RESUMO
Studies of exposure to petroleum (crude oil/fuel) often involve monitoring benzene, toluene, ethylbenzene, xylenes (BTEX), and styrene (BTEXS) because of their toxicity and gas-phase prevalence, where exposure is typically by inhalation. However, BTEXS levels in the general U.S. population are primarily from exposure to tobacco smoke, where smokers have blood levels on average up to eight times higher than nonsmokers. This work describes a method using partition theory and artificial neural network (ANN) pattern recognition to classify exposure source based on relative BTEXS and 2,5-dimethylfuran blood levels. A method using surrogate signatures to train the ANN was validated by comparing blood levels among cigarette smokers from the National Health and Nutrition Examination Survey (NHANES) with BTEXS and 2,5-dimethylfuran signatures derived from the smoke of machine-smoked cigarettes. Classification agreement for an ANN model trained with relative VOC levels was up to 99.8% for nonsmokers and 100.0% for smokers. As such, because there is limited blood level data on individuals exposed to crude oil/fuel, only surrogate signatures derived from crude oil and fuel were used for training the ANN. For the 2007-2008 NHANES data, the ANN model assigned 7 out of 1998 specimens (0.35%) and for the 2013-2014 NHANES data 12 out of 2906 specimens (0.41%) to the crude oil/fuel signature category.
Assuntos
Petróleo , Xilenos , Benzeno , Derivados de Benzeno , Furanos , Humanos , Inquéritos Nutricionais , Fumaça , Estireno , ToluenoRESUMO
Purpose: The goal of the project was to develop evidence- and consensus-based practice guidelines for psychological interventions in the rehabilitation of patients with type 2 diabetes. Method: The practice guidelines were developed in several steps including a literature search, surveys of clinicians (psychologists and head physicians from rehabilitation centres) and an expert workshop. National experts from scientific departments, rehabilitation centres and patients were engaged in the development of the practice guidelines. Results: The recommendations refer to problems in the field of mental functions, body functions, environmental and personal factors. It is described (a) how specific problem areas can be detected (e. g., using screening-instruments), and (b) which psychological interventions are indicated when a specific problem area has been identified. Conclusions: The practice guidelines offer a practical decision support for psychological interventions in the rehabilitation of patients with type 2 diabetes.
Assuntos
Terapia Combinada/normas , Diabetes Mellitus Tipo 2/reabilitação , Transtornos Mentais/terapia , Guias de Prática Clínica como Assunto , Psicoterapia/normas , Reabilitação/normas , Diabetes Mellitus Tipo 2/psicologia , Medicina Baseada em Evidências , Feminino , Alemanha , Humanos , Masculino , Transtornos Mentais/psicologia , Resultado do TratamentoRESUMO
OBJECTIVE: To study the structural frame conditions and the contents of psychological activity in oncological rehabilitation as well as in rehabilitation of patients with type 2 diabetes. METHODS: We conducted a nationwide survey of psychological services in rehabilitation facilities treating oncological patients and patients with type 2 diabetes. RESULTS: 71 (of 145) oncological and 21 (of 63) diabetological rehabilitation facilities participated in the survey. In both indication areas an average of 1.1 psychologists is in charge of 100 patients. Between some rehabilitation facilities, however, there are considerable differences concerning the psychologist/patient ratio (in oncological rehabilitation facilities: standard deviation (SD)=0.52; in diabetological rehabilitation facilities: SD=0.35). Moreover, there is large heterogeneity among rehabilitation facilities as to the percentages of patients obtaining psychological interventions and the way in which psychological services allocate their working time. CONCLUSION: The general set-up of psychological services in oncological and diabetological rehabilitation facilities (especially the low psychologist/patient ratio in many facilities) can partly be considered insufficient. The heterogeneity with respect to the structural frame conditions and practice of psychological services reveals the low degree of standardization of psychological activity in both indication areas.
Assuntos
Diabetes Mellitus/reabilitação , Pessoas com Deficiência/reabilitação , Neoplasias/reabilitação , Psicologia/estatística & dados numéricos , Reabilitação/estatística & dados numéricos , Adulto , Idoso , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/psicologia , Pessoas com Deficiência/psicologia , Pessoas com Deficiência/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/psicologia , Padrões de Prática Médica/estatística & dados numéricos , Revisão da Utilização de Recursos de Saúde , Carga de Trabalho/estatística & dados numéricosRESUMO
STUDY OBJECTIVE: Structures and practice of psychological units in neurological rehabilitation centres treating post-stroke patients are described. METHODS: A nationwide survey of psychological services in neurological rehabilitation centres was conducted. RESULTS: Psychologist-patient ratios differed greatly among rehabilitation centres. Post-stroke patients showed a variety of complex problems. Psychological interventions mainly comprised diagnostic evaluation as well as individual interventions and cognitive training. CONCLUSION: The complex and manifold problems of patients in neurological rehabilitation require a comprehensive knowledge of (neuro)psychological functioning. In order to support appropriate and individual treatment decisions, practice guidelines for psychological interventions in the rehabilitation of post-stroke patients are necessary. The present survey constitutes the basis for developing such practice guidelines.
Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Psicoterapia/estatística & dados numéricos , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Psychologists from rehabilitation centres were surveyed about their current job situation. Following areas were included: (a) professional self-perception, (b) occupational resources and stress, (c) job satisfaction. METHODS: A nationwide survey of psychologists of all rehabilitation centres in Germany was conducted. Overall, 1,461 rehabilitation centres of all specialties were contacted in writing, of which 623 psychologists participated in the survey. Some of the results can be compared with reference data from previous surveys. RESULTS: The professional self-perception has hardly changed over the last 10 years. Counselling and psychotherapy in one-to-one sessions and group interventions still play an essential role. Overall, job satisfaction and resources are high. General job satisfaction can be best predicted by career opportunities and opportunities for qualification. CONCLUSIONS: The results of the study indicate which resources should be strengthened in order to enhance job satisfaction of psychologists in medical rehabilitation. Particular thought should be given to improving career opportunities for psychologists in rehabilitation centres.
Assuntos
Recursos em Saúde/estatística & dados numéricos , Satisfação no Emprego , Doenças Profissionais/epidemiologia , Psicologia/estatística & dados numéricos , Centros de Reabilitação , Estresse Psicológico/epidemiologia , Carga de Trabalho/estatística & dados numéricos , Adulto , Idoso , Comorbidade , Feminino , Alemanha , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Centros de Reabilitação/estatística & dados numéricos , Fatores de Risco , Autoavaliação (Psicologia) , Estresse Psicológico/psicologia , Recursos Humanos , Carga de Trabalho/psicologiaRESUMO
PURPOSE: The aim of this study was to develop evidence- and consensus-based practice guidelines for psychological interventions in the rehabilitation of patients with chronic low back pain. METHOD: The practice guidelines have been developed systematically in several steps. Experts from scientific departments and rehabilitation centres as well as rehabilitation patients participated in the development of the practice guidelines. In addition, a draft of the practice guidelines was circulated among head psychologists and chief physicians of somatic orthopaedic rehabilitation centres for their comments and approval. RESULTS: The final practice guidelines comprise recommendations regarding systematic screening and diagnostics of psychologically relevant problems. Furthermore, they include suggestions for the organisation of psychological interventions addressing specific problems. CONCLUSIONS: The detailed, evidence- and consensus-based practice guidelines offer an orientation for psychological practice in the somatic rehabilitation of patients with chronic low back pain.
Assuntos
Dor Crônica/reabilitação , Dor Lombar/reabilitação , Guias de Prática Clínica como Assunto , Escalas de Graduação Psiquiátrica/normas , Psicoterapia/normas , Reabilitação/normas , Dor Crônica/diagnóstico , Dor Crônica/psicologia , Alemanha , Humanos , Dor Lombar/diagnóstico , Dor Lombar/psicologiaRESUMO
Available guidelines and treatment standards are not sufficiently detailed to give practical guidance for psychological interventions in the rehabilitation of patients with coronary heart disease. We therefore aimed at developing evidence- and consensus-based practice guidelines for psychological interventions in the rehabilitation of individual patients with coronary heart disease. The following steps were taken: (1) A systematic search for guidelines and reviews, and a survey of rehabilitation centres concerning present structures and the practice of psychological services, (2) development of a first draft of the practice guidelines in an expert workshop, (3) a survey of all senior psychologists and chief physicians of the rehab centres for their approval, as well as focus groups with rehab patients, and (4) revision of the recommendations and final consensus development in an expert workshop. Significant aspects of the guidelines that go beyond present practice are routine screening for psychological comorbidity, neuropsychological screening for cognitive dysfunction in particular patients, and employment of defined psychologically grounded interventions by the entire rehab team. So far, the practice guidelines have been widely accepted by professionals in the field of rehabilitation.
Assuntos
Cardiologia/normas , Doença das Coronárias/psicologia , Doença das Coronárias/reabilitação , Medicina Baseada em Evidências , Guias de Prática Clínica como Assunto , Psicoterapia/normas , Reabilitação/normas , Alemanha , HumanosRESUMO
Febrile seizures are common in the first five years of life, and many factors that increase seizure risk have been identified. Initial evaluation should determine whether features of a complex seizure are present and identify the source of fever. Routine blood tests, neuroimaging, and electroencephalography are not recommended, and lumbar puncture is no longer recommended in patients with uncomplicated febrile seizures. In the unusual case of febrile status epilepticus, intravenous lorazepam and buccal midazolam are first-line agents. After an initial febrile seizure, physicians should reassure parents about the low risk of long-term effects, including neurologic sequelae, epilepsy, and death. However, there is a 15 to 70 percent risk of recurrence in the first two years after an initial febrile seizure. This risk is increased in patients younger than 18 months and those with a lower fever, short duration of fever before seizure onset, or a family history of febrile seizures. Continuous or intermittent antiepileptic or antipyretic medication is not recommended for the prevention of recurrent febrile seizures.
Assuntos
Convulsões Febris , Anticonvulsivantes/uso terapêutico , Antipiréticos/uso terapêutico , Pré-Escolar , Humanos , Lactente , Guias de Prática Clínica como Assunto , Prognóstico , Recidiva , Fatores de Risco , Convulsões Febris/complicações , Convulsões Febris/diagnóstico , Convulsões Febris/tratamento farmacológico , Convulsões Febris/prevenção & controleRESUMO
We aimed at comparing the present structural quality and practice of psychological services in ambulatory (outpatient) and inpatient rehabilitation in Germany.A nationwide survey of psychological services in orthopaedic and cardiac outpatient rehab centres was carried out. Results were compared to those of an identical study of inpatient services that was conducted simultaneously.Data were obtained from 81 ambulatory centres (return rate: 44%). Structures and practice (e. g., diagnostic procedures, psychological interventions) in ambulatory and inpatient rehabilitation only differed marginally. Differences concern the staff/patient ratio which is slightly better in ambulatory centres and some aspects of working conditions (e. g., less assisting staff or supervision).From its beginning, ambulatory rehabilitation in Germany has followed the standards of the inpatient model as far as structural quality and processes are concerned. Psychological practice in the ambulatory setting reflects that too. It is discussed whether the uniformity of ambulatory and inpatient rehabilitation services really is appropriate, or whether a more flexible model (e. g., regarding treatment duration) is needed in the German rehabilitation system.
Assuntos
Assistência Ambulatorial/organização & administração , Cardiologia/organização & administração , Administração Hospitalar/estatística & dados numéricos , Modelos Organizacionais , Ortopedia/organização & administração , Admissão e Escalonamento de Pessoal/organização & administração , Reabilitação/organização & administração , Alemanha/epidemiologia , Hospitalização/estatística & dados numéricos , Padrões de Prática MédicaRESUMO
OBJECTIVE: To summarize national and international evidence and recommendations for psychological interventions in the rehabilitation of patients with coronary heart disease. Background is a project for the development of evidence-based practice guidelines for psychological interventions in the rehabilitation of patients with coronary heart disease. METHODS: A systematic literature search in several databases and on the websites of professional associations was conducted in order to identify relevant reviews and guidelines. A handsearch was conducted in addition to the electronic search. Eligible publications were selected, and evidence for psychological interventions was extracted as well as recommendations relative to psychological diagnostics or interventions. RESULTS: 5 systematic reviews and 34 guidelines were included. Recommendations and (partially restricted) evidence from systematic reviews was found for the following psychological interventions: patient counselling and health education; screening and treatment of comorbid psychological disorders; occupational counselling; stress management; relaxation training; interventions for smoking cessation; interventions promoting appropriate nutrition and weight management; interventions enhancing sufficient, regular physical activity; interventions enhancing social support; specific interventions for women; involvement of family members or partners; discussion of sexual activity. DISCUSSION/CONCLUSION: For several psychological interventions in the treatment of patients with coronary heart disease we found empirical evidence from systematic reviews. For other psychological interventions, no empirical evidence from systematic reviews was found. The summary of guidelines shows that both in Germany and abroad, a number of psychologically grounded interventions are an inherent part of cardiac rehabilitation. However, many recommendations which refer to psychological diagnostics and interventions are not precise enough to guide psychological care of individual patients. In particular, there are no statements in many guidelines on which (psychological) treatments should be considered for which problems. Moreover, hardly any evidence or recommendations were found for specific interventions referring to special groups of patients (e.g., women, patients with low socio-economic status or migration background). Further research is needed in these respects in order to answer questions concerning the indication and effectiveness of such tailored interventions.
Assuntos
Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/reabilitação , Transtornos Mentais/epidemiologia , Transtornos Mentais/reabilitação , Guias de Prática Clínica como Assunto , Psicoterapia/estatística & dados numéricos , Comorbidade , Humanos , Incidência , Internacionalidade , Fatores de RiscoRESUMO
OBJECTIVE: A detailed analysis of the present structural quality and practice of psychological services in inpatient medical rehabilitation facilities was conducted. The study was carried out for the indications chronic back pain and coronary heart disease. METHODS: A nationwide postal survey of psychological services in orthopaedic and cardiac inpatient rehabilitation facilities was carried out. RESULTS: Data from psychology departments of 169 orthopaedic and 75 cardiac inpatient rehabilitation facilities are available. In both indication areas an average of one psychologist is in charge of 100 patients. In the treatment of patients with chronic back pain and coronary heart disease, several methods of psychological assessment and a wide range of psychological interventions are being applied. On the whole, there are notable parallels between the psychological interventions provided to patients with chronic back pain and coronary heart disease. At the same time, however, there is considerable heterogeneity among rehabilitation facilities as to the psychological interventions carried out. DISCUSSION/CONCLUSION: The heterogeneity found reveals the low degree of standardization of psychological practice in medical rehabilitation of patients with chronic back pain or coronary heart disease. This emphasizes the need for developing and implementing recommendations or practice guidelines for psychological interventions.
Assuntos
Dor nas Costas/epidemiologia , Dor nas Costas/reabilitação , Doença das Coronárias/epidemiologia , Doença das Coronárias/reabilitação , Ortopedia/estatística & dados numéricos , Terapias Somáticas em Psiquiatria/estatística & dados numéricos , Reabilitação/estatística & dados numéricos , Doença Crônica , Comorbidade , Coleta de Dados , Feminino , Alemanha/epidemiologia , Hospitalização , Humanos , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Prevalência , Fatores de Risco , Resultado do TratamentoRESUMO
Protein kinase B (PKB) is a proto-oncogene that is activated in signaling pathways initiated by phosphoinositide 3-kinase. Chromatographic separation of brain cytosol revealed a kinase activity that phosphorylated and activated PKB only in the presence of phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P3]. Phosphorylation occurred exclusively on threonine-308, a residue implicated in activation of PKB in vivo. PtdIns(3,4,5)P3 was determined to have a dual role: Its binding to the pleckstrin homology domain of PKB was required to allow phosphorylation by the upstream kinase and it directly activated the upstream kinase.
Assuntos
Fosfatos de Fosfatidilinositol/metabolismo , Fosfoproteínas , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Quinases Dependentes de 3-Fosfoinositídeo , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Animais , Proteínas Sanguíneas/química , Encéfalo/enzimologia , Células COS , Citosol/enzimologia , Ativação Enzimática , Humanos , Masculino , Dados de Sequência Molecular , Fosforilação , Fosfotreonina/metabolismo , Proteínas Serina-Treonina Quinases/química , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , EstereoisomerismoRESUMO
Protein kinase B (PKB) is activated in response to phosphoinositide 3-kinases and their lipid products phosphatidylinositol 3,4, 5-trisphosphate [PtdIns(3,4,5)P3] and PtdIns(3,4)P2 in the signaling pathways used by a wide variety of growth factors, antigens, and inflammatory stimuli. PKB is a direct target of these lipids, but this regulation is complex. The lipids can bind to the pleckstrin homologous domain of PKB, causing its translocation to the membrane, and also enable upstream, Thr308-directed kinases to phosphorylate and activate PKB. Four isoforms of these PKB kinases were purified from sheep brain. They bound PtdIns(3,4,5)P3 and associated with lipid vesicles containing it. These kinases contain an NH2-terminal catalytic domain and a COOH-terminal pleckstrin homologous domain, and their heterologous expression augments receptor activation of PKB, which suggests they are the primary signal transducers that enable PtdIns(3,4,5)P3 or PtdIns- (3,4)P2 to activate PKB and hence to control signaling pathways regulating cell survival, glucose uptake, and glycogen metabolism.
Assuntos
Fosfatos de Fosfatidilinositol/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais , Proteínas Quinases Dependentes de 3-Fosfoinositídeo , Processamento Alternativo , Sequência de Aminoácidos , Animais , Linhagem Celular , Membrana Celular/enzimologia , Clonagem Molecular , DNA Complementar , Drosophila , Proteínas de Drosophila , Ativação Enzimática , Humanos , Lipossomos/metabolismo , Dados de Sequência Molecular , Fases de Leitura Aberta , Fosforilação , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/isolamento & purificação , Proteínas Proto-Oncogênicas c-akt , Ratos , Proteínas Recombinantes/metabolismo , OvinosRESUMO
BACKGROUND: Protein kinase B (PKB), also known as c-Akt, is activated rapidly when mammalian cells are stimulated with insulin and growth factors, and much of the current interest in this enzyme stems from the observation that it lies 'downstream' of phosphoinositide 3-kinase on intracellular signalling pathways. We recently showed that insulin or insulin-like growth factor 1 induce the phosphorylation of PKB at two residues, Thr308 and Ser473. The phosphorylation of both residues is required for maximal activation of PKB. The kinases that phosphorylate PKB are, however, unknown. RESULTS: We have purified 500 000-fold from rabbit skeletal muscle extracts a protein kinase which phosphorylates PKBalpha at Thr308 and increases its activity over 30-fold. We tested the kinase in the presence of several inositol phospholipids and found that only low micromolar concentrations of the D enantiomers of either phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) or PtdIns(3,4)P2 were effective in potently activating the kinase, which has been named PtdIns(3,4,5)P3-dependent protein kinase-1 (PDK1). None of the inositol phospholipids tested activated or inhibited PKBalpha or induced its phosphorylation under the conditions used. PDK1 activity was not affected by wortmannin, indicating that it is not likely to be a member of the phosphoinositide 3-kinase family. CONLCUSIONS: PDK1 is likely to be one of the protein kinases that mediate the activation of PKB by insulin and growth factors. PDK1 may, therefore, play a key role in mediating many of the actions of the second messenger(s) PtdIns(3,4, 5)P3 and/or PtdIns(3,4)P2.
Assuntos
Músculo Esquelético/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Quinases Dependentes de 3-Fosfoinositídeo , Sequência de Aminoácidos , Animais , Apoptose , Linhagem Celular , Cromatografia de Afinidade , Cromatografia por Troca Iônica , Ativação Enzimática , Feminino , Humanos , Cinética , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/isolamento & purificação , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt , Coelhos , Proteínas Recombinantes de Fusão/metabolismo , Serina , Especificidade por Substrato , Treonina , TransfecçãoRESUMO
BACKGROUND: The activation of protein kinase B (PKB, also known as c-Akt) is stimulated by insulin or growth factors and results from its phosphorylation at Thr308 and Ser473. We recently identified a protein kinase, termed PDK1, that phosphorylates PKB at Thr308 only in the presence of lipid vesicles containing phosphatidylinositol 3,4,5-trisphosphate (Ptdlns(3,4,5)P3) or phosphatidylinositol 3,4-bisphosphate (Ptdlns(3,4)P2). RESULTS: We have cloned and sequenced human PDK1. The 556-residue monomeric enzyme comprises a catalytic domain that is most similar to the PKA, PKB and PKC subfamily of protein kinases and a carboxy-terminal pleckstrin homology (PH) domain. The PDK1 gene is located on human chromosome 16p13.3 and is expressed ubiquitously in human tissues. Human PDK1 is homologous to the Drosophila protein kinase DSTPK61, which has been implicated in the regulation of sex differentiation, oogenesis and spermatogenesis. Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2. Overexpression of PDK1 in 293 cells activated PKB alpha and potentiated the IGF1-induced phosphorylation of PKB alpha at Thr308. Experiments in which the PH domains of either PDK1 or PKB alpha were deleted indicated that the binding of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2 to PKB alpha is required for phosphorylation and activation by PDK1. IGF1 stimulation of 293 cells did not affect the activity or phosphorylation of PDK1. CONCLUSIONS: PDK1 is likely to mediate the activation of PKB by insulin or growth factors. DSTPK61 is a Drosophila homologue of PDK1. The effect of Ptdlns(3,4,5)P3/Ptdlns(3,4)P2 in the activation of PKB alpha is at least partly substrate directed.
Assuntos
Drosophila/enzimologia , Proteínas de Insetos/metabolismo , Fosfoproteínas , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Quinases Dependentes de 3-Fosfoinositídeo , Sequência de Aminoácidos , Animais , Proteínas Sanguíneas/química , Linhagem Celular Transformada , Proteínas de Drosophila , Ativação Enzimática , Glutationa Transferase/genética , Humanos , Proteínas de Insetos/química , Fator de Crescimento Insulin-Like I/metabolismo , Dados de Sequência Molecular , Músculo Esquelético/enzimologia , Fosfatos de Fosfatidilinositol/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/isolamento & purificação , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Coelhos , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Homologia de Sequência de Aminoácidos , Treonina/metabolismo , TransfecçãoRESUMO
The development and application of microsensor technology has enhanced the ability of scientists to further understand various biological activities, such as changes in the intracellular environment after injury or toxic exposure. NIR microsensor technology may be useful in detecting the cellular injuries or adverse changes during the early onset period, allowing for the administration of therapies to initiate recovery. The development and use of Infrared (IR) and near infrared (NIR) dyes as biological micro-sensors due to their advanced spectral characteristics may be helpful. Three of the more useful NIR dye characteristics include the ability to minimize background interference by extraneous biological matrices, the ability to exhibit optimal molar absorptivity and quantum yields, and the ability to maintain normal cellular activity. Thus, the current study was designed to investigate the ability of selected NIR micro-sensor dyes to undergo cellular internalization, demonstrate intracellular NIR fluorescent signaling, and maintain normal cellular activity. The results demonstrate that the selected NIR micro-sensor dyes undergo cellular internalization. The presence of the dyes within the cells did not affect cell viability. In addition, these dyes demonstrate changes in absorbance and fluorescence after the immune cells were challenged with a stimulant. Moreover, critical cellular functions, such as tumor necrosis factor release and superoxide production were not compromised by the internalization of the fluorescent dyes. These data suggest that selected NIR micro-sensor dyes can undergo intracellular internalization within isolated macrophages without adversely affecting various parameters of normal cellular activity.
Assuntos
Técnicas Biossensoriais/métodos , Corantes Fluorescentes/metabolismo , Macrófagos/metabolismo , Análise de Variância , Transporte Biológico/fisiologia , Quimiotaxia/efeitos dos fármacos , Corantes Fluorescentes/toxicidade , Fluorometria , Raios Infravermelhos , Macrófagos/citologia , Espectrometria de Fluorescência , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In human motion studies, discrete points such as peak or average kinematic values are commonly selected to test hypotheses. The purpose of this study was to describe a functional data analysis and describe the advantages of using functional data analyses when compared with a traditional analysis of variance (ANOVA) approach. Nineteen healthy participants (age: 22 ± 2 yrs, body height: 1.7 ± 0.1 m, body mass: 73 ± 16 kg) walked under two different conditions: control and pain+effusion. Pain+effusion was induced by injection of sterile saline into the joint capsule and hypertonic saline into the infrapatellar fat pad. Sagittal-plane ankle, knee, and hip joint kinematics were recorded and compared following injections using 2×2 mixed model ANOVAs and FANOVAs. The results of ANOVAs detected a condition × time interaction for the peak ankle (F1,18 = 8.56, p = 0.01) and hip joint angle (F1,18 = 5.77, p = 0.03), but did not for the knee joint angle (F1,18 = 0.36, p = 0.56). The functional data analysis, however, found several differences at initial contact (ankle and knee joint), in the mid-stance (each joint) and at toe off (ankle). Although a traditional ANOVA is often appropriate for discrete or summary data, in biomechanical applications, the functional data analysis could be a beneficial alternative. When using the functional data analysis approach, a researcher can (1) evaluate the entire data as a function, and (2) detect the location and magnitude of differences within the evaluated function.
RESUMO
The effects of progesterone on the growth of breast carcinoma cells are undefined. In the present study we investigated the effect of progestins on insulin receptor gene expression and insulin action in human breast cancer cells. Treatment of T47D cells with the synthetic progestin R5020 induced a time- and dose-dependent increase in insulin receptor content as measured by both ligand-binding studies and radioimmunoassay. Binding was half-maximally stimulated at 300 pM R5020 and maximal levels were reached after 4 days of treatment. Progesterone was 10-fold less potent than R5020. Cortisol had no effect on insulin receptor levels, while 17 beta-estradiol and dihydrotestosterone had minimal effects. Progestin treatment both increased insulin receptor mRNA levels and altered the relative distribution of the multiple insulin receptor mRNA transcripts. In order to study the functional significance of the increased insulin receptor levels, we incubated T47D cells with progesterone and then treated them with insulin. Insulin alone had a small effect on cell growth; however, the effect of insulin was markedly potentiated by progesterone treatment. These studies in breast cancer cells demonstrate, therefore, that insulin receptor gene expression is under the regulation of progestins and raise the possibility that progestin-insulin interactions may regulate breast cancer cell growth in vivo.
Assuntos
Divisão Celular/efeitos dos fármacos , Insulina/farmacologia , Progesterona/farmacologia , Promegestona/farmacologia , Receptor de Insulina/metabolismo , Anticorpos Monoclonais , Neoplasias da Mama , Linhagem Celular , Sinergismo Farmacológico , Feminino , Humanos , Imunoglobulina G , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Cinética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , Receptor de Insulina/efeitos dos fármacos , Receptor de Insulina/genética , Transcrição Gênica/efeitos dos fármacosRESUMO
Docosahexaenoic acid (DHA) is a good source of fat that can be taken up through food, such as fish, or taken as a supplement. Evidence is building that DHA provides a high yield, low risk strategy to reduce preterm birth and/or low birth weight. These births are great costs to society. A recently completed phase III trial revealed that higher birth weight and gestational age were associated with DHA dosed at 600 mg/day. In this paper we take a posterior predictive approach to assess impacts of these findings on public health. Simple statistical models are not adequate for accurate posterior predictive distribution estimation. Of particular interest is a paper by Schwartz et al. (2010) who discovered that the joint distribution of birth weight and gestational age is well modeled by a finite mixture of three normal distributions. Data from our own clinical trial exhibit similar features. Using the mean and variance-covariance matrices from Schwartz et al. (2010) and flexible commensurate priors (Hobbs et al., 2012) for the mixing parameters, we estimate the effect of DHA supplementation on the over 20,000 infants born in hospitals demographically similar to the hospital where the clinical trial was conducted.
RESUMO
Because serum cartilage oligomeric matrix protein (COMP) has been used to reflect articular cartilage condition, we aimed to identify walking and running mechanics that are associated with changes in serum COMP. Eighteen subjects (9 male, 9 female; age=23 ± 2 yrs.; mass=68.3 ± 9.6 kg; height=1.70 ± 0.08 m) completed 4000 steps on an instrumented treadmill on three separate days. Each day corresponded to a different ambulation speed: slow (preferred walking speed), medium (+50% of slow), and fast (+100% of slow). Synchronized ground reaction force and video data were collected to evaluate walking mechanics. Blood samples were collected pre-, post-, 30-minute post-, and 60-minute post-ambulation to determine serum COMP concentration at these times. Serum COMP increased 29%, 18%, and 5% immediately post ambulation for the fast, medium, and slow sessions (p<0.01). When the speeds were pooled, peak ankle inversion, knee extension, knee abduction, hip flexion, hip extension, and hip abduction moment, and knee flexion angle at impact explained 61.4% of total variance in COMP concentration change (p<0.001). These results indicate that (1) certain joint mechanics are associated with acute change in serum COMP due to ambulation, and (2) increased ambulation speed increases serum COMP concentration.