bluuebunny/crossref_metadata_2025 huggingface dataset:
The Protective Role of l‐Carnitine against Neurotoxicity Evoked by Drug of Abuse, Methamphetamine, Could Be Related to Mitochondrial Dysfunction
Authors: VIRMANI ASHRAF , GAETANI FRANCO , IMAM SYED , BINIENDA ZBIGNIEW , ALI SYED
Published: July 2010

Abstract:There is growing evidence that suggests that brain injury after amphetamine and methamphetamine (METH) administration is due to an increase in free radical formation and mitochondrial damage, which leads to a failure of cellular energy metabolism followed by a secondary excitotoxicity. Neuronal degeneration caused by drugs of abuse is also associated with decreased ATP synthesis. Defective mitochondrial oxidative phosphorylation and metabolic compromise also play an important role in atherogenesis, in the pathogenesis of Alzheimer's disease, Parkinson's disease, diabetes, and aging. The energy deficits in the central nervous system can lead to the generation of reactive oxygen and nitrogen species as indicated by increased activity of the free radical scavenging enzymes like catalase and superoxide dismutase. The METH‐induced dopaminergic neurotoxicity may be mediated by the generation of peroxynitrite and can be protected by antioxidants selenium, melatonin, and selective nNOS inhibitor, 7‐nitroindazole. L‐Carnitine (LC) is well known to carry long‐chain fatty acyl groups into mitochondria for β‐oxidation. It also plays a protective role in 3‐nitropropioinc acid (3‐NPA)‐induced neurotoxicity as demonstratedin vitroandin vivo. LC has also been utilized in detoxification efforts in fatty acid‐related metabolic disorders.

In this study we have tested the hypothesis that enhancement of mitochondrial energy metabolism by LC could prevent the generation of peroxynitrite and free radicals produced by METH. Adult male C57BL/6N mice were divided into four groups. Group I served as control. Groups III and IV received LC (100 mg/kg, orally) for one week. Groups II and IV received 4 × 10 mg/kg METH i.p. at 2‐h intervals after one week of LC administration. LC treatment continued for one more week to groups III and IV. One week after METH administration, mice were sacrificed by decapitation, and striatum was dissected to measure the formation of 3‐nitrotyrosine (3‐NT) by HPLC/Coularry system. METH treatment produced significant formation of 3‐NT, a marker of peroxynitrite generation, in mice striatum.

The pre‐ and post‐treatment of mice with LC significantly attenuated the production of 3‐NT in the striatum resulting from METH treatment. The protective effects by the compound LC in this study could be related to the prevention of the possible metabolic compromise by METH and the resulting energy deficits that lead to the generation of reactive oxygen and nitrogen species. These data further confirm our hypothesis that METH‐induced neurotoxicity is mediated by the production of peroxynitrite, and LC may reduce the peroxynitrite levels and protect against the underlying mechanism of METH toxicity, which are models for several neurodegenerative disorders like Parkinson's disease.
Ontogeny of Neurokinin‐1 Receptor Mediation of Methamphetamine Neurotoxicity in the Striatum of the Mouse Brain
Authors: YU JING , ALLISON SIMONE , IBRAHIM DINA , CADET JEAN LUD , ANGULO JESUS A.
Published: July 2010

Abstract:We studied the role of the peptide substance P, signaling through the neurokinin‐1 (NK‐1) receptor, on methamphetamine‐induced loss of dopamine transporter sites, a well‐documented marker of toxicity in the striatum of the mouse brain, because this peptide is under dynamic regulation by the neurotransmitter dopamine. Methamphetamine is a psychostimulant that induces dopamine overflow from dopamine terminals of the striatum. Mice were given four injections of methamphetamine (7.5 mg/kg of body weight) at two‐hour intervals and were sacrificed three days after the treatment. Dopamine transporter levels in the striatum were assessed by receptor autoradiography with [125I]RTI‐121. Exposure to methamphetamine resulted in significant loss of dopamine transporters in the caudate‐putamen. This loss was prevented by preexposure (30 min before the first injection of methamphetamine) of the neurokinin‐1 receptor antagonist L‐733,060. The inactive enantiomer of L‐733,060 (L‐733,061) failed to protect dopamine transporter sites from methamphetamine, suggesting specificity for the neurokinin‐1 receptor. Moreover, the protective effect of L‐733,060 was observed in mice that were 10 weeks of age or older (dopamine transporter sites in mice six and eight weeks old were not protected from methamphetamine by the neurokinin‐1 receptor antagonist). The results demonstrate that the deleterious effect of methamphetamine on dopamine transporter sites of the striatum is mediated via the neurokinin‐1 receptor. The involvement of the NK‐1 receptor appears after the eighth week of postnatal life, suggesting that the link between dopamine transporters and the neurokinin‐1 receptor becomes functional at approximately the time when the mouse reaches reproductive age.
From Receptor to Effector: Insulin Signal Transduction in Skeletal Muscle from Type II Diabetic Patients
Authors: ZIERATH JULEEN R. , WALLBERG‐HENRIKSSON HARRIET
Published: July 2010

Abstract: Insulin resistance is a characteristic feature of type II diabetes mellitus and obesity. Although defects in glucose homeostasis have been recognized for decades, the molecular mechanisms accounting for impaired whole body glucose uptake are still not fully understood. Skeletal muscle constitutes the largest insulin‐sensitive organ in humans; thus, insulin resistance in this tissue will have a major impact on whole body glucose homeostasis. Intense efforts are under way to define the molecular mechanisms that regulate glucose metabolism and gene expression in insulin‐sensitive tissues. Knowledge of the human genome sequence, used in concert with gene and/or protein array technology, will provide a powerful means to facilitate efforts in revealing molecular targets that regulate glucose homeostasis in type II diabetes mellitus. This will offer quicker ways forward to identifying gene expression profiles in insulin‐sensitive and insulin‐resistant human tissue. This review will present our current understanding of potential defects in insulin signal transduction pathways, with an emphasis on mechanisms regulating glucose transport in skeletal muscle from people with type II diabetes mellitus. Elucidation of the pathways involved in the regulation of glucose homeostasis will offer insight into the causation of insulin resistance and type II diabetes mellitus. Furthermore, this will identify biochemical entry points for drug intervention to improve glucose homeostasis.
Skeletal Muscle Triglycerides
Authors: KELLEY DAVID E.
Published: July 2010

Abstract: The composition and biochemistry of skeletal muscle are altered in obesity and type 2 diabetes mellitus (DM) as compared to nonobese individuals. In health, skeletal muscle has a clear capacity to utilize both carbohydrate and lipid fuels and to transition between these in response to hormonal, chiefly insulin, and substrate signals. This metabolic flexibility is key for the major role that skeletal muscle can have in overall fuel balance. In obesity and type 2 DM, there is a loss of this plasticity and, instead, there is metabolic inflexibility. Rates of lipid oxidation do not suppress effectively in response to insulin, but neither do rates of lipid oxidation effectively increase during the transition to fasting conditions. An important morphological characteristic of skeletal muscle in obesity and type 2 DM is an increased content of triglyceride. The accretion of fat within muscle tissues appears to strongly correlate with insulin resistance and may not be simply a passive process, paralleling fat storage in other tissues. Instead, and of particular metabolic interest, a concept is emerging that biochemical characteristics of skeletal muscle in obese individuals dispose to fat accumulation in muscle. An effort to modify skeletal muscle in individuals with obesity and type 2 DM so that the capacity for fat oxidation and metabolic flexibility is improved should be among the goals of treatment for these disorders.
Treatment of Hypertriglyceridemia with Fenofibrate, Fatty Acid Composition of Plasma and LDL, and Their Relations to Parameters of Lipoperoxidation of LDL
Authors: ZEMAN M. , ŽÁK A. , VECKA M. , TVRZICKÁ E. , ROMANIV S. , KONÁRKOVÁ M.
Published: July 2010

Abstract: The purpose of this study was to determine oxidation and oxidability of VLDL and LDL in connection with changes in their composition and content of FA in LDL after treatment with fenofibrate in patients with HTG.
A Novel Mammalian Homologue of a Bacterial Citrate‐Metabolizing Enzyme
Authors: SÖDERBERG CHARLOTTE , LIND PETER
Published: July 2010

Abstract: Mammals metabolize citrate to acetyl‐CoA and oxaloacetate via the enzyme, ATP:citrate lyase. Bacteria lack this enzyme, but have the ability to cleave citrate in the form of citryl‐CoA in an analogous manner using a structurally distinct enzyme. We have identified a novel mammalian gene that shows significant amino acid sequence homology to the bacterial CitE gene product that is responsible for cleavage of citryl‐CoA. We propose that this gene encodes an enzyme that catalyzes cleavage of substrates related to CoA esters of citrate or an analogous intermediary metabolite. The product of this novel gene may represent a component of an unknown metabolic pathway in mammals.
Increased Abdominal Obesity in Subjects with a Mutation in the 5‐HT2AReceptor Gene Promoter
Authors: ROSMOND ROLAND , BOUCHARD CLAUDE , BJÖRNTORP PER
Published: July 2010

Abstract:In the present study, we examined the potential impact of the 5‐HT2A−1438G/A promoter polymorphism on obesity and estimates of insulin, glucose, and lipid metabolism as well as circulating hormones, including salivary cortisol, in 284 unrelated Swedish men born in 1944. The subjects were genotyped by using PCR amplification of the promoter region of the gene for 5‐HT2Afollowed by digestion with the restriction enzymeMspI. The frequencies were 0.39 for allele −1438A and 0.61 for allele −1438G. Homozygotes for the −1438G allele had, in comparison with −1438A/A subjects, higher body mass index (BMI), waist‐to‐hip ratio (WHR), and abdominal sagittal diameter. Moreover, cortisol escape from 0.25 mg dexamethasone suppression was found in subjects with the −1438A/G genotype. Serum leptin, fasting insulin and glucose, as well as serum lipids were not different across the −1438G/A genotype groups. From these results, we suggest the possibility that an abnormal production rate of the 5‐HT2Agene product might lead to the development of abdominal obesity. The pathophysiology could involve stress factors that destabilize the serotonin‐hypothalamic‐pituitary‐adrenal systems in those with genetic vulnerability in the serotonin receptor gene.
Toward a Topological Model of the NCX1 Exchanger
Authors: NICOLL DEBORA A. , OTTOLIA MICHELA , PHILIPSON KENNETH D.
Published: July 2010

Abstract: The Na+/Ca2+ exchanger (NCX1) catalyzes the counter‐transport of sodium and calcium ions. Understanding how this is accomplished requires knowledge of the structure of NCX1 and identifying amino acid residues involved in binding and transport of ions. The amino acid sequence of NCX1 has been known for more than a decade. Based on hydropathy analysis, NCX1 was modeled to contain 12 transmembrane segments. In this model, the α‐repeat regions, which are the result of a gene duplication event (see below), are oriented on the extracellular face of NCX1. In the years since NCX1 was sequenced, a considerable amount of effort has gone into testing the initial 12‐transmembrane‐segment model. Immunologic and protein‐processing studies as well as functional analyses of mutants have determined the location of the amino and carboxy termini and several intracellular regions. However, disulfide bond analysis and cysteine mutagenesis coupled with accessibility studies indicate that the structure of NCX1 diverges from a simple membrane protein consisting only of transmembrane α‐helical segments. These recent data support a model containing 9 transmembrane α‐helices with the α‐repeat regions forming nonhelical re‐entrant loops. A bacterial protein containing a pair of α‐repeat regions but of unknown function has also been shown to have oppositely oriented α‐repeats.
Binding of the Retinal Rod Na+/Ca2+‐K+ Exchanger to the cGMP‐Gated Channel Indicates Local Ca2+‐Signaling in Vertebrate Photoreceptors
Authors: BAUER PAUL J.
Published: July 2010

Abstract: Ca2+ ions enter the outer segment of rod or cone photoreceptors exclusively through the cGMP‐gated channel and are extruded by the Na+/Ca2+‐K+ exchanger. Recent evidence indicates that in the plasma membrane, the Na+/Ca2+‐K+ exchanger is associated with the cGMP‐gated channel. In this contribution, the possible physiologic significance of this protein complex is considered. Based on recent experimental evidence, the possibility of a direct functional interaction between the cGMP‐gated channel and the Na+/Ca2+‐K+ exchanger is discussed. Furthermore, a quantitative estimation of the cytoplasmic Ca2+ diffusion at the cGMP‐gated channel indicates that Ca2+ diffusion is largely confined to the complex of the cGMP‐gated channel and the associated Na+/Ca2+‐K+ exchanger molecules.
Immunohistochemical Detection of the Sodium‐Calcium Exchanger in Rat Hippocampus Cultures Using Subtype‐Specific Antibodies
Authors: THURNEYSEN T. , NICOLL D. A. , PHILIPSON K. D. , PORZIG H.
Published: July 2010

Abstract: All of the known Na+/Ca2+ exchanger subtypes, NCX1‐3, are expressed in the brain, albeit with marked regional differences. On the mRNA level, overall expression seems most prominent for NCX2, intermediate for NCX1, and, except for a few regions, low for NCX3. Using three subtype‐specific antibodies, we have now studied the cellular expression of the NCX subtypes in rat hippocampus cultures by immunohistochemical techniques. Our results provide evidence for a highly cell‐specific expression pattern of NCX subtypes and show surprisingly little colocalization. NCX1 and NCX3 are both primarily expressed in neuronal cells. While NCX1 is found in the large majority of neurons, NCX3 expression was restricted to a small minority of cells. By contrast, NCX2 was almost exclusively present in glial cells. The NCX2 antibody, a IgM, stained glial cell membranes as well as an intermediate fibrillar system. In spite of extensive screening, the nature of this fiber system has not yet been identified.
Is Na/Ca Exchange during Ischemia and Reperfusion Beneficial or Detrimental?
Authors: MURPHY ELIZABETH , CROSS HEATHER R. , STEENBERGEN CHARLES
Published: July 2010

Abstract: Cytosolic calcium increases to approximately 3 μM after 15 min of global ischemia. Manipulations that attenuate this increase in cytosolic Ca2+ reduce myocyte death and dysfunction. The increase in cytosolic Ca2+ during ischemia is dependent on an increase in intracellular Na+, suggesting a role for Na/Ca exchange. Typical ischemic values for ionized intra‐ and extracellular Na+, Ca2+, and membrane potential are consistent with the Na/Ca exchanger operating near equilibrium during ischemia. Studies were undertaken using hearts from mice that overexpress the Na/Ca exchanger to determine if Na/Ca exchanger overexpression enhances or reduces ischemic injury. These studies suggest that overexpression of the Na/Ca exchanger enhances injury in males, but females are protected by a gender‐related mechanism.
Role of the Na/Ca Exchanger in Arrhythmias in Compensated Hypertrophy
Authors: SIPIDO KARIN R. , VOLDERS PAUL G. A. , SCHOENMAKERS MARIEKE , MARIEKE DE GROOT S. H. , VERDONCK FONS , VOS MARC A.
Published: July 2010

Abstract: Sudden, presumably arrhythmic, death is common in heart failure patients. Although total mortality is highest in end‐stage failure, the fraction of sudden death in total mortality is higher in the early stages. In each of these stages various, not necessarily identical, ionic mechanisms may contribute to arrhythmogenesis. Dogs with chronic complete atrioventricular block (6‐8 weeks) have an increased risk for arrhythmias and sudden death and have compensated biventricular hypertrophy. In this animal model, Ca2+ release from the sarcoplasmic reticulum (SR) is not reduced. For low frequencies of stimulation, the SR Ca2+ content is increased, related to a higher activity of the Na/Ca exchanger. Spontaneous Ca2+ release induces inward Na/Ca exchange current, which can lead to delayed afterdepolarizations (DADs) triggering a new action potential. Such arrhythmogenic DADs and ectopic beats also can be observed in vivo during monophasic action potential recording. They appear after pacing protocols, and/or administration of ouabain, which result in contractile potentiation, suggestive of a enhanced sarcoplasmic reticulum Ca2+ content. Other arrhythmogenic mechanisms related to increased dispersion of repolarization also can be identified in vivo. Downregulation of delayed K+ currents is an important factor in prolongation of action potentials. In conclusion, in this animal model of compensated hypertrophy, Ca2+ handling is different from end‐stage heart failure. It is possible that arrhythmogenic mechanisms related to a higher Ca2+ load contribute to the high incidence of sudden death in stages of compensated hypertrophy before overt heart failure. However, more than one ionic remodeling process is likely to be present, and different cellular mechanisms of arrhythmias can coexist.
The Molecular Architecture of Calcium Microdomains in Rat Cardiomyocytes
Authors: SCRIVEN DAVID R. L. , KLIMEK AGNIESZKA , LEE KELLY L. , MOORE EDWIN D. W.
Published: July 2010

Abstract:We have used standard indirect immunofluorescence techniques in combination with wide‐field microscopy and image deconvolution to assess the distribution of proteins implicated in excitation‐contraction coupling and Ca2+homeostasis in adult rat cardiomyocytes. We begin by discussing our earlier results and summarizing what is known about the molecular architecture of this species to provide a rationale for the work presented here. The previous results showed that the dyads contain Ca2+channels and ryanodine receptors, but few Na+channels or Na+/Ca2+exchangers. The latter proteins were not colocalized elsewhere on the membrane, and we have now found that they appear to be minimally associated with caveolin‐3. None of the molecules examined are distributed uniformly in the membranes in which they are located but are organized into discrete clusters attached to the underlying cytoskeleton, an arrangement that, at the level of light microscopy, does not appear to be affected by the enzymatic dissociation used to study single cells. Analysis of how the clusters are organized and distributed throughout the volume of the cell suggests that there may be differences in excitation‐contraction coupling between the cell surface and the interior.
Pharmacology of Na+/Ca2+Exchanger
Authors: KIMURA JUNKO , WATANABE YASUHIDE , LI LIBING , WATANO TOMOKAZU
Published: July 2010

Abstract:KB‐R7943 inhibits the Na+/Ca2+exchanger in an independent manner or in a manner dependent on the direction of the current. This effect may be due to the experimental protocols bawed on the competition between the drug and external substrate ions. Some antiarrhythmic drugs inhibit NCX. A new column of NCX was added in Sicilian Gambit.
The Genome in Its Ecological Context
Authors: Gilbert Scott F.
Published: July 2010

Abstract:Epigenesis concerns the interactions through which the inherited potentials of the genome become actualized into an adult organism. In addition to epigenetic interactions occurring within the developing embryo, there are also critical epigenetic interactions occurring between the embryo and its environment. These interactions can determine the sex of the embryo, increase its fitness, or even be involved in the formation of particular organs. This essay will outline the history of environmental concerns in developmental biology and provide some reasons for the decline and resurgence of these ideas, and it will then focus on two areas that have recently gained much attention: predator‐induced polyphenisms and developmental symbioses. Research in these two areas of interspecies cooperation in morphogenesis has profound implications for what we consider to be normal development and how we proceed to study it. Studies of predator‐induced polyphenism have shown that soluble factors from predators can change the development of prey in specific ways. Prey has evolved mechanisms to sense compounds released from their predators and to use these chemical cues to change their development in ways that prevent predation. New techniques in molecular biology, especially polymerase chain reaction and microarray analysis, have shown that symbioses between embryos and bacteria are widespread and that animals may use bacterial cues to complete their development.
Genes and Mechanisms in the Amygdala Involved in the Formation of Fear Memory
Authors: PAPE HANS‐CHRISTIAN , STORK OLIVER
Published: July 2010

Abstract: With a combined molecular, electrophysiological, and behavioral approach we have sought to correlate conditioned fear behavior with electrophysiological activities in the lateral amygdala and hippocampal formation in mice and rats and to determine the potential contribution of effector genes that are expressed in the basolateral amygdaloid complex during the late phase of pavlovian fear conditioning. Our data indicate that resonant/oscillatory electrical activity in projection neurons of the lateral amygdala provide an important cellular element of coherent theta activity in amygdalohippocampal pathways, which may represent a nondiscriminating neural correlate of conditioned fear. Correlated activity seems to contribute to the formation of synaptic plasticity in these networks, such as input‐specific long‐term depression of thalamoamygdaloid signals and consolidation of long‐term potentiation in the dentate gyrus. Moreover, associative fear conditioning results in selective gene expression in the basolateral amygdaloid complex, involving molecular factors of structural reorganization and signal transduction, particularly GABA function, supporting the view that the amygdala is a site of neural plasticity and information storage during formation of fear memory.
Role of the Basolateral Amygdala in Memory Consolidation
Authors: McINTYRE CHRISTA K. , POWER ANN E. , ROOZENDAAL BENNO , McGAUGH JAMES L.
Published: July 2010

Abstract:Memories of emotionally arousing events tend to be more vivid and to persist longer than do memories of neutral or trivial events. Moreover, memories of emotionally influenced information may endure after a single experience. Recent findings strongly suggest that the influence of emotional arousal on memory consolidation is mediated by the release of adrenal stress hormones (epinephrine and glucocorticoids) and neurotransmitters that converge in modulating the noradrenergic system within the amygdala. Considerable evidence also indicates that amygdala activation influences memory by regulating consolidation in other brain regions. The findings suggest further that this memory‐modulatory system may be involved in the formation of traumatic memories and posttraumatic stress disorder in human subjects.
The Amygdala, Panic Disorder, and Cardiovascular Responses
Authors: SHEKHAR ANANTHA , SAJDYK TAMMY J. , GEHLERT DONALD R. , RAINNIE DONALD G.
Published: July 2010

Abstract: The amygdala is implicated in a number of emotional responses including conditioned fear and anxiety, and it appears to regulate the behavioral and autonomic responses associated with such emotional responses. The basolateral nucleus of the amygdala (BLA) is under tonic GABAergic inhibition, and acutely blocking this inhibition results in increased anxiety‐like behavior, conditioned avoidance, and sympathetically mediated cardiovascular activation. By contrast, activation of the BLA with the stress‐related neuropeptide corticotropin‐releasing factor results in anxiety‐like behavior, but not cardiovascular activation. Furthermore, repeated activation of this region with subthreshold GABA blockade or corticotropin‐releasing factor‐mediated excitation (priming) results in a chronic anxiety‐like state, with susceptibility to panic‐like arousal following intravenous lactate infusions. The chronic anxiety state appears to result from a loss of basal inhibitory drive in the BLA as a result of NMDA‐dependent synaptic plasticity involving cyclic AMP and calcium calmodulin kinase II (CAM KII)‐mediated changes. The lactate‐induced panic‐like response appears to involve angiotensin‐II mediated activation of the BLA. These results suggest that the BLA has a significant role in regulating anxiety, autonomic responses, and the development of anxiety disorders.
Role of the Amygdala in Decision‐Making
Authors: BECHARA ANTOINE , DAMASIO HANNA , DAMASIO ANTONIO R.
Published: July 2010

Abstract: The somatic marker hypothesis proposes that both the amygdala and the orbitofrontal cortex are parts of a neural circuit critical for judgment and decision‐making. Although both structures couple exteroceptive sensory information with interoceptive information concerning somatic/emotional states, they do so at different levels, thus making different contributions to the process. We define ‘primary inducers’ as stimuli that unconditionally, or through learning (e.g., conditioning and semantic knowledge), can (perceptually or subliminally) produce states that are pleasurable or aversive. Encountering a fear object (e.g., a snake), a stimulus predictive of a snake, or semantic information such as winning or losing a large sum of money are all examples of primary inducers. ‘Secondary inducers’ are entities generated by the recall of a personal or hypothetical emotional event or perceiving a primary inducer that generates ‘thoughts’ and ‘memories’ about the inducer, all of which, when they are brought to memory, elicit a somatic state. The episodic memory of encountering a snake, losing a large sum of money, imagining the gain of a large sum of money, or hearing or looking at primary inducers that bring to memory ‘thoughts’ pertaining to an emotional event are all examples of secondary inducers. We present evidence in support of the hypothesis that the amygdala is a critical substrate in the neural system necessary for triggering somatic states from primary inducers. The ventromedial cortex is a critical substrate in the neural system necessary for the triggering of somatic states from secondary inducers. The amygdala system is a priori a necessary step for the normal development of the orbitofrontal system for triggering somatic states from secondary inducers. However, once this orbitofrontal system is developed, the induction of somatic states by secondary inducers via the orbitofrontal system is less dependent on the amygdala system. Perhaps the amygdala is equivalent to the hippocampus with regard to emotions, that is, necessary for acquiring new emotional attributes (anterograde emotions), but not for retrieving old emotional attributes (retrograde emotions). Given the numerous lesion and functional neuroimaging studies illustrating the involvement of the amygdala in complex cognitive and behavioral functions, including ‘social cognition,’ we suggest that this involvement is a manifestation of a more fundamental function mediated by the amygdala, which is to couple stimuli/entities with their emotional attributes, that is, the processing of somatic states from primary inducers.
Assessment of Sex Offenders
Authors: SERIN RALPH C. , MAILLOUX DONNA L.
Published: July 2010

Abstract: Notwithstanding significant progress in the areas of risk appraisal and treatment of sex offenders, the contention is that further advancements could be realized through attention to research on non‐sex offenders. Specifically, it is proposed that sex offenders share many characteristics of non‐sex offenders and research with these populations should be integrated, not discrete. In particular, work in the area of multi‐method offender assessment regarding criminogenic need is highlighted to suggest common treatment targets for sex offenders and non‐sex offenders. As well, recent research in terms of treatment readiness is described and contrasted with the constructs of denial and minimization. Measurement strategies for cognitive schemas in use with violent offenders are also presented in order to expand the repertoire of approaches clinicians might consider as part of an assessment protocol. Further, performance‐based measures of empathy and relapse prevention are described and compared with self‐reports in terms of program participation and social desirability. Finally, a brief discussion of change scores and their application to post‐treatment risk appraisal is provided, as is the requirement for a systematic decision model to inform post‐treatment supervision.
Asking What Before We Ask Why: Taxonomy, Etiology, and Rape
Authors: BAKER KATHARINE K.
Published: July 2010

Abstract: This article presents a spectrum of sexual coersion. By looking at the social meaning of the different acts of coercion along the spectrum, the author suggests that most acts of sexual coercion can be classified as either rape (a sexual act with intent to do harm to the victim) or sex (a sexual act engaged in without any intent to harm the victim). Ironically, though, the author suggests that the most and least egregious acts of sexual aggression, that is, the acts we most readily identify as rape and the acts we are most reluctant to label rape are the ones that most easily evade explanation as either rape or sex.
Sexual Aggression: Mad, Bad, and Mad
Authors: SCHOPP ROBERT F.
Published: July 2010

Abstract:Legal institutions in the Western liberal tradition ordinarily rely primarily on the criminal justice system to address conduct by some individuals that deliberately harms other individuals. The mental health system provides an alternative institutional structure through which societies can address such harmful behavior. Those who deliberately engage in conduct that causes harm to others are traditionally addressed through either the criminal justice or mental health systems on the basis of their being categorized as either ‘bad or mad.’ This paper examines some of the relevant reasons for categorizing sexual aggression as bad or mad. It emphasizes the significance of such categorization for the broader set of legal institutions of coercive social control and for the manner in which we respond to persons within those institutions.
Overview of Rehabilitative Efforts in Understanding and Managing Sexually Coercive Behaviors
Authors: SCHWARTZ BARBARA K.
Published: July 2010

Abstract: In reviewing approaches to rehabilitative efforts in understanding and managing sexually coercive behaviors within the past two decades, one is struck by the development of two totally divergent paths. In 1971, there were a few civil commitment programs operated by mental health departments—most notably were the Sexual Psychopath Program at Western State Hospital in Fort Steilacoom, Washington, and the Massachusetts Treatment Center for Sexually Dangerous Persons. There were a few programs in prisons started by therapists who were interested in this population but given little recognition and even fewer resources. Additionally there were a handful of community‐based programs including the J.J. Peters Institute in Philadelphia and PASO (Positive Approaches to Sex Offenders) in Albuquerque, New Mexico. Today there are thousands of specialized sexual offender treatment programs treating sexual abusers of every age, gender, ethnicity, and with a wide range of comorbid conditions. They are treated in the community, prisons, mental hospitals, residential facilities, and private practices. There is an international organization, a specialized research journal, and a specialized branch of the Department of Justice, the Center for Sex Offender Management. This chapter will provide an overview of the developments in the field, primarily covering the last 25 years. It will look at the evolution of theoretical approaches, the development of specialized approaches for subpopulations, significant landmarks, and possible future trends.
PET Studies on the Function of Dopamine in Health and Parkinson's Disease
Authors: BROOKS DAVID J.
Published: July 2010

Abstract: Positron emission tomography (PET) can detect the presence of striatal, pallidal, midbrain, and cortical dopamine terminal dysfunction in vivo in Parkinson's disease (PD). In addition, dopamine release during motor tasks can be assessed as reflected by changes in receptor availability to PET ligands. Furthermore, the functional effects of focal dopamine replacement via implantation of fetal cells or glia‐derived neurotrophic factor (GDNF) infusion into putamen can be monitored. In this review, the insight that PET has given us concerning the role of dopamine in motor control is presented, and the functional substrates underlying PD symptomatologies are discussed.
Postnatal Developmental Programmed Cell Death in Dopamine Neurons
Authors: BURKE ROBERT E.
Published: July 2010

Abstract: The prenatal development of dopamine (DA) neurons of the substantia nigra (SN) is characterized by their birth, specification, and migration to their final positions. Their postnatal development is characterized by the establishment of contact and interactions between the SN and other neural nuclei, particularly the striatal target, by extension of axons, terminal differentiation, and synapse formation. In this postnatal context there is a natural cell death event, which is apoptotic in nature and biphasic in time course, with an initial peak on postnatal day (PND) 2, and a second on PND14. By PND20 the event has largely subsided. This natural cell death event is regulated in vivo by interaction with striatal target: it is augmented by axon‐sparing target lesion, DA terminal destruction, and medial forebrain bundle axotomy. This target dependence is present largely within only the first two postnatal weeks. The striatal target‐derived neurotrophic factor(s) that regulate this death event are unknown. We have shown, in a postnatal primary culture model of mesencephalic DA neurons, that glia‐derived neurotrophic factor (GDNF) is unique in its ability to support their viability by suppressing apoptosis. We have also recently found that intrastriatal injection of GDNF in vivo suppresses apoptosis, and injection of neutralizing antibodies augments it. Thus, GDNF is a leading candidate for a striatum‐derived neurotrophic factor for DA neurons during development.
Mitochondria, Oxidative Damage, and Inflammation in Parkinson's Disease
Authors: BEAL M. FLINT
Published: July 2010

Abstract:The pathogenesis of Parkinson's disease (PD) remains obscure, but there is increasing evidence that impairment of mitochondrial function, oxidative damage, and inflammation are contributing factors. The present paper reviews the experimental and clinical evidence implicating these processes in PD. There is substantial evidence that there is a deficiency of complex I activity of the mitochondrial electron transport chain in PD. There is also evidence for increased numbers of activated microglia in both PD postmortem tissue as well as in animal models of PD. Impaired mitochondrial function and activated microglia may both contribute to oxidative damage in PD. A number of therapies targeting inflammation and mitochondrial dysfunction are efficacious in the MPTP model of PD. Of these, coenzyme Q10appears to be particularly promising based on the results of a recent phase 2 clinical trial in which it significantly slowed the progression of PD.
Cellular Models to Study Dopaminergic Injury Responses
Authors: COLLIER TIMOTHY J. , STEECE‐COLLIER KATHY , McGUIRE SUSAN , SORTWELL CARYL E.
Published: July 2010

Abstract:The study of immature midbrain dopamine (DA) neurons and dopaminergic cell lines in culture provides an opportunity to analyze mechanisms of cell death and avenues of potential intervention relevant to Parkinson's disease (PD) in a controlled environment. Use of cell culture models has provided evidence for different sets of intracellular changes associated with DA neuron death following exposure to the neurotoxins 6‐hydroxydopamine and MPP+, supporting roles for oxidative stress and impaired energy metabolism as significant factors endangering these cells. Interference with death of cultured DA neurons has provided an initial test system that has yielded all the identified neurotrophic factors for DA neurons. More recent work suggests that combinations of molecules secreted by myelinating glial cells and their precursors provide even greater neuroprotection for DA neurons. Most recently, culture systems have been used to implicate microglial activation in DA neuron injury, providing impetus to the investigation of antiinflammatory agents as potential therapeutics for PD. Thus, cell culture models provide an important bidirectional link between mechanistic studies and clinically relevant observations.
The Role of Glial Reaction and Inflammation in Parkinson's Disease
Authors: HIRSCH E. C. , BREIDERT T. , ROUSSELET E. , HUNOT S. , HARTMANN A. , MICHEL P. P.
Published: July 2010

Abstract:The glial reaction is generally considered to be a consequence of neuronal death in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. In Parkinson's disease, postmortem examination reveals a loss of dopaminergic neurons in the substantia nigra associated with a massive astrogliosis and the presence of activated microglial cells. Recent evidence suggests that the disease may progress even when the initial cause of neuronal degeneration has disappeared, suggesting that toxic substances released by the glial cells may be involved in the propagation and perpetuation of neuronal degeneration. Glial cells can release deleterious compounds such as proinflammatory cytokines (TNF‐α, Il‐1β, IFN‐γ), which may act by stimulating nitric oxide production in glial cells, or which may exert a more direct deleterious effect on dopaminergic neurons by activating receptors that contain intracytoplasmic death domains involved in apoptosis. In line with this possibility, an activation of proteases such as caspase‐3 and caspase‐8, which are known effectors of apoptosis, has been reported in Parkinson's disease. Yet, caspase inhibitors or invalidation of TNF‐α receptors does not protect dopaminergic neurons against degeneration in experimental models of the disease, suggesting that manipulation of a single signaling pathway may not be sufficient to protect dopaminergic neurons. In contrast, the antiinflammatory drugs pioglitazone, a PPAR‐γ agonist, and the tetracycline derivative minocycline have been shown to reduce glial activation and protect the substantia nigra in an animal model of the disease. Inhibition of the glial reaction and the inflammatory processes may thus represent a therapeutic target to reduce neuronal degeneration in Parkinson's disease.
Neuroprotection Trek—The Next Generation
Authors: ANDREWS RUSSELL J.
Published: July 2010

Abstract: Animal trials of many pharmacological neuroprotective agents have been quite successful, whereas trials in humans have been uniformly disappointing. A major difference between laboratory research in animals and clinical research in humans is the amount and/or quality of data obtained. The goal of this presentation is to argue that when clinical studies consist of more valid, objective data—that is, as our measurement capabilities in clinical research become as robust as they are in laboratory research—we are likely to gain new insights into both (1) injury to the nervous system and (2) neuroprotective treatment strategies. Technological advances (in data acquisition and analysis)—often novel even in the laboratory—will be the “scale” that will enable progress in measurement. As examples of such technological advances, two projects initiated at NASA Ames Research Center are cited. The NASA Smart Probe Project, with the goal of combining multiple microsensors and neural networks for real‐time tissue identification (e.g., for tumor detection), has recently moved into the clinical realm, with a prototype being used to diagnose breast cancer in women “on the spot”. The NASA Nanoelectrode Array Project has fabricated nanoscale devices that can simultaneously monitor electrical activity and neurotransmitter concentrations, while providing electrical stimulation focally and precisely (and potentially in a closed‐loop fashion based on the input from the nanosensors). The large amounts of data that such techniques can acquire and analyze—separated spatially and temporally throughout the nervous system, if necessary—will provide insights not only into neuroprotective strategies, but also into the workings of the nervous system itself.
Evaluation of the Genotoxicity of Chitosan Nanoparticles for Use in Food Packaging Films
Authors: De Lima Renata , Feitosa Leandro , Pereira Anderson do Espírito Santo , De Moura Márcia Regina , Aouada Fauze Ahmad , Mattoso Luiz Henrique Capparelli , Fraceto Leonardo Fernandes
Published: July 2010

Abstract:  The use of nanoparticles in food packaging has been proposed on the basis that it could improve protection of foods by, for example, reducing permeation of gases, minimizing odor loss, and increasing mechanical strength and thermal stability. Consequently, the impacts of such nanoparticles on organisms and on the environment need to be investigated to ensure their safe use. In an earlier study, Moura and others (2008a) described the effect of addition of chitosan (CS) and poly(methacrylic acid) (PMAA) nanoparticles on the mechanical properties, water vapor, and oxygen permeability of hydroxypropyl methylcellulose films used in food packaging. Here, the genotoxicity of different polymeric CS/PMAA nanoparticles (size 60, 82, and 111 nm) was evaluated at different concentration levels, using the Allium cepa chromosome damage test as well as cytogenetic tests employing human lymphocyte cultures. Test substrates were exposed to solutions containing nanoparticles at polymer mass concentrations of 1.8, 18, and 180 mg/L. Results showed no evidence of DNA damage caused by the nanoparticles (no significant numerical or structural changes were observed), however the 82 and 111 nm nanoparticles reduced mitotic index values at the highest concentration tested (180 mg/L), indicating that the nanoparticles were toxic to the cells used at this concentration. In the case of the 60 nm CS/PMAA nanoparticles, no significant changes in the mitotic index were observed at the concentration levels tested, indicating that these particles were not toxic. The techniques used show promising potential for application in tests of nanoparticle safety envisaging the future use of these materials in food packaging.
Development of a Sandwich Enzyme‐Linked Immunosorbent Assay (ELISA) for Detection of Buckwheat Residues in Food
Authors: Panda Rakhi , Taylor Steve L. , Goodman Richard E.
Published: July 2010

Abstract:  Buckwheat is a pseudocereal (an eudicot with seed qualities and uses similar to those of monocot cereals, family Poaceae) that is consumed in some Asian countries as a staple, and in some western countries as a health food. Allergic reactions to buckwheat are common in some countries. The objective was to develop a specific and sensitive sandwich enzyme‐linked immunosorbent assay (ELISA) to detect traces of buckwheat that might inadvertently contaminate other foods in order to assure accurate labeling and consumer protection. Buckwheat‐specific antibodies produced in 3 species of animals were tested for specificity and titer by direct ELISA and immunoblot. A sandwich ELISA was developed utilizing pooled rabbit antibuckwheat sera to capture buckwheat proteins and pooled goat antibuckwheat sera, followed by enzyme‐labeled rabbit antigoat immunoglobulin G (IgG), to detect bound buckwheat proteins. The lower limit of quantification (LOQ) of the sandwich ELISA was 2 parts per million (ppm) of buckwheat in the presence of complex food matrices. The ELISA is highly specific with no cross‐reactivity to any of 80 food ingredients and matrices tested. Validation studies conducted with buckwheat processed into noodles and muffins showed greater than 90% and 60% recovery, respectively. The percent recovery of buckwheat from noodles was similar to that achieved with a commercial buckwheat ELISA kit (ELISA Systems Pty. Ltd., Windsor, Queensland, Australia) at high buckwheat concentrations. However, the sensitivity of this ELISA was greater than the commercial ELISA. This newly developed ELISA is sufficiently specific and sensitive to detect buckwheat residues in processed foods to protect buckwheat‐allergic subjects from potential harm.

Practical Application:  Buckwheat is becoming a common food ingredient in a number of processed foods due to potentially beneficial nutritional properties, without the celiac disease inducing glutenin proteins of wheat and related cereals. However, buckwheat causes allergy in some individuals and must be labeled and tested accurately to protect those with allergy to buckwheat. We describe the development of a new test assay to help food producers ensure that buckwheat is not present in foods that are not intended to contain buckwheat.
Chlorogenic Acid UVA–UVB Photostability
Authors: Rivelli Diogo P. , Filho Carlos A. H. , Almeida Rebeca L. , Ropke Cristina D. , Sawada Tânia C. H. , Barros Silvia B. M.
Published: July 2010

Chlorogenic acid is a natural potent antioxidant. It can be used in cosmetics formulations, but for this purpose its photochemical stability should be determined to ensure that the compound will not be degraded after UV radiation exposure. To evaluate this possibility, the concentration of a chlorogenic acid solution was determined by HPLC before and after UVA and UVB irradiation. The results indicate that chlorogenic acid is not degraded under UVA or UVB irradiation.
Enhancement of Storage Capacity and Conversion Efficiency of Photoelectrochemical Cells: Effect of Dyes Adsorbed on Carbon Nano Tubes
Authors: Mondal Anindita , Basu Ruma , Das Sukhen , Nandy Papiya
Published: July 2010

We report here our studies on photoelectrochemical (PEC) cells where two commonly used photosensitive dyes, thionine and Rose Bengal were used as photosensitizers for conversion of light energy to electrical energy. The performance of the cells increased radically in presence of oxidized multiwalled carbon nano tubes (OMWCNTs) as reflected by the values of conversion efficiency (∼3.69%) and open circuit voltage (∼548.9 mV). To understand the role of OMWCNTs in enhancing the performance of the cells, the spectral study of dye–OMWCNT mixed systems were performed. The absorption spectra indicated more absorption of incident photons in presence of OMWCNT, whereas the infrared spectra suggested that the basic structure of dyes remained unaltered. The spectral studies implied that the dye molecules got adsorbed on OMWCNTs side walls causing efficient absorption of the incident light quanta. Moreover, insertion of planar lipid membrane (PLM) separating the two chambers of PEC cell could effectively counteract the recombination of photodissociated charges and thereby caused better storage capacity of the PEC cells with further increase in efficiency.