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1.
J Comput Aided Mol Des ; 25(2): 145-61, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21181429

RESUMO

Four new potential agents muscarinic (allosteric modulators) were synthesized and studied by using the B3LYP density functional method. The optimum conformation and geometry structure of these compounds were determined and analyzed. Solvent effects were considered including a variable number (1-15) of explicit water molecules surrounding the compound in order to simulate the first hydration shell, as well as using the Tomasi's polarized continuum model (PCM). A similar simultaneous analysis of the potents W84 and DUO-3O allosteric modulator of muscarinic receptors was also carried out. The effect of the hydration on the total atomic charges and several intermolecular distances of interest were also discussed. The biological activity against acetylcholine of our four synthesized bispyridinium salts was determined. Relationships/tendencies structure-activity were established. Several general conclusions were underlined.


Assuntos
Colinérgicos/química , Colinérgicos/síntese química , Biologia Computacional , Ftalimidas/química , Ftalimidas/síntese química , Compostos de Piridínio/química , Compostos de Piridínio/síntese química , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/síntese química , Bases de Schiff/química , Bases de Schiff/síntese química , Acetilcolina/química , Regulação Alostérica , Animais , Colinérgicos/farmacologia , Feminino , Conformação Molecular , Ftalimidas/farmacologia , Compostos de Piridínio/farmacologia , Compostos de Amônio Quaternário/farmacologia , Ensaio Radioligante , Ratos , Ratos Wistar , Receptores Muscarínicos/química , Receptores Muscarínicos/efeitos dos fármacos , Bases de Schiff/farmacologia , Relação Estrutura-Atividade
2.
Radiologia (Engl Ed) ; 63(5): 391-399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34625194

RESUMO

OBJECTIVE: To analyze the anatomic characteristics of the left atrium and pulmonary veins in individuals undergoing ablation for atrial fibrillation and to identify possible anatomic factors related with recurrence. MATERIAL AND METHODS: We retrospectively reviewed the CT angiography studies done to plan radiofrequency ablation for atrial fibrillation in 95 patients (57 men; mean age, 65 ±â€¯10 y). We reviewed the anatomy of the pulmonary veins and recorded the diameters of their ostia as well as the diameter and volume of the left atrium. We analyzed these parameters according to the type of arrhythmia and the response to treatment. RESULTS: In 71 (74.7%) patients, the anatomy of the pulmonary veins was normal (i.e., two right pulmonary veins and two left pulmonary veins). Compared to patients with paroxysmal atrial fibrillation, patients with persistent atrial fibrillation had slightly larger diameter of the left pulmonary veins (left superior pulmonary vein 17.9 ±â€¯2.6 mm vs. 16.7 ±â€¯2.2 mm, p = 0.04; left inferior pulmonary vein 15.3 ± 2 mm vs. 13.8 ±â€¯2.2 mm, p = 0.009) and larger left atrial volume (91.9 ±â€¯24.9 cm3 vs. 70.7 ±â€¯20.3 mm3, p = 0.001). After 22.1 ±â€¯12.1 months' mean follow-up, 41 patients had sinus rhythm. Compared to patients in whom the sinus rhythm was restored, patients with recurrence had greater left atrial volume (81.4 ±â€¯23.0 mm3 vs. 71.1 ±â€¯23.2 mm3, p = 0.03). No significant differences in pulmonary vein diameters or clinical parameters were observed between patients with recurrence and those without. CONCLUSION: The volume of the left atrium is greater in patients with persistent atrial fibrillation and in those who do not respond to ablation.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Idoso , Fibrilação Atrial/cirurgia , Átrios do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/diagnóstico por imagem , Estudos Retrospectivos
3.
Clin Simul Nurs ; 60: 32-41, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34336011

RESUMO

BACKGROUND: The COVID-19 pandemic has made it necessary to adapt university health-education. Virtual simulation has been proposed to be a suitable tool. METHODS: A quasi-experimental study was conducted on nursing students in the final year. The virtual simulation platform vSim® was used. Improvements in knowledge, skills during simulation, satisfaction and selfconfidence obtained through the training provided were analyzed, as well as satisfaction with the platform. RESULTS: Prepost training knowledge improved. Skill acquisition improved between the first and last attempts in all cases. The levels of selfconfidence and satisfaction with the training and the platform used were high. CONCLUSIONS: The vSim® was a useful solution during the pandemic. Knowledge improved and high selfconfidence was obtained.

4.
Rev Neurol ; 70(12): 461-477, 2020 Jun 16.
Artigo em Espanhol | MEDLINE | ID: mdl-32500525

RESUMO

INTRODUCTION: Spinal cord injury is a traumatic or non-traumatic event that causes an alteration of sensory, motor or autonomic functioning and ultimately affects the physical, psychological and social well-being of the person who suffers it. A comprehensive approach to spinal cord injury requires many health resources and can place a considerable financial burden on patients, their families and the community. AIM: To review the literature published to date on the use of non-invasive brain stimulation, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcutaneous non-invasive spinal cord stimulation (tcSCS), as therapeutic strategies to improve the functionality of patients with spinal cord injury. The studies were grouped as addressing either non-invasive brain stimulation or non-invasive spinal cord stimulation. DEVELOPMENT: Altogether 32 studies were identified: 21 involving brain stimulation (14 in rTMS and 7 in tDCS) and 11 with spinal cord stimulation (tcSCS). All the studies were conducted in adult patients who had undergone a spinal cord injury. Despite significant variability in treatment protocols, patient characteristics and clinical assessment, the changes observed were reported in almost all the studies without producing any side effects and with motor or functional improvement. CONCLUSION: Non-invasive brain stimulation, as well as spinal cord stimulation, are promising techniques for the rehabilitation of patients with spinal cord injury due to their novelty, effectiveness and minimal side effects.


TITLE: Estimulación no invasiva cerebral y medular para la recuperación motora y funcional tras una lesión medular.Introducción. La lesión medular es un evento traumático o no traumático que causa una alteración de la función sensorial, motora o autonómica y, en última instancia, afecta a las características físicas, psicológicas y el bienestar social de la persona que lo sufre. El abordaje integral de la lesión medular requiere muchos recursos de salud y puede representar una considerable carga financiera para los pacientes, sus familias y la comunidad. Objetivo. Revisar la bibliografía publicada sobre el uso de la estimulación cerebral no invasiva, incluida la estimulación magnética transcraneal repetitiva (EMTr), la estimulación de corriente continua directa transcraneal (tDCS), así como la estimulación medular no invasiva transcutánea (tcSCS), como estrategias terapéuticas para mejorar la funcionalidad de los pacientes con lesión medular. Los estudios se agruparon bien como de estimulación no invasiva cerebral, bien como de estimulación medular no invasiva. Desarrollo. Se identificaron 32 estudios: 21 de estimulación cerebral (14 en EMTr y 7 en tDCS) y 11 de estimulación medular (tcSCS). Todos los estudios se realizaron en pacientes adultos que sufrieron una lesión medular. A pesar de la variabilidad significativa en los protocolos de tratamiento, las características de los pacientes y la evaluación clínica, los cambios observados se describieron en casi todos los estudios sin producir efectos secundarios con mejoría motora o funcional. Conclusión. La estimulación cerebral no invasiva, así como la estimulación medular, son técnicas prometedoras para la rehabilitación de pacientes con lesión medular debido a su novedad, su efectividad y mínimos efectos secundarios.


Assuntos
Terapia por Estimulação Elétrica/métodos , Traumatismos da Medula Espinal/terapia , Encéfalo , Humanos , Recuperação de Função Fisiológica , Estimulação da Medula Espinal/métodos
5.
Int Dent J ; 58(4): 187-93, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18783110

RESUMO

UNLABELLED: Latin American dental schools are at diverse stages in the continuum of implementation of infection control (IC) programmes that comply with evidence-based recommendations. Poor IC training may result in low compliance and negative attitudes against patients infected with blood borne pathogens (BBP). OBJECTIVE: To evaluate students' knowledge on IC and attitudes toward occupational BBP risks, in six dental schools in Latin America. METHODS: This survey was administered to convenience samples of dental students at one school in Costa Rica; four schools in Mexico, and one in Venezuela. The questionnaire included Likert-type scale evaluations of agreement with statements. Study variables included knowledge about and confidence in recommended IC procedures, degree of concern about HIV and HBV transmission in dental settings, and attitudes toward patients infected with BBP. Possible associations between variables were analysed using Pearson's Chi square and Kruskal Wallis tests. RESULTS: Substantial numbers of students had incomplete knowledge and often lacked confidence on IC and procedures; believed that HIV and HBV could be transmitted during clinical procedures; felt worried about occupational exposure to BBP, and held prejudices towards HIV and HBV infected individuals. CONCLUSIONS: Educational efforts are needed to enhance IC teaching and compliance. Diverse educational resources and international networks for research collaboration are available from organisations specialised in IC, hopefully paving the way to harmonising regional standards.


Assuntos
Atitude do Pessoal de Saúde , Educação em Odontologia , Controle de Infecções Dentárias , Estudantes de Odontologia/psicologia , Patógenos Transmitidos pelo Sangue , Costa Rica , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Hepatite B/prevenção & controle , Hepatite B/psicologia , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Masculino , México , Inquéritos e Questionários , Venezuela
6.
Granul Matter ; 19(4): 75, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-32009842

RESUMO

The mechanical behaviour of fibre-reinforced sands is primarily governed by the three-dimensional fibre architecture within the sand matrix. In laboratory, the normal procedures for sample preparation of fibre-sand mixtures generally produce a distribution of fibre orientations with a preferential bedding orientation, generating strength anisotropy of the composite's response under loading. While demonstrating the potential application of X-ray tomography to the analysis of fibre-reinforced soils, this paper provides for the first time a direct experimental description of the three-dimensional architecture of the fibres induced by the laboratory sample fabrication method. Miniature fibre reinforced sand samples were produced using two widely used laboratory sample fabrication techniques: the moist tamping and the moist vibration. It is shown that both laboratory fabrication methods create anisotropic fibre orientation with preferential sub-horizontal directions. The fibre orientation distribution does not seem to be affected by the concentration of fibres, at least for the fibre concentrations considered in this study and, for both fabrication methods, the fibre orientation distribution appears to be axisymmetric with respect to the vertical axis of the sample. The X-ray analysis also demonstrates the presence of an increased porosity in the fibre vicinity, which confirms the assumption of the "stolen void ratio" effect adopted in previous constitutive modelling. A fibre orientation distribution function is tested and a combined experimental and analytical method for fibre orientation determination is further validated.

7.
Rev. nefrol. diál. traspl ; 42(4): 4-4, Dec. 2022.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1508779

RESUMO

RESUMEN Introducción: La infección relacionada con catéter venoso central (CVC) es la complicación más frecuente y grave en los pacientes en hemodiálisis, asociada a una elevada mortalidad y morbilidad. En España, se ha publicado una incidencia de bacteriemia de 0.9 a 2 episodios por catéter y año. Diversas variables se han relacionado con la tasa de bacteriemia asociada a CVC, tales como disfunciones del catéter, la formación y experiencia del personal de enfermería, el número de sesiones de hemodiálisis y la duración de las mismas. El objetivo del presente estudio es analizar la influencia de las variables citadas en la aparición de bacteriemias, en pacientes portadores de catéteres en una unidad de hemodiálisis de un hospital de tercer nivel en España. Material y métodos: Estudio analítico, observacional y retrospectivo en el que se obtuvieron los datos relativos a la formación recibida y experiencia del personal de enfermería, el número y duración de sesiones de hemodiálisis por paciente y disfunciones de CVC. Se contabilizaron las bacteriemias acontecidas en un año, a través de la base de datos de la unidad, y se analizó la posible relación de tales variables en la tasa de bacteriemia. Resultados: Sobre un total de 41 catéteres tunelizados en 35 pacientes, observados durante 365 días, se obtuvo una tasa de incidencia de 1.45/1000 días de catéter, no habiendo encontrada relación estadísticamente significativa con la formación del personal de enfermería (p=0.330), experiencia (p=0.668), número de disfunciones y manipulaciones de catéter (p=0.718; p=0.118). Se objetivó relación inversa con el número y duración de sesiones (p=0.02). Conclusiones: Es preciso seguir analizando la relación entre las variables mencionadas y la tasa de bacteriemias. Abordarlo desde un punto de vista multicéntrico o aumentar el tiempo de observación de forma prospectiva pueden ser aspectos a tener en cuenta para determinar las variables que parecen tener una relación directa con la infección de CVC, que en otros contextos se ha llegado a evidenciar.


ABSTRACT Introduction: Central venous catheter (CVC)-related infection is the most frequent and serious complication in hemodialysis patients, associated with high mortality and morbidity. In Spain, an incidence of bacteremia of 0.9 to 2 episodes per catheter and year has been published. Variables have been related to the rate of bacteremia associated with CVC, such as catheter malfunctions, the training and experience of the nursing, the number of hemodialysis sessions and their duration. The objective of the present study is to analyze the influence of the aforementioned variables on the appearance of bacteremia in patients with catheters in a hemodialysis unit of a tertiary care hospital in Spain. Methods: Analytical, observational, and retrospective study in which data on the training received and experience of the nursing staff, the number and duration of hemodialysis sessions per patient and CVC dysfunctions were obtained. The bacteremia's that occurred in a year were counted, through the unit's database, and the possible relationship of such variables in the rate of bacteremia was analyzed. Results: On a total of 41 tunneled catheters in 35 patients, observed for 365 days, an incidence rate of 1.45/1000 catheter days was obtained, not having found a statistically significant relationship with the training of nursing staff (p = 0.330), experience (p=0.668), number of dysfunctions and manipulations of catheter (p=0.718; p=0.118). An inverse relationship was observed with the number and duration of sessions (p=0.02). Conclusions: It is necessary to continue analyzing the relationship between the mentioned variables and the rate of bacteremia. Approaching it from a multicenter point of view or increasing the observation time prospectively may be aspects to consider to determine the variables that seem to have a direct relationship with CVC infection, which has been shown in other contexts.

8.
J Biomed Mater Res A ; 77(3): 632-8, 2006 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-16514603

RESUMO

Fluconazole poly(D,L-lactic) acid (PLA) and poly(L-lactic) acid (L-PLA) implantable delivery rods were studied, in vitro and in vivo, as an alternative treatment of fungal osteomyelitis. Implantable rods loaded with 5% fluconazole (FLU) were prepared by the injection-molding method and sterilized by gamma-irradiation at a dose of 25 kGy. Loading efficiency, physical chemistry (high performance liquid chromatography, X-ray diffraction, gel permeation chromatography), and in vitro and in vivo release assays were performed to evaluate the novel delivery systems and the sterilization effect on implant characteristics. In spite of polymer degradation after gamma-irradiation, the loading efficiency, chemical stability, and crystallographic structure of FLU were not affected. In vivo studies were carried out in femoral bone marrow of rabbits. Approximately 85 and 80% of the total dose were released within 12 and 4 weeks from PLA and L-PLA rods, respectively. This showed a faster release rate of FLU in vivo than in vitro, showing almost zero-order kinetics from PLA rods.


Assuntos
Antifúngicos/administração & dosagem , Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos , Fluconazol/administração & dosagem , Raios gama , Micoses/tratamento farmacológico , Osteomielite/tratamento farmacológico , Esterilização , Animais , Ácido Láctico , Masculino , Micoses/microbiologia , Osteomielite/microbiologia , Poliésteres , Polímeros , Coelhos
9.
Arq. bras. med. vet. zootec. (Online) ; 73(3): 647-652, May-June 2021. ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1278370

RESUMO

The treatment of fractures from the thoracic limb in giant anteaters is extremely challenging. Unfamiliar and peculiar anatomical characteristics, robust musculature and the imminent need for an early return to limb function highlight such challenges. The objective of this report was to describe the successful use of anatomical osteosynthesis with a robust locking compression plate in a humeral fracture of an adult giant anteater. The patient was rescued on the highway after being run over and presented for treatment at the Veterinary Teaching Hospital. Surgical stabilization was performed using a craniomedial approach to the humerus, using a customized broad 3.5mm locking compression plate. The patient presented early limb support at 24 hours postoperatively. Radiographic monitoring was performed at 30, 60 and 90 days postoperatively, and bone healing was observed without any complications. It is concluded that the treatment of humerus fractures in giant anteaters requires robust fixation. The use of a reinforced locking compression plate system proved to be effective and adequate to the mechanical load that an adult individual of this species needs for early use of the thoracic limb and, at the same time, efficient in controlling interfragmentary movement, which allowed fracture consolidation.(AU)


O tratamento das fraturas do membro torácico dos tamanduás-bandeira (Myrmecophaga tridactyla) é extremamente desafiador. Características anatômicas pouco familiares e peculiares, musculatura muito desenvolvida e necessidade iminente de retorno precoce à função do membro destacam tais desafios. Objetivou-se, neste relato, descrever a utilização com sucesso da osteossíntese anatômica com placa bloqueada robusta em fratura umeral de um tamanduá-bandeira. O paciente foi resgatado em rodovia após atropelamento e atendido no Hospital Veterinário Universitário. Após sedação e avaliação física completa, foi realizado exame radiográfico, o qual revelou fratura completa oblíqua curta em diáfise média de úmero esquerdo. A estabilização cirúrgica foi realizada por abordagem craniomedial ao úmero, utilizando-se placa bloqueada (LCP) do sistema 3,5mm customizada. O paciente apresentou apoio precoce do membro com 24 horas de pós-operatório. Realizou-se acompanhamento radiográfico aos 30, 60 e 90 dias, sendo observada união clínica sem quaisquer complicações. Conclui-se que o tratamento das fraturas do úmero em tamanduás-bandeira exige robustez na fixação. A utilização de sistema reforçado de placa bloqueada mostrou-se efetiva e adequada à carga mecânica de que um indivíduo adulto dessa espécie necessita para uso precoce do membro torácico e, ao mesmo tempo, eficiente no controle da movimentação interfragmentária, o qual permitiu consolidação da fratura.(AU)


Assuntos
Animais , Consolidação da Fratura , Eutérios/cirurgia , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/veterinária , Fraturas do Úmero/cirurgia , Fraturas do Úmero/veterinária , Placas Ósseas/veterinária , Animais Selvagens/cirurgia
10.
Eur J Pharm Biopharm ; 60(3): 401-6, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15996581

RESUMO

A ciprofloxacin implant formulation composed of 12% hydroxyapatite, 36% tricalcium phosphate, 12% poly(DL-lactide) (PLA) and 40% ciprofloxacin was characterized in vivo for use in treatment of multibacterial bone infection. After the implant was inserted in the femur of rabbits, approximately 90% of the total ciprofloxacin was released within 8 weeks, maintaining therapeutic levels in the femur and tibia. Throughout the femoral cortex and marrow these remained higher than the minimum inhibitory concentrations (MIC) against the most common pathogens causing osteomyelitis. Levels in tibia cortex were also above MIC for 6 weeks. The implant was characterized in terms of polymer degradation and morphological and crystallographic changes. X-ray analyses confirmed the osteoconductivity and biocompatibility of these materials. The sequential changes in the femur were those of a normal surgical trauma reaction followed by a repair process. All the results confirmed that ciprofloxacin release is limited by its low solubility, and that implant erosion and bone ingrowth into the implants enhance the antibiotic release.


Assuntos
Doenças Ósseas Infecciosas/tratamento farmacológico , Ciprofloxacina/administração & dosagem , Animais , Materiais Biocompatíveis/química , Doenças Ósseas Infecciosas/microbiologia , Medula Óssea/diagnóstico por imagem , Medula Óssea/metabolismo , Medula Óssea/cirurgia , Ciprofloxacina/farmacocinética , Preparações de Ação Retardada , Portadores de Fármacos/química , Implantes de Medicamento , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Fêmur/cirurgia , Masculino , Coelhos , Radiografia , Propriedades de Superfície , Fatores de Tempo
11.
Int J Pharm ; 292(1-2): 43-52, 2005 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-15725552

RESUMO

Previous studies have shown that PLA-PEG nanoparticles (NP) are able to enhance the transport of the encapsulated model protein, tetanus toxoid (TT), across the rat nasal mucosa. The aim of this work was to study if the size of PLA-PEG particles affects the nasal transport of the encapsulated protein and, also, the potential contribution of blank nanoparticles to the transport of the free protein. To achieve this purpose, 125I-TT was encapsulated into PLA-PEG particles of different sizes (200 nm, 1.5, 5 and 10 microm) prepared by the water-in-oil-in-water solvent evaporation technique. Firstly, in order to investigate the carrier role of the particles, two series of either conscious or anaesthetized rats were nasally treated with 125I-TT-loaded NP, free 125I-TT, and a physical mixture of blank NP and free 125I-TT. Secondly, the influence of the particle size on the nasal transport of TT encapsulated into PLA-PEG particles was evaluated in conscious rats. The amount of radioactivity recovered in the blood compartment, lymph nodes and other relevant tissues was monitored for up to 24h. Finally, the nasal bioavailability of 125I-TT-loaded PLA-PEG NP was calculated. The results indicated that the use of anaesthesia enhances the transport of 125I-TT and that the physical presence of PLA-PEG NP does not affect the transport of the toxoid. In contrast, when TT was encapsulated into the particles its transport across the nasal mucosa of conscious rats was significantly enhanced. Furthermore, the efficacy of this transport was related to the particle size, reaching the most important transport for the smallest particle size. The intensity of this transport was also illustrated by the high nasal bioavailability of TT encapsulated into nanoparticles (200 nm) (F = 70-80%). These results led us to conclude that PLA-PEG NP can be accepted as nasal protein carriers for nasal administration.


Assuntos
Proteínas de Transporte/farmacocinética , Mucosa Olfatória/metabolismo , Tamanho da Partícula , Poliésteres/farmacocinética , Polietilenoglicóis/farmacocinética , Administração Intranasal , Animais , Disponibilidade Biológica , Proteínas de Transporte/química , Avaliação Pré-Clínica de Medicamentos/métodos , Radioisótopos do Iodo , Masculino , Nanoestruturas , Mucosa Olfatória/efeitos dos fármacos , Poliésteres/química , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/metabolismo , Toxoide Tetânico/farmacocinética
13.
J Control Release ; 68(1): 121-34, 2000 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-10884585

RESUMO

Implants to prevent or treat osteomyelitis are described, composed of phosphate/poly(d,l-lactide) blends containing the antibiotic gentamicin. Seven formulations of implants containing 3% gentamicin sulfate (GS) were prepared at 433 MPa and 693 MPa of compression pressure. The blends contained phosphates (25% hydroxyapatite (HAP), 75% tricalcium phosphate (TCP)) and 20% dl-PLA (weight average molecular weight, M(w): 30 kD). To prolong GS release, implants were coated with PLGA (M(w):100 kD) or dl-PLA (M(w): 200 kD). Various durations of GS release from these devices were demonstrated as feasible. Release times of more than 10 weeks were attained with implants coated with dl-PLA (M(w): 200 kD), greatly exceeding the performance of the commercial formulation.


Assuntos
Implantes Absorvíveis , Fosfatos de Cálcio/farmacocinética , Sistemas de Liberação de Medicamentos , Gentamicinas/farmacocinética , Hidroxiapatitas/farmacocinética , Fosfatos de Cálcio/uso terapêutico , Gentamicinas/uso terapêutico , Hidroxiapatitas/uso terapêutico , Osteomielite/tratamento farmacológico , Periósteo/metabolismo , Polímeros/farmacocinética , Polímeros/uso terapêutico
14.
J Control Release ; 93(3): 341-54, 2003 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-14644584

RESUMO

To elucidate the antibiotic release mechanism from implants composed of calcium phosphates (hydroxyapatite [HAP] and tricalcium phosphate [TCP]), 30 kDa poly(DL-lactide) (PLA-30) and ciprofloxacin (CFX), nine formulations were prepared. In vitro results show that the release rate decreased as compression load and PLA/phosphates ratio increased. In contrast, a slower percent release rate was observed with higher drug loading. Swelling-erosion-disintegration of the implants was observed during the release assays, due to CFX swelling. Two CFX implant formulations were selected for implantation in the femur of rabbits, according to in vitro results. The implant drug loads tested were 10% and 40% of CFX. The in vivo results showed that the antibiotic concentrations achieved throughout the femur were higher for 4 weeks than the minimum inhibitory concentrations (MIC) against the most common of the pathogens that cause osteomyelitis. The CFX-10% implant was considered the best formulation as CFX was totally released within 6 weeks, and therapeutic bone levels were achieved, and the histological and radiographic analyses showed the osteoconductive properties of the materials. All these results showed that CFX release is limited by its solubility, and the erosion-disintegration and bone ingrowth into the implants enhanced the antibiotic release.


Assuntos
Doenças Ósseas Infecciosas/tratamento farmacológico , Ciprofloxacina/administração & dosagem , Implantes de Medicamento/administração & dosagem , Animais , Doenças Ósseas Infecciosas/metabolismo , Doenças Ósseas Infecciosas/patologia , Ciprofloxacina/farmacocinética , Implantes de Medicamento/farmacocinética , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Fêmur/cirurgia , Masculino , Coelhos , Radiografia
15.
J Control Release ; 51(2-3): 143-52, 1998 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-9685911

RESUMO

This study examines the potential of 1,2-dipalmitoylphosphatidylcholine (DPPC), a major component of lung surfactant, to reduce the phagocytosis of microspheres by altering the cellular interactions occurring in the alveoli. These microspheres could be designed to act as a controlled delivery system for small molecules, peptides or proteins for pulmonary administration. Microspheres were prepared using poly (lactic-co-glycolic acid) (PLGA, 50/50 and encapsulated peroxidase as a model protein. DPPC was included in some formulations. The interaction of PLGA and DPPC-PLGA microspheres with phagocytic cells was evaluated using lung macrophages in culture. X-ray Photoelectron Spectra (XPS) results indicate that the inclusion of DPPC in the microspheres alters the microsphere surface chemistry, with the DPPC covering a large portion of the microsphere surface. The dominance of DPPC on the microsphere surface is highly beneficial in moderating the interaction occurring between the microspheres and phagocytic cells in the lung. Fluorescent confocal microscopy indicates that only 25% of cells internalized DPPC-coated particles, whereas 70% of those cells exposed to particles without the DPPC coating internalized particles after one hour of incubation.


Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Macrófagos Alveolares/efeitos dos fármacos , Microesferas , Fagocitose/efeitos dos fármacos , 1,2-Dipalmitoilfosfatidilcolina/farmacologia , Animais , Células Cultivadas , Ácido Láctico/química , Macrófagos Alveolares/metabolismo , Masculino , Microscopia Confocal , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/química , Surfactantes Pulmonares/química , Ratos , Ratos Wistar
16.
Eur J Pharm Biopharm ; 52(2): 151-8, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11522480

RESUMO

Three implants composed of phosphate (25% hydroxyapatite, 75% tricalcium phosphate), 20% poly(DL-lactide) (DL-PLA; weight-average molecular weight (Mw), 30 kD) and 3% gentamicin sulphate (GS) were assayed in vitro and in vivo to study their release profiles as potential drug delivery systems to prevent or treat osteomyelitis. To prolong GS release, some implants were coated with poly(lactide-co-glycolide) (PLGA; Mw, 100 kD; I-PLGA) or DL-PLA (Mw, 200 kD; I-PLA). GS levels were measured in bone, kidney and blood after implantation into the femur of rats. The release profiles show a burst in the first few days, followed by a slower release rate. After I-PLA implantation, bone antibiotic concentrations higher than the minimum bactericidal concentration were maintained for 4 weeks. A linear correlation between in vitro and in vivo GS release was found to continue until complete drug release. Histological and radiological analysis showed that the implants were well tolerated and gradual new bone formation was observed.


Assuntos
Implantes Absorvíveis , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Osso e Ossos/metabolismo , Gentamicinas/administração & dosagem , Gentamicinas/farmacocinética , Animais , Osso e Ossos/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Técnicas In Vitro , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Ratos , Ratos Wistar
17.
Eur J Pharm Biopharm ; 50(2): 227-36, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10962232

RESUMO

The effect on lung accumulation of modifying the surface compositions of (99m)Tc poly(lactide-co-glycolide) (PLGA) and (99m)Tc poly(ethylene glycol)-poly(lactide-co-glycolide) (PEG-PLGA) microspheres with different surfactants was assessed after intravenous injection into rats. Microspheres were prepared with PLGA or PEG-PLGA by the emulsion solvent evaporation method using polyvinyl alcohol (PVA), polyethylene glycol (PEG), albumin (BSA) or poloxamer 188 as surfactant, in the external aqueous phase. Commercial human albumin microspheres (Sferotec((R)), HAM) were used as reference. According to the European Pharmacopeia, >80% of (99m)Tc-HAM in the size range 10-50 microm, must be accumulated in the lung 15 min after intravenous administration. By modifying the surfactant, the resulting lung accumulation was 99% for (99m)Tc-HAM, and more than 50% for PLGA microspheres prepared with poloxamer 188 (1 and 4%), reaching 67% with 8% Poloxamer 188 and around 30-39% for PLGA and PEG-PLGA microspheres prepared with the other surfactants. PLGA microspheres made with 8% poloxamer 188 gave good quality lung images under a gamma camera for the first few minutes, subsequently liver radioactivity masked lung images.


Assuntos
Pulmão/diagnóstico por imagem , Tecnécio , Animais , Ácido Láctico/administração & dosagem , Microesferas , Tamanho da Partícula , Poliésteres/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/administração & dosagem , Cintilografia , Ratos , Ratos Wistar , Tensoativos/administração & dosagem , Distribuição Tecidual
18.
Phytopathology ; 94(11): 1207-14, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18944456

RESUMO

ABSTRACT The induction of defense compounds in oats (Avena sativa) in response to invasion by parasitic nematodes and to application of the wound hormone methyl jasmonate was examined. Oats cv. Quoll seedlings were challenged with Pratylenchus neglectus, Heterodera avenae, and Ditylenchus dipsaci and treated with 1 x 10(-4) M methyl jasmonate. Three compounds, isolated in methanolic root and shoot extracts of oats, exhibiting an absorbance spectrum typical of flavone glycosides, were induced by nematode invasion and methyl jasmonate. These were identified as flavone-C-glycosides by mass spectrometry. The effect of the flavone-C-glycosides on the invasion by and development of cereal cyst nematode H. avenae was assessed using methanolic extracts of shoots and roots from methyl jasmonate-treated plants. Both extracts impaired nematode invasion and development. When the extracts were fractionated by high voltage paper electrophoresis, only one flavone-C-glycoside, O-methyl-apigenin-C-deoxyhexoside-O-hexoside, inhibited nematode invasion. The protective effect of the induction of flavone-C-glycosides in oats by methyl jasmonate was evaluated against H. avenae and P. neglectus. Treatment with methyl jasmonate reduced invasion of both nematodes and increased plant mass, compensating for damage caused by the nematodes, and is attributed to the active flavone-C-glycoside. The active compound, O-methyl-apigenin-C-deoxyhexoside-O-hexoside, has not been implicated previously in plant defense against any pest or pathogen, and appears to provide protection against the major cereal nematodes Heterodera and Pratylenchus.

19.
J Aerosol Med ; 17(2): 174-85, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15294069

RESUMO

This report presents an overview of the potential of nanoparticles as nasal carriers for drug/vaccine administration. In addition, this report shows, for the first time, the efficacy of polylactic acid nanoparticles coated with a hydrophilic polyethyleneglycol coating (PEG-PLA nanoparticles) as carriers for the nasal transport of bioactive compounds. For this purpose, tetanus toxoid (TT), a high molecular weight protein (Mw 150,000 Da), was chosen as a model antigen and encapsulated in the PEG-PLA nano- and microparticles (200 nm and 1.5 microm respectively). These nanosystems were first characterized for their stability in the presence of lysozyme and also for their size, electrical charge, loading efficiency, in vitro release of antigenically active toxoid and afterwards, these formulations were administered intranasally to mice and the systemic and mucosal anti-tetanus responses were evaluated for up to 24 weeks. Additionally, PEG-PLA particles labeled with rhodamine 6G were administered intranasally to rats in order to visualize their interaction with the nasal mucosae by fluorescence microscopy. Their behavior was compared with that of the well known PLA nanoparticles (200 nm). The results showed that PLA nanoparticles suffered an immediate aggregation upon incubation with lysozyme, whereas the PEG-coated nanoparticles remained totally stable. The antibody levels elicited following i.n. administration of PEG-coated nanoparticles were significantly higher than those corresponding to PLA nanoparticles. Furthermore, PEG-PLA nanoparticles generated an increasing and a long lasting response. The qualitative fluorescence microscopy studies revealed that PEG-PLA particles are able to cross the rat nasal epithelium. These studies indicate that the PEG coating around the particles has a role in stabilizing PLA particles in mucosal fluids and that it facilitates the transport of the nanoencapsulated antigen, hence eliciting a high and long lasting immune response.


Assuntos
Portadores de Fármacos , Polietilenoglicóis/farmacologia , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/farmacocinética , Administração Intranasal , Animais , Disponibilidade Biológica , Líquido da Lavagem Broncoalveolar/química , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Imunização/métodos , Camundongos , Microscopia de Fluorescência , Modelos Animais , Tamanho da Partícula , Lavagem Peritoneal , Ratos , Saliva/química , Sensibilidade e Especificidade , Distribuição Tecidual , Vacinas/administração & dosagem
20.
Mil Med ; 165(7 Suppl 2): 52-6, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10920641

RESUMO

Military global influenza surveillance began in 1976 as an Air Force program. In 1997, the Department of Defense (DoD) Global Emerging Infections Surveillance and Response System expanded the program to include all services. Also included were local residents in areas where DoD overseas research activities operated. This new, worldwide DoD surveillance infrastructure provides valuable information and can respond quickly to outbreaks. This was demonstrated during the current influenza season when a suspected outbreak was reported in Panama. In less than 3 weeks, specimens were collected, transported, and cultured, and isolates were subtyped and sent to the Centers for Disease Control and Prevention for further studies. This influenza surveillance initiative combines viral isolation, antigenic characterization, and molecular sequencing with clinical and public health management of information. The information obtained is shared with the Centers for Disease Control and Prevention and the World Health Organization and has contributed to important decisions in influenza vaccine composition.


Assuntos
Influenza Humana/epidemiologia , Medicina Militar/organização & administração , Vigilância da População , Saúde Global , Órgãos Governamentais , Humanos , Vacinas contra Influenza , Vigilância da População/métodos , Estados Unidos
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