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1.
J Phys Chem B ; 115(12): 2979-87, 2011 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-21384835

RESUMEN

We use molecular dynamics (MD) and dynamic light scattering (DLS) measurements to analyze the size of reverse micellar structures in the AOT-water-isooctane system at different water-to-surfactant ratios at ambient temperature and pressure. We find good qualitative agreement for the size and morphology behavior of the reverse micelle structures between molecular dynamics calculations and DLS measurements; however, the average values for the reverse micelle size distributions are systematically larger for the DLS measurements. The latter tends to capture the average hydrodynamic size of the structures based on self-diffusion rather than the average physical size as measured in MD simulations, explaining the systematic deviations observed. The combination of MD with DLS allows a better interpretation of the experimental results, in particular for conditions where the structures are nonspherical, commonly observed at lower water-to-surfactant ratios. We also present and analyze the effect of zirconyl chloride on the micellar size distributions in this system. These type of salts are common for reverse micellar synthesis processes. We find that zirconyl chloride affects significantly the size distributions.


Asunto(s)
Ácido Dioctil Sulfosuccínico/química , Luz , Micelas , Simulación de Dinámica Molecular , Octanos/química , Dispersión de Radiación , Agua/química , Conformación Molecular
2.
J Mol Endocrinol ; 32(3): 869-77, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15171718

RESUMEN

Vasoactive intestinal peptide (VIP) shows a wide tissue distribution and exerts numerous physiological actions. VIP was shown in a dose-dependent manner to increase cortisol secretion in the NCI-H295R human adrenocortical carcinoma (H295) cell line (threshold dose 3.3x10(-10) M, maximal dose 10(-7) M), coupled with a parallel increase in cAMP accumulation. Receptor-specific agonists were employed to determine which of the two known VIP receptor subtypes was involved in cortisol secretion. Treatment with the VPAC1 receptor agonist, [K(15), R(16), L(27)]VIP(1-7)/GRF(8-27), produced a dose-dependent increase in H295 cell cortisol secretion (threshold dose 10(-11) M, maximal dose 10(-7) M) similar to that seen with VIP. Meanwhile, the high-affinity VPAC2 receptor agonist, RO-25-1553, failed to stimulate significantly cortisol or cAMP production from H295 cells. Inhibition of VIP-mediated H295 cell cortisol secretion by PG97-269, a competitive VPAC1-specific antagonist, produced parallel shifts of the dose-response curve and a Schild regression slope of 0.99, indicating competitive inhibition at a single receptor subtype. VIP is known also to interact with the PAC1 receptor, albeit with lower affinity (EC(50) of approximately 200 nM) than the homologous ligand, PACAP (EC(50) of approximately 0.5 nM). PACAP stimulated cortisol secretion from H295 cells (EC(50) of 0.3 nM), suggesting the presence of functional PAC1 receptors. However, stimulation of cortisol secretion by nanomolar concentrations of VIP (EC(50) of 5 nM), coupled with real-time PCR estimation that VPAC1 receptor transcripts appear 1000-fold more abundant than PAC1 transcripts in H295 cells, makes it unlikely that VIP signals via PAC1 receptors. Together, these data suggest that VIP directly stimulates cortisol secretion from H295 cells via activation of the VPAC1 receptor subtype.


Asunto(s)
Línea Celular Tumoral/efectos de los fármacos , Hidrocortisona/metabolismo , Receptores de Péptido Intestinal Vasoactivo/metabolismo , Péptido Intestinal Vasoactivo/farmacología , Animales , AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Factores de Crecimiento Nervioso/metabolismo , Neuropéptidos/metabolismo , Neurotransmisores/metabolismo , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Radioinmunoensayo , Receptores de Péptido Intestinal Vasoactivo/agonistas , Receptores de Péptido Intestinal Vasoactivo/antagonistas & inhibidores , Receptores de Péptido Intestinal Vasoactivo/genética , Receptores de Tipo II del Péptido Intestinal Vasoactivo , Receptores de Tipo I del Polipéptido Intestinal Vasoactivo
3.
Circulation ; 104(23): 2832-7, 2001 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-11733403

RESUMEN

BACKGROUND: 11beta-Hydroxysteroid dehydrogenase (11betaHSD) isozymes catalyze the interconversion of active and inactive glucocorticoids, allowing local regulation of corticosteroid receptor activation. Both are present in the vessel wall; here, using mice with selective inactivation of 11betaHSD isozymes, we test the hypothesis that 11betaHSDs influence vascular function. METHODS AND RESULTS: Thoracic aortas were obtained from weight-matched male wild-type (MF1x129 cross(+/+)), 11betaHSD1(-/-), and 11betaHSD2(-/-) mice. mRNA for both isozymes was detected in wild-type aortas by RT-PCR. 11betaHSD activity in aortic homogenates (48.81+/-4.65% conversion) was reduced in both 11betaHSD1(-/-) (6.36+/-2.47% conversion; P<0.0002) and 11betaHSD2(-/-) (24.71+/-3.69; P=0.002) mice. Functional responses were unaffected in aortic rings isolated from 11betaHSD1(-/-) mice. In contrast, aortas from 11betaHSD2(-/-) mice demonstrated selectively enhanced constriction to norepinephrine (E(max) 4.28+/-0.56 versus 1.72+/-0.47 mN/mm; P=0.004) attributable to impaired endothelium-derived nitric oxide activity. Relaxation responses to endothelium-dependent and -independent vasodilators were also impaired. To control for chronic renal mineralocorticoid excess, MF1 mice were treated with fludrocortisone (16 weeks) but did not reproduce the functional changes observed in 11betaHSD2(-/-) mice. CONCLUSIONS: Although both 11betaHSD isozymes are present in the vascular wall, reactivation of glucocorticoids by 11betaHSD1 does not influence aortic function. Mice with 11betaHSD2 knockout, however, have endothelial dysfunction causing enhanced norepinephrine-mediated contraction. This appears to be independent of renal sodium retention and may contribute to hypertension in 11betaHSD2 deficiency.


Asunto(s)
Endotelio Vascular/fisiopatología , Hidroxiesteroide Deshidrogenasas/deficiencia , Molsidomina/análogos & derivados , 11-beta-Hidroxiesteroide Deshidrogenasas , Acetilcolina/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/enzimología , Aorta Torácica/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Fludrocortisona/farmacología , Hidroxiesteroide Deshidrogenasas/genética , Técnicas In Vitro , Isoenzimas/deficiencia , Isoenzimas/genética , Masculino , Ratones , Ratones Endogámicos , Ratones Noqueados , Mineralocorticoides/farmacología , Molsidomina/farmacología , Norepinefrina/farmacología , Cloruro de Potasio/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Serotonina/farmacología , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Aumento de Peso/efectos de los fármacos
5.
J Hum Hypertens ; 15(8): 539-48, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11494092

RESUMEN

OBJECTIVES: This study compared the prevalence and intensity of symptoms and the health-related quality of life (HQL) of patients taking antihypertensive medications and patients without disease. METHODS: This cross-sectional study used surveys mailed to patient's homes. All consecutive patients over age 30 years attending either a general medicine or hypertension clinic during 3 months were eligible (n = 437). Hypertension group (HTN-G) patients were diagnosed with primary hypertension, prescribed antihypertensive medications, and had no other symptomatic conditions or drug therapies. Control group (CNTL-G) patients were seen in the general medicine clinic and had no chronic symptomatic conditions or drug therapies. Measures included the Symptom Distress Checklist (SDC, list of 51 symptoms, frequency, and level of distress), the Medical Outcomes Study Short Form-36 (SF-36), medications, blood pressures, and other data obtained from medical records and patient self-report. RESULTS: A total of 222 patients responded (46% CNTL-G, 55% HTN-G). HTN-G patients were somewhat older (59.0 +/- 11.2 vs 48.5 +/- 11.7 years, P = 0.001) and had a higher percent of minorities (24.8% vs 13.5%, P = 0.02), but otherwise similar. After adjusting for age and race differences, HTN-G patients reported significantly more symptoms (8.8 +/- 7.8 vs 4.7 +/- 4.8, P = 0.001) and related distress (32.2 +/- 4.2 vs 12.0 +/- 18.2, P = 0.001) as well as lower scores (reduced HQL) for most of the SF-36 domains. In general, hypertensive patients had more physical, but not mental symptoms than control patients. CONCLUSIONS: Hypertensive patients receiving antihypertensive medications have more symptoms and lower HQL. Differences were detected by both a brief, general HQL instrument and a detailed, disease-specific instrument. Routine screening of treated hypertensive patients using a brief HQL questionnaire to detect physical symptoms may prove feasible and useful.


Asunto(s)
Hipertensión/epidemiología , Hipertensión/psicología , Calidad de Vida/psicología , Adulto , Anciano , Antihipertensivos/uso terapéutico , Presión Sanguínea/fisiología , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prevalencia , Encuestas y Cuestionarios
6.
Bioresour Technol ; 79(3): 227-30, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11499576

RESUMEN

The Irish mushroom industry has expanded rapidly in the last decade, particularly in the border counties. Its success has generated concern, however, as the production of spent mushroom compost (SMC) has increased. Until recently, SMC as an agricultural waste has been disposed of without due consideration to the environment. As County Councils increasingly address river pollution, restrictions will prevent expansion of the mushroom industry without an SMC waste management solution. This paper looks at the availability and composition of SMC and considers its potential as an energy feedstock. Variability in SMC composition was investigated by sampling from various locations over several months. Analyses showed that, on a dry ash free basis, SMC has a calorific value equivalent to sewage sludge which has been successfully fired for many years. Compositional analysis confirmed the dry fuel as consistent in make-up and showed the moisture content to vary within 60-77%, on an as-received basis.


Asunto(s)
Agaricales , Conservación de los Recursos Naturales , Suministros de Energía Eléctrica , Eliminación de Residuos , Agricultura , Fuentes de Energía Bioeléctrica , Industrias
7.
Br J Pharmacol ; 133(6): 902-8, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11454664

RESUMEN

This investigation examined the hypothesis that release of K(+) accounts for EDHF activity by comparing relaxant responses produced by ACh and KCl in human subcutaneous resistance arteries. Resistance arteries (internal diameter 244+/-12 microm, n=48) from human subcutaneous fat biopsies were suspended in a wire myograph. Cumulative concentration-response curves were obtained for ACh (10(-9) - 3x10(-5) M) and KCl (2.5 - 25 mM) following contraction with noradrenaline (NA; 0.1 - 3 microM). ACh (E(max) 99.07+/-9.61%; -LogIC(50) 7.03+/-0.22; n=9) and KCl (E(max) 74.14+/-5.61%; -LogIC(50) 2.12+/-0.07; n=10)-induced relaxations were attenuated (P<0.0001) by removal of the endothelium (E(max) 8.21+/-5.39% and 11.56+/-8.49%, respectively; n=6 - 7). Indomethacin (10 microM) did not alter ACh-induced relaxation whereas L-NOARG (100 microM) reduced this response (E(max) 61.7+/-3.4%, P<0.0001; n=6). The combination of ChTx (50 nM) and apamin (30 nM) attenuated the L-NOARG-insensitive component of ACh-induced relaxation (E(max): 15.2+/-10.5%, P<0.002, n=6) although these arteries retained the ability to relax in response to 100 microM SIN-1 (E(max) 127.6+/-13.0%, n=3). Exposure to BaCl(2) (30 microM) and Ouabain (1 mM) did not attenuate the L-NOARG resistant component of ACh-mediated relaxation (E(max), 76.09+/-8.92, P=0.16; n=5). KCl-mediated relaxation was unaffected by L-NOARG+indomethacin (E(max); 68.1+/-5.6%, P=0.33; n=5) or the combination of L-NOARG/indomethacin/ChTx/apamin (E(max); 86.61+/-14.02%, P=0.35; n=6). In contrast, the combination of L-NOARG, indomethacin, ouabain and BaCl(2) abolished this response (E(max), 5.67+/-2.59%, P<0.0001, n=6). The characteristics of KCl-mediated relaxation differed from those of the nitric oxide/prostaglandin-independent component of the response to ACh, and were endothelium-dependent, indicating that K(+) does not act as an EDHF in human subcutaneous resistance arteries.


Asunto(s)
Arterias/efectos de los fármacos , Factores Biológicos/fisiología , Potasio/farmacología , Vasodilatación/efectos de los fármacos , Acetilcolina/farmacología , Adulto , Anciano , Apamina/farmacología , Arterias/fisiología , Compuestos de Bario/farmacología , Caribdotoxina/farmacología , Cloruros/farmacología , Relación Dosis-Respuesta a Droga , Endotelio Vascular/fisiología , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Técnicas In Vitro , Indometacina/farmacología , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa/antagonistas & inhibidores , Nitroarginina/farmacología , Norepinefrina/farmacología , Ouabaína/farmacología , Piel/irrigación sanguínea , Factores de Tiempo , Vasodilatación/fisiología , Vasodilatadores/farmacología
8.
Eval Health Prof ; 24(1): 53-60, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11233585

RESUMEN

Recognizing and rewarding teaching faculty are increasingly important to medical schools and are often hampered by low perceived reliability and validity of measures of teaching ability. The purpose of this study was to cross-validate two independently generated measures of teaching from medical students and residents. A total of 2,318 medical student and 4,425 resident scores for single-item measures of teaching ability for 129 teaching faculty members of a department of internal medicine over a 6-year period were compared. Results showed that average teaching scores were higher for medical students than residents. Rank order of faculty were within 2 quintiles for the two groups for over 90% of faculty. Highly discordant evaluations were seen for only 8% of faculty. The authors conclude the general concordance of two independent measures of teaching ability adds evidence to the existing literature of the validity of single-item measures of teaching ability from two different types of learners.


Asunto(s)
Docentes Médicos/normas , Internado y Residencia , Estudiantes de Medicina , Enseñanza/normas , Actitud del Personal de Salud , Encuestas y Cuestionarios , Estados Unidos
9.
Bioresour Technol ; 76(3): 183-90, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11198168

RESUMEN

Targets for a considerable increase in electricity generation from renewables have been set in order to reduce greenhouse gas emissions and fossil fuel dependence. Extensive planting of willow, poplar and alder as energy crops has been planned for power generation plants which use wood as the fuel. The current trend is to use gasification or pyrolysis technology, but alternatively a case may be made for wood combustion, if wood becomes readily available. A range of wood-fired circulating fluidised bed combustion (CFBC) plants, using from 10 to 10,000 dry tonne equivalent (DTE)/day, was examined using the ECLIPSE process simulation package. Various factors, such as wood moisture content, harvest yield, afforestation level (AL) and discounted cash flow rate (DCF) were investigated to test their influence on the efficiency and the economics of the systems. Steam cycle conditions and wood moisture content were found to have the biggest effects on the system efficiencies; DCF and AL had the largest influences on the economics. Plants which could handle more than 500 dry tonnes/day could be economically viable; those using more than 1000 dry tonnes wood/day could be competitive with large-scale, conventional coal-fired plants, if sufficient wood were available.


Asunto(s)
Fuentes Generadoras de Energía/economía , Incendios , Madera , Carbón Mineral/economía , Simulación por Computador , Electricidad , Ingeniería , Incendios/economía , Combustibles Fósiles/economía , Efecto Invernadero , Industrias/economía , Centrales Eléctricas/economía , Programas Informáticos , Transportes/economía , Árboles/química , Agua/análisis
10.
Clin Sci (Lond) ; 100(3): 311-8, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11222118

RESUMEN

Type I diabetes mellitus is associated with abnormal vascular function, but few studies have documented its effects on human resistance arteries. This study aimed to determine whether endothelial cell and smooth muscle cell function was impaired in resistance arteries isolated from patients with this condition. Biopsies of subcutaneous gluteal fat were taken from 12 patients with Type I diabetes (age 32.3+/-1.9 years; duration of diabetes 13.9+/-2.5 years) and 12 matched controls (age 31.5+/-2.2 years). Levels of glycosylated haemoglobin were higher (P<0.0001) in patients (9.38+/-0.35%) than in controls (5.48+/-0.11%), but most (11 out of 12) patients showed no evidence of microvascular disease. Small resistance arteries were isolated from the biopsies, and isometric responses to vasoconstrictors and vasodilators were measured in a small-vessel myograph. The magnitude and sensitivity of responses to noradrenaline and potassium were not different in diabetic patients compared with controls. In contrast, the sensitivity (pD(2); negative logarithm of the concentration of the vasoconstrictor required to produce 50% of the maximum effect), but not the magnitude, of contraction in response to endothelin-1 in vessels from patients (8.87+/-0.12) was significantly (P=0.02) greater than in those from controls (8.40+/-0.13). Endothelium-dependent (acetylcholine, bradykinin, A23187) and -independent (3'-morpholinosydnonimine) relaxation responses were unaltered in patients with Type I diabetes. These results suggest a selective alteration in receptor activity in the endothelium, and contrast strikingly with the considerable evidence of impaired endothelium-dependent relaxation in Type I diabetes. The present study indicates, therefore, that endothelial cell function is largely maintained in resistance arteries from patients with well controlled Type I diabetes. The increased response to endothelin-1 supports the possibility that more significant abnormalities would be evident in patients with severe microvascular complications.


Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Angiopatías Diabéticas/fisiopatología , Endotelina-1/fisiología , Adulto , Biopsia , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/patología , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/patología , Endotelio Vascular , Femenino , Hemoglobina Glucada/análisis , Humanos , Contracción Isométrica/efectos de los fármacos , Masculino , Músculo Liso Vascular , Miografía , Resistencia Vascular/fisiología , Vasoconstrictores , Vasodilatadores
11.
Waste Manag Res ; 19(6): 526-32, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12201682

RESUMEN

Plastics wastes from a municipal solid waste plant have a high energy content which make it an interesting option for co-processing with coal. The potential for adding plastic waste to a coal fired Texaco IGCC (Integrated Gasification Combined Cycle) power station is examined. The resulting efficiency increases due to the improved gasification qualities of plastic over coal. For the overall economics to be the same as the coal only case, the maximum amount that the power station can afford to spend on preparing the plastic waste for use is similar to the assumed coal cost, plus the avoided landfill cost, minus the transport cost. The location of the power station plays a key role, since this has an effect on the transport costs as well as on the landfill charges. The sensitivity of the economics of co-processing plastic waste with coal for a variety of power station operational parameters is presented.


Asunto(s)
Carbón Mineral , Conservación de los Recursos Naturales , Plásticos , Centrales Eléctricas , Eliminación de Residuos/métodos , Costos y Análisis de Costo , Gases , Eliminación de Residuos/economía , Transportes/economía
12.
Acad Med ; 75(11): 1144-6, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11078678

RESUMEN

PURPOSE: Faculty development programs and faculty incentive systems have heightened the need to validate a connection between the quality of teaching and students' learning. This study was designed to determine the association between attending physicians' and residents' teacher ratings and their students' examination scores. METHOD: From a database of 362 students, 138 faculty, and 107 residents in internal medicine, student-faculty (n = 476) and student-resident (n = 474) pairs were identified. All students were in their third year, rotating on inpatient general medicine and cardiology services, July 1994 through June 1996, at a single institution. The outcome measure for students' knowledge was the NBME Subject Examination in internal medicine. To control for students' baseline knowledge, the predictors were scores on the USMLE Step 1 and a sequential examination (a clinically-based pre- and post-clerkship examination). Teaching abilities of faculty and residents were rated by a global item on the post-clerkship evaluation. Faculty's ratings used only scores from prior to the study period; residents' ratings included those scores students gave during the study period. RESULTS: Multivariate analyses showed faculty's teaching ratings were a small but significant predictor of the increase in students' knowledge. Residents' teaching ratings did not predict an increase in students' knowledge. CONCLUSION: Attending faculty's clinical teaching ability has a positive and significant effect on medical students' learning.


Asunto(s)
Competencia Clínica , Evaluación Educacional , Medicina Interna/educación , Internado y Residencia , Cuerpo Médico , Médicos , Enseñanza/métodos , Cardiología/educación , Prácticas Clínicas , Educación Médica , Docentes Médicos , Predicción , Humanos , Aprendizaje , Modelos Lineales , Análisis Multivariante , Desarrollo de Personal , Estudiantes de Medicina
13.
Gastroenterology ; 118(4): 765-71, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10734028

RESUMEN

BACKGROUND & AIMS: Impaired pressor function in cirrhosis may be specific to certain agonists and vascular territories. This investigation determined whether responses to arginine vasopressin (AVP) and 5-hydroxytryptamine (5-HT) were impaired in hepatic arteries from cirrhotic patients. METHODS: Cumulative concentration-response curves were produced for AVP (10(-11) to 3 x 10(-6) mol/L), 5-HT (10(-9) to 3 x 10(-5) mol/L), and potassium chloride (2.5 -120 mmol/L) in hepatic arteries from liver donors (noncirrhotic) and recipients (cirrhotic). The receptor stimulated by AVP was identified using a V(1)-receptor antagonist (d[CH(2)](5)Tyr[Me]AVP) and a selective V(2)-receptor agonist (desmopressin [DDAVP]). RESULTS: Cirrhotic patients had a high heart rate (98 +/- 4 beats/min) and cardiac output (9.87 +/- 0.51 L/min) but low peripheral vascular resistance (711 +/- 35 dyn. s/cm(5)). None of the arteries had a functional endothelium. Maximal contraction (but not sensitivity) to AVP was smaller (P = 0.0002) in hepatic arteries from recipients (34.03% +/- 3.42% KCl) than donors (60.69% +/- 5.56% KCl). 5-HT-mediated contraction was enhanced in recipient hepatic arteries (88.81% +/- 5.43% KCl vs. 71.63% +/- 4. 46% KCl; P = 0.01), but sensitivities were similar (P = 0.20). KCl-mediated contractions were similar (P = 0.87) in both groups. Arteries did not respond to DDAVP, but d(CH(2))(5)Tyr(Me)AVP produced a concentration-dependent rightward shift in the response to AVP. CONCLUSIONS: These results demonstrate a selective impairment of V(1) receptor-mediated contraction in denuded hepatic arteries from cirrhotic patients, suggesting an abnormality within the vascular smooth muscle.


Asunto(s)
Arginina Vasopresina/farmacología , Arteria Hepática/efectos de los fármacos , Cirrosis Hepática/fisiopatología , Serotonina/farmacología , Vasoconstricción , Vasoconstrictores/farmacología , Femenino , Arteria Hepática/fisiopatología , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Preservación de Órganos , Receptores de Vasopresinas/efectos de los fármacos , Receptores de Vasopresinas/fisiología
14.
Endocr Res ; 26(4): 603-8, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11196436

RESUMEN

Primary cultures of bovine ZF cells were incubated for 1 h or 6h with the agonists 8-bromo-cyclic AMP (8-Br-cAMP) an activator of protein kinase A (PKA), the phorbol ester phorbol 12-myristate 13-acetate (PMA) a protein kinase C (PKC) activator, the Ca2+ ionophore, A23187, or the L-type Ca2+ channel agonist Bay K8644. Both cortisol secretion (determined by radioimmunoassay of cell medium) and cellular StAR protein levels (quantified by western blotting) were significantly increased at 6h, by all agonists. However, while all agonists stimulated cortisol secretion at 1h, StAR protein levels remained unchanged by these treatments. We conclude that in bovine ZF cells, StAR protein synthesis can be regulated by mechanisms involving activation of PKA, PKC and Ca2+ influx. However, a net increase in cellular StAR protein does not appear to be essential for the initiation for the first stage of acute steroidogenesis.


Asunto(s)
Hidrocortisona/metabolismo , Fosfoproteínas/metabolismo , Zona Fascicular/metabolismo , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Animales , Calcimicina/farmacología , Agonistas de los Canales de Calcio/farmacología , Bovinos , Células Cultivadas , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Activación Enzimática/fisiología , Ionóforos/farmacología , Acetato de Tetradecanoilforbol/farmacología , Zona Fascicular/citología , Zona Fascicular/efectos de los fármacos
15.
Endocr Res ; 26(4): 705-9, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11196446

RESUMEN

We have studied the effects of inhibitors of arachidonic acid (AA) metabolism, nordihydroguaiaretic acid (NDGA), a lipoxygenase (LPX) inhibitor, and indomethacin (INDO), a cyclooxygenase (COX) inhibitor, on cortisol secretion and StAR protein in primary cultures of bovine adrenal zona fasciculata (ZF) cells. NDGA inhibited cortisol secretion in response to both 10(-12) M and 10(-8) M ACTH. AA (10(-4) M) partially reversed the inhibition of cortisol secretion by NDGA at 10(-12) M ACTH but not at 10(-8) M ACTH. On the other hand, INDO potentiated the cortisol response to 10(-12) M ACTH. Neither NDGA nor INDO significantly affected StAR protein levels. These results suggest a StAR protein-independent role for the LPX and COX pathways in acute cortisol secretion, and support the hypothesis that LPX products of AA metabolism are key cellular signals when bovine ZF cells are acutely stimulated by physiological concentrations of ACTH (10(-12) M).


Asunto(s)
Hormona Adrenocorticotrópica/farmacología , Ácido Araquidónico/metabolismo , Hidrocortisona/metabolismo , Zona Fascicular/metabolismo , Animales , Bovinos , Células Cultivadas , Inhibidores de la Ciclooxigenasa/farmacología , Hidrocortisona/antagonistas & inhibidores , Hidrocortisona/biosíntesis , Indometacina/farmacología , Inhibidores de la Lipooxigenasa/farmacología , Masoprocol/farmacología , Fosfoproteínas/metabolismo , Zona Fascicular/citología , Zona Fascicular/efectos de los fármacos
16.
Endocr Res ; 26(4): 737-45, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11196450

RESUMEN

Immunohistochemistry using a StAR peptide antiserum had previously revealed strong staining in rat and bovine adrenal medulla, suggesting the presence of a protein immunogenically related to StAR. Western blots of bovine medulla tissue homogenates showed the principal adrenal medullary immuno-reactive species to have a higher molecular weight (50 kDa) compared to StAR protein (30 kDa). Subcellular fractionation localised the 50 kDa species principally to the medulla cytosol. StAR peptide antiserum binding to both the 30 kDa and 50 kDa species could be specifically competed by the peptide antigen. These data suggest that the adrenal medullary immuno-reactive species and StAR protein are distinct entities, which share some features in common.


Asunto(s)
Médula Suprarrenal/metabolismo , Fosfoproteínas/metabolismo , Proteínas/metabolismo , Animales , Bovinos , Citosol/metabolismo , Sueros Inmunes , Inmunohistoquímica/métodos , Peso Molecular , Fosfoproteínas/química , Proteínas/química , Distribución Tisular
17.
J Cell Biol ; 146(1): 13-28, 1999 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-10402457

RESUMEN

We have characterized the Drosophila mitotic checkpoint control protein Bub1 and obtained mutations in the bub1 gene. Drosophila Bub1 localizes strongly to the centromere/kinetochore of mitotic and meiotic chromosomes that have not yet reached the metaphase plate. Animals homozygous for P-element-induced, near-null mutations of bub1 die during late larval/pupal stages due to severe mitotic abnormalities indicative of a bypass of checkpoint function. These abnormalities include accelerated exit from metaphase and chromosome missegregation and fragmentation. Chromosome fragmentation possibly leads to the significantly elevated levels of apoptosis seen in mutants. We have also investigated the relationship between Bub1 and other kinetochore components. We show that Bub1 kinase activity is not required for phosphorylation of 3F3/2 epitopes at prophase/prometaphase, but is needed for 3F3/2 dephosphorylation at metaphase. Neither 3F3/2 dephosphorylation nor loss of Bub1 from the kinetochore is a prerequisite for anaphase entry. Bub1's localization to the kinetochore does not depend on the products of the genes zw10, rod, polo, or fizzy, indicating that the kinetochore is constructed from several independent subassemblies.


Asunto(s)
Apoptosis , Ciclo Celular , Segregación Cromosómica , Drosophila melanogaster/citología , Mutación , Proteínas Quinasas/metabolismo , Huso Acromático/fisiología , Animales , Encéfalo/citología , Encéfalo/embriología , Clonación Molecular , Drosophila melanogaster/embriología , Drosophila melanogaster/enzimología , Drosophila melanogaster/genética , Epítopos/inmunología , Epítopos/metabolismo , Genes Esenciales/genética , Genes de Insecto/genética , Genes de Insecto/fisiología , Cinetocoros/inmunología , Cinetocoros/metabolismo , Masculino , Meiosis , Mitosis , Datos de Secuencia Molecular , Mutagénesis Insercional , Neuronas/citología , Neuronas/metabolismo , Fosforilación , Proteínas Quinasas/química , Proteínas Quinasas/genética , Proteínas Serina-Treonina Quinasas , Espermatogénesis
18.
Am J Hypertens ; 12(2 Pt 1): 115-9, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10090337

RESUMEN

In essential hypertension, abnormal platelet function may induce vasospasm and predispose to thrombotic vascular occlusion. We studied in vitro aggregability in platelets from young men with contrasting predisposition to hypertension, defined by their own blood pressure and blood pressures of their parents. Among offspring of parents with low blood pressure, higher blood pressure was associated with impaired aggregation in response to epinephrine (2 x 10(-8) to 5 x 10(-6) mol/L), which was unaffected by endothelin-1 (10(-9) mol/L). By contrast, among offspring of parents with high blood pressure, higher blood pressure was associated with normal aggregation to epinephrine and potentiation of the primary phase of aggregation by endothelin-1. We conclude that enhanced platelet sensitivity to endothelin-1 appears to be a feature of the familial predisposition to hypertension, rather than a nonspecific consequence of high blood pressure.


Asunto(s)
Presión Sanguínea , Predisposición Genética a la Enfermedad/sangre , Hipertensión/sangre , Agregación Plaquetaria/fisiología , Adolescente , Adulto , Plaquetas/efectos de los fármacos , Causalidad , Endotelina-1/farmacología , Epinefrina/farmacología , Estudios de Seguimiento , Predisposición Genética a la Enfermedad/fisiopatología , Humanos , Hipertensión/genética , Hipertensión/fisiopatología , Masculino , Agregación Plaquetaria/efectos de los fármacos , Estudios Retrospectivos , Vasoconstrictores/farmacología
19.
Platelets ; 10(5): 298-305, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-16801106

RESUMEN

The effect of pure flavonoids and Gingko biloba extract (GBE) on human platelet aggregation was investigated. Most of the flavonoids and vitamin E did not affect platelet aggregation in platelet-rich plasma (PRP); however some of these flavonoids inhibited platelet aggregation in gel-filtered platelets (GFP). GBE inhibited both ADP- and collagen-induced platelet aggregation in PRP, GFP and in whole blood in a dose-dependent manner. GBE at very low concentrations inhibited whole blood aggregation induced by ADP compared with those used for PRP or GFP. Flavonoids and GBE decreased the production of TxA(2) induced by collagen and ADP in PRP. However, no correlation was observed between the inhibition of platelet aggregation and the decrease of TxA(2) synthesis. GBE and flavonoids did not affect platelet membrane fluidity. However, the incubation of PRP with GBE increased cAMP levels in platelets, which is known to inhibit platelet activation by lowering intracellular Ca2+ levels. GBE is a mixture of many compounds, including flavonoids and gingkoglides, which affect metabolism of cAMP, TxA(2) and Ca2+ in platelets. It is effective in the inhibition of platelet aggregation, both in PRP and whole blood, and thus may be potentially used as an effective oral anti-platelet therapeutic agent.

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