RESUMEN
There has been little information about the proteome of bovine faeces or about the contribution to the faecal proteome of proteins from the host, the feed or the intestinal microbiome. Here, the bovine faecal proteome and the origin of its component proteins was assessed, while also determining the effect of treating barley, the major carbohydrate in the feed, with either ammonia (ATB) or sodium propionate (PTB) preservative. Healthy continental crossbreed steers were allocated to two groups and fed on either of the barley-based diets. Five faecal samples from each group were collected on Day 81 of the trial and analysed by quantitative proteomics using nLC-ESI-MS/MS after tandem mass tag labelling. In total, 281 bovine proteins, 199 barley proteins, 176 bacterial proteins and 190 archaeal proteins were identified in the faeces. Mucosal pentraxin, albumin and digestive enzymes were among bovine proteins identified. Serpin Z4 a protease inhibitor was the most abundant barley protein identified which is also found in barley-based beer, while numerous microbial proteins were identified, many originating bacteria from Clostridium, while Methanobrevibacter was the dominant archaeal genus. Thirty-nine proteins were differentially abundant between groups, the majority being more abundant in the PTB group compared to the ATB group. SIGNIFICANCE: Proteomic examination of faeces is becoming a valuable means to assess the health of the gastro-intestinal tract in several species, but knowledge on the proteins present in bovine faeces is limited. This investigation aimed to characterise the proteome of bovine faecal extracts in order to evaluate the potential for investigations of the proteome as a means to assess the health, disease and welfare of cattle in the future. The investigation was able to identify proteins in bovine faeces that had been (i) produced by the individual cattle, (ii) present in the barley-based feed eaten by the cattle or (iii) produced by bacteria and other microbes in the rumen or intestines. Bovine proteins identified included mucosal pentraxin, serum albumin and a variety of digestive enzymes. Barley proteins found in the faeces included serpin Z4, a protease inhibitor that is also found in beer having survived the brewing process. Bacterial and archaeal proteins in the faecal extracts were related to several pathways related to the metabolism of carbohydrates. The recognition of the range of proteins that can be identified in bovine faeces raises the possibility that non-invasive sample collection of this material could provide a novel diagnostic approach to cattle health and welfare.
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Proteínas Arqueales , Hordeum , Serpinas , Bovinos , Animales , Serpinas/análisis , Proteoma/análisis , Cerveza/análisis , Proteómica , Espectrometría de Masas en Tándem , Dieta/veterinaria , Heces/microbiología , Bacterias , Extractos Vegetales , Alimentación Animal/análisisRESUMEN
Since its discovery in 1669, phosphorus (P) in the form of fertilizer has become an essential input for many agroecosystems. By introducing a concentrated P source, fertilizers increase short-term P export potential soon after their application and longer-term export potential by increasing soil fertility (legacy P). The 4R concept was developed to help mitigate P exports from the fertilizers that sustain agricultural productivity. This review investigates the factors affecting P exports soon after the application of mineral fertilizers to pasture-based grazing systems and studies quantifying its potential impact in different systems, with an emphasis on Australasia. Initially, P fertilizers and reactions that might affect their short-term P export potential are reviewed, along with P transport pathways, the forms of P exported from grazing systems, factors affecting P mobilization into water, and studies demonstrating the possible short-term effects of fertilizer application on P exports. Using that foundation, we review studies quantifying the short-term impact of fertilizer application in different regions; they show that under poor management, recently applied fertilizer can contribute a considerable proportion (30-80%) of total farm P exports in drainage, but when fertilizer is well-managed, that figure is expected to be <10%. We then use three model systems of varying hydrology that are common to Australasia to demonstrate the principles for selecting fertilizers that are likely to minimize P exports soon after their application.
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Fertilizantes , Fósforo , Agricultura , Suelo , AguaRESUMEN
The historical build up and future cadmium (Cd) concentrations in top soils and in crops of four Australian agricultural systems are predicted with a mass balance model, focusing on the period 1900-2100. The systems include a rotation of dryland cereals, a rotation of sugarcane and peanuts/soybean, intensive dairy production and intensive horticulture. The input of Cd to soil is calculated from fertilizer application and atmospheric deposition and also examines options including biosolid and animal manure application in the sugarcane rotation and dryland cereal production systems. Cadmium output from the soil is calculated from leaching to deeper horizons and removal with the harvested crop or with livestock products. Parameter values for all Cd fluxes were based on a number of measurements on Australian soil-plant systems. In the period 1900-2000, soil Cd concentrations were predicted to increase on average between 0.21 mg kg(-1) in dryland cereals, 0.42 mg kg(-1) in intensive agriculture and 0.68 mg kg(-1) in dairy production, which are within the range of measured increases in soils in these systems. Predicted soil concentrations exceed critical soil Cd concentrations, based on food quality criteria for Cd in crops during the simulation period in clay-rich soils under dairy production and intensive horticulture. Predicted dissolved Cd concentrations in soil pore water exceed a ground water quality criterion of 2 µg l(-1) in light textured soils, except for the sugarcane rotation due to large water leaching fluxes. Results suggest that the present fertilizer Cd inputs in Australia are in excess of the long-term critical loads in heavy-textured soils for dryland cereals and that all other systems are at low risk. Calculated critical Cd/P ratios in P fertilizers vary from <50 to >1000 mg Cd kg P(-1) for the different soil, crop and environmental conditions applied.
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Agricultura/métodos , Cadmio/análisis , Fertilizantes/análisis , Contaminación de Alimentos/análisis , Modelos Químicos , Suelo/química , Calidad del Agua/normas , Australia , Fósforo/análisisRESUMEN
Surface broadcast of broiler litter to no-till row crops exposes the litter and its nutrients to risks of loss in runoff water and volatilization and may limit the potential benefit of litter to the crops. Subsurface banding of litter could alleviate these risks. A field study was conducted in 2008 and 2009 on an upland Falkner silt loam soil to determine the effect of broiler litter placement on runoff nutrient losses from no-till cotton ( L.). Treatments included surface broadcast broiler litter applied manually, subsurface-banded litter applied by tractor-drawn equipment, and no broiler litter, all in combination with or without winter wheat ( L.) cover crop residue. Broiler litter rate was 5.6 Mg ha. The experimental design was a randomized complete block with a split-plot arrangement of treatments replicated three times. In 2008, simulated rainfall was used to generate runoff 27 d after litter application. Subsurface-banded litter reduced runoff total C, N, P, NH, NO, Cu, Zn and water-soluble P (WP) concentrations by 72, 64, 51, 49, 70, 36, 65, and 77%, respectively, compared with surface broadcast. The reductions were greater in 2009 where runoff occurred 1 d after litter application. Bacterial runoff was decreased by one log with subsurface-banded litter compared to surface broadcast. Except for C, NH, N, and WP, the presence of winter cover crop residue did not affect the load or runoff nutrient concentrations in either year. The results indicate that subsurface banding litter to no-till cotton substantially reduces nutrient and bacterial losses in runoff compared with surface broadcasting.
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Fertilizantes , Estiércol , Agricultura , Animales , Pollos , Fósforo , Movimientos del AguaRESUMEN
Increasing costs associated with inorganic fertilizer have led to widespread use of broiler litter. Proper land application, typically limiting nutrient loss, is essential to protect surface water. This study was designed to evaluate litter-borne microbial runoff (heterotrophic plate count bacteria, staphylococci, Escherichia coli, enterococci, and Clostridium perfringens) while applying typical nutrient-control methods. Field studies were conducted in which plots with high and low litter rates, inorganic fertilizer, AlCl(3)-treated litter, and controls were rained on five times using a rain generator. Overall, microbial runoff from poultry litter applied plots was consistently greater (2-5 log(10) plot(-1)) than controls. No appreciable effect on microbial runoff was noted from variable litter application rate or AlCl(3) treatments, though rain event, not time, significantly affected runoff load. C. perfringens and staphylococci runoff were consistently associated with poultry litter application, during early rain events, while other indicators were unreliable. Large microbial runoff pulses were observed, ranging from 10(2) to 10(10) CFU plot(-1); however, only a small fraction of litter-borne microbes were recoverable in runoff. This study indicated that microbial runoff from litter-applied plots can be substantial, and that methods intended to reduce nutrient losses do not necessarily reduce microbial runoff.
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Compuestos de Aluminio/química , Bacterias/aislamiento & purificación , Cloruros/química , Fertilizantes/microbiología , Estiércol/microbiología , Contaminación del Agua/análisis , Cloruro de Aluminio , Animales , Pollos , Monitoreo del Ambiente , Nitrógeno/análisis , Fósforo/análisis , LluviaRESUMEN
OBJECTIVE: To describe the experiences, knowledge and views of both parents and professionals regarding the consent process for perinatal postmortem. DESIGN: Internet-based survey. SETTING: Obstetricians, midwives and perinatal pathologists currently working in the UK. Parents who have experienced a stillbirth in the UK in the previous 10 years. SAMPLE: Obstetricians, midwives and perinatal pathologists registered with their professional bodies. Parents who accessed the Sands website or online forum. METHODS: Online self-completion questionnaire with both fixed-choice and open-ended questions. RESULTS: Responses were analysed from 2256 midwives, 354 obstetricians, 21 perinatal pathologists and 460 parents. The most common reason for parents to request postmortem examination was to find a cause for their baby's death; the prevention of stillbirths in others also ranked highly. Perinatal pathologists possessed greatest knowledge of the procedure and efficacy of postmortem, but were unlikely to meet bereaved parents. The majority of professionals and parents ranked emotional distress and a lengthy wait for results as barriers to consent. The majority of staff ranked workload, negative publicity, religion and cultural issues as important barriers, whereas most parents did not. Almost twice as many parents who declined postmortem examination later regretted their decision compared with those who accepted the offer (34.4 versus 17.4%). CONCLUSION: Emotional, practical and psychosocial issues can act as real or perceived barriers for staff and bereaved parents. Education is required for midwives and obstetricians, to increase their knowledge to ensure accurate counselling, with due regard for the highly individual responses of bereaved parents. The contribution of perinatal pathologists to staff education and parental decision-making would be invaluable.
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Actitud del Personal de Salud , Autopsia , Consentimiento Informado/psicología , Padres/psicología , Aceptación de la Atención de Salud/psicología , Mortinato/psicología , Adolescente , Adulto , Aflicción , Consejo , Humanos , Persona de Mediana Edad , Partería , Obstetricia , Patología Clínica , Relaciones Profesional-Paciente , Adulto JovenRESUMEN
Surface application of broiler litter to no-till cotton could lead to degradation of water quality. Incorporation of broiler litter into the top surface soil (0.05 m) could alleviate this risk. A 2-yr field study was conducted on a silt loam upland soil to determine the effect of incorporation of broiler litter into the soil surface on nutrient and bacterial transport in runoff. The experimental design was a randomized complete block with four treatments and three replications. Treatments were (i) unfertilized control; (ii) surface-appliedbroiler litter at 7.8 Mg ha(-1) without incorporation; (iii) surface-applied broiler litter at 7.8 Mg ha(-1) with immediate incorporation; and (iv) inorganic fertilizer N (urea ammonium nitrate, 32% N) and inorganic fertilizer P (triple superphosphate) at the recommended rate. Phosphorus was surface appliedat 25 kg ha(-1) and N was injected at 101 kg ha(-1) into the soil using a commercial liquid fertilizer applicator. Runoff was collected from small runoff plots (2.4 m by 1.6 m) established at the bottom side of main plots (13.7 m by 6.0 m). Incorporation of broiler litter reduced total N (TN), NO3-N, water soluble P (WSP), and total P (TP) concentrations in runoffby 35, 25, 61, and 64%, respectively, and litter-associated bacteria by two to three orders of magnitude compared with unincorporated treatment. No significant difference in total suspended solids (TSS) in runoffwas obtained between incorporated and unincorporated treatments. Incorporation of broiler litter into the surface soil in the no-till system immediately after application minimized the potential risk for surface nutrient losses and bacteria transport in runoff.
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Agricultura/métodos , Productos Agrícolas , Gossypium/fisiología , Estiércol , Animales , Fertilizantes , Sedimentos Geológicos/química , Nitrógeno/metabolismo , Compuestos de Nitrógeno/metabolismo , Fósforo/metabolismo , Aves de Corral , Lluvia , Suelo/química , Microbiología del Suelo , Contaminantes Químicos del Agua/metabolismo , Abastecimiento de AguaRESUMEN
Water treatment residuals (WTRs) are produced by the treatment of potable water with coagulating agents. Beneficial recycling in agriculture is hampered by the fact that WTRs contain potentially toxic contaminants (e.g. copper and aluminium) and they bind phosphorus strongly. These issues were investigated using a plant bioassay (Lactuca sativa), chemical extractions and an isotopic dilution technique. Two WTRs were applied to an acidic and a neutral pH soil at six rates. Reductions in plant growth in amended soils were due to WTR-induced P deficiency, rather than Al or Cu toxicity. The release of potentially toxic Al from WTRs was found to be mitigated by their alkaline nature and pH buffering capacity. However, acidification of WTRs was shown to release more soluble Al than soil naturally high in Al. Copper availability was relatively low in all treatments. However, the lability of WTR-Cu increased when the WTR was applied to the soil.
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Aluminio/toxicidad , Cobre/toxicidad , Lactuca/efectos de los fármacos , Fósforo/toxicidad , Contaminantes del Suelo/toxicidad , Purificación del Agua/métodos , Aluminio/química , Aluminio/farmacocinética , Cobre/química , Cobre/farmacocinética , Relación Dosis-Respuesta a Droga , Monitoreo del Ambiente , Lactuca/metabolismo , Fósforo/química , Fósforo/farmacocinética , Suelo/análisis , Suelo/normas , Contaminantes del Suelo/química , Contaminantes del Suelo/farmacocinética , SolubilidadRESUMEN
The uptake and distribution of Cd in potatoes over the course of a growing season was investigated in two cultivars of potatoes that differed in tuber Cd concentration. Plants were grown in soil with supplemental Cd. The concentrations of Cd in different tissues varied greatly in the order roots>shoots>> tubers. After the initiation of tuber bulking, shoot growth ceased and the increase in total plant Cd was mostly due to accumulation in the tubers. The constancy of the Cd concentration in shoots suggested that import of Cd via the xylem must be matched by export in the phloem, which implied that Cd must have significant phloem mobility. It was found that the differences in tuber Cd between cultivars Wilwash and Kennebec were not due to differences in total uptake or growth, but to differences in Cd partitioning within the plant. This partitioning was specific to Cd and was not observed for a range of nutrient elements. Most of the differences in tuber Cd concentration between the cultivars could be accounted for by a 3-fold higher retention of Cd in the roots of cv. Wilwash. The involvement of root sequestration, and xylem and phloem pathways in the loading of Cd into tubers is considered.
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Cadmio/metabolismo , Solanum tuberosum/metabolismo , Solanum tuberosum/crecimiento & desarrollo , Especificidad de la EspecieRESUMEN
The cedrene carbon skeleton was rapidly assembled from a simple monocyclic precursor by the strategic use of a high yielding intramolecular Khand cyclization reaction. Further synthetic manipulations provided a concise formal total synthesis of alpha- and beta-cedrene. Reaction: see text.
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Aceites de Plantas/síntesis química , Compuestos Heterocíclicos con 3 Anillos/síntesis química , Isomerismo , Juniperus/química , Sesquiterpenos Policíclicos , Sesquiterpenos/síntesis química , EstereoisomerismoRESUMEN
The pharmacological characteristics of levobetaxolol, a single active isomer of betaxolol, were determined and compared with activities of other beta-adrenoceptor antagonists. Levobetaxolol (43-fold beta1-selective) exhibited a higher affinity at cloned human beta1 (Ki = 0.76 nM) than at beta2 (Ki = 32.6 nM) receptors, while dextrobetaxolol was much weaker at both receptors. Levobetaxolol potently antagonized functional activities at cloned human beta1 and beta2 receptors, and also at guinea pig atrial beta1, tracheal beta2 and rat colonic beta3 receptors (IC50s = 33.2 nM, 2970 nM and 709 nM, respectively). Thus, levobetaxolol was 89-times beta1-selective (vs beta2). Levobetaxolol (Ki = 16.4 nM) was more potent than dextrobetaxolol (Ki = 2.97 microM) at inhibiting isoproterenol-induced cAMP production in human non-pigmented ciliary epithelial cells. Levobunolol and (l)-timolol had high affinities at beta1 and beta2 receptors but were considerably less beta1-selective than levobetaxolol. Levo-, dextro- and racemic-betaxolol exhibited little or no affinity, except at sigma sites and Ca2+-channels (IC50s > 1 microM), at 89 other receptor/ligand binding sites. Levobetaxolol exhibited a micromolar affinity for L-type Ca2+-channels. In conscious ocular hypertensive cynomolgus monkeys, levobetaxolol was more potent than dextrobetaxolol, reducing intraocular pressure by 25.9+/-3.2% at a dose of 150 microg/eye (n = 15-30). Quantitative [3H]-levobetaxolol autoradiography revealed high levels of binding to human ciliary processes, iris, choroid/retina, and ciliary muscles. In conclusion, levobetaxolol is a potent, high affinity and beta1-selective IOP-lowering beta-adrenoceptor antagonist.
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Antagonistas Adrenérgicos beta/farmacología , Betaxolol/farmacología , Cuerpo Ciliar/efectos de los fármacos , Presión Intraocular/efectos de los fármacos , Agonistas Adrenérgicos beta/farmacología , Animales , Línea Celular , Cuerpo Ciliar/citología , Cuerpo Ciliar/metabolismo , AMP Cíclico/biosíntesis , Evaluación Preclínica de Medicamentos , Células Epiteliales/efectos de los fármacos , Femenino , Cobayas , Humanos , Isomerismo , Isoproterenol/antagonistas & inhibidores , Isoproterenol/farmacología , Macaca fascicularis , Masculino , Epitelio Pigmentado Ocular/efectos de los fármacos , Ratas , Receptores Adrenérgicos beta/metabolismoRESUMEN
While the number of women entering U.S. medical schools has risen substantially in the past 25 years, the number of women in leadership positions in academic medicine is disproportionately small. The traditional pathway to academic leadership is through research. Women's health research is an ideal venue to fill the pipeline with talented women physicians and scientists who may become academic leaders in positions where they can promote positive change in women's health as well as mentor other women. The Office on Women's Health (OWH) in the U.S. Department of Health and Human Services has contracted with 18 academic medical centers to develop National Centers of Excellence in Women's Health. Emphasizing the integral link between women's health and women leaders, each of the Centers of Excellence must develop a leadership plan for women in academic medicine as part of the contract requirements. This paper describes the training programs in women's health research that have developed at five of the academic medical centers: the University of Wisconsin, Magee Women's Hospital, the University of Maryland, Medical College of Pennsylvania Hahnemann University, and the University of Illinois at Chicago. We discuss some of the challenges faced for both initiation and future viability of these programs as well as criteria by which these programs will be evaluated for success.
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Centros Médicos Académicos/organización & administración , Movilidad Laboral , Educación de Postgrado en Medicina/organización & administración , Docentes Médicos , Becas/organización & administración , Relaciones Interinstitucionales , Liderazgo , Médicos Mujeres , Investigación/educación , Investigación/organización & administración , Salud de la Mujer , Femenino , Predicción , Humanos , Mentores , Médicos Mujeres/provisión & distribución , Desarrollo de Programa/métodos , Evaluación de Programas y Proyectos de Salud , Estados UnidosRESUMEN
Travoprost is the isopropyl ester prodrug of a high affinity, selective FP prostaglandin full receptor agonist. In contrast to travoprost acid's high affinity and efficacy at the FP receptor, there is only sub-micromolar affinity for the DP, EP1, EP3, EP4, IP, and TP receptors. Travoprost produced a lower incidence of ocular irritation than PGF20 isopropyl ester at a dose of 1 microg in the New Zealand albino (NZA) rabbit. Topical ocular application of travoprost produced a marked miotic effect in cats following doses of 0.01, 0.03 and 0.1 microg. In the ocular hypertensive monkey, b.i.d. application of 0.1 and 0.3 microg of travoprost afforded peak reduction in intraocular pressure (IOP) of 22.7% and 28.6%, respectively. Topical application of travoprost was well tolerated in rabbits, cats and monkeys, causing no ocular irritation or discomfort at doses up to 1 microg. Travoprost is a promising ocular hypotensive prostaglandin FP derivative that has the ocular hypotensive efficacy of PGF2alpha isopropyl ester but with less severe ocular side effects.
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Antihipertensivos/farmacología , Cloprostenol/farmacología , Receptores de Prostaglandina/agonistas , Adenilil Ciclasas/metabolismo , Administración Tópica , Animales , Gatos , Bovinos , Cloprostenol/análogos & derivados , Cuerpo Lúteo/metabolismo , Dinoprost/metabolismo , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Femenino , Fibroblastos/efectos de los fármacos , Humanos , Presión Intraocular/efectos de los fármacos , Macaca , Ratones , Hipertensión Ocular/tratamiento farmacológico , Soluciones Oftálmicas , Fosfatidilinositoles/metabolismo , Conejos , Malla Trabecular/efectos de los fármacos , TravoprostRESUMEN
OBJECTIVE: The objective of this chart review was to determine the frequency of transfusion and prevalence of anemia (hemoglobin result < 100 g/L) in patients receiving chemotherapy. DESIGN: This study was a retrospective review of medical charts. SETTING: Patients receiving chemotherapy were included from 12 tertiary care comprehensive cancer centres across Canada. MAIN OUTCOME MEASURE: The primary study outcome measure was red blood cell transfusion rate, controlling for patient variables. RESULTS: The 616 patients included had started chemotherapy in January-June 1992. For each subject, data collection finished 4 weeks after the end of the first regimen or after a maximum follow-up period of 26 weeks. Seventy-two patients (12%; 95% confidence interval 9.5% to 14.5%) were transfused for anemia (reasons other than blood loss), and 28% (95% confidence interval 24.5% to 31.5%) of the subjects were anemic during treatment. The univariate analyses of transfusion for anemia yielded significant associations with prognostic factors. In the multivariate analyses, platinum (odds ratio [OR] = 6.69) and anthracycline (OR = 3.56) chemotherapy, baseline hemoglobin (OR = 0.96) and disease stage (OR = 1.72) were statistically significant contributors. CONCLUSION: In this patient cohort, red blood cell transfusion was infrequent (12%). However, patient groups at high risk of transfusion could be identified, with platinum-based chemotherapy being the most significant contributing factor. The information obtained from this multicentre study may prove helpful in developing supportive care guidelines for the management of chemotherapy-related anemia requiring transfusion.
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Anemia/epidemiología , Anemia/terapia , Antineoplásicos/efectos adversos , Transfusión de Eritrocitos/estadística & datos numéricos , Neoplasias/tratamiento farmacológico , Adolescente , Adulto , Distribución por Edad , Anciano , Anemia/inducido químicamente , Canadá/epidemiología , Estudios de Cohortes , Femenino , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate the radioprotectant effects of the 21-aminosteroid U-74389G on the rat C6 glioma model after stereotactic radiosurgery. Because radiosurgery causes both tumor cytotoxicity, as well as regional brain edema, we hypothesized that this drug might exhibit advantageous or deleterious effects on healthy and neoplastic tissue. METHODS: Rats were implanted with 10(6) C6 glioma cells into the right frontal brain and randomized to a Control Group (n = 18), radiosurgery on Day 14 (50% isodose = 35 Gy) (n = 15), or radiosurgery preceded by a single 15 mg/kg intravenous dose of 21-aminosteroid (n = 27). All animals were killed by 90 days and evaluated for survival, tumor size, the presence or absence of regional parenchymal edema, or radiation-induced vasculopathy. RESULTS: After tumor implantation, median survival in the Control Group was 23 days. Significant improvements in median survival were noted after RS alone (median, 31 days; p = 0.02), and RS plus 21-aminosteroid (median, 59 days; p < 0.0001). In the Control Group, mean tumor diameter was 5.4 mm. After RS alone, the mean diameter was 3.2 mm (p = 0.002), and after RS plus 21-aminosteroid, 2.9 mm (p = 0.0002). In the Control Group, the tumor grew as a hypercellular, compact mass. Only 3 of 18 animals had peritumoral edema. In contrast, 7 of 15 animals in the RS group had evidence of edema (p = 0.006), but rats that received 21-aminosteroid showed no increase compared to controls (p = 0.38). Similarly, 6 of 15 animals that had radiosurgery alone showed evidence of vasculopathy (p = 0.005) compared to no animals in the control group and only 2 of 27 aminosteroid-treated animals. CONCLUSIONS: The 21-aminosteroid U-74389G exhibits a radioprotectant effect on normal brain tissue, but does not appear to protect the tumor in an in vivo rat radiosurgery model. We believe that the observed beneficial effects on healthy brain led to significant prolongation of animal survival; perhaps, by limiting the adverse effects of high-dose radiosurgery. This radioprotectant should now be evaluated in randomized clinical trials in patients with malignant brain tumors.
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Encéfalo/efectos de los fármacos , Pregnatrienos/uso terapéutico , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/uso terapéutico , Radiocirugia/efectos adversos , Animales , Encéfalo/efectos de la radiación , Edema Encefálico/etiología , Edema Encefálico/prevención & control , Neoplasias Encefálicas/cirugía , Evaluación Preclínica de Medicamentos , Glioma/cirugía , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Acute promyelocytic leukemia (APL) is associated with a hemorrhagic disorder of unknown cause that responds to treatment with all-trans-retinoic acid. METHODS: We studied a newly described receptor for fibrinolytic proteins, annexin II, in cells from patients with APL or other leukemias. We examined initial rates of in vitro generation of plasmin by tissue plasminogen activator (t-PA) in the presence of APL cells that did or did not have the characteristic translocation of APL, t(15;17). We also determined the effect of all-trans-retinoic acid on the expression of annexin II and the generation of cell-surface plasmin. RESULTS: The expression of annexin II, as detected by a fluorescein-tagged antibody, was greater on leukemic cells from patients with APL than on other types of leukemic cells (mean fluorescence intensity, 6.9 and 2.9, respectively; P<0.01). The t(15;17)-positive APL cells stimulated the generation of cell-surface, t-PA-dependent plasmin twice as efficiently as the t(15;17)-negative cells. This increase in plasmin was blocked by an anti-annexin II antibody and was induced by transfection of t(15;17)-negative cells with annexin II complementary DNA. The t(15;17)-positive APL cells contained abundant messenger RNA for annexin II, which disappeared through a transcriptional mechanism after treatment with all-trans-retinoic acid. CONCLUSIONS: Abnormally high levels of expression of annexin II on APL cells increase the production of plasmin, a fibrinolytic protein. Overexpression of annexin II may be a mechanism for the hemorrhagic complications of APL.
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Anexina A2/metabolismo , Fibrinolisina/biosíntesis , Leucemia Promielocítica Aguda/metabolismo , Adolescente , Adulto , Anexina A2/efectos de los fármacos , Anexina A2/genética , Anexina A2/inmunología , Anticuerpos/fisiología , Niño , Preescolar , Femenino , Fibrinólisis/efectos de los fármacos , Fibrinólisis/inmunología , Trastornos Hemorrágicos/etiología , Humanos , Leucemia/metabolismo , Leucemia Promielocítica Aguda/complicaciones , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/fisiopatología , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Transcripción Genética/efectos de los fármacos , Transfección , Translocación Genética , Tretinoina/farmacología , Células Tumorales CultivadasRESUMEN
In a double blind, placebo controlled trial of 40 volunteers, the burning discomfort associated with application of capsaicin cream (0.025%) was compared to placebo, GTN cream (1.33%) and to the combination of capsaicin cream (0.025%) plus GTN cream 1.33%. Median VAS for burning pain were 0 for the placebo, GTN and GTN + capsaicin groups and 3 for the capsaicin group after single application of each cream at daily intervals. This study demonstrates that after single application the addition of GTN to capsaicin significantly reduces the burning discomfort associated with application of capsaicin alone.
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Capsaicina/administración & dosificación , Capsaicina/efectos adversos , Nitroglicerina/uso terapéutico , Dolor/inducido químicamente , Dolor/tratamiento farmacológico , Vasodilatadores/uso terapéutico , Capsaicina/farmacología , Método Doble Ciego , Quimioterapia Combinada , Humanos , Nitroglicerina/administración & dosificación , Pomadas , Resultado del Tratamiento , Vasodilatadores/administración & dosificación , VoluntariosRESUMEN
Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds. Using radiolabelled and radio-photoaffinity-labelled chemical probes, the target of these compounds was identified as a pair of closely related mitogen-activated protein kinase homologues, termed CSBPs. Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production.
Asunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Citocinas/biosíntesis , Mediadores de Inflamación , Proteínas Quinasas Activadas por Mitógenos , Secuencia de Aminoácidos , Secuencia de Bases , Proteínas Quinasas Dependientes de Calcio-Calmodulina/genética , Línea Celular , Cromosomas Humanos Par 6 , Clonación Molecular , Citocinas/antagonistas & inhibidores , ADN Complementario , Humanos , Imidazoles/farmacología , Interleucina-1/biosíntesis , Datos de Secuencia Molecular , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Fragmentos de Péptidos , Piridinas/farmacología , Ensayo de Unión Radioligante , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
The biological effects of extracts of two Chinese medicinal herbs, Astragalus membranaceus and Ligustrum lucidum, on in vitro lymphocyte blastogenesis were assessed. Aqueous extracts augmented the spontaneous [3H]thymidine incorporation in the mononuclear cells (MNC) of 14 normal subjects from 273.0 to 609.3 counts per minute (cpm) and 252.9 to 656.9 cpm for the two herbs, respectively. The stimulation indices were 2.4 and 3.1, respectively (p less than 0.001). They also augmented the proliferation of normal subjects' lymphocytes induced by suboptimal concentrations of phytohemagglutinin (PHA) from 5084.6 to 23,398.3 and 221.7 to 24,132.8 cpm, of concanavalin A (con A) from 4046.5 to 15,661.5 and 677.6 to 14,644.6 cpm, and of pokeweed mitogen (PWM) from 4377.9 to 24,405.6 and 322.7 to 11,730.0 cpm, respectively (p less than 0.00). Herb extracts augmented the PHA responses of the MNC from 14 cancer patients significantly (p less than 0.01 and p less than 0.05, respectively). Extracts of L. lucidum also augmented the con A response of patients (p less than 0.05). The augmenting effect of the herbs on the PHA, con A, and PWM responses was dose dependent, and proliferation was inhibited at higher concentrations. The optimal concentration for stimulating the MNC of cancer patients was 100 micrograms/ml, compared to 10 micrograms/ml for the MNC of normal donors. MNC of seven patients depressed the mitogen responses of normal cells in a co-culture system. This was partially abrogated in five by preincubating the patients' cells in herb extracts for 45 min or by irradiation of the patients' cells. These results suggest that the herb extracts contain immunomodulatory components which may be useful in the immunotherapy of disease.
Asunto(s)
Linfocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Adulto , Astragalus propinquus , Blastómeros/efectos de los fármacos , Concanavalina A/farmacología , Femenino , Humanos , Técnicas In Vitro , Masculino , Medicina Tradicional China , Monocitos/efectos de los fármacos , Fitohemaglutininas/farmacología , Mitógenos de Phytolacca americana/farmacologíaRESUMEN
Replicate field plots comprising a control, plus oil, plus oil and bacteria, plus oil and fertilizer (urea-phosphate; 27:27:0), and plus oil, bacteria, and fertilizer were monitored over a 308-day period for changes in bacterial and mold numbers. Changes in the chemical composition of the oil applied to the plots was followed by using chromatographic techniques. Application of fertilizer resulted in a stimulation of bacterial numbers and in the rate of utilization of n-alkane components of the saturate fraction. The application of oil-utilizing bacteria, however, resulted in only a slightly accelerated rate of utilization of n-alkane components of chain lengths C20 to C25. The isoprenoids, phytane and pristane, were still present in gas-liquid chromatography profiles after digestion of the n-alkane components of the saturate fraction. Those plots which received fertilizer showed an accelerated rate of recovery of native vegetation.