Parkinson’s disease and dementia

Neurological Sciences - Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, affecting about 1% of the population over the age of 60. In addition to motor...     

Hepatic histology of patients with HIV infection and chronic hepatitis C treated with interferon.

AIMS: To evaluate the histological changes seen in liver biopsies after interferon (IFN) treatment in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection. METHODS: Twenty four intravenous drug users with chronic hepatitis C were investigated histologically before beginning a 12 month course of IFN treatment and 18 months later. Twelve were HIV positive, without opportunistic or other viral infections (group A), and 12 were HIV negative (group B). RESULTS: According to alanine amino-transferase concentrations, four sustained responders and eight non-responders were found in group A; six sustained responders, five relapsers, and one non-responder were found in group B. HCV RNA became negative in one sustained responder of group A and in the six sustained responders of group B. When histological findings of biopsies performed before therapy and 18 months later were compared, no significant changes in the mean value of Knodell's index and subindices were found in group A, whereas in group B Knodell's index, piecemeal necrosis, and focal hepatocellular necrosis decreased significantly. CONCLUSIONS: In chronic hepatitis C, coinfection with HIV showed a tendency towards a lower response to IFN, although this did not reach statistical significance; however, none of the HIV positive patients developed cirrhosis during the follow up and this should be considered in clinical management of such patients.     

Tissue distribution and macromolecular interactions of 14[C-ring] melphalan in the rat

Summary The kinetics of uptake and elimination, covalent binding, and macromolecular interactions of ¹⁴[C-ring] melphalan was studied after a single oral dose (20 mg/kg, 0.1 mCi/kg) in normal rats. Peak radioactivity level in tissues was observed at 2–4 h after administration. Uptake of label in most tissues was rapid, with a t_1/2 of less than 1 h. Elimination was biphasic. Tissues of the gastrointestinal tract showed the most rapid rates of elimination, with t_1/2 of 13, 24, 18, and 19 h for stomach, duodenum, and small and large intestines, respectively. Bone marrow also showed a fast rate of elimination of radioactivity, with a t_1/2 of 30 h. Tissues with the slowest rates of elimination were skin, eye, spleen, pancreas, and lung, with t_1/2 of 333, 241, 149, 122, and 109 h, respectively. Covalent binding studies showed that melphalan, or its metabolites, bound irreversibly to all tissue macromolecular fractions. The percentage of covalently bound radioactivity increased with time in all tissues except kidney and eye, reaching up to 70%–80% of the total radioactivity remaining at 72 h. Elimination of covalently bound radioactivity was slower in the DNA fractions of the tissues of the gastrointestinal tract and heart compared with the elimination rate from lipid, protein, or RNA fractions. Slow elimination rates of ¹⁴[C-ring] melphalan equivalents from the protein fraction were observed in the skin, eye, and brain. Accumulation, rather than elimination, of radioactivity in this fraction was most prominent in the pancreas. In the bone marrow accumulation of radioactivity was observed in the lipid fraction.Abbreviations used in this paper are L-Pam Melphalan, l-phenylalanine mustard 4-bis (2-chloroethyl) amino-1-phenylalanine - l-DOH 4-bis (2-hydroxyethyl) amino-1-phenylalanine - l-MOH 4-2 hydroxyethyl 2 chloroethyl amino-1-phenylalanine - HPLC high-pressure liquid chromatography - TCA trichloroacetic acid - AUC area under the curve - GIT gastrointestinal tract     

Haplotypes in cathechol-O-methyltransferase gene confer increased risk for psychosis in Alzheimer disease

BackgroundThe gene encoding catechol-O-methyltransferase (COMT) has been suggested as a candidate for Alzheimer-related psychosis (AD-P) susceptibility, and an association between AD-P and a functional valine to methionine polymorphism has been reported.ObjectiveThe aim of this study was to assess the genetic contribution of other COMT variants to the risk of AD-P.MethodsTwo hundred and forty-six AD patients underwent clinical and neuropsychological examination as well as an evaluation of behavioural and psychiatric disturbances. They were subsequently divided into two subgroups according to the presence (AD-P) or the absence (AD-nP) of psychotic symptoms. Four single-nucleotide polymorphisms (SNPs) within COMT gene were evaluated, i.e. rs737865, rs737864, intron 1 C2754delC, and the well-known valine/methionine variant (rs4680). Analyses were performed on the single locus and pairwise disequilibrium of loci, and multi-locus haplotype.ResultsThe individual SNP analysis confirmed an association for the valine/methionine variant with AD-P. Haplotype analyses revealed that the alleles at four loci (rs737865, rs737864, intron 1 C2754delC, rs4680) interacted to create the risk of psychosis in AD, as A-C-C-G haplotype (OR = 2.08, 95% CI = 1.02–4.27, P = 0.044) and G-C-delC-G haplotype (OR = 2.54, 95% CI = 1.32–4.90, P = 0.006) in respect to the most common and not-at-risk A-C-C-A haplotype which was significantly overrepresented in AD-P.ConclusionsThe present findings provide evidence of COMT genetic variations’ role in the susceptibility to AD-related psychosis. The observation of a haplotype effect of different polymorphisms within the COMT gene puts emphasis on the usefulness of haplotype analysis in better defining individualized genetic risk profiles in AD.