Browsing by Author "Daniels W."
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- ItemBiochemical model for inflammation of the brain: The effect of iron and transferrin on monocytes and lipid peroxidation(2004) Van Rensburg S.J.; Van Zyl J.; Hon D.; Daniels W.; Hendricks J.; Potocnik F.; Erasmus R.Cerebral inflammation plays a role in diseases such as multiple sclerosis (MS), Alzheimer's disease (AD), and depression. Iron is involved in infection and inflammation through free radical production. Theoretically transferrin should prohibit iron from participating in oxidative reactions, but transferrin has also been found to promote free radical damage. We reported previously that isolation of transferrin from plasma by ion exchange column chromatography produced a broad pink protein band that subsequently separated on a gel filtration column into three proteins containing many metals. In this study some properties of the three proteins were studied in 20 volunteers. Protein 3 (identified as transferrin by nephelometry) contained the most iron while Protein 1 (called "toxiferrin") contained significantly less iron (p < 0.00001). Plasma from volunteers obtained under conditions of infection/inflammation with fever (n = 5) had a significantly increased toxiferrin to transferrin ratio compared to healthy volunteers (n = 15; p < 0.001). In vitro, Protein 2 and transferrin inhibited lipid peroxidation, while toxiferrin (possibly a protease degradation product of transferrin), enhanced lipid peroxidation. Also, toxiferrin (1 mg/mL) caused a significant increase in viability of monocytes as measured by the 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) reduction test, as well as the morphological transformation of monocytes to macrophages.
- ItemHoarding in obsessive-compulsive disorder: Clinical and genetic correlates(2005) Lochner C.; Kinnear C.J.; Hemmings, Sian M. J.; Seller C.; Niehaus D.J.H.; Knowles J.A.; Daniels W.; Moolman-Smook J.C.; Seedat S.; Stein D.J.Objective: Hoarding may be an important symptom dimension in obsessive-compulsive disorder (OCD). Hoarding in OCD has been associated with poor insight, poorer response to selective serotonin reuptake inhibitors than other OCD symptom dimensions, and a distinctive psychobiological profile. The clinical and genetic correlates of hoarding in OCD therefore deserve additional investigation. Method: Adult OCD patients (N = 315) underwent a comprehensive clinical assessment that included the Structured Clinical Interview for DSM-IV Axis I Disorders (Patient Edition) and for Diagnosis of Obsessive-Compulsive Spectrum Disorders. DNA extracted from venous blood (10-30 mL) in a Caucasian subset of the interviewed OCD patients (N = 204) and Caucasian controls (N = 169), including patients (N = 94) and controls (N = 138) of Afrikaner descent, was genotyped to investigate polymorphisms in genes involved in monoamine function and previously hypothesized to be relevant to OCD. Data were collected from 1998 through 2004. Results: OCD patients with hoarding made up 18.1% of the total sample. Compared with nonhoarding OCD, OCD with hoarding was associated with a number of comorbid Axis I disorders, obsessive-compulsive personality disorder, significantly higher OCD severity scores, and more functional impairment. In subjects of Afrikaner descent, the L/L genotype of the COMT Val158Met polymorphism was significantly more common in the OCD hoarding group, with a preponderance of low activity alleles, compared with nonhoarding patients and controls. Conclusions: These data are consistent with the hypothesis that hoarding represents a unique symptom subtype in OCD with a distinctive clinical and psychobiological profile. Further work is needed to determine the psychobiological mechanisms responsible for hoarding and to replicate the genetic findings noted here.
- ItemMaternal separation fails to render animals more susceptible to methamphetamine-induced conditioned place preference(2009) Faure J.; Stein D.J.; Daniels W.The maternal separation (MS) paradigm is an animal model that has been successfully used to study the long term effects of child abuse and neglect. Experiments showed that animals subjected to trauma and stress early in life display behavioural, endocrinological and growth factor abnormalities at a later stage in life, results that mirrored clinical conditions. It is apparent that adverse events early in life may affect the development and maturation of the brain negatively. The purpose of the present study was to investigate whether the abnormal brain development occurring in separated animals would also enhance the development of a preference for psychostimulant drug usage. Rats were subjected to maternal deprivation and further exposed to methamphetamine-induced conditioned place preference (CPP) which primarily measures drug reward (ventral striatum) learning and memory. Apomorphine-induced locomotor activity was also assessed to investigate the effects of methamphetamine on the dorsal (primarily locomotor activity) striatal dopaminergic system. We found that four consecutive injections of methamphetamine resulted in CPP behaviour 24 h after the 4th injection. A further four injections yielded similar CPP results and this effect lasted for at least 7 days until the third CPP assessment. These animals also had decreased ACTH and corticosterone secretions, but the prolactin levels were increased. Prior exposure to maternal separation did not have any effect on the CPP test. The ACTH and corticosterone secretions were also similarly reduced. However maternal separation decreased the release of prolactin and this reduction was not evident in the separated group that received methamphetamine. There was no significant difference in the apomorphine-induced locomotor activity of normally reared animals whether they received methamphetamine or saline. Interestingly there was a significant difference in locomotor activity between the two groups of animals that were subjected to maternal deprivation. The separated animals that received methamphetamine displayed markedly reduced locomotor activity upon apomorphine administration when compared to those that were treated with saline. Taken together, we conclude that maternal deprivation differentially influences dorsal and ventral striatal regions implicating dopaminergic mechanisms. © 2009 Springer Science+Business Media, LLC.
- ItemMind and muscle: The cognitive-affective neuroscience of exercise(2007) Stein D.J.; Collins M.; Daniels W.; Noakes T.D.; Zigmond M.There is growing basic-science interest in the mechanisms underpinning the positive effects of exercise on brain function and cognitive-affective performance. There is also increasing clinical evidence that exercise may prevent and treat various neuropsychiatric disorders. At the same time, there is growing awareness that athletic performance is mediated in crucial ways by central nervous system mechanisms. The relevant mechanisms in all these cases requires further exploration, but likely includes neurotrophic, neuroendocrine, and neurotransmitter systems, which in turn are crucial mediators of psychopathology and resilience. The hypothesis that Homo sapiens evolved as a specialist endurance runner provides an intriguing context against which to research the proximal mechanisms relevant to a cognitive-affective neuroscience of exercise.
- ItemPsychopharmacology of maternal separation anxiety in vervet monkeys.(2006) Marais L.; Daniels W.; Brand L.; Viljoen F.; Hugo C.; Stein D.J.Maternal separation in non-human primates has been proposed as a model of early adversity. The symptoms of separation anxiety were studied in vervet monkeys, during the weaning period, when psychotropic medications were administered. The control group received a normal diet and treatment groups received citalopram, reboxetine or lamotrigine in their food daily. Treatment was given for 7 weeks starting 1 month prior to weaning. Behavior was recorded twice weekly for 8 weeks, and was rated for anxiety and depression. Cerebrospinal fluid was collected at the beginning and end of the trial and analyzed for monoamines and metabolites using High Performance Liquid Chromatography. Citalopram pretreatment prevented the reduction of affiliation behavior and reduced stereotypies after weaning, and both citalopram and reboxetine abolished the increase in activity seen in control monkeys after weaning, but no statistically significant differences were found between groups. Citalopram pretreatment also significantly increased noradrenaline and 5-hydroxyindolacetic acid (5-HIAA) levels and reboxetine significantly decreased dopamine levels over time. The 5-HIAA levels of reboxetine and lamotrigine treated monkeys were significantly lower than that of the control group at the end of the trial. Although limited by a small sample size, this study demonstrates the possibility of investigating the psychopharmacology of early adversity in a non-human primate model.
- ItemSuffer the children: The psychobiology of early adversity(2005) Stein D.J.; Harvey B.H.; Uys J.; Daniels W.[No abstract available]