Jacopo Tagliabue

Reduced collagenolytic activity of matrix metalloproteinases and development of liver fibrosis in the aging rat

Although moderate fibrosis is a histological hallmark of the aging liver, the molecular mechanisms underlying this phenomenon are little known. Here, we provide a comprehensive description of hepatic collagen expression and metabolism during natural aging in rats. Interstitial collagen accumulated significantly in the oldest animals, mainly in the periportal area (P<0.05, 19- vs. 2-month-old rats). This was ascribed to COL-III protein deposition (P<0.05 vs. 2-month-old rats), rather than COL-I. Conversely, the transcription activity of COL-III gene decreased (P<0.05) during the considered lifespan (2-19-months), whereas COL-I and transforming growth fator-beta1 (TGF-beta1) mRNA content was substantially unchanged. In the aged rats, hepatic matrix metalloproteinases (MMP) activity, (both MMP-1 and MMP-2) dropped significantly (P<0.05), with a concomitant increase of the inactive tissue inhibitor of MMP (TIMP-1)/MMP-1 complex (P<0.05). MMP-2 and TIMP-1 levels were weakly affected. All together, these results suggest that during natural aging, (i) COL III is the protein that accumulates preferentially in the liver; (ii) liver fibrosclerosis is mainly explained by a reduced proteolytic activity of matrix MMP, in which TIMP-1 seems to be a major regulating factor.

Alpha-1-antichymotrypsin and oxidative stress in the peripheral blood from patients with probable Alzheimer disease: a short-term longitudinal study

To evaluate the stability and reproducibility of selected peripheral oxidative stress markers and their possible relation to cognitive performance, three different blood samples were taken at 7- to 10-day intervals from 11 patients with probable Alzheimer disease (AD) and 11 nondemented controls. Blood samples were also collected once from 6 patients with vascular dementia (VD). Alpha-1-antichymotrypsin (ACT), C-reactive protein (CRP), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), lactoferrin (LTF), and total lipid peroxidation (LPO) were then measured. Blood levels of ACT and GSH-Px were increased in AD patients but not in patients with VD. Levels of LTF, CRP, and LPO were comparable between AD patients and controls. Erythrocyte SOD activity was increased in AD patients. Blood levels of ACT negatively correlated with LPO levels and positively correlated with scores of the Global Deterioration Scale of AD patients. ACT might be implicated in controlling oxidative damage of blood lipids and their turnover during the progression of AD.

Anomalous Monism in a Digital Universe

Bermúdez (Philosophy of psychology: a contemporary introduction, Routledge, London, 2005) identifies the “Interface Problem” as the central problem in the philosophy of psychology: how commonsensical psychological explanations can be integrated with lower-level (cognitive, biological, etc.) explanations? In particular, since folk psychology is meant to provide causal explanations on a par with, say, neurobiological explanations, the question of how to understand the relation between the two layers arises naturally. Donald Davidson claimed that the interface problem is actually ill-posed and put forward his version of the “Autonomy Picture”, the view known as anomalous monism. This work reviews Davidson’s proposal in the light of digital universes: we model the key claims of the theory using cellular automata and show that Davidson’s original version of the Autonomy Picture (which differs, in some respects, from what is discussed by Bermúdez) is immune to two arguments against autonomy.

Apolipoprotein E Genotype in Vascular Dementia

The e4 allele of apolipoprotein E (ApoE) has been associated with Alzheimer’s disease (AD): the frequency of the e4 allele is elevated in samples of AD patients1,2 and individuals with a single or double dose of the s4 allele have earlier onset of AD symptoms1. Furthermore, subjects with one or two e4 alleles have been shown to have increased amounts of the neurofibrillary tangles and amyloid plaques associated with AD3.