RESUMEN
Aerosol dynamics is important to quantify in drug delivery to the lungs with the aim of delivering therapeutics to a target location and optimising drug efficacy. The macrocycle (2-hydroxypropyl)-ß-cyclodextrin (2-HP-ß-CD) is thought to alleviate symptoms associated with neurodegenerative diseases when inhaled but the hygroscopic response is not well understood. Here we measure the hygroscopic growth of individual aqueous aerosol containing 2-HP-ß-CD in optical tweezers through analysis of morphology-dependent resonances arising in Raman spectra. Droplets are analysed in the size range of 3-5 µm in radius. The evolving radius and refractive index of each droplet are measured in response to change in relative humidity from 98-20% to determine mass and radius based hygroscopic growth factors, and compared with dynamic vapour sorption measurements. Bulk solution refractive index and density measurements were used in accordance with the self-consistent Lorenz-Lorentz rule to determine melt solute and droplet properties. The refractive index of 2-HP-ß-CD was determined to be 1.520 ± 0.002 with a density of 1.389 ± 0.005 g cm-3. To our knowledge, we show the first aerosol measurements of 2-HP-ß-CD and determine hygroscopicity. By quantifying the hygroscopic growth and physicochemical properties of 2-HP-ß-CD, the impact of aerosol dynamics can be accounted for in tailoring drug formulations and informing models used to predict drug deposition patterns within the respiratory system.
Asunto(s)
2-Hidroxipropil-beta-Ciclodextrina/química , Aerosoles/química , Humectabilidad , Pinzas Ópticas , Espectrometría RamanRESUMEN
We utilize advanced laser fields to clear a path through a dynamic turbid medium, a concept termed "Optical path clearing (OPC)." Particles are evacuated from a volume of the medium using the gradient and/or scattering forces due to an applied laser field with a suitably tailored spatial profile. Our studies encompass both an analytical model and proof-of-principle experiments where paths are cleared in dense bulk colloidal suspensions. Based on our results we suggest that high-performance and high efficiency OPC will be achieved by multiple-step clearing using dynamic laser fields based on Airy or inverted axicon beams.
Asunto(s)
Electrónica/instrumentación , Rayos Láser , Luz , Procesamiento de Señales Asistido por Computador/instrumentación , Suspensiones/química , Diseño de EquipoRESUMEN
We present evidence that aerosol droplets, approximately 1-2microm in diameter, can be optically bound over a 4mm distance within a volume formed by the overlap of the central cores and rings of two counterpropagating Bessel beams. The sizes of the individual polydisperse aerosol particles can be estimated from the angular variation of the elastic light scattering. Scattered light from the two orthogonally polarized trapping beams and from a Gaussian probe beam of different wavelength can be used to provide independent estimations of size. The coalescence of two droplets was observed and characterized.
Asunto(s)
Aerosoles/química , Pinzas Ópticas , Agua/química , Rayos Láser , Nebulizadores y Vaporizadores , Tamaño de la Partícula , Dispersión de RadiaciónRESUMEN
The tremendous success of botulinum toxin type A (BOTOX(R), Allergan Inc.) in the cosmetic arena has acted as a stimulus for the development of other neurotoxins. After more than 2 decades of use, BOTOX(R) has become synonymous with wrinkle reduction and is considered to be the one of the most common non-surgical cosmetic procedures performed worldwide. Because of its vast popularity among patients seeking non-invasive methods to achieve facial rejuvenation, physicians from diverse specialties have integrated botulinum toxin injections into their existing practices. Herein, we present an overview of botulinum toxin products for cosmetic applications that have received regulatory approval or are under development.
Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Toxinas Botulínicas/uso terapéutico , Fármacos Neuromusculares/uso terapéutico , Envejecimiento de la Piel/efectos de los fármacos , Técnicas Cosméticas , Humanos , Inyecciones , RejuvenecimientoRESUMEN
We characterize a single beam supercontinuum "white light" trap and determine the trap stiffness in the transverse trapping plane. We realize a holographic white light trapping system using a spatial light modulator, and explore the generation of a dual beam trap and characterize its performance. We also demonstrate optical trapping and rotation of particles using a supercontinuum vortex beam. It is shown that orbital angular momentum can be transferred to spheres trapped in a supercontinuum vortex. Quantified rotation rates are demonstrated.
Asunto(s)
Micromanipulación/instrumentación , Pinzas Ópticas , Óptica y Fotónica , Algoritmos , Diseño de Equipo , Holografía/métodos , Rayos Láser , Luz , Micromanipulación/métodos , Microscopía , Modelos Estadísticos , Modelos Teóricos , Distribución NormalRESUMEN
This study was undertaken to examine GLUT1 quaternary structure. Independent but complementary methodologies were used to investigate the influence of membrane-solubilizing detergents on GLUT1/lipid/detergent micelle hydrodynamic radii. Hydrodynamic size analysis and electron microscopy of GLUT1/lipid/detergent micelles and freeze-fracture electron microscopy of GLUT1 proteoliposomes support the hypothesis that the glucose transporter is a multimeric (probably tetrameric) complex of GLUT1 proteins. GLUT1 forms a multimeric complex in octyl glucoside that dissociates upon addition of reductant. Some detergents (e.g., CHAPS and dodecyl maltoside) promote the dissociation of GLUT1 oligomers into smaller aggregation states (dimers or monomers). These complexes do not reassemble as larger oligomers when dissociating detergents are subsequently replaced with nondissociating detergents such as octyl glucoside or cholic acid. When dissociating detergents are replaced with lipids, the resulting proteoliposomes catalyze protein-mediated sugar transport, and the subsequent addition of solubilizing, nondissociating detergents generates higher (tetrameric) GLUT1 aggregation states. These findings suggest that some detergents stabilize while others destabilize GLUT1 quaternary structure. GLUT1 does not appear to exchange rapidly between protein/lipid/detergent micelles but is able to self-associate in the plane of the lipid bilayer.
Asunto(s)
Eritrocitos/ultraestructura , Transportador de Glucosa de Tipo 1/sangre , Transportador de Glucosa de Tipo 1/ultraestructura , Glucemia/metabolismo , Detergentes/farmacología , Técnica de Fractura por Congelación , Humanos , Cinética , Luz , Lípidos/farmacología , Micelas , Microscopía Electrónica , Conformación Proteica , Estructura Cuaternaria de Proteína , Dispersión de RadiaciónRESUMEN
We demonstrate enhanced optical guiding distances for microscopic particles using a supercontinuum light beam. The enhanced spectral bandwidth of the source leads to an elongated focal region. As a result we obtain a significant radial gradient force and axial radiation pressure force over a longer distance when compared to a monochromatic Gaussian beam. The guiding distances of up to 3mm that are observed for micron-sized particles with the supercontinuum beam are approximately twice those observed using continuous wave and femtosecond laser sources when considering beams of equivalent diameter. This guiding scheme is expected to be applicable to colloidal particles, biological cells and cold atom ensembles.
RESUMEN
There is no ideal filler, nor will there be a single product that can satisfy all requirements. However, RESTYLANE, a non-animal, stabilized hyaluronic acid (NASHA, Medicis), is a very versatile augmenting agent. It has been in clinical use for 8 years and experience has shown it to be close to the ideal filler in many respects. This review will outline the background to the use of RESTYLANE, and will focus on the clinical use of this material.
Asunto(s)
Técnicas Cosméticas , Fármacos Dermatológicos/uso terapéutico , Ácido Hialurónico/análogos & derivados , Ácido Hialurónico/uso terapéutico , Envejecimiento de la Piel/efectos de los fármacos , Fármacos Dermatológicos/efectos adversos , Humanos , Ácido Hialurónico/efectos adversosRESUMEN
The introduction and subsequent expression of foreign DNA inside living mammalian cells (transfection) is achieved by photoporation with a violet diode laser. We direct a compact 405 nm laser diode source into an inverted optical microscope configuration and expose cells to 0.3 mW for 40 ms. The localized optical power density of ~1200 MW/m2 is six orders of magnitude lower than that used in femtosecond photoporation (~104 TW/m2). The beam perforates the cell plasma membrane to allow uptake of plasmid DNA containing an antibiotic resistant gene as well as the green fluorescent protein (GFP) gene. Successfully transfected cells then expand into clonal groups which are used to create stable cell lines. The use of the violet diode laser offers a new and simple poration technique compatible with standard microscopes and is the simplest method of laser-assisted cell poration reported to date.
RESUMEN
Counterpropagating light fields have the ability to create self-organized one-dimensional optically bound arrays of microscopic particles, where the light fields adapt to the particle locations and vice versa. We develop a theoretical model to describe this situation and show good agreement with recent experimental data [Phys. Rev. Lett. 89, 128301 (2002)] for two and three particles, if the scattering force is assumed to dominate the axial trapping of the particles. The extension of these ideas to two- and three-dimensional optically bound states is also discussed.
RESUMEN
A one-dimensional optically coupled array of colloidal particles is created in a potential well formed by two counterpropagating Gaussian light beams. This array has analogies to linear chains of trapped atomic ions. Breathing modes and oscillations of the center of mass are observed. The stability of the array is in accordance with the Kramers model.
RESUMEN
At any instant, the human erythrocyte sugar transporter presents at least one sugar export site but multiple sugar import sites. The present study asks whether the transporter also presents more than one sugar exit site. We approached this question by analysis of binding of [3H]cytochalasin B (an export conformer ligand) to the human erythrocyte sugar transporter and by analysis of cytochalasin B modulation of human red blood cell sugar uptake. Phloretin-inhibitable cytochalasin B binding to human red blood cells, to human red blood cell integral membrane proteins, and to purified human red blood cell glucose transport protein (GluT1) displays positive cooperativity at very low cytochalasin B levels. Cooperativity between sites and K(d(app)) for cytochalasin B binding are reduced in the presence of intracellular ATP. Red cell sugar uptake at subsaturating sugar levels is inhibited by high concentrations of cytochalasin B but is stimulated by lower (<20 nM) concentrations. Increasing concentrations of the e1 ligand forskolin also first stimulate then inhibit sugar uptake. Cytochalasin D (a cytochalasin B analogue that does not interact with GluT1) is without effect on sugar transport over the same concentration range. Cytochalasin B and ATP binding are synergistic. ATP (but not AMP) enhances [3H]cytochalasin B photoincorporation into GluT1 while cytochalasin B (but not cytochalasin D) enhances [gamma-32P]azidoATP photoincorporation into GluT1. We propose that the red blood cell glucose transporter is a cooperative tetramer of GluT1 proteins in which each protein presents a translocation pathway that alternates between uptake (e2) and export (e1) states but where, at any instant, two subunits must present uptake (e2) and two subunits must present exit (e1) states.
Asunto(s)
Adenosina Trifosfato/metabolismo , Metabolismo de los Hidratos de Carbono , Eritrocitos/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , 3-O-Metilglucosa/metabolismo , Adenosina Trifosfato/química , Carbohidratos/química , Citocalasina B/metabolismo , Eritrocitos/química , Transportador de Glucosa de Tipo 1 , Humanos , Cinética , Maltosa/metabolismo , Modelos Químicos , Proteínas de Transporte de Monosacáridos/química , Unión Proteica , Estructura Cuaternaria de Proteína , Transporte de ProteínasRESUMEN
This article reviews the cosmetic use of botulinum toxin in upper face from both the historic and clinical viewpoints. The published literature and our current experience are outlined. Botulinum toxin type A in the upper face has become an extremely poplular cosmetic procedure and is outstandingly safe.
Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Técnicas Cosméticas , Músculos Faciales/efectos de los fármacos , Fármacos Neuromusculares/farmacología , Fármacos Neuromusculares/uso terapéutico , Toxinas Botulínicas Tipo A/historia , Toxinas Botulínicas Tipo A/inmunología , Toxinas Botulínicas Tipo A/farmacología , Relación Dosis-Respuesta a Droga , Cara , Músculos Faciales/anatomía & histología , Historia del Siglo XX , Humanos , Inyecciones Intramusculares , Fármacos Neuromusculares/historia , Fármacos Neuromusculares/inmunologíaRESUMEN
BOTOX is the universally accepted gold standard treatment for upper facial rejuvenation. BOTOX application in the mid and lower face and neck is a more advanced treatment requiring a detailed knowledge of underlying facial muscular anatomy and function as well as the patient's aesthetic desires and an ability to interpret the effects of BOTOX chemodenervation on their function.
Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Técnicas Cosméticas , Músculos Faciales/efectos de los fármacos , Músculos del Cuello/efectos de los fármacos , Fármacos Neuromusculares/uso terapéutico , Relación Dosis-Respuesta a Droga , Cara , Asimetría Facial/tratamiento farmacológico , Músculos Faciales/anatomía & histología , Encía/efectos de los fármacos , Humanos , Cuello , Músculos del Cuello/anatomía & histologíaRESUMEN
A positive attitude toward life at any age is now seen to be consistent with inclusion in all societal activities. A mere increase in years is no longer enough reason for "ageism." Botulinum Toxin (Botox) aesthetic treatments, because of their outstanding effectiveness and safety, can continue to play a positive role in the rebuttal of "ageism."
Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Técnicas Cosméticas , Cara , Fármacos Neuromusculares/administración & dosificación , Envejecimiento de la Piel , Músculos Faciales/efectos de los fármacos , Músculos Faciales/inervación , Humanos , Inyecciones , Desnervación Muscular , Músculos del Cuello/efectos de los fármacos , Músculos del Cuello/inervaciónRESUMEN
Radiofrequency resurfacing has recently emerged as a new modality for treating facial wrinkles. This approach uses a novel method of energy-mediated, "cool" cellular disintegration that is distinct from the tissue effects associated with heat-based lasers. Early clinical findings have shown that radio-frequency resurfacing results in significant improvement in wrinkles and overall cosmetic appearance. The technique is also assocaited with rapid healing, minimal pain, and a low incidence of adverse events. If initial clinical experience is confirmed in broader use, radiofrequency resurfacing could help expand the number of resurfacing procedures performed and could extend treatment to new and perhaps younger patients.
Asunto(s)
Procedimientos Quirúrgicos Dermatologicos , Electrocirugia , Envejecimiento de la Piel , Animales , Electrocirugia/instrumentación , Electrocirugia/métodos , Humanos , Terapia por Láser , Piel/patologíaRESUMEN
Calcitonin gene-related peptide (CGRP), a potent vasodilator, has been implicated in the pathogenesis of migraine. Its release from adult rat trigeminal neurons in culture was shown to be markedly increased by the activation of adenylate cyclase with forskolin. Modulation of this secretion was investigated by a number of agents with known inhibitory effects on cAMP generation mediated via receptor coupling to G(i/o) proteins. Significantly, forskolin-stimulated CGRP release could be closely correlated with the phosphorylation of the protein kinase A (PKA) substrate cyclic AMP response element-binding protein (CREB). Forskolin-stimulated CGRP release could be potently and effectively inhibited by the adenosine A(1) receptor-selective agonist GR79236X (pIC(50) = 7.7 +/- 0.1, maximal inhibition 65 +/- 2.5% at 300 nM), whereas the A(2A) (CGS21680) and the A(3) (2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide) receptor-selective agonists were without effect. GR79236X-mediated inhibition was abolished by the A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. Immunocytochemical studies and Western analysis revealed the presence of adenosine A(1) receptors on trigeminal neurons. However, despite the additional detection of 5-hydroxytryptamine (5-HT)(1B) receptors on these cells, the clinically effective antimigraine 5-HT(1B/1D) agonist sumatriptan did not inhibit forskolin-stimulated CGRP release nor did it show any effect on the concomitant CREB phosphorylation. In contrast, the mu-opioid agonist fentanyl elicited a 74 +/- 4% reduction in CGRP levels. Forskolin-stimulated CGRP release and CREB phosphorylation could be mimicked by incubation of the cells with chlorophenylthio-cAMP and blocked by pretreatment with the PKA inhibitor myrPKI(14-22). Taken together, the present data confirm the PKA-dependence of forskolin-stimulated CGRP release and suggest that A(1) adenosine agonists may warrant further investigation in models of migraine and neurogenic inflammation.
Asunto(s)
Adenosina/análogos & derivados , Péptido Relacionado con Gen de Calcitonina/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Neuronas/metabolismo , Receptores Purinérgicos P1/metabolismo , Adenosina/farmacología , Analgésicos Opioides/farmacología , Animales , Células Cultivadas , Colforsina/farmacología , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Interacciones Farmacológicas , Fentanilo/farmacología , Masculino , Neuronas/efectos de los fármacos , Neuronas/enzimología , Fenetilaminas/farmacología , Fosforilación/efectos de los fármacos , Agonistas del Receptor Purinérgico P1 , Ratas , Ratas Wistar , Receptor de Serotonina 5-HT1B , Receptores de Serotonina/biosíntesis , Agonistas de Receptores de Serotonina/farmacología , Sumatriptán/farmacología , Vesículas Sinápticas/enzimología , Vesículas Sinápticas/metabolismo , Nervio Trigémino/citología , Nervio Trigémino/metabolismoAsunto(s)
Adenosina Trifosfato/farmacología , Proteínas de Transporte de Monosacáridos/efectos de los fármacos , Detergentes/farmacología , Membrana Eritrocítica/química , Transportador de Glucosa de Tipo 1 , Humanos , Proteínas de Transporte de Monosacáridos/química , Proteínas de Transporte de Monosacáridos/metabolismo , Estructura Cuaternaria de ProteínaRESUMEN
1. A P2Y (nucleotide) receptor activity in a clonal population (B10) of rat brain capillary endothelial cells is coupled to inhibition of adenylyl cyclase and has functional similarities to the P2Y(T) (previously designated 'P2T') receptor for ADP of blood platelets. However, the only P2Y receptor which was detectable in a previous study of B10 cells by mRNA analysis was the P2Y(1) receptor, which elsewhere shows no transduction via cyclic nucleotides. We have sought here to clarify these issues. 2. The inhibition of forskolin-stimulated adenylyl cyclase induced by purified nucleotides was measured on B10 cells. The EC(50) value for 2-methylthioADP (2-MeSADP) was 2.2 nM and, surprisingly, 2-MeSATP was an almost equally strong agonist (EC(50)=3.5 nM). ATP and 2-ClATP were weak partial agonists (EC(50)=26 microM and 10 microM respectively) and under appropriate conditions could antagonise the activity on 2-MeSADP. 3. A known selective antagonist of the platelet P2Y(T) receptor, 2-propylthioadenosine-5'-(beta,gamma)-difluoromethylene) triphosphonate (AR-C 66096), was a competitive antagonist of this B10 cell receptor, with pK(B)=7.6. That ligand is inactive at the P2Y(1) receptor in the same cells. Conversely, the competitive P2Y(1) receptor antagonists, the 3', 5'- and 2', 5'-adenosine bis-monophosphates, are, instead, weak agonists at the adenylyl cyclase-inhibitory receptor. 4. The inhibition of adenylyl cyclase by 2-MeSADP was completely abolished by pertussis toxin. 5. In summary, these brain endothelial cells possess a P2Y(T)-type receptor in addition to the P2Y(1) receptor. The two have similarities in agonist profiles but are clearly distinguishable by antagonists and by their second messenger activations. The possible relationships between the B10 and platelet P2Y(T) receptors are discussed.