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1.
Mol Neurobiol ; 58(1): 362-374, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32948930

RESUMO

Alpha synuclein (α-synuclein) is a neuronal protein found predominately in presynaptic terminals. While the pathological effect of α-synuclein aggregates has been a topic of intense study in several neurodegenerative conditions, less attention has been placed on changes in monomeric α-synuclein and related physiological consequences on neuronal function. A growing body of evidence supports an important physiological role of α-synuclein in neurotransmission. In the context of traumatic brain injury (TBI), we hypothesized that the regional abundance of soluble monomeric α-synuclein is altered over a chronic time period post-injury. To this end, we evaluated α-synuclein in the cortex, hippocampus, and striatum of adult rats at 6 h, 1 day, 1, 2, 4, and 8 weeks after controlled cortical impact (CCI) injury. Western blot analysis demonstrated decreased levels of monomer α-synuclein protein in the ipsilateral hippocampus at 6 h, 1 day, 1, 2, and 8 weeks, as well as in the ipsilateral cortex at 1 and 2 weeks and in the ipsilateral striatum at 6 h after CCI compared with sham animals. Immunohistochemical analysis revealed lower α-synuclein and a modest reduction in synaptophysin staining in the ipsilateral hippocampus at 1 week after CCI compared with sham animals, with no evidence of intracellular or extracellular α-synuclein aggregates. Collectively, these findings demonstrate that monomeric α-synuclein protein abundance in the hippocampus is reduced over an extensive (acute-to-chronic) post-injury interval. This deficit may contribute to the chronically impaired neurotransmission known to occur after TBI.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , alfa-Sinucleína/metabolismo , Animais , Lesões Encefálicas Traumáticas/patologia , Masculino , Neuraminidase/metabolismo , Ratos Sprague-Dawley , Solubilidade , Sinaptofisina/metabolismo
2.
Ergonomics ; 53(2): 198-210, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20099174

RESUMO

Management of risk in complex domains such as aviation relies heavily on post-event investigations, requiring complex approaches to fully understand the integration of multi-causal, multi-agent and multi-linear accident sequences. The Event Analysis of Systemic Teamwork methodology (EAST; Stanton et al. 2008) offers such an approach based on network models. In this paper, we apply EAST to a well-known aviation accident case study, highlighting communication between agents as a central theme and investigating the potential for finding agents who were key to the accident. Ultimately, this work aims to develop a new model based on distributed situation awareness (DSA) to demonstrate that the risk inherent in a complex system is dependent on the information flowing within it. By identifying key agents and information elements, we can propose proactive design strategies to optimize the flow of information and help work towards avoiding aviation accidents. Statement of Relevance: This paper introduces a novel application of an holistic methodology for understanding aviation accidents. Furthermore, it introduces an ongoing project developing a nonlinear and prospective method that centralises distributed situation awareness and communication as themes. The relevance of findings are discussed in the context of current ergonomic and aviation issues of design, training and human-system interaction.


Assuntos
Acidentes Aeronáuticos , Causalidade , Gestão da Informação/métodos , Modelos Organizacionais , Gestão de Riscos/organização & administração
3.
Eur J Clin Invest ; 39(9): 775-83, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19531154

RESUMO

BACKGROUND: Inflammation is implicated in chronic heart failure (CHF). In this study, the potential inhibitory effect of peroxisome proliferator-activated receptor-alpha (PPARalpha) activator fenofibrate on monocyte adhesion in CHF patients was investigated in vitro. MATERIALS AND METHODS: Isolated peripheral blood mononuclear cells (PBMCs) were collected from 36 patients (aged 65 +/- 8 years) with symptomatic CHF and from 12 healthy control subjects. The cultured human aortic endothelial cells (HAECs) were stimulated with or without 2 ng mL(-1) tumour necrosis factor-alpha (TNF-alpha) and the inhibitory effects of fenofibrate at 25, 50, 100 and 200 microM on endothelial mononuclear cell adhesion were tested. Furthermore, the HAECs were stimulated with 70% sera obtained from CHF patients and control individuals, respectively, with or without pretreatments with fenofibrate. The endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was then confirmed by mRNA expression and Western blot. RESULTS: We found that the increased adhesion of PBMCs to TNF-alpha-stimulated HAECs in CHF patients was reduced when the HAECs were pretreated with fenofibrate (31% inhibition, P = 0.0121). However, pretreatment of the isolated PBMCs collected from CHF patients with fenofibrate failed to suppress their adherence to TNF-alpha-stimulated HAECs. Furthermore, stimulation of cultured HAECs with CHF patient sera significantly increased VCAM-1 and ICAM-1 expression, which could also be inhibited by fenofibrate. CONCLUSIONS: The fenofibrate directly inhibits monocyte binding by TNF-alpha-activated HAECs, probably through preventing up-regulation of cell adhesion molecules by endothelial cells in response to inflammatory stimuli. This PPARalpha activator may have the potential to ameliorate vascular inflammation in patients with CHF.


Assuntos
Adesão Celular/efeitos dos fármacos , Fenofibrato/farmacologia , Insuficiência Cardíaca/patologia , Monócitos/fisiologia , Molécula 1 de Adesão de Célula Vascular/efeitos dos fármacos , Idoso , Western Blotting , Doença Crônica , Feminino , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Molécula 1 de Adesão de Célula Vascular/biossíntese
4.
Rev Sci Instrum ; 79(3): 035103, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18377041

RESUMO

This paper presents a simple alternative method and system for noninvasive respiratory airflow monitoring. The proposed system uses a piezoceramic transducer to measure respiratory airflow. When a piezoceramic transducer is impacted by respiratory airflow, there is a piezoelectric and a pyroelectric response to pressure and thermal airflow fluctuations. In this study, the selected transducer's response output is dominated by the pyroelectricity factor. Therefore, the piezoelectric effect is not significant and can be ignored in this study. Using the transducer's pyroelectricity to measure thermal flow variations, a subject's respiratory rate and respiratory air volumetric flow rate can be monitored. The proposed system was evaluated for accuracy and response time using quiet and postphysical exertion breathing modes. Using the pneumotach system as a benchmark, the proposed system's respiratory rate measurement accuracy for the two breathing modes is approximately 98.78%. In addition, the proposed system's output voltage is highly correlated with the respiratory volumetric flow rate measured by the selected pneumotach (r2=0.9783). The average correlation coefficient between the pneumotach system's output waveform and the proposed system is approximately 0.9389. Moreover, the proposed system and the selected pneumotach have almost the same rapid response time to respiratory airflow. When compared to a temperature measurement thermistor system, the thermistor on average is approximately 25.3 ms slower than the proposed system. Furthermore, compared to the selected screen-type pneumotach system, the proposed system simplifies the respiration monitoring requirements. Instead of sensing the pressure drop across a mesh screen, like the screen-type pneumotach, it measures respiration at one point within the respiratory airflow. The proposed system benefits from simplified processing circuits and a mesh-free design. The advantages of this new respiratory airflow measurement method are fast response time, high accuracy, low cost, and ease of implementation.


Assuntos
Cerâmica , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Mecânica Respiratória , Trabalho Respiratório , Feminino , Humanos , Masculino
5.
Rev Sci Instrum ; 78(11): 115102, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18052499

RESUMO

A new microcomputer based air temperature measurement system is presented. An accurate temperature measurement is derived from the measurement of sound velocity by using an ultrasonic time-of-flight (TOF) technique. The study proposes a novel algorithm that combines both amplitude modulation (AM) and phase modulation (PM) to get the TOF measurement. The proposed system uses the AM and PM envelope square waveform (APESW) to reduce the error caused by inertia delay. The APESW ultrasonic driving waveform causes an envelope zero and phase inversion phenomenon in the relative waveform of the receiver. To accurately achieve a TOF measurement, the phase inversion phenomenon was used to sufficiently identify the measurement pulse in the received waveform. Additionally, a counter clock technique was combined to compute the phase shifts of the last incomplete cycle for TOF. The presented system can obtain 0.1% TOF resolution for the period corresponding to the 40 kHz frequency ultrasonic wave. Consequently, with the integration of a humidity compensation algorithm, a highly accurate and high resolution temperature measurement can be achieved using the accurate TOF measurement. Experimental results indicate that the combined standard uncertainty of the temperature measurement is approximately 0.39 degrees C. The main advantages of this system are high resolution measurements, narrow bandwidth requirements, and ease of implementation.

6.
Rev Sci Instrum ; 78(6): 065103, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17614634

RESUMO

A novel microcomputer-based ultrasonic distance measurement system is presented. This study proposes an efficient algorithm which combines both the amplitude modulation (AM) and the phase modulation (PM) of the pulse-echo technique. The proposed system can reduce error caused by inertia delay and amplitude attenuation effect when using the AM and PM envelope square wave form (APESW). The APESW ultrasonic driving wave form causes a phase inversion phenomenon in the relative wave form of the receiver. The phase inversion phenomenon sufficiently identifies the "measurement pulse" in the received wave forms, which can be used for accurate time-of-flight (TOF) measurement. In addition, combining a countertechnique to compute the phase shifts of the last cycle for TOF, the presented system can obtain distance resolution of 0.1% of the wavelength corresponding to the 40 kHz frequency of the ultrasonic wave. The standard uncertainty of the proposed distance measurement system is found to be 0.2 mm at a range of 50-500 mm. The APESW signal generator and phase detector of this measuring system are designed on a complex programmable logic device, which is used to govern the TOF measurement and send the data to a personal computer for distance calibration and examination. The main advantages of this APESW system are high resolution, low cost, narrow bandwidth requirement, and ease of implementation.


Assuntos
Eletrônica , Processamento de Sinais Assistido por Computador/instrumentação , Transdutores , Ultrassom , Desenho de Equipamento , Análise de Falha de Equipamento , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
7.
Diabetes Metab ; 32(3): 229-35, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16799399

RESUMO

OBJECTIVES: Peroxisome proliferator-activated receptor gamma is the master regulator of adipocyte differentiation and controls many adipocyte genes in response to anti-diabetic thiazolidinediones (TZDs) and lipid-lowering fibrates. We hypothesized that the combination of TZD+fibrate may be better than the sulfonylurea + statin approach regarding modifying the adipokine profile in diabetic patients with dyslipidemia. METHODS: We measured the lipid profiles and circulating levels of adiponectin, resistin, and inflammatory markers before and after treatment in 24 type 2 diabetic patients with dyslipidemia (aged 64+/-9 years; M/F=5/19). The study patients were randomly assigned to receive an 8-week treatment of either rosiglitazone 4 mg daily and fenofibrate 160 mg daily (PPAR group) or glibenclamide 5 mg daily and atorvastatin 10 mg daily (non-PPAR group). RESULTS: Even though the administration of sulfonylurea+statin can achieve a greater reduction of total cholesterol and LDL-cholesterol levels and a comparable glucose control compared to PPAR treatment, their administration did not change the plasma adipokine levels significantly. In contrast, a significant greater increase of the plasma concentrations of adiponectin (P<0.0001), a trend to a greater decrease of the plasma resistin levels (P=0.061), a significantly greater increase of HDL-cholesterol (P=0.002), and a significantly greater reduction of triglyceride levels (P=0.018) were seen in the PPAR group. CONCLUSIONS: Considering the clinical significance of the adipokine-endothelial interaction in the progression and long-term prognosis of atherosclerosis, the differential effects of PPAR ligands and sulfonylurea+statin on plasma adipokine concentrations demonstrated in this study are interesting foci of investigation in the future.


Assuntos
Adiponectina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Receptores Ativados por Proliferador de Peroxissomo/fisiologia , Compostos de Sulfonilureia/uso terapêutico , Idoso , Glicemia/análise , Índice de Massa Corporal , Estudos de Coortes , Citocinas/sangue , Diabetes Mellitus Tipo 2/complicações , Dislipidemias/sangue , Feminino , Glibureto/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Inflamação , Ligantes , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Rosiglitazona , Tiazolidinedionas/uso terapêutico
8.
Electromyogr Clin Neurophysiol ; 46(2): 67-77, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16795996

RESUMO

To investigate change in coordinative strategies due to wrist immobilization and index loading, postural tremors from the index, hand, and forearm were recorded during different postural holding tasks. The wrist joint was immobilized with a thermoplastic splint in the constrained condition, and a copper mass of 100 grams was applied to the index finger in the loaded condition. The structures of the postural tremors of all upper limb segments among the unloaded-unconstrained, unloaded-constrained, loaded-unconstrained, and loaded-constrained conditions were compared. Index loading exaggerated index/forearm postural tremor, while the load-induced tremor enhancement was no longer evident for wrist immobilization. In the unloaded condition, wrist immobilization resulted specifically in enhancement of carpal postural tremor, rather than in the index and forearm. Index loading induced a marked tremor peak and relative power in the range of 5-8 Hz. Wrist immobilization potentiated the carpal tremor peak of 1-4 Hz in association with enhancement of carpal-forearm mechanical coupling. In light of structural changes in postural tremor, our data suggest that (1) a wrist splint is effective to counteract load-induced enhancement of postural tremor, and (2) freezing of the wrist joint might facilitate compensatory strategies to minimize passive fluctuation transmission from the carpal to index.


Assuntos
Restrição Física/fisiologia , Tremor/fisiopatologia , Suporte de Carga/fisiologia , Articulação do Punho/fisiopatologia , Adolescente , Adulto , Eletromiografia , Feminino , Humanos , Masculino , Músculo Esquelético/fisiopatologia , Postura/fisiologia , Contenções
9.
Neurology ; 49(5): 1278-83, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9371908

RESUMO

We compared the duration of the EMG cortical stimulation silent period (CSSP) elicited in abductor pollicis brevis using transcranial magnetic stimulation (TMS) before and after stereotactic unilateral globus pallidus internus pallidotomy (PAL) in 12 patients with Parkinson's disease. We used TMS stimulus intensities of 200, 150, 120, and 100% of motor evoked potential (MEP) threshold before and after (86 +/- 25 days) PAL. PAL increased CSSP duration at stimulus intensities of 200% of MEP threshold in the hand contralateral to the stereotactic lesion. In a subset of five patients able to remain at rest during pre-PAL testing sessions, PAL decreased the resting MEP/M-wave area ratio in the hand contralateral to the lesion at a stimulus intensity of 120% of MEP threshold. PAL did not significantly modify the effects of TMS in the hand ipsilateral to the globus pallidus lesion. The results suggest that PAL improves the function of cortical motor inhibitory circuits in Parkinson's disease.


Assuntos
Globo Pálido/cirurgia , Magnetismo , Doença de Parkinson/fisiopatologia , Doença de Parkinson/cirurgia , Idoso , Idoso de 80 Anos ou mais , Estimulação Elétrica , Potencial Evocado Motor , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Desempenho Psicomotor , Fatores de Tempo
10.
Neurology ; 53(3): 605-11, 1999 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-10449127

RESUMO

OBJECTIVE: To evaluate the sensitivity of transcranial magnetic stimulation (TMS) to identify upper motor neuron involvement in patients with motor neuron disease. BACKGROUND: Diagnosis of ALS depends on upper and lower motor neuron involvement. Lower motor neuron involvement may be documented with electromyography, whereas definite evidence of upper motor neuron involvement may be elusive. A sensitive, noninvasive test of upper motor neuron function would be useful. METHODS: TMS and clinical assessment in 121 patients with motor neuron disease. RESULTS: TMS revealed evidence of upper motor neuron dysfunction in 84 of 121 (69%) patients, including 30 of 40 (75%) patients with only probable upper motor neuron signs and unsuspected upper motor neuron involvement in 6 of 22 (27%) patients who had purely lower motor neuron syndromes clinically. In selected cases, upper motor neuron involvement identified with TMS was verified in postmortem examination. Increased motor evoked potential threshold was the abnormality observed most frequently and was only weakly related to peripheral compound muscle action potential amplitude. In a subset of 12 patients reexamined after 11+/-6 months, TMS showed progression of abnormalities, including progressive inexcitability of central motor pathways and loss of the normal inhibitory cortical stimulation silent period. CONCLUSIONS: TMS provides a sensitive means for the assessment and monitoring of excitatory and inhibitory upper motor neuron function in motor neuron disease.


Assuntos
Doença dos Neurônios Motores/fisiopatologia , Neurônios Motores/fisiologia , Estimulação Magnética Transcraniana , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
J Neurosci Methods ; 95(1): 55-63, 2000 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-10776815

RESUMO

In this study, we have developed a combined animal motion activity measurement system that combines an infrared light matrix subsystem with an ultrasonic phase shift subsystem for animal activity measurement. Accordingly, in conjunction with an IBM PC/AT compatible personal computer, the combined system has the advantages of both infrared and ultrasonic subsystems. That is, it can at once measure and directly analyze detailed changes in animal activity ranging from locomotion to tremor. The main advantages of this combined system are that it features real time data acquisition with the option of animated real time or recorded display/playback of the animal's motion. Additionally, under the multi-task operating condition of IBM PC, it can acquire and process behavior using both IR and ultrasound systems simultaneously. Traditional systems have had to make separate runs for gross and fine movement recording. This combined system can be profitably employed for normative behavioral activity studies and for neurological and pharmacological research.


Assuntos
Sistemas Computacionais , Raios Infravermelhos , Atividade Motora , Ultrassom , Anfetamina/farmacologia , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Diazepam/farmacologia , Hipnóticos e Sedativos/farmacologia , Atividade Motora/efeitos dos fármacos , Ratos
12.
J Neurosci Methods ; 63(1-2): 205-9, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8788065

RESUMO

A new electronic system has been developed to trace the location and movement of small animals in an open-field environment. The system, incorporated with a conventional touch panel position sensor (TPPS) and an IBM AT compatible computer, automtically digitizes and records the moving path of the animal. The detection principle of the TPPS is based on the pressure effect. Whenever an animal is put on the TPPS, the location of the animal can be detected. The personal computer system is in corporate to record the locomotion data of the animal. The system described here is shown to be a reliable and accurate tool to record the moving path of an animal. This measurement did not require extra light or other stimuli, and the apparatus is low priced, and simple to build up and user friendly.


Assuntos
Comportamento Animal/fisiologia , Periféricos de Computador , Locomoção/fisiologia , Software , Animais , Computadores , Processamento Eletrônico de Dados , Estudos de Avaliação como Assunto , Ratos
13.
J Neurosci Methods ; 70(1): 45-9, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8982981

RESUMO

A new ultrasonic method is presented for measuring the minute motion activities of rats. A pair of low-cost 40 kHz ultrasonic transducers are used to transmit ultrasound toward a rat and receive the ultrasound reflected from the rat. The relative motion of the rat modulates the phase difference between the transmitted and received ultrasound signals. An 8-bit digital phase meter was designed to record the phase difference signal which was used to reconstruct the relative motion waveform of the rat in an 8751 single-chip microcomputer. The reconstructed data are then sent to a PC-AT microcomputer for further processing. This method employs a spectrum analysis for the reconstructed data and can measure three minute motion activities including locomotor activity (LMA), tremor and myoclonia. Finally, the method has been tested with real animal experiments. The main advantages of this new method are that it is non-invasive, non-contact, low cost and high precision. This new method could also be profitably employed for other behavioral studies and offer potential for research in basic medicine.


Assuntos
Comportamento Animal , Etologia/instrumentação , Atividade Motora , Mioclonia , Processamento de Sinais Assistido por Computador , Tremor , Ultrassom , Animais , Eletromiografia/instrumentação , Desenho de Equipamento , Análise de Fourier , Masculino , Microcomputadores , Atividade Motora/fisiologia , Mioclonia/diagnóstico por imagem , Mioclonia/fisiopatologia , Ratos , Ratos Sprague-Dawley , Software , Tremor/diagnóstico por imagem , Tremor/fisiopatologia , Ultrassonografia
14.
J Neurosci Methods ; 50(3): 291-9, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8152240

RESUMO

A method for selecting a usable carbon-fiber electrode using the equivalent resistance and capacitance is presented. This method uses an instrument with a PC-based look-up table for measuring the electrical characteristics of a carbon-fiber electrode in pulse voltammetry. Using this instrument, the equivalent resistance and capacitance of the carbon-fiber electrode in saturated sodium chloride solution can be obtained. This instrument includes a decade resistance box, a peak current detection and hold circuit, a half peak comparator and a decay duration counter. A look-up table is established by using RC circuits to emulate the electrochemical reaction of the carbon-fiber electrode in pulse voltammetry. The equivalent resistance is obtained from the decade resistance box according to Kirchhoff's law. Then the equivalent capacitance is determined from the decay duration counter reading and equivalent resistance with the look-up table via a PC interpolation program. After obtaining the equivalent resistance and capacitance of an electrode, the values are compared with the usable thresholds. This method provides an effective quality evaluation index of carbon-fiber electrode for the user in order to reduce electrode-induced experimental failure. The method is also available for other kinds of carbon-fiber electrodes as long as their look-up table and desired thresholds are established.


Assuntos
Eletrofisiologia/instrumentação , Microeletrodos , Condutividade Elétrica , Oxirredução , Cloreto de Sódio , Soluções
15.
Clin Ther ; 23(6): 858-70, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11440286

RESUMO

BACKGROUND: Most published studies on the use of lipid-lowering agents to treat hypercholesterolemia have focused on Western populations, with few data on Asian populations. OBJECTIVE: The Simvastatin Treats Asians to Target (STATT) study used a titrate-to-goal protocol to evaluate the efficacy and tolerability of simvastatin 20 to 80 mg/d in the treatment of Asian patients with coronary heart disease. METHODS: This was a multicenter, open-label, uncontrolled, 14-week study in patients with coronary heart disease and serum low-density lipoprotein cholesterol (LDL-C) levels of 115-180 mg/dL and triglyceride levels of < or = 400 mg/dL. The dose of simvastatin was titrated from 20 to 80 mg/d to achieve the National Cholesterol Education Program (NCEP) LDL-C target of < or = 100 mg/dL. The primary efficacy measure was the percentage of patients achieving the NCEP target. Among secondary measures were the percentage of patients achieving European Society of Cardiology/European Atherosclerosis Society/European Society of Hypertension target LDL-C levels of < or = 115 mg/dL and the percentage change from baseline in lipid parameters. Tolerability was assessed in terms of the overall incidence of adverse experiences and the incidences of the most commonly reported adverse experiences. RESULTS: The intent-to-treat analysis included 133 Asian patients (93 men, 40 women; mean age, 59.5 years), of whom 125 completed 14 weeks of therapy. Their mean blood pressure was 130.2/79.4 mm Hg. Overall, 104 (78.2%) patients treated with simvastatin achieved LDL-C levels < or = 100 mg/dL at week 14, and 125 (94.0%) achieved this target at some point during the study. Similarly, 122 (91.7%) patients achieved an LDL-C level < or = 115 mg/dL at week 14, and 130 (97.7%) achieved this target at some point during the study. Treatment with simvastatin had favorable effects on the lipid profile, producing significant percentage changes from baseline in all parameters (P < 0.001). Simvastatin was well tolerated across the dose range. Overall, 40 patients (30.1%) had > or = 1 clinical adverse experience. Only 14 (10.5%) had adverse experiences that were possibly, probably, or definitely related to study drug; none of these experiences were considered serious. The most common adverse experiences (> or = 3% incidence) were abdominal pain (6%); chest pain (5%); dizziness (4%); and asthenia/fatigue, fibromyalgia, headache, insomnia, and upper respiratory tract infection (3% each). No new or unexpected adverse experiences were seen at the higher doses. CONCLUSIONS: Simvastatin was effective and well tolerated at doses of 20, 40, and 80 mg/d in Asian patients with coronary heart disease. Titration enabled the majority to achieve target LDL-C levels of < or = 100 mg/dL.


Assuntos
Anticolesterolemiantes/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Sinvastatina/uso terapêutico , Idoso , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Povo Asiático , LDL-Colesterol/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Cooperação do Paciente , Fatores de Risco , Sinvastatina/administração & dosagem , Sinvastatina/efeitos adversos
16.
Naunyn Schmiedebergs Arch Pharmacol ; 346(5): 504-10, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1470222

RESUMO

The effects of stimulating the pars compacta of the substantia nigra (SNC) on thermoregulation were assessed in normal rats, in rats with chemical lesion of the SNC dopamine (DA) pathways and in rats with striatal DA receptor blockade. Electrical stimulation of the SNC produced hypothermia, decreased metabolism and/or cutaneous vasoconstriction in rats at ambient temperatures (Ta) below 22 degrees C, as well as hyperthermia and cutaneous vasoconstriction in rats at Ta of 30 degrees C. Microinjection of an excitotoxic amino acid (kainic acid) at the same brain sites also produced the same thermal responses. In vivo voltammetric studies revealed that electrical or chemical stimulation of the SNC produced an increase in striatal DA release. The enhanced striatal DA release induced by SNC stimulation was attenuated in rats after selective destruction of the nigrostriatal DA pathway by administration of 6-hydroxydopamine into the medial forebrain bundle. In addition, the magnitude of the thermal responses produced by the SNC stimulation in the cold was attenuated by selective bilateral destruction of the nigrostriatal DA pathways or selective blockade of the striatal DA produced by intrastriatal infusion of haloperidol, a DA receptor antagonist. The results indicate that stimulation of the SNC inhibits both heat production and heat loss mechanisms in the rat.


Assuntos
Regulação da Temperatura Corporal/fisiologia , Corpo Estriado/fisiologia , Dopamina/fisiologia , Substância Negra/fisiologia , Animais , Temperatura Corporal/efeitos dos fármacos , Corpo Estriado/metabolismo , Antagonistas de Dopamina , Estimulação Elétrica , Haloperidol/farmacologia , Injeções , Ácido Caínico/farmacologia , Masculino , Feixe Prosencefálico Mediano , Vias Neurais/fisiologia , Oxidopamina/farmacologia , Ratos , Ratos Sprague-Dawley , Temperatura Cutânea/efeitos dos fármacos , Substância Negra/efeitos dos fármacos
17.
Naunyn Schmiedebergs Arch Pharmacol ; 348(3): 258-63, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8232603

RESUMO

The effects of stimulation of the paramedian reticular nucleus (PRN) in the rat medulla oblongata on both amphetamine-induced locomotor activity and striatal release of dopamine-like material were assessed. PRN stimulation (by intra-PRN injection of the excitatory amino acid, kainic acid) decreased vertical motion and total distance travelled, and increased postural freezing, in freely moving rats. On the other hand, a small dose (e.g. 1.25 mg/kg, i.p.) of amphetamine increased locomotor activity (including horizontal motion, vertical motion, total distance travelled and lines crossed counts), increased the number of turnings (both clockwise and anti-clockwise), induced locomotor stereotypy (including both gamma value and number of trip types), and inhibited postural freezing. The changes in activity induced by amphetamine administration were suppressed following PRN stimulation. In vivo voltammetric data revealed that electrical stimulation of the PRN decreased the release of dopamine-like material in the corpus striatum. This effect could be mimicked by intra-PRN injection of kainic acid in anesthetized rats. In contrast, i.p. administration of amphetamine increased the release of dopamine-like material in the corpus striatum. Furthermore, the enhanced release of dopamine-like material induced by amphetamine was attenuated by simultaneous stimulation of the PRN. The results reported here indicate that PRN stimulation decreases the striatal dopamine release and results in attenuation of the amphetamine-induced locomotor activity responses in rats.


Assuntos
Anfetamina/farmacologia , Corpo Estriado/metabolismo , Dopamina/metabolismo , Bulbo/fisiologia , Atividade Motora/fisiologia , Anestesia , Animais , Pressão Sanguínea/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Depressão Química , Estimulação Elétrica , Frequência Cardíaca/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Comportamento Estereotipado/efeitos dos fármacos
18.
Cortex ; 36(1): 19-29, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10728894

RESUMO

OBJECTIVE: Both motor imagery and selective motor cues enhance performance. Motor cortex is activated during motor imagery. We wanted to learn if selective motor cueing also activates motor cortex. METHODS: We gave normal right-handed subjects information about which hand to use to respond to an imperative stimulus (selective intention) or where in space an imperative stimulus would occur (selective attention). To minimize anticipatory responses, warning stimulus validity was 80%. During this choice reaction time task, we recorded magnetic motor evoked potentials. Imperative stimuli and transcranial magnetic stimulation were presented randomly to assess the effect of warning cues on reaction times and corticospinal excitability. RESULTS: Selective intentional and attentional warning cues reduced reaction times, but neither stimulus altered motor evoked potentials. CONCLUSIONS: These results suggest that unlike motor imagery, selective intention to respond to an imperative stimulus and shifting spatial attention to an imperative stimulus do not alter corticospinal excitability.


Assuntos
Imaginação/fisiologia , Atividade Motora/fisiologia , Córtex Motor/fisiologia , Tratos Piramidais/fisiologia , Adulto , Comportamento de Escolha/fisiologia , Sinais (Psicologia) , Potencial Evocado Motor , Mãos/fisiologia , Humanos , Magnetismo , Masculino , Pessoa de Meia-Idade , Tempo de Reação/fisiologia
19.
Physiol Behav ; 53(3): 545-51, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8451322

RESUMO

The current study provides a new modularized infrared light matrix system (about $200 cost) which is designed to measure the horizontal gross or fine movements, vertical motion, clockwise or anticlockwise turnings, freezing time, and total distance traveled in rats. The system records the sequences of animal's activity in a computer-aided system with a resolution of 0.2 s in time or 1.6 cm in space, and permanently stores all the resulting data in file. The behavioral apparatus was tested for its sensitivity and usability by amphetamine-injected rats. It was found that intraperitoneal administration of amphetamine (1.25-2.50 mg/kg), but not normal saline, produced a dose-related increase in either the horizontal gross or fine movements, vertical motion, clockwise or anticlockwise turnings, or total distance traveled. However, amphetamine injections produced a dose-related decrease in freezing time. Apparently, most of the amphetamine-induced responses obtained by other detecting apparatus can be reproduced easily by the present apparatus. The current detection system possesses the following advantages: a) high resolution, b) high expansion potential, and c) precise and simplified algorithms for behavioral parameter analysis.


Assuntos
Anfetamina/farmacologia , Raios Infravermelhos , Microcomputadores , Atividade Motora/efeitos dos fármacos , Processamento de Sinais Assistido por Computador/instrumentação , Algoritmos , Animais , Ritmo Circadiano/efeitos dos fármacos , Masculino , Orientação/efeitos dos fármacos , Ratos , Software
20.
Physiol Behav ; 56(4): 781-4, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7800748

RESUMO

A microcomputer-aided ultrasonic system was used to measure vertical displacement of rats in response to drug injection. The system utilizes an inexpensive PC/AT microcomputer for data collection and can distinguish between number of vertical movements of small (i.e., greater than 5 mm, but less than 15 mm), and large (i.e., greater than 15 mm) displacements. In addition, rest time denotes the time elapsed for the vertical motion of less than 5-mm displacements. As little as 0.32 mg/kg of d-amphetamine increased the average amount of both small and large activity (i.e., number of movements), but decreased the average amount of rest time in rats. On the contrary, as little as 2.5 mg/kg of chlorpromazine decreased the average amount of both small and large activity, but increased the rest time in rats. When the animal activity was measured with an infrared light system, the activity responses to drugs were not detectable. Thus, it appears that the ultrasonic method provides a high-precision system for measuring animal behaviors.


Assuntos
Atividade Motora/fisiologia , Psicofisiologia/instrumentação , Processamento de Sinais Assistido por Computador/instrumentação , Ultrassom , Animais , Nível de Alerta/efeitos dos fármacos , Nível de Alerta/fisiologia , Clorpromazina/farmacologia , Dextroanfetamina/farmacologia , Relação Dose-Resposta a Droga , Raios Infravermelhos , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
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