Triptofán és bizonyos metabolitjainak koncentrációjának meghatározása Creutzfeldt-Jakob betegeknél = The assessment of concentrations of certain tryptophan metabolites in Creutzfeldt-Jakob disease

The kynurenine (KYN) pathway (KP), also known as the route where more than 95% of the tryptophan (TRP) is metabolized, in its steps of catabolism forms different metabolites which contribute to the neuroprotective–neurodegenerative changes in central nervous system. For this reason, TRP metabolism is extensively studied in neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease), where the neurologically active metabolite concentration changes are followed. Kynurenic acid (KYNA), which is an endogenous N-methyl-D-aspartate receptor (NMDAR) antagonist, is considered to be a neuroprotective agent. In the present study TRP, KYN and KYNA were determined from human serum and cerebrospinal fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD) and age- and gender-matched controls, using high performance liquid chromatography (HPLC) applying UV and fluorescent detectors. The developed method was optimized and validated according to the International Congress Harmonization Guidelines. The precision and recovery values ranged between 1.60-4.36%, 81.61-101.09%, respectively. There were no differences between the groups with regard all the measured metabolites. The application of the developed validated method enabled the simultaneous determination of certain metabolites of the KP of TRP metabolism, but no evident alterations were found in patients with CJD

Neurodegenerative proteinopathies associated with neuroinfections

Infectious agents, including viruses and bacteria, are proposed to be involved in the pathogenesis of Alzheimer’s disease (AD). According to this hypothesis, these agents have capacity to evade the host immune system leading to chronic infection, inflammation, and subsequent deposition of Aβ and phosphorylated-tau in the brain. Co-existing proteinopathies and age-related pathologies are common in AD and the brains of elderly individuals, but whether these are also related to neuroinfections remain to be established. This study determined the prevalence and distribution of neurodegenerative proteinopathies in patients with infection-induced acute or chronic inflammation associated with herpes simplex virus (HSV) encephalitis (n = 13) and neurosyphilis (n = 23). The mean age at death in HSV patients was 53 ± 12 years (range 24–65 years) and survival was 9 days–6 years following initial infection. The mean age at death and survival in neurosyphilis patients was 60 ± 15 years (range 36–86 years) and 1–5 years, respectively. Neuronal tau-immunoreactivity and neurites were observed in 8 HSV patients and 19 neurosyphilis patients, and in approximately half of these, this was found in regions associated with inflammation and expanding beyond regions expected from the Braak stage of neurofibrillary degeneration. Five neurosyphilis patients had cortical ageing-related tau astrogliopathy. Aβ-plaques were found in 4 HSV patients and 11 neurosyphilis patients. Lewy bodies were observed in one HSV patient and two neurosyphilis patients. TDP-43 pathology was absent. These observations provide insights into deposition of neurodegenerative proteins in neuroinfections, which might have implications for COVID-19 patients with chronic and/or post-infectious neurological symptoms and encephalitis

A COVID–19 patológiája

A SARS-CoV-2-pandémia óta a Semmelweis Egyetemen és egyéb intézményekben rendszeresen végeznek boncolá-sokat, melyek feltárták a COVID–19 jellegzetességeit. A legsúlyosabb kép a tüdőben mutatkozik, melynek légtelen-sége változó kiterjedésű, oka összetett, így tüdővizenyő, fehérjében gazdag izzadmány, az erek vérrög okozta elzáró-dása és gyulladás. A szív, a vese, az agy és a máj változó mértékben érintett, érrögösödés, elhalás, degeneratív elváltozások mutatkoznak. A SARS-CoV-2-vírus fehérjéi (tüske, nukleokapszid) és a vírus genetikai anyaga (RNS) kimutatható az egyes szervekben, leginkább a tüdőben. Klinikopatológiai elemzéssel megállapítható, hogy a halál a SARS-CoV-2-fertőzés mint közvetlen kórok következménye, vagy egyéb krónikus megbetegedés, melyet súlyosbí-tott a SARS-CoV-2-fertőzés, vagy a halál a vírusfertőzéstől függetlenül következett be