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1.
For Ecol Manage ; 536: 120847, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37193248

RESUMO

European forests are threatened by increasing numbers of invasive pests and pathogens. Over the past century, Lecanosticta acicola, a foliar pathogen predominantly of Pinus spp., has expanded its range globally, and is increasing in impact. Lecanosticta acicola causes brown spot needle blight, resulting in premature defoliation, reduced growth, and mortality in some hosts. Originating from southern regions of North American, it devastated forests in the USA's southern states in the early twentieth century, and in 1942 was discovered in Spain. Derived from Euphresco project 'Brownspotrisk,' this study aimed to establish the current distribution of Lecanosticta species, and assess the risks of L. acicola to European forests. Pathogen reports from the literature, and new/ unpublished survey data were combined into an open-access geo-database (http://www.portalofforestpathology.com), and used to visualise the pathogen's range, infer its climatic tolerance, and update its host range. Lecanosticta species have now been recorded in 44 countries, mostly in the northern hemisphere. The type species, L. acicola, has increased its range in recent years, and is present in 24 out of the 26 European countries where data were available. Other species of Lecanosticta are largely restricted to Mexico and Central America, and recently Colombia. The geo-database records demonstrate that L. acicola tolerates a wide range of climates across the northern hemisphere, and indicate its potential to colonise Pinus spp. forests across large swathes of the Europe. Preliminary analyses suggest L. acicola could affect 62% of global Pinus species area by the end of this century, under climate change predictions. Although its host range appears slightly narrower than the similar Dothistroma species, Lecanosticta species were recorded on 70 host taxa, mostly Pinus spp., but including, Cedrus and Picea spp. Twenty-three, including species of critical ecological, environmental and economic significance in Europe, are highly susceptible to L. acicola, suffering heavy defoliation and sometimes mortality. Variation in apparent susceptibility between reports could reflect variation between regions in the hosts' genetic make-up, but could also reflect the significant variation in L. acicola populations and lineages found across Europe. This study served to highlight significant gaps in our understanding of the pathogen's behaviour. Lecanosticta acicola has recently been downgraded from an A1 quarantine pest to a regulated non quarantine pathogen, and is now widely distributed across Europe. With a need to consider disease management, this study also explored global BSNB strategies, and used Case Studies to summarise the tactics employed to date in Europe.

2.
Gen Comp Endocrinol ; 246: 88-98, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26497253

RESUMO

Some animals can undergo a remarkable transition from active normal life to a dormant state called aestivation; entry into this hypometabolic state ensures that life continues even during long periods of environmental hardship. In this study, we aimed to identify those central nervous system (CNS) peptides that may regulate metabolic suppression leading to aestivation in land snails. Mass spectral-based neuropeptidome analysis of the CNS comparing active and aestivating states, revealed 19 differentially produced peptides; 2 were upregulated in active animals and 17 were upregulated in aestivated animals. Of those, the buccalin neuropeptide was further investigated since there is existing evidence in molluscs that buccalin modulates physiology by muscle contraction. The Theba pisana CNS contains two buccalin transcripts that encode precursor proteins that are capable of releasing numerous buccalin peptides. Of these, Tpi-buccalin-2 is most highly expressed within our CNS transcriptome derived from multiple metabolic states. No significant difference was observed at the level of gene expression levels for Tpi-buccalin-2 between active and aestivated animals, suggesting that regulation may reside at the level of post-translational control of peptide abundance. Spatial gene and peptide expression analysis of aestivated snail CNS demonstrated that buccalin-2 has widespread distribution within regions that control several physiological roles. In conclusion, we provide the first detailed molecular analysis of the peptides and associated genes that are related to hypometabolism in a gastropod snail known to undergo extended periods of aestivation.


Assuntos
Biomarcadores/análise , Estivação/fisiologia , Regulação da Expressão Gênica , Fragmentos de Peptídeos/metabolismo , Proteoma/análise , Caramujos/metabolismo , Animais , Sistema Nervoso Central/metabolismo , Hibridização In Situ , Fragmentos de Peptídeos/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Caramujos/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
3.
Diabet Med ; 31(4): 403-11, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24246138

RESUMO

AIMS: The response to glucagon-like peptide 1 receptor agonist treatment may be influenced by endogenous ß-cell function. We investigated whether urinary C-peptide creatinine ratio assessed before or during liraglutide treatment was associated with treatment response. METHODS: A single, outpatient urine sample for urinary C-peptide creatinine ratio was collected 2 h after the largest meal of the day among two separate groups: (1) subjects initiating liraglutide (0.6 â†’ 1.2 mg daily) or (2) subjects already treated with liraglutide for 20-32 weeks. The associations between pretreatment and on-treatment urinary C-peptide creatinine ratio and HbA1c change at 32 weeks were assessed using univariate and multivariate analyses (the ratio was logarithm transformed for multivariate analyses). Changes in HbA1c according to pretreatment urinary C-peptide creatinine ratio quartiles are shown. RESULTS: One hundred and sixteen subjects (70 pretreatment, 46 on treatment) with Type 2 diabetes from 10 diabetes centres were studied. In univariate analyses, neither pretreatment nor on-treatment urinary C-peptide creatinine ratio correlated with HbA1c change (Spearman rank correlation coefficient, r = -0.17, P = 0.17 and r = -0.20, P = 0.19, respectively). In multi-linear regression analyses, entering baseline HbA1c and log urinary C-peptide creatinine ratio, pretreatment and on-treatment log urinary C-peptide creatinine ratio became significantly associated with HbA1c change (P = 0.048 and P = 0.040, respectively). Mean (sd) HbA1c changes from baseline in quartiles 1 to 4 of pretreatment urinary C-peptide creatinine ratio were -3 ± 17 mmol/mol (-0.3 ± 1.6%) (P = 0.52), -12 ± 15 mmol/mol (-1.1 ± 1.4%) (P = 0.003), -11 ± 13 mmol/mol (-1.0 ± 1.2%) (P = 0.002) and -12±17 mmol/mol (-1.1±1.6%) (P=0.016), respectively. CONCLUSIONS: Postprandial urinary C-peptide creatinine ratios before and during liraglutide treatment were weakly associated with the glycaemic response to treatment. Low pretreatment urinary C-peptide creatinine ratio may be more useful than higher values by predicting poorer glycaemic response.


Assuntos
Peptídeo C/urina , Creatinina/urina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Incretinas/uso terapêutico , Período Pós-Prandial , Idoso , Diabetes Mellitus Tipo 2/urina , Feminino , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Hemoglobinas Glicadas/análise , Humanos , Liraglutida , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
4.
J Microsc ; 253(3): 204-18, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24467513

RESUMO

BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) fluorophores are widely used in bioimaging to label proteins, lipids and nucleotides, but in spite of their attractive optical properties they tend to be prone to self-quenching because of their notably small Stokes shift. Herein, we compare two BODIPY compounds from a recently developed family of naphthyridine substituted BODIPY derivatives, one a visible emitting derivative (BODIPY-VIS) and one a near-infrared emitting fluorophore with a Stokes shift of approximately 165 nm as contrast reagents for live mammalian cells and murine brain tissue. The compounds were rendered water soluble by their conjugation to polyethylene glycol (PEG). Both PEGylated compounds exhibited good cell uptake compared with their parent compounds and confocal fluorescence microscopy revealed all dyes explored to be nuclear excluding, localizing predominantly within the lipophilic organelles; the endoplasmic reticulum and mitochondria. Cytotoxicity studies revealed that these BODIPY derivatives are modestly cytotoxic at concentrations exceeding 10 µM where they induce apoptosis and necrosis. Although the quantum yield of emission of the visible emitting fluorophore was over an order of magnitude greater than the Mega-Stokes shifted probe, the latter showed considerably reduced tendency to self quench and less interference from autofluorescence. The near-infrared probe also showed good penetrability and staining in live tissue samples. In the latter case similar tendency to exclude the nucleus and to localize in the mitochondria and endoplasmic reticulum was observed as in live cells. This to our knowledge is the first demonstration of such a Mega-Stokes BODIPY probe applied to cell and tissue imaging.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Histocitoquímica/métodos , Microscopia de Fluorescência/métodos , Animais , Apoptose/efeitos dos fármacos , Compostos de Boro/farmacocinética , Compostos de Boro/farmacologia , Química Encefálica , Células CHO , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Cricetulus , Feminino , Corantes Fluorescentes/farmacocinética , Corantes Fluorescentes/farmacologia , Células HeLa , Humanos , Camundongos , Água
5.
Psychopharmacology (Berl) ; 201(4): 557-68, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18795267

RESUMO

RATIONALE: The use of animal models to study existing medications for smoking cessation can elucidate the mechanism(s) of action of cessation agents and further validate the models for medication development. OBJECTIVE: The objective of the study was to evaluate the response of nicotine self-administration (NSA) to pharmacological agents related to the smoking cessation medication bupropion and to nicotine dosing mimicking nicotine replacement on fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. MATERIALS AND METHODS: NSA was maintained at a nicotine dose of 30 microg/kg/infusion i.v. in rats trained on FR5 and PR40% schedules. Pharmacological manipulations related to bupropion were examined by treating animals with a dopamine reuptake inhibitor [GBR 12909 (GBR)], a norepinephrine reuptake inhibitor [nisoxetine (NIS)], and a nicotinic antagonist [dihydro-beta-erythroidine (DHbetaE)]. The effect of nicotine replacement was examined on the PR schedule by chronic dosing with osmotic minipumps. RESULTS: Significant treatment effects occurred with NIS and combinations of NIS-DHbetaE and with GBR on response rates. Chronic nicotine dosing reduced self-administration. The two schedules yielded different results with some treatments. CONCLUSIONS: Noradrenergic-nicotinic cholinergic interactions and enhanced responding consequent to dopamine reuptake inhibition may be part of the complex behavioral pharmacology of bupropion-like compounds. Observation of differential results with the two schedules has implication for the use of self-administration techniques to elaborate the mechanisms of dependence as well as drug discovery.


Assuntos
Bupropiona/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Animais , Dopamina/metabolismo , Esquema de Medicação , Infusões Intravenosas , Masculino , Norepinefrina/metabolismo , Ratos , Ratos Long-Evans , Receptores Nicotínicos/efeitos dos fármacos , Receptores Nicotínicos/metabolismo , Esquema de Reforço , Autoadministração , Abandono do Hábito de Fumar
6.
J Perinatol ; 38(2): 110-117, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29048413

RESUMO

Aplasia cutis congenita (ACC) is a term describing absence of skin at birth. ACC is a rare cutaneous finding, often noted with no other physical abnormalities. The etiology of ACC varies, and there are likely several causes for its development. ACC can be located anywhere on the body. Its clinical appearance and location can alert the clinician to other potential abnormalities and associations. This discussion covers the diagnosis of ACC and its subtypes and associations in order to provide a pragmatic, clinically relevant and patient-centered approach to evaluation and treatment.


Assuntos
Displasia Ectodérmica/etiologia , Displasia Ectodérmica/cirurgia , Diagnóstico Diferencial , Displasia Ectodérmica/classificação , Displasia Ectodérmica/diagnóstico , Humanos , Recém-Nascido
7.
Peptides ; 80: 61-71, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26303007

RESUMO

Hypometabolism is a physiological state of dormancy entered by many animals in times of environmental stress. There are gaps in our understanding of the molecular components used by animals to achieve this metabolic state. The availability of genomic and transcriptome data can be useful to study the process of hypometabolism at the molecular level. In this study, we use the land snail Theba pisana to identify peptides that may be involved in the hypometabolic state known as aestivation. We found a total of 22 neuropeptides in the central nervous system (CNS) that were differentially produced during activity and aestivation based on mass spectral-based neuropeptidome analysis. Of these, 4 were upregulated in active animals and 18 were upregulated in aestivation. A neuropeptide known to regulate muscle contractions in a variety of molluscs, the small cardioactive peptide A (sCAPA), and a peptide of yet unknown function (termed Aestivation Associated Peptide 12) were chosen for further investigation using temporal and spatial expression analysis of the precursor gene and peptide. Both peptides share expression within regions of the CNS cerebral ganglia and suboesophageal ganglia. Relative transcript abundance suggests that regulation of peptide synthesis and secretion is post-transcriptional. In summary, we provide new insights into the molecular basis of the regulation of aestivation in land snails through CNS peptide control.


Assuntos
Sistema Nervoso Central/metabolismo , Peptídeos/metabolismo , Caramujos/fisiologia , Animais , Expressão Gênica , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Peptídeos/genética , Regulação para Cima
8.
Sci Rep ; 6: 20685, 2016 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-26852673

RESUMO

The land snail Theba pisana is native to the Mediterranean region but has become one of the most abundant invasive species worldwide. Here, we present three transcriptomes of this agriculture pest derived from three tissues: the central nervous system, hepatopancreas (digestive gland), and foot muscle. Sequencing of the three tissues produced 339,479,092 high quality reads and a global de novo assembly generated a total of 250,848 unique transcripts (unigenes). BLAST analysis mapped 52,590 unigenes to NCBI non-redundant protein databases and further functional analysis annotated 21,849 unigenes with gene ontology. We report that T. pisana transcripts have representatives in all functional classes and a comparison of differentially expressed transcripts amongst all three tissues demonstrates enormous differences in their potential metabolic activities. The genes differentially expressed include those with sequence similarity to those genes associated with multiple bacterial diseases and neurological diseases. To provide a valuable resource that will assist functional genomics study, we have implemented a user-friendly web interface, ThebaDB (http://thebadb.bioinfo-minzhao.org/). This online database allows for complex text queries, sequence searches, and data browsing by enriched functional terms and KEGG mapping.


Assuntos
Bases de Dados Genéticas , Caramujos/genética , Transcriptoma , Animais , Sistema Nervoso Central/metabolismo , Mapeamento de Sequências Contíguas , , Hepatopâncreas/metabolismo , Internet , Músculo Esquelético/metabolismo , Interface Usuário-Computador
9.
Peptides ; 80: 32-39, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26752717

RESUMO

Increased understanding of the molecular components involved in mollusc reproduction may assist in understanding the evolutionary adaptations used by animals, including hermaphrodites, to produce offspring. The neuropeptide conopressin, a member of the vasopressin/oxytocin-like peptide family, can modulate various reproductive activities in invertebrates. In this study, we used the hermaphroditic land snail, Theba pisana, to investigate the presence and tissue-specific distribution of a conopressin gene. Our transcriptomic analysis of T. pisana CNS sheath tissue has revealed two conopressin gene transcripts (Tpi-conopressin-1 and Tpi-conopressin-2), each encoding for precursors containing an identical conopressin nonapeptide and a variable neurophysin. T. pisana conopressins share high identity with other land snails and slugs, as well as other mollusc and vertebrate vasopressin/oxytocin, supported by phylogenetic analysis. Conserved residues in the T. pisana neurophysin are important for peptide binding, and we present molecular dynamic models demonstrating the most likely stable structure of the Tpi-conopressin-1 peptide when associated with neurophysin. RT-PCR shows that Tpi-conopressin-1 is additionally expressed in reproductive tissues, including the dart sac, where abundant spatial expression throughout the sac region is found; this implies a role in 'love' dart synthesis or dart injection during mating. The presence of a conopressin receptor in the CNS sheath indicates CNS neural excitation. In summary, this study represents a detailed molecular analysis of conopressin in a land snail.


Assuntos
Peptídeos/genética , Peptídeos/metabolismo , Precursores de Proteínas/metabolismo , Caramujos/química , Animais , Expressão Gênica , Simulação de Dinâmica Molecular , Neurofisinas/química , Ocitocina/análogos & derivados , Ocitocina/química , Peptídeos/química , Filogenia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Precursores de Proteínas/química , Precursores de Proteínas/genética , Receptores de Vasopressinas/genética , Receptores de Vasopressinas/metabolismo , Homologia de Sequência de Aminoácidos , Caramujos/genética , Caramujos/metabolismo
10.
J R Coll Physicians Edinb ; 45(2): 143-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26181532

RESUMO

There is increasing evidence of the benefits of having a mentor during the early years as a consultant. Mentoring encourages and provides support to an individual in their professional development. Although there are different forms of mentoring there is recognition that developing a formal mentoring scheme can provide a consistent approach and support within a framework. The Royal College of Physicians of Edinburgh has introduced a mentoring scheme for new consultants that provides a forum for supporting them in their ongoing professional wellbeing. There is potential that the process of mentoring can improve an individual's development, and motivate and encourage them to develop the skills needed to achieve their goals, thus having an impact on ultimately improving their ability to deliver an effective patient-centred service.


Assuntos
Consultores , Educação Médica Continuada , Mentores , Humanos
11.
Neuroscience ; 96(4): 735-42, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10727791

RESUMO

The objective of this study was to determine whether the pedunculopontine tegmental nucleus plays a role in the maintenance of nicotine self-administration, and whether the ascending cholinergic projection from this nucleus to midbrain dopamine neurons in the ventral tegmental area might be involved. Studies were done with rats trained to self-administer nicotine intravenously. Self-administration was examined before and after the pedunculopontine tegmental nucleus was lesioned with the ethylcholine mustard aziridinium ion, a selective cholinergic toxin. Lesions were assessed qualitatively and quantitatively in histological sections stained for either nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry to identify cholinergic neurons, or for Nissl. Self-administration was also tested after an acute manipulation in which microinfusions of the nicotinic cholinergic antagonist dihydro-beta-erythroidine were made into the pedunculopontine tegmentum. Infusions of neurotoxin into the pedunculopontine tegmentum reduced nicotine self-administration behaviour when tested weeks later. Toxin treatment reduced the number of cholinergic neurons in the tegmentum, while largely sparing the non-cholinergic population in this area. Lesions were limited to the pedunculopontine area and did not extend to the neighboring laterodorsal tegmental nucleus or to the substantia nigra. Acute manipulation of the pedunculopontine tegmental nucleus with microinfusions of dihydro-beta-erythroidine also produced an attenuation of nicotine self-administration. Collectively these data show that the pedunculopontine tegmental nucleus is part of the neuronal circuitry mediating nicotine self-administration, and that the population of cholinergic neurons is likely a critical element.


Assuntos
Acetilcolina/metabolismo , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Fibras Colinérgicas/efeitos dos fármacos , Fibras Colinérgicas/metabolismo , Degeneração Neural/induzido quimicamente , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Ponte/efeitos dos fármacos , Ponte/metabolismo , Tegmento Mesencefálico/efeitos dos fármacos , Tegmento Mesencefálico/metabolismo , Animais , Aziridinas/farmacologia , Colina/análogos & derivados , Colina/farmacologia , Fibras Colinérgicas/ultraestrutura , Denervação , Di-Hidro-beta-Eritroidina/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Ibotênico/farmacologia , Masculino , Bloqueadores Neuromusculares/farmacologia , Neurônios/citologia , Neurotoxinas/farmacologia , Ponte/citologia , Ratos , Ratos Long-Evans , Autoadministração , Tegmento Mesencefálico/citologia , Tabagismo/fisiopatologia
12.
Psychopharmacology (Berl) ; 158(2): 190-7, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11702093

RESUMO

RATIONALE: The pedunculopontine tegmental nucleus (PPTg) is part of the neuronal circuit activated by self-administered nicotine. The cholinergic neurons of the PPTg comprise a prominent projection to midbrain dopamine neurons. However, anatomical studies of Fos expression suggest that nicotine targets primarily non-cholinergic neurons in the PPTg, especially GABAergic and glutamatergic neurons. OBJECTIVE: The objective of these experiments was to examine the role of GABA manipulations in the PPTg on nicotine self-administration. METHODS AND RESULTS: Rats trained to self-administer nicotine or cocaine intravenously were prepared with brain microcannulae directed to the PPTg. Intra-PPTg microinfusions of the GABA agonists muscimol (10-50 ng) and baclofen (30-60 ng) reduced nicotine self-administration maintained on a fixed-ratio schedule of reinforcement (30 microg/kg per infusion); self-administration of cocaine (0.3 mg/kg per infusion) under an identical schedule was not affected. Muscimol and baclofen were also examined after intra-PPTg microinfusion in animals trained to self-administer nicotine on a progressive-ratio schedule (10 and 30 microg/kg per infusion). Progressive-ratio responding was sensitive to pharmacological manipulations such as a change in the nicotine dose available for self-administration, or intra-PPTg microinfusion of the nicotinic antagonist dihydro-beta-erythroidine (30 microg). However, nicotine self-administration on a progressive-ratio schedule was not altered by intra-PPTg microinfusions of GABA agonists. CONCLUSIONS: These data confirm that the PPTg is involved in nicotine self-administration, a conclusion that is independent of the schedule of reinforcement that is used. GABAergic mechanisms in the PPTg play a selective role in nicotine reinforcement compared to cocaine, and that role is restricted to the characteristics of reinforcement measured by fixed-ratio responding.


Assuntos
Agonistas GABAérgicos/farmacologia , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Tegmento Mesencefálico/efeitos dos fármacos , Animais , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/fisiologia , Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Long-Evans , Esquema de Reforço , Autoadministração , Tegmento Mesencefálico/fisiologia
13.
Psychopharmacology (Berl) ; 149(2): 107-14, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10805604

RESUMO

RATIONALE: The mesolimbic dopamine system has been implicated in the reinforcing effects of nicotine, a drug which appears to act at least in part through the ventral tegmental area (VTA). Other neuronal elements in the VTA are important in drug reward. In particular, mu opioid receptors in the VTA have been shown to influence cocaine reinforcement. OBJECTIVE: The aim of this study was to test whether the mu opioid receptors in the VTA also regulate the intake of nicotine. METHODS: This research was carried out with animals trained to self-administer nicotine or cocaine, or to respond for food. Mu receptors were targeted with the selective agonist [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) and gamma-aminobutyric acid (GABA) receptors with the selective agonists baclofen and muscimol; each of these compounds was delivered by microinfusion into the VTA. RESULTS: The mu-selective agonist DAMGO, tested over a dose range of 0.005-0.05 microg, had an effect at the highest dose only, where it produced a reduction in self-administration maintained by doses of either 10 microg/kg or 30 microg/kg per infusion of nicotine. Intra-VTA microinfusions of DAMGO did not reinstate extinguished responding previously established for nicotine, nor did they have prominent effects on operant behavior maintained by food. In contrast to the overall limited effects of DAMGO on nicotine self-administration, the GABA agonists muscimol and baclofen each reduced nicotine self-administration substantially when delivered into the VTA, whereas they were less effective against cocaine self-administration. CONCLUSIONS: The lesser effect of DAMGO microinfusions in the VTA on nicotine than cocaine self-administration is associated with the opposite efficacy of GABA agonists. These findings suggest that nicotine and cocaine differentially activate circuitry in which mu receptors are situated, especially GABAergic elements.


Assuntos
Nicotina/farmacologia , Receptores de GABA/metabolismo , Receptores Opioides mu/metabolismo , Área Tegmentar Ventral/metabolismo , Analgésicos Opioides/farmacologia , Animais , Transporte Biológico , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Masculino , Nicotina/administração & dosagem , Nicotina/farmacocinética , Agonistas Nicotínicos/administração & dosagem , Agonistas Nicotínicos/farmacocinética , Ratos , Ratos Long-Evans , Autoadministração , Área Tegmentar Ventral/efeitos dos fármacos
14.
Psychopharmacology (Berl) ; 145(4): 412-7, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10460318

RESUMO

RATIONALE: The pedunculopontine tegmental nucleus (PPTg) has been implicated in drug reward, particularly in the development of dependence. However, little is known of the receptor systems within this nucleus which might be involved. Furthermore, some research suggests that the PPTg may also be part of the neuronal circuitry involved in established drug-taking behavior. OBJECTIVE: The objective of these experiments was to examine the role of mu-opioid and nicotinic cholinergic mechanisms in the PPTg in cocaine self-administration. METHODS: Microinfusions of mu-opioid and nicotinic receptor selective compounds were made into the PPTg of rats trained to self-administer cocaine intravenously, in the vicinity of cholinergic cells which are known to project to the midbrain dopamine neurons of the ventral tegmental area (VTA). RESULTS: The mu-opioid selective agonist DAMGO, tested at doses of 0, 0.05 and 0.5 microg, produced a dose-related reduction in the number of cocaine infusions obtained during the 1-h self-administration sessions. The mu-selective antagonist CTOP (0-2 microg) and nicotine (0-10 microg) did not produce significant changes in cocaine self-administration. Microinfusions of the nicotinic antagonist dihydro-beta-erythroidine (0-30 microg) produced a small but significant increase in cocaine-maintained responding. CONCLUSIONS: These data show that mu-opioid mechanisms in the PPTg can influence cocaine self-administration markedly. Moreover, the data demonstrate that PPTg circuitry can influence drug reward in already-established drug-reinforced behavior, as well as during the development of dependence (as shown by previous research).


Assuntos
Cocaína/administração & dosagem , Ponte/fisiologia , Receptores Nicotínicos/fisiologia , Receptores Opioides mu/fisiologia , Animais , Ala(2)-MePhe(4)-Gly(5)-Encefalina , Encefalinas/farmacologia , Masculino , Microinjeções , Ratos , Ratos Long-Evans , Autoadministração , Somatostatina/análogos & derivados , Somatostatina/farmacologia , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/fisiologia
15.
Psychopharmacology (Berl) ; 141(4): 428-35, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10090651

RESUMO

Microinfusions of the opioid subtype-selective agonist DAMGO and antagonist CTOP into the ventral tegmental area (VTA) were used to examine the role of mu opioid receptors in this area of the mesolimbic dopamine system in regulating cocaine reinforcement. Long-Evans rats were trained to self-administer cocaine intravenously and prepared with intracranial cannulae directed to the VTA. At doses of cocaine on the descending limb of the cocaine dose-response curve, the mu-selective agonist DAMGO produced a dose-related decrease in cocaine self-administration when delivered by microinfusion into the VTA. At a dose of cocaine on the ascending limb of the self-administration dose-response curve, DAMGO microinfusions produced an increase in responding for the drug. The mu-selective antagonist CTOP produced small effects on cocaine self-administration. A kappa-selective agonist and antagonist (U50,488 and norbinaltorphimine, respectively) produced either no effects or small effects that did not show consistent trends with dose. These experiments suggest that the mu agonist DAMGO is able to shift the dose-response curve for cocaine self-administration to the left. This effect appears to be specific for mu as compared to kappa agonists. These data are consistent with the known differential distribution of opioid receptor subtypes within the VTA, and with the effects of opioid compounds in the VTA on dopamine release in the mesolimbic synaptic field. The data show that a mu opioid mechanism in the somatodendritic region can alter reinforcement processes for cocaine, which acts predominantly at the terminal field of dopamine cells.


Assuntos
Analgésicos Opioides/farmacologia , Cocaína/farmacologia , Encefalinas/farmacologia , Receptores Opioides mu/agonistas , Área Tegmentar Ventral/metabolismo , Animais , Inibidores da Captação de Dopamina/farmacologia , Ala(2)-MePhe(4)-Gly(5)-Encefalina , Injeções Intravenosas , Masculino , Ratos , Ratos Long-Evans , Receptores Opioides delta/agonistas , Receptores Opioides delta/antagonistas & inibidores , Autoadministração , Área Tegmentar Ventral/efeitos dos fármacos
16.
Brain Res ; 653(1-2): 278-84, 1994 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-7982062

RESUMO

Microinfusions of the nicotinic antagonist dihydro-beta-erythroidine (DH beta E) were used to examine the role of the mesolimbic dopamine system in nicotine reinforcement in rats. Infusions of DH beta E into the ventral tegmental area (VTA) prior to the start of i.v. nicotine self-administration sessions resulted in a significant decrease in the number of nicotine infusions voluntarily obtained. In contrast, the same doses of DH beta E infused into the nucleus accumbens were without effect on nicotine self-administration. The reductions caused by DH beta E were specific to nicotine reinforcement; neither operant responding maintained by food, cocaine self-administration, or spontaneous locomotor activity were altered by local applications of DH beta E within the VTA. The reduction in nicotine self-administration following treatment in the VTA was also specific to the nicotinic antagonist, and was not duplicated by infusions of the muscarinic antagonist atropine. Partial lesions of the pedunculopontine tegmental nucleus, the likely origin of cholinergic fibers to the VTA, were without effect on nicotine self-administration, suggesting that the effects of DH beta E were not due to disruption of a tonically active cholinergic input to the VTA from this source. These data show that nicotine acts within the VTA region to initiate processes which are critical to the reinforcing properties of the drug.


Assuntos
Dopamina/fisiologia , Sistema Límbico/fisiologia , Nicotina/administração & dosagem , Tegmento Mesencefálico/fisiologia , Animais , Atropina/farmacologia , Cocaína/administração & dosagem , Di-Hidro-beta-Eritroidina/farmacologia , Alimentos , Sistema Límbico/efeitos dos fármacos , Masculino , Microinjeções , Atividade Motora/efeitos dos fármacos , Nicotina/antagonistas & inibidores , Nicotina/farmacologia , Ratos , Ratos Endogâmicos , Reforço Psicológico , Autoadministração
17.
Phys Med Biol ; 46(6): 1679-93, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11419627

RESUMO

Antibody-targeted therapy of cancer has shown benefits in the treatment of some cancers but selective delivery has not been optimized. Many parameters influence antibody targeting; some will have a greater effect than others and their effects will generally be interrelated. They include effects of blood flow and pressure, vascular permeability, venous and lymphatic drainage, permeation through extravascular spaces, antibody clearance, specificity, affinity and resistance to degradation. Quantitative data about the behaviour of targeting systems can be collected, and it is possible to describe the system in terms of compartments interconnected by equations defining the passage of targeting agents between them. A mathematical model of antibody targeting can thus be built. We have collected data on the time course of the distribution of four different antibody molecules of molecular weight 27, 100 and 150 kDa directed against carcinoembryonic antigen in patients with colorectal cancer. Laboratory data were used for parameters which could not be measured in patients. These data have been used to test the validity of the model for man and to develop it so that it is consistent with the diverse clinical data. The model is then used to understand the effects of changes to a parameter on tumour targeting efficiency and to select those parameters which have the greatest effect in therapy. Affinity of antibody, flow of antibody through the tumour and rate of elimination of antibody from the tumour were shown to be the most powerful parameters determining antibody localization. These concepts can be used to determine design parameters for antibody-targeted cancer therapy.


Assuntos
Reações Antígeno-Anticorpo , Antígeno Carcinoembrionário/imunologia , Antígeno Carcinoembrionário/metabolismo , Ensaios Clínicos como Assunto , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Humanos , Fígado/imunologia , Fígado/fisiologia , Modelos Teóricos , Fatores de Tempo
18.
IEEE Trans Biomed Eng ; 46(10): 1181-5, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10513121

RESUMO

This paper presents an information fusion technique based on a knowledge discovery model, and the case-based reasoning decision framework. Using signal data and database records from the heart disease risk estimation domain, three data fusion methods are discussed. Two of these methods combine information at the retrieval-outcome level, and one method merges data at the discovery-input level. The result of these three models are compared and evaluated against the performance of single-source models. It is shown that the methods that fuse information at the retrieval-outcome level are significantly superior.


Assuntos
Tomada de Decisões Assistida por Computador , Modelos Cardiovasculares , Redes Neurais de Computação , Adulto , Algoritmos , Simulação por Computador , Doença das Coronárias/diagnóstico , Doença das Coronárias/etiologia , Eletrocardiografia , Humanos , Armazenamento e Recuperação da Informação , Masculino , Programas de Rastreamento , Testes de Função Respiratória , Medição de Risco , Fatores de Risco
19.
Artif Intell Med ; 15(3): 275-97, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10206111

RESUMO

Coronary heart disease is a multifactorial disease and it remains the most common cause of death in many countries. Heart rate variability has been used for non-invasive measurement of parasympathetic activity and prediction of cardiac death. Patterns of heart rate variability associated with respiratory sinus arrhythmia have recently been considered as possible indicators of coronary heart disease risk in asymptomatic subjects. The aim of this work is to detect individuals at varying risk of coronary heart disease based on short-term heart rate variability measurements under controlled respiration. Artificial neural networks are used to recognise Poincaré-plot-encoded heart rate variability patterns related to coronary heart disease risk. The results indicate a relatively coarse binary representation of Poincaré plots could be superior to an analogue encoding which, in principle, carries more information.


Assuntos
Doença das Coronárias/diagnóstico , Eletrocardiografia , Redes Neurais de Computação , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco
20.
J Learn Disabil ; 26(10): 674-81, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8151207

RESUMO

Researchers investigated the effects of three different previewing interventions on the oral reading rates of 12 junior and senior high school students with learning disabilities. Under fast-rate listening previewing (FRLP), students were instructed to follow silently as experimenters read from a text at an average rate that was 77.7% faster than the students' current oral reading rate. During slow-rate listening previewing (SRLP), students followed along as experimenters read at an average rate that was 22.5% faster than the students' reading rate. Students were instructed to read passages silently under silent previewing (SP). Immediately following each previewing intervention, students read the same passage aloud. The number of words read correctly per minute and the number of errors per minute served as dependent variables. The results showed statistically significant decreases in error rates under SRLP and SP. The results also showed that SRLP resulted in statistically significantly fewer errors per minute than FRLP. These results suggest that orally reading while students follow along at a rate much higher than their current reading rates may not be as beneficial as reading aloud at slower rates.


Assuntos
Deficiências da Aprendizagem/diagnóstico , Leitura , Adolescente , Feminino , Humanos , Masculino , Projetos de Pesquisa , Instituições Acadêmicas , Estudantes
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