RESUMO
Improved therapies for inflammatory bowel diseases are sorely needed. Novel therapeutic agents and the development of controlled release systems for targeted tissue delivery are interesting approaches to overcome these barriers. We investigated the activity of trans-chalcone (T) in acetic acid-induced colitis in mice and developed, characterized, and determined the therapeutic effect of pectin/casein polymer microcapsules containing T (MT) in a colitis mouse model. In vitro, compound release was achieved in simulated intestinal fluid but not in the simulated gastric fluid. In vivo, since T at the dose of 3 mg/kg but not 0.3 mg/kg ameliorated colitis, we next tested the effects of MT at 0.3 mg/kg (non-effective dose). MT, but not free T at 0.3 mg/kg, significantly improved colitis outcomes such as neutrophil recruitment, antioxidant capacity, cytokine production, and NF-kB activation. This translated into reduced macro and microscopic damage in the colon. T release from the microcapsules is mediated by a pH-dependent and pectinase-regulated mechanism that provide controlled and prolonged release of T. Moreover, MT lowered the required dose for T therapeutic effect, indicating that could be a suitable pharmaceutical approach to colitis treatment. This is the first demonstration that T or MT is effective at reducing the signs of colitis.
Assuntos
Chalcona , Chalconas , Colite , Camundongos , Animais , Caseínas , Chalcona/farmacologia , Cápsulas/farmacologia , Pectinas , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , NF-kappa B , Modelos Animais de DoençasRESUMO
ABSTRACT Laser photocoagulation is a safe method for the treatment of retinal disorders. We present a case of a 21-year-old woman with high myopia, retinal detachment in the right eye, and bilateral lattice degeneration. She underwent surgical repair in the right eye followed by bilateral retinal laser therapy. During laser photocoagulation of the left eye, she experienced a generalized tonic-clonic seizure for the first time in her life. She had a positive family history of epilepsy. Neurological examination and brain magnetic resonance imaging findings were normal, but an electroencephalogram revealed epileptogenic discharges, more frequent during photostimulation. She avoided flickering lights during the 2-year follow-up, without seizure recurrence. Approximately 5% of patients with epilepsy have photosensitive epilepsy, of whom a considerable proportion will experience seizures only during exposition to flashing lights. Laser photocoagulation was already successfully employed in an animal model of photosensitive epilepsy. Personal or family history of photosensitivity warrants a neurological consultation before retinal treatment with laser therapy.
RESUMO Fotocoagulação a laser é método seguro para tratamento de retinopatias. Apresentamos o caso de uma mulher de 21 anos com alta miopia e degeneração lattice bilateral que sofreu descolamento de retina no olho direito e foi submetida a tratamento cirúrgico e ulterior laserterapia. Durante a fotocoagulação no olho esquerdo, ela teve uma convulsão tônico-clônica generalizada, a primeira em sua vida. Havia história familiar de epilepsia. O exame neurológico e a ressonância magnética de en céfalo foram normais, mas o electroencefalograma revelou descargas epileptogênicas, mais frequentes durante a fotoesti mulação. Ela evitou luzes piscantes durante os 2 anos subsequentes, sem recorrência de convulsões. Cerca de 5% dos pacientes com epilepsia têm fotossensibilidade. Proporção considerável deles terá convulsões somente durante exposição à luz piscante. Fotocoagulação a laser já foi empregada como modelo animal de sucesso para epilepsia fotossensível. Presença de fotossensibilidade na história pessoal ou familiar deve merecer avaliação neurológica antes do tratamento retiniano.
RESUMO
Laser photocoagulation is a safe method for the treatment of retinal disorders. We present a case of a 21-year-old woman with high myopia, retinal detachment in the right eye, and bilateral lattice degeneration. She underwent surgical repair in the right eye followed by bilateral retinal laser therapy. During laser photocoagulation of the left eye, she experienced a generalized tonic-clonic seizure for the first time in her life. She had a positive family history of epilepsy. Neurological examination and brain magnetic resonance imaging findings were normal, but an electroencephalogram revealed epileptogenic discharges, more frequent during photostimulation. She avoided flickering lights during the 2-year follow-up, without seizure recurrence. Approximately 5% of patients with epilepsy have photosensitive epilepsy, of whom a considerable proportion will experience seizures only during exposition to flashing lights. Laser photocoagulation was already successfully employed in an animal model of photosensitive epilepsy. Personal or family history of photosensitivity warrants a neurological consultation before retinal treatment with laser therapy.
Assuntos
Epilepsia Reflexa , Terapia a Laser , Descolamento Retiniano , Feminino , Humanos , Epilepsia Reflexa/cirurgia , Convulsões/etiologia , Convulsões/diagnóstico , Convulsões/cirurgia , Descolamento Retiniano/cirurgia , LasersRESUMO
UVB radiation is certainly one of the most important environmental threats to which we are subjected to. This fact highlights the crucial protective role of the skin. However, the skin itself may not be capable of protecting against UVB depending on irradiation intensity and time of exposition. Sun blockers are used to protect our skin, but they fail to fully protect it against oxidative and inflammatory injuries initiated by UVB. To solve this issue, topical administration of active molecules is an option. 15-Deoxy-Δ 12,14-prostaglandin J2 (15d-PGJ2) is an arachidonic acid-derived lipid with proresolution and anti-inflammatory actions. However, as far as we are aware, there is no evidence of its therapeutic use in a topical formulation to treat the deleterious events initiated by UVB, which was the aim of the present study. We used a nonionic cream to vehiculate 15d-PGJ2 (30, 90, and 300 ng/mouse) (TFcPGJ2) in the skin of hairless mice. UVB increased skin edema, myeloperoxidase activity, metalloproteinase-9 activity, lipid peroxidation, superoxide anion production, gp91phox and COX-2 mRNA expression, cytokine production, sunburn and mast cells, thickening of the epidermis, and collagen degradation. UVB also diminished skin ability to reduce iron and scavenge free radicals, reduced glutathione (GSH), sulfhydryl proteins, and catalase activity. TFcPGJ2 inhibited all these pathological alterations in the skin caused by UVB. No activity was observed with the unloaded topical formulation. The protective outcome of TFcPGJ2 indicates it is a promising therapeutic approach against cutaneous inflammatory and oxidative pathological alterations.
Assuntos
Estresse Oxidativo , Prostaglandinas , Administração Tópica , Animais , Camundongos , Camundongos Pelados , Prostaglandinas/metabolismo , Pele/metabolismo , Raios UltravioletaRESUMO
This study aims to investigate the associations between bullying and moral disengagement in a Brazilian sample, using a mixed method design. Two-thousand three hundred and thirty-four adolescents (11-19 years; 42.9% girls) answered self-report measures on bullying and moral disengagement in response to bullying situations. Fifty-five participants were randomly selected and interviewed on their experiences on bullying at school. Results allowed to identify specific mechanisms of moral disengagement associated with bullying behavior among Brazilian adolescents. Qualitative analysis highlighted how moral disengagement mechanisms were spontaneously used by the adolescents to explain both the bullying and the bystander behaviors. Findings support the relevance of moral disengagement mechanisms in explaining bullying behaviors. The value of addressing these mechanisms when designing anti-bullying interventions is discussed.
RESUMO
The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. Recruited neutrophils and macrophages contribute to intestinal tissue damage via production of ROS and NF-κB-dependent pro-inflammatory cytokines. The introduction of anti-TNF-α therapies in the treatment of IBD patients was a seminal advance. This therapy is often limited by a loss of efficacy due to the development of adaptive immune response, underscoring the need for novel therapies targeting similar pathways. Vinpocetine is a nootropic drug and in addition to its antioxidant effect, it is known to have anti-inflammatory and analgesic properties, partly by inhibition of NF-κB and downstream cytokines. Therefore, the present study evaluated the effect of the vinpocetine in a model of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema, MPO activity, microscopic score and macroscopic damage, and visceral mechanical hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS radical scavenging ability, and normalized levels of anti-inflammatory cytokine IL-10. Moreover, vinpocetine reduced NF-κB activation and thereby NF-κB-dependent pro-inflammatory cytokines IL-1ß, TNF-α, and IL-33 in the colon. Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory, antioxidant, and analgesic effects in a model of acid acetic-induced colitis in mice and deserves further screening to address its suitability as an approach for the treatment of IBD.
Assuntos
Colite/tratamento farmacológico , NF-kappa B/efeitos dos fármacos , Alcaloides de Vinca/farmacologia , Ácido Acético , Analgésicos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Colite/induzido quimicamente , Camundongos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologiaRESUMO
Quercetin (1) is an anti-inflammatory and antioxidant flavonoid. However, the oral administration of 1 did not lead to beneficial effects in experimental animal colitis models, which involve cytokines and oxidative stress. A possible explanation is that the absorption profile of 1 prevents its activity. Therefore, it was reasoned that the controlled release of 1 would improve its therapeutic effect. Thus, the therapeutic effect and mechanisms of 1-loaded microcapsules in acetic acid-induced colitis in mice were evaluated. Microcapsules were prepared using pectin/casein polymer and 1. The oral administration of 1-loaded microcapsules decreased neutrophil recruitment, attenuated histological alterations, and reduced macroscopical damage, edema, and IL-1ß and IL-33 production in the colon samples. Microcapsules loaded with 1 also prevented the reduction of anti-inflammatory cytokine IL-10 and the antioxidant capacity of the colon. These preclinical data indicate that pectin/casein polymer microcapsules loaded with 1 improved the anti-inflammatory and antioxidant effects of 1 compared to the nonencapsulated drug. Therefore, quercetin seems to be a promising active molecule in inflammatory bowel disease if provided with adequate controlled release.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Colite/induzido quimicamente , Quercetina/farmacologia , Ácido Acético/efeitos adversos , Administração Oral , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/sangue , Anti-Inflamatórios/uso terapêutico , Antioxidantes/análise , Antioxidantes/química , Cápsulas , Colite/tratamento farmacológico , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos/métodos , Edema , Interleucina-1beta/efeitos dos fármacos , Interleucina-33 , Interleucinas/metabolismo , Masculino , Camundongos , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Peroxidase/efeitos dos fármacos , Quercetina/análise , Quercetina/sangue , Quercetina/químicaRESUMO
La causa de muerte más frecuente en los países desarrollados es la ateroesclerosis. Sus lesiones características, además del depósito lipídico, son el engrosamiento focal de la pared arterial con proliferación de células musculares lisas (CML) e infiltración mononuclear y presencia de vasos neoformados. En este trabajo estudiamos el fenómeno proliferativo y las alteraciones citogenéticas de las CML. Estas células, identificadas mediante inmunohistoquímica por su expresión de actina muscular específica, eran dipolides, con un alto índice de proliferación demostrado por expresión de la proteína nuclear PCNA. Un porcentaje elevado de CML expresó intensamente a la oconproteína p53. Además se encontraron claros indicios de inestabilidad cromosómica. Los hallazgos más frecuentes fueron trisomía del cromosoma 11. También se observó ampliación del gen FGF-3. Estos hallazgos permiten inferir que la proliferación de CML es activa, tiene relación con la acumulación o mutación de la oncoproteína p53 y además presenta alteraciones cromosómicas específicas y relacionadas con los factores de crecimiento. La presencia de este tipo de cambios nos lleva a considerar a la hiperplasia de las CML en la placa ateromatosa como una expresión celular de carácter clonal.