5-fluorouracil metabolite patterns in viable and necrotic tumor areas of murine colon carcinoma determined by 19F NMR spectroscopy

High-resolution ¹⁹F NMR spectroscopy at 9.4 T was used to study the difference in the metabolite pattern of 5-fluorouracil (5-FU) between viable and necrotic tissues of C38 murine colon tumors grown in C57BI/6 mice. Studies were performed on perchloric acid extracts of these tumor fractions after 5-FU treatment. The ¹⁹F nuclear magnetic resonance spectra exhibited resonances representing 5-FU, the catabolites α-fluoro-β-ureidopropionic acid and α-fluoro-β-alanine, as well as several fluoronucleotide anabolites. The absolute concentrations of anabolites and catabolites and the anabolite-to-catabolite ratio were significantly lower in the necrotic fraction than in the viable tumor fraction 50 min after administration of 5-FU, whereas the absolute concentration of 5-FU was the same. Therefore, in 5-FU metabolism studies with NMR spectroscopy, it is important to consider the necrotic contribution to the tumor volume.     

Development and psychometric properties of the “Suicidality: Treatment Occurring in Paediatrics (STOP) Risk and Resilience Factors Scales” in adolescents

European Child & Adolescent Psychiatry - Suicidality in the child and adolescent population is a major public health concern. There is, however, a lack of developmentally sensitive valid and...     

Antibodies to infectious agents and the positive symptom dimension of subclinical psychosis: The TRAILS study

Infections have been suggested to play a role in the etiology of schizophrenia, but the evidence for this has been inconsistent. Schizophrenia patients have an increased risk of infections as a result of hospitalizations or life style factors. Therefore a study on early subclinical manifestations of psychosis in relation to virus infections is warranted. We examined whether serum antibodies against human Herpes viruses and Toxoplasma gondii were associated with subclinical symptoms of psychosis in adolescents. Data were collected as part of the TRacking Adolescents' Individual Lives Survey (TRAILS) cohort, a large prospective cohort of Dutch adolescents. A total of 1176 participants with an available Community Assessment of Psychic Experiences (CAPE) and an available blood sample were included in this analysis. Solid-enzyme immunoassay methods were used to measure the presence of immunoglobulin G (IgG) antibodies in serum to the Herpes virus family and to T. gondii. There was no significant association between serologic evidence of infection with human Herpes viruses or T. gondii and the risk of subclinical positive experience of psychosis. Subjects with a positive serological reaction to Epstein-Barr Virus (EBV) had higher scores on the positive dimension of psychosis measured by CAPE (b=0.03, P=0.02). This significant association was observed in males, but not in females. The current study suggests that there is no significant association between serological evidence of infection to human Herpes viruses and positive subclinical experience of psychosis, whereas there was an association between EBV infection and subclinical psychotic symptoms in boys.     

Why don’t young people volunteer to give blood? An investigation of the correlates of donation intentions among young nondonors

BACKGROUND: In the past decade, the number of blood donors has steadily declined in the Netherlands, and young adults are underrepresented among registered donors. An understanding of the correlates of donation intentions among nondonors could facilitate targeting psychological prerequisites of donation decisions in recruitment campaigns. STUDY DESIGN AND METHODS. A cross-sectional study with self-administered questionnaires based on an extension of the Theory of Planned Behavior (TPB; a social cognition model to study the determinants of volitional behavior) was conducted to assess potential cognitive determinants of willingness to donate blood in a student sample. A response rate of 50.5 percent yielded a sample of 311. RESULTS: Just over 7 percent of participants were registered blood donors but most (61.7%) had never seriously considered becoming donors. Self-efficacy (confidence in performing the behavior), attitude (the overall evaluation of the behavior), and personal moral norm (the perceived personal responsibility to perform the behavior) regarding blood donation were the most important correlates of the intention to become a blood donor. In total, 43 percent of the variance in the intentions toward blood donation could be explained by a TPB-based model. CONCLUSION: Among students, determinants of the intention to become a blood donor include self-efficacy, attitude, personal moral norm regarding blood donation, and subjective norm (perceived social support). Future research could establish whether campaigns targeting these psychological prerequisites would be more effective than current strategies.     

Role of Sonography and Magnetic Resonance Imaging in Detecting Deltoideal Acromial Enthesopathy

The acromial origin of the deltoid is a target structure of ankylosing spondylitis and related spondyloarthritis, which are often overlooked and underdiagnosed as causes of posterior shoulder pain. The objective of this article is to review the roles of sonography and magnetic resonance imaging in detecting deltoideal acromial enthesopathy and their importance for optimizing management in individuals with posterior shoulder pain. Adequate awareness of such enthesopathy as a potential manifestation of inflammatory rheumatic disorders is critical for early diagnosis of spondyloarthritis.     

trans‐resveratrol alone and hydroxystilbenes of rhubarb (Rheum rhaponticum L.) root reduce liver damage induced by chronic ethanol administration: a comparative study in mice

The hepatoprotective effects and pharmacokinetics of trans‐resveratrol and hydroxystilbenes of the garden rhubarb (Rheum rhaponticum L., R. rhaponticum) root ethanol extract were studied. Ethanol was administered to male BALB/c mice for 35 days in an inhalation chamber. During this time vehicle, trans‐resveratrol (20 mg/kg per day) or R. rhaponticum extract was intraperitoneally (i.p.) administered and mice were sacrificed for the collection of liver and blood. In an additional experiment, the level of parent compounds and metabolites was estimated in the blood after acute i.p. administration of trans‐resveratrol or R. rhaponticum extract. The levels of hydroxystilbenes, their metabolites and fatty acid oxy‐metabolites (oxylipins) were studied by LC‐tandem DAD‐MS/MS. Ethanol induced hepatotoxicity, as evidenced by histological changes and accumulation of oxylipins in the blood. Both trans‐resveratrol and R. rhaponticum extract reduced the extent of these changes. The pharmacokinetics of trans‐resveratrol was characterized by a rapid removal from the blood and metabolism to sulfates and glucuronides. After the administration of R. rhaponticum extract, in addition to trans‐resveratrol glucoside and its metabolites, several other hydroxystilbenes were found. Inhibition of oxidation of polyunsaturated fatty acids is proposed as a basis of the hepatoprotective effect of both trans‐resveratrol and R. rhaponticum extract. Copyright © 2008 John Wiley & Sons, Ltd.     

Dearterialization of the liver causes intrahepatic cholestasis due to reduced bile transporter expression

BACKGROUND: Bile duct injury after hepatic artery thrombosis (HAT) in liver transplantation is believed to be caused by ischemia predominantly. We aimed to define the involvement of bile secretory dysfunction in the pathogenesis of liver injury after HAT. METHODS: In a murine model, the main hepatic artery, the extrahepatic peribiliary plexus, or both arterial connections to the liver were interrupted (n=5 for each group). After 1, 14, or 28 days, hepatobiliary function was assessed by analysis of bile transporter expression, serum bile acids and bilirubin, and hepatic ATP content. In addition, cellular injury was assessed by light microscopy and biochemical markers. RESULTS: There were no signs of hepatobiliary dysfunction or injury in sham-operated animals or in mice with interruption of the hepatic artery or the extrahepatic peribiliary plexus alone. However, as early as 24 hr after complete dearterialization, bile transporter expression was significantly reduced and intrahepatic cholestasis started to progress the following weeks. Histologic studies at 28 days after complete dearterialization showed severe hepatobiliary injury. CONCLUSIONS: This study indicates that arterial blood supply is critical for normal bile secretion. Bile duct injury after complete arterial deprivation is preceded by a loss of bile secretory function and subsequent intrahepatic cholestasis.