RESUMO
In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.
Assuntos
Nanopartículas , Neoplasias , Humanos , Lipossomos/uso terapêutico , Portadores de Fármacos/química , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológicoRESUMO
Circadian rhythms are an adaptive response of organisms to the environment that enables them to measure time. Circadian rhythms are some of the most studied biological rhythms. Serotonin (5HT) has been proposed as their modulator of circadian rhythms, playing a pivotal role in their establishment. However, 5HT concentrations are altered in insect organisms when they feed on some plant extracts. Insects show a variety of rhythms. The larval stage of the lepidopteran Spodoptera frugiperda is a pest of economically important crops. As a response, plants have developed secondary metabolites, such as azadirachtin, obtained from Azadirachta indica. We assessed the circadian rhythm of 5HT in the brain and digestive tube of larvae of S. frugiperda; furthermore, the effect of A. indica extract on the oscillations was evaluated. 5HT modulates the rhythms of locomotor activity, and if extracts of A. indica alter the concentration of 5HT, it can indirectly alter the rhythms of locomotor activity, as well as peristaltic movements of the intestine. Larvae were exposed to a 12 h:12 h light-dark (LD) photoperiod, and half of them remained for 72 h under constant darkness (DD). Tissue samples were obtained at six different times during a single 24 h period, and the amount of 5HT was quantified by high-performance liquid chromatography (HPLC). Data were statistically compared by a one-way ANOVA followed by a Tukey post hoc test and subjected to Cosinor analysis for assessment of 24 h rhythmicity. The results showed that the A. indica methanolic extract had an effect on the 5HT concentration of the brain and digestive tube of the larvae. In the brain, the 5HT increase in larvae fed with the extract could alter memory, learning, sleep, and locomotor activity processes. Whereas in the intestine, the 5HT decrease in the larvae fed with the extract could decrease peristalsis movements and, therefore, indirectly influence the antifeedant effect.
Assuntos
Azadirachta , Meliaceae , Animais , Ritmo Circadiano , Serotonina , SpodopteraRESUMO
OBJECTIVE: Some evidences indicate that exposure to molds or their products can be relevant for the loss of asthma control. Thus, we measured the mold burden present inside houses of subjects with asthma, and evaluated its relationship with asthma control. METHODS: Markers of asthma control in adult patients residing in Mexico City were evaluated through questionnaires and spirometry. Dust was collected from the patients' houses and its fungal content was determined by mold specific quantitative PCR (MSQPCR) for 36 fungal species. RESULTS: Forty-two patients with asthma (12 males, 30 females) with a mean age of 45 years (18-76 years) were included in the study. The level of asthma control measured through the Asthma Control Test ranged from 9 to 25 (mean 20.9). The FEV1/FVC ratio fluctuated from 38 to 106 %predicted (mean, 87.4 %predicted). Associations between mold burden and asthma control differed between males and females. Thus, concentrations of some molds, particularly Aspergillus fumigatus, Aureobasidium pullulans, Stachybotrys chartarum, Alternaria alternata, Cladosporium cladosporioides 2, Cladosporium herbarum, and Epicoccum nigrum, were negatively associated with parameters of asthma control in male subjects, but not in female patients. CONCLUSION: Our results showed that potential indoor exposure to some molds is associated with less asthma control in male subjects.
Assuntos
Poluição do Ar em Ambientes Fechados/análise , Asma/microbiologia , Poeira/imunologia , Fungos/metabolismo , Adulto , Alternaria/metabolismo , Aspergillus fumigatus/metabolismo , Asma/fisiopatologia , Cladosporium/metabolismo , Feminino , Volume Expiratório Forçado , Fungos/crescimento & desenvolvimento , Habitação , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Espirometria/métodos , Stachybotrys/metabolismo , Avaliação de Sintomas/métodos , Avaliação de Sintomas/estatística & dados numéricos , Capacidade VitalRESUMO
There is mounting evidence that 5-hydroxytryptamine (5-HT) plays a role in asthma. However, scarce information exists about the pulmonary expression of 5-HT receptors and its modification after allergic sensitization. In the present work, we explored the expression of 5-HT1A, 5-HT2A, 5-HT3, 5-HT4, 5-ht5a, 5-HT6, and 5-HT7 receptors in lungs from control and sensitized guinea pigs through qPCR and Western blot. In control animals, mRNA from all receptors was detectable in lung homogenates, especially from 5-HT2A and 5-HT4 receptors. Sensitized animals had decreased mRNA expression of 5-HT2A and 5-HT4 receptors and increased that of 5-HT7 receptor. In contrast, they had increased protein expression of 5-HT2A receptor in bronchial epithelium and of 5-HT4 receptor in lung parenchyma. The degree of airway response to the allergic challenge was inversely correlated with mRNA expression of the 5-HT1A receptor. In summary, our results showed that major 5-HT receptor subtypes are constitutively expressed in the guinea pig lung, and that allergic sensitization modifies the expression of 5-HT2A, 5-HT4, and 5-HT7 receptors.
Assuntos
Asma/metabolismo , Hipersensibilidade/metabolismo , Imunização , Receptores de Serotonina/metabolismo , Animais , Modelos Animais de Doenças , Cobaias , Masculino , Receptor 5-HT2A de Serotonina/metabolismo , Receptores 5-HT4 de Serotonina/metabolismoRESUMO
Practically all organs of the respiratory system are under the control of the autonomic nervous system. Double vegetative innervation, sympathetic and parasympathetic, contributes to the regulation of airway smooth muscle tone, and modulates secretion from the submucosal glands. Nevertheless, more than 20 years ago, the classical view of excitatory cholinergic and inhibitory adrenergic innervation changed considerably when the existence was proved of the non-adrenergic non-cholinergic system (NANC), which is able to produce both effects. Several purines and peptides have been postulated as neurotransmitters of this system, and some of them coexist with the acetylcholine or norepinephrine; for example, vasoactive intestinal peptide (VIP) on cholinergic nerves and neuropeptide Y in the adrenergic nerves. The aim of this paper is to describe the anatomo-physiological aspects of the airways' autonomic innervation and the possible implication of a neural mechanism that contributes in the development of the symptomatology in respiratory diseases.
Assuntos
Pulmão/inervação , Neurônios Adrenérgicos/fisiologia , Neurônios Colinérgicos/fisiologia , HumanosRESUMO
BACKGROUND: Passive smoking is associated with poor asthma control in children, but the mechanism is unknown. Leukotrienes are involved in the asthma pathogenesis and their synthesis is increased in adult subjects who actively smoke. OBJECTIVE: To evaluate whether passive smoking, as assessed by urinary cotinine levels, increases leukotriene production in children with or without asthma. METHODS: This was a prospective, cross-sectional study in which children with stable intermittent asthma (without exacerbation) and healthy control children were studied through spirometry and urinary concentrations of cotinine and leukotriene E(4) (LTE(4)). Both groups were balanced to include children with and without passive smoking. RESULTS: Ninety children (49 with asthma and 41 controls, 54.4% females) aged 9 years (range, 5-13 years) were studied. Urinary LTE(4) concentrations were progressively higher as cotinine levels increased (r(S) = 0.23, p = .03). LTE(4) also correlated with body mass index (BMI) (r(S) = 0.30, p = .004), and multiple regression analysis revealed that BMI was even more influential than cotinine for determining LTE(4) levels. LTE(4) concentrations were unrelated with gender, age, or spirometry. In turn, cotinine inversely correlated with forced expiratory volume in one second (FEV(1)) (r(S) = -0.22, p = .04) and forced vital capacity (FVC) (r(S) = -0.25, p = .02), but when analyzed by groups, these relationships were statistically significant only in children with asthma. CONCLUSIONS: Exposure to environmental tobacco smoke, as assessed by urinary cotinine levels, was associated with an increased urinary concentration of LTE(4), although BMI exerted more influence in determining its concentration. Urinary cotinine was associated with decreased lung function, mainly in children with asthma.
Assuntos
Asma/metabolismo , Leucotrieno E4/biossíntese , Poluição por Fumaça de Tabaco/efeitos adversos , Adolescente , Asma/urina , Criança , Pré-Escolar , Cotinina/urina , Estudos Transversais , Feminino , Volume Expiratório Forçado , Humanos , Leucotrieno E4/urina , Masculino , Análise Multivariada , Estudos Prospectivos , Análise de Regressão , Capacidade VitalRESUMO
OBJECTIVE: To assess airway resistance values and urinary leukotriene E4 (LTE4) concentrations before and after salbutamol inhalation in children with bronchopulmonary dysplasia (BPD). MATERIAL AND METHODS: Children with BPD were cross-sectionally studied to measure airway resistance by the interrupter technique (Rint), before and after inhaling 200 ig salbutamol, and to quantify urinary leukotriene E4 (LTE4) by immunoassay. RESULTS: Thirty one children with BPD (15 females) aged between 3 months and 9 years were studied. Our results showed that LTE4 did not correlate with Rint values (r = 0.12, p = 0.52) even after adjusting by gender, atopy history, steroid use, and gastroesophageal reflux. Likewise, LTE4 did not correlate with the degree of the airway response to salbutamol (r = -0.13, p = 0.50). A strong inverse association between age and Rint (r = -0.58, p < 0.001) was observed. CONCLUSION: We concluded that urinary LTE, did not correlate with airway resistance or with the response to a bronchodilator drug in children with BPD, suggesting that leukotrienes are not involved in airway obstruction in this disease.
Assuntos
Resistência das Vias Respiratórias , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/urina , Leucotrieno E4/urina , Adolescente , Criança , Pré-Escolar , Comorbidade , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/fisiopatologia , Doenças do Prematuro/urina , Masculino , Estudos ProspectivosRESUMO
El trasplante pulmonar es la única posibilidad terapéutica para los pacientes con pulmón en estado terminal; sin embargo, las complicaciones que se presentan después del transplante como la cicatrización bronquial deficiente, no han permitido que esta medida terapéutica sea muy exitosa. Esta complicación puede ser el resultado de varios factores como la inmunosupresión, la isquemia, las infecciones y/o el fenómeno de rechazo. En este trabajo se estudió el efecto de tres inmunosupresores (prednisona, azatioprina y ciclosporina A) en la cicatrización bronquial, en un modelo de autotransplante pulmonar canino. Se usaron tres parámetros comparativos para evaluar el efecto de los inmunosupresores sobre la anastomosis bronquial: el histológico (evaluación subjetiva de la cantidad de colágena que aparece en la anastomosis), la cuantificación de la concentración de la colágena por el método de Woessner y la medición de la fuerza tensil de ruptura (FTR). El grupo de prednisona a dosis alta mostró índice histológico de la colágena significativamente menor con respecto de los demás grupos. De la misma forma, la FTR fue también significativamente menor en el grupo de prednisona a dosis alta. La concentración de la colágena depositada no presentó diferencia entre ninguno de los grupos. Se concluye que las dosis altas de prednisona (4 mg/kg/día), afectan la anastomosis bronquial, pues disminuyen significativamente la FTR y el índice histológico de la colágena que se observó; sin embargo, este efecto no se debió a la cantidad de la colágena depositada, sino probablemente a la forma de depositarse de ésta o a una polimerización deficiente
Assuntos
Animais , Masculino , Feminino , Cães , Anastomose Cirúrgica , Grupos Controle/veterinária , Cães/anatomia & histologia , Cães/cirurgia , Tratamento Farmacológico/estatística & dados numéricos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Transplante Autólogo , Transplante de Pulmão , CicatrizaçãoRESUMO
El presente trabajo pretende describir algunos conceptos básicos del bypass cardiopulmonar cuando es utilizado en protocolos de investigación en modelos animales. Describimos los aspectos técnicos de interés que debe conocer el investigador y el personal que trabaja en centros hospitalarios donde se realizan estos procedimientos de perfusión. El perfusionista es el especialista calificado en manejar la bomba de circulación extracorpórea durante situaciones médicas donde es necesario el soporte temporal de la función circulatoria. Además, es el experto en el conocimiento de la variedad de equipo y es responsable de su buen funcionamiento. Está capacitado para poder administrar algunos medicamentos de acuerdo al protocolo de perfusión. Es así como describimos parte del equipo de circulación extracorpórea, y algunos aspectos fisiológicos durante el bypass cardiopulmonar. En esta monografía no intentamos discutir la multitud de variaciones posibles de cómo realizar el bypass cardiopulmonar, sino que muestra los principios básicos para poder entender los circuitos extracorpóreos
Assuntos
Circulação Extracorpórea/história , Circulação Extracorpórea/instrumentação , Circulação Extracorpórea/métodos , PerfusãoRESUMO
En el presente trabajo evaluamos la utilidad, cicatrización, cambios macroscópicos y microscópicos del pericardio bovino tratado con glutaraldehído (PBTG) preparado en nuestro laboratorio al reforzar resecciones no anatómicas de tejido pulmonar en perros. Utilizamos 12 perros mestizos que fueron divididos en dos grupos de estudios a los cuales se les resecó el 30 por ciento del lóbulo craneal del pulmón derecho y dicha resección fue reforzada con tiras de pericardio bovino tratado con glutaraldehído. Grupo I (n = 6), las tiras de pericardio bovino tratado con glutaraldehído se fijaron con material de sutura no absorbible. Grupo II (n = 6), la resección y fijación de las tiras de pericardio bovino tratado con glutaraldehído se llevó a cabo por medio de una engrapadora. Los animales fueron evaluados clínicamente y radiológicamente a diario durante la primera semana postcirugía y, cada tercer día el tiempo restante. Al finalizar el estudio fueron sometidos a eutanasia con sobredosis de pentobarbital sódico y se evaluó macroscópica y microscópicamente el estado de la bioprótesis y el pulmón. Todos los animales sobrevivieron al procedimiento quirúrgico y al tiempo de estudio que fue de ocho semanas, sin presentar ninguna alteración clínica o radiológica. En los dos grupos, macroscópicamente, el pericardio bovino tratado con glutaraldehído se adaptó bien el tejido pulmonar. Microscópicamente los animales de ambos grupos presentaron buena cicatrización con presencia de una capa de tejido fibroso sobre y en la periferia del pericardio bovino tratado con glutaraldehído y pulmón. Sin embargo, en el grupo I se observaron células gigantes a cuerpo extraño en la zona de las suturas. El pericardio bovino tratado con glutaraldehído preparado en nuestro laboratorio es un material útil para el reforzamiento de resecciones pulmonares no anatómicas en perros