Review of Shifting the paradigm in community mental health: Towards empowerment and community.

Reviews the book, Shifting the paradigm in community mental health: Towards empowerment and community by Geoffrey Nelson, John Lord, and Joanna Ochocka (2001). This book, as it combines theory, practice, and research (a case study) about the processes of empowerment and integration of consumers of mental health care in a Canadian setting, delineates strategies and approaches that can be factors in fulfilling this important aim. Shifting the Paradigm in Community Mental Health is a welcome contribution to the literature on the implementation of consumer empowerment and involvement in mental health treatment and care. The authors offer an approach enabling the reader to see the dimensions for empowerment and community integration termed the empowerment-community integration paradigm. The book will be useful for a wide audience, including consumers, professionals, stakeholders, researchers, and policy makers, and should be in the libraries of all institutions, formal and informal, that deliver mental health care. The overall clarity of the writing and all the approaches will be very much appreciated by all those who work or receive services in mental health. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of Leakage in Simulations of Positive Pressure Ventilation

The fire service uses a number of tactics to reduce hazards for fire-fighters and civilians within a structure on fire. One offensive fire-fighting tactic that has potential for rapidly improving or degrading conditions within the structure is ventilating the structure. Positive pressure ventilation is a tactic in which a fan is used to push hot products of combustion out of a burning structure. While a recent body of work has been produced on the effects of positive pressure ventilation in a number of fire systems, there is still widespread uncertainty on how the tactic affects the fire environment. Computational tools will play an important role in exploring the impact of positive pressure ventilation in various fire scenarios. In many simulations of structure fires, the impact of leakage on the evolution of the fire is not addressed. We find in this study that ad hoc models of leakage have significant impact on the evolution of the fire. Several ad hoc leakage models are proposed and these are studied in terms of their impact of the fire. We show that one particular leakage geometry is able to best model leakage effects in a series of fire simulations that are compared to experiments. Simple, first-order analysis is used to understand how these leakage flows affect the predictions.     

Mitochondrial dysfunction in neurodegenerative diseases

A potential pivotal role for mitochondrial dysfunction in neurodegenerative diseases is gaining increasing acceptance. Mitochondrial dysfunction leads to a number of deleterious consequences including impaired calcium buffering, generation of free radicals, activation of the mitochondrial permeability transition and secondary excitotoxicity. Neurodegenerative diseases of widely disparate genetic etiologies may share mitochondrial dysfunction as a final common pathway. Recent studies using cybrid cell lines suggest that sporadic Alzheimer's disease is associated with a deficiency of cytochrome oxidase. Friedreich's ataxia is caused by an expanded GAA repeat resulting in dysfunction of frataxin, a nuclear encoded mitochondrial protein involved in mitochondrial iron transport. This results in increased mitochondrial iron and oxidative damage. Familial amyotrophic lateral sclerosis is associated with point mutations in superoxide dismutase, which may lead to increased generation of free radicals and thereby contribute to mitochondrial dysfunction. Huntington's disease (HD) is caused by an expanded CAG repeat in an unknown protein termed huntingtin. The means by which this leads to energy impairment is unclear, however studies in both HD patients and a transgenic mouse model show evidence of bioenergetic defects. Mitochondrial dysfunction leads to oxidative damage which is well documented in several neurodegenerative diseases. Therapeutic approaches include methods to buffer intracellular ATP and to scavenge free radicals.     

MPP+ induced substantia nigra degeneration is attenuated in nNOS knockout mice

Differential scanning calorimetry was used to characterize thermal events associated with freezing and melting of suspensions and extracts of Panagrolaimus davidi, an Antarctic nematode which can survive intracellular freezing. Nematode suspensions produced a single freezing exotherm with a shoulder on the peak representing the freezing of the nematodes. A shoulder on the peak of melting endotherms indicates the melting of the nematodes and of the water surrounding them. Exotherms were also detected from individual nematodes mounted in liquid paraffin. The freezing of nematodes was very rapid and in marked contrast to that of freezing-tolerant insects and vertebrates, which take hours or days to freeze. Eighty-two percent of the nematodes' body water froze. High levels of survival were obtained in nematodes exposed to temperatures down to -40 degrees C. No additional thermal events were observed after the freezing event and before the melting of samples cooled to -40 degrees C, indicating no changes in the proportion of body water frozen. Ice nucleating activity is present in nematode suspensions but not in supernatants from nematode extracts. No thermal hysteresis activity was detected in nematode extracts.     

LIQUID PHASE OXIDATION OF OCTANAL BY CUMENE HYDROPEROXIDE

Reactions that lead to fuel instability can be closely linked to the presence of active oxygen species. An increasing body of evidence links oxidation reactions of hydroperoxides to the instability observed in fuels. The active oxygen compounds present in fuels are alkyl and aromatic hydroperoxides. Cumene hydroperoxide represents a logical choice for an active oxygen compound that could be present in a middle distillate fuel. This paper reports on the reactions of cumene hydroperoxide with octanal in benzene solvent at 140°C for various time periods. The complete slate of products is presented along with a suggested mechanism to explain the observed products and the implications for fuel instability reactions.     

CHARACTERIZATION OF POLAR EXTRACTS FROM TWO PETROLEUM-DERIVED FUELS

Petroleum fuels of marginal stability have been used as a source of nitrogen-rich polar extracts. Polar compounds were isolated by mild acid extraction followed by silica gel adsorption. The extracts were characterized and identified by combined capillary column GC/MS. Both fuels were studied by two methods under accelerated storage conditions, bottle tests and oxygen overpressure. Bottle tests were conducted at 80°C for 14 days and the oxygen overpressure at both 65 and 43°C for 6 days and 4 weeks respectively. Filterable insolubles and adherent gum were measured for both methods. Peroxide numbers were determined by ASTM D3703-85 for both stressed and original fuel samples.     

Increased vulnerability to 3-nitropropionic acid in an animal model of Huntington's disease

There is substantial evidence for both metabolic dysfunction and oxidative damage in Huntington's disease (HD). In the present study, we used in vivo microdialysis to measure the conversion of 4-hydroxybenzoic acid to 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of hydroxyl radical production in a transgenic mouse model of HD, as well as in littermate controls. The conversion of 4-hydroxybenzoic acid to 3,4-DHBA was unchanged in the striatum of transgenic HD mice at baseline. Following administration of the mitochondrial toxin 3-nitropropionic acid (3-NP), there were significant increases in 3,4-DHBA generation in both control and transgenic HD mice, and the increases in the transgenic HD mice were significantly greater than those in controls. Furthermore, administration of 3-NP produced significantly larger striatal lesions in transgenic HD mice than in littermate controls. The present results show increased sensitivity to the mitochondrial toxin 3-NP in transgenic HD mice, which suggests metabolic dysfunction in this mouse model of HD.     

Determination of pindolol enantiomers in human plasma and urine by simple liquid-liquid extraction and high-performance liquid chromatography

Ethanol disrupts signal transduction mediated by a variety of G-protein coupled receptors. We examined the effects of ethanol on arachidonic acid release mediated by muscarinic acetylcholine receptors. Chinese hamster ovary (CHO) cells transfected with the different subtypes of human muscarinic receptors (M1 to M5) were incubated with [3H]arachidonic acid ([3H]AA) for 18 hr, washed, and exposed to the cholinergic agonist carbamylcholine for 15 min. Carbamylcholine induced [3H]AA release from CHO cells expressing M1, M3, or M5, but not M2 or M4, muscarinic receptors. Dose response curves revealed that carbamylcholine stimulated [3H]AA release by up to 12-fold with an ECo of approximately 0.4 microM; maximal responses were obtained with 10 microM carbamylcholine. Exposure of M1-, M3-, or M5-expressing cells to ethanol for 5 min before stimulating with carbamylcholine reduced [3H]AA release by 40 to 65%; 50% of the maximal inhibition was obtained with an ethanol concentration of 30 to 50 mM. Ethanol did not affect basal [3H]AA release measured in the absence of carbamylcholine. Dose response curves suggest that ethanol acts as a noncompetitive inhibitor of muscarinic receptor-induced [3H]AA release insofar as maximal [3H]AA release was depressed in the presence of ethanol with no apparent change in the EC50 for stimulation by carbamylcholine. Exposure of CHO cells to 38 mM ethanol for 48 hr increased [3H]AA release induced by carbamylcholine without affecting basal [3H]AA release or altering the EC50 for carbamylcholine. These results indicate that ethanol acutely inhibits muscarinic receptor signaling through the arachidonic acid pathway in a noncompetitive manner, but chronically enhances muscarinic signaling through the same pathway.     

The role of mitochondrial dysfunction and neuronal nitric oxide in animal models of neurodegenerative diseases

Excitotoxicity, mitochondrial dysfunction and free radical induced oxidative damage have been implicated in the pathogenesis of several different neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease. Much of the interest in the association of neurodegeneration with mitochondrial dysfunction and oxidative damage emerged from animal studies using mitochondrial toxins. Within mitochondria 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), acts to inhibit NADH-coenzyme Q reductase (complex I) of the electron transport chain. MPTP produces Parkinsonism in humans, primates, and mice. Similarly, lesions produced by the reversible inhibitor of succinate dehydrogenase (complex II), malonate, and the irreversible inhibitor, 3-nitropropionic acid (3-NP), closely resemble the histologic, neurochemical and clinical features of HD in both rats and non-human primates. The interruption of oxidative phosphorylation results in decreased levels of ATP. A consequence is partial neuronal depolarization and secondary activation of voltage-dependent NMDA receptors, which may result in excitotoxic neuronal cell death (secondary excitotoxicity). The increase in intracellular Ca2+ concentration leads to an activation of Ca2+ dependent enzymes, including the constitutive neuronal nitric oxide synthase (cnNOS) which produces NO.. NO. may react with the superoxide anion to from peroxynitrite. We show that systemic administration of 7-nitroindazole (7-NI), a relatively specific inhibitor of cnNOS in vivo. attenuates lesions produced by striatal malonate injections or systemic treatment with 3-NP or MPTP. Furthermore 7-NI attenuated increases in lactate production and hydroxyl radical and 3-nitrotyrosine generation in vivo, which may be a consequence of peroxynitrite formation. Our results suggest that neuronal nitric oxide synthase inhibitors may be useful in the treatment of neurologic diseases in which excitotoxic mechanisms play a role.