/NAA was associated with a 0.93 increase of MSSS, for a typical value of atrophy; P value 0.090. There were significant linear correlations between Glx/Cr and MSSS, Glx/NAA and MSSS, and between mIns/NAA and 3VW. CONCLUSIONS: The results suggest that both NAA and Glx are associated with neurodegeneration of hypothalamic DGM and severe disease course. Glx related 1H-MRS parameters seem to be superior to other metabolites in determining disease burden, independently of otherwise powerful 3VW planimetry. Significantly increased mIns/NAA in MS patients compared to controls point to gliosis, which parallels the atrophy of hypothalamic DGM.

• MeSH
• atrofie MeSH
• dospělí MeSH
• kyselina asparagová analogy a deriváty   metabolismus   MeSH
• kyselina glutamová metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• mladý dospělý MeSH
• prediktivní hodnota testů MeSH
• progrese nemoci MeSH
• roztroušená skleróza diagnostické zobrazování   metabolismus   patofyziologie   MeSH
• stupeň závažnosti nemoci MeSH
• thalamus patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Glutamate carboxypeptidases II and III (GCPII and GCPIII) are highly homologous di-zinc metallopeptidases belonging to the M28 family. These enzymes are expressed in a variety of tissues, including the brain, prostate, kidney, testis and jejunum. GCPII has been recognized as a neuropeptidase in the central nervous system, as a folate hydrolase participating in absorption of folates in the jejunum and, most importantly, as a prostate-specific membrane antigen that is highly expressed in prostate adenocarcinoma. Furthermore, it has been identified in the neovasculature of most human solid tumors. In contrast, GCPIII has not been associated with any specific physiological function or pathology, and its expression, activity and inhibition have not been as well-studied. In this review, we provide an overview of the current understanding of the structure, enzymatic activity, substrate specificity, and tissue distribution of these two homologous enzymes. We discuss their potential physiological functions and describe the available animal models, including genetically modified mice. We also review the potential use of specific monoclonal antibodies and small-molecule inhibitors recognizing GCPII/III for diagnosis, imaging and experimental therapy of human cancers and other pathologies.

• MeSH
• adenokarcinom metabolismus   MeSH
• antigeny povrchové metabolismus   MeSH
• fenotyp MeSH
• glutamátkarboxypeptidasa II metabolismus   MeSH
• glutamáty chemie   MeSH
• hydrolýza MeSH
• idiopatické střevní záněty metabolismus   MeSH
• jejunum metabolismus   MeSH
• karboxypeptidasy metabolismus   MeSH
• krysa rodu rattus MeSH
• kyselina asparagová analogy a deriváty   chemie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• monoklonální protilátky chemie   MeSH
• mozek metabolismus   MeSH
• mutantní kmeny myší MeSH
• myši transgenní MeSH
• myši MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory prostaty metabolismus   MeSH
• neuropeptidy chemie   MeSH
• proteasy metabolismus   MeSH
• tenké střevo metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Here we present the preparation of 14 pairs of cis- and trans-diammine monochlorido platinum(II) complexes, coordinated to heterocycles (i.e., imidazole, 2-methylimidazole and pyrazole) and linked to various acylhydrazones, which were designed as potential inhibitors of the selenium-dependent enzymes glutathione peroxidase 1 (GPx-1) and thioredoxin reductase 1 (TrxR-1). However, no inhibition of bovine GPx-1 and only weak inhibition of murine TrxR-1 was observed in in vitro assays. Nonetheless, the cis configured diammine monochlorido Pt(II) complexes exhibited cytotoxic and apoptotic properties on various human cancer cell lines, whereas the trans configured complexes generally showed weaker potency with a few exceptions. On the other hand, the trans complexes were generally more likely to lack cross-resistance to cisplatin than the cis analogues. Platinum was found bound to the nuclear DNA of cancer cells treated with representative Pt complexes, suggesting that DNA might be a possible target. Thus, detailed in vitro binding experiments with DNA were conducted. Interactions of the compounds with calf thymus DNA were investigated, including Pt binding kinetics, circular dichroism (CD) spectral changes, changes in DNA melting temperatures, unwinding of supercoiled plasmids and ethidium bromide displacement in DNA. The CD results indicate that the most active cis configured pyrazole-derived complex causes unique structural changes in the DNA compared to the other complexes as well as to those caused by cisplatin, suggesting a denaturation of the DNA structure. This may be important for the antiproliferative activity of this compound in the cancer cells.

• MeSH
• aktivace enzymů účinky léků   MeSH
• chondroitin analogy a deriváty   chemie   farmakologie   MeSH
• DNA chemie   účinky léků   MeSH
• enzymy metabolismus   MeSH
• glutathionperoxidasa antagonisté a inhibitory   MeSH
• inhibiční koncentrace 50 MeSH
• kyselina asparagová analogy a deriváty   chemie   farmakologie   MeSH
• molekulární struktura MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• organoplatinové sloučeniny chemická syntéza   chemie   farmakologie   MeSH
• oxidace-redukce MeSH
• platina chemie   farmakologie   toxicita   MeSH
• proliferace buněk účinky léků   MeSH
• selen chemie   farmakologie   toxicita   MeSH
• skot MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: To assess whether noninvasive proton magnetic resonance spectroscopy ((1)H-MRS) tissue metabolite measurements at baseline can predict an increase in the rate of β-amyloid (Aβ) accumulation on serial PET in clinically normal (CN) older adults. METHODS: Consecutive participants aged 60 years and older (n = 594) from the Mayo Clinic Study of Aging who were CN at baseline and who underwent (1)H-MRS from the posterior cingulate voxel and longitudinal (11)C-Pittsburgh compound B (PiB)-PET were included. The rate of Aβ accumulation by serial cortical PiB standardized uptake value ratios was estimated as a function of baseline (1)H-MRS metabolite ratios and time using mixed-effect models adjusted for age, sex, and APOE ε4. Effect of APOE ε4 on the relationship between baseline MRS and an increased rate of Aβ accumulation was also assessed. RESULTS: Among all participants, a higher myo-inositol (mI)/creatine (p = 0.011) and a lower N-acetylaspartate/mI (p = 0.006) at baseline were associated with an increased Aβ accumulation over time after adjusting for age, sex, and APOE ε4. APOE ε4 did not modify the association of baseline (1)H-MRS metabolite ratios and rate of Aβ accumulation. However, APOE ε4 carriers accumulated Aβ faster than noncarriers regardless of the baseline Aβ load (p = 0.001). CONCLUSION: Among CN older adults, early metabolic alterations on (1)H-MRS and APOE ε4 status are independently associated with an increased rate of Aβ accumulation. Our findings could have important implications for early diagnosis and identification of individuals for secondary prevention trials, because an increased rate of Aβ accumulation in CN older adults may confer a higher risk for cognitive decline and mild cognitive impairment.

• MeSH
• amyloidní beta-protein metabolismus   MeSH
• apolipoprotein E4 genetika   MeSH
• heterozygot MeSH
• inositol metabolismus   MeSH
• kreatin metabolismus   MeSH
• kyselina asparagová analogy a deriváty   metabolismus   MeSH
• lidé MeSH
• longitudinální studie MeSH
• mozek diagnostické zobrazování   metabolismus   MeSH
• následné studie MeSH
• pozitronová emisní tomografie * MeSH
• protonová magnetická rezonanční spektroskopie * MeSH
• senioři MeSH
• stárnutí metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Excessive adipose tissue, particularly with a central distribution, consists of visceral fat, which is metabolically active and could impinge upon central nervous system functioning. The aim of the current study was to examine levels of visceral adiposity in relation to key cerebral metabolite ratios localized in the occipitoparietal grey matter. Seventy-three adults, aged between 40 and 60 years, underwent structural magnetic resonance imaging and single voxel1H Magnetic Resonance Spectroscopy (1H MRS). Visceral fat was assessed using Dual Energy X Ray Absorptiometry (DXA). Individuals with higher visceral fat mass and volume had significantly lower ratios of N-acetyl-aspartate to total creatine (phosphocreatine + creatine, PCr + Cr) (NAA/PCr + Cr) (β = -0.29, p = 0.03, β = -0.28, p = 0.04). They also had significantly higher ratios of myo-inositol to total creatine (mI/PCr + Cr ) (β = 0.36, p = 0.01, β = 0.36, p = 0.01). Visceral fat mass and volume were not significantly related to ratios of glutamate to total creatine (Glu/PCr + Cr). While future studies are necessary, these results indicate central adiposity is associated with metabolic changes that could impinge upon the central nervous system in middle age.

• MeSH
• absorpční fotometrie metody   MeSH
• dospělí MeSH
• kyselina asparagová analogy a deriváty   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nitrobřišní tuk diagnostické zobrazování   metabolismus   MeSH
• průřezové studie MeSH
• temenní lalok diagnostické zobrazování   metabolismus   MeSH
• týlní lalok diagnostické zobrazování   metabolismus   MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND PURPOSE: The aim of this prospective study is to evaluate post-whole brain radiotherapy (WBRT) changes in hippocampal concentration of N-acetylaspartate (h-tNAA) as a marker of neuronal loss and to correlate those changes to neurocognitive function. MATERIAL AND METHODS: Thirty-five patients with brain metastases underwent baseline single slice multi-voxel MR spectroscopy (MRS) examination for measurement of hippocampal h-tNAA together with baseline battery of neurocognitive tests focused on memory (Auditory Verbal Learning Test and Brief Visuospatial Memory Test - Revised) as well as quality of life questionnaires (EORTC QLQ-C30 a EORTC QLQ-BN20). Eighteen patients completed follow-up evaluation four months after standard WBRT (2 laterolateral fields, 10×3.0Gy, 6MV photons) and were included in this analysis. MRS and cognitive examinations were repeated and compared to baseline measurements. RESULTS: Statistically significant decreases in h-tNAA were observed in the right (8.52-7.42mM; -12.9%, 95%CI: -7.6 to -16.4%) as well as in the left hippocampus (8.64-7.60mM; -12%, 95%CI: -7.9 to -16.2%). Statistically significant decline was observed in all AVLT and BVMT-R subtests with exception of AVLT_Recognition. Quality of life declined after WBRT (mean Δ -14.1±20.3 points in transformed 0-100 point scale; p=0.018) with no correlation to changes in hippocampal metabolite concentrations. Moderate positive correlation was observed between left h-tNAA concentration decrease and AVLT_TR decline (r=+0.32; p=0.24) as well as with AVLT_DR (r=+0.33; p=0.22) decline. Changes in right h-tNAA/Cr negatively correlated with AVLT_DR (r=-0.48; p=0.061). No correlation between right hippocampus h-tNAA and memory decline (AVLT) was observed. CONCLUSIONS: Our results suggest hippocampal NAA concentrations decline after WBRT and MRS may be a useful biomarker for monitoring neuronal loss after radiotherapy.

• MeSH
• biologické markery metabolismus   MeSH
• degenerace nervu etiologie   metabolismus   MeSH
• hipokampus diagnostické zobrazování   metabolismus   účinky záření   MeSH
• kognitivní dysfunkce etiologie   metabolismus   MeSH
• kraniální ozáření škodlivé účinky   MeSH
• kvalita života MeSH
• kyselina asparagová analogy a deriváty   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• nádory mozku radioterapie   sekundární   MeSH
• následné studie MeSH
• neuropsychologické testy MeSH
• paměť účinky záření   MeSH
• prospektivní studie MeSH
• průzkumy a dotazníky MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Protonová MR spektroskopie umožňuje neinvazivní hodnocení metabolitů vyšetřované tkáně, poskytuje informaci o složení intrakraniálních lézí, zvyšuje specificitu strukturální magnetické rezonance a tudíž ovlivňuje léčbu pacientů a případná rozhodnutí o změně léčebné strategie, jako je tomu například u rozlišení poléčebných změn a recidivy vysokostupňových gliomů po komplexní onkologické léčbě. Biochemické změny intrakraniálních nádorů se mohou lišit v závislosti na histologii a stupni malignity. Výsledky spektroskopie lze využít v neuroonkologii v mnohých klinických indikacích. Při interpretaci těchto závěrů je nutné mít na paměti limitace spektroskopie a nutnost adekvátní zkušenosti provádějícího pracoviště.

Proton MR spectroscopy provides the non-invasive assessment of metabolites in examined tissue, can be used to get intracranial neoplasms structural information, increases the specificity of structural magnetic resonance and may serve as an additional examination for evaluation of the response to treatment and decisions to change the treatment strategy as it is in diferentiation of posttreatment changes and recurrence after comlex oncologic treatment of glioma patients. Biochemic changes in glioma differ according to histology and tumor grading. The results of MR spectroscopy can be used for several indications in neurooncology. However, it is important to remember spectroscopy limitations and the necessity of an adequate institutional experience.

• Klíčová slova
• N-acetylaspartát,
• MeSH
• cholin metabolismus   MeSH
• gliom diagnostické zobrazování   metabolismus   MeSH
• kreatin metabolismus   MeSH
• kyselina asparagová analogy a deriváty   metabolismus   MeSH
• kyselina mléčná metabolismus   MeSH
• lidé MeSH
• nádory mozku * diagnostické zobrazování   metabolismus   MeSH
• protonová magnetická rezonanční spektroskopie * MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé MeSH