Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia

BACKGROUND: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. METHODS: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset). RESULTS: CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (rs =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs =-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival. CONCLUSION: CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities

Effect of bis(tri-n-butyltin) oxide and di-n-butyltindichloride on phagocytic activity of macrophages

Bis(tri-n-butyltin)oxide (TBTO) is in staat in vitro fagocytose van erythrocyten door macrofagen te remmen, maar niet zonder de macrofagen te beschadigen, zodat ze hun viabiliteit verliezen. Een dibutylverbinding, di-n-butyltindichloride, heeft een uitgesproken effect op de fagocytose door macrofagen, zonder een invloed te vertonen op de viabiliteit, zij het bij hogere concentraties dan die waarbij TBTO al toxisch is. Toch kan een specifiek effect van TBTO op fagocytose niet worden uitgesloten, daar bij met Corynebacterium parvum of met BCG geactiveerde macrofagen ook met TBTO reeds bij lagere concentraties een remming van de fagocytose kon worden waargenomen waarbij de viabiliteit van de cellen nog niet werd beinvloed.RIV

New Mexico Lobo, Volume 059, No 53, 2/7/1956

New Mexico Lobo, Volume 059, No 53, 2/7/195

METABOLISM OF 3 PHARMACOLOGICALLY ACTIVE-DRUGS IN ISOLATED HUMAN AND RAT HEPATOCYTES - ANALYSIS OF INTERSPECIES VARIABILITY AND COMPARISON WITH METABOLISM IN-VIVO

1. The metabolism of the three drugs (Org GB 94, Org 3770 and Org OD 14) was studied in isolated human and rat hepatocytes. The metabolic profiles in rat and human hepatocytes were compared with the available in vivo data in both species. 2. All three drugs were metabolized extensively under the conditions used, both in human and rat hepatocytes, showing both extensive phase I and II metabolism. 3. During 3-h incubation with rat hepatocytes the three compounds were metabolized completely, whereas incubation with human hepatocytes only resulted in partial metabolism, amounting for 58% (Org GB 94), 36% (Org 3770) and 94% (Org OD 14) of the dose. In addition, rat hepatocytes excreted relatively more of the formed metabolites than human hepatocytes. 4. For both species, the metabolites formed in the isolated cells were quite similar to those found in vivo. With respect to Org GB 94 and Org 3770, metabolites were detected in man in vivo and in isolated human hepatocytes that were not found in any of the animal species studied previously. 5. The reflection of interspecies differences in isolated hepatocytes, with respect to both metabolite profiles and human-specific metabolites, renders isolated human hepatocytes a very valuable tool during preclinical drug development