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Animal Research (animal + research)
Selected AbstractsAnimal Research: Reporting In Vivo Experiments: The ARRIVE guidelinesEXPERIMENTAL PHYSIOLOGY, Issue 8 2010Article first published online: 9 JUL 2010 No abstract is available for this article. [source] The ARRIVE guidelines, a welcome improvement to standards for reporting animal researchTHE JOURNAL OF GENE MEDICINE, Issue 7 2010Olivier Danos Abstract Here we introduce the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, produced by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), which are published in this issue of the journal with our endorsement, and will be incorporated into our Instructions to Authors. Copyright © 2010 John Wiley & Sons, Ltd. [source] Animal Research: Reporting In Vivo Experiments: The ARRIVE guidelinesTHE JOURNAL OF PHYSIOLOGY, Issue 14 2010Article first published online: 16 JUL 2010 No abstract is available for this article. [source] Hippocampal structure and the action of cholinomimetic drugsDRUG DEVELOPMENT RESEARCH, Issue 3 2002John G. Csernansky Abstract Cholinomimetic drugs have become the clinical standard for the treatment of patients with dementia of the Alzheimer type (DAT). However, uncertainty remains as to the proportion of patients that respond to such drugs, and how one might predict the capacity for response before treatment is begun. The thesis of the present review is that the neuroanatomical integrity of the hippocampus determines, at least in part, the capacity of DAT patients to respond to cholinomimetic drugs. Neuroimaging studies suggest that volume losses and other neuroanatomical deformities of the hippocampus are common in patients with even mild DAT. Moreover, more severe neuroanatomical deformities of the hippocampus are associated with more severe dementia symptoms and more rapid clinical decline. Animal research, including studies of cholinergic antagonists, glutamatergic antagonists, hippocampal lesions, and animals with mutant amyloid precursor protein genes, demonstrate that behavioral abnormalities similar to those found in DAT patients, especially those related to memory, are associated with hippocampal pathology. Cholinomimetic drugs, in particular, the cholinesterase inhibitors, have been shown to reverse some but not all of these behavioral abnormalities. More research is needed in DAT patients to determine whether an analysis of hippocampal structure or function can reliably predict the outcome of treatment with cholinomimetic drugs. Further work in animals is also needed to determine the limitations of cholinomimetic drugs for reversing various types of cognitive deficits, and to develop and test other pharmacological strategies for the treatment of DAT. Drug Dev. Res. 56:531,540, 2002. © 2002 Wiley-Liss, Inc. [source] Initial, habitual and compulsive alcohol use is characterized by a shift of cue processing from ventral to dorsal striatumADDICTION, Issue 10 2010Sabine Vollstädt-Klein ABSTRACT Aims During the development of drug addiction, initial hedonic effects decrease when substance use becomes habitual and ultimately compulsive. Animal research suggests that these changes are represented by a transition from prefrontal cortical control to subcortical striatal control and within the striatum from ventral to dorsal domains of the striatum, but only limited evidence exists in humans. In this study we address this hypothesis in the context of alcohol dependence. Design, setting and participants Non-abstinent heavy social drinkers (n = 21, 5.0 ± 1.5 drinks/day, 13 of them were alcohol-dependent according to DSM-IV) and light social drinkers (n = 10, 0.4 ± 0.4 drinks/day) were examined. Measurements We used a cue-reactivity functional magnetic resonance imaging (fMRI) design during which pictures of alcoholic beverages and neutral control stimuli were presented. Findings In the dorsal striatum heavy drinkers showed significant higher activations compared to light drinkers, whereas light social drinkers showed higher cue-induced fMRI activations in the ventral striatum and in prefrontal areas compared to heavy social drinkers [region of interest analyses, P < 0.05 false discovery rate (FDR)-corrected]. Correspondingly, ventral striatal activation in heavy drinkers correlated negatively with obsessive-compulsive craving, and furthermore we found a positive association between cue-induced activation in the dorsal striatum and obsessive-compulsive craving in all participants. Conclusions In line with our hypothesis we found higher cue-induced activation of the ventral striatum in social compared to heavy drinkers, and higher dorsal striatal activation in heavy drinkers. Increased prefrontal activation may indicate that social drinkers activate cortical control when viewing alcohol cues, which may prevent the development of heavy drinking or alcohol dependence. Our results suggest differentiating treatment research depending on whether alcohol use is hedonic or compulsive. [source] GENETIC STUDY: H2 haplotype at chromosome 17q21.31 protects against childhood sexual abuse-associated risk for alcohol consumption and dependenceADDICTION BIOLOGY, Issue 1 2010Elliot C. Nelson ABSTRACT Animal research supports a central role for corticotropin-releasing factor (CRF) in actions of ethanol on brain function. An examination of alcohol consumption in adolescents reported a significant genotype × environment (G × E) interaction involving rs1876831, a corticotropin-releasing hormone receptor 1 (CRHR1) polymorphism, and negative events. CRHR1 and at least four other genes are located at 17q21.31 in an extremely large block of high linkage disequilibrium resulting from a local chromosomal inversion; the minor allele of rs1876831 is contained within the H2 haplotype. Here, we examine whether G × E interactions involving this haplotype and childhood sexual abuse (CSA) are associated with risk for alcohol consumption and dependence in Australian participants (n = 1128 respondents from 476 families) of the Nicotine Addiction Genetics project. Telephone interviews provided data on DSM-IV alcohol dependence diagnosis and CSA and enabled calculation of lifetime alcohol consumption factor score (ACFS) from four indices of alcohol consumption. Individuals reporting a history of CSA had significantly higher ACFS and increased risk for alcohol dependence. A significant G × E interaction was found for ACFS involving the H2 haplotype and CSA (P < 0.017). A similar G × E interaction was associated with protective effects against alcohol dependence risk (odds ratio 0.42; 95% confidence interval 0.20,0.89). For each outcome, no significant CSA-associated risk was observed in H2 haplotype carriers. These findings support conducting further investigation of the H2 haplotype to determine the gene(s) responsible. Our results also suggest that severe early trauma may prove to be an important clinical covariate in the treatment of alcohol dependence. [source] Animal research: the debate continuesJOURNAL OF INTERNAL MEDICINE, Issue 6 2007D. Weatherall No abstract is available for this article. [source] Calcium and Exercise Affect the Growing SkeletonNUTRITION REVIEWS, Issue 11 2005Jo M. Welch PhD Adequate dietary calcium and bone-stimulating exercise during growth are known to affect skeletal development, but the combined effects of dietary calcium and osteogenic exercise have received scant attention. Animal research has showed a compensatory effect of impact loading on calcium-deprived bones, while various human studies have suggested compensatory, additive, or possibly synergistic effects in certain skeletal locations. Current evidence suggests that the best strategy for strong bones by the end of childhood may be either high-impact exercise with a moderate or greater calcium intake or a combination of moderate-impact exercise and adequate calcium during growth. [source] The Future of Zoos: A New Model for Cultural InstitutionsCURATOR THE MUSEUM JOURNAL, Issue 1 2007John Fraser World-class zoos have invested substantially in species conservation and animal research as part of their involvement in wildlife conservation. However, zoo exhibit interpretation, policy development, and strategic planning are yet to be organized around a well-developed agenda with a clear set of conservation objectives. As museums increasingly redefine their role in society to speak about alternative futures for living with nature, zoos have the potential to become much more focused cultural change agents, potentially crafting a new vision for how society can live in a productive relationship with the world's remaining biodiversity. This article argues for an activist approach in which institutions with living collections would take on unique conservation tasks including scientifically grounded promotion of conservation values. [source] Gastrointestinal motility and the brain-gut axisDIGESTIVE ENDOSCOPY, Issue 2 2003TADASHI ISHIGUCHI The role of the brain-gut axis in gastrointestinal motility is discussed according to the specific organs of the gastrointestinal tract. Not only clinical studies but basic animal research are reviewed. Although the mechanism of functional gut disorders remains to be clarified, recent data suggest that there is evidence that the brain-gut axis has significant effects on gastrointestinal motility. The major role of endoscopy in the diagnosis of functional gastrointestinal disorders is to exclude organic gastrointestinal disorders. In the esophagus, the lower esophageal sphincter and a gamma-aminobutyric acid B mechanism are considered to play important roles in gastroesophageal reflux disease. In the stomach, corticotropin-releasing factor, neuropeptide Y and other substances might be involved in the pathogenesis of non-ulcer dyspepsia. In the small intestine, corticotropin-releasing factor, gamma-aminobutyric acid B and other substances are considered to modulate intestinal transit via central mechanisms. In the colon, it is known that psychiatric factors are related to the onset and clinical course of irritable bowel syndrome. Serotonin, corticotropin-releasing factor, gamma-aminobutyric acid, orphanin FQ and neuropeptide Y have been reported as putative neurotransmitters. More efforts in basic science studies and animal and human studies of physiology of the gastointestinal tract are still required. These efforts will elucidate further mechanisms to clarify the etiology of motility disorders and encourage the investigation of new therapies in this field. [source] The Influence of Gonadal Hormones on Neuronal Excitability, Seizures, and Epilepsy in the FemaleEPILEPSIA, Issue 9 2006Helen E. Scharfman Summary:, It is clear from both clinical observations of women, and research in laboratory animals, that gonadal hormones exert a profound influence on neuronal excitability, seizures, and epilepsy. These studies have led to a focus on two of the primary ovarian steroid hormones, estrogen and progesterone, to clarify how gonadal hormones influence seizures in women with epilepsy. The prevailing view is that estrogen is proconvulsant, whereas progesterone is anticonvulsant. However, estrogen and progesterone may not be the only reproductive hormones to consider in evaluating excitability, seizures, or epilepsy in the female. It seems unlikely that estrogen and progesterone would exert single, uniform actions given our current understanding of their complex pharmacological and physiological relationships. Their modulatory effects are likely to depend on endocrine state, relative concentration, metabolism, and many other factors. Despite the challenges these issues raise to future research, some recent advances have helped clarify past confusion in the literature. In addition, testable hypotheses have developed for complex clinical problems such as "catamenial epilepsy." Clinical and animal research, designed with the relevant endocrinological and neurobiological issues in mind, will help advance this field in the future. [source] Caloric restriction for longevity: II,The systematic neglect of behavioural and psychological outcomes in animal researchEUROPEAN EATING DISORDERS REVIEW, Issue 6 2004Kelly M. Vitousek Abstract Research on caloric restriction for longevity (CRL) has generated hundreds of articles on the physiology of food deprivation, yet almost no data on consequences in other domains. The first paper in this series outlined the generally positive physical effects of CRL; the second analyses the meagre and sometimes disturbing record of research on behaviour, cognition and affect. The available evidence suggests that nutrient-dense CRL in animals,just like nutrient-poor semi-starvation in people,is associated with a number of adverse effects. Changes include abnormal food-related behaviour, heightened aggression and diminished sexual activity. Studies of learning and memory in underfed rodents yield inconsistent findings; no information is available on cognitive effects in primates. To date, the CRL field has ignored other variables that are crucial to the human case and known to be disrupted by chronic hunger, including sociability, curiosity and emotionality. Promotion of CRL for people is irresponsible in the absence of more reassuring data on the full range of expected outcomes. Eating disorder specialists should be contributing to scientific and public discussions of this increasingly prominent paradigm. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Caloric restriction for longevity: I. Paradigm, protocols and physiological findings in animal researchEUROPEAN EATING DISORDERS REVIEW, Issue 5 2004Kelly M. Vitousek Abstract The initial article in this series reviews basic findings in the field of caloric restriction for longevity (CRL). To eating disorder specialists, the data are disconcerting. The chronic dieting and subnormal weight we endeavour to prevent and treat in humans appear highly beneficial when imposed on animals. In the laboratory, organisms from nematodes to monkeys thrive when forced to undereat, as long as they receive sufficient micronutrients. The most remarkable results are obtained through the most extreme measures: mice, for example, do best if limited to a third of expected caloric intake, beginning soon after weaning and continuing throughout adulthood. Deprivation can be achieved through an ,anorexic' protocol of steady underconsumption or a ,bulimic' pattern in which periods of fasting alternate with bouts of binge eating. The benefits of such regimens include delayed senescence, postponement and/or attenuation of age-related disease and dramatic increases in average and maximum lifespan. Although some biological functions are impaired (including growth, reproduction and perhaps resistance to certain stressors), the cost/benefit ratio clearly favours CRL when calculated on the basis of physical outcomes in late age. Advocacy of comparable regimens for people, however, is ill-considered. Enthusiasm for CRL can be sustained only by detaching deprivation from the context of daily life, ignoring psychological effects, and dismissing data on human semi-starvation and eating disorders. The experiences of participants in Biosphere 2 and individuals with anorexia nervosa suggest that the price of CRL is unacceptably high when a wider range of outcome variables is examined. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association. [source] REVIEW: Ethanol consumption: how should we measure it?ADDICTION BIOLOGY, Issue 2 2010Achieving consilience between human, animal phenotypes ABSTRACT There is only modest overlap in the most common alcohol consumption phenotypes measured in animal studies and those typically studied in humans. To address this issue, we identified a number of alcohol consumption phenotypes of importance to the field that have potential for consilience between human and animal models. These phenotypes can be broken down into three categories: (1) abstinence/the decision to drink or abstain; (2) the actual amount of alcohol consumed; and (3) heavy drinking. A number of suggestions for human and animal researchers are made in order to address these phenotypes and enhance consilience. Laboratory studies of the decision to drink or to abstain are needed in both human and animal research. In human laboratory studies, heavy or binge drinking that meets cut-offs used in epidemiological and clinical studies should be reported. Greater attention to patterns of drinking over time is needed in both animal and human studies. Individual differences pertaining to all consumption phenotypes should be addressed in animal research. Lastly, improved biomarkers need to be developed in future research for use with both humans and animals. Greater precision in estimating blood alcohol levels in the field, together with consistent measurement of breath/blood alcohol levels in human laboratory and animal studies, provides one means of achieving greater consilience of alcohol consumption phenotypes. [source] ARRIVE: new guidelines for reporting animal researchEXPERIMENTAL PHYSIOLOGY, Issue 8 2010Gordon B. Drummond No abstract is available for this article. [source] Genetic and Environmental Influences on Ethanol Consumption: Perspectives From Preclinical ResearchALCOHOLISM, Issue 6 2010Ricardo M. Pautassi Background:, Alcohol use disorders (abuse and dependence, AUD) are multifactorial phenomena, depending on the interplay of environmental and genetic variables. Method:, This review describes current developments in animal research that may help (a) develop gene therapies for the treatment of alcoholism, (b) understand the permissive role of stress on ethanol intake, and (c) elucidate why exposure to ethanol early in life is associated with a greater risk of AUD. Results:, The polymorphisms found in liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) affect the elimination of ethanol and the susceptibility to ethanol intake. A highly active ADH protects against alcoholism, an effect related to a presteady state burst in arterial acetaldehyde. Social stressors, such as repeated early maternal separation or social defeat, exert a permissive effect on ethanol intake, perhaps by altering the normal development of the hypothalamic-pituitary-adrenal axis. Ethanol exposure during gestation, infancy, or adolescence increases the likelihood of AUD later in life. Early perception of ethanol's positive and negative (anti-anxiety) reinforcing effects may play a role in this phenomenon. Conclusions:, The review underscores the advantages of using preclinical animal models of AUD and highlights points of intersection between the topics to help design a more integrated approach for the study of alcohol-related problems. [source] What are 60 warblers worth?OIKOS, Issue 8 2007Killing in the name of conservation Ecological research sometimes entails animal suffering and even animal killing. The ethical appropriateness of animal suffering and killing in conservation research may entail considerations that differ from many other kinds of research. This is true, insomuch as conservation research is specifically motivated by an ethical premise: an appreciation for non-human life. In striking contrast with other academic fields (e.g. medicine), however, the ethical dimension of conservation research is only rarely discussed. When it is discussed, it tends to be characterized by logical errors. These errors are important because they are general (i.e. both common and with far-reaching implications), and they are easily made by intelligent people; especially those with no formal training in ethics or logic. Failure to recognize these errors could stymie efforts to increase the ethical quality of ecological research conducted in the name of conservation. We take advantage of a recently published dialogue concerning the ethical appropriateness of a specific field experiment that entailed killing black-throated blue warblers, Dendroica caerulescens. Both sides of this debate exemplify the kinds of errors to which we refer. In this paper we briefly review the arguments presented on each side of this debate, highlight their mistakes, and indicate necessary corrections. We argue that: (1) compliance with animal research regulations, while important, inadequately accommodates the ethical aspects of animal research, and (2) individual ecologists ought to understand themselves what does and does not represent sound and valid arguments for ethical decisions. Finally, we discuss how any ecological researcher might begin to apply our analysis to his or her own research. [source] Ethical issues faced by field primatologists: asking the relevant questionsAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2010Linda Marie Fedigan Abstract Field primatologists face unusual ethical issues. We study animals rather than people and receive research approval from animal care rather than ethics committees. However, animal care evaluation forms are developed from concerns about laboratory animal research and are based on the "Three R's" for humane treatment of captive experimental subjects (replacement, reduction and refinement), which are only debatably relevant to field research. Scientists who study wild, free-ranging primates in host countries experience many ethical dilemmas seldom dealt with in animal care forms. This paper reviews the ethical issues many field primatologists say they face and how these might be better addressed by animal care forms. The ethical issues arising for field researchers are divided into three categories: "Presence, Protocols and People" and for each the most frequent issues are described. The most commonly mentioned ethical concern arising from our presence in the field is the possibility of disease transmission. Although most primate field studies employ only observational protocols, the practice of habituating our study animals to close human presence is an ethical concern for many since it can lessen the animals' fear of all humans, thereby facilitating undesirable behaviors (e.g., crop-raiding) and rendering them vulnerable to harm. Field primatologists who work in host countries must observe national laws and local traditions. As conservationists, primatologists must often negotiate between the resource needs and cultural practices of local people and the interests of the nonhuman primates. Many say they face more ethical dilemmas arising from human interactions than from research on the animals per se. This review concludes with suggestions for relevant questions to ask on animal care forms, and actions that field primatologists can take to better inform animal care committees about the common ethical issues we experience as well as how to develop guidelines for addressing them. Am. J. Primatol. 72:754,771, 2010. © 2010 Wiley-Liss, Inc. [source] Research Review: Dopamine transfer deficit: a neurobiological theory of altered reinforcement mechanisms in ADHDTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 7 2008Gail Tripp This review considers the hypothesis that changes in dopamine signalling might account for altered sensitivity to positive reinforcement in children with ADHD. The existing evidence regarding dopamine cell activity in relation to positive reinforcement is reviewed. We focus on the anticipatory firing of dopamine cells brought about by a transfer of dopamine cell responses to cues that precede reinforcers. It is proposed that in children with ADHD there is diminished anticipatory dopamine cell firing, which we call the dopamine transfer deficit (DTD). The DTD theory leads to specific and testable predictions for human and animal research. The extent to which DTD explains symptoms of ADHD and effects of pharmacological interventions is discussed. We conclude by considering the neural changes underlying the etiology of DTD. [source] Habituation and desensitization as methods for reducing fearful behavior in singly housed rhesus macaquesAMERICAN JOURNAL OF PRIMATOLOGY, Issue 1 2009Andrea W. Clay Abstract Operant conditioning using positive reinforcement techniques has been used extensively in the management of nonhuman primates in both zoological and laboratory settings. This research project was intended to test the usefulness of counter-conditioning techniques in reducing the fear-responses of singly housed male rhesus macaques living in the laboratory environment. A total of 18 male rhesus macaques (Macaca mulatta) were selected for this project and randomly assigned to one of three groups: a desensitization training group, a husbandry training group, or a control group. Behavioral data were collected before and after a 6 weeks training and/or habituation period during which the first two groups received a total of 125,min of positive reinforcement training (and also were assumed to undergo habituation to the environment) and the control group experienced only simple habituation to the environment. Based on a Wilcoxon Matched-Pairs Sign Test, we found that a significant proportion of animals exposed to desensitization training showed a reduction in the rate at which they engaged in cringing toward humans (exact significance=0.016, one-tailed, N,ties=6), cringing in general (exact significance=0.016, one-tailed, N,ties=6), and in stress-related behaviors (exact significance=0.016, one-tailed, N,ties=6). This was not the case for animals exposed to basic husbandry training or animals in the control group. A significant proportion of desensitization-exposed animals also showed a reduction in the duration of time spent cringing toward humans (exact significance=0.016, one-tailed, N,ties=6), but not in cringing behaviors in general or in stress-related behaviors. There were not a significant proportion of animals in either the husbandry training group or the control group that showed a decrease in duration of these behaviors. Results of this study could enhance both laboratory animal welfare and laboratory animal research, and could be a first step in developing techniques for reducing fearful behavior in rhesus monkeys in the laboratory environment. Am. J. Primatol. 71:30,39, 2009. © 2008 Wiley-Liss, Inc. [source] The ARRIVE guidelines, a welcome improvement to standards for reporting animal researchTHE JOURNAL OF GENE MEDICINE, Issue 7 2010Olivier Danos Abstract Here we introduce the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, produced by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), which are published in this issue of the journal with our endorsement, and will be incorporated into our Instructions to Authors. Copyright © 2010 John Wiley & Sons, Ltd. [source] ARRIVE: new guidelines for reporting animal researchTHE JOURNAL OF PHYSIOLOGY, Issue 14 2010Gordon B. Drummond No abstract is available for this article. [source] Canal Wall Reconstruction with Mimix Hydroxyapatite Cement: Results in an Animal Model and Case Study,THE LARYNGOSCOPE, Issue 12 2003John Dornhoffer MD Abstract Objective/Hypothesis To assess Mimix hydroxyapatite cement for its applicability in canal wall reconstruction using the gerbil as a canal wall model. A case is presented to illustrate a novel technique of canal wall reconstruction using Mimix on the basis of the findings of our animal research. Study Design This was a preclinical study. Methods Ten Mongolian gerbils were implanted with Mimix, with the left side used to simulate mastoid obliteration and the right side used to simulate canal wall reconstruction. Pre- and postsurgery auditory-evoked brainstem responses were used to assess ototoxicity, and hematoxylin-eosin staining of histologic sections was used to assess inflammatory and foreign-body response and new bone formation. Results Rapid wound healing was achieved with each of the nine animals evaluated, with no erythema, edema, or drainage. Inspection of the ear canal at the time of sacrifice revealed no signs of otitis media and no middle ear effusions. Microscopic examination showed no inflammatory response or foreign-body reaction, good mucosalization on the side of the implant facing the bulla, and minimal fibrosis adjacent to the skin. Eight of nine specimens showed new woven bone ingrowth at the bone implant interface, with active osteoblasts and viable lacunae cells. There were no apparent fractures in the implanted material. Conclusions Mimix hydroxyapatite cement is biocompatible and suitable for canal wall reconstruction in the animal model. The characteristics of this cement, namely its ability to set quickly in a moist environment, offer advantages over previously used cements for canal wall reconstruction. [source] The Animal Research DebateTHE POLITICAL QUARTERLY, Issue 4 2005SIMON FESTING Animal rights extremism has encouraged the media to examine the benefits and justification of animal research. There is broad support from the scientific community and government for carefully conducted animal research; however, Parliament is hindered, as many MPs are ill-informed. The recent Nuffield Council on Bioethics investigated the issue and determined that in carefully considered cases animal research is justified, scientifically valid, and has contributed to human health. The great majority of the public accept the need for animal research for medical progress when there is no alternative method available. Arguments used by anti-vivisectionists are discussed, many of which are unfounded and based on misconceptions. [source] Lipid rescue: small trials and animal researchANAESTHESIA, Issue 12 2009P. Isherwood No abstract is available for this article. [source] Abnormal activity in reward brain circuits in human narcolepsy with cataplexyANNALS OF NEUROLOGY, Issue 2 2010Aurélie Ponz PhD Objective Hypothalamic hypocretins (or orexins) regulate energy metabolism and arousal maintenance. Recent animal research suggests that hypocretins may also influence reward-related behaviors. In humans, the loss of hypocretin-containing neurons results in a major sleep-wake disorder called narcolepsy-cataplexy, which is associated with emotional disturbances. Here, we aim to test whether narcoleptic patients show an abnormal pattern of brain activity during reward processing. Methods We used functional magnetic resonance imaging in 12 unmedicated patients with narcolepsy-cataplexy to measure the neural responses to expectancy and experience of monetary gains and losses. We statistically compared the patients' data with those obtained in a group of 12 healthy matched controls. Results and Interpretation Our results reveal that activity in the dopaminergic ventral midbrain (ventral tegmental area) was not modulated in narcolepsy-cataplexy patients during high reward expectancy (unlike controls), and that ventral striatum activity was reduced during winning. By contrast, the patients showed abnormal activity increases in the amygdala and in dorsal striatum for positive outcomes. In addition, we found that activity in the nucleus accumbens and the ventral-medial prefrontal cortex correlated with disease duration, suggesting that an alternate neural circuit could be privileged over the years to control affective responses to emotional challenges and compensate for the lack of influence from ventral midbrain regions. Our study offers a detailed picture of the distributed brain network involved during distinct stages of reward processing and shows for the first time, to our knowledge, how this network is affected in hypocretin-deficient narcoleptic patients. ANN NEUROL 2010;67:190,200 [source] Verapamil Toxicity Dysregulates the Phosphatidylinositol 3-Kinase PathwayACADEMIC EMERGENCY MEDICINE, Issue 4 2008Laura K. Bechtel PhD Abstract Objectives:, Recent animal research and clinical case reports suggest benefit from high-dose insulin therapy (HDIT) for the treatment of calcium channel blocker (CCB) toxicity. One molecular signaling pathway, the phosphatidylinositol 3-kinase (PI3K) pathway, that contributes to CCB toxicity and the efficacy of HDIT, was examined for a role in this phenomenon. Methods:, A differentiated 3T3-L1 adipocyte model system was utilized to characterize metabolic and molecular signaling events dysregulated in response to acute CCB toxicity. Glucose uptake assays were performed in the presence of representatives of three classes of CCB drugs, and the ability of HDIT to reverse observed inhibition was assessed. Western blot analyses were utilized to probe which insulin-dependent signaling pathway was inhibited by CCB toxicity. Results:, Representative compounds from the dihydropyridine and phenylalkylamine classes of CCBs were more effective at inhibiting glucose uptake in differentiated 3T3-L1 adipocytes than a representative from the benzothiazepine class. Phosphorylation at serine 473 of the Akt protein (P-Akt), a protein representing a common pathway for insulin receptors (IR), insulinlike growth factor receptors (IGFR), and hybrid receptors formed by IR and IGFR subunits, was abolished in the presence of toxic doses of the phenylalkylamine CCB verapamil. Phosphorylation at serine 473 of Akt was rescued in the presence high concentrations of insulin. Conclusions:, These data suggest that dysregulation of the insulin-dependent PI3K pathway is partially responsible for insulin resistance and the hyperglycemic state observed in response to acute CCB toxicity. [source] Mouse isolated perfused heart: Characteristics and cautionsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2003Fiona J Sutherland Summary 1.,Owing to the considerable potential for manipulating the murine genome and, as a consequence, the increasing availability of genetically modified models of cardiovascular diseases, the mouse is fast becoming a cornerstone of animal research. However, progress in the use of various murine preparations is hampered by the lack of facilities and skills for the adequate physiological assessment of genetically modified mice. 2.,We have attempted to address this problem by refining and characterizing a mouse isolated heart preparation that was originally developed for use with larger hearts. 3.,We used the isolated buffer-perfused Langendorff preparation (perfused at constant flow or constant pressure) to characterize: (i) the frequency,response characteristics; (ii) heart isolation conditions; (iii) perfusion chamber conditions; (iv) temperature,function relationships; (v) stability over extended periods of perfusion; (vi) perfusate calcium,function relationships; (vii) pressure,volume relationships; (viii) pressure,rate relationships; and (ix) flow,function relationships. [source] | ||||||||||||||||||||||||||||