bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Catecholamines during an Ultrarapid Heroin Detoxification
Authors: MACEDO T. R.A. , RELVAS J. , FONTES RIBIERO C. A. , PACHECO F. , MORGADINHO M. T. , PINTO C. M. , GOMES P. C. , VENTURA M. , HENRIQUES V. , NUNES S. V. , RUIS G. R. , RAMALHEIRA C. , BOTO I. , VALE L. L. 
Published: July 2010

AbstractThe adrenergic system has long been known to be activated in a situation of stress and thus during opiate withdrawal. A method for detoxification that decreases the stimulation of the sympathetic nervous system will prevent changes of catecholamine levels. Some of such methods have been developed. One of them uses direct transition from heroin to oral naltrexone after deep sedation with midazolam in conjunction with naloxone, droperidol, ondansetron, and clonidine treatment for 24 hours. Can such method prevent adrenergic changes? Moreover, 5‐HT has been related to mood disorders. This study aims to determine plasma catecholamines and 5‐HT before heroin withdrawal, during the day of the withdrawal, and at the ends of the first day, the first week, and the first 6 months. Forty‐three patients with more than 6 years of drug abuse volunteered to seek help to detoxify. After clinical evaluation, blood samples were taken. Plasma catecholamines were isolated by standard alumina procedures and measured by high‐performance liquid chromatography with electrochemical detection. Only for NE was there a significant decrease in the day of heroin withdrawal with deep sedation, followed the next day by an increase. During the following days, NE plasma concentrations returned slowly to basal levels. Epinephrine and dopamine plasma levels did not significantly change. Platelet 5‐HT levels progressively decreased from the day before detoxification until the last period of observation. We also found that there were no abrupt changes in cardiovascular functions. In conclusion, our results suggest that this type of ultrarapid opiate detoxification prevents the dramatic activation of the autonomic nervous system.
Ca2+Oscillations in Response to Methamphetamine in Dopamine Neurons of the Ventral Tegmental Area in Rats Subchronically Treated with This Drug
Authors: URAMURA KAZUHIDE , YADA TOSHIHIKO , MUROYA SHINJI , TAKIGAWA MORIKUNI 
Published: July 2010

AbstractMesolimbic dopamine neurons in the ventral tegmental area (VTA), which project to the nucleus accumbens and prefrontal cortex, play an important role in the regulation of emotion, rewarding, and cognition. The dopamine neurons in the VTA have also been implicated in schizophrenia and drug abuse. Methamphetamine (METH) can induce a schizophrenia‐like psychosis. Thus, the VTA is a likely effector site for the action of METH. However, effects of METH on the mesolimbic dopamine neurons are largely unknown. We treated adult SD rats with METH (5 mg/kg/day) or saline for 7 days, isolated single VTA neurons from these treated rats, and monitored the neuronal activities by measuring cytosolic Ca2+concentration ([Ca2+]i), which was followed by immunocytochemical identification of dopamine neurons. Acute administration of METH under superfusion conditions concentration‐dependently increased [Ca2+]iin VTA dopamine neurons isolated from METH‐ and saline‐treated rats. Furthermore, acutely administered METH induced oscillations of [Ca2+]ionly in the dopamine neurons of the METH‐treated group. The METH‐induced [Ca2+]ioscillations were inhibited by Ca2+‐free conditions and by Ca2+ channel blockers. In conclusion, subchronic METH treatment sensitizes VTA dopamine neurons to this drug, resulting in induction of [Ca2+]ioscillations. This sensitization of VTA dopamine neurons may account, at least in part, for the psycho‐stimulant effects of METH, such as the dependence on and sensitization to METH.
The Neurochemical Basis for the Behavioral Effects of Triadimefon
Authors: HILL DONNA , IKAIDDI MARGARETMARY , MAZZIO ELIZABETH , SOLIMAN KARAM F.A. 
Published: July 2010

AbstractAdministration of triadimefon (TDF) [1‐(4‐chlorophenoxy)‐3,3‐dimethyl‐1‐(1‐H‐1,2,4‐triazol‐1‐yl)‐2‐butanone] in rodents incites heightened locomotor and stereotypy response, primarily through potentiation of dopaminergic activity. In the present study, 8 male Sprague‐Dawley rats received repeated injections, on alternate days (100 mg/kg, 14 days) of TDF or corn oil. Enhanced locomotor and stereotypy behavioral patterns occurred in response to TDF injections, lasting until the 12thday of injection. Tolerance to this effect was evident by a lack of response to TDF injection by the 14thday. Similarly, a withdrawal period and challenge dose of TDF (5 days, 25 mg/kg) was ineffective in espousing locomotor or stereotypy behavioral changes. Cross sensitization to cocaine was also evident, since withdrawal and a challenge dose (8 days, 5 mg/kg) was also ineffective. Adaptative biochemical changes in dopaminergic function were examined after both acute (100 mg/kg) and repeated administration of TDF (100 mg/kg, 14 days) by examining [3H]dopamine (DA) uptake and DA release in both striatal (ST) and nucleus accumbens (NA) tissue. In corroboration with behavioral pattern indicating development of tolerance, there were significant changes in dopaminergic function. Repeated TDF exposurein vivoresulted in significant attenuation of ST and NA DA uptake in response to TDF (10−4to 10−7M) or cocaine (10−5to 10−8M)in vitro. Acute exposure to TDFin vivoalso attenuated ST DA inhibitory effects of cocaine and TDF. Repetitive administration of TDFin vivohad no effect onin vitroTDF‐ or amphetamine‐stimulated release of ST or NA DA. However, there was a significant reduction in amphetamine‐stimulated DA release in animals after acute exposure to TDFin vivo. It was concluded from this study that the effects of chronic TDF exposure may primarily involve effects on DA uptake in the ST and NA.
The Relationship between Neural Alterations and Behavioral Deficits after Prenatal Exposure to Heroin
Authors: YANAI JOSEPH , STEINGART RUTH A. , SNAPIR NACHUM , GVARYAHU GADI , ROZENBOIM ISRAEL , KATZ AMNON 
Published: July 2010

AbstractThe present studies employ multitudinous approaches in order to overcome the methodological obstacles in the understanding of the relationship between neurochemical alterations and behavioral deficits induced by heroin during prenatal development. Mice were exposed prenatally to heroin via daily subcutaneous injections of 10 mg/kg, on gestation days 9‐18. At age 50 days, the heroin‐exposed offspring displayed behavioral deficits as assessed in the eight‐arm and Morris mazes, pointing to possible alteration in the septohippocampal cholinergic innervations. Biochemically there was increased presynaptic activity of these innervations as attested to by the increased [3H]hemicholinium‐3 (HC‐3) binding sites and by K+‐stimulated inositol phosphate (IP) formation. Postsynaptically, there was global hyperactivation along the different components of the nerve conduction cascade, including an increase in M1 muscarinic receptor Bmax, a general increase in G‐proteins (GP) including the most relevant, Gq subtype, and an increase in IP formation and in basal protein kinase C (PKC) activity. However, there was desensitization of PKC activity in response to cholinergic agonist in the heroin‐exposed offspring. Transplantation of normal embryonic cholinergic cells to the impaired hippocampus reserved the behavioral deficits and both the pre‐ and postsynaptic hyperactivity and resensitized PKC activity.To support and further strengthen the findings of the neural grafting study, correlation of the heroin‐induced behavioral deficits with the biochemical alterations, done within individuals, was applied. The results showed high |r|| values for IP formation, basal PKC, and PKC desensitization. The |r|| values for HC‐3 binding were statistically significant but relatively low. Taken together, the findings of the neural grafting and correlation studies bring us closer to understanding the relationship between the prenatal heroin‐induced biochemical and behavioral changes.However, mammalian models possess the inherent methodological hindrances, stemming from possible maternal effects. To provide a control for these confounding variables, a chick embryo model was applied in which filial imprinting, a behavior related to a specific hyperstriatal nucleus, served as an endpoint. Heroin was administered to developing chick embryos by injecting the eggs (20 mg/kg) on incubation days (ID) 0 or 5. Prehatch exposure to heroin markedly diminished the ability for filial imprinting in the hatched chicks.
Convection in Slab and Spheroidal Geometries
Authors: PORTER DAVID H. , WOODWARD PAUL R. , JACOBS MICHAEL L. 
Published: July 2010

Abstract: Three‐dimensional numerical simulations of compressible turbulent thermally driven convection, in both slab and spheroidal geometries, are reviewed and analyzed in terms of velocity spectra and mixing‐length theory. The same ideal gas model is used in both geometries, and resulting flows are compared. The piecewise‐parabolic method (PPM), with either thermal conductivity or photospheric boundary conditions, is used to solve the fluid equations of motion.Fluid motions in both geometries exhibit a Kolmogorov‐like k−5/3 range in their velocity spectra. The longest wavelength modes are energetically dominant in both geometries, typically leading to one convection cell dominating the flow. In spheroidal geometry, a dipolar flow dominates the largest scale convective motions. Downflows are intensely turbulent and up drafts are relatively laminar in both geometries. In slab geometry, correlations between temperature and velocity fluctuations, which lead to the enthalpy flux, are fairly independent of depth. In spheroidal geometry this same correlation increases linearly with radius over the inner 70 percent by radius, in which the local pressure scale heights are a sizable fraction of the radius. The effects from the impenetrable boundary conditions in the slab geometry models are confused with the effects from non‐local convection. In spheroidal geometry nonlocal effects, due to coherent plumes, are seen as far as several pressure scale heights from the lower boundary and are clearly distinguishable from boundary effects.
EDG Receptors as a Therapeutic Target in the Nervous System
Authors: BEER MARGARET S. , STANTON JOSEPHINE A. , SALIM KAMRAN , RIGBY MICHAEL , HEAVENS ROBERT P. , SMITH DAVID , MCALLISTER GEORGE 
Published: July 2010

Abstract:EDG receptors are a family of closely related G‐protein‐coupled receptors, so‐called since the first family member to be cloned is encoded by anendothelialdifferentiationgene. Of the six family members identified, five use lysophospholipids as their endogenous ligands. The sixth receptor, EDG‐6, remains an orphan. These receptors activate multiple secondary‐messenger pathways involving coupling to Gi, Gq/11, and G12/13 trimeric guanine nucleotide‐binding proteins and are thought to play an important role in cell growth, development and maintenance, and cytoskeletal‐dependent changes.EDG receptors are expressed in most mammalian cells and tissues, each subtype having a distinct distrubution pattern, raising the possibility of tissue‐specific biological roles that could be explored in drug‐discovery programs. In this study the distribution of EDG‐receptor mRNA within the nervous system has been investigated. As seen in peripheral tissues, these receptors appear to be discretely localized within specific brain regions and cell types. For example, EDG‐1, ‐3, ‐4 receptors are confined to neuronal cells, EDG‐2 receptors to white matter tracts, while EDG‐5 receptors appear to be expressed in various cell types, including neuronal cells, white matter tracts, and ependymal cells. EDG‐6‐receptor mRNA was not detected in the nervous system.Speculation as to the role of these receptors in physiological/pathophysiological processes, particularly those involving cell development, proliferation, maintenance, migration, differentiation, plasticity, and apoptosis can be made from such distribution studies. EDG receptors located in brain neuronal cells might, for example, influence apoptosis and be involved in cell rescue following ischemic damage or during the early stages of progressive neurodegenerative diseases. Those restricted to oligodendrocytes might play a crucial role in myelination and offer a potential target in the treatment of demyelinating diseases, such as multiple sclerosis. In order to explore the role of these receptors, it is necessary to identify selective compounds. To this end we have developed an agonist‐induced [35S]GTPγS binding assay using an HEK cell line expressing a pertussis‐toxin‐insensitive human‐EDG‐2‐receptor‐rat‐Giα1‐fusion protein. Such as assay system ovecomes the problems associated with the almost ubiquitous responsiveness of mammalian cells to lysophospholipid. This assay lends itself to high throughput application, opening up the possibility of identifying compounds to further probe the therapeutic potential of EDG receptor manipulation
Regulation of APP Synthesis and Secretion by Neuroimmunophilin Ligands and Cyclooxygenase Inhibitors
Authors: LEE ROBERT K.K. , WURTMAN RICHARD J. 
Published: July 2010

Abstract:We and others previously showed that both the synthesis of the amyloid precursor protein (APP) and its processing (i.e., to amyloidogenic Aβ peptides; soluble nonamyloidogenic APPs; and other APP fragments) are regulated by neurotransmitters. Transmitters that elevate cellular cAMP levels (like norepinephrine and prostaglandins, which act on β‐adrenergic receptors and prostaglandin E2receptors respectively) enhance APP synthesis and the formation of amyloidogenic APP holoprotein. Transmitters that stimulate phosphatidylinositol hydrolysis (by activating muscarinic m1 or m3 receptors, serotoninergic 5HT2a or 5HT2c receptors, or metabotropic glutamate receptors of subtypes 1 or 5) increase the conversion of APP to soluble APPs, and decrease the formation of Aβ. These findings suggest that drugs that regulate the activity of neurotransmitter receptors might be useful in preventing the excessive formation of Aβ or other amyloid precursors in Alzheimer's disease.We now show that neuroimmunophilin ligands (like cyclosporin A or FK‐506) and nonsteroidal antiinflammatory agents (NSAIDs), including cyclooxygenase (COX)‐2 inhibitors, can also prevent APP overexpression and the overproduction of amyloidogenic peptides. We observe that the enhancement of APP over‐expression by prostaglandin E2is inhibited by neuroimmunophilin ligands like cyclosporin A or FK‐506 (tacrolimus). We also find that the NSAIDs, which reduce prostaglandin synthesis by inhibiting COX‐1 and ‐2 enzymes, might also be expected to lower APP levels. Our present data confirm that these drugs, as well as drugs that selectively inhibit COX‐2, reduce the levels of amyloidogenic APP holoprotein in cultured neurons or in cultured astrocytes. We previously showed that elevations in cAMP, perhaps generated in response to prostaglandins, can suppress APPs secretion. The NSAIDs and COX inhibitors also increased levels of soluble APPs in the media of cultured astrocytes and neurons, perhaps acting by inhibition of prostaglandin production. Since APP holoprotein can be amyloidogenic, while APPs may be neurotrophic, our findings suggest that some neuroimmunophilin ligands, NSAIDs and COX‐2 inhibitors might suppress amyloid formation and enhance neuronal regeneration in Alzheimer's disease.
Development of Bowman‐Birk Inhibitor for Chemoprevention of Oral Head and Neck Cancer
Authors: MEYSKENS FRANK L. 
Published: July 2010

AbstractLeukoplakia in the oral cavity has been used as a putative surrogate marker of head and neck cancer development. A class of chemoprevention compounds, called protease inhibitors, has been shown in vitro and in animal models to effectively suppress premalignant lesions. Bowman‐Birk inhibitor (BBI) is a protease inhibitor derived from soybeans that has demonstrated chemoprevention activity in many in vitro and animal systems, including the hamster cheek pouch model. Pilot, Phase I and Phase IIa studies of Bowman‐Birk Inhibitor in patients with oral leukoplakia have demonstrated no detectable side effects. In the Phase IIa trial, changes in the protease activity in oral mucosal cells after BBI Concentrate© (BBIC) treatment correlated with the changes in neu protein levels. Additionally, evidence for a dose‐related treatment effect of BBIC on oral leukoplakia was demonstrated. These results indicate that BBIC should be investigated for chemopreventive activity in a randomized clinical trial.
Preneoplastic Prostate Lesions
Authors: NELSON WILLIAM G. , DE MARZO ANGELO M. , DEWEESE THEODORE L. , LIN XIAOHUI , BROOKS JAMES D. , PUTZI MATTHEW J. , NELSON CHAD P. , GROOPMAN JOHN D. , KENSLER THOMAS W. 
Published: July 2010

AbstractEnvironmental factors, especially the diet, play a prominent role in the epidemic of prostate cancer (PCA), in the United States. Many candidate dietary components have been proposed to influence human prostatic carcinogenesis, including fat, calories, fruits and vegetables, anti‐oxidants, and various micronutrients, but the specific roles dietary agents play in promoting or preventing PCA remain controversial. We have collected evidence to suggest that GSTP1, the gene encoding the π‐class glutathione S‐transferase (GST), may serve a “caretaker” function for prostatic cells. Although GSTP1 can be detected in normal prostatic epithelium, in almost all PCA cases, PCA cells fail to express GSTP1 polypeptides, and lack of GSTP1 expression most often appears to be the result of somatic “CpG island” DNA methylation changes. Loss of GSTP1 function also appears to be characteristic of prostatic epithelial neoplasia (PIN) lesions, thought to represent PCA precursors. We have recently learned that a new candidate early PCA precursor lesion, proliferative inflammatory atrophy (PIA), characterized by proliferating prostatic cells juxtaposed to inflammatory cells, contains epithelial cells that express high levels of GSTP1. These findings have formed the basis for a new model of prostatic carcinogenesis, in which prostatic cells in PIA lesions, subjected to a barrage of inflammatory oxidants, induce GSTP1 expression as a defense against oxidative genome damage. When cells with defective GSTP1 genes appear amongst the PIA cells, such cells become vulnerable to oxidants and electrophiles that inflict genome damage that tends to promote neoplastic transformation to PIN and PCA cells. Subsequently, PIN and PCA cells with defective GSTP1 genes remain vulnerable to similar stresses tending to promote malignant progression. This new model for prostatic carcinogenesis has implications for the design of new prostate cancer prevention strategies. Rational prevention approaches might include: (i) restoration of GSTP1 expression via treatment with inhibitors of CpG methylation, (ii) compensation for inadequate GSTP1 activity via treatment with inducers of general GST activity, and (iii) abrogation of genome‐damaging stresses via avoidance of exogenous carcinogens and/or reduction of endogenous carcinogenic (particularly oxidant) stresses.
Age‐Related Changes in Vestibular Function
Authors: BALOH ROBERT W. , ENRIETTO JANE , JACOBSON KATHLEEN M. , LIN ADAM 
Published: July 2010

Abstract: The objective of this study was to identify age‐related changes in the vestibulo‐ocular reflex (VOR) in normal older subjects and patients complaining of disequilibrium followed serially over time. Cross‐sectional studies have found decreases in vestibular function in older subjects compared to younger subjects, but no prior longitudinal studies have been made following the same older subjects over time. We measured VOR responses using step and sinusoidal stimuli in 110 normal subjects and 51 patients with disequilibrium of unknown cause. This report focuses on 57 normal subjects who were able to return for five yearly examinations and 7 patients who were found to have severe bilateral vestibulopathy on the initial examination. In the normal subjects, there was a significant shortening of the VOR time constant to step changes in angular velocity and an amplitude‐dependent decrease in gain and increase in phase lead of low‐frequency sinusoidal responses over the five examinations. There was also a decrease in the gain of visual‐vestibular responses at low frequencies of sinusoidal stimulation over the five examinations. The patients with bilateral vestibulopathy showed relatively little change in vestibular function over the five years of follow‐up.This is the first longitudinal study to show age‐related decreases in vestibular responses in normal older subjects. The VOR changes identified were not associated with symptoms or signs of disequilibrium. A small subgroup of patients with disequilibrium of unknown cause had profound bilateral vestibulopathy that remained stable during follow‐up. These patients likely had an underlying disease even though in most cases the disease process could not be identified.
Vestibulospinal Control of Reflex and Voluntary Head Movement
Authors: BOYLE R. 
Published: July 2010

Abstract: Secondary canal‐related vestibulospinal neurons respond to an externally applied movement of the head in the form of a firing rate modulation that encodes the angular velocity of the movement, and reflects in large part the input “head velocity in space” signal carried by the semicircular canal afferents. In addition to the head velocity signal, the vestibulospinal neurons can carry a more processed signal that includes eye position or eye velocity, or both (see Boyle1 on ref. list).To understand the control signals used by the central vestibular pathways in the generation of reflex head stabilization, such as the vestibulocollic reflex (VCR), and the maintenance of head posture, it is essential to record directly from identified vestibulospinal neurons projecting to the cervical spinal segments in the alert animal. The present report discusses two key features of the primate vestibulospinal system. First, the termination morphology of vestibulospinal axons in the cervical segments of the spinal cord is described to lay the structural basis of vestibulospinal control of head/neck posture and movement. And second, the head movement signal content carried by the same class of secondary vestibulospinal neurons during the actual execution of the VCR and during self‐generated, or active, rapid head movements is presented.