Antonis Goulas

Changes in pupil reaction to light in Alzheimer's disease patients: a preliminary report.

The aim of this preliminary study was to compare the pupil reaction to light in Alzheimers disease (AD) patients before and after treatment and in normal controls. Ten AD patients diagnosed according to DSM-IV and NINCDS-ADRDA criteria (five medication-free and five under anticholinesterase treatment) and five age- and gender-matched controls took part in the study. Drug-free patients and all control subjects were free of any medication for at least four weeks. An optical method was used to assess the pupil reaction to a single flash. Medication-free AD patients manifested shorter latency and lower amplitude of maximum response to light in comparison to controls. These findings are in agreement with the presence of a cholinergic deficit in AD patients. Pharmacological treatment with donepezil, which is an anticholinesterase agent partially improves this deficit. The results of this preliminary investigation suggest that dynamic pupillometry could be a useful adjunct to assist the diagnosis of early AD, and the differential diagnosis between different types of dementia. AD patients seem to manifest a specific pattern of pupil reaction to light, and some characteristics of this pattern are detectable even in patients receiving anticholinesterase medication. However, this is only a preliminary report and further research is mandatory.

Oligophosphopeptides of varied structural complexity derived from the egg phosphoprotein, phosvitin.

Phosvitins are the principal phosphoproteins in the eggs of oviparous vertebrates. They have an exceptionally high serine content and most, or even all, of the serine residues are esterified to phosphate. The phosphorylated residues tend to occur in uninterrupted runs of as many as 28 phosphoserines (as inXenopus phosvitin). This unique structural feature gives phosvitins extraordinary properties and can be expected to play a key role in phosvitin function. For example, the concentration of phosphate groups provides for numerous highly efficient metal-binding sites in clusters. The mode of binding had been shown to be affected by the size of the protein and the degree to which serine residues are phosphorylated. For structure-function studies of phosvitins (and other polyphospho-proteins), phosphopeptides of differentiated structural complexity are desirable. Such model peptides were produced in this work by limited proteolysis of chicken phosvitin, and oligophosphopeptides of widely varying sizes, phosphoserine content, and sequence were purified and characterized. These include phosvitin segments containing one, two, or several oligophosphoserine runs, corresponding to segments of the N-terminal, C-terminal, and core sequence of the protein.

Synthesis and anti-inflammatory effects of a series of novel 7-hydroxycoumarin derivatives.

A number of 7-hydroxycoumarins have been synthesised by Pechmann cyclisation using differently substituted resorcinols employing perchloric acid as the condensing agent. All the compounds have been characterised by analytical and spectroscopic methods. The anti-inflammatory properties were tested with LPS-induced inflammation in J774 macrophages. Expression of iNOS and COX-2 was determined by Western blot, NO by nitrite assay and IL-6 by ELISA analyses. Fifteen of the tested 7-hydroxycoumarins also inhibited IL-6 production but none of them had any major inhibitory effect on COX-2 expression.

PDE5 Inhibitors: In Vitro and In Vivo Pharmacological Profile

PDE5 inhibitors have been clearly established as first-line therapy for the treatment of erectile dysfunction (ED). Three PDE5 inhibitors--sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis)--are currently approved by the FDA and the EMEA for use in ED, whereas sildenafil is also marketed under a different proprietary name (Revatio) for the treatment of pulmonary arterial hypertension (PAH). A forth PDE5 inhibitor, udenafil (Zydena), is currently marketed. In the present review the molecular basis and the mechanism of action of PDE5 inhibitors is discussed. In addition experimental and clinical data concerning their effects on different tissues, organs and systems is systematically reviewed and their possible beneficial action in numerous disorders is presented.

Methylenetetrahydrofolate reductase C677T polymorphism: Association with risk for childhood acute lymphoblastic leukemia and response during the initial phase of chemotherapy in greek patients

As of late, a number of studies have focused on the association of the gene for methyletetrahydrofolate reductase (MTHFR) with risk for acute lymphoblastic leukemia (ALL) in children and in adults, as well as with response to chemotherapy. The degree of this association may vary according to the ethnic background and geographic localization of the population under study, or the phase of treatment when response to chemotherapy is concerned.

Changes in pupil reaction to light in melancholic patients

The aim of the current study was to compare the pupil reaction to light in depressed patients and normal control subjects. Seven depressed patients with melancholic features according to DSM-IV criteria and 14 age- and gender-matched control subjects took part in the study. All were free of any medication for at least 2 weeks. All were aged between 25 and 50 years. An optical method was used to assess the pupil reaction to a single flash. Depressed patients manifested shorter latency for constriction than control subjects, and a marginal difference in the total work produced by acetylcholine. The results of the current study support the theory that there is a norepinephrine hypoactivity in melancholic depression, with less affected acetylcholine activity.

An association study of a functional catalase gene polymorphism, −262C→T, and patients with Alzheimer's disease

According to the oxidative stress hypothesis which has been proposed as one of a number of possible mechanisms underlying pathogenesis of Alzheimers disease (AD), accumulation of hydrogen peroxide in the brain of affected individuals, due to overproduction and/or insufficient detoxification, can trigger a cascade of neurotoxic events, thus contributing to the neuronal damage characteristic of the disease. The upregulation of enzymes that are able to neutralize hydrogen peroxide (catalase, peroxidases) would then be conceivably able to offer at least some protection from the damaging effects of this agent. In this study we examined the distribution of a functional polymorphism in the gene for catalase, -262C-->T, in an independent population of 137 AD patients and 130 control individuals. The presence of the polymorphism, which results in the elimination of a SmaI restriction site, was tested with a PCR amplification/SmaI digestion-based assay. No significant difference has emerged from the comparison of either genotype or allele frequencies (P>0.5). We conclude that the catalase gene -262C-->T polymorphism does not confer a protective effect with respect to AD.

Association of the Tau haplotype with Parkinson's disease in the Greek population.

We compared the distribution of the Tau H1 haplotype and related subhaplotypes in a group of clinically diagnosed Parkinsons disease patients (n = 133) and in control individuals (n = 113) from northern Greece. We were able to detect a statistically significant overrepresentation of the H1H1 genotype in our patient group (OR for H1H1 vs. H1H2 and H2H2: 1.73; 95% CI: 1.03–2.90; P = 0.037). The H1 subhaplotype significantly associated with the disease in our population was different from the one previously reported for a Norwegian population, suggesting that the nature of the association of Tau with Parkinsons disease is influenced by ethnic variation.

An association study of the cholesteryl ester transfer protein TaqI B polymorphism with late onset Alzheimer's disease

Cholesteryl ester transfer protein (CETP) is reportedly able to affect the amount of cholesterol available for deposition and/or removal from peripheral tissues, in its capacity to mediate the transfer of cholesterol from high density lipoprotein (HDL) to very low density lipoprotein, in exchange for triacylglycerols from the latter. The TaqI B polymorphism of the human CETP gene has been associated with decreased CETP mass and an increase in HDL-cholesterol. While many studies have addressed the atherogenic or anti-atherogenic potential of this polymorphism, little is known about its effect on neurodegeneration, despite the fact that CETP is expressed in the brain and the disturbance of cholesterol homeostasis appears to be an important factor in the pathogenesis of Alzheimers disease (AD). In this report, we have compared the distribution of the TaqI B polymorphism in an independent population of 102 clinically diagnosed late onset AD patients and a spousal control group of 97 individuals. We have also examined the possible interaction between this polymorphism and two other polymorphisms suspected of affecting cholesterol flux, namely apolipoprotein E APOE epsilon4, and lipoprotein lipase LPLS447X. No statistically significant differences have emerged with respect to either genotype or allele frequencies between the AD and control populations. CETP TaqI B did not interact significantly with either APOE epsilon4 or LPLS447X, in this study.

No association between the lipoprotein lipase S447X polymorphism and Alzheimer's disease

Results from various genetic association studies of the lipoprotein lipase (LPL) S447X polymorphism and Alzheimers disease (AD), range from a statistically significant negative association of clinically examined patients to a non-significant but consistent trend for under-representation of the X447 allele in neuropathologically confirmed subjects. In this report we have compared the distribution of the above polymorphism in an independent group of clinically diagnosed AD patients, including a subgroup where the disease was pathologically confirmed, and a spousal control group. No statistically significant differences emerged from this comparison. We conclude that LPL cannot be a major factor in pathogenesis of AD.