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1.
BMC Chem ; 18(1): 7, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184656

RESUMO

This study marks a pioneering effort in utilizing Vachellia tortilis subsp. raddiana (Savi) Kyal. & Boatwr., (commonly known as acacia raddiana) leaves as both a reducing and stabilizing agent in the green "eco-friendly" synthesis of silver nanoparticles (AgNPs). The research aimed to optimize the AgNPs synthesis process by investigating the influence of pH, temperature, extract volume, and contact time on both the reaction rate and the resulting AgNPs' morphology as well as discuss the potential of AgNPs in detecting some heavy metals. Various characterization methods, such as UV-vis spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), infrared spectroscopy (IR), Zeta sizer, EDAX, and transmitting electron microscopy (TEM), were used to thoroughly analyze the properties of the synthesized AgNPs. The XRD results verified the successful production of AgNPs with a crystallite size between 20 to 30 nm. SEM and TEM analyses revealed that the AgNPs are primarily spherical and rod-shaped, with sizes ranging from 8 to 41 nm. Significantly, the synthesis rate of AgNPs was notably higher in basic conditions (pH 10) at 70 °C. These results underscore the effectiveness of acacia raddiana as a source for sustainable AgNPs synthesis. The study also examined the AgNPs' ability to detect various heavy metal ions colorimetrically, including Hg2+, Cu2+, Pb2+, and Co2+. UV-Vis spectroscopy proved useful for this purpose. The color of AgNPs shifts from brownish-yellow to pale yellow, colorless, pale red, and reddish yellow when detecting Cu2+, Hg2+, Co2+, and Pb2+ ions, respectively. This change results in an alteration of the AgNPs' absorbance band, vanishing with Hg2+ and shifting from 423 to 352 nm, 438 nm, and 429 nm for Cu2+, Co2+, and Pb2+ ions, respectively. The AgNPs showed high sensitivity, with detection limits of 1.322 × 10-5 M, 1.37 × 10-7 M, 1.63 × 10-5 M, and 1.34 × 10-4 M for Hg2+, Cu2+, Pb2+, and Co2+, respectively. This study highlights the potential of using acacia raddiana for the eco-friendly synthesis of AgNPs and their effectiveness as environmental sensors for heavy metals, showcasing strong capabilities in colorimetric detection.

2.
Proc Math Phys Eng Sci ; 476(2236): 20190692, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32398930

RESUMO

The method of oncotripsy, first proposed in Heyden & Ortiz (Heyden & Ortiz 2016 J. Mech. Phys. Solids 92, 164-175 (doi:10.1016/j.jmps.2016.04.016)), exploits aberrations in the material properties and morphology of cancerous cells in order to ablate them selectively by means of tuned low-intensity pulsed ultrasound. We propose the dynamical model of oncotripsy that follows as an application of cell dynamics, statistical mechanical theory of network elasticity and 'birth-death' kinetics to describe the processes of damage and repair of the cytoskeleton. We also develop a reduced dynamical model that approximates the three-dimensional dynamics of the cell and facilitates parametric studies, including sensitivity analysis and process optimization. We show that the dynamical model predicts-and provides a conceptual basis for understanding-the oncotripsy effect and other trends in the data of Mittelstein et al. (Mittelstein et al. 2019 Appl. Phys. Lett. 116, 013701 (doi:10.1063/1.5128627)), for cells in suspension, including the dependence of cell-death curves on cell and process parameters.

3.
Eur J Cancer ; 81: 81-89, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28618305

RESUMO

BACKGROUND: Preclinical studies suggest synergistic antitumour effects of mammalian target of rapamycin (mTOR) inhibitor such as temsirolimus combined with anti-EGFR monoclonal antibody such as cetuximab. METHODS: Temsirolimus (T) and cetuximab (C) were combined and escalated in cohorts of patients with advanced or metastatic solid tumours, respectively from 15 to 25 mg and 150-250 mg/m2, until the maximum tolerated dose (MTD) was determined. Effort was made in the expansion cohort to enrol patients harbouring a molecular aberration in the human epidermal growth factor receptor (EGFR) and/or phosphoinositide 3-kinase (PI3K) pathways. Paired biopsies were optional to evaluate pathway modulation. RESULTS: Among 39 patients enrolled, three experienced dose-limiting toxicities (DLTs): pulmonary embolism (C200 + T20), stomatitis (C250 + T20) and acneiform rash (C250 + T25). The weekly C 250 mg/m2 and T 25 mg dose level was selected as the MTD. The most common treatment-related adverse events were: acneiform rash (97%), oral mucositis (82%), fatigue (59%), nausea (41%) and diarrhoea (36%). The median progression-free survival (PFS) and overall survival (OS) were respectively 2.0 months [95% CI: 1.8, 3.5] and 7.5 months [95% CI: 5.5, 11.9]. Among all patients, partial responses (PRs) and stable diseases (SDs) were observed in 2 (5.1%) and 18 patients (46.2%), respectively. The objective response rate (ORR) in patients with a molecular aberration was 2/14 (14%), versus 0/24 in those without molecular aberration. CONCLUSIONS: Combination of T + C showed significant but manageable toxicities. Due to modest clinical activity, further evaluation is not recommended. Molecular selection could potentially increase the objective response rate and should be implemented during drug development.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Análise de Sobrevida
4.
Appl Radiat Isot ; 108: 129-132, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26720262

RESUMO

In this study, shielding calculation and criticality safety analysis were carried out for general material testing reactor (MTR) research reactors interim storage and relevant transportation cask. During these processes, three major terms were considered: source term, shielding, and criticality calculations. The Monte Carlo transport code MCNP5 was used for shielding calculation and criticality safety analysis and ORIGEN2.1 code for source term calculation. According to the results obtained, a cylindrical cask with body, top, and bottom thicknesses of 18, 13, and 13 cm, respectively, was accepted as the dual-purpose cask. Furthermore, it is shown that the total dose rates are below the normal transport criteria that meet the standards specified.

5.
J Matern Fetal Neonatal Med ; 26(7): 716-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23205864

RESUMO

OBJECTIVES: To compare vaginal with intramuscular progesterone administration to prevent preterm labor in women with singleton pregnancies and at increased risk of preterm birth. STUDY DESIGN: Prospective comparative clinical trial. POPULATION: One hundred and sixty pregnant women at 20-24 weeks gestation at the risk of preterm labor were classified into: 80 women who received micronized progesterone tablets 200 mg vaginally daily (Group A) and 80 women who received 100 mg progesterone in the form of intramuscular every third day (Group B). METHODS: Estimation of gestational age, assessment of fetal growth and fetal biophysical profile by trans-abdominal ultrasonographic examination was done every 4 weeks till delivery. Measurement of cervical length was achieved by transvaginal ultrasonography, done every 4 weeks till delivery. MAIN OUTCOME MEASURES: Incidence of preterm delivery, mean gestational age and the incidence of adverse events of intramuscular versus vaginal route of progesterone administration. RESULTS: The incidence of preterm delivery in Group A was 20% and in Group B was 27.5%. The difference between both groups was statistically insignificant. In addition, the rate of adverse events reported in women received injectable progesterone was significantly higher than the rate of adverse events reported in women who received vaginal progesterone therapy. CONCLUSION: Vaginally administrated progesterone was nearly as equally effective as intramuscular progesterone in the prevention of preterm labor in women at risk and in the meantime has less undesirable events.


Assuntos
Nascimento Prematuro/prevenção & controle , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Administração Intravaginal , Adulto , Feminino , Humanos , Injeções Intramusculares , Gravidez , Estudos Prospectivos , Adulto Jovem
6.
Artigo em Inglês | MEDLINE | ID: mdl-22580139

RESUMO

An interesting series of heterocyclic mixed ligand of oxovanadium(IV) complexes have been synthesized by the reaction of vanadium(IV) sulfate with rhodanine azo (HL(n)) in the presence of ß-diketon (LH). The elemental analysis, magnetic moments, spectral (UV-Vis, IR, (1)HNMR and ESR) with thermal studies were used to characterize the isolated complexes. The IR showed that the ligands (HL(n) and LH) act as a monobasic bidentate through the (NN), oxygen keto moiety and oxygen atom of the two enolate groups thereby forming a six-membered. The molar conductivities show that all the complexes are non-electrolytes. The ESR spectra indicate that the free electron is in d(xy) orbital. The calculated bonding parameter indicates that in-plane σ-bonding is more covalent than in-plane π-bonding. The coordination geometry around oxovanadium(IV) in all complexes is a hex-coordinated trans octahedral, with one bidentate ligand (L(n)), and one bidentate ligand (L). Electronic and magnetic data proposed the octahedral structure for all complexes under investigation. ESR spectra of VO(2+) reveal data that confirmed the proposed structure. The value of covalency factor (ß(1)(∗))(2) and orbital reduction factor K accounts for the covalent nature of the complexes. All electronic transitions were assigned. The Hammett's constant is also discussed.


Assuntos
Química Bioinorgânica , Química Farmacêutica , Complexos de Coordenação/química , Vanadatos/química , Condutividade Elétrica , Espectroscopia de Ressonância de Spin Eletrônica , Elétrons , Cinética , Ligantes , Espectroscopia de Ressonância Magnética , Magnetismo , Rodanina/química , Espectrofotometria Infravermelho , Termogravimetria
7.
Pediatr Blood Cancer ; 54(1): 166-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19606456

RESUMO

We describe four cases of a localized, granulomatous reaction to BCG including ipsilateral painful, suppurative lymphadenopathy associated with donor immune reconstitution following allogeneic haematopoietic stem cell transplant performed in infancy and preceded by uneventful, routine BCG immunisation. The management of the inflammatory disease in these cases with surgery, antimycobacterial chemotherapy and steroids, is discussed.


Assuntos
Vacina BCG/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Inflamação/imunologia , Linfadenite/imunologia , Linfadenite/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Transplante Homólogo
8.
Bioinspir Biomim ; 3: 014001, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18364559

RESUMO

The marine boxfishes have rigid keeled exteriors (carapaces) unlike most fishes, yet exhibit high stability, high maneuverability and relatively low drag given their large cross-sectional area. These characteristics lend themselves well to bioinspired design. Based on previous stereolithographic boxfish model experiments, it was determined that vortical flows develop around the carapace keels, producing self-correcting forces that facilitate swimming in smooth trajectories. To determine if similar self-correcting flows occur in live, actively swimming boxfishes, two species of boxfishes (Ostracion meleagris and Lactophrys triqueter) were induced to swim against currents in a water tunnel, while flows around the fishes were quantified using digital particle image velocimetry. Significant pitch events were rare and short lived in the fishes examined. When these events were observed, spiral flows around the keels qualitatively similar to those observed around models were always present, with greater vortex circulation occurring as pitch angles deviated from 0 degrees . Vortex circulation was higher in live fishes than models presumably because of pectoral fin interaction with the keel-induced flows. The ability of boxfishes to modify their underlying self-correcting system with powered fin control is important for achieving high levels of both stability and maneuverability. Although the challenges of performing stability and maneuverability research on fishes are significant, the results of this study together with future studies employing innovative new approaches promise to provide valuable inspiration for the designers of bioinspired aquatic vehicles.


Assuntos
Relógios Biológicos/fisiologia , Biomimética/métodos , Retroalimentação/fisiologia , Modelos Biológicos , Reologia/métodos , Natação/fisiologia , Tetraodontiformes/fisiologia , Animais , Simulação por Computador
10.
Conf Proc IEEE Eng Med Biol Soc ; 2004: 3615-7, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-17271074

RESUMO

The zebrafish (Danio rerio) has emerged as one of the primary experimental models of developmental cardiovascular research. Recent progress in flow visualization techniques along with the existing genetic map of the species has made zebrafish amenable to a variety of experiments relating cardiac developmental structure and function. One essential tool in establishing the proper functioning of the heart is the electrocardiogram (ECG). This study presents a methodology whereby the ECGs of embryonic zebrafish could be used in assessing the electrophysiological consequences of genetically-, mechanically-, or pharmacokinetically-induced cardiac perturbations. Five day post-fertilization (dpf) embryos produced repeating bimodal ECGs with clearly distinguished atrial (P) and ventricular (R) depolarization waves. P-R intervals along with P-P intervals are cited.

11.
Conf Proc IEEE Eng Med Biol Soc ; 2004: 3654-7, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-17271085

RESUMO

The course of cardiac remodeling after an acute cardiac MI, might affect the orientation of the cardiac muscle fibers as well as their contraction behavior. This may result in alteration of the untwisting during isovolumic relaxation phase, which might have effects on rapid early filling phase. In the present article, the variation of the time constant of isovolumic pressure drop (tau) has been studied during the course of cardiac remodeling after different types of induced myocardial infarction (MI) in sheep. The results for each group show different patterns of change in tau. The normalized tau curve in all three groups of anteroapical, anterobasal and posterobasal MI group show a rise 30 minutes after infarction. Two weeks later, the pressure drop constants decline to a lower level than baseline and by eight weeks after infarction, the time constant reached around the baseline level.

12.
Rev Epidemiol Sante Publique ; 51(1 Pt 2): 151-8, 2003 Feb.
Artigo em Francês | MEDLINE | ID: mdl-12684573

RESUMO

The French SEROCO and HEMOCO hospital-based cohorts have enrolled and followed HIV-infected patients, before and after the highly active antiretroviral therapy era. Among the objectives in 1988, was explicitly mentioned the constitution of a centralised bank of biological material (serums at enrollment and every 6 months, PBMC at enrollment and every 18 months). This paper details the organisation of the bank and the numerous studies performed from this bank, and presents a few simple decision rules which have been developed with the growing acquired experience.


Assuntos
Bancos de Sangue/organização & administração , Preservação de Sangue , Estudos de Coortes , Criopreservação , Terapia Antirretroviral de Alta Atividade , Feminino , França , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Manejo de Espécimes/métodos
13.
Pediatr Cardiol ; 24(4): 375-80, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12632224

RESUMO

Computational fluid dynamic (CFD) experimentation provides a unique medium for detailed examination of flow through complex embryonic heart structures. The purpose of this investigation was to demonstrate that streaming blood flow patterns exist in the early embryonic heart and that fluid surface stresses change significantly with anomalous alterations in fetal heart lumen shape. Stages 10 and 11 early human embryo hearts were digitized as calibrated two-dimensional (2D) cross-sectional sequential images. A 3D surface was constructed from the stacking of these 2D images. CFD flow solutions were obtained (steady and pulsatile flow). Particle traces were placed in the inlet and outlet portions of these two stages. Sections of the embryonic heart were artificially reshaped. CFD flow solutions were obtained and surface stress changes analyzed. Streaming was shown to exist, with particles released on one or the other side of the cardiac lumen tending not to cross over and mix with particles released from the opposite side of the cardiac lumen. Shear stress changes (stage 10) occur in the altered lumens. Streaming exists in steady and pulsatile flow scenarios in the embryonic heart models. There are differences in local shear stress distributions with surface shape anomalies of the fetal heart lumen. These observations may help shed light on the potential role of fluid dynamic factors in determining patterns of abnormal heart development.


Assuntos
Cardiopatias Congênitas/diagnóstico , Coração/embriologia , Coração/fisiopatologia , Processamento de Imagem Assistida por Computador , Modelos Cardiovasculares , Fluxo Pulsátil , Velocidade do Fluxo Sanguíneo , Simulação por Computador , Humanos , Pesquisa , Estresse Mecânico
14.
Eur J Heart Fail ; 4(3): 235-42, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12034146

RESUMO

Cardiotoxicity is a potential side effect of few chemotherapeutic agents. The anthracycline class of cytotoxic antibiotics are the most famous, but other chemotherapeutic agents can also cause serious cardiotoxicity and are not so well recognised. Examples include cyclophosphamide, ifosfamide, mitomycin and fluorouracil. Prediction and hence prophylaxis has always been a difficult task. Ideal monitoring techniques, upon which efficient prophylaxis depends, are yet to be determined. Current prophylaxis relies upon early detection of systolic and/or diastolic dysfunction. While somewhat useful, in some cases by the time defects are detected progression of chemotherapy-induced cardiomyopathy is beyond prevention. Prophylaxis would be much more efficient if a biochemical marker of myocardiocyte damage could be reliably used to stop further chemotherapy at the correct time before irreversible progressive 'macroscopic' damage becomes evident upon imaging. Work is currently progressing to identify the role of markers such as troponins and natriuretic peptides in this regard.


Assuntos
Antineoplásicos/efeitos adversos , Cardiopatias/induzido quimicamente , Coração/efeitos dos fármacos , Antibióticos Antineoplásicos/efeitos adversos , Antineoplásicos Alquilantes/efeitos adversos , Biomarcadores , Cardiopatias/prevenção & controle , Humanos , Fatores de Risco
15.
Comput Med Imaging Graph ; 25(6): 459-63, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11679207

RESUMO

Scaled physical models can be useful in analyzing stage-specific hemodynamics in the embryonic human heart to address correlations between early physical stressors and myocardial wall responses. We generated models of the cardiac blood space from reconstructions of four digitized human embryo images from Carnegie Collection at the Armed Forces Institute of Pathology. From physical scale models manufactured by stereolithography, compliant sleeves can be created for flow dynamics studies. This novel use of Carnegie collection images and graphical modeling software provides tools for broadening our understanding of normal and aberrant heart formation.


Assuntos
Coração/embriologia , Modelos Anatômicos , Software , Desenvolvimento Embrionário e Fetal/fisiologia , Coração/fisiologia , Hemodinâmica , Humanos , Fluxo Sanguíneo Regional
16.
Semin Thorac Cardiovasc Surg ; 13(4): 301-19, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11807730

RESUMO

The Gordian knot of anatomy has been the architectural arrangement of ventricular muscle mass, which may have finally become understood. The description of Francisco Torrent-Guasp's model of the helical heart is presented, which includes the cardiac structures that produce 2 simple loops that start at the pulmonary artery and end in the aorta. An unscrolled ventricular band is shown, achieved by blunt dissection that extends between the points of origin of the right ventricle, at the pulmonary artery root, to termination at the aortic root, in the left ventricle. These components include a spiral horizontal basal loop that surrounds the right and left ventricular cavities, and changes direction to cause a second spiral, produced by almost vertically oriented fibers, giving rise to the helical configuration of the ventricular myocardial band. These anatomic structures are successively activated, as with a peristaltic wave, starting at the right ventricle (just below the pulmonary artery) and progressing toward the aorta to produce a sequence of narrowing, caused by the basal loop contraction, shortening (related predominantly to the descendant segment contraction), lengthening (produced by the ascendant segment contraction), and widening, as a consequence of several factors that act during ventricular myocardium relaxation. These sequences control the ventricular events responsible for ejection to empty and suction to fill. These mechanical interactions of structure and function are defined in relation to chronologic location of the successive cardiac functional events in the aortic, left ventricular, and left atrial recordings.


Assuntos
Coração/anatomia & histologia , Coração/fisiologia , Animais , Ventrículos do Coração/anatomia & histologia , Ventrículos do Coração/ultraestrutura , Humanos , Modelos Cardiovasculares , Contração Miocárdica/fisiologia , Miocárdio/ultraestrutura , Função Ventricular
17.
Semin Thorac Cardiovasc Surg ; 13(4): 333-41, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11807732

RESUMO

The study of the dissemination of the electric impulse throughout the ventricular myocardium, which gave rise to the current theories, was performed without taking into consideration the complex architecture of the cardiac muscle elucidated by more recent researchers. We propose a novel hypothesis based on the special macroscopic structure of the heart, the anisotropic electric and mechanical behavior of the myocardium, the characteristics of the intercellular matrix and its very special collagen scaffolding, chemical composition, and biochemistry. The unique properties of the intercellular matrix would make it especially suited to function, in conjunction with the specialized conducting system (His-Purkinje system), as an efficient anisotropic conductor for the spread of electric activation in the heart, and to allow an optimal sequence of excitation-contraction coupling that results in the coordination of effective myocardial contraction in birds and mammals of the most varied known heart rates.


Assuntos
Matriz Extracelular/fisiologia , Sistema de Condução Cardíaco/anatomia & histologia , Sistema de Condução Cardíaco/fisiologia , Coração/anatomia & histologia , Coração/fisiologia , Animais , Eletrofisiologia , Hemodinâmica/fisiologia , Humanos , Modelos Cardiovasculares , Miocárdio/ultraestrutura
18.
Semin Thorac Cardiovasc Surg ; 13(4): 342-57, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11807733

RESUMO

Torrent-Guasp's model of the helical heart is presented, which includes the cardiac muscular structures that produce 2 simple loops and that start at the pulmonary artery and end in the aorta. These components include a horizontal basal loop that surrounds the right and left ventricles, changes direction through a spiral fold in the ventricular band to cause a ventricular helix produced by now obliquely oriented fibers, forming a descending and ascending segment of the apical loop with an apical vortex. These anatomic concepts are successively activated to produce a sequence of narrowing by the basal loop, shortening by the descending segment, lengthening by the ascending segment, and widening in the cardiac cycle that causes ventricular ejection to empty and suction to fill. The factors responsible for internal torsional movements for cardiac output and suction are defined, together with mechanisms responsible for electromechanical activity produced during sequential changes in contraction and relaxation properties. These interactions of mechanical structure and function are defined in relation to pressure-related cardiac events observed from aortic, left ventricular, and left atrial recordings.


Assuntos
Coração/anatomia & histologia , Coração/fisiologia , Hemodinâmica/fisiologia , Animais , Eletrofisiologia , Humanos , Modelos Cardiovasculares , Função Ventricular
19.
Semin Thorac Cardiovasc Surg ; 13(4): 459-67, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11807741

RESUMO

Ishemic dilated cardiomyopathy results from altered muscle mechanics. Ventricular restoration is aimed at altering the volume and shape changes that follow myocardial infarction. Optimal surgical methods to achieve this goal are not well defined, but it has been shown that sphericity is an important determinant of long-term outcome. We present the rationale and techniques for returning the globular remodeled ventricle to a more elliptical shape. Clinical data from our RESTORE registry does not suggest an improvement in early or late mortality with such methods but opens the way for late evaluation of functional and exercise capacity.


Assuntos
Ventrículos do Coração/patologia , Ventrículos do Coração/cirurgia , Procedimentos Cirúrgicos Cardiovasculares , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/cirurgia , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia
20.
Pharmacol Biochem Behav ; 70(4): 515-30, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11796151

RESUMO

A paradox exists regarding the reinforcing properties of nicotine. The abuse liability associated with smoking equals or exceeds that of other addictive drugs, yet the euphoric, reinforcing and other psychological effects of nicotine, compared to these other drugs, are more subtle, are manifest under more restricted conditions, and do not readily predict the difficulty most smokers experience in achieving abstinence. One possible resolution to this apparent inconsistency is that environmental cues associated with drug delivery become conditioned reinforcers and take on powerful incentive properties that are critically important for sustaining smoking in humans and nicotine self-administration in animals. We tested this hypothesis by using a widely employed self-administration paradigm in which rats press a lever at high rates for 1 h/day to obtain intravenous infusions of nicotine that are paired with two types of visual stimuli: a chamber light that when turned on signals drug availability and a 1-s cue light that signals drug delivery. We show that these visual cues are at least as important as nicotine in sustaining a high rate of responding once self-administration has been established, in the degree to which withdrawing nicotine extinguishes the behavior, and in the reinstatement of lever pressing after extinction. Additional studies demonstrated that the importance of these cues was manifest under both fixed ratio and progressive ratio (PR) schedules of reinforcement. The possibility that nicotine-paired cues are as important as nicotine in smoking behavior should refocus our attention on the psychology and neurobiology of conditioned reinforcers in order to stimulate the development of more effective treatment programs for smoking cessation.


Assuntos
Sinais (Psicologia) , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Fumar/psicologia , Tabagismo/psicologia , Animais , Humanos , Autoadministração/psicologia
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