Proteomic evaluation of intermediary metabolism enzyme proteins in fetal Down's syndrome cerebral cortex

Trisomy 21 (Down's syndrome) is the most common genetic cause of human mental retardation. In Down's syndrome (DS) patients, deteriorated glucose, lipid, purine, folate and methionine/homocysteine metabolism has been reported. In our study, we used a proteomic approach to evaluate protein expression of enzyme proteins of intermediary metabolism in the brain of Down's syndrome fetuses. In fetal DS brain, we detected increased protein levels of mitochondrial aconitase as well as NADP-linked isocitrate dehydrogenase, decreased protein expression of citrate synthase and cytosolic aspartate aminotransferase. From two spots that corresponded to either pyruvate kinase M1 or M2 isozymes, significant elevation was observed only in one, while the second spot as well as the sum of the spots showed no differences between DS and controls. These results suggest derangement of intermediary metabolism during prenatal development of DS individuals.     

Aberrant expression of centractin and capping proteins, integral constituents of the dynactin complex, in fetal down syndrome brain

Down syndrome (DS, trisomy 21) is the most frequent genetic cause of mental retardation. Although known for more than a hundred years the underlying pathomechanisms for the phenotype and impaired brain functions remain elusive. Performing protein hunting in fetal DS brain, we detected a series of cytoskeleton proteins with aberrant expression in fetal DS cortex. Fetal brain cortex samples of controls and DS of the early second trimenon of gestation were used for the experiments. We applied two-dimensional electrophoresis with in-gel digestion of protein spots, subsequent mass spectroscopical (MALDI) identification, and quantification of spots using specific software. Centractin alpha, F-actin capping protein alpha-1, alpha-2 and beta subunits were significantly reduced in fetal DS cortex, whereas dynein intermediate clear 2, dynein intermediate chain 2, and kinesin light chain protein levels were unchanged. Centractins and F-actin capping proteins are major determinants of the cytoskeleton and are involved in pivotal functions including cellular, organelle, and nuclear motility. Deranged centractins and F-actin capping proteins may represent or induce deficient axonal transport and may well contribute to deterioration of the cytoskeleton's mitotic functions in trisomy 21.     

Unipolar late-onset depression: A comprehensive review

BACKGROUND: The older population increases all over the world and so also does the number of older psychiatric patients, which manifest certain specific and unique characteristics. The aim of this article is to provide a comprehensive review of the international literature on unipolar depression with onset at old age. METHODS: The authors reviewed several pages and books relevent to the subject but did not search the entire literature because of it's overwhelming size. They chose to review those considered most significant. RESULTS: The prevalence of major depression is estimated to be 2% in the general population over 65 years of age. The clinical picture of geriatric depression differs in many aspects from depression in younger patients. It is not yet clear whether it also varies across cultures and different socio-economic backgrounds. Biological data suggest that it is associated with an increased severity of subcortical vascular disease and greater impairment of cognitive performance. Many authors consider the existence of a somatic disorder to be related to the presence of depression in late life, even constituting a negative prognostic factor for the outcome of depression. Most studies support the opinion that geriatric depression carries a poorer prognosis than depression in younger patients. The therapeutic intervention includes pharmacotherapy, mainly with antidepressants, which is of established value and psychotherapy which is not equally validated. CONCLUSION: A significant number of questions regarding the assessment and treatment of geriatric depression remain unanswered, empirical data are limited, and further research is necessary.     

Mating disruption for the control of the olive moth, Prays oleae (Bern) (Lep., Yponomeutidae) with the ajor sex pheromone component

Abstract: Mating disruption to control the olive moth Prays oleae (Bern) was tested from 1992 to 1996 in olive groves in Greece. The major sex pheromone component (Z)-7-tetradecenal was formulated in β-cyclodextrin (β-CD) and polyvinyl chloride (PVC) polymers. Pheromone trap catches were reduced by up to 96–100% in the mating-disruption plots. During the first year of mating disruption a treatment with Bacillus thuringiensis (var. kurstaki ) (Bt) was applied to reduce the first generation or larvae. Fruit damage in the mating disruption plots was lower compared with the fruit damage in Bt, insecticide and untreated plots. In high fruiting years, the proportion of fruit damage was lower than in low fruiting years. Mating disruption applied in the same olive grove over several years progressively reduced the olive moth population from year to year.     

Proteomic analysis of amniotic fluid in pregnancies with Down syndrome

Proteomic analysis is widely used for the detection of diagnostic markers. In the present study amniotic fluid supernatants (AFS) from pregnancies with Down syndrome (DS) fetuses and from chromosomally normal fetuses in the 17th week of gestation were analyzed by 2-DE. Gel comparison revealed significant differences in the two groups. Spots with different expression levels were excised and proteins were identified by MALDI-MS and nano-ESI-MS/MS. Splicing factor arginine/serine-rich 4 (SFRS4; Q08170) was present only in AFS from DS fetuses and completely absent in the control group. Quantitative differences were detected for alpha-1-microglobulin (AMBP; P02760), collagen alpha 1 (I) chain (CO1A1; P02452), collagen alpha 1 (III) chain (CO3A1; P02461), collagen alpha 1 (V) chain d (CO5A1; P20908), and basement membrane-specific heparin sulfate proteoglycan core protein (PGBM; P98160). These proteins were increased in cases with DS, whereas protein IBP-1 (P08833) was decreased by 40% compared with chromosomally normal fetuses. Four proteins, CO1A1, CO3A1, CO5A1, and PGBM, appeared as fragments. As differentially expressed proteins were present in all pregnancies with DS tested, they may represent useful potential markers for prenatal diagnosis. However, for protein biomarkers to be of any clinical utility, systematic analysis of the maternal serum should be conducted.     

EuPA achieves visibility - an activity report on the first three years

Plans for the European Proteomics Association (EuPA) were conceived and established during 2004 and 2005, and culminated in the formal inception of the organisation during the 4th HUPO World Congress held in Munich in 2005. The mission from the outset has been three-tiered and is to: i) strengthen the national Proteomics organizations in their efforts; ii) to co-ordinate and provide educational programs, and iii) to advance the networking of scientists through meetings, workshops and student exchange. Linked to the mission were objectives to emphasise the benefits and contributions of Proteomics to biological and industrial researchers, the general public and science policy makers in Europe. In addition, the EuPA set out to promote scientific exchange for all applications and technology development related to Proteomics, and coordinate joint activities of national Proteomics societies at the European level. To achieve these tasks an organisational structure was conceived whereby four Activity Committees (Conferences/Communications, Education, EuPA-HUPO-Interactions and Funding) were implemented and a General Council consisting of all member countries. The remarkable rise and progress the EuPA has achieved in this small time frame is reported here.     

Proteomic analysis of amniotic fluid in pregnancies with Turner syndrome fetuses

Turner syndrome, occurring in 1:2500 female births, is caused by the complete or partial absence of one X chromosome. Amniotic fluid supernatant proteins from five second trimester pregnancies with Turner syndrome fetuses and five normal ones were analyzed by 2DE, MALDI-TOF-MS, and Western blot. Serotransferin, lumican, plasma retinol-binding protein, and apolipoprotein A-I were increased in Turner syndrome, while kininogen, prothrombin, and apolipoprotein A-IV were decreased. Since differentially expressed proteins are likely to cross the placenta barrier and be detected in maternal plasma, proteomic analysis may enhance research for noninvasive prenatal diagnosis of Turner syndrome.     

The effect of pharmaceuticals on the kinetics of methanogenesis and acetogenesis

In this study, the widely used anaerobic digestion model (ADM1) was used in order to simulate the inhibition of three pharmaceuticals, propranolol hydrochloride, ofloxacin and diclofenac sodium, on two groups of microorganisms, acetogens and acetoclastic methanogens, the most sensitive microorganisms groups involved in the anaerobic digestion process. The specific maximum consumption rate and saturation constant of acetate and propionate degraders were estimated through fitting the model to experimental data taken from continuous and batch experiments. A modified non-competitive inhibition function was used, and the inhibition constants were estimated using data from Batch experiments conducted at various concentrations of pharmaceuticals using enriched cultures with propionate and acetate degraders. It was found that propranolol hydrochloride was the most inhibitory pharmaceutical to both microorganisms groups.     

Proteomic determination of metabolic enzymes of the amnion cell: Basis for a possible diagnostic tool?

Amniocentesis is a valuable and standard procedure for prenatal diagnosis of genetic or inborn errors of metabolism. Amnion cells are cultivated and chromosomes or proteins can be examined to provide molecular diagnosis. Mainly individual proteins are searched for based upon pedigrees and/or anamnesis. As inborn errors of metabolism involve a vast diversity of metabolic enzymes, we aimed to find a screening method for a large series of metabolic enzymes. Amnion cells were obtained from amniocentesis and subjected to proteomic analysis. We used two-dimensional gel electrophoresis with in-gel digestion followed by matrix-assisted laser desorption/ionization-time of flight analysis, to identify metabolic enzymes. Furthermore, we compared metabolic proteins in amnion cells from controls with those from Down Syndrome (DS). Enzymes involved in carbohydrate handling, amino acid handling, -purine metabolism and intermediary metabolism as well as miscellaneous metabolic pathways were detected. Protein levels of several enzymes were significantly deranged in samples obtained from patients with DS. This approach, with the advantage of the concomitant determination of many enzyme proteins, may form the basis for future metabolic screens when amniocentesis is carried out.     

Off-label indications for atypical antipsychotics: A systematic review

INTRODUCTION: With the introduction of newer atypical antipsychotic agents, a question emerged, concerning their use as complementary pharmacotherapy or even as monotherapy in mental disorders other than psychosis. MATERIAL AND METHOD: MEDLINE was searched with the combination of each one of the key words: risperidone, olanzapine and quetiapine with key words that refered to every DSM-IV diagnosis other than schizophrenia and other psychotic disorders, bipolar disorder and dementia and memory disorders. All papers were scored on the basis of the JADAD index. RESULTS: The search returned 483 papers. The selection process restricted the sample to 59 papers concerning Risperidone, 37 concerning Olanzapine and 4 concerning Quetiapine (100 in total). Ten papers (7 concerning Risperidone and 3 concerning Olanzapine) had JADAD index above 2. Data suggest that further research would be of value concerning the use of risperidone in the treatment of refractory OCD, Pervasive Developmental disorder, stuttering and Tourette's syndrome, and the use of olanzapine for the treatment of refractory depression and borderline personality disorder. DISCUSSION: Data on the off-label usefulness of newer atypical antipsychotics are limited, but positive cues suggest that further research may provide with sufficient hard data to warrant the use of these agents in a broad spectrum of psychiatric disorders, either as monotherapy, or as an augmentation strategy.