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1.
Conserv Biol ; 35(5): 1437-1450, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33543510

RESUMEN

Recovery and conservation of threatened species require adequate institutional responses. We tested an approach to systematically identify and measure how an institutional framework acknowledges threats and required responses for the recovery of endangered species. We measured institutional functional fit with a drivers-pressure-state-impacts-response (DPSIR) model integrated with a quantitative text mining method and qualitative analysis of statutory instruments to examine regulatory responses that support the recovery of 2 endangered species native to Australia, the bridled nailtail wallaby (Onychogalea fraenata) and the Eastern Bristlebird (Dasyornis brachypterus). The key components of the DPSIR model were present in the institutional framework at statutory and operational levels, but some institutional gaps remained in the protection and recovery of the Eastern Bristlebird, including feral predator control, weed control, and grazing management in some locations. However, regulatory frameworks varied in their geographic scope and the application and implementation of many instruments remained optional. Quantitative text mining can be used to quickly navigate a large volume of regulatory documents, but challenges remain in selection of terms, queries of co-occurrence, and interpretation of word frequency counts. To inform policy, we recommend that quantitative assessments of institutional fit be complemented with qualitative analysis and interpreted in light of the sociopolitical and institutional context.


La recuperación y la conservación de las especies amenazadas requieren de respuestas institucionales adecuadas. Evaluamos una estrategia para identificar y medir sistemáticamente cómo un marco de trabajo reconoce las amenazas y las respuestas requeridas para la recuperación de las especies en peligro. Medimos la aptitud funcional institucional mediante un modelo de fuerzas motrices-presión-estado-impacto-respuesta (DPSIR) integrado con un método cuantitativo de extracción de textos y un análisis cualitativo de los instrumentos legales para examinar las respuestas regulatorias que apoyan a la recuperación de dos especies en peligro nativas de Australia: Onychogalea fraenata y Dasyornis brachypterus. Los componentes clave del modelo DPSIR estuvieron presentes en el marco de trabajo institucional a niveles legales y operativos, pero algunos vacíos institucionales permanecieron en la protección y recuperación de D. brachypterus, incluyendo el control de depredadores ferales, el control de malezas y el manejo del pastoreo en algunas localidades. Sin embargo, los marcos de trabajo regulatorios variaron en cuanto a su enfoque geográfico y la aplicación e implementación de muchos de los instrumentos siguieron siendo opcionales. La extracción cuantitativa de textos puede usarse para navegar rápidamente un gran volumen de documentación regulatoria, pero todavía existen obstáculos en la selección de términos, consultas sobre la coocurrencia e interpretación de los conteos de frecuencia de palabras. Para orientar a las políticas recomendamos que las evaluaciones cuantitativas de la aptitud institucional estén complementadas con análisis cuantitativos e interpretadas a la luz del contexto institucional y sociopolítico.


Asunto(s)
Conservación de los Recursos Naturales , Especies en Peligro de Extinción , Animales , Australia
2.
Conserv Biol ; 34(3): 733-742, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31943349

RESUMEN

Attempts to better understand the social context in which conservation and environmental decisions are made has led to increased interest in human social networks. To improve the use of social-network analysis in conservation, we reviewed recent studies in the literature in which such methods were applied. In our review, we looked for problems in research design and analysis that limit the utility of network analysis. Nineteen of 55 articles published from January 2016 to June 2019 exhibited at least 1 of the following problems: application of analytical methods inadequate or sensitive to incomplete network data; application of statistical approaches that ignore dependency in the network; or lack of connection between the theoretical base, research question, and choice of analytical techniques. By drawing attention to these specific areas of concern and highlighting research frontiers and challenges, including causality, network dynamics, and new approaches, we responded to calls for increasing the rigorous application of social science in conservation.


Consideraciones y Retos Importantes en la Aplicación de la Investigación por medio de Redes Sociales para la Toma de Decisiones Ambientales Resumen Los intentos por tener un mejor entendimiento del contexto social en el que se toman las decisiones ambientales y de conservación han derivado en un incremento en el interés por las redes sociales humanas. Para mejorar el uso del análisis de redes sociales en la conservación, buscamos en la literatura los estudios recientes que hayan aplicado dichos métodos y los sometimos a una revisión. En esta revisión, examinamos los problemas en el diseño de la investigación y del análisis que limitan la utilidad del análisis de redes. Diecinueve de los 55 artículos publicados entre enero 2016 y junio 2019 exhibieron al menos uno de los siguientes problemas: aplicación de métodos analíticos inadecuados o sensibles a la información incompleta sobre las redes; aplicación de estrategias estadísticas que ignoran la dependencia en la red; o falta de conexión entre la base teórica, la pregunta de investigación y la selección de técnica analítica. Al llamar la atención hacia estas áreas específicas de interés y resaltar las fronteras y retos de la investigación, incluyendo la causalidad, las dinámicas de redes y las estrategias nuevas, respondimos a la necesidad de incrementar la aplicación rigurosa de las ciencias sociales en la conservación.


Asunto(s)
Conservación de los Recursos Naturales , Ciencias Sociales , Toma de Decisiones , Humanos , Organizaciones , Medio Social
3.
Biochemistry (Mosc) ; 80(10): 1354-61, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26567580

RESUMEN

Legumin and vicilin are two-domain seed storage globulins similar in primary and higher order structures of their domains to single-domain plant germins as well as to the domains of two-domain and single-domain bacterial oxalate decarboxylases. Independent evolutionary pathways have been shown for the descent of the storage globulins and germins from two-domain and single-domain bacterial oxalate decarboxylases, respectively. As compared to vicilins, the primary and tertiary structures of legumins were found to most closely reflect the ancient features characteristic of a common precursor of storage globulins. During the evolution of the storage globulins, a mechanism specifically controlling their degradation has been formed. We found that limited proteolysis of soybean legumin and kidney bean vicilin in germinating seeds and in vitro leads to their regular changes, which initiate an extensive cleavage of storage globulin molecules by the one-by-one mechanism. As also shown, limited proteolysis of soybean legumin loosens the intersubunit interactions in its oligomeric molecule. Based on these data, we hypothesize that the deep one-by-one degradation of soybean legumin is triggered by its dissociation, which bares peptide bonds potentially susceptible to proteolytic attack but are masked in the oligomer.


Asunto(s)
Proteínas de Plantas/metabolismo , Proteínas de Almacenamiento de Semillas/metabolismo , Semillas/metabolismo , Secuencia de Aminoácidos , Biología Computacional , Evolución Molecular , Germinación , Modelos Moleculares , Datos de Secuencia Molecular , Proteínas de Plantas/química , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Proteolisis , Proteínas de Almacenamiento de Semillas/química , Semillas/crecimiento & desarrollo , Leguminas
4.
J Laryngol Otol ; 137(3): 270-272, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35346410

RESUMEN

OBJECTIVE: Nasal obstruction and congestion can occur because of turbinate and septal variations with or without rhinitis. A combined treatment for nasal obstruction and congestion was examined retrospectively in cases where the nasal swell body was addressed with inferior turbinectomy, with or without posterior nasal nerve ablation. METHODS: A 940 nm laser was utilised for contact (nasal swell body, septum and inferior turbinate) and non-contact (posterior nasal nerve) ablation. Total Nasal Symptoms Score, visual analogue scale pain score, complications and procedure location (office vs operating theatre) were recorded. RESULTS: All 242 patients underwent nasal swell body reduction with inferior turbinate reduction, and 150 had posterior nasal nerve ablation also. No laser complications were observed. An 80 per cent reduction in medication usage was noted. Total Nasal Symptoms Score decreased by 73 per cent; rhinorrhoea and congestion scores decreased by 54 per cent and 81 per cent respectively. Crusting, epistaxis and infections were minimal, and resolved within two weeks. CONCLUSION: Nasal swell body with inferior turbinate reduction, with or without posterior nasal nerve ablation, is a new method of treating nasal obstruction and congestion. Laser posterior nasal nerve ablation can be utilised as a complementary tool to deliver anatomical obstruction relief.


Asunto(s)
Técnicas de Ablación , Obstrucción Nasal , Procedimientos Quírurgicos Nasales , Rinitis , Humanos , Hipertrofia/cirugía , Obstrucción Nasal/cirugía , Obstrucción Nasal/complicaciones , Estudios Retrospectivos , Rinitis/complicaciones , Rinitis/cirugía , Resultado del Tratamiento , Cornetes Nasales/patología , Cornetes Nasales/cirugía , Procedimientos Quírurgicos Nasales/métodos
5.
Ecol Appl ; 20(6): 1721-32, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20945770

RESUMEN

Alternative land uses make different contributions to the conservation of biodiversity and have different implementation and management costs. Conservation planning analyses to date have generally assumed that land is either protected or unprotected, and that the unprotected portion does not contribute to conservation goals. We develop and apply a new planning approach that explicitly accounts for the contribution of a diverse range of land uses to achieving conservation goals. Using East Kalimantan (Indonesian Borneo) as a case study, we prioritize investments in alternative conservation strategies and account for the relative contribution of land uses ranging from production forest to well-managed protected areas. We employ data on the distribution of mammals and assign species-specific conservation targets to achieve equitable protection by accounting for life history characteristics and home range sizes. The relative sensitivity of each species to forest degradation determines the contribution of each land use to achieving targets. We compare the cost effectiveness of our approach to a plan that considers only the contribution of protected areas to biodiversity conservation, and to a plan that assumes that the cost of conservation is represented by only the opportunity costs of conservation to the timber industry. Our preliminary results will require further development and substantial stakeholder engagement prior to implementation; nonetheless we reveal that, by accounting for the contribution of unprotected land, we can obtain more refined estimates of the costs of conservation. Using traditional planning approaches would overestimate the cost of achieving the conservation targets by an order of magnitude. Our approach reveals not only where to invest, but which strategies to invest in, in order to effectively and efficiently conserve biodiversity.


Asunto(s)
Agricultura , Biodiversidad , Conservación de los Recursos Naturales , Vivienda , Borneo , Humanos , Árboles
6.
Conserv Biol ; 23(4): 834-40, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19627315

RESUMEN

Oceania is a diverse region encompassing Australia, Melanesia, Micronesia, New Zealand, and Polynesia, and it contains six of the world's 39 hotspots of diversity. It has a poor record for extinctions, particularly for birds on islands and mammals. Major causes include habitat loss and degradation, invasive species, and overexploitation. We identified six major threatening processes (habitat loss and degradation, invasive species, climate change, overexploitation, pollution, and disease) based on a comprehensive review of the literature and for each developed a set of conservation policies. Many policies reflect the urgent need to deal with the effects of burgeoning human populations (expected to increase significantly in the region) on biodiversity. There is considerable difference in resources for conservation, including people and available scientific information, which are heavily biased toward more developed countries in Oceania. Most scientific publications analyzed for four threats (habitat loss, invasive species, overexploitation, and pollution) are from developed countries: 88.6% of Web of Science publications were from Australia (53.7%), New Zealand (24.3%), and Hawaiian Islands (10.5%). Many island states have limited resources or expertise. Even countries that do (e.g., Australia, New Zealand) have ongoing and emerging significant challenges, particularly with the interactive effects of climate change. Oceania will require the implementation of effective policies for conservation if the region's poor record on extinctions is not to continue.


Asunto(s)
Biodiversidad , Conservación de los Recursos Naturales , Ambiente , Animales , Contaminación Ambiental , Humanos , Oceanía
7.
Nat Commun ; 7: 11042, 2016 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-27025894

RESUMEN

The high incidence of armed conflicts in biodiverse regions poses significant challenges in achieving international conservation targets. Because attitudes towards risk vary, we assessed different strategies for protected area planning that reflected alternative attitudes towards the risk of armed conflicts. We find that ignoring conflict risk will deliver the lowest return on investment. Opting to completely avoid conflict-prone areas offers limited improvements and could lead to species receiving no protection. Accounting for conflict by protecting additional areas to offset the impacts of armed conflicts would not only increase the return on investment (an effect that is enhanced when high-risk areas are excluded) but also increase upfront conservation costs. Our results also demonstrate that fine-scale estimations of conflict risk could enhance the cost-effectiveness of investments. We conclude that achieving biodiversity targets in volatile regions will require greater initial investment and benefit from fine-resolution estimates of conflict risk.


Asunto(s)
Conflictos Armados , Actitud , Conservación de los Recursos Naturales , Biodiversidad , Factores de Riesgo , Incertidumbre
8.
Biochim Biophys Acta ; 1545(1-2): 192-206, 2001 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-11342045

RESUMEN

The protease that degrades the beta subunit of the soybean (Glycine max (L.) Merrill) storage protein beta-conglycinin was purified from the cotyledons of seedlings grown for 12 days. The enzyme was named protease C2 because it is the second enzyme to cleave the beta-conglycinin storage protein, the first (protease C1) being one that degrades only the alpha' and alpha subunits of the storage protein to products similar in size and sequence to the remaining intact beta subunit. Protease C2 activity is not evident in vivo until 4 days after imbibition of the seed. The 31 kDa enzyme is a cysteine protease with a pH optimum with beta-conglycinin as substrate of 5.5. The action of protease C2 on native beta-conglycinin produces a set of large fragments (52-46 kDa in size) and small fragments (29-25 kDa). This is consistent with cleavage of all beta-conglycinin subunits at the region linking their N- and C-domains. Protease C2 also cleaves phaseolin, the Phaseolus vulgaris vicilin homologous to beta-conglycinin, to fragments in the 25-28 kDa range. N-Terminal sequences of isolated beta-conglycinin and phaseolin products show that protease C2 cleaves at a bond within a very mobile surface loop connecting the two compact structural domains of each subunit. The protease C2 cleavage specificity appears to be dictated by the substrate's three-dimensional structure rather than a specificity for a particular amino acid or sequence.


Asunto(s)
Cisteína Endopeptidasas/metabolismo , Globulinas/metabolismo , Glycine max/enzimología , Proteínas de Plantas , Proteínas de Soja/metabolismo , Secuencia de Aminoácidos , Antígenos de Plantas , Cisteína Endopeptidasas/aislamiento & purificación , Datos de Secuencia Molecular , Fragmentos de Péptidos/metabolismo , Inhibidores de Proteasas/farmacología , Conformación Proteica , Proteínas de Almacenamiento de Semillas , Semillas , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Proteínas de Soja/química , Especificidad por Sustrato
9.
Lab Chip ; 15(16): 3397-404, 2015 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-26167949

RESUMEN

The dose-dependent bioactivity of small molecules on cells is a crucial factor in drug discovery and personalized medicine. Although small-molecule microarrays are a promising platform for miniaturized screening, it has been a challenge to use them to obtain quantitative dose-response curves in vitro, especially for lipophilic compounds. Here we establish a small-molecule microarray assay capable of controlling the dosage of small lipophilic molecules delivered to cells by varying the sub-cellular volumes of surface supported lipid micro- and nanostructure arrays fabricated with nanointaglio. Features with sub-cellular lateral dimensions were found necessary to obtain normal cell adhesion with HeLa cells. The volumes of the lipophilic drug-containing nanostructures were determined using a fluorescence microscope calibrated by atomic-force microscopy. We used the surface supported lipid volume information to obtain EC-50 values for the response of HeLa cells to three FDA-approved lipophilic anticancer drugs, docetaxel, imiquimod and triethylenemelamine, which were found to be significantly different from neat lipid controls. No significant toxicity was observed on the control cells surrounding the drug/lipid patterns, indicating lack of interference or leakage from the arrays. Comparison of the microarray data to dose-response curves for the same drugs delivered liposomally from solution revealed quantitative differences in the efficacy values, which we explain in terms of cell-adhesion playing a more important role in the surface-based assay. The assay should be scalable to a density of at least 10,000 dose response curves on the area of a standard microtiter plate.


Asunto(s)
Antineoplásicos/química , Liposomas/química , Análisis por Micromatrices , Aminoquinolinas/química , Aminoquinolinas/toxicidad , Antineoplásicos/toxicidad , Adhesión Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Docetaxel , Descubrimiento de Drogas , Células HeLa , Humanos , Imiquimod , Microscopía de Fuerza Atómica , Microscopía Fluorescente , Nanoestructuras/química , Medicina de Precisión , Taxoides/química , Taxoides/toxicidad , Trietilenomelamina/química , Trietilenomelamina/toxicidad
10.
Protein Sci ; 7(7): 1612-9, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9684894

RESUMEN

We present a novel protein crystallization strategy, applied to the crystallization of human T cell leukemia virus type 1 (HTLV-1) transmembrane protein gp21 lacking the fusion peptide and the transmembrane domain, as a chimera with the Escherichia coli maltose binding protein (MBP). Crystals could not be obtained with a MBP/gp21 fusion protein in which fusion partners were separated by a flexible linker, but were obtained after connecting the MBP C-terminal alpha-helix to the predicted N-terminal alpha-helical sequence of gp21 via three alanine residues. The gp21 sequences conferred a trimeric structure to the soluble fusion proteins as assessed by sedimentation equilibrium and X-ray diffraction, consistent with the trimeric structures of other retroviral transmembrane proteins. The envelope protein precursor, gp62, is likewise trimeric when expressed in mammalian cells. Our results suggest that MBP may have a general application for the crystallization of proteins containing N-terminal alpha-helical sequences.


Asunto(s)
Transportadoras de Casetes de Unión a ATP , Antígenos de Deltaretrovirus/química , Proteínas de Escherichia coli , Productos del Gen env/química , Proteínas de Transporte de Monosacáridos , Conformación Proteica , Proteínas Oncogénicas de Retroviridae/química , Secuencia de Aminoácidos , Amilosa , Proteínas Portadoras/química , Centrifugación por Gradiente de Densidad , Cromatografía en Gel , Reactivos de Enlaces Cruzados , Cristalización , Cristalografía por Rayos X , Antígenos de Deltaretrovirus/biosíntesis , Escherichia coli , Productos del Gen env/biosíntesis , Proteínas de Unión a Maltosa , Espectrometría de Masas , Datos de Secuencia Molecular , Oxidación-Reducción , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/química , Proteínas Oncogénicas de Retroviridae/biosíntesis , Productos del Gen env del Virus de la Inmunodeficiencia Humana
11.
J Immunol Methods ; 61(1): 99-106, 1983 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-6406614

RESUMEN

Radial immunodiffusion can be used to determine relative antigen-antibody avidities in exactly the same way as demonstrated previously for quantitative immunoelectrophoresis (Birkmeyer et al., 1981). Antigen-antibody interactions of greater avidity result in a greater value of (delta Area/delta [Antigen]) in plots of immunoprecipitin circle area versus antigen concentration while interactions of equal avidity will yield equal values of (delta Area/delta [Antigen]). This was demonstrated using antigens of different weight ranging from 8000 to 66,000.


Asunto(s)
Complejo Antígeno-Anticuerpo/análisis , Hemoglobina A/inmunología , Inhibidores de Tripsina/inmunología , Hemoglobina A/análisis , Sueros Inmunes , Inmunodifusión/métodos , Inmunoelectroforesis/métodos , Plantas , Inhibidores de Tripsina/análisis
12.
Br J Pharmacol ; 53(1): 59-66, 1975 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-1125492

RESUMEN

1 The energy dependence of angiotensin and acetylcholine-induced contractions of rat descending colon and uterus was investigated. 2 Differences were observed in the effect of anaerobic substrate depletion upon responses of colon and oestrous and dioestrous uterus. These were attributed to differences in the energy metabolism of the tissues and were correlated with differences in tissue levels of glycogen. 3 The preferential reduction of angiotensin responses of dioestrous uterus and descending colon when exposed to 2,4-dinitrophenol, was evidence for an energy dependent stage in the angiotensin response distinct from the contraction process itself. 4 The absence of a preferential reduction of the angiotensin response of oestrous uterus when exposed to 2,4-dinitrophenol appeared to be related to the ability of this tissue to generate ATP by anaerobic glycolysis. 5 It was concluded that the energy for the angiotensin response may be derived either anaerobically or aerobically, depending upon the tissue.


Asunto(s)
Angiotensina II/farmacología , Colon/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Útero/efectos de los fármacos , Animales , Dinitrofenoles/farmacología , Femenino , Glucosa/farmacología , Glucógeno/metabolismo , Hipoxia/metabolismo , Ratas
13.
Br J Pharmacol ; 51(1): 73-9, 1974 May.
Artículo en Inglés | MEDLINE | ID: mdl-4374288

RESUMEN

1 Acetylcholine and angiotensin elicit a contraction of guinea-pig ileum. The metabolic requirements for these actions have been investigated.2 The angiotensin-induced response was far more dependent upon the presence of glucose than was the response to acetylcholine.3 Anoxia and oxidative enzyme inhibition preferentially reduced the angiotensin-induced response.4 The significance of these results is discussed. It is concluded that the response to angiotensin is dependent upon an ATP source distinct from that required by the contractile process. It is further shown that this energy-dependent stage cannot be identified with the indirect, cholinergic component of the angiotensin response in this tissue.


Asunto(s)
Angiotensina II/farmacología , Íleon/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Acetilcolina/farmacología , Adenosina Trifosfato/metabolismo , Angiotensina II/metabolismo , Animales , Monóxido de Carbono/farmacología , Estimulación Eléctrica , Metabolismo Energético , Glucosa/metabolismo , Glucosa/farmacología , Cobayas , Histamina/farmacología , Íleon/metabolismo , Técnicas In Vitro , Masculino , Manitol/farmacología , Músculo Liso/metabolismo , Nitrógeno/farmacología , Oxígeno/farmacología , Escopolamina/farmacología , Factores de Tiempo
14.
Br J Pharmacol ; 67(4): 527-33, 1979 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-519106

RESUMEN

1. The effect of the prostaglandin synthesis inhibitors aspirin and indomethacin (Ind) was investigated upon contractions of the perfused isolated terminal ileum of the rat to bradykinin (Bk) or potassium chloride (KCl). The release of a prostaglandin-like substance (PGLS) from the ileum was simultaneously assayed on the rat fundus strip (RFS). 2. Aspirin (610 micro M) or Ind (28 micro M) reduced contractions of the ileum to Bk perfused over the mucosal surface but not to Bk perfused over the serosal surface. 3. After perfusion of either ileal surface the effluent potentiated the contractions of the RFS to Bk. No potentiation was observed in the presence of either Ind or aspirin. 4. Contractions of the RFS to Bk were potentiated by prostaglandin E2 (PGE2) (0.7 X 10(-12) M and 1.4 X 10(-12) M) but not by either a higher (2.8 x 10(-12) M) or a lower (0.35 X 10(-12) M) concentration of PGE2. No potentiation was observed with prostaglandin F2 alpha (PGF2 alpha) at the concentrations studied. 5. Only the contractile action of Bk acting on the mucosal surface of the rat isolated perfused ileum seems to involve prostaglandin synthesis.


Asunto(s)
Bradiquinina/farmacología , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Prostaglandinas/fisiología , Animales , Aspirina/farmacología , Íleon/efectos de los fármacos , Técnicas In Vitro , Indometacina/farmacología , Masculino , Cloruro de Potasio/farmacología , Prostaglandinas E/farmacología , Prostaglandinas F/farmacología , Ratas
15.
Br J Pharmacol ; 80(2): 315-22, 1983 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-6140057

RESUMEN

alpha-Adrenoceptor antagonists have been compared for their effects on dose-response curves of fast and slow components of contraction of the rat aorta to noradrenaline (NA). All agents caused a competitive antagonism of the slow component of contraction to NA. The order of potency was: prazosin greater than WB4101 = doxazosin greater than tiodazosin greater than phentolamine greater than corynanthine greater than trimazosin greater than rauwolscine. For the fast component, doxazosin, prazosin, tiodazosin and WB4101 caused some depression of the maximum response. Doxazosin (25 nM) and prazosin (25 nM) produced a complete and unsurmountable antagonism of the maximum fast component. Phentolamine, corynanthine, trimazosin and rauwolscine all competitively antagonized the fast component. The degree of antagonism of the fast component by prazosin and its analogues appeared to be directly related to the potency of individual agents for the slow component. WB4101, which was equipotent with doxazosin and more potent than tiodazosin was less effective than either in reducing the fast component. The antagonism of the fast component by prazosin or doxazosin was easily reversed by washing and prevented by phentolamine (2.5 microM). Neither prazosin nor doxazosin in concentrations of up to 2.5 microM has any effect on contractions of the aorta to 5-hydroxytryptamine (5-HT, 0.25-250 microM) or caffeine (20mM). It is concluded that the ability of some alpha-adrenoceptor antagonists to produce a non-competitive antagonism of the fast component of contraction is (a) dependent upon blockade of alpha-adrenoceptors; (b) unrelated to selectivity for alpha 1-adrenoceptors; (c) related to potency and structure. 8 EGTA (3.0 mM) caused a selective suppression of the slow component of contraction to NA. Both doxazosin and prazosin caused a non-competitive antagonism of EGTA-resistant contractions to NA whereas corynanthine showed competitive antagonism. These observations, together with those above imply that prazosin and doxazosin non-competitively antagonize alpha-adrenoceptorinduced release of calcium in the rat aorta, but competitively antagonize alpha-adrenoceptor-induced calcium entry.


Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Prazosina/farmacología , Quinazolinas/farmacología , Vasoconstricción/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Aorta/efectos de los fármacos , Calcio/fisiología , Relación Dosis-Respuesta a Droga , Doxazosina , Técnicas In Vitro , Masculino , Norepinefrina/farmacología , Prazosina/análogos & derivados , Ratas , Ratas Endogámicas
16.
Br J Pharmacol ; 92(2): 381-8, 1987 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-3676600

RESUMEN

1 The influence of the epithelium on contractions produced by the peptidoleukotrienes, 5-hydroxytryptamine (5-HT) and the thromboxane mimetic, U-44069, was examined in trachea from control and ovalbumin-sensitized guinea-pigs. 2 In control tissues removal of the epithelium produced an approximately 2 to 4 fold leftward shift in leukotriene C4 (LTC4) and LTD4 concentration-response curves, but no effect on LTE4-induced contractions. Similar results were obtained in preparations from ovalbumin-sensitized animals. 3 Responses produced by 5-HT or U-44069 were similar in the presence and absence of the epithelium in control guinea-pigs. 4 Indomethacin produced contrasting effects on leukotriene-induced contractions in control guinea-pigs: an increase in sensitivity to LTC4 in the presence but not absence of the epithelium, no effect on LTD4-induced contractions and a decrease in sensitivity to LTE4 in both epithelium-containing and epithelium-free preparations. 5 These results indicate that there is selectivity in the effects of epithelium removal on agonist-induced contractions of the guinea-pig trachea. This provides further evidence for the modulatory influence of the epithelium on the reactivity of mammalian airway smooth muscle and supports the postulated existence of an epithelium-derived inhibitory factor. The observation that in intact trachea indomethacin mimics the effects of epithelium removal on LTC4-induced responses, suggests the involvement of a prostanoid(s) in this phenomenon.


Asunto(s)
Bronquios/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Animales , Asma/fisiopatología , Bronquios/patología , Epitelio/fisiología , Cobayas , Técnicas In Vitro , Indometacina/farmacología , Masculino , Contracción Muscular/efectos de los fármacos , Endoperóxidos de Prostaglandinas Sintéticos/farmacología , SRS-A/farmacología , Serotonina/farmacología , Tráquea/efectos de los fármacos
17.
Eur J Pharmacol ; 98(2): 249-53, 1984 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-6714306

RESUMEN

Strychnine (10(-5)-3 x 10(-4) M) increased the amplitude and duration of the spontaneous electrical and mechanical activity of the rat isolated portal vein. Similar effects were seen with tetraethylammonium and 4-aminopyridine. This stimulant action of strychnine was unaffected by tetrodotoxin (3 x 10(-7) M) or prazosin (5 x 10(-8) M) but was significantly reduced by verapamil (3 x 10(-8) M). On the isolated aorta, only inhibitory actions of strychnine were observed, yet tetraethylammonium and 4-aminopyridine had excitatory actions. It is suggested that the stimulant actions of strychnine on the portal vein are likely to be due to a reduction in potassium conductance and/or an increase in calcium conductance of the smooth muscle cell membrane.


Asunto(s)
Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Estricnina/farmacología , 4-Aminopiridina , Aminopiridinas/farmacología , Animales , Aorta Torácica , Fármacos Cardiovasculares/farmacología , Masculino , Vena Porta , Prazosina/farmacología , Ratas , Ratas Endogámicas , Tetraetilamonio , Compuestos de Tetraetilamonio/farmacología , Tetrodotoxina/farmacología , Verapamilo/farmacología
18.
Eur J Pharmacol ; 60(2-3): 121-9, 1979 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-230977

RESUMEN

The effect of procedures which affect calcium availability and tissue levels of cyclic AMP were investigated upon the contractions of rat colon to angiotensin II, PGE2 and KCl. Calcium free Tyrode containing EDTA (25 microM) reduced the response to angiotensin more than to PGE2 and KCl. An increase in calcium concentration to 3.6 mM potentiated responses to angiotensin and KCl. A further increase to either 7.2 mM or 10.8 mM still potentiated responses to angiotensin but those to KCl wre reduced. SKF 525A (2.6 x 10(-5) M) and verapamil (3.5 x 10(-6) M) inhibited the responses to KCl but the responses to PGE2 and angiotensin were less affected. Isoprenaline, Theophylline and dibutyryl cyclic AMP preferentially reduced the responses to angiotensin and PGE2. It is suggested that part of the response to angiotensin involves an influx of calcium, independent of depolarisation.


Asunto(s)
Angiotensina II/farmacología , Calcio/fisiología , AMP Cíclico/fisiología , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Animales , Bucladesina/farmacología , Colon/efectos de los fármacos , Imidazoles/farmacología , Técnicas In Vitro , Isoproterenol/farmacología , Masculino , Proadifeno/farmacología , Ratas , Teofilina/farmacología , Factores de Tiempo , Verapamilo/farmacología
19.
Eur J Pharmacol ; 126(3): 323-7, 1986 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-3093250

RESUMEN

In the presence of l-serine borate, salbutamol was much more effective in reversing rather than preventing LTC4-induced contractions of guinea-pig trachea. This suggests that different mechanisms are involved in initiating versus maintaining LTC4-induced contractions. In addition, the ability of salbutamol pretreatment to prevent LTC4-induced contractions was reduced substantially in the presence of l-serine borate, suggesting that the metabolites of LTC4 (LTD4 and LTE4) are more sensitive to inhibition by beta-adrenoceptor agonists than is LTC4 itself.


Asunto(s)
Albuterol/farmacología , Boratos/farmacología , SRS-A/antagonistas & inhibidores , Serina/farmacología , Tráquea/efectos de los fármacos , Animales , Cobayas , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , SRS-A/farmacología , Tráquea/fisiología
20.
Eur J Pharmacol ; 136(2): 247-50, 1987 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-3595724

RESUMEN

Using a novel preparation of guinea-pig trachea, direct evidence was obtained for the release of an epithelium-derived inhibitory factor modulating contractions elicited by antigen. Thus, epithelium removal produced a 6.1-fold leftward shift in ovalbumin concentration-response curves in tracheal strips from ovalbumin-sensitized guinea-pigs. This increase in sensitivity to ovalbumin was not evident when a tracheal portion containing epithelium was positioned in close proximity to the tissue from which tension was recorded.


Asunto(s)
Tráquea/metabolismo , Resistencia de las Vías Respiratorias , Animales , Epitelio/metabolismo , Epitelio/fisiología , Cobayas , Técnicas In Vitro , Masculino , Ovalbúmina/inmunología , Hipersensibilidad Respiratoria/fisiopatología , Tráquea/fisiopatología
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