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1.
Trop Med Int Health ; 24(6): 671-691, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30843627

RESUMO

OBJECTIVE: A myriad of physical and psychosocial sequelae have been reported among Ebola survivors from previous Ebola virus disease (EVD) outbreaks, including the most recent in West Africa. This review examines the various forms of psychological distress experienced by EVD survivors, family and community reactions to EVD survivors and EVD survivors' coping mechanisms. METHODS: We conducted a literature search of original articles employing Medline (Ovid), PubMed, Web of Science, Scopus, CINAHL, EBSCO host academic search complete, PsycINFO (EBSCO) and Embase databases. RESULTS: Our search identified 1890 articles of which 24 met our inclusion criteria. Various forms of psychological distress were prevalent among EVD survivors including depression, anxiety, anger, grief, guilt, flashbacks, sadness, worthlessness, substance addiction, suicidal tendencies and self-stigmatisation. Family and community responses to EVD survivors ranged from acceptance to rejection, isolation, stigmatisation and discrimination. EVD survivors' coping strategies included engagement with religious faith, EVD survivors associations and involvement in EVD prevention and control interventions. CONCLUSION: Psychological distress, including that resulting from family and community stigma and discrimination, appears common among EVD survivors. Community-based mental health and psychosocial interventions integrated within a broader package of care for EVD survivors that also recognises the physical health challenges are required. Well-designed longitudinal studies can provide clear insights on the nature and trajectory of the psychosocial issues currently experienced by EVD survivors.


OBJECTIF: Une myriade de séquelles physiques et psychosociales a été rapportée parmi les survivants d'Ebola lors des épidémies précédentes de la maladie du virus Ebola (MVE) et dans la plus récente en Afrique de l'Ouest. Cette revue examine les différentes formes de détresse psychologique vécue par les survivants de la MVE, les réactions de la famille et de la communauté à l'égard des survivants de la MVE et leurs mécanismes d'adaptation. MÉTHODES: Nous avons effectué une recherche de la littérature dans des articles originaux en utilisant les bases de données Medline (Ovid), PubMed, Web of Science, Scopus, CINAHL, EBSCO host academic search complete, PsycINFO (EBSCO) et Embase. RÉSULTATS: Notre recherche a identifié 1.890 articles dont 24 répondaient aux critères d'inclusion. Diverses formes de détresse psychologique étaient prévalentes parmi les survivants de la MVE, notamment la dépression, l'anxiété, la colère, le deuil, la culpabilité, les flashbacks, la tristesse, le sentiment d'inutilité, la toxicomanie, les tendances suicidaires et l'auto-stigmatisation. Les réactions des familles et des communautés vis-à-vis des survivants de la MVE vont de l'acceptation au rejet, à l'isolement, à la stigmatisation et à la discrimination. Les stratégies d'adaptation des survivants de la MVE comprenaient l'engagement avec la religion, dans les associations de survivants de la MVE et une implication dans des interventions de prévention et de lutte contre la MVE. CONCLUSION: La détresse psychologique, y compris celle résultant de la stigmatisation et de la discrimination familiale et communautaire, semble être fréquente chez les survivants de la MVE. Des interventions communautaires intégrées psychosociales et de santé mentale dans un ensemble plus large de soins pour les survivants de la MVE, qui reconnaît également les problèmes de santé physique sont nécessaires. Des études longitudinales bien conçues peuvent fournir des informations claires sur la nature et la trajectoire des problèmes psychosociaux actuellement rencontrés par les survivants de la MVE.


Assuntos
Adaptação Psicológica , Família/psicologia , Doença pelo Vírus Ebola/psicologia , Estresse Psicológico/epidemiologia , Sobreviventes/psicologia , Serviços Comunitários de Saúde Mental , Surtos de Doenças , Doença pelo Vírus Ebola/epidemiologia , Humanos , Estigma Social
2.
Int J Cosmet Sci ; 39(6): 610-616, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28748540

RESUMO

BACKGROUND: The deposit and adherence of particulate matter (PM) from aerial pollution onto the surface of human hair is a poorly studied phenomenon. OBJECTIVES: (i) To reproduce in vitro the deposit of known PM on standardized hair swatches in a closed box, (ii) to compare in vitro data with those obtained under 'real-life' conditions of severe aerial pollution and (iii) to assess the changes of the hair surface properties, potentially caused by the adherence of airborne PM onto the hair. METHODS: In vitro: a PM was sprayed onto untreated or sebum-coated hair swatches. Real-life conditions: other swatches were exposed to a severely polluted environment, for 24 to 72 h, in Baoding (PR China). In both cases, swatches were examined using scanning electron microscopy. The shine, the frictional properties and the level of metals were measured and compared to those same properties for the unexposed swatches. RESULTS: This work clearly indicates that, under real-life conditions, a large number of PM of various sizes are deposited onto the hair surface. This phenomenon is increased by the presence of sebum and longer exposure times. The in vitro level of PM deposited onto the hair surface is comparable to the in vivo level. The presence of sebum seems to favour the deposit of larger PM. The shine of the exposed swatches is significantly decreased, whereas their respective friction coefficients are significantly increased. Both the presence of sebum and length of exposure time increased the amount of analysed metals present on the exposed hair surface (Al, Fe, Cu, Ba and Zn). CONCLUSION: This work indicates that a very high amount (e.g. billions) of PM can be deposited on a full head of hair for subjects living in a severely aerially polluted environment. This process can be reproduced in vitro. In real-life, pollution has a strong impact on hair surface properties, leading to a modification of the visual aspect (loss of shine) and the alteration of hair surface (increase in friction force). This work may be used to pave the way for prevention and cleansing studies in the field of hair care.


Assuntos
Cabelo/química , Material Particulado/química , Humanos , Propriedades de Superfície
3.
J Interprof Care ; 31(6): 734-743, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28876144

RESUMO

Complementary and alternative medicine (CAM) is an increasingly prevalent part of contemporary health care. Whilst there have been some attempts to understand the dynamics of CAM integration in the health care system from the perspective of conventional care providers and patients, little research has examined the view of CAM practitioners. This study aims to identify the experiences of integration within a conventional healthcare system as perceived by naturopaths. Qualitative semi-structured interviews were conducted using a purposeful sample of 20 practising naturopaths in South East Queensland, Australia to discuss their experiences and perceptions of integrating with conventional medical providers. Analysis of the interviews revealed five broad challenges for the integration of CAM according to naturopaths: competing paradigms between CAM and conventional medicine; co-option of CAM by conventional medical practitioners; the preservation of separate CAM and conventional medical worlds by patients and providers due to lack of formalised relations; negative feedback and biases created through selective or limited experience or information with CAM; and indifferent, reactive and one-sided interaction between CAM and conventional medical providers. Naturopaths support the integration of health services and attempt to provide safe and appropriate care to their patients through collaborative approaches to practice. The challenges identified by naturopaths associated with integration of CAM with conventional providers may impact the quality of care of patients who choose to integrate CAM and conventional approaches to health. Given the significant role of naturopaths in contemporary health-care systems, these challenges require further research and policy attention.


Assuntos
Comportamento Cooperativo , Relações Interprofissionais , Medicina , Naturologia/psicologia , Percepção , Atitude do Pessoal de Saúde , Austrália , Humanos , Medicina Integrativa/organização & administração , Entrevistas como Assunto , Pesquisa Qualitativa , Queensland
4.
Metab Brain Dis ; 31(3): 497-515, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26883429

RESUMO

The prevalence of both diabetes and Alzheimer's disease (AD) are reaching epidemic proportions worldwide. Alarmingly, diabetes is also a risk factor for Alzheimer's disease. The AD brain is characterised by the accumulation of peptides called Aß as plaques in the neuropil and hyperphosphorylated tau protein in the form of neurofibrillary tangles within neurons. How diabetes confers risk is unknown but a simple linear relationship has been proposed whereby the hyperinsulinemia associated with type 2 diabetes leads to decreased insulin signaling in the brain, with downregulation of the PI3K/AKT signalling pathway and its inhibition of the major tau kinase, glycogen synthase kinase 3ß. The earliest studies of post mortem AD brain tissue largely confirmed this cascade of events but subsequent studies have generally found either an upregulation of AKT activity, or that the relationship between insulin signaling and AD is independent of glycogen synthase kinase 3ß altogether. Given the lack of success of beta-amyloid-reducing therapies in clinical trials, there is intense interest in finding alternative or adjunctive therapeutic targets for AD. Insulin signaling is a neuroprotective pathway and represents an attractive therapeutic option. However, this incredibly complex signaling pathway is not fully understood in the human brain and particularly in the context of AD. Here, we review the ups and downs of the research efforts aimed at understanding how diabetes modifies AD risk.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/patologia , Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo , Receptor de Insulina/metabolismo , Encéfalo/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/fisiologia
5.
J Obstet Gynaecol ; 36(4): 462-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26472482

RESUMO

The aim of this study was to analyse women's attitudes towards the use of complementary and alternative medicine (CAM) products during pregnancy. The study sample was obtained via the Australian Longitudinal Study on Women's Health or ALSWH. A response rate of 79.2% (n = 1,835) was attained. Women who use herbal medicines (34.5%, n = 588) view CAM as a preventative measure, are looking for something holistic and are concerned about evidence of clinical efficacy when considering the use of these products during pregnancy. Women who use aromatherapy (17.4%, n = 319) and homoeopathy (13.3%, n = 244) want more personal control over their body and are concerned more about their own personal experience of the efficacy of CAM than clinical evidence of efficacy. As CAM use in pregnancy appears to be increasingly commonplace, insights into women's attitudes towards CAM are valuable for maternity healthcare providers.


Assuntos
Atitude Frente a Saúde , Terapias Complementares/psicologia , Gestantes/psicologia , Adolescente , Adulto , Austrália , Feminino , Humanos , Estudos Longitudinais , Gravidez , Inquéritos e Questionários , Adulto Jovem
8.
Anaesthesia ; 68 Suppl 1: 40-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23210555

RESUMO

Major trauma is a leading cause of death and disability in the UK, particularly in the young. Pre-hospital emergency medicine (PHEM) involves provision of immediate medical care to critically ill and injured patients, across all age ranges, often in environments that may be remote and are not only physically challenging but also limited in terms of time and resources. PHEM is now a GMC-recognised subspecialty of anaesthesia or emergency medicine and the first recognised training program in the UK commenced in August 2012. This article discusses subspeciality development in PHEM, the competency based framework for training in PHEM, and the provision of pre-hospital emergency anaesthesia.


Assuntos
Anestesia/métodos , Serviços Médicos de Emergência/métodos , Ferimentos e Lesões/terapia , Anestesiologia/educação , Serviços Médicos de Emergência/economia , Serviços Médicos de Emergência/tendências , Medicina de Emergência/educação , Humanos , Equipe de Assistência ao Paciente , Transferência de Pacientes
9.
Anaesthesia ; 67(9): 1021-4, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22734812

RESUMO

We present the case of a 20-year-old woman who developed rhabdomyolysis, disseminated intravascular coagulopathy and multi-organ failure induced by ecstasy. Following initial improvement, she developed delayed rhabdomyolysis then haloperidol-induced neuroleptic malignant syndrome, which was treated with a total of 50 mg.kg(-1) dantrolene. Subsequent genetic testing revealed a novel potentially pathogenic variant in the ryanodine receptor type 1 gene. However, caffeine-halothane contracture testing of the patient's mother who carried the same gene variant was negative for malignant hyperthermia.


Assuntos
Alucinógenos/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Síndrome Maligna Neuroléptica/genética , Síndrome Maligna Neuroléptica/fisiopatologia , Rabdomiólise/induzido quimicamente , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Anestésicos Inalatórios , Antipsicóticos/efeitos adversos , Temperatura Corporal , Cafeína , Estimulantes do Sistema Nervoso Central , Cromatografia Líquida de Alta Pressão , Creatina Quinase/sangue , Dantroleno/uso terapêutico , Coagulação Intravascular Disseminada/etiologia , Feminino , Variação Genética , Haloperidol/efeitos adversos , Halotano , Humanos , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Insuficiência de Múltiplos Órgãos/fisiopatologia , Recidiva , Rabdomiólise/genética , Rabdomiólise/fisiopatologia , Análise Espectral , Adulto Jovem
10.
BMC Complement Med Ther ; 21(1): 67, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602181

RESUMO

BACKGROUND: This descriptive study provides the first examination of global naturopathic education, regulation and practice frameworks that have potential to constrain or assist professional formation and integration in global health systems. Despite increasing public use, a significant workforce, and World Health Organization calls for national policy development to support integration of services, existent frameworks as potential barriers to integration have not been examined. METHODS: This cross-sectional survey utilized purposive sampling of 65 naturopathic organisations (educational institutions, professional associations, and regulatory bodies) from 29 countries. Organizational representatives completed an on-line survey, conducted between Nov 2016 - Aug 2019. Frequencies and cross-tabulation statistics were analyzed using SPSSv.25. Qualitative responses were hand-coded and thematically analysed where appropriate. RESULTS: Sixty-five of 228 naturopathic organizations completed the survey (29% response rate) from 29 of 46 countries (63% country response rate). Most education programs (68%) were delivered via a national framework. Higher education qualifications (60%) predominated. Organizations influential in education were professional associations (75.4%), particularly where naturopathy was unregulated, and accreditation bodies (41.5%) and regulatory boards (33.8%) where regulated. Full access to controlled acts, and to health insurance rebates were more commonly reported where regulated. Attitude of decision-makers, opinions of other health professions and existing legislation were perceived to most impact regulation, which was globally heterogeneous. CONCLUSION: Education and regulation of the naturopathic profession has significant heterogeneity, even in the face of global calls for consistent regulation that recognizes naturopathy as a medical system. Standards are highest and consistency more apparent in countries with regulatory frameworks.


Assuntos
Educação Profissionalizante , Saúde Global , Naturologia , Prática Profissional , Controle Social Formal , Acreditação , Atitude , Estudos Transversais , Atenção à Saúde , Humanos , Medicina Integrativa , Organizações , Inquéritos e Questionários
12.
13.
Anaesthesia ; 64(9): 978-83, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19686483

RESUMO

We conducted a pilot study of the effects of simulation as a tool for teaching doctor-paramedic teams to deliver pre-hospital anaesthesia safely. Participants undertook a course including 43 full immersion, high-fidelity simulations. Twenty videos taken from day 4 and days 9/10 of the course were reviewed by a panel of experienced pre-hospital practitioners. Participants' performance at the beginning and the end of the course was compared. The total time from arrival to inflation of the tracheal tube cuff was longer on days 9/10 than on day 4 (mean (SD) 14 min 52 s (2 min 6 s) vs 11 min 28 s (1 min 54 s), respectively; p = 0.005), while the number of safety critical events per simulation were fewer (median (IQR [range]) 1.0 (0-1.8 [0-2]) vs 3.5 (1.5-4.8 [0-8], respectively; p = 0.011). Crew resource management behaviours also improved in later simulations. On a personal training needs analysis, participants reported increased confidence after the course.


Assuntos
Anestesiologia/educação , Educação Médica Continuada/métodos , Serviços Médicos de Emergência/normas , Anestesia/normas , Competência Clínica , Auxiliares de Emergência/educação , Humanos , Intubação Intratraqueal/normas , Equipe de Assistência ao Paciente/normas , Simulação de Paciente , Projetos Piloto , Segurança , Fatores de Tempo
14.
Emerg Med J ; 26(5): 365-70, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19386879

RESUMO

AIMS: There is a lack of consensus regarding the role for critical care in the prehospital environment in the UK. It was hypothesised that this related to differences in views and understanding among opinion leaders within influential prehospital care organisations. METHODS: A 38-item survey was developed by an established paramedic-physician prehospital critical care service. The survey was distributed to individuals in senior positions within seven organisations that have a major influence on UK prehospital services. Analysis comprised a description of the distribution of results, assessment of the level of agreement with each statement by professional background and current involvement in prehospital critical care and evaluation of the overall consistency of responses. Free-text comments were invited to illustrate the reasoning behind each response. RESULTS: There were 32 respondents. The estimated response rate was 40%. The consistency of the questionnaire responses was very high. Overall, all individuals agreed with most of the statements. Paramedic respondents were more likely to disagree with statements that suggested that critical care involved interventions that exceed the current capability of the NHS ambulance service (p<0.05). Free-text comments revealed wide differences of opinion. CONCLUSION: Although there appears to be broad agreement among opinion leaders regarding the concepts underpinning existing prehospital critical care services, areas of contention are highlighted that may help explain the current lack of consensus. Cooperative efforts to assess the current demand and clinical evidence would assist in the creation of a joint consensus and allow effective future planning for the provision of prehospital critical care throughout the UK.


Assuntos
Atitude do Pessoal de Saúde , Cuidados Críticos/organização & administração , Serviços Médicos de Emergência/organização & administração , Consenso , Atenção à Saúde/organização & administração , Auxiliares de Emergência , Pesquisas sobre Atenção à Saúde , Pesquisa sobre Serviços de Saúde/métodos , Humanos , Psicometria , Reino Unido
15.
J Obstet Gynaecol ; 29(6): 464-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19697190

RESUMO

The stillbirth rate for singletons in the UK is approximately 5.3/1,000 births/year. Macrosomic babies are associated with obstructed labour and shoulder dystocia. Some 3.3% of stillborns weigh over 4 kg, when such problems are likely to be encountered. In developed countries, caesarean section is regarded as being more civilised than destructive operations for obstructed labour prior to full cervical dilatation in an interuterine death. However, when the cervix is fully dilated or severe shoulder dystocia is encountered, fetal destructive operations have half the maternal mortality rate of that associated with caesarean section, with fewer long-term sequelae. A significant obstacle in performing destructive operations in developed countries is the lack of skilled practitioners. It is difficult to acquire these skills in the UK, however simulated training can be provided with manikins. We feel mothers should be informed of the alternative of a destructive operation, potentially avoiding unnecessary caesarean section.


Assuntos
Cesárea , Distocia/cirurgia , Natimorto , Adulto , Contraindicações , Craniotomia , Feminino , Humanos , Gravidez , Adulto Jovem
16.
J Obstet Gynaecol ; 29(1): 17-20, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19280489

RESUMO

Elective cerclage is a rare procedure, but is reported to be relatively more common in developing countries. This variation in rate may be reflected in a multi-ethnic population as seen in London. Our study analysed the epidemiology and rate of elective cerclage performed in a London district general hospital. Factors contributing to the outcome of the procedures were also reviewed. A total of 41 elective cerclages were performed in the hospital between 2000 and 2007. Data from these were collected retrospectively, including maternal history, operative details, and gestational age at delivery. Fisher's exact test was used for statistical analysis. Of the 41 cases, 19 pregnancies were carried to term (>or=37 weeks' gestation), nine were pre-term (24-36 weeks' gestation) and seven miscarried (<24 weeks' gestation); six cases had not yet delivered. All of the patients were immigrants from developing countries but ethnicity did not affect the operative outcome (p = 0.89, Fisher's exact). The other factors studied were also noted to have no significant impact on success. These included cervical length at insertion (p = 1.00, Fisher's exact), type of suture (p = 0.90, Fisher's exact) and average gestation at insertion (p = 0.20, Fisher's exact). In conclusion, all patients requiring intervention in this study originated from developing countries. This is a disproportionately high figure relative to the demographic breakdown of the study population. Such a finding may be due to geographical variation of risk factors for cervical incompetence but may also be influenced by observer bias. Additional studies are needed to further investigate the influence of ethnicity on the rate of elective cerclage. None of the variables analysed in this study significantly affected the outcome of the procedure.


Assuntos
Cerclagem Cervical/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Emigrantes e Imigrantes/estatística & dados numéricos , Países em Desenvolvimento , Feminino , Hospitais Gerais/estatística & dados numéricos , Humanos , Londres/epidemiologia , Gravidez , Estudos Retrospectivos
17.
Sci Rep ; 9(1): 1573, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30733573

RESUMO

Concomitant complementary medicine (CM) and conventional medicine use is frequent and carries potential risks. Yet, CM users frequently neglect to disclose CM use to medical providers. Our systematic review examines rates of and reasons for CM use disclosure to medical providers. Observational studies published 2003-2016 were searched (AMED, CINAHL, MEDLINE, PsycINFO). Eighty-six papers reporting disclosure rates and/or reasons for disclosure/non-disclosure of CM use to medical providers were reviewed. Fourteen were selected for meta-analysis of disclosure rates of biologically-based CM. Overall disclosure rates varied (7-80%). Meta-analysis revealed a 33% disclosure rate (95%CI: 24% to 43%) for biologically-based CM. Reasons for non-disclosure included lack of inquiry from medical providers, fear of provider disapproval, perception of disclosure as unimportant, belief providers lacked CM knowledge, lacking time, and belief CM was safe. Reasons for disclosure included inquiry from medical providers, belief providers would support CM use, belief disclosure was important for safety, and belief providers would give advice about CM. Disclosure appears to be influenced by the nature of patient-provider communication. However, inconsistent definitions of CM and lack of a standard measure for disclosure created substantial heterogeneity between studies. Disclosure of CM use to medical providers must be encouraged for safe, effective patient care.


Assuntos
Terapias Complementares , Pessoal de Saúde , Revelação da Verdade , Estudos Transversais , Humanos , Prevalência , Viés de Publicação
18.
Complement Ther Clin Pract ; 33: 100-106, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30396606

RESUMO

BACKGROUND AND PURPOSE: This study examines the relationship between the use of complementary medicine (CM) interventions or consultations with CM practitioners and women's choice of contraceptive method. MATERIALS AND METHODS: A secondary analysis of a cross-sectional survey of Australian Women aged 34-39 years from the Australian Longitudinal Study on Women's Health (ALSWH) was conducted. Associations between use of CM and contraception were analysed using Chi-squared tests and multivariate logistic regression. RESULTS: Based on the responses from the included women (n = 7299), women who consulted a naturopath/herbalist were less likely to use implant contraceptives (OR 0.56; 95% confidence interval (CI) 0.33; 0.95). Those consulting a chiropractor (OR 1.54; 95%CI 1.05; 2.25) or an osteopath (OR 2.16; 95% CI 1.32; 3.54) were more likely to use natural contraception. CONCLUSION: There may be a link between women's choice of contraceptive method and their use of CM, in particular, with CM practitioner consultations.


Assuntos
Comportamento de Escolha , Terapias Complementares , Anticoncepção , Adulto , Austrália/epidemiologia , Terapias Complementares/métodos , Terapias Complementares/psicologia , Terapias Complementares/estatística & dados numéricos , Anticoncepção/métodos , Anticoncepção/psicologia , Anticoncepção/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Encaminhamento e Consulta , Saúde da Mulher
19.
J Clin Invest ; 98(11): 2580-7, 1996 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-8958221

RESUMO

Absorption of urea in the renal inner medullary collecting duct (IMCD) contributes to hypertonicity in the medullary interstitium which, in turn, provides the osmotic driving force for water reabsorption. This mechanism is regulated by vasopressin via a cAMP-dependent pathway and activation of a specialized urea transporter located in the apical membrane. We report here the cloning of a novel urea transporter, designated UT1, from the rat inner medulla which is functionally and structurally distinct from the previously reported kidney urea transporter UT2. UT1 expressed in Xenopus oocytes mediated passive transport of urea that was inhibited by phloretin and urea analogs but, in contrast to UT2, was strongly stimulated by cAMP agonists. Sequence comparison revealed that the coding region of UT1 cDNA contains the entire 397 amino acid residue coding region of UT2 and an additional 1,596 basepair-stretch at the 5' end. This stretch encodes a novel 532 amino acid residue NH2-terminal domain that has 67% sequence identity with UT2. Thus, UT1 consists of two internally homologous portions that have most likely arisen by gene duplication. Studies of the rat genomic DNA further indicated that UT1 and UT2 are derived from a single gene by alternative splicing. Based on Northern analysis and in situ hybridization, UT1 is expressed exclusively in the IMCD, particularly in its terminal portion. Taken together, our data show that UT1 corresponds to the previously characterized vasopressin-regulated urea transporter in the apical membrane of the terminal IMCD which plays a critical role in renal water conservation.


Assuntos
Proteínas de Transporte/biossíntese , Proteínas de Transporte/química , Medula Renal/metabolismo , Túbulos Renais Coletores/metabolismo , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/química , Proteínas de Membrana Transportadoras , Transcrição Gênica , Vasopressinas/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Transporte/fisiologia , Clonagem Molecular , Sequência Conservada , Cisteína , Sondas de DNA , Éxons , Biblioteca Gênica , Hibridização In Situ , Medula Renal/fisiologia , Túbulos Renais Coletores/fisiologia , Glicoproteínas de Membrana/fisiologia , Dados de Sequência Molecular , Especificidade de Órgãos , Estrutura Secundária de Proteína , RNA Mensageiro/biossíntese , Ratos , Homologia de Sequência de Aminoácidos , Ureia/metabolismo , Transportadores de Ureia
20.
J Clin Invest ; 102(11): 2011-8, 1998 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-9835627

RESUMO

Intestinal epithelial cells express hPepT1, an apical transporter responsible for the uptake of a broad array of small peptides. As these could conceivably include n-formyl peptides, we examined whether hPepT1 could transport the model n-formylated peptide fMLP and, if so, whether such cellular uptake of fMLP influenced neutrophil-epithelial interactions. fMLP uptake into oocytes was enhanced by hPepT1 expression. In addition, fMLP competitively inhibited uptake of a known hPepT1 substrate (glycylsarcosine) in hPepT1 expressing oocytes. hPepT1 peptide uptake was further examined in a polarized human intestinal epithelial cell line (Caco2-BBE) known to express this transporter. Epithelial monolayers internalized apical fMLP in a fashion that was competitively inhibited by other hPepT1 recognized solutes, but not by related solutes that were not transported by hPepT1. Fluorescence analyses of intracellular pH revealed that fMLP uptake was accompanied by cytosolic acidification, consistent with the known function of hPepT1 as a peptide H+ cotransporter. Lumenal fMLP resulted in directed movement of neutrophils across epithelial monolayers. Solutes that inhibit hPepT1-mediated fMLP transport decreased neutrophil transmigration by approximately 50%. Conversely, conditions that enhanced the rate of hPepT1-mediated fMLP uptake (cytosolic acidification) enhanced neutrophil-transepithelial migration by approximately 70%. We conclude that hPepT1 transports fMLP and uptake of these peptide influences neutrophil-epithelial interactions. These data (a) emphasize the importance of hPepT1 in mediating intestinal inflammation, (b) raise the possibility that modulating hPepT1 activity could influence states of intestinal inflammation, and (c) provide the first evidence of a link between active transepithelial transport and neutrophil-epithelial interactions.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Transporte/fisiologia , Fatores Quimiotáticos/metabolismo , Células Epiteliais/efeitos dos fármacos , Escherichia coli/metabolismo , N-Formilmetionina Leucil-Fenilalanina/metabolismo , Simportadores , Animais , Cálcio/metabolismo , Quimiotaxia de Leucócito/efeitos dos fármacos , Neoplasias do Colo/patologia , Dipeptídeos/metabolismo , Células Epiteliais/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Transporte de Íons/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Transportador 1 de Peptídeos , Células Tumorais Cultivadas , Xenopus laevis
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