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Laboratory Models (laboratory + models)
Selected AbstractsGUEST EDITORIAL: New dimensions in human laboratory models of addictionADDICTION BIOLOGY, Issue 1 2009GEORGE F. KOOB First page of article [source] REVIEW: Modeling stress and drug craving in the laboratory: implications for addiction treatment developmentADDICTION BIOLOGY, Issue 1 2009Rajita Sinha ABSTRACT Addition is a chronic relapsing illness affected by multiple social, individual and biological factors that significantly impact course and recovery of the illness. Stress interacts with these factors and increases addiction vulnerability and relapse risk, thereby playing a significant role in the course of the illness. This paper reviews our efforts in developing and validating laboratory models of stress and drug cue-related provocation to assess stress responses and stress-related adaptation in addicted individuals compared with healthy controls. Empirical findings from human laboratory and brain imaging studies are presented to show the specific stress-related dysregulation that accompanies the drug-craving state in addicted individuals. In order to adequately validate our laboratory model, we have also carefully examined relapse susceptibility in the addicted individuals and these data are reviewed. The overarching goal of these efforts is to develop a valid laboratory model to identify the stress-related pathophysiology in addiction with specific regard to persistent craving and compulsive seeking. Finally, the significant implications of these findings for the development of novel treatment interventions that target stress processes and drug craving to improve addiction relapse outcomes are discussed. [source] REVIEW: Developing human laboratory models of smoking lapse behavior for medication screeningADDICTION BIOLOGY, Issue 1 2009Sherry A. McKee ABSTRACT Use of human laboratory analogues of smoking behavior can provide an efficient, cost-effective mechanistic evaluation of a medication signal on smoking behavior, with the result of facilitating translational work in medications development. Although a number of human laboratory models exist to investigate various aspects of smoking behavior and nicotine dependence phenomena, none have yet modeled smoking lapse behavior. The first instance of smoking during a quit attempt (i.e. smoking lapse) is highly predictive of relapse and represents an important target for medications development. Focusing on an abstinence outcome is critical for medication screening as the US Food and Drug Administration approval for cessation medications is contingent on demonstrating effects on smoking abstinence. This paper outlines a three-stage process for the development of a smoking lapse model for the purpose of medication screening. The smoking lapse paradigm models two critical features of lapse behavior: the ability to resist the first cigarette and subsequent ad libitum smoking. Within the context of the model, smokers are first exposed to known precipitants of smoking relapse (e.g. nicotine deprivation, alcohol, stress), and then presented their preferred brand of cigarettes. Their ability to resist smoking is then modeled and once smokers ,give in' and decide to smoke, they participate in a tobacco self-administration session. Ongoing and completed work developing and validating these models for the purpose of medication screening is discussed. [source] A likely role for anoxygenic photosynthetic microbes in the formation of ancient stromatolitesGEOBIOLOGY, Issue 2 2007T. BOSAK ABSTRACT Although cyanobacteria are the dominant primary producers in modern stromatolites and other microbialites, the oldest stromatolites pre-date geochemical evidence for oxygenic photosynthesis and cyanobacteria in the rock record. As a step towards the development of laboratory models of stromatolite growth, we tested the potential of a metabolically ancient anoxygenic photosynthetic bacterium to build stromatolites. This organism, Rhodopseudomonas palustris, stimulates the precipitation of calcite in solutions already highly saturated with respect to calcium carbonate, and greatly facilitates the incorporation of carbonate grains into proto-lamina (i.e. crusts). The appreciable stimulation of the growth of proto-lamina by a nonfilamentous anoxygenic microbe suggests that similar microbes may have played a greater role in the formation of Archean stromatolites than previously assumed. [source] Effects of HCV proteins in current HCV transgenic modelsHEPATOLOGY RESEARCH, Issue 2 2010Jian Jiao Hepatits C virus (HCV) is an enveloped virus with positive-sense single-stranded RNA genome that causes both acute and persistent infections associated with chronic hepatitis, cirrhosis and hepatocellular carcinoma, which needs fully functional human hepatocytes for its development. Due to the strict human tropism of HCV, only human and higher primates such as chimpanzees have been receptive to HCV infection and development, cognition about pathophysiololgy and host immune responses of HCV infection is limited by lacking of simple laboratory models of infection for a long time. During the past decade, gene transfer approaches have been helpful to the understanding of the molecular basis of human disease. Transgenic cell lines, chimeric and transgenic animal models were developed and had been demonstrated their invaluable benefits. This review focuses on the existing HCV transgenic models and summarize the relative results about probable pathophysical changes induced by HCV proteins. [source] Laboratory Models Available to Study Alcohol-Induced Organ Damage and Immune Variations: Choosing the Appropriate ModelALCOHOLISM, Issue 9 2010Nympha B. D'Souza El-Guindy The morbidity and mortality resulting from alcohol-related diseases globally impose a substantive cost to society. To minimize the financial burden on society and improve the quality of life for individuals suffering from the ill effects of alcohol abuse, substantial research in the alcohol field is focused on understanding the mechanisms by which alcohol-related diseases develop and progress. Since ethical concerns and inherent difficulties limit the amount of alcohol abuse research that can be performed in humans, most studies are performed in laboratory animals. This article summarizes the various laboratory models of alcohol abuse that are currently available and are used to study the mechanisms by which alcohol abuse induces organ damage and immune defects. The strengths and weaknesses of each of the models are discussed. Integrated into the review are the presentations that were made in the symposium "Methods of Ethanol Application in Alcohol Model,How Long is Long Enough" at the joint 2008 Research Society on Alcoholism (RSA) and International Society for Biomedical Research on Alcoholism (ISBRA) meeting, Washington, DC, emphasizing the importance not only of selecting the most appropriate laboratory alcohol model to address the specific goals of a project but also of ensuring that the findings can be extrapolated to alcohol-induced diseases in humans. [source] Morphine, opioids, and the feline pulmonary vascular bedACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2008A. D. KAYE Background: Opioid-induced vasodepressor responses have been reported in a variety of species and laboratory models. The aim of this study was to ascertain the relative potencies of different clinically relevant opioids compared with traditional vasodepressor agents in the feline pulmonary vascular bed. A second aim was to study the effects of morphine and to identify the receptors involved in the mediation or the modulation of these effects. Methods: This was a prospective vehicle-controlled study involving an intact chest preparation of adult mongrel cats. The effects of various opioids, morphine, fentanyl, remifentanil, sufentanil, and meperidine were compared with other vasodepressor agents. Additionally, the effects of l - N5 -(1-iminoethyl) ornithine hydrochloride (l -NIO) (nitric oxide synthase inhibitor), nimesulide [selective cyclooxygenase (COX)-2 inhibitor], glibenclamide (ATP-sensitive K+ channel blocker), naloxone (non-selective opioid receptor antagonist), and diphenhydramine (histamine H1 -receptor antagonist) were investigated on pulmonary arterial responses to morphine and other selected agonists in the feline pulmonary vascular bed. The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and recorded. Results: In the cat pulmonary vascular bed of the isolated left lower lobe, morphine, remifentanil, fentanyl, sufentanil, and meperidine induced a dose-dependent moderate vasodepressor response and it appeared that sufentanil was the most potent on a nanomolar basis. The effects of morphine were not significantly altered after administration of l -NIO, nimesulide, and glibenclamide. However, the vascular responses to morphine were significantly attenuated following administration of naloxone and diphenhydramine. Conclusion: The results of the present study suggest that sufentanil appears to have slightly more potency and morphine the least of the five opioid agonists studied on a nanomolar basis. Morphine-induced vasodilatory responses appeared to be mediated or modulated by both opioid receptor and histamine-receptor-sensitive pathways. [source] The gut, immunoregulation and micro-organisms from man's evolutionary pastNUTRITION BULLETIN, Issue 2 2010G. A. W. Rook Summary Man has moved rapidly from the hunter-gatherer environment to the living conditions of the rich industrialised countries. The hygiene hypothesis suggests that the resulting changed and reduced pattern of exposure to certain critical micro-organisms, mostly derived from mud, animals and faeces, has led to disordered regulation of the immune system and, hence, to increases in chronic inflammatory disorders such as allergies, inflammatory bowel diseases and autoimmunity. Epidemiology, backed up by laboratory models, indicates that the relevant organisms are those that have very long associations with the mammalian immune system, traceable back to the Palaeolithic or earlier. Often, these organisms have been present as commensals (notably in the intestinal microbiota), environmental ,pseudocommensals', sub-clinical infections or asymptomatic carrier states, and the mammalian immune system is in a state of ,evolved dependence' on their continued presence. Several of these ,Old Friends', often operating primarily in the gut, act as modulators of dendritic cells and T cells, leading to the establishment of immunoregulatory circuits. Clinical trials are in progress to test living helminths (Trichuris suis and Necator americanus) in allergies, inflammatory bowel disease and multiple sclerosis. We can anticipate rapid increases in the use of these and other organisms or their components in novel types of therapy with applications in several branches of medicine. Probiotics tested in clinical trials targeting chronic inflammatory disorders have so far given unconvincing results, but if strains for these indications are selected on the basis of their ability to induce immunoregulation, and not merely imposed by companies that have intellectual property rights, we can anticipate rapid progress. [source] Involutions resulting from annual freeze,thaw cycles: a laboratory simulation based on observations in northeastern JapanPERMAFROST AND PERIGLACIAL PROCESSES, Issue 4 2007Yoshiko Ogino Abstract A pilot laboratory experiment using a reversed two-layer soil model simulated small-scale involutions formed in a seasonal frost environment during the last glacial period. At the modelled site, the interface between the upper aeolian sandy loam and the lower volcanic pumice constitutes small-scale involutions that display upward-extending tapered projections and downward-extending round hollows. Two scale-reduced laboratory models were subjected to three accelerated annual freeze,thaw cycles with monitoring of frost heave, soil temperature, moisture and pressure. Ice segregation near the layer interface induces upheaving of coarse pumice grains on freezing and earlier settlement of mobilised loam on thawing, resulting in deformation of the interface. A reconstructed 3-D interface displays mounds and depressions with a diameter of 15,20,cm and a height increasing with freeze, thaw alternations. The experimental results imply that the repetition of differential heave and soft-loam settlement promotes decimetre-scale involutions in near-saturated soils subject to deep seasonal frost penetration. Copyright © 2007 John Wiley & Sons, Ltd. [source] Toward full restoration of synaptic and terminal function of the dopaminergic system in Parkinson's disease by stem cellsANNALS OF NEUROLOGY, Issue S3 2003Ole Isacson DrMedSci New therapeutic nonpharmacological methodology in Parkinson's disease (PD) involves cell and synaptic renewal or replacement to restore function of neuronal systems, including the dopaminergic (DA) system. Using fetal DA cell therapy in PD patients and laboratory models, it has been demonstrated that functional motor deficits associated with parkinsonism can be reduced. Similar results have been observed in animal models with stem cell-derived DA neurons. Evidence obtained from transplanted PD patients further shows that the underlying disease process does not destroy transplanted fetal DA cells, although degeneration of the host nigrostriatal system continues. The optimal DA cell regeneration system would reconstitute a normal neuronal network capable of restoring feedback-controlled release of DA in the nigrostriatal system. The success of cell therapy for PD is limited by access to preparation and development of highly specialized dopaminergic neurons found in the A9 and A10 region of the substantia nigra pars compacta as well as the technical and surgical steps associated with the transplantation procedure. Recent laboratory work has focused on using stem cells as a starting point for deriving the optimal DA cells to restore the nigrostriatal system. Ultimately, understanding the cell biological principles necessary for generating functional DA neurons can provide many new avenues for better treatment of patients with PD. Ann Neurol 2003;53 (suppl 3):S135,S148 [source] | ||||||||||