RESUMO
Reconstituted high-density lipoprotein (rHDL) nanoparticles are excellent transporters of molecules and very useful for targeted therapy as they specifically recognize the scavenger receptor, class B1 (SR-B1) that is present on the surface of a wide range of tumor cells. However, they have rarely been employed to transport photosensitizers (PS) for photodynamic therapy (PDT). Rhodamine (R) compounds have been dismissed as useful PSs for PDT due to their low 1O2 production, excitation wavelengths with little tissue penetration, and poor selectivity for tumor cells. It was recently demonstrated that when irradiating at 532 nm or with Cerenkov radiation (CR) from a ß-emitting radionuclide, R123, R6G, and RB undergo electron transfer reactions (type I reaction) with folic acid. R6G also produces type I reactions with O2. In this work, the photodynamic effects of the rHDL-R system were evaluated in vitro. rHDL nanoparticles loaded with R123, R6G, and RB were synthesized, and the PS was internalized into T47D tumor cells. When cells were irradiated with a 532-nm laser in the presence of an rHDL-R systems, a cytotoxic photodynamic effect was obtained in the order R6G > R123 > RB. In the presence of CR from a 177Lu source, cytotoxicity showed the order R6G > RB > R123. The higher cytotoxicity induced by R6G in both cases corresponds to higher cellular internalization and larger production of type I and II reactions. Thus, in this work, it is proposed that rHDL-R/177Lu system can be applied in theragnostics as a multimodal radiotherapy-PDT-imaging system (imaging by SPECT or Cerenkov) and in hypoxic solid tumors in which external radiation is not effective and 177Lu-CR acts as light source.
Assuntos
Nanopartículas , Fotoquimioterapia , Linhagem Celular Tumoral , Humanos , Lipoproteínas HDL , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , RodaminasRESUMO
We analyzed the participation of N-methyl-d-aspartate (NMDA) receptors in the neuronal damage caused by adult-onset hypothyroidism. Wistar rats were randomly assigned into four groups. The euthyroid group received tap water. The hypothyroid group received methimazole (60 mg/kg) in their drinking water to induce hypothyroidism. Two more groups of rats received the antithyroid treatment and were injected daily with the NMDA antagonist ketamine (15 mg/kg, sc) or MK-801 (0.5mg/kg, ip). Treatments were administered during 4 weeks. At the end of the respective treatments rats were deeply anaesthetized and perfused intracardially with 0.9% NaCl followed by 4% paraformaldehyde. The brains were removed from the skull, and coronal brain sections (7microm thick) were obtained. Neurons were counted in the CA1, CA2, CA3, and CA4 hippocampal regions differentiating between normal and atrophic cells by an experimenter blind to the treatment. The percentage of neuronal damage found in the MMI group was significantly greater in the hippocampal regions compared to the euthyroid group. In contrast, both NMDA antagonists were able to prevent the neuronal damage secondary to hypothyroidism in all hippocampal regions. Our results suggest that the neuronal damage caused in the hippocampus of adult-onset hypothyroid rats requires activation of NMDA channels.
Assuntos
Hipocampo/patologia , Hipotireoidismo/patologia , Neurônios/patologia , Receptores de N-Metil-D-Aspartato/fisiologia , Animais , Antitireóideos , Contagem de Células , Maleato de Dizocilpina/farmacologia , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/metabolismo , Ketamina/farmacologia , Masculino , Metimazol , Distribuição Aleatória , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
Aromatase CYP19 catalyzes the synthesis of estrogen from androgens in a tissue-specific manner. This enzyme is present in several tissues, including gonads, brain and fatty tissue. More recently, its presence has been described in vessels. Here, we describe the expression of aromatase in human uterine artery and compare its expression with that found in arteries of estrogen-dependent uterine leiomyomata from women. To do this, we employed immunohystochemical and in situ hybridization techniques. We used, a polyclonal antibody raised against the carboxyl terminus of aromatase (ARO) and RNAm probes, of the exon 1 of ARO. We found an increased immunoreactivity of ARO in uterine arteries of patients with leiomyoma as compared with control group. Probe showing positive signal in skin fibroblasts (1b), showed positive hybridization signal in normal artery, while probes with positive signal in placenta (1a), ovary (1c) and testis (1d) were over-expressed in arteries of leiomyomas.
Assuntos
Aromatase/biossíntese , Artérias/metabolismo , Leiomioma/metabolismo , Neoplasias Uterinas/enzimologia , Útero/enzimologia , Aromatase/química , Aromatase/metabolismo , Estrogênios/metabolismo , Éxons , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Modelos Estatísticos , Neovascularização Patológica , Sondas de Oligonucleotídeos/química , Ovário/metabolismo , Placenta/metabolismo , Estrutura Terciária de Proteína , Testículo/metabolismo , Distribuição Tecidual , Neoplasias Uterinas/irrigação sanguínea , Neoplasias Uterinas/patologia , Útero/irrigação sanguínea , Útero/patologiaRESUMO
A high-calorie (cafeteria) diet is known to cause changes in the intestinal morphology and functioning that seem to be related to calorie overfeeding. Among the cell lineages found in the small intestine epithelium, the Paneth cell (PC) population is known to be influenced by factors related mainly to the intestinal microbiota. The role of PCs in the intestinal cell concert remains unclear, because experimental evidence suggests PC involvement in local processes other than protection against pathogens. Participation of PC in digestive mechanisms has been proposed on this basis. We have analyzed the effect of high-carbohydrate (HC) and high-fat (HF) cafeteria diets on the PC population in the small intestine of the adult rat. For 8 weeks, both HC and HF diets caused a gain in body weight, but whereas the HC-fed rats showed reduced counts of intestinal crypts per 5-mum section, the HF-fed group showed the opposite. In control rats, the number of crypts per section showed a slight tendency to decrease along the duodenum - ileum axis, whereas the number of PCs per crypt was increased towards the ileum. As a result, the number of PCs per section (calculated from these data) remained constant along the three segments of the intestine. The hypercaloric diets did not modify the general tendencies seen in the crypt and PC counts, but reduced the number of PCs per section in the duodenum by 50%. HC-fed, but not HF-fed, rats showed a similar reduction in jejunum also. These changes do not correlate particularly with any of the predictable effects of diet composition, so that a multifactorial control of PC density is proposed.
Assuntos
Ração Animal , Ingestão de Energia/fisiologia , Mucosa Intestinal/citologia , Intestino Delgado/citologia , Celulas de Paneth/citologia , Tecido Adiposo/citologia , Animais , Peso Corporal , Contagem de Células , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Digestão/fisiologia , Mucosa Intestinal/microbiologia , Intestino Delgado/microbiologia , Masculino , Celulas de Paneth/microbiologia , Ratos , Ratos WistarRESUMO
La prueba de equilibrio peritoneal (PET) fue descrita en 1987 por Z. Twardovsky, como una prueba para conocer la difusión de solutos y capacidad de ultrafiltración (UFR) en la membrana peritoneal (MP). La PET ha permitido clasificar el tipo de transporte peritoneal (TP), en los pacientes que se encuentran en diálisis peritoneal (DP) en: promedio alto, promedio bajo, alto y bajo. El presente trabajo tiene como objetivo, presentar el análisis prospectivo de 80 casos de PET, realizadas en el Servicio de Nefrología del hospital Juárez de México.Se incluyeron a 80 pacientes en DP, de ambos sexos, adultos, sin peritonitis, ni inestabilidad cardiovascular, que tuvieran por lo menos 6 meses en el programa de diálisis peritoneal continua ambulatoria (DPCA). Se les hizo PET en la unidad ambulatoria de diálisis del hospital. Después de hacer la PET. los resultados fueron: 35 pacientes como promedio alto, 15 promedio bajo, 25 alto y 5 transporte bajo. 25 pacientes con falla tipo I de ultrafiltración y 55 con UFR adecuada.La PET, es una prueba muy útil para clasificar el tipo de transporte peritoneal y conocer la tasa de UFR. Permite adecuar la DP y decidir en qué tipo de modalidad de DP puede estar el paciente.