ABSTRACT
BACKGROUND: Matricaria Chamomilla L. (Mch), popularly known as chamomile, has been used for centuries as an herbolary remedy due to its broad clinical spectrum. The aim of this study was to evaluate the effect of Mch associated to a vehicle with emollient function in induced atopic dermatitis (AD)-like lesions in a murine model. METHODS: AD was induced with dinitrochlorobenzene on 12 male seven-week old BALB/c mice. Animals were divided in three groups (control, GC; control negative, GCN; and experimental, GE). Liquid petrolatum was applied to the GCN and liquid petrolatum with aqueous extract of Mch at 7% to the GE. Induction and evolution of the lesions were verified by biopsy at 2nd and 6th week. Evaluation of peripheral blood cells to correlate inflammatory cells was made as well at the same weeks. Lesions were clinically evaluated at 2nd, 4th and 6th week. Scratching was monitored according to the observation methodology of Kobayashi et al. RESULTS: Mch aqueous extract associated to a vehicle with emollient function improves atopic dermatitis-like lesions after two weeks.
INTRODUCCIÓN: Matricaria chamomilla L. (Mch), conocida popularmente como manzanilla, ha sido utilizada por cientos de años como remedio herbolario debido a su amplio espectro en cuanto a sus usos clínicos. El objetivo de este trabajo fue evaluar el efecto de Mch asociada a un vehículo con función emoliente como tratamiento de lesiones tipo-dermatitis atópica (DA) en un modelo murino. MÉTODOS: se indujo DA con dinitroclorobenceno a 12 ratones BALB/c macho de siete semanas de edad, divididos en tres grupos (control, GC; control negativo, GCN y; experimental, GE). Se aplicó petrolato líquido al GCN y petrolato líquido con extracto acuoso de Mch al 7% al GE durante cuatro semanas. La inducción y evolución de las lesiones se corroboraron por biopsia a las dos y seis semanas, analizando sangre periférica en búsqueda de células inflamatorias en los mismos tiempos. Las lesiones fueron evaluadas clínicamente a las dos, cuatro y seis semanas. El rascado se evaluó de acuerdo a la metodología de observación de Kobayashi et al. RESULTADOS: el extracto acuoso liofilizado de Mch asociado a un vehículo con función emoliente demostró mejoría del aspecto de las lesiones tipo DA después de dos semanas.
Subject(s)
Dermatitis, Atopic/drug therapy , Emollients/therapeutic use , Matricaria , Phytotherapy , Plant Extracts/therapeutic use , Animals , Male , Mice , Mice, Inbred BALB C , Treatment OutcomeABSTRACT
Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis. Materials and Methods: Thirty-five female nude mice were transplanted subcutaneously with MDA-MB-231 triple negative human cancer cell line. Once tumors were visible, mice were treated with doxorubicin, metformin, oxamate or all possible pharmacologic combinations. Treatments were administered daily for 15 days and tumors were measured by calipers every day. MicroPET images were taken in three different occasions, basal state, in the middle of the treatment, and at the end of treatment. Western blot analyses, qRT-PCR, flow cytometry, and cytotoxicity assays were performed to elucidate the mechanism of cell death promoted by the drugs in vitro. Results: In this work we assessed the proof of concept of metabolic correction in solid tumors as an effective drug treatment; hence, mice bearing tumors treated with the DoxMetOx therapy showed a complete inhibition of the tumor mass growing in 15 days of treatment depicted by the micro PET images. In vitro studies displayed that the three drugs together act by inhibiting both, mTOR-phosphorylation and expression of LDH-A gene, promoting apoptosis via dependent on the caspase-3 pathway, accompanied by cleavage of PARP. Moreover, induction of autophagy process was observed by the accumulation of LC3-II, a primordial protein implicated in the conformation and elongation of the autophagolysosome. Conclusions: The lack of effective drugs to inhibit TNBC growth is the main cause of therapy failure and tumor relapse. We have showed that targeting crucial molecular pathways in cancer by the combination of Doxorubicin, Metformin, and Oxamate resulted as an efficient and rapid tumor growth inhibitor in a triple negative xenograft model. Our findings are promising for patients diagnosed with TNBC tumors, for which unfortunately there are no reliable drug therapies.
ABSTRACT
BACKGROUND AND AIM: Bone-seeking radiopharmaceuticals have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other haematological malignancies. The aim of this research was to examine the feasibility of labelling ethylenediaminetetramethylenephosphonate (EDTMP) with Dy/Ho as an in vivo generator system and to evaluate whether the in vitro and in vivo stability of Dy-EDTMP and Ho-EDTMP complexes is maintained when the daughter Ho is formed. METHODS: Dy was obtained by neutron irradiation of enriched Dy2O3 in a TRIGA Mark III reactor. Labelling was carried out in an aqueous phosphate medium at pH 8.0 by addition of DyCl3 to EDTMP at a molar ratio 1:1.75. Dy/Ho labelled EDTMP was obtained with a 99.3+/-0.6% radiochemical purity determined by thin-layer chromatography and high-performance liquid chromatography. RESULTS: In vitro studies demonstrated that Dy/Ho-EDTMP is unstable after dilution in saline and stable in human serum and no translocation of the daughter nucleus occurring subsequent to beta decay of Dy which could produce release of Ho. Biodistribution in mice shows a fast blood clearance after administration of Dy/Ho-EDTMP with a skeletal uptake of 22.32+/-1.86% ID/g at 2 h and 20.12+/-1.94% ID/g after 10 d, a rapid renal elimination and no accumulation in other organs. Theoretical bone marrow absorbed dose calculations indicate that the Dy/Ho-EDTMP in vivo generator system would produce 7.80 times more radiation dose to marrow than that produced by Sm-EDTMP and 3.47 times more than Ho-DOTMP per unit of initial activity retained in the skeleton. CONCLUSION: The prepared radiolabelled EDTMP has adequate properties as a stable in vivo generator system for bone marrow ablation.
Subject(s)
Bone Marrow/metabolism , Isotope Labeling/methods , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacokinetics , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/pharmacokinetics , Animals , Bone Marrow Neoplasms/radiotherapy , Drug Stability , Feasibility Studies , Male , Metabolic Clearance Rate , Mice , Mice, Inbred BALB C , Organ Specificity , Organometallic Compounds/therapeutic use , Organophosphorus Compounds/therapeutic use , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/therapeutic use , Tissue DistributionABSTRACT
El presente trabajo se realizó con el propósito de conocer el efecto de las ondas ultrasónicas generadas por un dispositivo diseñado para ahuyentar roedores y disminuir su reproducción. El efecto de este equipo fue estudiado en ratas Wistar mantenidas en condiciones de bioterio. Con ese propósito se formaron dos grupos de ratas Wistar, uno testigo y el otro experimental, en donde se determinó si la acción constante de un dispositivo productor de ondas ultrasónicas, durante 12 semanas, interfiere con la capacidad reproductiva de ratas Wistar, evaluada por el número de días a parto, número de crías nacidas y destetadas. También se determinó la influencia de las ondas ultrasónicas en el crecimiento y desarrollo de las crías, utilizando como indicador la ganancia de peso semanal desde el destete hasta la doceava semana experimental. Los resultados obtenidos indican que las ondas ultrasónicas no afectan el peso corporal, ya que mediante la prueba de mediciones repetidas se comprobó que si bien existe diferencia aritmética, no hay diferencia estadística entre ambos grupos (P>0.05). En lo que respecta a las crías, el grupo tratado obtuvo 20 crías más que el grupo testigo; sin embargo, no existe diferencia estadística entre ambos grupos (P>0.05). La presencia continua de ondas ultrasónicas tampoco interfirió con la ganancia de peso de las crías, en comparación con el grupo testigo (P>0.05). Se concluye que las ondas ultrasónicas generadas por el aparato no afectan el tamaño y curva de crecimiento posterior al destete de la camada. Como consecuencia de lo anterior no parece recomendable utilizar este tipo de aparatos como un método para el control de roedores.
