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J Child Adolesc Psychopharmacol. 2003;13 Suppl 1:S31-8.
Localized functional neurochemical marker abnormalities in dorsolateral prefrontal cortex in pediatric obsessive-compulsive disorder.

Russell A, Cortese B, Lorch E, Ivey J, Banerjee SP, Moore GJ, Rosenberg DR.

Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, USA.

BACKGROUND: Neurobiological abnormalities in the prefrontal cortex have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Although OCD commonly arises during childhood and adolescence, to our knowledge, no prior study has examined prefrontal cortex neurochemistry in pediatric patients with OCD. METHODS: A multislice spectroscopic imaging sequence with validated phantom replacement methodology was used to measure N-acetyl-aspartate (NAA), a putative neuronal marker; choline compounds (Cho); and creatine/phosphocreatine (Cr) in right and left dorsolateral prefrontal cortex (DLPFC) of 15 treatment-naive OCD patients, 8-15 years of age, and 15 case-matched healthy comparison subjects. RESULTS: A significant increase (21% higher) in NAA was observed in left but not right DLPFC in OCD patients versus control subjects. No significant differences in Cho or Cr were observed between groups in left or right DLPFC. CONCLUSIONS: These results provide new evidence of localized functional neurochemical marker alterations in left DLPFC in pediatric OCD. Increased left DLPFC NAA may represent neuronal hypertrophy or hyperplasia, glial hypoplasia, and/or abnormal pruning of neural brain elements in DLPFC.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12880498&dopt=Abstract [PubMed - in process]

Ann Clin Biochem. 2003 Jul;40(Pt 4):369-73.
Glutathione peroxidase activity in blood cells from aspirin-induced asthma patients.

Hassan AM.

Research Laboratory, University Hospital of South Manchester, Manchester, UK. afaf.hassammc.nhs.uk

Aspirin and other inhibitors of cyclo-oxygenase precipitate acute bronchospasm in about 10% of adult asthmatics. It has been assumed that cyclo-oxygenase is involved in the pathogenesis of bronchospasm, but the precise mechanism remains poorly understood. The oxygenation products of arachidonic acid include hydroperoxyeicosatetraenoic acid and cyclic endoperoxides. Glutathione peroxidase (GPX) reduces semi-stable hydroperoxides to less reactive alcohols and removes H(2)O(2) involved in inflammation. GPX could, therefore, modulate oxidation of arachidonic acid in the cyclo-oxygenase and lipoxygenase pathways, but the involvement of GPX in the pathogenesis of asthma has received little attention. We measured GPX activity in platelets, peripheral blood lymphocytes (PBL), red blood cells (RBC) and plasma from 13 patients with aspirin-induced asthma (AIA). Age- and sex-matched healthy individuals served as the comparison group. The patients had significantly higher GPX activity in platelets (P = 0.05) and tended to have high GPX activity (P = 0.08) in plasma but not in RBC or PBL. The results suggest that the increased GPX activity may be an adaptive advantage in AIA to protect against increased free radical production by inflammatory cells. That the higher GPX activity was not evident in all cell types studied may indicate a differential role played by them as effector cells in the pathogenesis of AIA.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12880537&dopt=Abstract [PubMed - in process]

Exp Parasitol. 2003 Mar-Apr;103(3-4):120-6.
Recombinant Plasmodium falciparum NADP-dependent isocitrate dehydrogenase is active and harbours a unique 26 amino acid tail.

Chan M, Sim TS.

Department of Microbiology, Medicine Faculty, National University of Singapore, Block MD4, 5 Science Drive 2, 117597 Singapore, Republic of Singapore.

During infection, Plasmodium spp. require reducing equivalents such as NADPH to support the function of specific enzymes in overcoming oxidative stress. The catalysis of isocitrate by the NADP-dependent isocitrate dehydrogenase of Plasmodium falciparum (pfICDH) generates NADPH and is thus crucial for the parasite's survival and pathogenecity. In this study, pfICDH was cloned from a clinical isolate of P. falciparum. This was facilitated by designing primers based on the P. falciparum genome sequence resource PlasmoDB. DNA sequence of the cloned gene revealed an ORF that encodes a protein of 468 aa. Furthermore, after expression in Esherichia coli BL21, enzyme assays of cell-free extracts confirmed the overexpression and function of pfICDH. Further, pfICDH purified by affinity chromatography retained its enzyme activity. Substitution of NADP for NAD, or the use of EDTA, in enzyme assays abolished pfICDH activity. ATP and chloroquine, as well as cupric and argentic ions, inhibited pfICDH activity. Phylogenetic analysis revealed high primary structure homology (45-97%) among genes coding for eukaryal NADP-dependent ICDH, and the occurrence of three subfamilies of ICDH genes. Interestingly, there were significant sequence dissimilarities between pfICDH and its mammalian or bacterial homologs, particularly at the N- and C-termini. Confirming the functionality of the cloned pfICDH, and asserting its distance from the human homolog by molecular definitions, are important prerequisites for promoting this gene as a drug target screen.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12880588&dopt=Abstract

Clin Nutr. 2003 Aug;22(4):407-13.
Modulating effect of glutamine on IL-1beta-induced cytokine production by human gut.

Coeffier M, Marion R, Ducrotte P, Dechelotte P.

Appareil Digestif Environnement et Nutrition (ADEN EA 3234) and Institut Federatif de Recherches Multidisciplinaires sur les peptides (IFR no23), CIC-INSERM-CHU, Rouen, France

Background & aims: Balance between pro-and anti-inflammatory mediators plays a key role in the pathogenesis and treatment of inflammatory bowel disease. Glutamine can modulate cytokine production by intestinal mucosa in healthy subjects, but studies in inflammatory states are still limited. The aim of this work was to evaluate the effects of glutamine on IL-1beta-induced cytokine production by human gut.METHODS: Duodenal biopsies from healthy volunteers were stimulated in vitro by IL-1beta in the presence of increasing glutamine concentrations. Cytokine production was assessed in culture media by ELISA and cytokine mRNA expression in biopsies by RT-PCR. Results, in pg/mg of tissue, (median [range]), were compared by non-parametric paired tests.RESULTS: IL-1beta stimulation increased IL-6 and IL-8, but did not affect IL-4 and IL-10 production. IL-8 and IL-6 production from stimulated biopsies significantly decreased with increasing glutamine concentration from 0.5 to 10mM, (2543 [828-3634] to 1499 [282-2617] for IL-8, 62 [22-117] to 24 [12-99] for IL-6, both P<0.05), whereas IL-10 production was increased (0.7 [0.2-1.6] to 1.2 [2.6-0.5],P<0.05). Glutamine also increased IL-10 mRNA level in biopsies (P<0.05). IL-4 production was not affected by glutamine.CONCLUSIONS: Glutamine was shown in human intestinal mucosa to reduce the production of the pro-inflammatory cytokines IL-6 and IL-8, and enhance the production of the anti-inflammatory cytokine, IL-10.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12880609&dopt=Abstract [PubMed - in process]

Behav Res Ther. 2003 Aug;41(8):863-78.
Psychometric validation of the Obsessive Beliefs Questionnaire and the Interpretation of Intrusions Inventory: Part I.

Obsessive Compulsive Cognitions Working Group.

This article reports on the validation of the Obsessive Beliefs Questionnaire (OBQ) and Interpretations of Intrusions Inventory (III) developed by the Obsessive Compulsive Cognitions Working Group (OCCWG) to assess the primary beliefs and appraisals considered critical to the pathogenesis of obsessions. A battery of questionnaires that assessed symptoms of anxiety, depression, obsessive-compulsive symptoms and worry was administered to 248 outpatients with a DSM-IV diagnosis of Obsessive-Compulsive Disorder (OCD), 105 non-obsessional anxious patients, 87 non-clinical adults from the community, and 291 undergraduate students. Tests of internal consistency and test-retest reliability indicated that the OBQ and III assessed stable aspects of OC-related thinking. Between-group differences and correlations with existing measures of OC symptoms indicated that the OBQ and III assess core cognitive features of obsessionality. However, the various subscales of the OBQ and III are highly correlated, and both measures evidenced low discriminant validity. The findings are discussed in terms of the relevance and specificity of cognitive constructs like responsibility, control and importance of thoughts, overestimated threat, tolerance of uncertainty and perfectionism for OCD.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12880642&dopt=Abstract [PubMed - in process]

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