RESUMEN
Post-traumatic stress disorder (PTSD) develops in only some people following trauma exposure, but the mechanisms differentially explaining risk versus resilience remain largely unknown. PTSD is heritable but candidate gene studies and genome-wide association studies (GWAS) have identified only a modest number of genes that reliably contribute to PTSD. New gene-based methods may help identify additional genes that increase risk for PTSD development or severity. We applied gene-based testing to GWAS data from the Grady Trauma Project (GTP), a primarily African American cohort, and identified two genes (NLGN1 and ZNRD1-AS1) that associate with PTSD after multiple test correction. Although the top SNP from NLGN1 did not replicate, we observed gene-based replication of NLGN1 with PTSD in the Drakenstein Child Health Study (DCHS) cohort from Cape Town. NLGN1 has previously been associated with autism, and it encodes neuroligin 1, a protein involved in synaptogenesis, learning, and memory. Within the GTP dataset, a single nucleotide polymorphism (SNP), rs6779753, underlying the gene-based association, associated with the intermediate phenotypes of higher startle response and greater functional magnetic resonance imaging activation of the amygdala, orbitofrontal cortex, right thalamus and right fusiform gyrus in response to fearful faces. These findings support a contribution of the NLGN1 gene pathway to the neurobiological underpinnings of PTSD.
Asunto(s)
Encéfalo/fisiopatología , Moléculas de Adhesión Celular Neuronal/genética , Trastornos por Estrés Postraumático/genética , Adulto , Negro o Afroamericano/genética , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/fisiopatología , Encéfalo/diagnóstico por imagen , Expresión Facial , Reconocimiento Facial , Miedo , Femenino , Neuroimagen Funcional , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Antígenos de Histocompatibilidad Clase I/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Reflejo de Sobresalto/fisiología , Trastornos por Estrés Postraumático/diagnóstico por imagen , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/psicología , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/fisiopatología , Tálamo/diagnóstico por imagen , Tálamo/fisiopatología , Población Blanca/genética , Adulto JovenRESUMEN
The protein palmitoylation cycle has been shown to be important for protein signaling and synaptic plasticity. Data from our lab showed a change in the palmitoylation status of certain proteins with age. A greater percentage of the NMDA receptor subunits GluN2A and GluN2B, along with Fyn and PSD95 proteins, were palmitoylated in the old mice. The higher level of protein palmitoylation was also associated with poorer learning scores. Xanthohumol is a prenylated flavonoid that has been shown to increase beta-oxidation in the livers of rodents, decreasing circulating free fatty acids in the serum. What is not known is whether the application of xanthohumol could influence the palmitoylation status of proteins. In this study, young and old mice were fed a diet supplemented with xanthohumol for 8 weeks. Spatial memory was assessed with the Morris water maze and protein palmitoylation quantified. The young xanthohumol-treated mice showed a significant improvement in cognitive flexibility. However, this appeared to be associated with the young control mice, on a defined, phytoestrogen-deficient diet, performing as poorly as the old mice and xanthohumol reversing this effect. The old mice receiving xanthohumol did not significantly improve their learning scores. Xanthohumol treatment was unable to affect the palmitoylation of NMDA receptor subunits and associated proteins assessed in this study. This evidence suggests that xanthohumol may play a role in improving cognitive flexability in young animals, but it appears to be ineffective in adjusting the palmitoylation status of neuronal proteins in aged individuals.
Asunto(s)
Cognición/efectos de los fármacos , Flavonoides/farmacología , Propiofenonas/farmacología , Envejecimiento , Análisis de Varianza , Animales , Peso Corporal/efectos de los fármacos , Homólogo 4 de la Proteína Discs Large , Ácidos Grasos/metabolismo , Flavonoides/metabolismo , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Guanilato-Quinasas , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Proteínas de la Membrana , Ratones , Propiofenonas/metabolismo , Proteínas Proto-Oncogénicas c-fyn , Receptores de N-Metil-D-Aspartato , Distribución Tisular/efectos de los fármacosRESUMEN
AIMS/HYPOTHESES: Glucagon-like peptide-1 (GLP-1), an important mediator of postprandial glycaemia, could potentially be stimulated by delivering small quantities of nutrient to a long length of distal gut. We aimed to determine whether enteric-coated pellets, releasing small amounts of lauric acid throughout the ileum and colon, could reduce glycaemic responses to meals in type 2 diabetes, associated with stimulation of GLP-1. METHODS: Eligible patients, who had type 2 diabetes controlled by diet or metformin, were each studied on two occasions in a hospital setting. After an overnight fast, patients consumed 5 g active pellets (47% lauric acid by weight) or placebo with breakfast (T = 0 min) and lunch (T = 240 min), in a crossover design with order randomised by the hospital pharmacy and allocation concealed by numbered containers. Patients and investigators making measurements were blinded to the intervention. Blood was sampled frequently for blood glucose (the primary outcome) and hormone assays. RESULTS: Eight patients were randomised (four to receive either intervention first), and all completed the study without adverse effects. Blood glucose was lower after breakfast (T = 0-240 min, area under the curve (AUC) 2,075 ± 368 vs 2,216 ± 163 mmol/l × min) and lunch (T = 240-480 min, AUC 1,916 ± 115 vs 2,088 ± 151 mmol/l × min) (p = 0.02 for each) after active pellets than after placebo. Plasma GLP-1 concentrations were higher after breakfast (p = 0.08) and lunch (p = 0.04) for active pellets. While there were no differences in insulin or glucose-dependent insulinotropic polypeptide concentrations, glucagon concentrations were higher after breakfast and lunch (p = 0.002 for each) for active pellets. CONCLUSIONS/INTERPRETATION: Delivering small amounts of nutrient to the ileum and colon can stimulate substantial endogenous GLP-1 release and attenuate postprandial glycaemia. This novel approach has therapeutic potential in type 2 diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000600842. FUNDING: The study was funded by Meyer Nutriceuticals.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/metabolismo , Hiperglucemia/complicaciones , Comprimidos Recubiertos/uso terapéutico , Área Bajo la Curva , Glucemia/metabolismo , Colon/metabolismo , Estudios Cruzados , Femenino , Glucagón/metabolismo , Humanos , Íleon/metabolismo , Insulina/metabolismo , Ácidos Láuricos/uso terapéutico , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Factores de TiempoRESUMEN
The flowers of the ornamental tobacco produce high levels of a series of 6 kDa serine protease inhibitors (NaPIs) that are effective inhibitors of trypsins and chymotrypsins from lepidopteran species. These inhibitors have a negative impact on the growth and development of lepidopteran larvae and have a potential role in plant protection. Here we investigate the effect of NaPIs on the activity and levels of serine proteases in the gut of Helicoverpa armigera larvae and explore the adaptive mechanisms larvae employ to overcome the negative effects of NaPIs in the diet. Polyclonal antibodies were raised against a Helicoverpa punctigera trypsin that is a target for NaPIs and two H. punctigera chymotrypsins; one that is resistant and one that is susceptible to inhibition by NaPIs. The antibodies were used to optimize procedures for extraction of proteases for immunoblot analysis and to assess the effect of NaPIs on the relative levels of the proteases in the gut and frass. We discovered that consumption of NaPIs did not lead to over-production of trypsins or chymotrypsins but did result in excessive loss of proteases to the frass.
Asunto(s)
Quimotripsina/metabolismo , Proteínas de Insectos/metabolismo , Mariposas Nocturnas/enzimología , Extractos Vegetales/metabolismo , Solanum tuberosum/química , Inhibidores de Tripsina/metabolismo , Tripsina/metabolismo , Secuencia de Aminoácidos , Animales , Quimotripsina/antagonistas & inhibidores , Quimotripsina/genética , Clonación Molecular , Tracto Gastrointestinal/enzimología , Control de Insectos , Proteínas de Insectos/química , Proteínas de Insectos/genética , Datos de Secuencia Molecular , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/genética , Mariposas Nocturnas/metabolismo , Extractos Vegetales/química , Alineación de Secuencia , Tripsina/química , Tripsina/genética , Inhibidores de Tripsina/químicaRESUMEN
BACKGROUND: While evidence shows high-dose statins reduce cardiovascular events compared with moderate doses in individuals with acute coronary syndrome (ACS), many primary care trusts (PCT) advocate the use of generic simvastatin 40 mg/day for these patients. METHODS AND RESULTS: Data from 28 RCTs were synthesized using a mixed treatment comparison model. A Markov model was used to evaluate the cost-effectiveness of treatments taking into account adherence and the likely reduction in cost for atorvastatin when the patent expires. There is a clear dose-response: rosuvastatin 40 mg/day produces the greatest reduction in low-density lipoprotein cholesterol (56%) followed by atorvastatin 80 mg/day (52%), and simvastatin 40 mg/day (37%). Using a threshold of £20,000 per QALY, if adherence levels in general practice are similar to those observed in RCTs, all three higher dose statins would be considered cost-effective compared to simvastatin 40 mg/day. Using the net benefits of the treatments, rosuvastatin 40 mg/day is estimated to be the most cost-effective alternative. If the cost of atorvastatin reduces in line with that observed for simvastatin, atorvastatin 80 mg/day is estimated to be the most cost-effective alternative. CONCLUSION: Our analyses show that current PCT policies intended to minimize primary care drug acquisition costs result in suboptimal care.
Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/economía , Costos de los Medicamentos , Medicamentos Genéricos/administración & dosificación , Medicamentos Genéricos/economía , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/economía , Prevención Secundaria/economía , Atorvastatina , Teorema de Bayes , Enfermedades Cardiovasculares/prevención & control , Ensayos Clínicos Fase III como Asunto , Análisis Costo-Beneficio , Prescripciones de Medicamentos/economía , Fluorobencenos/administración & dosificación , Fluorobencenos/economía , Ácidos Heptanoicos/administración & dosificación , Ácidos Heptanoicos/economía , Humanos , Cadenas de Markov , Cumplimiento de la Medicación , Modelos Económicos , Pirimidinas/administración & dosificación , Pirimidinas/economía , Pirroles/administración & dosificación , Pirroles/economía , Indicadores de Calidad de la Atención de Salud/economía , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Rosuvastatina Cálcica , Simvastatina/administración & dosificación , Simvastatina/economía , Sulfonamidas/administración & dosificación , Sulfonamidas/economía , Factores de Tiempo , Resultado del TratamientoRESUMEN
Elevated serum levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) are found in patients with phosphate wasting diseases and chronic kidney disease-mineral and bone disorder (CKD-MBD). These diseases are associated with rickets and renal osteodystrophy, respectively. FGF23 is secreted from osteoblastic cells and signals through FGFRs, membrane coreceptor alpha-Klotho (Klotho), and, possibly, a circulating form of Klotho. Despite the absence of detectable Klotho on osteoblastic cells, studies have suggested that forced FGF23 expression in osteoblasts inhibited mineralization. Thus, we examined the effects of exogenously applied FGF23 on osteoblastic MC3T3.E1 cell proliferation and differentiation, with and without soluble Klotho. MC3T3.E1 cells were cultured in osteoblast differentiation medium, supplemented with FGF23 (0.1-1,000 ng/mL), Klotho (50 ng/mL), the combination FGF23 + Klotho, and FGF2 (100 ng/mL) as a control. Neither FGF23 nor Klotho exposure affected proliferation of day 4 growth phase cells or mineralization of day 14 cultures. In contrast, FGF23 + Klotho resulted in inhibition of mineralization and osteoblast activity markers at day 14, and a slight, reproducible induction of proliferation. Inhibition of FGFR1, but not FGFR2 or FGFR3, completely restored FGF23 + Klotho-induced inhibition of alkaline phosphatase (ALP) activity at day 7. ALP activity was partially restored by the MAPK inhibitor U0126 but not inhibitors p38 and P13K. Thus, soluble Klotho enables FGF23 signaling in MC3T3.E1 cells, likely through FGFR 1(IIIc). Elevated FGF23 actions, in part, appear to parallel FGF2 with lower potency. In addition to affecting bone via indirect phosphate wasting pathways, supraphysiological FGF23 and soluble Klotho may directly impact bone in diseases with elevated FGF23 levels.
Asunto(s)
Calcificación Fisiológica/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Factores de Crecimiento de Fibroblastos/farmacología , Glucuronidasa/farmacología , Osteoblastos/efectos de los fármacos , Animales , Células CHO , Células Cultivadas , Cricetinae , Cricetulus , Evaluación Preclínica de Medicamentos , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/metabolismo , Humanos , Proteínas Klotho , Ratones , Osteoblastos/metabolismo , Osteoblastos/fisiología , Receptores de Factores de Crecimiento de Fibroblastos/genética , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Estudios de Validación como AsuntoRESUMEN
In Australia private homebirth remains unfunded and uninsured and publicly funded homebirth models are not widely available. Doulas are increasingly hired by women for support during childbirth and freebirth (birth intentionally unattended by a health professional) appears to be on the rise. The recently released Improving Maternity Services in Australia--The Report of the Maternity Services Review (MSR) exclude homebirth from the funding and insurance reforms proposed. Drawing on recent research we argue that homebirth has become a casualty of a broken maternity system. The recent rise in the numbers of women employing doulas and choosing to birth at home unattended by any health professional, we argue, is in part a consequence of not adequately meeting the needs of women for continuity of midwifery care and non-medicalised birthing options.
Asunto(s)
Parto Obstétrico/métodos , Doulas , Necesidades y Demandas de Servicios de Salud , Parto Domiciliario/métodos , Servicios de Salud Materna/economía , Actitud del Personal de Salud , Australia , Conducta de Elección , Continuidad de la Atención al Paciente , Parto Obstétrico/efectos adversos , Femenino , Parto Domiciliario/efectos adversos , Humanos , Bienestar Materno , Partería , Embarazo , Factores de Riesgo , Recursos HumanosRESUMEN
Potato type I and II serine protease inhibitors are produced by solanaceous plants as a defense mechanism against insects and microbes. Nicotiana alata proteinase inhibitor (NaPI) is a multidomain potato type II inhibitor (pin II) that is produced at high levels in the female reproductive tissues of the ornamental tobacco, Nicotiana alata. The individual inhibitory domains of NaPI target the major classes of digestive enzymes, trypsin and chymotrypsin, in the gut of lepidopteran larval pests. Although consumption of NaPI dramatically reduced the growth and development of a major insect pest, Helicoverpa punctigera, we discovered that surviving larvae had high levels of chymotrypsin activity resistant to inhibition by NaPI. We found a potato type I inhibitor, Solanum tuberosum potato type I inhibitor (StPin1A), was a strong inhibitor of the NaPI-resistant chymotrypsin activity. The combined inhibitory effect of NaPI and StPin1A on H. armigera larval growth in the laboratory was reflected in the increased yield of cotton bolls in field trials of transgenic plants expressing both inhibitors. Better crop protection thus is achieved using combinations of inhibitors in which one class of proteinase inhibitor is used to match the genetic capacity of an insect to adapt to a second class of proteinase inhibitor.
Asunto(s)
Gossypium/metabolismo , Gossypium/parasitología , Mariposas Nocturnas/patogenicidad , Control Biológico de Vectores/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Inhibidores de Proteasas/metabolismo , Solanum tuberosum/metabolismo , Animales , Quimotripsina/antagonistas & inhibidores , Expresión Génica , Genes de Plantas , Gossypium/genética , Proteínas de Insectos/antagonistas & inhibidores , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Datos de Secuencia Molecular , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/crecimiento & desarrollo , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/prevención & control , Proteínas de Plantas/farmacología , Plantas Modificadas Genéticamente , Inhibidores de Proteasas/farmacología , Solanum tuberosum/genéticaRESUMEN
An AOAC collaborative study was conducted to evaluate an affinity LC procedure for measuring immunoglobulin G (IgG) in selected dairy powders. The powders were extracted with 0.15 M sodium chloride solution and the pH was adjusted to 4.6 to precipitate caseins, which would otherwise lead to an overestimation of IgG. The analyte was then bound to a commercially available Protein G affinity cartridge and selectively eluted with a glycine buffer at pH 2.5. Detection was at 280 nm and quantification was made against a calibration curve prepared from bovine serum IgG. The samples analyzed included the likely matrixes for which this assay will find commercial use, namely, high- and low-protein-content colostrum powders, tablets containing colostrum powder, and some IgG-containing dairy powders; milk protein isolate, whey protein concentrate, and skim milk powder. Eleven laboratories provided data for the study and assayed blind duplicates of six materials. The repeatability RSD values ranged from 2.1 to 4.2% and the reproducibility RSD values ranged from 6.4 to 18.5%. The Protein G method with casein removal has adequate reproducibility for measuring IgG in colostrum-derived powders that are traded on the basis of IgG content as a colostral marker.
Asunto(s)
Técnicas de Química Analítica , Cromatografía Liquida/métodos , Calostro/metabolismo , Inmunoglobulina G/análisis , Leche/metabolismo , Proteínas del Tejido Nervioso/química , Animales , Biomarcadores , Calibración , Bovinos , Concentración de Iones de Hidrógeno , Inmunoglobulina G/química , Polvos , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
In insects, a family of peptides with sequence homology to the vertebrate calcitonins has been implicated in the control of diuresis, a process that includes mixing of the hemolymph. Here, we show that a member of the insect calcitonin-like diuretic hormone (CLDH) family is present in the American lobster, Homarus americanus, serving, at least in part, as a powerful modulator of cardiac output. Specifically, during an ongoing EST project, a transcript encoding a putative H. americanus CLDH precursor was identified; a full-length cDNA was subsequently cloned. In silico analyses of the deduced prepro-hormone predicted the mature structure of the encoded CLDH to be GLDLGLGRGFSGSQAAKHLMGLAAANFAGGPamide (Homam-CLDH), which is identical to a known Tribolium castaneum peptide. RT-PCR tissue profiling suggests that Homam-CLDH is broadly distributed within the lobster nervous system, including the cardiac ganglion (CG), which controls the movement of the neurogenic heart. RT-PCR analysis conducted on pacemaker neuron- and motor neuron-specific cDNAs suggests that the motor neurons are the source of the CLDH message in the CG. Perfusion of Homam-CLDH through the isolated lobster heart produced dose-dependent increases in both contraction frequency and amplitude and a dose-dependent decrease in contraction duration, with threshold concentrations for all parameters in the range 10(-11) to 10(-10) mol l(-1) or less, among the lowest for any peptide on this system. This report is the first documentation of a decapod CLDH, the first demonstration of CLDH bioactivity outside the Insecta, and the first detection of an intrinsic neuropeptide transcript in the crustacean CG.
Asunto(s)
Calcitonina/análogos & derivados , Hormonas/aislamiento & purificación , Hormonas/metabolismo , Nephropidae/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Gasto Cardíaco , Clonación Molecular , ADN Complementario/genética , Diuréticos/análisis , Diuréticos/aislamiento & purificación , Diuréticos/metabolismo , Hormonas/análisis , Hormonas/genética , Datos de Secuencia Molecular , Miocardio/químicaRESUMEN
BACKGROUND AND PURPOSE: DWI using a standard b-value of 1000 s/mm(2) has emerged as the most sensitive sequence for the diagnosis of CJD. The purpose of this study was to investigate whether DWI at a high b-value (b = 3000 s/mm(2)) and ADC measurements in the basal nuclei improve the diagnosis of vCJD and sCJD compared with visual assessment of DWI at a standard b-value (b = 1000 s/mm(2)). MATERIALS AND METHODS: Eight patients with vCJD, 9 patients with sCJD, and 5 healthy volunteers underwent DWI at b = 1000 s/mm(2), and 5 vCJD patients, 4 sCJD patients, and 1 growth hormone-related CJD patient underwent DWI at b = 3000 s/mm(2). Two consultant neuroradiologists performed a visual comparison of the b = 1000 and b = 3000 images. Mean MR SI and ADC values were determined for C, P, and DM thalamus ROIs bilaterally at each b-value. SI ratios for each ROI relative to white matter were calculated. RESULTS: In 9 out of 10 patients, the higher b-value images were more sensitive to SI change, particularly in cortex and thalamus, with higher SI ratios at b = 3000 in the DM thalamus. For sCJD at b = 1000, we found significantly lower ADC values in the C and P compared with controls (mean C ADC = 587.3 +/- 84.7 mm(2)/s in sCJD patients versus 722.7 +/- 16.6 mm(2)/s in controls; P = .007), and at b = 3000, the differences were more pronounced. In comparison, in vCJD at b = 1000, ADC values were elevated in the Pu (mean Pu ADC = 837.6 +/- 33.0 mm/s(2) in vCJD patients versus 748.0 +/- 17.3 mm/s(2) in controls; P < .001) but failed to reach significance at b = 3000. CONCLUSIONS: Our results demonstrate that b = 3000 DWI, being more sensitive to slowly diffusing tissue water, is more sensitive to pathology in sCJD than is conventional DWI. High-b-value DWI increases confidence in the radiologic diagnosis of human prion disease.
Asunto(s)
Ganglios Basales/metabolismo , Ganglios Basales/patología , Síndrome de Creutzfeldt-Jakob/metabolismo , Síndrome de Creutzfeldt-Jakob/patología , Imagen de Difusión por Resonancia Magnética/métodos , Adulto , Anciano , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Tálamo/metabolismo , Tálamo/patología , Agua/metabolismo , Adulto JovenRESUMEN
pQDLDHVFLRFamide is a highly conserved crustacean neuropeptide with a structure that places it within the myosuppressin subfamily of the FMRFamide-like peptides. Despite its apparent ubiquitous conservation in decapod crustaceans, the paracrine and/or endocrine roles played by pQDLDHVFLRFamide remain largely unknown. We have examined the actions of this peptide on the cardiac neuromuscular system of the American lobster Homarus americanus using four preparations: the intact animal, the heart in vitro, the isolated cardiac ganglion (CG), and a stimulated heart muscle preparation. In the intact animal, injection of myosuppressin caused a decrease in heartbeat frequency. Perfusion of the in vitro heart with pQDLDHVFLRFamide elicited a decrease in the frequency and an increase in the amplitude of heart contractions. In the isolated CG, myosuppressin induced a hyperpolarization of the resting membrane potential of cardiac motor neurons and a decrease in the cycle frequency of their bursting. In the stimulated heart muscle preparation, pQDLDHVFLRFamide increased the amplitude of the induced contractions, suggesting that myosuppressin modulates not only the CG, but also peripheral sites. For at least the in vitro heart and the isolated CG, the effects of myosuppressin were dose-dependent (10(-9) to 10(-6) mol l(-1) tested), with threshold concentrations (10(-8)-10(-7) mol l(-1)) consistent with the peptide serving as a circulating hormone. Although cycle frequency, a parameter directly determined by the CG, consistently decreased when pQDLDHVFLRFamide was applied to all preparation types, the magnitudes of this decrease differed, suggesting the possibility that, because myosuppressin modulates the CG and the periphery, it also alters peripheral feedback to the CG.
Asunto(s)
Crustáceos/química , Corazón/efectos de los fármacos , Nephropidae/efectos de los fármacos , Nephropidae/fisiología , Sistema Nervioso/efectos de los fármacos , Neuropéptidos/farmacología , Hormonas Peptídicas/farmacología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , FMRFamida/farmacología , Ganglios de Invertebrados/efectos de los fármacos , Ganglios de Invertebrados/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Datos de Secuencia Molecular , Contracción Miocárdica/efectos de los fármacos , Miocardio , Neuropéptidos/química , Neuropéptidos/genética , Hormonas Peptídicas/química , Perfusión , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
BACKGROUND: This national investigation of older Australians was conducted to explore the relationship between their health, lifestyle, use of dietary supplements and nutritional risk. OBJECTIVE: The objective of this study was to examine the extent of poor health status and nutritional risk among Australians aged 65 years and over, as determined by the Australian Nutrition Screening Initiative. DESIGN: The 12 statements that comprise the Australian Nutrition Screening Initiative (ANSI) were incorporated in a comprehensive, self-administered national postal survey designed to elicit information on the health and lifestyle practices of older Australians. In 2001, data were obtained from 1,263 individuals (641 males, 622 females) aged between 65 and 98 years, randomly chosen from the 2000 Australian Electoral roll. RESULTS: According to the ANSI, 59% (n=747) of the sample was at risk of poor nutritional status as well as poor health status. The most frequently occurring risk factors were; taking 3 or more different prescription or over-the-counter drugs each day (44%), having an illness that led to changes to the kind and/or amount of food consumed (34%), eating alone most of the time (28%), not eating dairy products most days (18%), and consuming 3 or more alcoholic beverages each day (18%). Gender differences were observed for several ANSI statements. CONCLUSION: These results suggest that because the ANSI may exaggerate the true extent of nutritional risk among community living older individuals it is of limited value as a screening tool per se. The future of the ANSI should be dependent on verifying its reliability as a public health measure.
Asunto(s)
Evaluación Geriátrica , Estado de Salud , Evaluación Nutricional , Trastornos Nutricionales/diagnóstico , Estado Nutricional , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Estudios Transversales , Femenino , Indicadores de Salud , Humanos , Estilo de Vida , Masculino , Tamizaje Masivo , Trastornos Nutricionales/epidemiología , Encuestas Nutricionales , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
Four experiments were completed to characterize the utilization of visual imagery and motor imagery during the mental representation of human action. In Experiment 1, movement time functions for a motor imagery human locomotion task conformed to a speed-accuracy trade-off similar to Fitts' Law, whereas those for a visual imagery object motion task did not. However, modality-specific interference effects in Experiment 2 demonstrate visual and motor imagery as cooperative processes when the action represented is tied to visual coordinates in space. Biomechanic-specific motor interference effects found in Experiment 3 suggest one basis for separation of processing channels within motor imagery. Finally, in Experiment 4 representations of motor actions were found to be generated using only visual imagery under certain circumstances: namely, when the imaginer represented the motor action of another individual while placed at an opposing viewpoint. These results suggest that the modality of representation recruited to generate images of human action is dependent on the dynamic relationship between the individual, movement, and environment.
Asunto(s)
Imaginación , Locomoción , Percepción Visual , Adolescente , Adulto , Femenino , Humanos , Masculino , Destreza Motora , Análisis y Desempeño de TareasRESUMEN
The purpose of this Grounded Theory based study was to add to the limited understanding about the perception and observation of pain by the formal and informal carers of people with dementia. Thirty-one carers talked about how they know when their person with dementia has pain. Findings showed there is no one set of signs or behaviours that indicate pain in all people with dementia. However, a common pain assessment process amongst carers involved being able to detect deviation from normal behaviours based upon their intimate knowledge of what is normal for their person. A central hypothesis was thus generated from the data that considered that effective pain assessment for people with dementia is dependent on carers having an intimate knowledge of the individual's normal state of being with dementia. Implications for nursing practice are discussed.
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Cuidadores/psicología , Demencia/complicaciones , Demencia/enfermería , Salud Holística , Atención Domiciliaria de Salud/métodos , Dolor/enfermería , Anciano , Anciano de 80 o más Años , Anécdotas como Asunto , Empatía , Femenino , Atención Domiciliaria de Salud/psicología , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Rol de la Enfermera , Dolor/diagnóstico , Dolor/etiología , Dimensión del Dolor/métodos , Dimensión del Dolor/enfermeríaRESUMEN
Several known anti-cancer agents have been shown to lead to increased expression of phase 2 metabolic enzymes without affecting phase 1 enzymes. Phase 1 cytochrome P450 (CYP) enzymes are relevant in cancer studies in that they are involved in oxidative metabolism, biotransformation and detoxification, whereas phase 2 enzyme catalysis leads to clearance. In this study, we obtained semi-quantitative measurements of cytochrome P450 (phase 1) and phase 2 microsomal epoxide hydrolase (mEH) gene expression levels in response to treatment of MCF-7 breast cancer cells with water-soluble Vernonia amygdalina (V.A.) extract. V.A., a vegetable grown in Nigeria, has potential as an anti-cancer agent. The results of Western blot and RT-PCR analyses show that V.A. extract acts as a monofunctional inducer within exposure times ranging from 2-16 hr and dose ranges from 3-100 microg/ml of V.A. Exposure of cells to low doses of V.A. did not affect expression levels of CYP1A1/1A2 mRNA, but lead to induction of mEH, thus supporting the chemotherapeutic potential of VA. However, in parallel studies, CYP3A4 gene expression was also induced, suggesting potential intermediates which influence drug-drug interactions. These data are useful toward further validating V.A. extract as a potential clinically useful natural anti-cancer agent and provide some support for the concept that modulation in CYP3A4 expression in response to treatment is relevant to prognosis.
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Neoplasias de la Mama/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Fitoterapia , Veronica , Neoplasias de la Mama/enzimología , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450/metabolismo , Epóxido Hidrolasas/metabolismo , Femenino , Humanos , Extractos Vegetales/farmacología , Células Tumorales CultivadasRESUMEN
In a complex seven-period cross-over trial to study the effects of a drug in attenuating capsaicin-induced coughing, counts of numbers of coughs were recorded 32 times in each period. Subjects were subjected to four escalating levels of capsaicin at each of one and five hours after treatment, with counts of coughs being recorded in four one-minute intervals at each level. Such longitudinal count studies often show considerable individual variability about any regression curve that might be fitted. We develop a non-linear autoregressive model for such count data that also allows for overdispersion.
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Tos/tratamiento farmacológico , Estudios Cruzados , Modelos Estadísticos , Tiazoles/farmacología , Agonistas Adrenérgicos beta/farmacología , Albuterol/farmacología , Capsaicina/administración & dosificación , Tos/inducido químicamente , Domperidona/farmacología , Antagonistas de Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Estudios Longitudinales , Masculino , Receptores de Dopamina D2/agonistasRESUMEN
UNLABELLED: Automatic atrial anti-tachy pacing (aATP) is a novel approach to treat paroxysmal/persistent atrial tachyarrhythmias in pacemaker patients. To evaluate the efficacy of aATP in terminating spontaneous atrial flutter/tachycardia episodes (AT), a dual-chamber stimulator with extensive diagnostic capabilities and programmable aATP therapies (AT500(TM), Medtronic Inc.) was implanted in 30 patients with conventional pacing indications. During a mean follow-up time of 5.5 (1-12) months, aATP was delivered for 10494 AT. According to automatic device analysis, 8289 AT were treated with success (success-rate 79.0%). On 468 AT stored with the corresponding atrial EGM, an additional manual analysis was performed. The success-rate based on automatic analysis of these AT episodes (73.1%) was comparable to that found for all treated AT (79.0%), but manual EGM analysis revealed that only 209 of the 468 treated AT episodes (44.7%) were actually terminated by aATP. The aATP success-rate in the slower (cycle length 360-270 ms) AT detection zone was significantly higher (73.8%, 62/84 eps) than in the overlapping, faster (cycle length 270-220 ms) AT zone (38.3%, 147/384 eps, P<0.01). CONCLUSIONS: According to manual analysis, 1. aATP was safe and had a success-rate of 44.7%, 2. aATP success-rate was higher for AT in the slower than in the faster detection zone and 3. automatic analysis overestimated the efficacy of aATP.
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Estimulación Cardíaca Artificial , Atrios Cardíacos/cirugía , Taquicardia Atrial Ectópica/terapia , Adulto , Anciano , Anciano de 80 o más Años , Técnicas Electrofisiológicas Cardíacas/instrumentación , Seguridad de Equipos/instrumentación , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Marcapaso Artificial , Sensibilidad y Especificidad , Taquicardia Atrial Ectópica/diagnóstico , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Persistent residual quadriceps femoris muscle force deficits after total knee arthroplasty (TKA) are commonly reported and can prevent patients from returning quickly and fully to functional activities. Neuromuscular electrical stimulation offers a potentially more effective means of increasing muscle force than current rehabilitation protocols. CASE DESCRIPTION: The patient was a 66-year-old man. Neuromuscular electrical stimulation for increasing quadriceps femoris muscle force was initiated 3 weeks after TKA for 11 sessions to supplement stretching exercises and a high-intensity volitional strengthening program. OUTCOME: The patient's isometric quadriceps femoris muscle force increased from 50% (involved/uninvolved) at 3 weeks after surgery to 86% at 8 weeks after surgery. A concurrent increase in his uninvolved quadriceps femoris muscle force concealed the patient's true increase in his involved quadriceps femoris muscle force in a side-to-side comparison. The patient's final involved quadriceps femoris muscle force (10 weeks after surgery) was 93% of the initial uninvolved quadriceps femoris muscle force. DISCUSSION: Our patient was able to return to independent activities of daily living and recreational activities, with force gains that surpassed those reported in the literature.
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Artroplastia de Reemplazo de Rodilla , Músculo Esquelético/fisiopatología , Muslo , Estimulación Eléctrica Transcutánea del Nervio , Anciano , Terapia por Ejercicio , Humanos , Contracción Isométrica , MasculinoRESUMEN
A grounded theory methodology was used to generate theory about the experiences of women undergoing laparoscopic sterilisation in a day surgery unit. Theories were developed on the role of client education in relieving anxiety, and the importance of privacy in all stages of client care. The grounded theory approach offered a client-centered model for day surgery planning.