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Abstract: The effects of 1-methyl-4-phenylpyridinium (MPP+) has been extensively researched due to its selective toxicity to dopaminergic neurons. Mitochondrial dysfunction which is common in the etiology of Parkinson''s disease (PD), has been widely implicated in MPP+-induced toxicity. MPP+-induced mitochondrial dysfunction is believed to result in the generation of free radicals. This study was therefore performed to assess the effect of MPP+ on mitochondrial function and the ability of MPP+ to generate superoxide free radicals. Furthermore, we assessed the ability of the non-narcotic analgesics, acetaminophen and acetylsalicylic acid to prevent any diliterious effects of the potent neurotoxin, MPP+, on mitochondrial function and superoxide anion generation, in vivo. Acetylsalicylic acid and acetaminophen prevented the MPP+-induced inhibition of the electron transport chain and complex I activity. In addition, acetylsalicylic acid and acetaminophen significantly attenuated the MPP+-induced superoxide anion generation. Furthermore the results provide novel data explaining the ability of these agents to prevent MPP+-induced mitochondrial dysfunction and subsequent reactive oxygen species generation. While these findings suggest the usefulness of non-narcotic analgesics in neuroprotective therapy in neurodegenerative diseases, acetylsalicylic acid appears to be a potential candidate in prophylactic as well as in adjuvant therapy in Parkinson''s disease. [Copyright &y& Elsevier]

Oxidative damage of biological macromolecules is a hallmark of most neurodegenerative disorders such as Alzheimer, Parkinson and diffuse Lewy body diseases. Another important phenomenon involved in these disorders is the alteration of iron homeostasis, with an increase in iron levels. The present study investigated whether 6-hydroxymelatonin (6-OHM) can reduce Fe2+-induced lipid peroxidation and necrotic cell damage in the rat hippocampus in vivo. It was found that 6-OHM administration proved successful in reducing Fe2+-induced neurotoxicity in rat hippocampus. This study provides some evidence of the neuroprotective effects of 6-OHM.

The therapeutic success of L-3,4-dihydroxyphenylalanine (L-DOPA) treatment in Parkinson's disease (PD) patients remains controversial as many patients become tolerant requiring higher dosage regimens. However, the increase in dosage regimens results in the patients experiencing intolerable side effects. This study sought to investigate whether dopamine (DA) can chemically react with iron to form the potent neurotoxin 6-hydroxydopamine (6-OHDA). Furthermore, rats were treated with L-DOPA for a period of 7 and 28 days to determine whether L-DOPA treatment results in 6-OHDA formation in rat striatum. In addition, this study also investigates the complex interactions of L-DOPA with iron by performing in vitro and in vivo lipid peroxidation studies and the detection of endogenous 6-OHDA in iron-infused rats. In each study, melatonin was used to determine whether it could quench any free radical effects that may occur. The results of the present study show that DA chemically reacts with iron to form 6-OHDA. Moreover, L-DOPA treatment results in endogenous 6-OHDA formation in rat brain as well as enhances iron-induced lipid peroxidation both in vitro and in vivo in the rat striatum. The L-DOPA-induced increase in lipid peroxidation, in iron-infused rats, corresponds with an increase in levels of 6-OHDA in the rat striatum. The use of melatonin significantly decreases the L-DOPA-stimulated 6-OHDA formation in the rat striatum. The present study provides novel information on L-DOPA-induced neurotoxicity and suggests the concomitant use of an antioxidant with L-DOPA in order to enhance the life span of L-DOPA therapy.

AIDS-related encephalopathy, including AIDS dementia complex (ADC) and the opportunistic disease, herpes simplex encephalitis (HSE), are postulated to arise due to the release of neurotoxic products, such as quinolinic acid (QUIN), by activated microglial cells in the brain. QUIN causes a cascade of events to occur, which leads to the production of reactive oxygen species (ROS), these being ultimately responsible for oxidative neurotoxicity. The antiherpes antiviral aciclovir has been reported to protect against neuron loss in HSE, but the mechanism for this neuroprotection is unknown. Therefore, this study was conducted to investigate whether aciclovir has the ability to inhibit QUIN-induced lipid peroxidation in rat brain homogenates, after in-vitro and in-vivo exposure to QUIN and aciclovir. The thiobarbituric acid (TBA) assay was the method used to analyse lipid peroxidation. Rat brains were also examined histologically after in-vivo exposure to visually assess whether neuron loss was suppressed. The results show that aciclovir inhibits the QUIN-induced lipid peroxidation, in a dose-dependent manner. Furthermore, aciclovir reduced necrosis of hippocampal neurons and retained the characteristic morphology, integrity and arrangement of these cells. Thus, it appears that aciclovir has neuroprotective properties, which could possibly be useful in the treatment of AIDS-related encephalopathy.

Melatonin, a naturally occurring chemical mediator, although assigned a diverse range of functions, has attracted interest because of its ability to function as a free radical scavenger. Its major hepatic metabolite and photoproduct, 6-hydroxymelatonin (6-OHM), also shares this property. Since singlet oxygen and quinolinic acid (QUIN) are critically involved in the pathology of neurotoxicity, the objective of this study was to investigate the ability of 6-OHM to scavenge singlet oxygen and evaluate its ability to scavenge superoxide anions and reduce QUIN-induced neurotoxicity in the hippocampus in-vivo. The results show that 6-OHM is an efficient inhibitor of singlet oxygen formation as indicated by the rate constants and quantum yields reported for 6-OHM and zinc phthalocyanine (ZnPc), respectively. 6-OHM, appears to reduce QUIN-induced superoxide anion generation in the hippocampus, which provides some evidence of the neuroprotective effects of 6-OHM.

We previously showed that acetaminophen administration to rats increases forebrain serotonin levels as a result of the inhibition of liver tryptophan-2,3-dioxygenase (TDO). In this study we determined whether aspirin alone and in combination with acetaminophen could further influence brain serotonin as well as norepinephrine levels and if so whether the status of the liver TDO activity would be altered. The results show that acetaminophen alone increases brain serotonin as well as norepinephrine levels with a concomitant inhibition of liver TDO activity. In contrast, aspirin did not alter the levels of these monoamines but increased serotonin turnover in the brain while acetaminophen decreased the turnover. When combined with acetaminophen, aspirin overrides the reduced serotonin turnover induced by acetaminophen. This report demonstrates the potential of these agents to alter neurotransmitter levels in the brain.

The purpose of this paper is to characterize the apoptotic response of various subpopulations of human white blood cells after in vitro exposure to ionizing radiation using the modified neutral comet assay (MNCA). White blood cells, isolated from human whole blood, were fractionated into granulocytes and mononuclear cells which were further separated into B-cells, natural killer (NK) cells, and CD4(+) and CD8(+) T-cells. The separated fractions were exposed to low doses of X-rays and then MNCA was used to measure the apoptotic fraction (AF) at different time points in irradiated and unirradiated aliquots of sorted cultures. The spontaneous AF in unirradiated control cells was the most critical determinant of whether an apoptotic response could be detected in irradiated cells. When cultured in isolation granulocytes and B-cells had the highest background AF, with NK cells having the next highest. CD4(+) and CD8(+) T-cells had a low, stable, spontaneous AF which gave them the highest signal-to-noise ratio. Although B-cells demonstrated the highest radiation-induced apoptotic response to 1Gy of X-rays, CD8(+) T-cells were the most radiation-responsive lymphocytes due to their low spontaneous AF. By generating dose response curves for CD4(+) and CD8(+) T-cells, the sensitivity of the MNCA for detecting apoptosis in these two cell types was also examined.

A questionnaire survey of 1,603 secondary school students, aged 14-18 years, was conducted in Trinidad and Tobago in 1988. Prevalence of alcohol use was 84%, tobacco 35%, marijuana 8% and cocaine 2%. Alcohol was the substance most consistently used and students' first exposure to drinking alcohol was with family members. Transitions from primary to secondary schools and from junior to senior schools were associated with increased reporting of alcohol use. Significantly more Indo-Trinidadian than Afro-Trinidadian students reported using alcohol frequently. Conversely more Afro-Trinidadian students than Indo-Trinidadians reported using marijuana. The use of alcohol by students was positively correlated to its use by fathers and negatively with religious activities. The use of drugs among students appears to be a growing problem. There is a need for the implementation of culturally relevant educational prevention programmes in schools.

The dose in the build-up region for four different Cobalt-60 therapy units was measured. It was found that, for large collimator openings and relatively short SSDs, a new dose peak occurs at a depth very much smaller than 0.5 cm. The dose at this peak is a function of collimator openings and SSDs and, in some extreme case, could be 15% or more higher than the dose at the conventional peak dose of 0.5 cm. The new dose peak is probably due to electrons produced in the source capsule and the part of the collimator close to the source; it can be almost eliminated by a filter placed just below the collimator.