RESUMO
OBJECTIVE: To determine the value of microbubble contrast cystosonography in the diagnosis of bladder rupture in animals. DESIGN: Prospective, method comparison study from November 2019 to October 2020. SETTING: University teaching hospital. ANIMALS: Thirty-four ethically sourced cadavers of dogs, rats, and rabbits. INTERVENTIONS: In a prospective and blinded study, the cadavers were divided into 2 randomized groups: with bladder rupture (CR), and without bladder rupture (SR). Urinary catheterization was performed in all cadavers. Through the urethral catheter, bladders in CR group were ruptured using a rigid stainless steel guide wire. Microbubble contrast was infused into the bladder through the urethral catheter, while a single, blinded observer sonographically assessed the bladder. The time to diagnosis and the number of attempts needed for diagnosis were recorded. MEASUREMENTS AND MAIN RESULTS: The study included cadavers of 16 female Wistar rats, 6 female dogs, 11 male dogs, and 1 male rabbit. Time to diagnosis in dogs (2.25 ± 0.91 min) was statistically higher when compared to rats (1.15 ± 0.75 min; P = 0.03). Of the 34 cases, incorrect diagnosis of bladder rupture was made in only 2 dogs (6%), indicating a diagnostic sensitivity of 88.88%, specificity of 100%, and an accuracy of 94%. The positive predictive value was 1 and the negative predictive value was 0.9. CONCLUSIONS: Our study showed that the described method is accurate, sensitive, and specific for the detection of bladder rupture in animal cadavers of different species, size, and sex.
Assuntos
Traumatismos Abdominais , Doenças do Cão , Traumatismos Torácicos , Doenças da Bexiga Urinária , Masculino , Feminino , Ratos , Cães , Animais , Coelhos , Bexiga Urinária/diagnóstico por imagem , Meios de Contraste , Estudos Prospectivos , Ratos Wistar , Doenças da Bexiga Urinária/diagnóstico por imagem , Doenças da Bexiga Urinária/veterinária , Traumatismos Abdominais/veterinária , Traumatismos Torácicos/veterináriaRESUMO
The endothelium is a single cell layer of the vessel wall and a key regulator of blood flow in vascular beds. Local and systemic pathologies have been associated with alterations in endothelial function. However, targeting the endothelium with vasoconstrictor or vasodilator drugs is often accompanied by systemic effects. Here, we evaluated a liposome-microbubble delivery system as a vascular hydrophilic agonist carrier. Phenylephrine (Phe) or acetylcholine (Ach)-loaded liposomes were conjugated to microbubbles. The drug release was triggered by ultrasound (US), and the vascular response was assessed in rat aortic rings using an isolated organ chamber. Aortic rings incubated with Phe-liposome-microbubble conjugate, exposed to US showed a marked contractile response (0.79 ± 0.04 g) compared to empty liposomes conjugated to microbubbles, aortic rings exposed only to US, and Phe-liposome-microbubble conjugate without US exposure that elicited a minimal or no response. Expressed as %, contractile responses were 85.24 ± 4.31% and 12.62 ± 3.23% for Phe-Chol-liposome-microbubble conjugate and empty Chol-liposome-microbubble conjugate exposed to US, respectively. Addition of 1 × 10-5 M Ach to pre-contracted aortic rings decreased the contraction response from 1 to 0.21 g. The addition of Ach-liposome conjugate and exposure to US decreased the contraction response to 0.32 g. Additionally, the ED50 values for Phe and Ach released by US from liposome-microbubble conjugates were 3.6 × 10-8 M ± 2.8 × 10-9 M for Phe and 2.0 × 10-8 M ± 1.8 × 10-9 M. In conclusion, we evaluated a hybrid delivery system that consisted of loaded liposomes conjugated to microbubbles to deliver and release vascular agonists using UMMD.
Assuntos
Lipossomos , Microbolhas , Animais , Ratos , UltrassonografiaRESUMO
In the present paper, we show the experimental measurement of the growth of a microbubble created on the tip of a single mode optical fiber, in which zinc nanoparticles were photodeposited on its core by using a single laser source to carry out both the generation of the microbubble by photothermal effect and the monitoring of the microbubble diameter. The photodeposition technique, as well as the formation of the microbubble, was carried out by using a single-mode pigtailed laser diode with emission at a wavelength of 658 nm. The microbubble's growth was analyzed in the time domain by the analysis of the Fabry-Perot cavity, whose diameter was calculated with the number of interference fringes visualized in an oscilloscope. The results obtained with this technique were compared with images obtained from a CCD camera, in order to verify the diameter of the microbubble. Therefore, by counting the interference fringes, it was possible to quantify the temporal evolution of the microbubble. As a practical demonstration, we proposed a vibrometer sensor using microbubbles with sizes of 83 and 175 µm as a Fabry-Perot cavity; through the time period of a full oscillation cycle of an interferogram observed in the oscilloscope, it was possible to know the frequency vibration (500 and 1500 Hz) for a cuvette where the microbubble was created.
RESUMO
In this work, we have developed numerical simulations and weakly nonlinear analysis based on the multiple-scales perturbation technique for a coated microbubble that performs radial pulsations subject to an acoustic pressure disturbance in the far-field and whose encapsulated hyperelastic material obeys the Mooney-Rivlin equation. Departing from an elastic coating as a hyperelastic shell of finite thickness, we assume eventually that the shell is of very small thickness in comparison with the microbubble radius. Under this condition, we then perform weakly nonlinear analysis, to identify resonance conditions for small pressure disturbances of the acoustic field. In parallel and also for the limit of small thickness, we have carried out numerical simulations of the radial motion of the microbubble, identifying the onset of limit cycles via the construction of Poincare maps. Under both schemes, we have recognized the importance of two dimensionless hyperelastic parameters that dictate the main behavior of the oscillations: α∗ and ß∗. Decreasing the values of these parameters, the resonance conditions are drastically amplified, which is an expected result because of the weak rigidity of the hyperelastic solid, prevails. In this manner, we suggest that moderate values for these previous parameters can be widely advisable when, in medical diagnostic applications, we are applying microbubbles as contrast agents. Therefore, we recommend widely the use of shell softens, because in this case the amplitude of radial pulsation is always amplified.
RESUMO
BACKGROUND: Magnetic Fluid Hyperthermia (MFH) is a promising adjuvant for chemotherapy, potentiating the action of anticancer agents. However, drug delivery to cancer cells must be optimized to improve the overall therapeutic effect of drug/MFH combination treatments. PURPOSE: The aim of this work was to demonstrate the potentiation of 2-phenylethynesulfonamide (PES) at various combination treatments with MFH, using low-intensity ultrasound as an intracellular delivery enhancer. METHODS: The effect of ultrasound (US), MFH, and PES was first evaluated individually and then as combination treatments. Definity® microbubbles and polyethylene glycol (PEG)-coated iron oxide nanoparticles were used to induce cell sonoporation and MFH, respectively. Assessment of cell membrane permeabilization was evaluated via fluorescence microscopy, iron uptake by cells was quantified by UV-Vis spectroscopy, and cell viability was determined using automatic cell counting. RESULTS: Notable reductions in cancer cell viability were observed when ultrasound was incorporated. For example, the treatment US+PES reduced cell viability by 37% compared to the non-toxic effect of the drug. Similarly, the treatment US+MFH using mild hyperthermia (41°C), reduced cell viability by an additional 18% when compared to the effect of MH alone. Significant improvements were observed for the combination of US+PES+MFH with cell viability reduced by an additional 26% compared to the PES+MFH group. The improved cytotoxicity was attributed to enhanced drug/nanoparticle intracellular delivery, with iron uptake values nearly twice those achieved without ultrasound. Various treatment schedules were examined, and all of them showed substantial cell death, indicating that the time elapsed between sonoporation and magnetic field exposure was not significant. CONCLUSION: Superior cancer cell-killing patterns took place when ultrasound was incorporated thus demonstrating the in vitro ultrasonic potentiation of PES and mild MFH. This work demonstrated that ultrasound is a promising non-invasive enhancer of PES/MFH combination treatments, aiming to establish a sono-thermo-chemotherapy in the treatment of ovarian cancer.
Assuntos
Antineoplásicos/farmacologia , Hipertermia Induzida/métodos , Neoplasias Ovarianas/terapia , Sulfonamidas/farmacologia , Terapia por Ultrassom/métodos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Feminino , Humanos , Magnetismo , Microbolhas/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêuticoRESUMO
PURPOSE: Improved therapeutic options for cervical cancer are needed. The purpose of this study was to evaluate the synergetic, inhibitory effects of ultrasound-mediated paclitaxel (PTX)- and miR-34a-loaded microbubbles (MBs) on cervical cancer. METHODS: U14 cervical cancer cells and xenograft mouse tumors were treated with PTX-miR-34a-MBs. RESULTS: Levels of miR-34a increased in vitro and vivo after treatment with ultrasound-mediated PTX-miR-34a-MBs. Furthermore, this treatment decreased the proliferation of cervical cancer cells, microvessel density, and the expression of Bcl-2 and CDK6, both in vitro and in vivo. Furthermore, Bax expression was increased in the in vivo model. And, tumor volume and weight were significantly reduced by 78.57% and 87.97%, respectively (P < 0.01). CONCLUSIONS: These results indicate that ultrasound-mediated PTX-miR-34a-MBs synergistically inhibit the growth of cervical cancer via the upregulation of miR-34a and downregulation of Bcl-2 and CDK6. Thus, PTX-miR-34a-MBs in combination with ultrasound microbubbles are a promising anticancer delivery strategy for treating cervical cancer.
Assuntos
Sinergismo Farmacológico , MicroRNAs/genética , Microbolhas , Paclitaxel/farmacologia , Ultrassonografia/métodos , Neoplasias do Colo do Útero/terapia , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Proliferação de Células , Terapia Combinada , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/administração & dosagem , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Acoustic bubbles have wide and important applications in ultrasonic cleaning, sonochemistry and medical ultrasonics. A two-microbubble system (TMS) under ultrasonic wave excitation is explored in the present study, by using the boundary element method (BEM) based on the potential flow theory. A parametric study of the behaviour of a TMS has been carried out in terms of the amplitude and direction of ultrasound as well as the sizes and separation distance of the two bubbles. Three regimes of the dynamic behaviour of the TMS have been identified in terms of the pressure amplitude of the ultrasonic wave. When subject to a strong wave with the pressure amplitude of 1â¯atm or larger, the two microbubbles become non-spherical during the first cycle of oscillation, with two counter liquid jets formed. When subject to a weak wave with the pressure amplitude of less than 0.5â¯atm, two microbubbles may be attracted, repelled, or translate along the wave direction with periodic stable separation distance, depending on their size ratio. However, for the TMS under moderate waves, bubbles undergo both non-spherical oscillation and translation as well as liquid jet rebounding.
RESUMO
La ecografía Doppler transcraneal (EDTC) y el dúplex carotídeo (DC) pueden realizarse mediante dispositivos portátiles, lo que permite su utilización junto a la cama del paciente en el Servicio de Urgencias y en la sala de neuro intervencionismo. Ambas técnicas permiten el diagnóstico del estado del árbol vascular cerebral y facilitan un diagnóstico rápido y una decisión terapéutica adecuada. Existe una creciente utilización del dúplex transcraneal (DuTC), que nos permite, además, la valoración del parénquima cerebral, lo que es especialmente útil en la monitorización de la evolución de las hemorragias cerebrales, el efecto masa intracraneal y la hidrocefalia. Finalmente, la EDTC tiene un efecto terapéutico, ya que potencia la recanalización con activador tisular del plasminógeno (tPA). La EDTC, el DuTC y el DC son herramientas diagnósticas excelentes que deberían utilizarse en la evaluación inmediata de todos los pacientes con ictus isquémico o hemorrágico agudo.
Transcranial Doppler (TCD) and carotid duplex (CD) can be used as portable tests, thus allowing for bedside use in the Emergency Service and Neurointerventional Room. Both tests broaden the abilities of the stroke neurologist to rapidly evaluate the vascular tree, facilitating a rapid diagnosis and appro-priate therapeutic decisions. There is a growing use of transcranial duplex (TCDu), which also allows assessment of the brain parenchyma, which is especially useful in monitoring the evolution of brain hemorrhage, intracranial mass effect and hydrocephalus. Finally, the TCD has a therapeutic effect be-cause it enhances arterial recanalization after tPA administration. The TCD, TCDu and CD are excellent diagnostic tools that should be used in all patients with ischemic or hemorrhagic stroke.