RESUMO
Nearly 80% of the world's population trusts traditional medicine and plant-based drug compounds to improve health, and more than 50% of women who participated in a study have used herbal remedies during pregnancy. Bocconia frutescens L. is a plant native to tropical America, where infusion of its leaves has been widely used for the treatment of several gastrointestinal disorders. We have already shown that orogastric consumption of B. frutescens L. during the organogenesis period at concentrations equivalent to human consumption produces teratogenic effects in rats, but effects on progeny development have not yet been studied. In this study, we aimed to investigate the possible association between the consumption of B. frutescens L. at a dose equivalent to that consumed by humans and the neurological development of rat progeny. Pregnant Wistar rats were administered lyophilized B. frutescens L. extract at 300 mg/kg/day or vehicle via the orogastric route during the organogenesis period (gestation days 7-13). The physical development and sensory and motor maturation of their offspring during lactation were analyzed with a battery of reflex and physical tests. B. frutescens L. produced a significant delay in physical development and sensorimotor maturation, compared to the control group. Proton nuclear magnetic resonance spectroscopy analysis showed signals for both flavonoids and alkaloids in the B. frutescens L. extract. We conclude that the delay in physical and neurological development could be interpreted as alterations in the maturation of some neuronal circuitries induced by B. frutescens L.
Assuntos
Extratos Vegetais , Efeitos Tardios da Exposição Pré-Natal , Ratos Wistar , Animais , Feminino , Ratos , Gravidez , Extratos Vegetais/farmacologia , MasculinoRESUMO
The dopamine D2-type receptor agonist quinpirole (QNP) facilitates the development of conditioned same-sex partner preference in males during cohabitation, but not in ovariectomized (OVX) females, primed with estradiol benzoate (EB) and progesterone (P). Herein we tested the effects of QNP on OVX, EB-only primed females. Females received a systemic injection (every four days) of either saline (Saline-conditioned) or QNP (QNP-conditioned) and then cohabited for 24h with lemon-scented stimulus females (CS+), during three trials. In test 1 (female-female) preference was QNP-free, and females chose between the CS+ female and a novel female. In test 2 (male-female) they chose between the CS+ female and a sexually experienced male. In test 1 Saline-conditioned females displayed more hops & darts towards the novel female, but QNP-conditioned females displayed more sexual solicitations towards the CS+ female. In test 2 Saline-conditioned females displayed a clear preference for the male, whereas QNP-conditioned females displayed what we considered a bisexual preference. We discuss the effect of dopamine and ovarian hormones on the development of olfactory conditioned same-sex preference in females.
Assuntos
Condicionamento Psicológico/fisiologia , Hormônios Gonadais/fisiologia , Homossexualidade Feminina , Preferência de Acasalamento Animal/fisiologia , Percepção Olfatória/fisiologia , Animais , Condicionamento Psicológico/efeitos dos fármacos , Dopamina/farmacologia , Agonistas de Dopamina/farmacologia , Feminino , Hormônios Gonadais/metabolismo , Hormônios Gonadais/farmacologia , Homossexualidade Feminina/psicologia , Preferência de Acasalamento Animal/efeitos dos fármacos , Percepção Olfatória/efeitos dos fármacos , Ovário/metabolismo , Progesterona/farmacologia , Ratos , Ratos Wistar , Receptores de Dopamina D2/metabolismo , Comportamento Sexual Animal/efeitos dos fármacos , OlfatoRESUMO
The anti-human epidermal growth factor receptor (EGF-R) humanized antibody h-R3 (IgG(1)), which binds to an extracellular domain of EGF-R, was used to evaluate the biodistribution on nude mice xenografted with A431 epidermoid carcinoma cell line. Results are compared with its murine version ior egf/r3 monoclonal antibody (mAb). Twenty-one athymic female 4NMRI nu/nu mice were injected intravenously with 10 microg/100 microCi of (99m)Tc-labeled mAbs. The mAb ior C5 that recognizes an antigen expressed preferentially on the surface of malignant and cytoplasm of normal colorectal cells was used as negative control. Immunoreactivity of (99m)Tc-labeled mAbs was measured by enzyme linked immunosorbent assay on A431 cell line and the immunoreactive fractions determined by Lindmo method. Among all organs significative accumulation was found in tumor (6.14 +/- 2.50 %ID/g, 5.06 +/- 2.61 %ID/g for murine and humanized mAbs, respectively) 4 h after injection. The immunoreactive fractions were found to be 0.88 and 0.81 for murine and humanized mAb, respectively. Thus, we expect better results using the humanized mAb h-R3 for diagnostic immunoscintigraphy.
Assuntos
Anticorpos Monoclonais , Receptores ErbB/imunologia , Compostos Radiofarmacêuticos , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacocinética , Ligação Competitiva , Carcinoma de Células Escamosas/diagnóstico por imagem , Ensaio de Imunoadsorção Enzimática , Feminino , Liofilização , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Radioimunoensaio , Ensaio Radioligante , Cintilografia , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Compostos de Sulfidrila/química , Distribuição Tecidual , Transplante HeterólogoRESUMO
Monoclonal antibodies (MAbs) have been useful for immunoscintigraphic applications in clinical diagnosis since they were introduced in nuclear medicine practice. The MAb ior egf/r3 developed at the Center of Molecular Immunology (Havana, Cuba) is a murine antibody that recognizes the human epidermal growth factor receptor (EGF-R) and has been used widely in the radioimmunodiagnosis of tumors of epithelial origin. Based on the direct Schwarz method, the present report describes the preparation of a freeze-dried formulation for radiolabeling the MAb ior egf/r3 with 99mTc for immunoscintigraphic applications. Radiolabeling efficiency, effects on immunoreactivity, biodistribution, pharmacokinetic, and stability of the formulation are reported. The study demonstrated that the freeze-dried formulation can be labeled with 99mTc at high yield. The resulting 99mTc-labeled ior egf/r3 MAb can be used to visualize in vivo human tumors of epithelial origin by immunoscintigraphy studies. The kit does not need any other addition or purification at the time of tagging other than the requisite amount of pertechnetate (40-50 mCi). Because the contents of the kit are lyophilized, no special storage or transportation is required.
Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacocinética , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio/farmacocinética , Animais , Estabilidade de Medicamentos , Feminino , Liofilização , Glucose , Humanos , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
Monoclonal antibodies (MAbs) are being widely used for imaging studies, coupled mainly with 99mTc. The antibody ior egf/r3 is a MAb against human epidermal growth factor receptor (hEGF-r), and we have developed a method for optimum labeling of this MAb with 99mTc. The reduction was performed with 2-mercaptoethanol (2-ME) at a molar ratio of 2000:1 (2-ME:MAb) and methylene diphosphonate as transchelant. The integrity of reduced MAb was checked by mean of native polyacrylamide gel electrophoresis (PAGE) and gel filtration chromatography on Superose 12 (purity >99%). Radio colloids remained lower than 2%, and the labeling efficiency was 98.5%. The number of sulfhydryl groups generated was quantified using Ellman's reagent and was found to be 6.65+/-0.69 per antibody molecule. In vitro stability studies in several challenging conditions (DTPA, human serum albumin and human serum) were performed, and no significant loss in binding percentage was seen. Radio receptor assay was used to test immunoreactivity of the reduced MAb. Both labeled and unlabeled MAbs were able to compete for binding to the hEGF-r with radioiodinated EGF. Biodistribution studies in BALB/c mice are reported.