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New results are reported from a measurement of π^{0} electroproduction near threshold using the p(e,e^{'}p)π^{0} reaction. The experiment was designed to determine precisely the energy dependence of s- and p-wave electromagnetic multipoles as a stringent test of the predictions of chiral perturbation theory (ChPT). The data were taken with an electron beam energy of 1192 MeV using a two-spectrometer setup in Hall A at Jefferson Lab. For the first time, complete coverage of the Ï_{π}^{*} and θ_{π}^{*} angles in the pπ^{0} center of mass was obtained for invariant energies above threshold from 0.5 up to 15 MeV. The 4-momentum transfer Q^{2} coverage ranges from 0.05 to 0.155 (GeV/c)^{2} in fine steps. A simple phenomenological analysis of our data shows strong disagreement with p-wave predictions from ChPT for Q^{2}>0.07 (GeV/c)^{2}, while the s-wave predictions are in reasonable agreement.
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A model for the selective adsorption phenomenon in an isotropic liquid accounting for a van der Waals interaction between the ions and the surface is presented, in the framework of the Poisson-Boltzmann theory. The fundamental equations governing the electric field distribution are exactly solved for low and high potential regimes.
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The study demonstrated that lipid microspheres (LM) containing rifampicin (LM-RFP) could deliver the drug to alveolar macrophages in vitro and in vivo, and that intranasal administration to animals could achieve preferential accumulation in the lungs with less effect on the liver. The LM-RFP particles had a mean diameter of 247.2 +/- 75.7 nm, and their size remained stable when stored at 4 degrees C or 25 degrees C for at least 4 weeks. In vitro uptake of [(3)H]LM-RFP by alveolar macrophages was over 4 times higher than that of unencapsulated [(3)H]RFP, whereas the in vivo uptake was 30 times higher. Flow cytometric analysis and confocal laser scanning microscopy confirmed that LM could deliver the encapsulated drug effectively to alveolar macrophages in vitro and in vivo. Intranasal administration of [(3)H]LM-RFP to normal mice resulted in preferential pulmonary uptake of the drug and lower levels in the blood and liver compared with administration of unencapsulated [(3)H]RFP. In conclusion, LM-RFP could be a promising preparation for delivery via the respiratory tract to tuberculosis (TB) and TB/HIV patients.
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Lípidos/química , Macrófagos Alveolares/metabolismo , Microesferas , Rifampin/farmacocinética , Administración Intranasal , Administración Oral , Animales , Líquido del Lavado Bronquioalveolar/citología , Línea Celular , Sistemas de Liberación de Medicamentos/métodos , Inyecciones Espinales , Riñón/metabolismo , Hígado/metabolismo , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Miocardio/metabolismo , Ratas , Ratas Wistar , Rifampin/administración & dosificación , Rifampin/química , Bazo/metabolismo , Distribución Tisular , TritioRESUMEN
The nitrogen-vacancy (NV) centre in diamond is a promising candidate for quantum computing applications and magnetic sensing applications, because it is an atomic-scale defect with stable coherence time (T2) and reliable accessibility at room temperature. We demonstrated a method for improving the NV spin properties (the full width half maximum (FWHM) value of the magnetic resonance spectrum and T2) through a near-field (NF) etching method under ambient conditions. The NF etching method, based on a He-Cd ultraviolet laser (325 nm), which is longer than the absorption edge of the oxygen molecule, enabled selective removal of defects on the nanodiamond surface. We observed a decrease in the FWHM value close to 15% and an increase in T2 close to 25%. Since our technique can be easily reproduced, a wide range of NV centre applications could be improved, especially magnetic sensing applications. Our results are especially attractive, because they have been obtained under ambient conditions and only require a light source with wavelength slightly above the O2 absorption edge.
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The variable line spacing plane grating monochromator beamline at the Canadian Light Source (CLS) employs three grazing incidence variable line spacing gratings to cover a photon energy range of 5-250 eV. It uses a 185 mm period length planar permanent magnet insertion device as the photon source, sharing a straight section with another soft x-ray beamline at the CLS. The commissioning and performance of the beamline is reported. The high resolution photoabsorption spectra of Ar and PF(5) gases are reported. A resolving power of over 40,000 for photons in the low energy region and >10,000 for a wider energy range (8-200 eV) can be achieved. A photon flux of up to 2 x 10(12) photons/s per 100 mA with slit settings of 50 microm has been measured.
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Iluminación/instrumentación , Iluminación/normas , Refractometría/instrumentación , Refractometría/normas , Canadá , Diseño de Equipo , Análisis de Falla de Equipo , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
AIMS: To examine the impact of glucose tolerance status on the development of coronary artery disease (CAD) in working-age men in Japan. METHODS: This population-based retrospective cohort study included 111,621 men aged 31-60 years [63,558 with normal glucose tolerance (NGT); 37,126 with prediabetes; 10,937 with diabetes]. The Cox proportional-hazards regression model was used to identify variables related to the incidence of CAD. RESULTS: Multivariate analysis showed that, compared with NGT, diabetes increased the risk of CAD by 17.3 times (95% CI: 6.36-47.0) at ages 31-40 years, by 2.74 times (95% CI: 1.85-4.05) at ages 41-50 years and by 2.47 times (95% CI: 1.69-3.59) at ages 51-60 years. The HRs for CAD in men with diabetes aged 31-40 equaled that of men with NGT aged 51-60 [18.2 (7.15-46.4) and 19.4 (8.28-45.4), respectively]. CONCLUSION: The impact of diabetes on CAD was markedly greater in men aged 31-40 years compared with those aged 41-60 years.
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Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/epidemiología , Intolerancia a la Glucosa/complicaciones , Intolerancia a la Glucosa/epidemiología , Adulto , Glucemia , Diabetes Mellitus Tipo 2 , Prueba de Tolerancia a la Glucosa , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estado Prediabético , Estudios RetrospectivosRESUMEN
To show the possibility of sustained-release insulin formulation composed of PLGA, the optimum one was administered to BioBreeding rat, a model of spontaneous type I diabetes mellitus (IDDM). Every 2 weeks subcutaneous administration made their blood glucose level depend on the insulin release and food intake. However, all of them kept alive with little change or rather a little gain in body weight. Furthermore, some of pregnant rats with intermittent treatment bore fetuses, although additional insulin therapy seemed necessary. Therefore, the formulation could become a new tool as a provider of basal insulin for IDDM patients.
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Preparaciones de Acción Retardada/administración & dosificación , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Insulina/administración & dosificación , Ácido Láctico/química , Ácido Poliglicólico/química , Polímeros/química , Animales , Glucemia/análisis , Peso Corporal/efectos de los fármacos , Cápsulas , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/fisiopatología , Portadores de Fármacos , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Inyecciones Subcutáneas , Insulina/sangre , Insulina/química , Masculino , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Embarazo , Ratas , Ratas Endogámicas BB , Ratas Wistar , Factores Sexuales , Factores de TiempoRESUMEN
Tissue in body must quickly recognize injury to response to the rapid pace of epidermal growth. In skin, the epidermal cells must also react to danger signals from the surrounding extracellular lipid of the stratum corneum spaces and immediately participate by initiating the wound repair process. The topical administration of the lyotropic liquid crystal nanocube to stratum corneum rapidly broke down the lipid lamella structure which would be recognized as a wound without organ-change. This can activate a variety of biological processes. This study set out to determine whether the phase transition of the lipid to a neighbouring different physicochemical structure can stimulate keratinocyte cells and what mechanism is responsible for this response. Using small angle x-ray scattering (SAXS) analysis, a response to the transient structural change of lipid was detected which might result from the diffusion of oil and/or water from nanocube liquid crystal towards the lipid lamella phase. Simultaneously, a significant increase in growth factors and inflammatory cytokines was detected after administration of nanocube. Not only the excess expression of cytokines but also the extent of TEWL as a barrier marker of skin increased. These observations suggest that a structural change in lipid can stimulate and trigger recognition of a slight injury in the wound defence and a repair response as homeostasis. This method actually succeeded in improving photo-induced hyperpigmentation on a human face.
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Nanotecnología , Regeneración/efectos de los fármacos , Fenómenos Fisiológicos de la Piel/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Emulsiones , Factor de Crecimiento Epidérmico/metabolismo , Humanos , Ácido Hialurónico/metabolismo , Inmunohistoquímica , Interleucina-1/metabolismo , Queratolíticos/farmacología , Masculino , Ratones , Modelos Biológicos , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Dispersión de Radiación , Piel/química , Piel/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Tretinoina/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Rayos XRESUMEN
All-trans retinoic acid (atRA) which could smooth wrinkles and produce less pigmented skin after a few months of treatment has been studied in research into topical treatments for a potent inhibitor of new melanin production. However, the clinical responses of commercial atRA cream predominantly comprise severe inflammation. We report a novel nanotechnology "nanoegg" system giving improved effects of atRA self-assembly which were coated by CaCO3. Dorsal areas of hairless mouse and porcine skin were employed for administration of nanoegg ointment and commercial products. The mRNA for heparin-binding epidermal growth factor-like growth factor (HB-EGF) from tissues was measured by a real-time PCR method. All tissues were stained for detection of hyaluronate and the thickness of the epidermis. A clinical trial in humans was carried out at St. Marianna University in Japan. As a result, the irritation and inflammation associated with atRA molecules were substantially reduced. The physicochemical instability of atRA was also dramatically improved. Furthermore, nanoegg enhanced marked expression of mRNA for HB-EGF from keratinocytes, which is known as one of the markers of keratinocyte turnover. Also, production of hyaluronate was surprisingly in the intercellular spaces of the basal and spinous cell layers 2 days after treatment. Even at the low concentration of atRA in the nanoegg system, the proliferation and differentiation of keratinocyte was somewhat enhanced. A nanoegg may thus not only prevent adverse effects, but also markedly enhance the main effect.
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Queratolíticos/farmacología , Regeneración/efectos de los fármacos , Piel/efectos de los fármacos , Tretinoina/farmacología , Administración Tópica , Animales , Carbonato de Calcio/química , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Química Farmacéutica , Excipientes , Humanos , Ácido Hialurónico/farmacología , Técnicas In Vitro , Queratinocitos/efectos de los fármacos , Queratolíticos/administración & dosificación , Queratolíticos/química , Melaninas/biosíntesis , Ratones , Ratones Pelados , Pomadas , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Porcinos , Tretinoina/administración & dosificación , Tretinoina/químicaRESUMEN
Magnetic properties of Mn linear nanochains on a bcc Fe(1 1 0) surface have been studied using the first-principles real space-linear muffin-tin orbital atomic sphere approximation (RS-LMTO-ASA) method. We have considered up to nine Mn atoms deposited on bcc Fe(1 1 0). Our ab initio calculations reveal the competition between the antiferromagnetic Mn-Mn and Mn-Fe couplings, presenting a behavior which is very different from Mn nanowires on Fe(0 0 1), as shown in a previous publication. Due to this competition and non-negligible Dzyaloshinskii-Moriya interaction, noncollinear magnetic structures are stabilized as ground states for the Mn nanochains on Fe(1 1 0).
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The inhibitory effect of lecithinized superoxide dismutase (PC-SOD) on pulmonary metastasis in mice was investigated. In an experimental pulmonary metastasis model employing Meth A-T cells, significant and dose-dependent inhibition was observed after i.v. pre-administration of PC-SOD. Unmodified SOD (U-SOD) was also effective, but a 10-times higher dose was necessary to be significant. The pulmonary accumulation of Meth A-T cells labeled with 5-[125I]iodo-2'-deoxyuridine was not reduced by either PC-SOD or U-SOD, and neither of the compounds decreased pulmonary MPO activity. However, PC-SOD increased pulmonary SOD activity for longer, compared with U-SOD. In vitro addition of PC-SOD dose-dependently suppressed the growth of Meth A-T cells, while U-SOD had little effect. The combination of PC-SOD and S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a nitric oxide (NO)-generating agent, had an additive effect. It was also found that PC-SOD prevented a decrease of pulmonary NOx level following tumor cell inoculation. It was concluded that PC-SOD possessed antimetastatic activity, and its potency was superior to that of U-SOD. These results suggest that PC-SOD may prevent the excessive formation of oxygen radicals and peroxynitrite (ONOO-) which cause cell damage and facilitate tumor metastasis.
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Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Superóxido Dismutasa/farmacología , Animales , Sinergismo Farmacológico , Femenino , Radicales Libres/metabolismo , Pulmón/efectos de los fármacos , Pulmón/enzimología , Neoplasias Pulmonares/enzimología , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico/metabolismo , Donantes de Óxido Nítrico/administración & dosificación , Penicilamina/administración & dosificación , Penicilamina/análogos & derivados , Peroxidasa/metabolismo , Fosfatidilcolinas , Superóxido Dismutasa/administración & dosificación , Superóxido Dismutasa/aislamiento & purificación , Células Tumorales CultivadasRESUMEN
Recent studies have suggested that prolonged hypoxia results in increased production of reactive oxygen species in cardiomyocytes, which leads to apoptosis of these cells. We previously showed that lecithinized recombinant human copper, zinc-superoxide dismutase (rhSOD) showed increased bioavailability through greater membrane affinity and a longer half-life than unmodified SOD. The purpose of this study was to investigate whether lecithinized SOD plays a protective role against hypoxic injury in cardiomyocytes. Cultured rat cardiomyocytes incubated with lecithinized SOD (100 U/ml), unmodified SOD (100 U/ml), or vehicle alone were subjected to hypoxia for up to 72 h. Lecithinized SOD, but not unmodified SOD, was successfully delivered intracellularly, which was verified by Western blot and confocal laser-scanning microscopy. Treatment of cells with lecithinized SOD significantly suppressed hypoxia-induced cell damage. Since lecithinized SOD also suppressed hypoxia-induced DNA fragmentation, the improved cell survival provided by lecithinized SOD is thought to be mediated by its antiapoptotic effect. In summary, lecithinization resulted in a facilitated rhSOD delivery into cultured cardiomyocytes, which reduced mortality of cardiomyocytes exposed to prolonged hypoxia.
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Hipoxia de la Célula , Corazón/fisiología , Miocardio/patología , Superóxido Dismutasa/metabolismo , Animales , Animales Recién Nacidos , Células Cultivadas , Daño del ADN , Portadores de Fármacos , Corazón/efectos de los fármacos , Humanos , Cinética , Microscopía Confocal , Fosfatidilcolinas , Ratas , Ratas Wistar , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacología , Superóxido Dismutasa/farmacologíaRESUMEN
The study of T cells involved in the immune reaction that occurs in engrafted organs should provide information that would be helpful in the regulation of allograft rejection in organ transplantation. Toward this end, we focused on detection and characterization of accumulating T cells in mouse skin allografts from B10.A(4R) to C57BL/6 mice in vivo. T cell receptor beta genes were amplified by reverse transcriptase-PCR from mRNA of the skin grafts, and accumulating T cell receptor beta gene clonotypes were identified by their single strand conformation polymorphism. Their joining region usage and the amino acid sequences of the complementarity-determining region-3 were then determined. The results were as follows: (1) Distinct oligoclonal accumulation of T cells was more prevalent in the skin allografts than in the syngenic skin grafts. (2) Although the accumulating T cell clonotypes appeared to use many different variable-region gene families, preferential combinations of variable region-joining region were found. (3) Several homologous amino acid sequences were found in these accumulating TCR beta genes in allografts, suggesting that these T cells are driven by the same or similar antigens. (4) In addition, little T cell accumulation was found in spleens from the mice with allografts or syngenic skin grafts. Taken together, accumulating T cells in the skin allografts were detected in vivo, and some appeared to have characteristics in common. This may lead to T cell clonotype-specific therapy in organ transplantation.
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Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Trasplante de Piel , Linfocitos T/citología , Linfocitos T/ultraestructura , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células Clonales , Sondas de ADN , Ensayo de Inmunoadsorción Enzimática , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Transcripción GenéticaRESUMEN
Superoxide dismutase (SOD) is an enzyme used in the treatment of oxygen radical-related diseases. Lecithinization of SOD enhances its pharmacological activity. Lecithinized SOD (PC-SOD) inhibits human immunodeficiency virus (HIV) types 1 and 2 in MT-4 cells. HIV-1-infected MT-4 cells were cultured for 5 days in the presence of PC-SOD, at various concentrations. In an MTT assay, reverse transcriptase (RT) activity of the cell extract and p24 antigen production were measured. Untreated, HIV-1-infected MT-4 cells served as control. PC-SOD inhibited viral replication most effectively at 2500 U/ml, a concentration that did not affect cell viability, with an EC50 value of 718 U/ml. PC-SOD treatment inhibited RT activity and p24 production in a dose-dependent manner. Western blot analysis of the HIV-1-infected MT-4 cells treated with PC-SOD at 2500 U/ml did not detect any expression of viral proteins. Failure to inhibit virus adsorption, proviral DNA and mRNA synthesis, and RT and proteinase enzyme activity suggests that the mechanism of action of PC-SOD is entirely different from those of the currently available anti-HIV drugs. PC-SOD shows synergistic interaction with AZT, ddI, ddC, KNI-272, and dextran sulfate. PC-SOD also inhibited the oxidative stress-induced depletion of sulfhydryls, which are the cause of diminished antioxidant defenses in HIV-infected patients.
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Fármacos Anti-VIH/farmacología , VIH-1/efectos de los fármacos , VIH-2/efectos de los fármacos , Fosfatidilcolinas , Superóxido Dismutasa/farmacología , Ácido Aspártico Endopeptidasas/metabolismo , Western Blotting , Línea Celular Transformada , Interacciones Farmacológicas , Proteasa del VIH/metabolismo , Transcriptasa Inversa del VIH/metabolismo , VIH-1/fisiología , VIH-2/fisiología , Humanos , Reacción en Cadena de la Polimerasa , ADN Polimerasa Dirigida por ARN/metabolismo , Células Tumorales Cultivadas , Replicación ViralRESUMEN
Cross sections for quasifree Compton scattering from the deuteron were measured for incident energies of E(gamma) = 236-260 MeV at the laboratory angle straight theta(gamma(')) = -135 degrees. The recoil nucleons were detected in a liquid-scintillator array situated at straight theta(N) = 20 degrees. The measured differential cross sections were used, with the calculations of Levchuk et al., to determine the polarizabilities of the bound nucleons. For the bound proton, the extracted values were consistent with the accepted value for the free proton. Combining our results for the bound neutron with those from Rose et al., we obtain 1-sigma constraints of alpha;(n) = 7.6-14.0 and beta;(n) = 1.2-7.6.
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Cross sections for elastic Compton scattering from the deuteron were measured over the laboratory angles straight theta(gamma) = 35 degrees -150 degrees. Tagged photons in the laboratory energy range E(gamma) = 84-105 MeV were scattered from liquid deuterium and detected in the large-volume Boston University NaI spectrometer. Using the calculations of Levchuk and L'vov, along with the measured differential cross sections, the isospin-averaged nucleon polarizabilities in the deuteron were estimated. A best-fit value of (alpha;-beta;) = 2.6+/-1.8 was determined, constrained by dispersion sum rules. This is markedly different from the accepted value for the proton of (alpha;-beta;)(p) = 10.0+/-1.5+/-0.9.
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We investigated the controlled release of human insulin at an initial stage from poly(DL-lactic-co-glycolic acid) (PLGA, M(w) 6600) spherical matrices. PLGA microcapsules were prepared by the novel solvent evaporation multiple emulsion process. When the crystalline insulin was dispersed in dichloromethane as solid-in-oil (S/O) dispersion, it was found that most of insulin molecules were inlaid on the surface of PLGA microcapsules. Consequently, insulin-loaded PLGA microcapsules exhibited marked rapid release of insulin within several hours in both in vivo and in vitro experiments. On the other hand, the addition of glycerol or water in the primary dichloromethane dispersion results in drastically suppressed initial release. It was found by SEM observation that water- or glycerol-in-oil (W/O or G/O) type mini-emulsion droplets with a mean diameter of 300-500 nm were formed in this primary solution. This phenomenon can be theoretically presumed to occur because insulin and PLGA molecules, having amphiphilic properties, converge on the interface between the hydrophilic additive and dichloromethane. Hence, insulin molecules heterogeneously located in the inside of PLGA microcapsules, not on the surface, would be gradually released with PLGA hydrolytic decomposition. As an additional effect of glycerol, the initial burst was further suppressed due to the decrease of the glass transition temperature of PLGA from 42.5 to 36.7 degrees C. Since the annealing of PLGA molecules took place at around 37 degrees C, the porous structure of microspheres immediately disappeared after immersion in PBS or subcutaneous administration. The insulin diffusion through the water-filled pores would be effectively prevented. The strict controlled initial release of insulin from the PLGA microsphere suggested the possibility of utilization in insulin therapy for type I diabetic patients who need construction of a basal insulin profile.
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Materiales Biocompatibles/química , Insulina/química , Ácido Láctico/química , Ácido Poliglicólico/química , Polímeros/química , Animales , Materiales Biocompatibles/farmacocinética , Glucemia/análisis , Cápsulas , Cristalografía por Rayos X , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Diabetes Mellitus Experimental/sangre , Análisis Diferencial Térmico , Emulsiones , Humanos , Insulina/farmacocinética , Ácido Láctico/farmacocinética , Masculino , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/farmacocinética , Ratas , Ratas Wistar , Propiedades de Superficie , Factores de TiempoRESUMEN
Lipo-AS013 is being developed as an improved formulation of lipo-PGE(1), which is widely used in clinical practice in Japan and some Asian countries. We have previously reported that lipo-AS013, which is a lipid microsphere (LM) preparation of a chemically stable and lipophilic PGE(1) prodrug (AS013, Fig. 1), slowly releases small amounts of the active ingredient (AS013) in human plasma. In the present study, to estimate the vascular wall targeting ability and efficacy of lipo-AS013, we determined the hypotensive and blood flow-increasing effects of lipo-AS013, lipo-PGE(1), PGE(1)CD, and AS013. Lipo-AS013 was found to have longer-lasting hypotensive and blood flow-increasing effects than the other agents. The two LM preparations, lipo-PGE(1) and lipo-AS013, had a markedly stronger effect than PGE(1)CD and AS013 alone, demonstrating the benefit of drug delivery using LM. In spontaneously hypertensive rats (SHR), lipo-AS013 also had a significant hypotensive effect. To confirm vascular wall targeting by lipo-AS013, the localization of PGE(1) in the aorta and neovascular capillaries of rat was investigated by immunostaining. The results indicated that lipo-AS013 was more efficient at delivering the active ingredient (AS013) to the vessel wall. In conclusion, lipo-AS013 could supersede lipo-PGE(1) and PGE(1)CD in clinical use.
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Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Endotelio Vascular/metabolismo , Hipertensión/tratamiento farmacológico , Prostaglandinas F/farmacología , Vasodilatadores/farmacología , Alprostadil/metabolismo , Alprostadil/farmacología , Animales , Aorta Abdominal/metabolismo , Área Bajo la Curva , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Portadores de Fármacos , Endotelio Vascular/anatomía & histología , Humanos , Hipertensión/fisiopatología , Inmunohistoquímica , Masculino , Microscopía Confocal , Microesferas , Estructura Molecular , Prostaglandinas F/administración & dosificación , Ratas , Ratas Endogámicas SHR , Ratas WistarRESUMEN
The application of various resins for the nasal delivery of insulin was examined in rabbits. Intranasal administration of human insulin (28 U, 1 mg) mixed with fractionated sodium polystyrene sulfonate powder (an anionic resin with a particle size of 20-45 microns) caused a rapid increase of the plasma insulin level 413.0 +/- 71.7 microU/ml (mean +/- S.D.) after 15 min, while intranasal administration of insulin alone caused little increase. The blood glucose level decreased from 118.8 +/- 18.5 mg/dl to 65.8 +/- 13.8 mg/dl at 45 min after administration. These results were superior to those obtained with the unfractionated resin. Styrene-divinylbenzene copolymer (a nonionic resin; 20-45 microns fraction) showed similar enhancement of nasal insulin absorption. In contrast, polyacrylester (a nonionic resin; 20-45 microns fraction) and cholestyramine (a cationic resin) did not promote insulin absorption. These results suggest that some resins may be useful for nasal delivery of insulin.
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Sistemas de Liberación de Medicamentos , Insulina/administración & dosificación , Resinas de Plantas/administración & dosificación , Administración Intranasal , Animales , Glucemia/análisis , Humanos , Masculino , ConejosRESUMEN
A 23-year-old female with chronic leg ulcer was found to excrete the massive imidopeptides, among which Asp-Pro, Glu-Pro and Gly-Pro were identified. Essentially no prolidase activity was measured in her erythrocytes, while prolinase activity was within a normal range. Her 26-year-old brother also showed imidopeptiduria and erythrocyte prolidase deficiency, but no clinical symptoms were observed. Erythrocytes from her father and 30-year-old brother, who excreted no significant amounts of imidodipeptides, showed intermediate values for the prolidase activity between those for the patient and for normal adults, suggesting that they are heterozygous for this autosomal recessive disorder.