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1.
Chronic Dis Can ; 31(2): 49-57, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21466754

RESUMO

INTRODUCTION: The aging of the Canadian population is associated with a rising burden of heart failure (HF), a condition associated with significant morbidity, mortality and health service use. METHODS: We used data from the Ontario Resident Assessment Instrument-Home Care database for all long-stay home care clients aged 65 years or older to (1) describe the demographic and clinical characteristics of home care clients with HF and (2) examine service use among home care clients with HF to promote management at home with appropriate services. RESULTS: Compared with other home care clients, HF clients exhibit more health instability, take more medications, experience more comorbid conditions and receive significantly more nursing, homemaking and meal services. They are hospitalized more frequently, have significantly more emergency department visits and use more emergent care. DISCUSSION: HF clients are a more complex group than home care clients in general. Patient self-care must be tailored to the clinical characteristics, patterns of service use and barriers to self-care of the client. This is particularly true for older, frail and medically complex HF patients, many of whom require home care services. This work provides a background upon which to base initiatives to help these higher-needs clients manage their HF at home with appropriate support and services.


Assuntos
Insuficiência Cardíaca/terapia , Serviços de Assistência Domiciliar , Autocuidado , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Comorbidade , Bases de Dados Factuais , Feminino , Serviços de Alimentação , Avaliação Geriátrica/métodos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/enfermagem , Serviços de Assistência Domiciliar/estatística & dados numéricos , Humanos , Masculino , Ontário/epidemiologia , Qualidade de Vida , Autocuidado/métodos
2.
J Frailty Aging ; 9(1): 14-22, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32150209

RESUMO

With aging populations around the world, frailty is becoming more prevalent increasing the need for health systems and social systems to deliver optimal evidence based care. However, in spite of the growing number of frailty publications, high-quality evidence for decision making is often lacking. Inadequate descriptions of the populations enrolled including frailty severity and frailty conceptualization, lack of use of validated frailty assessment tools, utilization of different frailty instruments between studies, and variation in reported outcomes impairs the ability to interpret, generalize and implement the research findings. The utilization of common data elements (CDEs) and core outcome measures (COMs) in clinical trials is increasingly being adopted to address such concerns. To catalyze the development and use of CDEs and COMs for future frailty studies, the Canadian Frailty Network (www.cfn-nce.ca; CFN), a not-for-profit pan-Canadian nationally-funded research network, convened an international group of experts to examine the issue and plan the path forward. The meeting was structured to allow for an examination of current frailty evidence, ability to learn from other COMs and CDEs initiatives, discussions about specific considerations for frailty COMs and CDEs and finally the identification of the necessary steps for a COMs and CDEs consensus initiative going forward. It was agreed at the onset of the meeting that a statement based on the meeting would be published and herein we report the statement.


Assuntos
Pesquisa Biomédica/organização & administração , Fragilidade , Canadá , Elementos de Dados Comuns , Consenso , Humanos , Avaliação de Resultados em Cuidados de Saúde
3.
J Frailty Aging ; 8(3): 106-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237310

RESUMO

The Canadian Frailty Network (CFN), a pan-Canadian not-for-profit organization funded by the Government of Canada through the Networks of Centres of Excellence Program, is dedicated to improving the care of older Canadians living with frailty. The CFN has partnered with the Canadian Longitudinal Study on Aging (CLSA) to measure potential frailty biomarkers in biological samples (whole blood, plasma, urine) collected in over 30,000 CLSA participants. CFN hosted a workshop in Toronto on January 15 2018, bringing together experts in the field of biomarkers, aging and frailty. The overall objectives of the workshop were to start building a consensus on potential frailty biomarker domains and identify specific frailty biomarkers to be measured in the CLSA biological samples. The workshop was structured with presentations in the morning to frame the discussions for the afternoon session, which was organized as a free-flowing discussion to benefit from the expertise of the participants. Participants and speakers were from Canada, Italy, Spain, United Kingdom and the United States. Herein we provide pertinent background information, a summary of all the presentations with key figures and tables, and the distillation of the discussions. In addition, moving forward, the principles CFN will use to approach frailty biomarker research and development are outlined. Findings from the workshop are helping CFN and CLSA plan and conduct the analysis of biomarkers in the CLSA samples and which will inform a follow-up data access competition.


Assuntos
Biomarcadores , Fragilidade/diagnóstico , Idoso , Canadá , Idoso Fragilizado , Humanos , Estudos Longitudinais , Prognóstico , Medição de Risco
4.
J Frailty Aging ; 7(4): 208-216, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30298168

RESUMO

Canadian healthcare is changing to include individuals living with frailty, but frailty must be better operationalized and better framed by sound data standards and policy. Frailty results from deficit accumulation in multiple body systems, with exaggerated vulnerability to external stressors. A growing consensus on defining frailty sets the stage for consensus on operationalization and widespread implementation in care settings. Frailty measurement is not yet integrated into daily clinical practice in Canada. Here, we will present how this integration might occur. We hope to demonstrate that implementation must appeal to inter-professional practice needs in different settings or circumstances. In some settings, methods for frailty case finding are expected to evolve as deemed to be most appropriate to the front-line users. In this "hands-off" approach, care providers, supported by emerging knowledge translation on frailty operationalization, would be informed by their setting and local practices to establish patterns of ad hoc case finding and component definition of frailty. This more nimble case finding strategy would be opportunistic, and would appeal to expert clinicians and self-directed teams who emphasize an individualized health care experience for their patients. In other settings, we can shape frailty case finding by building care algorithms around existing standardized practices and data repositories, leading to a systematic application of frailty measures and a more coordinated process of component definition and care protocols. Here, recommended instruments and data standards must be endorsed by health networks locally, provincially and nationally. The interRAI suite of assessment instruments has pan-Canadian standards in place and its pervasiveness makes it the most obvious starting point, especially in home care and long-term care. We anticipate the evolution of an integrated model informed by stakeholders and settings, where policy makers focus on system supports for frailty case finding, while front-line clinicians use case finding strategies to pinpoint and act on key frailty components.


Assuntos
Atenção à Saúde/organização & administração , Fragilidade/diagnóstico , Avaliação Geriátrica , Idoso , Canadá , Idoso Fragilizado , Humanos
5.
J Med Chem ; 29(6): 984-8, 1986 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2940368

RESUMO

As part of a program to design potent antidiuretic vasopressin antagonists and to define the minimum effective pharmacophore requirements for vasopressin (VP) antagonist activity, we studied the importance of the C-terminal tripeptide of a previously reported peptide antagonist of arginine-vasopressin (AVP,1). The proline residue at position 7 in AVP is proposed to impart a conformational constraint to the peptide backbone that is essential for V2-receptor agonist activity. Since the structure-activity relationships for VP agonists and antagonists are different, we investigated the effect of proline on antagonist activity, by synthesizing analogue 3 lacking this residue. This analogue was found to retain a high degree of antidiuretic antagonist activity. Since deletion of the Gly residue at position 9 of the antagonist did not adversely affect VP antagonist potency, several vasopressin antagonist analogues (4-7 and 9) that lacked both the Pro and Gly residues were also studied. These, too, were found to block vasopressin V2-receptor activity. Our results indicate that neither the proline nor glycine residues are essential for antagonism of the V2 receptor.


Assuntos
Peptídeos/farmacologia , Vasopressinas/antagonistas & inibidores , Animais , Glicina/farmacologia , Masculino , Peptídeos/síntese química , Prolina/farmacologia , Ratos , Receptores de Angiotensina/efeitos dos fármacos , Receptores de Vasopressinas , Relação Estrutura-Atividade
6.
J Med Chem ; 32(2): 391-6, 1989 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2521519

RESUMO

We report the synthesis and biological activity of a series of analogues of the vasopressin antagonists [Pmp1,D-Tyr(Et)2,Val4]arginine-vasopressin (1) and [Pmp1,D-Tyr(Et)2,Val4,desGly9]arginine-vasopressin (2), where part or all of the tripeptide tail has been replaced by a simple alkyldiamine [NH(CH2)nNH2] or (aminoalkyl)guanidine [NH(CH2)nNHC(= NH)NH2] in order to examine the effects that variation of the length and orientation of the tripeptide tail have on renal vasopressin (V2) receptor antagonist activity. The results show that the entire tripeptide tail (Pro-Arg-Gly-NH2) can be replaced by an alkyldiamine or an (aminoalkyl)guanidine, compounds 15 and 16, respectively, indicating that there is no orientational requirement for the basic functional group coming off the cyclic hexapeptide ring. Also, there seems to be an "optimal" distance between the basic functional group and the hexapeptide ring since receptor affinity of the antagonists begins to fall off when the basic functional group is too close (compound 13) or extends too far (compounds 8-10) from the hexapeptide ring. These results suggest all that is necessary for retention of antagonist affinity and potency is a basic functional group, amine or guanidine, extended an optimal distance from the hexapeptide ring.


Assuntos
Vasopressinas/antagonistas & inibidores , Animais , Humanos , Masculino , Conformação Molecular , Peptídeos/síntese química , Peptídeos/farmacologia , Ratos , Receptores de Angiotensina/efeitos dos fármacos , Receptores de Vasopressinas , Relação Estrutura-Atividade , Suínos
7.
J Med Chem ; 30(12): 2291-4, 1987 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2960813

RESUMO

In a continuing effort to design more potent renal vasopressin (V2 receptor) antagonists, we have focused our attention on the carboxy-terminal tripeptide tail (Pro-Arg-Gly-NH2), a fragment common to both agonists and antagonists. Vasopressin antagonist analogues having a dibasic dipeptide tail, e.g., Arg-Arg-NH2 or Arg-Lys-NH2, attached directly to the cyclic hexapeptide ring are potent V2-receptor antagonists. Similar modification of a representative agonist drastically reduces its potency. We report the synthesis and pharmacological properties of a series of potent V2-receptor antagonists 3-9 where a combination of D or L dibasic dipeptide has been utilized to replace the common tripeptide fragment. Our results suggest a difference in the way agonists and antagonists bind to vasopressin receptor and further support the difference in the structure-activity relationships of agonists and antagonists. These results provide potentially useful insights for the design of novel V2-receptor antagonists.


Assuntos
Receptores de Angiotensina/efeitos dos fármacos , Vasopressinas/antagonistas & inibidores , Animais , Masculino , Ratos , Receptores de Vasopressinas , Relação Estrutura-Atividade , Suínos
8.
Biochem Pharmacol ; 35(21): 3813-20, 1986 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-3022740

RESUMO

Rat aortic smooth muscle cells in culture (A-10; ATCC CRL 1476) exhibited low levels of beta-adrenergic receptors as determined by specific binding of [125I]cyanopindolol ([125I]CYP) and marginal stimulation of adenylate cyclase in plasma membranes by (-)isoproterenol. When these cells were exposed to 5 mM sodium butyrate, the number of beta-adrenergic receptors and the beta-agonist-stimulated adenylate cyclase activity increased markedly. However, basal, GTP, Gpp(NH)p, and fluoride-stimulated activities did not change. The induction of beta-adrenergic receptors and beta-agonist stimulated adenylate cyclase activity was time- and dose-dependent, and was relatively specific for sodium butyrate. Propionate and valerate were less effective than butyrate, while isobutyrate, succinate, and malonate were ineffective. The induction involved RNA and protein synthesis because induction was prevented by treatment with cycloheximide, puromycin, and actinomycin D. Butyrate did not cause a general increase in cell surface receptors, because the number of vasopressin receptors did not change. The sustained presence of butyrate appeared to be necessary for the maintenance of the induced beta-receptors. When butyrate was removed, receptor number and beta-agonist-stimulated adenylate cyclase activity were decreased by 90% over 24 hr. We conclude that the poor response of rat aortic smooth muscle cell plasma membranes to beta-adrenergic agonists is due to the presence of a low number of beta-adrenergic receptors. Butyrate markedly increased the number of beta-receptors which resulted in a proportional increase in beta-agonist-stimulated adenylate cyclase activity. The increase in receptor number was dependent on RNA and protein synthesis. Butyrate treatment did not affect the activity of the cyclase unit and the efficiency of coupling between the receptors and the guanine nucleotide regulatory protein, Ns.


Assuntos
Butiratos/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Receptores Adrenérgicos beta/biossíntese , Adenilil Ciclases/biossíntese , Animais , Ácido Butírico , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Isoproterenol/farmacologia , Cinética , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/metabolismo , Pindolol/análogos & derivados , Pindolol/metabolismo , Ratos
9.
J Am Geriatr Soc ; 49(4): 458-61, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11347791

RESUMO

OBJECTIVES: To describe an older patient with delirium attributed to systemic lupus erythematosus (SLE) and to review the literature on neuropsychiatric manifestations of SLE in older people. DESIGN: Case report and literature review. MEDLINE search using terms systemic lupus erythematosus, neurologic, psychiatric, neuropsychiatric, autoantibodies (anti-nuclear antibody (ANA), antiphospholipid, anticardiolipin, anti-double stranded deoxyribonucleic acid (anti-dsDNA), anti-Smith), and elderly. Additional articles obtained from hand-searched references and through experts. SETTING: Hospital (case report). PARTICIPANTS: Case report and literature cases. MEASUREMENTS: None. RESULTS: SLE is increasingly diagnosed in older adults. Onset is insidious and diagnosis is delayed because of a different clinical spectrum and immunological profile than in younger adults. Autoantibodies have an important role in the pathogenesis of neuropsychiatric manifestations, while vasculitis is less common. Aggressive immunosuppressive therapy is typically indicated, although recent case reports suggest that lower doses may suffice. The American College of Rheumatology 1982 revised criteria may be inadequate to diagnose neuropsychiatric lupus in older persons. CONCLUSION: Neuropsychiatric symptoms can be prominent in older people, presenting features of SLE. This case illustrates the lowest dose of corticosteroids shown to be effective in an older patient with delirium due to SLE.


Assuntos
Delírio/etiologia , Lúpus Eritematoso Sistêmico/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico
10.
Adv Space Res ; 4(10): 165-72, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-11539624

RESUMO

The routine monitoring and prediction of solar proton events that may be a hazard to personnel and materials in space are a routine service of the Space Environment Services Center in Boulder, Colorado, U.S.A. The services provided are made available to the space centers in the United States for use in their operations. The real time monitoring consists primarily of Space Environment Monitors on both geosynchronous and polar orbiting weather satellites. The monitoring emphasizes proton fluxes but alpha particles, electrons, and in one case, heavier particles, are included. The predictions are of two types; a general outlook made 1 to 3 days in advance, and specific prediction of event size and probability of occurrence made after a solar flare occurs. The accuracy of the prediction made for solar cycle 21 are assessed.


Assuntos
Prótons , Monitoramento de Radiação , Atividade Solar , Astronave , Planeta Terra , Previsões , Probabilidade
11.
Adv Space Res ; 12(2-3): 313-20, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-11537021

RESUMO

Protection from the radiation effects of solar particle events for deep space mission crews requires a warning system to observe solar flares and predict subsequent charged particle fluxes. Such a system relates precursor information observed in each flare to the intensity, delay, and duration of the subsequent Solar Particle Event (SPE) at other locations in the solar system. A warning system of this type is now in operation at the NOAA Space Environment Services Center in Boulder, Colorado for support of space missions. It has been used to predict flare particle fluxes at the earth for flares of Solar Cycle 22. The flare parameters used and the effectiveness of the current warning system, based on Solar Cycle 22 experience, are presented, with an examination of the shortcomings. Needed improvements to the system include more complete observations of solar activity, especially information on the occurrences of solar mass ejections; and consideration of the effects of propagation conditions in the solar corona and interplanetary medium. Requirements for solar observations and forecasting systems on board the spacecraft are discussed.


Assuntos
Meio Ambiente Extraterreno , Modelos Teóricos , Prótons , Sistema Solar , Fenômenos Astronômicos , Astronomia , Marte , Probabilidade , Proteção Radiológica
12.
Adv Space Res ; 9(10): 275-80, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-11537303

RESUMO

For long duration missions beyond the magnetosphere, the hazards posed by solar particle events (SPE) require the development of new strategies to minimize both the radiation dose and the effects. Potential strategies include the development of improved short-term forecasting of SPE through better observations and research, consideration of HZE particles in real-time forecasting and monitoring, improved knowledge of the biological effects of the particles involved in SPE, and the development of methods for combining SPE forecasts with temporary shielding and chemical countermeasures. Evaluation of present capabilities and the identification of areas of further research to achieve the necessary capabilities are discussed.


Assuntos
Radiação Cósmica , Prótons , Proteção Radiológica , Atividade Solar , Voo Espacial , Meio Ambiente Extraterreno , Previsões , Humanos , Marte , Modelos Teóricos , Lua , Protetores contra Radiação/uso terapêutico , Pesquisa
13.
Chronic Dis Inj Can ; 34(2-3): 132-44, 2014 Jul.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-24991776

RESUMO

INTRODUCTION: This study provides a comprehensive summary of the sociodemographic, psychosocial and health characteristics of a large population-based cohort of Ontario home care clients (aged 50 years and over) with dementia and examines the variation in these characteristics in those with co-existing neurological conditions. METHODS: Clients were assessed with the Resident Assessment Instrument-Home Care (RAI-HC) between January 2003 and December 2010. Descriptive analyses examined the distribution of these characteristics among clients with dementia relative to several comparison groups, as well as clients with other recorded neurological conditions. RESULTS: Approximately 22% of clients (n=104 802) had a diagnosis of dementia (average age 83 years, 64% female) and about one in four within this group had a co-existing neurological condition (most commonly stroke or Parkinson disease). About 43% of those with dementia did not live with their primary caregiver. Relative to several comparison groups, clients with dementia showed considerably higher levels of cognitive and functional impairment, aggression, anxiety, wandering, hallucinations/delusions, caregiver distress and a greater risk for institutionalization. Conversely, they showed a lower prevalence of several chronic conditions and lower levels of recent health service use. Depressive symptoms were relatively common in the dementia and other neurological groups. CONCLUSION: Clients with co-existing neurological conditions exhibited unique clinical profiles illustrating the need for tailored and flexible home care services and enhanced caregiver assistance programs.


TITRE: Profil complet des caractéristiques sociodémographiques, psychosociales et sanitaires des clients des soins à domicile atteints de démence en Ontario. INTRODUCTION: Cette étude fournit une synthèse des caractéristiques sociodémographiques, psychosociales et sanitaires d'une vaste cohorte représentative des clients des soins à domicile en Ontario (âgés de 50 ans ou plus) atteints de démence et elle examine les variations de ces caractéristiques chez les clients atteints de maladies neurologiques concomitantes. MÉTHODOLOGIE: Les clients ont été évalués à l'aide de l'Instrument d'évaluation des résidents ­ Soins à domicile (RAI-HC) entre janvier 2003 et décembre 2010. Les analyses descriptives fournissent la répartition de ces caractéristiques en comparant les clients atteints de démence et ceux de plusieurs autres groupes ainsi que ceux atteints d'autres maladies neurologiques documentées. RÉSULTATS: Environ 22 % des clients (n = 104 802) avaient reçu un diagnostic de démence (âge moyen de 83 ans, 64 % de femmes) et un sur quatre parmi eux était atteint d'une maladie neurologique concomitante (AVC ou maladie de Parkinson la plupart du temps). Environ 43 % des clients atteints de démence n'habitaient pas avec leur principal aidant. Par rapport aux clients des groupes de comparaison, les clients atteints de démence présentaient des taux considérablement plus élevés de déficit cognitif et fonctionnel, d'agressivité, d'anxiété, d'errance et d'hallucinations ou de délire, avaient plus souvent un aidant en détresse et couraient un plus grand risque de placement en établissement. Par contre, ils étaient moins souvent atteints de diverses maladies chroniques et étaient moins nombreux à avoir eu recours à des services de santé récemment. Les symptômes de dépression étaient relativement fréquents chez les clients atteints de démence et chez ceux atteints d'une autre maladie neurologique. CONCLUSION: Les clients atteints de maladies neurologiques concomitantes présentaient des profils cliniques bien particuliers illustrant la nécessité de personnaliser et d'assouplir les services de soins à domicile et d'améliorer les programmes de soutien pour les aidants.


Assuntos
Demência/psicologia , Nível de Saúde , Serviços de Assistência Domiciliar/estatística & dados numéricos , Saúde Mental , Doença de Parkinson/complicações , Acidente Vascular Cerebral/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Agressão , Ansiedade/complicações , Cuidadores/psicologia , Transtornos Cognitivos/complicações , Estudos Transversais , Demência/complicações , Demência/tratamento farmacológico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Alucinações/complicações , Hospitalização/estatística & dados numéricos , Humanos , Estado Civil , Pessoa de Meia-Idade , Ontário , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Características de Residência , Fatores Sexuais , Apoio Social , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/psicologia , Comportamento Errante
14.
Can J Cardiol ; 26(1): 37-41, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20101356

RESUMO

BACKGROUND: In October 2006, federal funding was announced for the development of a national strategy to fight cardiovascular disease (CVD) in Canada. The comprehensive, independent, stakeholder-driven Canadian Heart Health Strategy and Action Plan (CHHS-AP) was delivered to the Minister of Health on February 24, 2009. OBJECTIVES: The mandate of CHHS-AP Theme Working Group (TWG) 6 was to identify the optimal chronic disease management model that incorporated timely access to rehabilitation services and end-of-life planning and care. The purpose of the present paper was to provide an overview of worldwide approaches to CVD and cardiac rehabilitation (CR) strategies and recommendations for CR care in Canada, within the context of the well-known Chronic Care Model (CCM). A separate paper will address end-of-life issues in CVD. METHODS: TWG 6 was composed of content representatives, primary care representatives and patients. Input in the area of Aboriginal and indigenous cardiovascular health was obtained through individual expert consultation. Information germane to the present paper was gathered from international literature and best practice guidelines. The CCM principles were discussed and agreed on by all. Prioritization of recommendations and overall messaging was discussed and decided on within the entire TWG. The full TWG report was presented to the CHHS-AP Steering Committee and was used to inform the recommendations of the CHHS-AP. RESULTS: Specific actionable recommendations for CR are made in accordance with the key principles of the CCM. CONCLUSIONS: The present CR blueprint, as part of the CHHS-AP, will be a first step toward reducing the health care burden of CVD in Canada.


Assuntos
Reabilitação Cardíaca , Atenção à Saúde/organização & administração , Modelos Organizacionais , Canadá , Gerenciamento Clínico , Humanos , Garantia da Qualidade dos Cuidados de Saúde
17.
J Biol Chem ; 258(21): 12886-94, 1983 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-6630211

RESUMO

Ascorbic acid transport by bovine adrenomedullary chromaffin cells in primary cultures has been characterized. Ascorbic acid uptake can be measured by either high performance liquid chromatography with electrochemical detection or radiometric techniques with L-[1-14C]ascorbic acid. The transport system is temperature- and energy-dependent and exhibits Michaelis-Menten kinetics with an apparent Km of 29 microM when the external Na+ concentration is 150 mM. Uptake of ascorbate by chromaffin cells is ouabain-sensitive and dependent on the presence of external Na+. Ascorbate transport by chromaffin cells is, thus, an active process driven by the Na+ electrochemical gradient. The kinetics of this co-transport system fits an "affinity type" model where binding of Na+ to the carrier increases the affinity to ascorbate and vice versa. Thus, the data suggest that binding of either Na+ or ascorbate induces a conformational change in the transporter, which results in a change in the association constant for the second ligand while the mobility of the carrier remains unchanged. Cellular uptake of ascorbate into adrenomedullary chromaffin cells appears to be followed by its distribution into several subcellular compartments. One subcellular compartment for concentration of ascorbate is the chromaffin vesicle where it accumulates at a relatively slow rate. The interrelationships between ascorbate transport and other aspects of ascorbate metabolism and chromaffin vesicle function and dopamine beta-hydroxylation are also considered.


Assuntos
Medula Suprarrenal/metabolismo , Ácido Ascórbico/metabolismo , Sódio/metabolismo , Animais , Ascorbato Oxidase/metabolismo , Transporte Biológico/efeitos dos fármacos , Bovinos , Células Cultivadas , Grânulos Cromafim/metabolismo , Líquido Intracelular/metabolismo , Cinética , Ouabaína/farmacologia , Plantas/enzimologia , Sódio/farmacologia
18.
Mol Pharmacol ; 31(3): 259-66, 1987 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2951584

RESUMO

We report the identification and characterization of specific vasopressin-binding sites on intact cells and membranes of the established vascular smooth muscle cell line A-10, the fate of vasopressin associated with the cells, the role of guanine nucleotides in the regulation of the affinity of the vasopressin-binding sites, and the determination of the vasopressin receptor subtype. We have found specific vasopressin-binding sites on intact cells in monolayer (110,000 sites per cell during log growth and 60,000 sites per cell in stationary culture) with a KD of 6 nM at 37 degrees. After incubation of [3H]-8-arginine vasopressin ([3H]AVP) and cells for less than 20 min, cell-associated AVP was intact; with longer incubation times, AVP was progressively degraded. The major metabolites included phenylalanine and a fraction that eluted from a C18 reverse phase high performance liquid chromatography column between AVP and 8-arginine, 9-desglycinamide vasopressin. Extensive degradation also occurred when AVP was allowed to dissociate from the cells. With increased time of incubation, the amount of specifically bound AVP that could dissociate decreased, suggesting receptor-mediated endocytosis. In saturation equilibrium binding experiments with plasma membranes, two affinity states with KD of 0.7 nM and 379 nM were observed. The number of high affinity binding sites was similar to the number of receptors found on intact cells. Guanosine 5'-(beta,gamma-imido)triphosphate decreased vasopressin binding to the high affinity sites and did not significantly affect the low affinity sites. Competition binding experiments indicated that the vasopressin-binding sites of A-10 cells belong to the vascular V1 receptor subtype. We conclude that the established vascular smooth muscle cell line A-10 expressed vasopressin receptors of the vascular V1 subtype. Vasopressin bound to the receptors reversibly, but could also be degraded by the cells presumably after receptor-mediated endocytosis. The receptors might exist in different affinity states; guanosine 5'-(beta,gamma-imido)triphosphate decreased the affinity of the high affinity binding state.


Assuntos
Arginina Vasopressina/metabolismo , Músculo Liso Vascular/metabolismo , Receptores de Angiotensina/metabolismo , Animais , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/antagonistas & inibidores , Divisão Celular , Linhagem Celular , Membrana Celular/metabolismo , Guanilil Imidodifosfato/farmacologia , Ratos , Receptores de Angiotensina/classificação , Receptores de Vasopressinas
19.
J Pharmacol Exp Ther ; 232(1): 100-5, 1985 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3965688

RESUMO

To understand the molecular mechanism of action of the novel class of diuretic agents, the antidiuretic hormone antagonists ["aquaretics" (specific water-losing activity as caused by vasopressin antagonists, as distinguished from the saluresis of conventional diuretics)], in the dog studies were made of the properties of the vasopressin-responsive adenylate cyclase system and the antagonist potencies of the vasopressin analogs [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-(O-ethyl)tyrosine,4-valine,8-arginine]vasopressin; [1-(beta-mercapto-beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-D-phenylalanine,4-valine,8-arginine]vasopressin; and [1-(beta-mercapto-beta, beta-cyclopenta-methylenepropionic acid), 2-D-(O-ethyl)tyrosine,4-valine,8-arginine]vasopressin (SK&F 100398, 101071 and 101498, respectively) using plasma membranes prepared from cortex, medulla and papilla of dog kidney. It was observed that the greatest sensitivity for vasopressin was in the papilla (concentration of 8-arginine vasopressin required for 50% activation of adenylate cyclase [Kact] was 2.0 X 10(-9)M, 1.1 X 10(-9)M and 5.1 X 10(-10) M in the cortex, medulla and papilla, respectively). The addition of 10(-5)M GTP did not alter the Kact of the cortex but enhanced 10-fold the vasopressin sensitivity of the papilla to 5.2 X 10(-11) M. The vasopressin analogs were competitive antagonists of vasopressin-stimulated adenylate cyclase of cortex and papilla with the greatest potency for the papillary enzyme (Ki in papilla was 3.6 X 10(-9)M, 4.6 X 10(-9)M and 1.0 X 10(-9)M for SK&F 100398, 101071 and 101498, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Água Corporal/metabolismo , Córtex Renal/efeitos dos fármacos , Medula Renal/efeitos dos fármacos , Vasopressinas/farmacologia , Adenilil Ciclases/metabolismo , Animais , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/farmacologia , Cães , Relação Dose-Resposta a Droga , Ativação Enzimática , Guanosina Trifosfato/farmacologia , Córtex Renal/enzimologia , Medula Renal/enzimologia
20.
J Dairy Sci ; 77(10): 3185-91, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7836607

RESUMO

Nonreturn rates to professional technician service of 7240 first AI Holstein cows were calculated to evaluate differences between once daily and a.m.-p.m. AI. To determine whether management practices affected nonreturn rates, participating herd owners were surveyed for methods used for detection of estrus. Nonreturn rates for once daily and a.m.-p.m. AI were 64.6 and 65.6% for 60-d, 60.1 and 60.6% for 75-d, and 58.4 and 57.8% for 90-d nonreturn periods. Signs of estrus for AI and interval from detection of estrus to AI were related to nonreturn rates. Nonreturn rate was highest, 63.4%, when cows were in standing estrus. Nonreturn rates were lowest, 36%, when cows were bred after treatment with PGF2 alpha without being detected in estrus or bred strictly on veterinary advice based on palpation. Nonreturn rates were similar for different times of the day when once daily AI was practiced. However, AI in the midmorning may have some advantages. The highest nonreturn rate for a 3-h period was 68.2% for 0800 and 1100 h; the lowest was 54.7% for 1300 to 1600 h. Movement before observation for estrus and an observation period > 15 min improved nonreturn rates for once daily AI. Once daily AI can be used effectively with no difference from the traditional a.m.-p.m. system; results are best when AI is based on standing estrus and performed between 0800 and 1100 h.


Assuntos
Indústria de Laticínios/métodos , Inseminação Artificial/veterinária , Animais , Bovinos , Estro , Detecção do Estro , Feminino , Inseminação Artificial/métodos , Masculino , Estatística como Assunto , Fatores de Tempo
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