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Six-membered heterocycles containing one phosphorus and one nitrogen atom, known as azaphosphinines, have existed in the shadows of their single heteroatom-containing analogues for almost 150 years. Despite this, recent chemistry has seen a rapid increase in publications concerning this uncommon scaffold. Azaphosphinines exist in one of six isomers-there are three possible orientations of the pnictogen atoms and in each of these, the phosphorus is in one of two valences (PIIIvs. PV). This review aims to outline and inform on the synthesis and applications of all six isomers. PV-oxo azaphosphinines are of particular interest to this review as many of the discussed heterocycles either form as the pentavalent species directly or oxidize to this over time. In very recent years the published applications of azaphosphinines have blossomed into subjects spanning several fields of chemistry such as asymmetric catalysis, supramolecular association, cellular imaging, and medicinal chemistry.
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Several phosphaquinolinone derivatives have been synthesized and characterized to explore their usefulness in the realm of cell imaging. Solution-state photophysical properties in both aqueous and organic solutions were collected for these derivatives. Additionally, CCK-8 cell viability assays and fluorescent imaging in HeLa cells incubated with the new heterocyclic derivatives show evidence of favorable cell permeability, cell viability, and moderate intracellular localization when appended with the well-known morpholine targeting motif.
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Colorantes Fluorescentes , Agua , Humanos , Estructura Molecular , Células HeLa , Ionóforos , Concentración de Iones de HidrógenoRESUMEN
Research has demonstrated that systemic transphobia and cissexism harms transgender youth in terms of social, educational, and health outcomes. All too often, research and policy emphasizes vulnerability among trans youth in a way that denies their capabilities as agents of change or active participants in their liberation. This article analyzes the development of Trans Youth Justice Project, a political education and youth leadership development program for trans youth ages 15-22. Based in principles of gender minority stress and social justice youth development, the 6-week remote program aims to increase the capacity and resilience of trans youth, develop youth leaders, and contribute to addressing social, educational, and health inequalities. We conducted a formative program evaluation of 2 cycles of the program with a total of 25 youth. Pre- and post-test surveys indicated increased feelings of belongingness to a trans community. Follow-up interviews highlighted the impact the program had on skills for social justice, self-efficacy, and community connection. We offer suggestions for implementing the open-source program more broadly.
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The phosphaquinolinone scaffold has been previously studied as a modular core for a variety of fluorescent species where use of substituent effects has focused on increasing or decreasing electron density in the core rings. We now report the synthesis and analysis of several pyridine-containing phosphaquinolinone species exhibiting notable linear conjugation from the aryl-substituent to electron-withdrawing pyridyl nitrogen. Varying the nature of the aryl substituent from electron-withdrawing to electron-donating leads to the generation of an internal charge-transfer (ICT) band in the absorbance spectrum, which becomes the dominant absorbance in terms of intensity in the most electron-rich -NMe2 example. This heterocycle exhibits improved photophysical properties compared to others in the set including high quantum yield and considerably red-shifted emission. The enhanced ICT can be observed in the X-ray data where a rare example of molecule co-planarity is observed. Computational data show increased localization of negative charge on the pyridyl nitrogen as the electron-donating character of the aryl-substituent increases.
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Inclusion of a second nitrogen atom in the aromatic core of phosphorus-nitrogen (PN) heterocycles results in unexpected tautomerization to a nonaromatic form. This tautomerization, initially observed in the solid state through X-ray crystallography, is also explained by computational analysis. We prepared an electron deficient analogue (2 e) with a fluorine on the pyridine ring and showed that the weakly basic pyridine resisted tautomerization, providing key insights to why the transformation occurs. To study the difference in solution vs. solid-state heterocycles, alkylated analogues that lock in the quinoidal tautomer were synthesized and their different 1 H NMR and UV/Vis spectra studied. Ultimately, we determined that all heterocycles are the aromatic tautomer in solution and all but 2 e switch to the quinoidal tautomer in the solid state. Better understanding of this transformation and under what circumstances it occurs suggest future use in a switchable on/off hydrogen-bond-directed receptor that can be tuned for complementary hydrogen bonding.
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Nitrógeno , Fósforo , Enlace de Hidrógeno , PiridinasRESUMEN
BACKGROUND: Despite the increasing importance of cardiopulmonary exercise testing (CPET) for preoperative risk assessment, the reliability of CPET interpretation is unclear. We aimed to assess inter-observer reliability of preoperative CPET. METHODS: We conducted a prospective, multi-centre, observational study of preoperative CPET interpretation. Participants were professionals with previous experience or training in CPET, assessed by a standardized questionnaire. Each participant interpreted 100 tests using standardized software. The CPET variables of interest were oxygen consumption at the anaerobic threshold (AT) and peak oxygen consumption (VO2 peak). Inter-observer reliability was measured using intra-class correlation coefficient (ICC) with a random effects model. Results are presented as ICC with 95% confidence interval, where ICC of 1 represents perfect agreement and ICC of 0 represents no agreement. RESULTS: Participants included 8/28 (28.6%) clinical physiologists, 10 (35.7%) junior doctors, and 10 (35.7%) consultant doctors. The median previous experience was 140 (inter-quartile range 55-700) CPETs. After excluding the first 10 tests (acclimatization) for each participant and missing data, the primary analysis of AT and VO2 peak included 2125 and 2414 tests, respectively. Inter-observer agreement for numerical values of AT [ICC 0.83 (0.75-0.90)] and VO2 peak [ICC 0.88 (0.84-0.92)] was good. In a post hoc analysis, inter-observer agreement for identification of the presence of a reportable AT was excellent [ICC 0.93 (0.91-0.95)] and a reportable VO2 peak was moderate [0.73 (0.64-0.80)]. CONCLUSIONS: Inter-observer reliability of interpretation of numerical values of two commonly used CPET variables was good (>80%). However, inter-observer agreement regarding the presence of a reportable value was less consistent.
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Competencia Clínica/estadística & datos numéricos , Prueba de Esfuerzo/métodos , Consumo de Oxígeno , Cuidados Preoperatorios/métodos , Umbral Anaerobio , Estudios Transversales , Frecuencia Cardíaca , Humanos , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
Human activity is leaving a pervasive and persistent signature on Earth. Vigorous debate continues about whether this warrants recognition as a new geologic time unit known as the Anthropocene. We review anthropogenic markers of functional changes in the Earth system through the stratigraphic record. The appearance of manufactured materials in sediments, including aluminum, plastics, and concrete, coincides with global spikes in fallout radionuclides and particulates from fossil fuel combustion. Carbon, nitrogen, and phosphorus cycles have been substantially modified over the past century. Rates of sea-level rise and the extent of human perturbation of the climate system exceed Late Holocene changes. Biotic changes include species invasions worldwide and accelerating rates of extinction. These combined signals render the Anthropocene stratigraphically distinct from the Holocene and earlier epochs.
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Biota , Planeta Tierra , Sedimentos Geológicos/química , Actividades Humanas , Aluminio/análisis , Ciclo del Carbono , Clima , Materiales de Construcción/análisis , Combustibles Fósiles/efectos adversos , Humanos , Hielo/análisis , Especies Introducidas , Plásticos/análisis , Ceniza Radiactiva/análisis , Radioisótopos/análisisRESUMEN
The ultimate origin of water in the Earth's hydrosphere is in the deep Earth--the mantle. Theory and experiments have shown that although the water storage capacity of olivine-dominated shallow mantle is limited, the Earth's transition zone, at depths between 410 and 660 kilometres, could be a major repository for water, owing to the ability of the higher-pressure polymorphs of olivine--wadsleyite and ringwoodite--to host enough water to comprise up to around 2.5 per cent of their weight. A hydrous transition zone may have a key role in terrestrial magmatism and plate tectonics, yet despite experimental demonstration of the water-bearing capacity of these phases, geophysical probes such as electrical conductivity have provided conflicting results, and the issue of whether the transition zone contains abundant water remains highly controversial. Here we report X-ray diffraction, Raman and infrared spectroscopic data that provide, to our knowledge, the first evidence for the terrestrial occurrence of any higher-pressure polymorph of olivine: we find ringwoodite included in a diamond from Juína, Brazil. The water-rich nature of this inclusion, indicated by infrared absorption, along with the preservation of the ringwoodite, is direct evidence that, at least locally, the transition zone is hydrous, to about 1 weight per cent. The finding also indicates that some kimberlites must have their primary sources in this deep mantle region.
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BACKGROUND AND PURPOSE: Insulin resistance is often found to be associated with high blood pressure. We propose that in insulin-resistant hypertension, endothelial dysfunction is the consequence of increased activity of vascular MMP-2. As MMP-2 proteolytically cleaves a number of extracellular matrix proteins, we hypothesized that MMP-2 impairs endothelial function by proteolytic degradation of endothelial NOS (eNOS) or its cofactor, heat shock protein 90 (HSP90). EXPERIMENTAL APPROACH: We tested our hypothesis in bovine coronary artery endothelial cells and fructose-fed hypertensive rats (FHR), a model of acquired systolic hypertension and insulin resistance. KEY RESULTS: Treatment of FHRs with the MMP inhibitor doxycycline, preserved endothelial function as well as prevented the development of hypertension, suggesting that MMPs impair endothelial function. Furthermore, incubating endothelial cells in vitro with a recombinant MMP-2 decreased NO production in a dose-dependent manner. Using substrate cleavage assays and immunofluorescence microscopy studies, we found that MMP-2 not only cleaves and degrades HSP90, an eNOS cofactor but also co-localizes with both eNOS and HSP90 in endothelial cells, suggesting that MMPs functionally interact with the eNOS system. Treatment of FHRs with doxycycline attenuated the decrease in eNOS and HSP90 expression but did not improve insulin sensitivity. CONCLUSIONS AND IMPLICATIONS: Our data suggest that increased activity of MMP-2 in FHRs impairs endothelial function and promotes hypertension. Inhibition of MMP-2 could be a potential therapeutic strategy for the management of hypertension.
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Doxiciclina/farmacología , Células Endoteliales/efectos de los fármacos , Hipertensión/prevención & control , Inhibidores de la Metaloproteinasa de la Matriz , Arterias Mesentéricas/efectos de los fármacos , Animales , Aorta Torácica/citología , Bovinos , Células Cultivadas , Células Endoteliales/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Fructosa , Proteínas HSP90 de Choque Térmico/metabolismo , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión/fisiopatología , Resistencia a la Insulina/fisiología , Masculino , Metaloproteinasa 2 de la Matriz/fisiología , Arterias Mesentéricas/fisiología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To identify variations in current antenatal screening programmes across one region and compare results with a previous survey. DESIGN: A cross section descriptive survey. SETTING: All maternity units within the region of Northern Ireland. SAMPLE: Eleven maternity units were invited and ten agreed to participate. MAIN OUTCOME MEASURES: The number of written policies for individual screening tests; the range of screening tests offered; the frequency of training opportunities for health professionals; and the information systems in place to record data. RESULTS: There is variation in service provision across maternity units and, in particular, inconsistency in the offer of serum screening tests for Down syndrome. A lack of training opportunities for health professionals involved in offering screening was highlighted, and no common information system employed. CONCLUSION: While improvements have been made since 2002, variations persist. This is leading to inequalities in the provision of antenatal screening services across Northern Ireland.
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Síndrome de Down/diagnóstico , Política de Salud , Tamizaje Masivo/tendencias , Diagnóstico Prenatal/tendencias , Estudios Transversales , Femenino , Geografía , Encuestas de Atención de la Salud , Maternidades/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Tamizaje Masivo/estadística & datos numéricos , Bienestar Materno , Irlanda del Norte , Embarazo , Diagnóstico Prenatal/estadística & datos numéricos , Evaluación de Programas y Proyectos de Salud , Estadística como AsuntoRESUMEN
Photoacoustic tomography (PAT) is a rapidly emerging non-invasive imaging technology that integrates the merits of high optical contrast with high ultrasound resolution. The ability to quantitatively and non-invasively image nanoparticles has important implications for the development of nanoparticles as in vivo cancer diagnostic and therapeutic agents. In this study, the ability of systemically administered poly(ethylene glycol)-coated (PEGylated) gold nanoparticles as a contrast agent for in vivo tumor imaging with PAT has been evaluated. We demonstrate that gold nanoparticles (20 and 50 nm) have high photoacoustic contrast as compared to mouse tissue ex vivo. Gold nanoparticles can be visualized in mice in vivo following subcutaneous administration using PAT. Following intravenous administration of PEGylated gold nanoparticles to tumor-bearing mice, accumulation of gold nanoparticles in tumors can be effectively imaged with PAT. With gold nanoparticles as a contrast agent, PAT has important potential applications in the image guided therapy of superficial tumors such as breast cancer, melanoma and Merkel cell carcinoma.
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Acústica , Medios de Contraste , Oro , Nanopartículas del Metal , Neoplasias/patología , Tomografía/métodos , Animales , Medios de Contraste/química , Oro/química , Hipodermoclisis , Nanopartículas del Metal/química , Ratones , Ratones Endogámicos C57BL , Trasplante de Neoplasias , Neoplasias/diagnóstico , Tamaño de la Partícula , Fantasmas de Imagen , Procesamiento de Señales Asistido por ComputadorRESUMEN
Two of the most potent vasoconstrictors, endothelin-1 (ET-1) and angiotensin II (Ang II), are upregulated in fructose hypertensive rats. It is unknown whether an interrelationship exists between these peptides that may contribute to the development of fructose-induced hypertension. The objective of this study was to investigate the existence of an interaction between the endothelin and renin angiotensin systems that may play a role in the development of fructose-induced hypertension. High fructose feeding and treatment with either bosentan, a dual endothelin receptor antagonist, or with L-158,809, an angiotensin type 1 receptor antagonist, were initiated simultaneously in male Wistar rats. Systolic blood pressure, fasted plasma parameters, insulin sensitivity, plasma Ang II, and vascular ET-1-immunoreactivity were determined following 6 weeks of high fructose feeding. Rats fed with a high fructose diet exhibited insulin resistance, hyperinsulinemia, hypertriglyceridemia, hypertension, and elevated plasma Ang II. Treatment with either bosentan or L-158,809 significantly attenuated the rise in blood pressure with no effect on insulin levels or insulin sensitivity in fructose-fed rats. Bosentan treatment significantly reduced plasma Ang II levels, while L-158,809 treatment significantly increased vascular ET-1-immunoreactivity in fructose-fed rats. Thus, treatment with the endothelin receptor antagonist prevented the development of fructose-induced hypertension and decreased plasma Ang II levels. These data suggest that ET-1 contributes to the development of fructose-induced hypertension through modulation of Ang II levels.
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Angiotensina II/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Endotelina-1/fisiología , Fructosa/administración & dosificación , Hipertensión/fisiopatología , Angiotensina II/antagonistas & inhibidores , Angiotensina II/sangre , Animales , Presión Sanguínea , Prueba de Tolerancia a la Glucosa , Imidazoles/farmacología , Inmunohistoquímica , Resistencia a la Insulina , Masculino , Ratas , Ratas Wistar , Tetrazoles/farmacologíaRESUMEN
The geochemical signature of diamond-forming fluids can be used to unravel diamond-forming processes and is of potential use in the detection of so-called 'conflict' diamonds. While fluid-rich fibrous diamonds can be analyzed by a variety of techniques, very few data have been published for fluid-poor, gem-quality diamonds because of their very low impurity levels. Here we present a new ICPMS-based (ICPMS: inductively coupled plasma mass spectrometry) method for the analysis of trace element concentrations within fluid-poor, gem-quality diamonds. The method employs a closed-system laser ablation cell. Diamonds are ablated and the products trapped for later pre-concentration into solutions that are analyzed by sector-field ICPMS. We show that our limits of quantification for a wide range of elements are at the sub-pg to low pg level. The method is applied to a suite of 10 diamonds from the Cullinan Mine (previously known as Premier), South Africa, along with other diamonds from Siberia (Mir and Udachnaya) and Venezuela. The concentrations of a wide range of elements for all the samples (expressed by weight in the solid) are very low, with rare earth elements along with Y, Nb, Cs ranging from 0.01 to 2 ppb. Large ion lithophile elements (LILE) such as Rb and Ba vary from 1 to 30 ppb. Ti ranges from ppb levels up to 2 ppm. From the combined, currently small data set we observe two kinds of diamond-forming fluids within gem diamonds. One group has enrichments in LILE over Nb, whereas a second group has normalized LILE abundances more similar to those of Nb. These two groups bear some similarity to different groups of fluid-rich diamonds, providing some supporting evidence of a link between the parental fluids for both fluid-inclusion-rich and gem diamonds.
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This article reviews the body of work aimed at elucidating the mechanisms of action by which natural products of plant origin exert a vasodilatory effect at the level of the vasculature. The search was restricted to 4 mechanisms: the nitric oxide system and (or) reactive oxygen species, the eicosanoid system, potassium channel function, and calcium channel function. The National Library of Medicine database was searched using "PubMed" without restriction to language. The search generated 266 references on 15 November 2005. Most studies were in vitro in nature and of these, most involved studies in the rat aorta. Many of the natural products evoked vasodilatation through an endothelium-dependent mechanism. The vasodilatation was attenuated or abolished by a nitric oxide synthase inhibitor and, in some of these studies, by an inhibitor of guanylate cyclase. A few studies reported a cyclooxygenase component, but most found no effect of the cyclooxygenase inhibitor, indomethacin. The vasorelaxation evoked by several natural products was attenuated by various potassium channel blocking agents, suggesting that some natural products exerted their effect either directly or indirectly through activation of potassium channels. Finally, a significant number of natural products evoked vasodilatation either through blockade of calcium channels or by inhibiting the release of calcium from intracellular stores. Many natural products evoked vasodilatation through multiple mechanisms. The information in this review on mechanisms of action should facilitate good clinical practice by increasing the predictive capabilities of the practitioner, notably the ability to predict adverse effects and interactions among medications. The knowledge should also help to provide leads to the ultimate goal of developing new therapeutic medications.
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Preparaciones de Plantas/farmacología , Vasodilatación/efectos de los fármacos , Animales , Calcio/fisiología , Eicosanoides/fisiología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Homeostasis , Humanos , Óxido Nítrico/fisiología , Canales de Potasio/fisiología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Several in vitro studies have shown that endothelium-dependent vasodilatation is maintained by endothelium-derived hyperpolarizing factor (EDHF) or prostacyclin in vessels isolated from endothelial nitric oxide synthase knockout mice. Since this has not been addressed by in vivo studies, we sought to define the magnitude and the onset time of this compensation by recording blood pressure responses to endothelium-dependent vasodilators in rats treated acutely or chronically with the NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME). Groups of male Sprague-Dawley rats were given plain water (control) or L-NAME (0.7 mg/ml) in drinking water for 1 day, 5 days, 3 wks or 6 wks. Dose-dependent hypotensive responses to acetylcholine, bradykinin and sodium nitroprusside were determined in anesthetized rats before and after acute intravenous infusion of either L-NAME or a combination of apamin plus charybdotoxin that would selectively inhibit EDHF. Acute L-NAME treatment increased the mean arterial pressure and inhibited acetylcholine- and bradykinin-induced fall in blood pressure in control but not in chronic L-NAME treated rats. The endothelium-dependent hypotensive responses to acetylcholine and bradykinin were restored in rats treated with L-NAME after a time period of 24 h along with increased sensitivity to sodium nitroprusside and reduced plasma nitrate+nitrite levels. While apamin+charybdotoxin pretreatment inhibited the responses to acetylcholine and bradykinin in both acute and chronic L-NAME treated groups, it was more pronounced in the latter group. In conclusion, chronic inhibition of nitric oxide synthase results in the development of a compensatory hypotensive response to acetylcholine within 24 h and this is mediated by EDHF.
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Acetilcolina/farmacología , Factores Biológicos/metabolismo , Hipotensión/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Vasodilatadores/farmacología , Animales , Apamina/farmacología , Factores Biológicos/antagonistas & inhibidores , Presión Sanguínea/efectos de los fármacos , Bradiquinina/farmacología , Caribdotoxina/farmacología , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Inhibidores Enzimáticos/farmacología , Hipotensión/fisiopatología , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/metabolismo , Nitroglicerina/farmacología , Nitroprusiato/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio Calcio-Activados/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
AIMS/HYPOTHESIS: Vascular dysfunction is a hallmark of diabetes mellitus and endothelial dysfunction is considered to be a key early component of vascular dysfunction. Attenuated agonist-evoked responses are considered to be a barometer of endothelial/vascular dysfunction. We sought to determine whether vascular endothelial growth factor (VEGF) could prevent dysfunction from developing in the streptozotocin (STZ)-induced rat model of type 1 diabetes. MATERIALS AND METHODS: One week after induction of diabetes, STZ rats began a 4-week treatment protocol of twice-weekly i.v. injections of 2 microg VEGF or inactivated VEGF. Corresponding non-diabetic rats served as controls. Agonist-evoked vascular responses were recorded 1 day after the last treatment in anaesthetised rats. RESULTS: Acetylcholine (0.1-12.5 microg/kg) evoked increases in superior mesenteric arterial conductance and decreases in mean blood pressure, while methoxamine (12.5-100 microg/kg) and endothelin-1 (100-1,200 pmol/kg) evoked decreases in superior mesenteric arterial conductance and increases in mean blood pressure. These responses to all three agonists were attenuated in STZ rats, and chronic treatment with VEGF improved these responses dramatically. Both the reduction in plasma nitrate and nitrite and the elevation in aortic superoxide associated with STZ diabetes were normalised with VEGF treatment. VEGF also prevented the apparent paradoxical increased endothelial nitric oxide synthase expression seen in untreated STZ rats. CONCLUSIONS/INTERPRETATION: Chronic treatment with VEGF early in diabetes is able to prevent the attenuated agonist-evoked vascular responses in STZ rats and normalise the oxidative environment associated with the disease.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Factor A de Crecimiento Endotelial Vascular/agonistas , Factor A de Crecimiento Endotelial Vascular/farmacología , Animales , Aniones/química , Aorta/efectos de los fármacos , Aorta/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Nitratos/sangre , Óxido Nítrico Sintasa de Tipo III/metabolismo , Nitritos/sangre , Ratas , Ratas Sprague-Dawley , Estreptozocina/farmacología , Superóxidos/sangre , Superóxidos/química , Factores de TiempoRESUMEN
Vanadium-based drugs lower glucose by enhancing the effects of insulin. Oral vanadium drugs are being tested for the treatment of diabetes. Vanadium accumulates in bone, though it is not known if incorporated vanadium affects bone quality. Nine- to 12-month-old control and streptozotocin-induced diabetic female Wistar rats were given bis(ethylmaltolato)oxovanadium(IV) (BEOV), a vanadium-based anti-diabetic drug, in drinking water for 12 weeks. Non-diabetic rats received 0, 0.25 or 0.75 mg/ml BEOV. Groups of diabetic rats were either untreated or treated with 0.25-0.75 mg/ml BEOV as necessary to lower blood glucose in each rat. In diabetic rats, this resulted in a Controlled Glucose group, simulating relatively well-managed diabetes, and an Uncontrolled Glucose group, simulating poorly managed diabetes. Plasma insulin, glucose and triglyceride assays assessed the diabetic state. Bone mineral density (BMD), mechanical testing, mineral assessment and histomorphometry measured the effects of diabetes on bone and the effects of BEOV on non-diabetic and diabetic bone. Diabetes decreased plasma insulin and increased plasma glucose and triglycerides. In bone, diabetes decreased BMD, strength, mineralization, bone crystal length, and bone volume and connectivity. Treatment was effective in incorporating vanadium into bone. In all treated groups, BEOV increased osteoid volume. In non-diabetic bone, BEOV increased cortical bone toughness, mineralization and bone formation. In controlled glucose rats, BEOV lowered plasma glucose and improved BMD, mechanical strength, mineralization, bone crystal length and bone formation rate. In poorly controlled rats, BEOV treatment slightly lowered plasma glucose but did not improve bone properties. These results suggest that BEOV improves diabetes-related bone dysfunction primarily by improving the diabetic state. BEOV also appeared to increase bone formation. Our study found no negative effects of vanadium accumulation in bone in either diabetic or non-diabetic rats at the dose given.
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Huesos/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Vanadatos/administración & dosificación , Vanadatos/farmacología , Absorciometría de Fotón , Administración Oral , Animales , Fenómenos Biomecánicos , Glucemia/metabolismo , Peso Corporal , Densidad Ósea , Huesos/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/fisiopatología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Insulina/sangre , Radioinmunoensayo , Distribución Aleatoria , Ratas , Ratas Wistar , Triglicéridos/sangre , Vanadatos/farmacocinética , Vanadatos/uso terapéutico , Difracción de Rayos XRESUMEN
OBJECTIVE: To evaluate the use of the phosphorylcholine (PC) coated BiodivYsio small vessel (SV) stent in native coronary vessels of small calibre. DESIGN AND SETTING: Prospective, multi-centre, multi-national registry with 6-month clinical and core-lab angiographic follow-up. Adverse events were adjudicated by a Clinical Events Committee (CEC) and included peri-procedural analysis of cardiac enzymes. PATIENTS: Patients with signs or symptoms of ischaemia with an identified target lesion in an epicardial vessel with reference diameter 2.0-2.75 mm were enrolled. Intervention in other epicardial territories in the same patient was permitted. RESULTS: Recruitment of 150 consecutive lesions (in 143 patients) was completed in 19 centres in Europe and Israel. The stent was deployed successfully in all but one lesion. At 6 months, 1 patient (1%) had experienced sudden cardiac death, 4 further patients (3%) had a non-Q wave MI, and a further 24 patients (17%) had repeat revascularisation of a study target vessel. The mean reference vessel diameter prior to stenting was 2.2 mm (S.D. 0.4). Mean minimal luminal diameters at pre-procedure, post procedure and follow-up were 0.6 mm (S.D. 0.3), 2.0 mm (S.D. 0.4) and 1.2 mm (S.D. 0.6), respectively. The late lumen loss index was 0.55 (S.D. 0.53) with a binary restenosis rate of 32%. CONCLUSIONS: In stenting of selected lesions in small vessels, the BiodivYsio SV stent demonstrated high rates of implant success. The rates of major adverse cardiac events (MACE), angiographic restenosis and repeat revascularisation are similar to those reported in other small vessel bare metal stent studies.
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Angioplastia Coronaria con Balón/instrumentación , Materiales Biocompatibles Revestidos , Angiografía Coronaria , Estenosis Coronaria/terapia , Vasos Coronarios/cirugía , Fosforilcolina/farmacología , Stents , Adulto , Anciano , Anciano de 80 o más Años , Reestenosis Coronaria/prevención & control , Estenosis Coronaria/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diseño de Prótesis , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Flexible endoscopy is a vital component of gastrointestinal surgery. It has and will replace many of the surgical procedures now commonly performed. Flexible endoscopy, unfortunately, is not an integral part of surgical residency training based on resident operative experience as reported by the Residency Review Committee. Moreover, general surgeons have deferred the practice of flexible endoscopy to the gastroenterologists because of concerns over turf battles and referral patterns. The purpose of this study was to assess the overall case load and the economic impact of flexible endoscopy on the practice of general surgery in a community hospital setting. METHODS: This retrospective review was performed over a 6-month period. The total cases and the total billings of inpatient and outpatient procedures for a group practice of five general surgeons in a community hospital were evaluated. The billings were the actual charges based on current procedural terminology (CPT) codes for these procedures using the Medicare fee schedule. RESULTS: Of the 2,159 procedures performed, 1,154 involved flexible endoscopy cases accounting for 54% of all cases (1,154 of 2,159) performed from February 1, 2003 to July 31, 2003. Flexible endocopy accounted for 43% of the total charges. A. total of 46 surgical procedures and 216 future endoscopies were generated from the flexible endoscopic procedures. Future endoscopic cases were for surveillance of colonic neoplasia and Barrett's esophagus. CONCLUSIONS: Flexible endoscopy contributed to a major portion of the caseload and revenue generated by the general surgery group studied. The overall impact of flexible endoscopy is even greater than reported because of the future endoscopic surveillance cases or surgical interventions generated on the basis of endoscopic findings.