Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
1.
Gen Comp Endocrinol ; 294: 113487, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32278883

RESUMO

Serum collected across the lifespan of four managed rhino species: black (Diceros bicornis, n = 16), white (Ceratotherium simum simum, n = 19), greater one-horned (GOH, Rhinoceros unicornis, n = 11) and Sumatran (Dicerorhinus sumatrensis, n = 6) were validated and analyzed in an anti-Müllerian hormone (AMH) enzyme- linked immunoassay. Concentrations of AMH were examined over time, between sexes and throughout different reproductive states which included n = 3 female white rhinos immunocontracepted with porcine zona pellucida (pZP). Across species, males produced higher AMH concentrations compared to females. Among males, AMH concentrations varied by species aside from comparable values secreted between black and white rhinos. The GOH and Sumatran rhino secreted the highest and lowest male AMH concentrations, respectively. However, within each species, AMH concentrations were similar across male age categories. Preliminary insight into male AMH changes from birth to sexual maturity suggest its potential as a marker for onset of testicular maturation. Female black, GOH and Sumatran rhinos secreted comparable AMH concentrations which were higher than those in white rhino. Within each species, inter-individual variation in AMH secretion occurred among females of similar age. While AMH secretion did not differ across the ages sampled for female white (4->26 yr) and GOH (4-26 yr) rhinos, black and Sumatran rhinos >26 and <4 yr, respectively secreted lower AMH compared to conspecific females 7-26 yr of age. Two idiopathic infertility cases corresponded to low (outside species range) AMH values. The establishment of normative AMH concentrations in managed African and Asian rhinos provides an additional metric beyond traditional sex steroids to assess gonadal function. Further work is needed to determine if AMH can predict fertility potential in rhinos.


Assuntos
Hormônio Antimülleriano/metabolismo , Perissodáctilos/metabolismo , África , Envelhecimento/fisiologia , Animais , Hormônio Antimülleriano/sangue , Ásia , Ciclo Estral/fisiologia , Feminino , Imunização , Masculino , Perissodáctilos/sangue , Reprodução/fisiologia , Especificidade da Espécie
2.
J Neonatal Perinatal Med ; 12(4): 443-448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256078

RESUMO

BACKGROUND: Creation of a clinical guideline to reduce the number of complete blood counts (CBCs) obtained on healthy term infants for early onset sepsis (EOS) evaluation secondary to maternal chorioamnionitis. METHODS: A clinical guideline was introduced at four neonatal intensive care units (NICU) to reduce laboratory tests during EOS evaluation. Measures include frequency and timing of CBCs, culture negative sepsis, length of stay, and readmission rate. RESULTS: Mean number of CBCs per patient significantly decreased (2.31±0.62 versus 1.52±0.65) without increasing trends for patients with culture negative sepsis, length of stay, or re-admission. CONCLUSION: The clinical guideline demonstrated a significant reduction in the number of CBCs obtained in well-appearing infants admitted to the NICU secondary to maternal chorioamnionitis.


Assuntos
Antibacterianos/uso terapêutico , Contagem de Células Sanguíneas/estatística & dados numéricos , Corioamnionite/sangue , Fidelidade a Diretrizes , Unidades de Terapia Intensiva Neonatal , Sepse Neonatal/sangue , Adulto , Infecções Assintomáticas , Corioamnionite/tratamento farmacológico , Corioamnionite/fisiopatologia , Protocolos Clínicos , Feminino , Humanos , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/fisiopatologia , Readmissão do Paciente/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Gravidez , Medição de Risco
3.
Free Radic Biol Med ; 126: 142-152, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30096434

RESUMO

F2-isoprostanes (F2-IsoP) are formed in vivo via free radical peroxidation of arachidonic acid. Enhanced oxidative stress is implicated in the development of atherosclerosis in humans and F2-IsoP have been detected in atherosclerotic plaque. Colony stimulating factor-1 (CSF-1) is essential to macrophage survival, proliferation and differentiation and has been detected in human atherosclerotic plaques. Accumulation of macrophages within the vascular wall is an important component of atherosclerosis but little is known about the effect of F2-IsoP on the migration of these cells. Our aim was to examine the effect of free and lipid-bound 15-F2t-isoprostane (15-F2t-IsoP) on macrophage migration and investigate the signalling pathways involved. Mouse macrophages (cell line BAC1.2F5) were pre-incubated with 15-F2t-IsoP (free, bound to cholesterol or monoacylglycerol or within oxidized phospholipid) and cell migration was assessed using chemotaxis towards CSF-1 in Boyden chambers. Migration was also measured using the wound healing assay with primary mouse bone marrow derived macrophages. We showed that 15-F2t-IsoP dose-dependently inhibited BAC1.2F5 macrophage spreading and adhesion but stimulated their migration towards CSF-1, with maximum effect at 10 µM. Analysis of CSF-1 stimulated signalling pathways in BAC1.2F5 macrophages showed that phosphorylation of Akt, a key mediator of cell migration, and one of its regulators, the mTORC2 component, Rictor, was significantly decreased. In contrast, phosphorylation of the adhesion kinases, FAK and Pyk2, and the adhesion scaffold protein, paxillin, was enhanced after treatment with 15-F2t-IsoP. Mouse bone marrow macrophages were transfected with FAK or Pyk2 small interfering RNA (siRNA) to examine the role of FAK and Pyk2 in 15-F2t-IsoP signalling. Pyk2 silencing inhibited 15-F2t-IsoP-induced reduction in cell area and phospho-paxillin adhesion numbers. The size distribution of adhesions in the presence of 15-F2t-IsoP was also affected by Pyk2 silencing and there was a trend for Pyk2 silencing to reduce 15-F2t-IsoP-stimulated macrophage migration. These results demonstrate that 15-F2t-IsoP affects macrophage adhesions and migration, which are integral components of macrophage involvement in atherosclerosis.


Assuntos
Aterosclerose/genética , F2-Isoprostanos/metabolismo , Fator Estimulador de Colônias de Macrófagos/genética , Placa Aterosclerótica/genética , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Adesão Celular/genética , Diferenciação Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , F2-Isoprostanos/genética , Radicais Livres/metabolismo , Humanos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/metabolismo , Camundongos , Estresse Oxidativo/genética , Fosforilação/genética , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteína Companheira de mTOR Insensível à Rapamicina/genética
4.
Aliment Pharmacol Ther ; 47(11): 1472-1479, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29665045

RESUMO

BACKGROUND: Though pharmacokinetic studies suggest accelerated biologic drug clearance with increasing body weight, evidence of obesity's impact on clinical outcomes in biologic-treated patients with ulcerative colitis (UC) is inconsistent. AIM: To evaluate the impact of obesity on real world response to biological therapy in patients with UC. METHODS: In a single-centre retrospective cohort study between 2011-2016 of biologic-treated patients with UC, we evaluated treatment response by baseline body mass index (BMI). Primary outcome was treatment failure (composite outcome of IBD-related surgery/hospitalisation or treatment modification including dose escalation, treatment discontinuation or addition of corticosteroids); secondary outcomes were risk of IBD-related surgery/hospitalisation and endoscopic remission. We conducted multivariate Cox proportional hazard analyses to evaluate the independent impact of BMI on clinical outcomes. Stratified analysis by weight-based regimens (infliximab) or fixed-dose regimens (adalimumab, golimumab, vedolizumab, certolizumab pegol) was performed. RESULTS: We included 160 biologic-treated UC patients (50% males, 55% on infliximab) with median (IQR) age 36 y (26-52) and BMI 24.3 kg/m2 (21.4-28.7). On multivariate analysis, each 1 kg/m2 increase in BMI was associated with 4% increase in the risk of treatment failure (adjusted hazard ratio [aHR], 1.04 [95% CI, 1.00-1.08]) and 8% increase in the risk of surgery/hospitalisation (aHR, 1.08 [1.02-1.14]). The effect on treatment failure was seen in patients on weight-based dosing regimens or fixed-dose therapies. CONCLUSION: BMI is independently associated with increased risk of treatment failure in biologic-treated patients with UC, independent of dosing regimen.


Assuntos
Produtos Biológicos/efeitos adversos , Índice de Massa Corporal , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Obesidade/cirurgia , Adalimumab/efeitos adversos , Adalimumab/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Produtos Biológicos/uso terapêutico , Terapia Biológica/efeitos adversos , Colite Ulcerativa/epidemiologia , Feminino , Hospitalização/tendências , Humanos , Infliximab/efeitos adversos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Fator de Necrose Tumoral alfa/uso terapêutico
6.
J Cyst Fibros ; 16(5): 628-630, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28625799

RESUMO

Patients with cystic fibrosis (CF) experience a significant decline in pulmonary status before the diagnosis of cystic fibrosis related diabetes (CFRD). We hypothesized that hyperglycemia may be a factor in the decline of pulmonary function and increased frequency of pulmonary exacerbations. Long term continuous glucose monitoring (CGM) has not been reported in patients with CF and impaired glucose tolerance. We performed CGM for three months in a 17year old male with F508del and F553X CF mutations, baseline forced expiratory volume in 1s (FEV1) of 92% predicted, and impaired glucose tolerance to evaluate changes in glucose levels prior to the diagnosis of a pulmonary exacerbation. Results revealed elevated overnight, fasting and post-prandial glucose levels up to one week prior to diagnosis of a pulmonary exacerbation compared to baseline. In addition, mean glucose was elevated and the patient spent a greater percentage of time with interstitial glucose>140mg/dL up to one week prior to diagnosis of a pulmonary exacerbation. This emphasizes the hypothesis that hyperglycaemia may be a factor in pulmonary exacerbations in this population. This case study strengthens the evidence base to support larger longitudinal studies to understand the impact of glycaemic control and pulmonary function in patients with CF and glucose intolerance.


Assuntos
Fibrose Cística , Diabetes Mellitus/prevenção & controle , Intolerância à Glucose , Hiperglicemia , Testes de Função Respiratória/métodos , Adolescente , Glicemia/análise , Fibrose Cística/sangue , Fibrose Cística/complicações , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etiologia , Progressão da Doença , Volume Expiratório Forçado/fisiologia , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/etiologia , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/terapia , Masculino , Monitorização Fisiológica/métodos , Valor Preditivo dos Testes , Estatística como Assunto , Exacerbação dos Sintomas
7.
Aliment Pharmacol Ther ; 40(5): 477-85, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25041724

RESUMO

BACKGROUND: Accurate and reproducible measurement of expression of pro-inflammatory cytokines in colonic biopsies from patients with ulcerative colitis (UC) is essential for proof-of-concept and mechanism-of-action studies. Few studies have rigorously established the number of biopsies required for accurate and reproducible biomarker measurements. AIM: To validate methods for measuring changes in gene expression in colonic biopsy samples. METHODS: Twelve colonic biopsies were obtained from each of six healthy controls, six patients with inactive UC and seven patients with active UC. Mayo endoscopic scores were used as a clinical reference standard. Quantitative PCR was used to assess mRNA expression of eight known inflammatory genes. The power to detect a reduction in gene expression in active vs. inactive UC was calculated using a linear mixed effect model. RESULTS: mRNA analysis of colonic biopsies is a sensitive and feasible approach for measuring inflammatory gene expression in colonic biopsies. Inflammatory biomarkers correlate with Mayo endoscopic subscores for each colonic region. For most genes, three rectal biopsies from two to four patients are required to detect changes in gene expression corresponding to active vs. inactive UC to achieve a power of 80% with an alpha of 0.05. CONCLUSION: Our data suggest that systematic measurement of inflammatory biomarkers at the mRNA level can be a valuable tool for hypothesis testing, and assessment of clinical activity and response to therapy in ulcerative colitis.


Assuntos
Colite Ulcerativa/genética , Citocinas/genética , Regulação da Expressão Gênica , Adulto , Idoso , Biomarcadores/análise , Biópsia , Ensaios Clínicos como Assunto , Colite Ulcerativa/patologia , Colo/metabolismo , Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo
8.
Aust J Prim Health ; 19(3): 184-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22951281

RESUMO

There is evidence for a team-based approach in the management of chronic disease in primary health care. However, the standard of care is variable, probably reflecting the limited organisational capacity of health services to provide the necessary structured and organised care for this group of patients. This study aimed to evaluate the impact of a structured intervention involving non-GP staff in GP practices on the quality of care for patients with diabetes or cardiovascular disease. A cluster randomised trial was undertaken across 60 GP practices. The intervention was implemented in 30 practices with staff and patients interviewed at baseline and at 12-15 months follow up. The change in team roles was evaluated using a questionnaire completed by practice staff. The quality of care was evaluated using the Patient Assessment of Chronic Illness Care questionnaire. We found that although the team roles of staff improved in the intervention practices and there were significant differences between practices, there was no significant difference between those in the intervention and control groups in patient-assessed quality of care after adjusting for baseline-level score and covariates at the 12-month follow up. Practice team roles were not significantly associated with change in Patient Assessment of Chronic Illness Care scores. Patients with multiple conditions were more likely to assess their quality of care to be better. Thus, although previous research has shown a cross-sectional association between team work and quality of care, we were unable to replicate these findings in the present study. These results may be indicative of insufficient time for organisational change to result in improved patient-assessed quality of care, or because non-GP staff roles were not sufficiently focussed on the aspects of care assessed. The findings provide important information for researchers when designing similar studies.


Assuntos
Pessoal Técnico de Saúde/organização & administração , Doença Crônica/terapia , Gerenciamento Clínico , Medicina Geral/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Qualidade da Assistência à Saúde/normas , Pessoal Técnico de Saúde/normas , Território da Capital Australiana , Diabetes Mellitus/terapia , Feminino , Medicina Geral/métodos , Humanos , Hipertensão/terapia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos Organizacionais , Isquemia Miocárdica/terapia , New South Wales , Equipe de Assistência ao Paciente/normas , Satisfação do Paciente , Avaliação de Programas e Projetos de Saúde , Padrão de Cuidado , Vitória , Recursos Humanos
9.
Qual Saf Health Care ; 19(5): e12, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20194220

RESUMO

BACKGROUND: Increasing demands on general practice to manage chronic disease may warrant organisational change at the practice level. Staff's readiness for organisational change can act as a facilitator or barrier to implementing interventions aimed at organisational change. OBJECTIVES: To explore general practice staff readiness for organisational change and its association with staff and practices characteristics. METHODS: This is a cross-sectional study of practices in three Australian states involved in a randomised control trial on the effectiveness of an intervention to enhance the role of non-general practitioner staff in chronic disease management. Readiness for organisational change, job satisfaction and practice characteristics were assessed using questionnaires. RESULTS: 502 staff from 58 practices completed questionnaires. Practice characteristics were not associated with staff readiness for change. A multilevel regression analysis showed statistically significant associations between staff readiness for organisational change (range 1 to 5) and having a non-clinical staff role (vs general practitioner; B=-0.315; 95% CI -0.47 to -0.16; p<0.001), full-time employment (vs part-time; B=0.175, 95% CI 0.06 to 0.29; p<0.01) and lower job satisfaction (B=-0.277, 95% CI -0.40 to -0.15; p<0.001). CONCLUSIONS: The results suggest that different approaches are needed to facilitate change which addresses the mix of practice staff. Moderately low job satisfaction may be an opportunity for organisational change.


Assuntos
Medicina Geral/organização & administração , Corpo Clínico , Adolescente , Adulto , Idoso , Austrália , Estudos Transversais , Feminino , Humanos , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Inovação Organizacional , Papel Profissional , Adulto Jovem
10.
Br J Clin Psychol ; 45(Pt 4): 499-514, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17076960

RESUMO

OBJECTIVES AND DESIGN: The efficacy of a Computerized Cognitive Behavioural Therapy (CCBT) package, Beating the Blues, has been demonstrated in a large randomized controlled trial. The current study tests the generalizability of this finding in a naturalistic non-randomized trial. METHOD: 219 patients with anxiety and/or depression were recruited to receive CCBT in routine care. The Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) and Work and Social Adjustment scale (WSA) were administered pre-treatment, immediately on completing treatment and at 6 months post-treatment. Single-item self-report measures of anxiety and depression were also collected during each treatment session. RESULTS: Completer and intention-to-treat analysis demonstrated statistically and clinically significant improvements on the CORE-OM, WSA and in self-reported anxiety and depression. Intention-to-treat analysis indicated an average 0.29-point drop on the CORE-OM, equating to an uncontrolled pre-post effect size of 0.50. Research completers achieved an average 0.61-point drop equating to an uncontrolled pre-post size of 1.00 on the same measure. Where data was available (18%), these benefits were maintained at week 32 (6 months follow-up). CONCLUSION: CCBT can be an effective first line tool within a stepped care framework for the management of common mental health problems.


Assuntos
Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/instrumentação , Transtorno Depressivo/terapia , Serviços de Saúde Mental/estatística & dados numéricos , Terapia Assistida por Computador/métodos , Adulto , Idoso , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Feminino , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , Periodicidade , Ajustamento Social , Inquéritos e Questionários , Resultado do Tratamento , Local de Trabalho/psicologia
12.
Avian Dis ; 47(2): 493-8, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12887213

RESUMO

During August 2001, a syndrome characterized by acute lethargy and dyspnea was observed in a population of 45 lorikeets and lories in an open-air zoologic exhibit. The first death occurred on August 10, and within the next 12 days, nine more birds died (22% mortality rate). Hepatomegaly, reddening and congestion of the lungs, and injection of the serosal surface of the intestines were the common gross findings. Histologic changes, including fibrinonecrotic hepatitis and splenitis, bacterial emboli (liver, spleen, lung, kidney, proventriculus), pulmonary congestion and hemorrhage, and enteritis, were indicative of an acute, overwhelming bacterial septicemia. Salmonella typhimurium, with the same antibiogram, was isolated from four birds. Several birds had attacked and killed a snake on July 24, and Salmonella serogroup B (untypeable) was isolated from intestine and kidney samples of a garter snake caught in the open-air exhibit on August 28. Salmonella was also isolated from environmental samples of the exhibit but not from food preparation areas. After antimicrobial therapy, Salmonella spp. was not isolated from the surviving birds. The source of Salmonella in this outbreak remains unknown, but infection either directly or indirectly from snakes in the exhibit is possible. Contact between captive psittacine populations and reptiles should be avoided to prevent the risk of salmonellosis.


Assuntos
Animais de Zoológico/microbiologia , Surtos de Doenças/veterinária , Fluoroquinolonas , Papagaios/microbiologia , Salmonelose Animal/epidemiologia , Animais , Anti-Infecciosos/uso terapêutico , Enrofloxacina , Controle de Infecções , Fígado/microbiologia , Pulmão/microbiologia , Quinolonas/uso terapêutico , Salmonelose Animal/tratamento farmacológico , Salmonelose Animal/prevenção & controle , Salmonella typhimurium , Serpentes/microbiologia , Baço/microbiologia
13.
Psychol Med ; 33(2): 217-27, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12622301

RESUMO

BACKGROUND: Cognitive-behavioural therapy (CBT) brings about significant clinical improvement in anxiety and depression, but therapists are in short supply. We report the first phase of a randomized controlled trial of an interactive multimedia program of cognitive-behavioural techniques, Beating the Blues (BtB), in the treatment of patients in general practice with anxiety, depression or mixed anxiety/depression. METHOD: One hundred and sixty-seven adults suffering from anxiety and/or depression and not receiving any form of psychological treatment or counselling were randomly allocated to receive, with or without medication, BtB or treatment as usual (TAU). Measures were taken on five occasions: prior to treatment, 2 months later, and at 1, 3 and 6 months follow-up using the Beck Depression Inventory, Beck Anxiety Inventory and Work and Social Adjustment Scale. RESULTS: Patients who received BtB showed significantly greater improvement in depression and anxiety compared to TAU by the end of treatment (2 months) and to 6 months follow-up. Symptom reduction was paralleled by improvement in work and social adjustment. There were no interactions of BtB with concomitant pharmacotherapy or duration of illness, but evidence, on the Beck Anxiety Inventory only, of interaction with primary care practice. Importantly, there was no interaction between the effects of BtB and baseline severity of depression, from which we conclude that the effects of the computer program are independent of starting level of depression. CONCLUSIONS: These results demonstrate that computerized interactive multimedia cognitive-behavioural techniques under minimal clinical supervision can bring about improvements in depression and anxiety, as well as in work and social adjustment, with and without pharmacotherapy and in patients with pre-treatment illness of durations greater or less than 6 months. Thus, our results indicate that wider dissemination of cognitive-behavioural techniques is possible for patients suffering from anxiety and/or depression.


Assuntos
Ansiedade/terapia , Terapia Cognitivo-Comportamental/instrumentação , Terapia Cognitivo-Comportamental/métodos , Transtorno Depressivo Maior/terapia , Multimídia , Atenção Primária à Saúde , Terapia Assistida por Computador , Adulto , Ansiedade/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Feminino , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde , Distribuição Aleatória , Índice de Gravidade de Doença , Ajustamento Social , Inquéritos e Questionários
14.
J Med Chem ; 44(15): 2421-31, 2001 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-11448224

RESUMO

p56lck is a member of the src family of tyrosine kinases and plays a critical role in the signal transduction events that lead to T cell activation. Ligands for the p56lck SH2 domain have the potential to disrupt the interaction of p56lck with its substrates and derail the signaling cascade that leads to the production of cytokines such as interleukin-2. Starting from the quintuply charged (at physiological pH) phosphorylated tetrapeptide, AcpYEEI, we recently disclosed (J. Med. Chem. 1999, 42, 722 and J. Med. Chem. 1999, 42, 1757) the design of the modified dipeptide 3, which carries just two charges at physiological pH. Here we present the elaboration of 3 to the nonpeptidic, monocharged compound, 9S. This molecule displays good binding affinity for the p56lck SH2 domain (K(d) 1 microM) and good cell permeation, and this combination of properties allowed us to demonstrate clear-cut inhibitory effects on a very early event in T cell activation, namely calcium mobilization.


Assuntos
Permeabilidade da Membrana Celular , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Fenilalanina/síntese química , Piridonas/síntese química , Domínios de Homologia de src , Células CACO-2 , Cálcio/metabolismo , Humanos , Células Jurkat , Ligantes , Modelos Moleculares , Fenilalanina/análogos & derivados , Fenilalanina/química , Fenilalanina/farmacologia , Piridonas/química , Piridonas/farmacologia
15.
J Reprod Fertil Suppl ; 57: 315-21, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11787168

RESUMO

Transrectal ultrasonography, electroejaculation and cryopreservation of spermatozoa were applied to the African wild dog (Lycaon pictus) to establish non-invasive protocols for assessing the reproductive health of one of the most endangered African canids. Transrectal ultrasonography was performed on immobilized male (n = 2) and female (n = 5) captive wild dogs. The testes and epididymides of the male dogs were imaged transcutaneously, followed by electrostimulation and cryopreservation of spermatozoa. The sonomorphology of the female and male urogenital tracts was characterized. In females, the vagina, cervix, non-pregnant uterus and ovary were imaged and the reproductive health of each female was evaluated. The sonographic assessment helped to identify one pyometra and extensive abdominal fat deposits in two other individuals in which pyometra had been suspected. Images of the adrenal glands showed differences in size among individuals of the same breeding group. Whether these differences were related to the dominance hierarchy remains to be determined. In males, visualization of the prostate gland, testis and epididymis indicated sexual maturity. Three ejaculatory fractions (1.0, 1.5 and 0.5 ml, with 50, 95 and 95% motility, respectively; 1.125 x 10(8) spermatozoa per ejaculate) were collected from one male. The motility of each of these fractions after thawing was 0, 30 and 40%, respectively. Electrostimulation of the second male, in which a cystic structure in a testis had been identified by sonography, resulted in an aspermic ejaculate (0.5 and 1.0 ml). These technologies provided basic data on reproduction in female and male African wild dogs and were an efficient way to evaluate reproductive health.


Assuntos
Animais Selvagens , Carnívoros , Genitália Feminina/diagnóstico por imagem , Genitália Masculina/diagnóstico por imagem , Técnicas Reprodutivas/veterinária , Glândulas Suprarrenais/diagnóstico por imagem , Animais , Criopreservação , Estimulação Elétrica , Hiperplasia Endometrial/diagnóstico por imagem , Hiperplasia Endometrial/veterinária , Feminino , Masculino , Preservação do Sêmen , Ultrassonografia
16.
Pharm Res ; 17(10): 1168-74, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11145220

RESUMO

PURPOSE: To investigate the mechanisms involved in transport of sulfasalazine in Caco-2 cells. METHODS: Permeability coefficients of sulfasalazine and its analogs across Caco-2 cell monolayers were measured as a function of direction of transport, energy and concentration dependence, and in the presence of inhibitors of various cellular efflux pumps and transporters. RESULTS: Permeability coefficients of sulfasalazine across Caco-2 cell monolayers were approximately 342-, 261-, and 176-fold higher from basolateral to apical direction (BL-->AP) than from apical to basolateral direction (AP-->BL) at 100, 200, and 500 microM, respectively. Carrier permeability coefficient, non-saturable membrane permeability coefficient, and Michaelis constant were estimated to be 1.4x10(-5) cm/s, 1.9x10(-8) cm/s, and 369 microM, respectively. The efflux of sulfasalazine was completely blocked at 4 degrees C and in the presence of an uncoupler of oxidative phosphorylation. Using cellular efflux inhibitors, the permeability of sulfasalazine was shown to depend on multidrug resistance-associated protein and anion sensitive transport mechanisms. Structure-permeability studies showed that the affinity of sulfasalazine for the cellular efflux pumps and transporters in Caco-2 cells depended strongly on the carboxylic acid functional group. CONCLUSIONS: The permeability of sulfasalazine across Caco-2 cell monolayer is very low due to its strong interaction with multiple cellular efflux pumps and transporters. This may partially explain its low absorption in vivo.


Assuntos
Células CACO-2/metabolismo , Fármacos Gastrointestinais/farmacocinética , Sulfassalazina/análogos & derivados , Sulfassalazina/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas de Transporte de Ânions , Transporte Biológico Ativo/efeitos dos fármacos , Células CACO-2/efeitos dos fármacos , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/fisiologia , Temperatura Baixa , Metabolismo Energético , Humanos , Absorção Intestinal/efeitos dos fármacos , Absorção Intestinal/fisiologia , Cinética , Mesalamina/farmacocinética , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Relação Estrutura-Atividade , Sulfapiridina/farmacocinética
17.
Free Radic Res ; 33(5): 643-59, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11200095

RESUMO

Oxidative damage is thought to play a critical role in cardiovascular and other chronic diseases. This has led to considerable interest in the antioxidant activity of dietary compounds. Flavonoids have received the most attention and much is known about the structural requirements for antioxidant activity. However, little is known about the antioxidant activity of other plant derived phenolic compounds such as the xanthones. We have previously shown that the prenylated xanthone, mangostin, can inhibit the oxidation of low density lipoprotein. In order to examine the effects of structure modification on antioxidant activity of this class of compound we have prepared a number of derivatives of mangostin and tested antioxidant activity in an isolated LDL and plasma assay. The results of this study show that structural modification of mangostin can have a profound effect on antioxidant activity. Derivatisation of the C-3 and C-6 hydroxyl groups with either methyl, acetate, propane diol or nitrile substantially reduces antioxidant activity. In contrast, derivatisation of C-3 and C-6 with aminoethyl derivatives enhanced antioxidant activity, which may be related to changes in solubility. Cyclisation of the prenyl chains had little influence on antioxidant activity.


Assuntos
Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Xantenos/farmacologia , Xantonas , Antioxidantes/síntese química , Antioxidantes/química , Humanos , Técnicas In Vitro , Relação Estrutura-Atividade , Xantenos/síntese química , Xantenos/química
18.
Anal Biochem ; 272(2): 209-15, 1999 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-10415090

RESUMO

This study aimed at comparing the two most commonly utilized methods for measuring urinary F(2)-isoprostanes, currently considered one of the best available markers of in vivo lipid peroxidation. The F(2)-isoprostanes were measured in 24-h urine samples from 14 male subjects using electron capture negative ionization gas chromatography-mass spectrometry (ECNI-GCMS) with 8-iso-PGF(2alpha)-d(4) as an internal standard and compared with levels obtained using an enzyme immunoassay (EIA, 8-iso-PGF(2alpha) kit, Cayman Chemical Co.). The methods were compared using Pearson correlation coefficients, and Bland-Altman plots were constructed for the difference in F(2)-isoprostane against the average F(2)-isoprostane measured by either method. Weighted least-products regression was used to determine fixed bias (where there is a consistent difference between the methods) and proportional bias (where one method gives values higher or lower than the other method by an amount proportional to the size of the measurement). The correlation between F(2)-isoprostane levels obtained using EIA and GCMS methods, although significant, was poor (r = 0.628, P < 0.02). Comparison of the methods using the Bland-Altman analysis showed that there were wide limits of agreement between the two methods with only 28% of the values falling within the 95% confidence limits for the difference. The GCMS gave higher values with a mean difference of 298.1 pM (636.6, -40.2; P = 0.079), and a near significant linear association between the differences and the mean F(2)-isoprostane level (r = -0.559, P = 0.05). Weighted least-product regression analysis confirmed the presence of both significant fixed and proportional bias with the EIA giving lower levels of F(2)-isoprostanes at low concentrations and higher levels at higher concentrations. The cross-reactivity in the EIA of 8-iso-15(R)-PGF(2alpha) and 9beta-PGF(2alpha) which coelute with the F(2)-isoprostane peak measured by GCMS was very low, 0.2 and 0.1%, respectively. The proportional bias observed between the methods may in part be due to differences in the relative amounts of 8-iso-15(R)-PGF(2alpha), 9beta-PGF(2alpha), and 8-iso-PGF(2alpha) with increasing lipid peroxidation. This study shows that the measurements of F(2)-isoprostanes by EIA and GCMS are not equivalent. Therefore, comparison of levels derived using a GCMS method which estimates concentration from a peak encompassing a number of F(2)-isoprostane isomers, and levels derived from enzyme immunoassay measuring a specific isoprostane, may be inappropriate.


Assuntos
Dinoprosta/análogos & derivados , Dinoprosta/urina , Adulto , Idoso , Biomarcadores/urina , Reações Cruzadas , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Valores de Referência , Análise de Regressão
19.
J Med Chem ; 42(10): 1757-66, 1999 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-10346928

RESUMO

p56lck is a member of the src family of tyrosine kinases. Through modular binding units called SH2 domains, p56lck promotes phosphotyrosine-dependent protein-protein interactions and plays a critical role in signal transduction events that lead to T-cell activation. Starting from the phosphorylated dipeptide (2), a high-affinity ligand for the p56lck SH2 domain, we have designed novel dipeptides that contain monocharged, nonhydrolyzable phosphate group replacements and bind to the protein with KD's in the low micromolar range. Replacement of the phosphate group in phosphotyrosine-containing sequences by a (R/S)-hydroxyacetic (compound 8) or an oxamic acid (compound 10) moiety leads to hydrolytically stable, monocharged ligands, with 83- and 233-fold decreases in potency, respectively. This loss in binding affinity can be partially compensated for by incorporating large lipophilic groups at the inhibitor N-terminus. These groups provide up to 13-fold increases in potency depending on the nature of the phosphate replacement. The discovery of potent (2-3 microM), hydrolytically stable dipeptide derivatives, bearing only two charges at physiological pH, represents a significant step toward the discovery of compounds with cellular activity and the development of novel therapeutics for conditions associated with undesired T-cell proliferation.


Assuntos
Dipeptídeos/síntese química , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Domínios de Homologia de src , Cristalografia por Raios X , Dipeptídeos/química , Ligantes , Modelos Moleculares , Ligação Proteica , Relação Estrutura-Atividade
20.
Int Arch Occup Environ Health ; 72 Suppl: S40-2, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10197475

RESUMO

The negative psychological effects of unemployment are well documented: lowered self-esteem and confidence, social isolation, anxiety, depression, reduced life satisfaction, hopelessness about the future. Further, it has been established that these effects often prevent re-employment. The need for interventions to help unemployed people to minimise such psychological effects is clearly warranted, yet little psychological assistance is usually given. This paper describes a psychological intervention based on cognitive behavioural therapy (CBT), the principles of which have been successfully applied through individual psychotherapy to several psychiatric disorders. We adapted these principles to create a group-training programme for a non-psychiatric group--long term (>12 months) unemployed. The results demonstrated that significantly more of the CBT group than the control group improved on measures of mental health, as well as on success in job-finding: four months after the completion of training 34% of the CBT group c.f. 12% of the control group had found full-time work. Taking part-time and temporary work into account, these figures increased to 49% (CBT group) and 28% (control group), indicating the value of psychological interventions in reducing the negative psychological effects of unemployment, and helping the unemployed find jobs.


Assuntos
Saúde Mental , Desemprego , Adulto , Terapia Cognitivo-Comportamental , Feminino , Humanos , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA