Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Ann Ig ; 29(6): 481-493, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29048447

RESUMO

The Erice 50 Charter titled "Strategies for Diseases Prevention and Health Promotion in Urban Areas" was unanimously approved at the conclusion of the 50th Residential Course "Urban Health. Instruments for promoting health and for assessing hygienic and sanitary conditions in urban areas", held from 29th March to 2nd April 2017 in Erice, at the "Ettore Majorana" Foundation and Centre for Scientific Culture and promoted by the International School of Epidemiology and Preventive Medicine "G. D'Alessandro" and the Study Group "Building Hygiene" of the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI). At the conclusion of the intense learning experience during the Course, with more than 20 lectures, workshops and long-lasting discussions between Professors and Students, the participants identified the major points connecting urban features and Public Health, claiming the pivotal role of urban planning strategies for the management of Diseases Prevention and Health Promotion activities. The Erice 50 Charter is configured as a Decalogue for Healthy Cities and as a Think Tank for designing effective strategic actions and best practices to develop urban regeneration interventions and improve the urban quality of contemporary cities. The Decalogue is structured into the following key strategic objectives: 1. Promoting urban planning interventions that address citizens towards healthy behaviours; 2. Improving living conditions in the urban context; 3. Building an accessible and inclusive city, with a special focus on the frail population; 4. Encouraging the foundation of resilient urban areas; 5. Supporting the development of new economies and employment through urban renewal interventions; 6. Tackling social inequalities; 7. Improving stakeholders' awareness of the factors affecting Public Health in the cities; 8. Ensuring a participated urban governance; 9. Introducing qualitative and quantitative performance tools, capable of measuring the city's attitude to promote healthy lifestyles and to monitor the population's health status; 10. Encouraging sharing of knowledge and accessibility to informations. Finally, all the participants underlined that a multidisciplinary team, composed of Physicians specialized in Hygiene, Preventive Medicine, Public Health and Technicians as Architects, Urban planners and Engineers, is needed to deepen the research topic of Urban Health.


Assuntos
Promoção da Saúde/métodos , Prevenção Primária/métodos , Saúde da População Urbana , Humanos , Itália
2.
Int J Dermatol ; 41(2): 93-5, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11982644

RESUMO

BACKGROUND: Travelers to tropical areas seem to be affected by nonhealing leg ulcers more frequently. One of the factors that can affect wound healing in a negative manner is leg edema. This study was performed to determine whether there is increased leg edema in travelers to tropical areas. METHOD: In this study, we measured the capillary filtration rate (CFR) of the lower leg by strain gauge plethysmography, as a measure of leg edema, on location in Surinam. Three groups were included: A, travelers in the first few weeks after arrival; B, travelers who had stayed in the tropics for a minimum of 2 months; C, native inhabitants. RESULTS: The mean CFR (mL/100 mL tissue/min) was significantly higher in group A than in groups B and C; the difference between groups B and C was not significant (group A 0.05 mL/100 mL tissue/min (standard deviation (SD), 0.03) vs. group B 0.02 mL/100 mL tissue/min (SD, 0.02), P = 0.01, and vs. group C 0.02 mL/100 mL tissue/min (SD, 0.02), P = 0.01). CONCLUSIONS: Travelers to tropical areas are affected by increased CFR in the first few weeks after arrival. A prolonged stay leads to the normalization of the CFR. Compression therapy is recommended for travelers to the tropics.


Assuntos
Edema/etiologia , Edema/fisiopatologia , Perna (Membro)/irrigação sanguínea , Perna (Membro)/fisiopatologia , Microcirculação/fisiopatologia , Doenças Vasculares Periféricas/etiologia , Doenças Vasculares Periféricas/fisiopatologia , Viagem , Clima Tropical/efeitos adversos , Adulto , Capilares/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pletismografia , Suriname , Fatores de Tempo
3.
Genetica ; 110(2): 163-75, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11678507

RESUMO

The aim of the present study was to assess the degree of genetic variation and divergence among six populations of Calomys hummelincki, a phyllotine rodent distributed in northern South America. With this information we will try to evaluate the two hypotheses of possible colonization and differentiation of this group of rodents postulated by Baskin and Reig. We studied 34 loci by electrophoretic analysis: 21 were monomorphic for all populations and 13 were polymorphic in at least one population, being P1% = 21.6% the mean value for all populations. The mean value of heterozygosity per locus was H = 0.075. Low values of genetic distance were observed among populations of the Llanos region (0.001 < D < 0.006). There was a larger genetic distance (D = 0.024) between the population from Isiro, in the northwestern semiarid region, and those from the Llanos region. The insular population of Aruba displayed the lowest value of genetic distance with the population from Isiro (D=0.014). The specimens from Sipao, on the right side of the Orinoco river, displayed the highest values of genetic distances in comparison with other populations of C. hummelincki (0.070 < D < 0.095). The relatively high differentiation was due to the fixation of new alleles, not found in other populations of C. hummelincki, at loci Idh-1 and Est-2. F-statistics and Nm values indicated reduced gene flow among the populations sampled. Despite the limited data, the results seem to support Reig's hypothesis about south to north colonization of genus Calomys in South America.


Assuntos
Variação Genética , Muridae/genética , Alelos , Animais , Enzimas/genética , Genética Populacional , Heterozigoto , Modelos Genéticos , Polimorfismo Genético , América do Sul
5.
J Pediatr Endocrinol Metab ; 11(6): 745-50, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9829230

RESUMO

Autoimmune phenomena, especially occurrence of non organ-specific autoantibodies, are common in congenitally acquired HIV infection, mostly in the symptomatic stages of the disease. Anti-thyroid autoantibodies detected in adult patients represent the only type of organ-specific autoantibodies reported in HIV infection. As far as we know, occurrence of these autoantibodies has not been observed in HIV infected children. In this study thyroid biochemical pattern and possible occurrence of anti-thyroid autoantibodies were investigated in 40 vertically HIV infected, 18 seroreverted and 22 healthy children. 34% of HIV infected symptomatic children showed anti-thyroglobulin antibodies. Asymptomatic patients, seroreverted and healthy controls did not show any anti-thyroid antibodies at the time of the study. High Tg levels were observed in 38% of the 40 HIV infected patients and high TSH concentrations were found in 27.5% of the HIV children. High TSH values were more frequently observed in the infected children with moderate or severe immunocompromised status. Thyroxine binding globulin levels were high in 68% of the HIV children and in 22% of the seroreverted. The finding of anti-thyroid autoantibodies in congenital HIV infected children confirms the thyroid's involvement in HIV infection and provides more information about the wide spectrum of autoimmune phenomena observed in the infection.


Assuntos
Autoanticorpos/análise , Infecções por HIV/imunologia , Infecções por HIV/transmissão , HIV-1 , Transmissão Vertical de Doenças Infecciosas , Glândula Tireoide/imunologia , Contagem de Linfócito CD4 , Pré-Escolar , Progressão da Doença , Feminino , Infecções por HIV/sangue , Infecções por HIV/fisiopatologia , Humanos , Masculino , Valores de Referência , Tireoglobulina/sangue , Tireotropina/sangue , Tiroxina/sangue , Proteínas de Ligação a Tiroxina/análise , Tri-Iodotironina/sangue
6.
J Law Med Ethics ; 26(4): 332-49, 263, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-11066893

RESUMO

Author argues that a complex "ethic of underprescribing" underlies the continued reluctance of physicians to use opioids to treat chronic pain. She contends that state medical boards are uniquely positioned to promote a new ethic for pain management, but stresses the difficulties for boards in attaining this goal. She thinks success may hinge on whether boards can change their approach to pain management and persuade a skeptical medical community that adopting a risk for underprescribing will serve the long-term interests of patients and the profession.


Assuntos
Analgésicos Opioides/uso terapêutico , Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , Ética Médica , Licenciamento em Medicina , Dor/tratamento farmacológico , Controle Social Formal , Valores Sociais , Doença Crônica/tratamento farmacológico , Princípio do Duplo Efeito , Pesquisa Empírica , Ética , Regulamentação Governamental , Humanos , Intenção , Má Conduta Profissional , Responsabilidade Social , Estresse Psicológico , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Estados Unidos , Suspensão de Tratamento
7.
Pediatr Radiol ; 25(3): 175-9, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7644295

RESUMO

The objective of the investigation was to determine what effect intracranial pathology has on alterations of superior sagittal sinus blood flow, and to determine the role of color flow Doppler imaging of the superior sagittal sinus in the diagnosis of intracranial pathology in the neonate and infant. One hundred examinations were performed prospectively in 96 patients. The velocity was determined with an angle correction at 30-60 degrees and was obtained with and without gentle transducer compression. Superior sagittal sinus thrombosis was identified in two patients by the absence of flow. Multiple t-tests for independent measures showed no clinically significant differences between flow velocities with regard to intracranial hemorrhage, ventriculomegaly, extracorporeal membrane oxygenation therapy or prematurity. The authors conclude that color flow Doppler can accurately diagnose superior sagittal sinus thrombosis and may be used to screen high risk neonates such as those with thrombosis elsewhere or those treated with extracorporeal membrane oxygenation. No clinically significant associations were found between superior sagittal sinus flow velocity and any of the parameters evaluated in this study.


Assuntos
Circulação Cerebrovascular/fisiologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Cavidades Cranianas/diagnóstico por imagem , Trombose dos Seios Intracranianos/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos de Casos e Controles , Transtornos Cerebrovasculares/fisiopatologia , Oxigenação por Membrana Extracorpórea , Humanos , Lactente , Recém-Nascido , Trombose dos Seios Intracranianos/fisiopatologia
8.
Minerva Pediatr ; 46(3): 83-8, 1994 Mar.
Artigo em Italiano | MEDLINE | ID: mdl-8035762

RESUMO

Neonatal abstinence syndrome (NAS) is one of the most frequent manifestations in the neonates of drug-addicted mothers. It is caused by the abrupt interruption of the transplacentar passage of drugs from the mother to the fetus. The aim of this study was to evaluate the correlation between drugs taken during pregnancy and NAS. Data were examined relating to 223 neonates born during 1975-1992 to drug-addict mothers. Neonates were subdivided into four groups according to the maternal toxicological profile. It was thus possible to observe that there is a greater prevalence of NAS in cases of polypharmacomania and that it gradually diminishes in the children of heroin addicts and those receiving methadone treatment. Moreover, the intensity of the syndrome is correlated to the high doses of methadone and/or heroin. In the group of neonates whose mothers had complied with the methadone treatment protocol, the severity of NAS was proportional to the dose taken by the mother. In conclusion, the management of pregnant drug addicts following a controlled methadone treatment programme is accompanied by improved obstetric help and is the most suitable way of reducing perinatal complications and the prevalence of NAS.


Assuntos
Heroína/efeitos adversos , Metadona/uso terapêutico , Mães , Síndrome de Abstinência Neonatal/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Troca Materno-Fetal , Metadona/administração & dosagem , Metadona/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal
9.
Pediatr Neurosurg ; 21(3): 201-4, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7803312

RESUMO

Intracerebral hematomas following evacuation of a subdural hematoma have been described in adults resulting from sudden decompression during the drainage of the hematoma. In infants an open fontanelle and patent sutures are expected to offer protection against sudden decompression. We report the occurrence of intracerebral hematoma in an infant following evacuation of a subdural hematoma. The multiplicity and centripetal spread of the postoperative hematomas suggested that they had resulted from sudden decompression.


Assuntos
Hemorragia Cerebral/etiologia , Hematoma Subdural/cirurgia , Complicações Pós-Operatórias/etiologia , Encéfalo/fisiopatologia , Encéfalo/cirurgia , Circulação Cerebrovascular , Drenagem , Hematoma Subdural/diagnóstico , Hematoma Subdural/fisiopatologia , Humanos , Lactente , Recém-Nascido , Pressão Intracraniana , Imageamento por Ressonância Magnética , Masculino , Espaço Subdural , Tomografia Computadorizada por Raios X
10.
Minerva Pediatr ; 44(6): 319-23, 1992 Jun.
Artigo em Italiano | MEDLINE | ID: mdl-1635534

RESUMO

Thirty-nine children (18 males, 21 females) suffering from intestinal stasis were treated with lactitol or a reference drug (lactulose in crystalline form), according to a balanced randomization, for 15 days. The first group of children included 19 subjects treated with lactitol, the second group included 20 subjects treated with lactulose. The dosages of lactitol and lactulose were, respectively, of 150-350 mg/kg and of 150-300 mg/kg daily per os with a single administration in the morning. During the trial, the children did not take any concomitant drug. For each patient the tested parameters were: number of intestinal evacuations, consistency of stool and adverse reactions (abdominal swelling, abdominal pain, nausea, vomiting, meteorism) daily; routine laboratory tests at the beginning and at the end of the trials. The results showed that the subjects treated with lactitol have manifested, besides a proved therapeutic efficacy, a better tolerability and compliance than the subjects treated with lactulose.


Assuntos
Constipação Intestinal/tratamento farmacológico , Álcoois Açúcares/uso terapêutico , Adolescente , Criança , Pré-Escolar , Constipação Intestinal/fisiopatologia , Defecação/efeitos dos fármacos , Avaliação de Medicamentos , Feminino , Humanos , Lactente , Lactulose/uso terapêutico , Masculino , Fatores de Tempo
11.
Pediatr Neurosurg ; 16(6): 321-5, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2134744

RESUMO

Neurologic complications of sickle cell anemia are most commonly ischemic strokes secondary to sludging in cerebral arterioles. We, therefore, report a case of progressive paraparesis in a child with sickle cell anemia which was initially thought to be secondary to a spinal cord ischemic event. Further diagnostics demonstrated that the neurologic deficits were secondary to salmonella osteomyelitis and an epidural abscess, compressing the upper thoracic spinal cord at the T6 level. The diagnostic and radiological features which help to distinguish between bone infarct and osteomyelitis, both responsible for bone pain in sickle cell patients, are also presented. In particular, Tc-sulfur colloid bone marrow imaging is the most helpful test for distinguishing between these similarly presenting clinical entities, as early as 48 h after bone pain develops.


Assuntos
Abscesso/cirurgia , Anemia Falciforme/complicações , Osteomielite/cirurgia , Infecções por Salmonella/cirurgia , Salmonella enteritidis , Compressão da Medula Espinal/cirurgia , Vértebras Torácicas/cirurgia , Abscesso/diagnóstico por imagem , Adolescente , Ampicilina/administração & dosagem , Anemia Falciforme/diagnóstico por imagem , Terapia Combinada , Gentamicinas/administração & dosagem , Humanos , Laminectomia , Masculino , Mielografia , Exame Neurológico , Osteomielite/diagnóstico por imagem , Infecções por Salmonella/diagnóstico por imagem , Compressão da Medula Espinal/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X
12.
Arch Neurol ; 45(7): 722-4, 1988 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3390025

RESUMO

Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy are all characterized by loss of neurons in the basal forebrain cholinergic system and by associated reductions in cortical presynaptic cholinergic markers, such as choline acetyltransferase. In this report, we identify that a major cortical receptor alteration in these disorders is a reduction in nicotinic receptors measured using both tritiated acetylcholine and levorotatory tritiated nicotine binding.


Assuntos
Acetilcolina/metabolismo , Doença de Alzheimer/metabolismo , Nicotina/metabolismo , Doença de Parkinson/metabolismo , Paralisia Supranuclear Progressiva/metabolismo , Idoso , Doença de Alzheimer/enzimologia , Córtex Cerebral/metabolismo , Colina O-Acetiltransferase/metabolismo , Humanos , Doença de Parkinson/enzimologia , Receptores Nicotínicos/metabolismo , Paralisia Supranuclear Progressiva/enzimologia
13.
Neurology ; 38(5): 720-3, 1988 May.
Artigo em Inglês | MEDLINE | ID: mdl-3362368

RESUMO

In Alzheimer's disease (AD) and Parkinson's disease (PD), dysfunction in the basal forebrain cholinergic system is accompanied by a consistent loss of presynaptic cholinergic markers in cortex, but changes in cholinergic receptor binding sites are poorly understood. In the present study, we used receptor autoradiography to map the distribution of nicotinic [3H]acetylcholine binding sites in cortices of individuals with AD and PD and matched control subjects. In both diseases, a profound loss of nicotinic receptors occurs in all cortical layers, particularly the deepest layers.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Parkinson/metabolismo , Receptores Nicotínicos/metabolismo , Idoso , Envelhecimento/metabolismo , Autorradiografia , Córtex Cerebral/metabolismo , Lobo Frontal/metabolismo , Humanos , Mudanças Depois da Morte , Trítio
14.
Exp Brain Res ; 71(3): 667-72, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-2458281

RESUMO

We injected wheat germ agglutinin conjugated to horseradish peroxidase into different segments of the spinal cord in order to examine the topographic organization of corticospinal projections from the medial wall of the hemisphere. We observed that substantial projections to the spinal cord originate not only from the supplementary motor area (SMA) in area 6, but also from 2 regions within the cingulate sulcus. The distribution of labeled neurons following tracer injections into different spinal cord segments indicates that corticospinal projections from the SMA and from the 2 cingulate regions are somatotopically organized. These findings together with other recent anatomical observations suggest that the corticospinal projections from the medial wall of the hemisphere provide the basal ganglia and limbic system with a somatotopically organized access to spinal cord mechanisms.


Assuntos
Giro do Cíngulo/anatomia & histologia , Macaca/anatomia & histologia , Córtex Motor/anatomia & histologia , Medula Espinal/anatomia & histologia , Animais , Mapeamento Encefálico , Peroxidase do Rábano Silvestre , Conjugado Aglutinina do Germe de Trigo-Peroxidase do Rábano Silvestre , Aglutininas do Germe de Trigo
15.
Brain Res ; 404(1-2): 307-12, 1987 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-3032334

RESUMO

We investigated the patterns of corticospinal projection to different segments of the cervical spinal cord using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. We confirmed prior suggestions that the arcuate premotor area (APA) has a significant projection to the spinal cord. In addition, we observed that the corticospinal projection from the APA terminates in upper, but not lower segments of the cervical spinal cord. Furthermore, the region of the APA which projects to the cervical cord also projects to the arm area of the primary motor cortex on the crest of the precentral gyrus. Thus, we conclude that the APA projection to upper cervical segments is involved in the cortical control of arm movements.


Assuntos
Núcleo Arqueado do Hipotálamo/fisiologia , Córtex Motor/fisiologia , Medula Espinal/fisiologia , Transmissão Sináptica , Animais , Peroxidase do Rábano Silvestre , Macaca nemestrina , Pescoço , Aglutininas do Germe de Trigo
17.
Brain Res ; 371(1): 146-51, 1986 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-3708340

RESUMO

In Alzheimer's disease (AD), there is a loss of presynaptic cholinergic markers in the cerebral cortex, but the nature of cholinergic receptor changes is unclear. In this study, [3H]acetylcholine and [3H]nicotine were used to label nicotinic cholinergic binding sites in cerebral cortical tissues obtained at autopsy from patients with AD and from matched controls. A consistent and severe loss of nicotinic receptors was found in AD.


Assuntos
Doença de Alzheimer/metabolismo , Córtex Cerebral/análise , Colina O-Acetiltransferase/metabolismo , Receptores Nicotínicos/análise , Acetilcolina/metabolismo , Idoso , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/enzimologia , Córtex Cerebral/enzimologia , Córtex Cerebral/metabolismo , Humanos , Nicotina/metabolismo
18.
Science ; 230(4723): 323-5, 1985 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-2996132

RESUMO

The role of serotonin axons in modulating the norepinephrine neurotransmission system in rat brain was investigated. Selective lesions of the forebrain serotonergic system were made by injecting 5,7-dihydroxytryptamine into the midbrain raphe nuclei. Four to six weeks after the lesion, the uptake of 3H-labeled serotonin in the frontal cortex and the hippocampus was reduced by more than 90 percent, while neither the uptake of 3H-labeled norepinephrine nor the content of norepinephrine was affected in either tissue. The number of beta-adrenergic receptors, as measured by radioligand binding with 3H-labeled dihydroalprenolol, was increased in the frontal cortex and hippocampus of rats with lesions. Similarly, specific lesions of central serotonin axons produced by systemically administered p-chloramphetamine resulted in an increase in the binding of 3H-labeled dihydroalprenolol to beta-adrenergic receptors and in the production of adenosine 3',5'-monophosphate in response to isoproterenol. These results indicate that serotonin axons may regulate beta-adrenergic receptor number and function in brain.


Assuntos
Axônios/fisiologia , Córtex Cerebral/metabolismo , Hipocampo/metabolismo , Receptores Adrenérgicos beta/metabolismo , Serotonina/fisiologia , Animais , Clonidina/análogos & derivados , Clonidina/metabolismo , Di-Hidroalprenolol/metabolismo , Cinética , Masculino , Norepinefrina/metabolismo , Prazosina/metabolismo , Ratos , Ratos Endogâmicos
19.
J Neurosci ; 5(6): 1577-82, 1985 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-4009247

RESUMO

High-affinity binding of [3H]acetylcholine to muscarinic cholinergic sites in rat CNS and peripheral tissues was measured in the presence of cytisin, which occupies nicotinic cholinergic receptors. The muscarinic sites were characterized with regard to binding kinetics, pharmacology, anatomical distribution, and regulation by guanyl nucleotides. These binding sites have characteristics of high-affinity muscarinic cholinergic receptors with a Kd of approximately 30 nM. Most of the muscarinic agonist and antagonist drugs tested have high affinity for the [3H]acetylcholine binding site, but pirenzepine, an antagonist which is selective for M-1 receptors, has relatively low affinity. The ratio of high-affinity [3H]acetylcholine binding sites to total muscarinic binding sites labeled by [3H]quinuclidinyl benzilate varies from 9 to 90% in different tissues, with the highest ratios in the pons, medulla, and heart atrium. In the presence of guanyl nucleotides, [3H] acetylcholine binding is decreased, but the extent of decrease varies from 40 to 90% in different tissues, with the largest decreases being found in the pons, medulla, cerebellum, and heart atrium. The results indicate that [3H]acetylcholine binds to high-affinity M-1 and M-2 muscarinic receptors, and they suggest that most M-2 sites have high affinity for acetylcholine but that only a small fraction of M-1 sites have such high affinity.


Assuntos
Acetilcolina/metabolismo , Sistema Nervoso Central/metabolismo , Receptores Colinérgicos/metabolismo , Receptores Muscarínicos/metabolismo , Animais , Ligação Competitiva , Átrios do Coração/metabolismo , Cinética , Masculino , Ratos , Ratos Endogâmicos , Trítio
20.
J Neurochem ; 41(2): 367-74, 1983 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-6308158

RESUMO

The binding properties of N6-cyclohexyl [3H]adenosine ( [3H]CHA) and 1,3-diethyl-8-[3H]phenylxanthine ( [3H]DPX) in rat forebrain membrane are compared. The kinetic parameters of binding for each ligand are quite distinct, with [3H]CHA displaying two populations of binding sites (KD = 0.4 +/- 0.05 nM and 4.2 +/- 0.3 nM; Bmax = 159 +/- 17 and 326 +/- 21 fmol/mg protein), whereas [3H]DPX yielded monophasic Scatchard plots (KD = 13.9 +/- 1.1 nM; Bmax = 634 +/- 27 fmol/mg protein). The metals copper, zinc, and cadmium are potent inhibitors of [3H]CHA binding, with respective IC50 concentrations of 36 microM, 250 microM, and 70 microM. Copper is a much less potent inhibitor of [3H]DPX binding (IC50 = 350 microM). The inhibitory effect of copper on both [3H]CHA and [3H]DPX binding is apparently irreversible, as membranes pretreated with copper cannot be washed free of its inhibitory effect. The inhibitory effect of both copper and zinc on [3H]CHA binding was reversed by the guanine nucleotide Gpp(NH)p. [3H]DPX binding is only partially inhibited by zinc and cadmium (60% of specific binding remains unaffected), suggesting that this adenosine receptor ligand binds to two separate sites. Guanine nucleotides had no effect on the inhibition of [3H]DPX binding by either copper or zinc. Differential thermal and proteolytic denaturation profiles are also observed for [3H]CHA and [3H]DPX binding, with the former ligand binding site being more labile in both cases. Stereospecificity is observed in the inhibition of both [3H]CHA and [3H]DPX binding, with L-N-phenylisopropyladenosine (PIA) being 50-fold more potent than D-PIA in both cases. Evidence is therefore provided that adenosine receptor agonists and antagonists have markedly different binding properties to brain adenosine receptors.


Assuntos
Adenosina/análogos & derivados , Adenosina/metabolismo , Encéfalo/metabolismo , Receptores de Superfície Celular/metabolismo , Xantinas/metabolismo , Adenosina/farmacologia , Animais , Ligação Competitiva , Captopril/farmacologia , Membrana Celular/metabolismo , Cinética , Masculino , Ratos , Ratos Endogâmicos , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Superfície Celular/isolamento & purificação , Receptores Purinérgicos , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA