Browsing by Author "Harvey B.H."
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- ItemCentral effects of the preservative, methylparaben. In vivo activation of cAMP-specific phosphodiesterase and reduction of cortical cAMP(1992) Harvey B.H.; Carstens M.E.; Taljaard J.J.F.The phenolic preservative, methylparaben (MPB), has in the past been demonstrated to harbour definite pharmacological effects. In an attempt to examine the possible central effects of MPB, notably on cyclic nucleotides and cyclic nucleotide phosphodiesterase (PDE; EC 3.1.4.17), rats were orally treated with the drug (0.4% in rat food) for 3 weeks with cortex extracts being used for the various determinations. Three isozymes were identified by DEAE-cellulose anion exchange chromatography, namely the calmodulin/calcium-stimulated form or PDE I (peak I), the cGMP-stimulated form or PDE II (peak II), and an independent form not affected by either calmodulin or cGMP also known as PDE IV (peak III). The presence of MPB induced a significant decrease in cortical cAMP, as well as strongly stimulating the activity of PDE IV (peak III). In addition, a small, yet significant, increase in cGMP levels was observed. Since no increase in cGMP hydrolysis was observed, we conclude that chronic ingestion of MPB induces a preference for cAMP hydrolysis, which was confirmed by the increase in PDE IV (peak III) activity. PDE IV is a membrane-bound, low K(m) PDE exhibiting high selectivity for cAMP hydrolysis. While there was an increase in cGMP, we failed to observe an increase in the activity of the cGMP-stimulated PDE (PDE II). These data are discussed with reference to the possible membrane effects of MPB allowing it to alter both the kinetic properties of PDE IV with the resultant effects on cAMP, as well as a means whereby it may activate guanyl cyclase and increase cGMP.
- ItemIsolation rearing-induced deficits in sensorimotor gating and social interaction in rats are related to cortico-striatal oxidative stress, and reversed by sub-chronic clozapine administration(2011) Moller M.; Du Preez J.L.; Emsley R.; Harvey B.H.Social isolation rearing (SIR) in rats induces behavioral and glutamatergic changes akin to schizophrenia. We studied the effects of 8 weeks SIR on cortico-striatal redox and social and cognitive behaviors in rats. SIR increased superoxide dismutase activity, decreased oxidized:reduced glutathione ratio and increased lipid peroxidation in both brain regions, and induced deficits in prepulse inhibition and social and self-directed interactive behaviors. Both behavioral and cortico-striatal redox disturbances were corrected by clozapine (5 mg/kg/day. × 11 days). Behavioral changes evoked by SIR are associated with cortico-striatal oxidative stress that is reversed by clozapine treatment, providing novel insight into the neurobiology and treatment of schizophrenia. © 2010 Elsevier B.V.
- ItemPhasic craving for carbohydrate observed with citalopram(1996) Bouwer C.D.; Harvey B.H.The serotonin selective reuptake inhibitors (SSRIs) have clinically and ancedotally been associated with nausea and weight loss as a side effect of their action. The tricyclic antidepressants have been linked to carbohydrate (CHO) craving and weight gain in patients with major depressive disorders. This side effect has been attributed to the strong anti-histaminergic actions of these agents and is recognized as a causal factor of non-compliance in a substantial percentage of patients. CHO craving is an important feature and complication of the treatment of depression and is often ignored. A total of 18 patients were treated with the SSRI citalopram in our mood disorder clinic. In eight cases there was a significant increase in CHO craving together with weight gain shortly after initiation of treatment. The craving for CHO took on a phasic presentation. These cases are presented, together with data on the change in mood and anxiety symptom rating scales. Our observations appear paradoxical, given that serotonin (5-HT) typically mediates a reduction in CHO intake and that citalopram displays potent and select 5-HT-enchancing actions. However, the receptor binding profile of citalopram may predict a risk for inducing this adverse event. These, together with serotonergic, dopaminergic, histaminergic and other possible mechanisms are discussed. A profound influence on patient acceptability was observed, suggesting that the impact on compliance needs to be considered.
- ItemSingle Photon Emission Computed Tomography (SPECT) in obsessive-compulsive disorder before and after treatment with inositol(2004) Carey P.D.; Warwick, James M.; Harvey B.H.; Stein D.J.; Seedat S.Inositol, a glucose isomer and second messenger precursor, regulates numerous cellular functions and has demonstrated efficacy in obsessive-compulsive disorder (OCD) through mechanisms that remain unclear. The effect of inositol treatment on brain function in OCD has not been studied to date. Fourteen OCD subjects underwent single photon emission computed tomography (SPECT) with Tc-99m HMPAO before and after 12 weeks of treatment with inositol. Whole brain voxel-wise SPM was used to assess differences in perfusion between responders and nonresponders before and after treatment as well as the effect of treatment for the group as a whole. There was 1) deactivation in OCD responders relative to nonresponders following treatment with inositol in the left superior temporal gyrus, middle frontal gyrus and precuneus, and the right paramedian post-central gyrus; 2) no significant regions of deactivation for the group as a whole posttreatment; and 3) a single cluster of higher perfusion in the left medial prefrontal region in responders compared to nonresponders at baseline. Significant reductions in the YBOCS and CGI - severity scores followed treatment. These data are only partly consistent with previous functional imaging work on OCD. They may support the idea that inositol effects a clinical response through alternate neuronal circuitry to the SSRIs and may complement animal work proposing an overlapping but distinct mechanism of action.
- ItemSocial isolation rearing in rats alters plasma tryptophan metabolism and is reversed by sub-chronic clozapine treatment(2012) Moller M.; Du Preez J.L.; Emsley R.; Harvey B.H.Schizophrenia is associated with increased oxidative stress, although the source of this redox disequilibrium requires further study. Altered tryptophan metabolism has been described in schizophrenia, possibly linked to inflammation and glutamate-directed excitotoxicity. Social isolation rearing (SIR) in rats induces various behavioural manifestations akin to schizophrenia, as well as altered frontal cortical glutamate N-methyl-d-aspartate (NMDA) receptor binding and increased oxidative stress, all reversed by antipsychotic treatment. Tryptophan is catabolized via the kynurenine pathway to kynurenine, 3-hydroxykynurenine, quinolinic acid (QA), kynurenic acid (KYNA), anthranilic acid and 3-hydroxyanthranilic acid (3-OHAA), ultimately contributing to neuronal integrity and redox balance in the brain. We studied tryptophan metabolism and neuroprotective-neurodegenerative balance in post-natal SIR rats, and its response to clozapine treatment. Male Sprague-Dawley (SD) rats (10 rats/group) were exposed to SIR or social rearing for 8 weeks, whereupon they received either sub-chronic vehicle or clozapine (5 mg/kg i.p) treatment. Plasma tryptophan metabolites were analysed by liquid-chromatography electrospray ionization tandem mass spectrometry. Plasma tryptophan, kynurenine, anthranilic acid, 3-OHAA and QA were significantly elevated in SIR vs. socially housed rats. KYNA and the neuroprotective ratio were significantly decreased. The latter implies a decrease in KYNA (neuroprotective) but an increase in QA (neurodegenerative) directed components of the pathway. Clozapine significantly reversed all the above alterations in SIR animals. Concluding, SIR in rats significantly disrupts tryptophan metabolism via the kynurenine pathway with increased risk for neurodegenerative changes in the brain. These changes are reversed by clozapine, emphasising the importance of these findings for the neurobiology and treatment of schizophrenia. © 2012 Elsevier Ltd. All rights reserved.
- ItemSuffer the children: The psychobiology of early adversity(2005) Stein D.J.; Harvey B.H.; Uys J.; Daniels W.[No abstract available]