RESUMO
Doxorubicin (DOX) is a chemotherapeutic agent that has been used in the treatment of breast cancer. However, serious toxic effects have limited its use, mainly cardiotoxicity. To minimize the adverse effects, liposomal preparations containing DOX have been developed. These preparations can reach the target in the tumor region as well as bypass the resistance-related problems. An alternative to increased therapeutic efficacy may be the fusion of liposomes with exosomes released from tumor cells to facilitate membrane and fusion interactions, achieving greater cell uptake. Thus, the purpose of this study was the fusion of exosomes derived from breast tumor cells with long-circulating and pH-sensitive liposomes loading DOX (ExoSpHL-DOX) for the treatment of breast cancer. The mean diameter of ExoSpHL-DOX was 100.8 ± 7.8 nm, the polydispersity index was 0.122 ± 0.004, and the encapsulated DOX content was equal to 83.5 ± 2.5%. The fusion of exosomes with long-circulating and pH-sensitive liposomes was confirmed by Fourier transform infrared spectroscopy, Raman spectroscopy, and nano-flow cytometry. The physicochemical characteristics of ExoSpHL-DOX were maintained for 60 days, at 4 °C. The study of the release of DOX from ExoSpHL-DOX in dilution media with different pH values showed the pH sensitivity characteristic of the nanosystem, since 96.6 ± 0.2% of DOX was released from ExoSpHL-DOX at pH 5.0, while at pH 7.4, the release was 70.1 ± 1.7% in the medium. The cytotoxic study against the breast cancer cell line demonstrated that ExoSpHL-DOX treatment significantly reduced the cancer cell viability.
Assuntos
Antineoplásicos , Neoplasias da Mama , Exossomos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Exossomos/patologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Lipossomos/químicaRESUMO
OBJECTIVE: The study is part of a project financed by the United Nations (FAO) and the Ministry of Education of Brazil (Fundação de Assistência ao Escolar) which intends to evaluate the nutritional status of public schools students in order to estimate, giving emphasis to geographical aspects, the magnitude and distribution of statural deficit of this population in the Paraíba State, Northeastern Brazil. METHODS: Schoolchildren, aged 6-9 years and enrolled in the first grade inall municipalities of Paraíba state went through a height survey. We consider as statural deficit values below -2 standard deviations according to the anthropometric pattern of National Center of Health Statistics. RESULTS: A frequency of 14. 5% of statural deficit was found in the whole state, as well as 18. 7% in the semidesertic region (sertão), 13.8% in Agreste area, 11. 9% in Borborema region and 10.9% in Mata zone. In rural area, the prevalence of statural deficit was higher (17.8%) than for those living in urban area (11.8%). CONCLUSIONS: The results reveal a process of inlanding of statural deficit, which contrasts with historical descriptions of the geographical distribution of this problem in the Northeastern region of Brazil
Assuntos
Estatura , Transtornos do Crescimento/epidemiologia , Inquéritos Nutricionais , Brasil/epidemiologia , Criança , Estudos Transversais , Nanismo/epidemiologia , Feminino , Transtornos do Crescimento/diagnóstico , Humanos , Masculino , Prevalência , Características de ResidênciaRESUMO
Forty-five patients with systemic lupus erythematosus (SLE) underwent a cross-sectional study to evaluate intestinal secretory immunity. Peroral jejunal biopsy with histologic and immunohistochemical assessment of the mucosa were carried out in the patients and in 12 healthy volunteers. It was observed that an altered pattern of immunoglobulin-bearing plasma cells distributed in the lamina propria and complementary components were invariably present, mainly in the patients with active disease. The basement membrane of the intestinal crypt epithelium exhibited immunoglobulin and complementary deposits, similar to the lupus band test. None of the immunologic findings correlated with the medical treatment and with the peripheral blood analysis. The local changes in humoral immunity in patients with SLE did not correlate with gastrointestinal symptoms and may reflect the systemic effects of the disease.
Assuntos
Mucosa Intestinal/patologia , Jejuno/patologia , Lúpus Eritematoso Sistêmico/imunologia , Adolescente , Adulto , Formação de Anticorpos , Membrana Basal/patologia , Estudos Transversais , Feminino , Imunofluorescência , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Mucosa Intestinal/metabolismo , Jejuno/metabolismo , Pessoa de Meia-IdadeRESUMO
Weight loss is a major component of the clinical syndrome in patients with acquired immunodeficiency syndrome (AIDS). The impact of malnutrition on the outcome of the disease has been unappreciated in many investigations. The authors evaluated the effects of oral nutritional supplementation on the morphology and immunology of the intestinal mucosa of patients with AIDS. Twelve patients with AIDS without diarrhea or opportunistic infections, with at least 10% of body weight loss over 1 year, were submitted to anthropometric measures, peripheral blood T-lymphocyte counts, and peroral jejunal biopsy before and after oral nutritional supplementation. An industrialized peptide-based formula containing omega-3 fatty acids was given for 6 weeks. Jejunal samples were analyzed by histomorphometry, including villous-to-crypt ratio, lamina propria, and intraepithelial lymphocyte count. Immunologic assessment of the intestinal mucosa was made by indirect immunoperoxidase using monoclonal antibodies against CD3, CD4, and CD8. Seven patients with irritable bowel syndrome and two healthy volunteers were selected as a control group for histologic and immunohistochemical comparisons. After 6 weeks the patient group maintained their body weight and increased their tricipital fold. The number of peripheral blood T cells, albumin, transferrin, and the number of CD3+, CD4+, and CD8+ cells in jejunal mucosa as well as the intestinal morphometry remained stable. Oral supplementation contributed to maintaining body weight and may constitute a reasonable adjuvant therapeutic tool against AIDS progression.
Assuntos
Síndrome da Imunodeficiência Adquirida/patologia , Suplementos Nutricionais , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Jejuno/patologia , Adulto , Peso Corporal/efeitos dos fármacos , Feminino , Humanos , Técnicas Imunoenzimáticas , Jejuno/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
BACKGROUND: We have investigated the intestinal mononuclear cell subpopulations in patients with systemic lupus erythematosus (SLE) and correlated these with the disease activity. METHODS: Eighteen female outpatients were studied; in 10 of them lupus activity was measured with the Lupus Activity Criteria Count and the SLE Disease Activity Index. Eight patients were in lupus remission. The control group consisted of 10 healthy volunteers. Peroral jejunal biopsy was performed in all individuals, at the angle of Treitz, using a Watson capsule, under X-ray control. Histologic studies analysed the villous to crypt ratio, lamina propria cells, and intraepithelial lymphocyte count. Immunohistochemical evaluation was carried out with the indirect immunoperoxidase technique, using monoclonal antibodies against CD3, CD4, CD8, D1, D7, D9, and M1. RESULTS: Lamina propria CD3+, CD8+, D7+, and M1+ cells from patients with SLE did not differ significantly from those of controls. CD4+ cells were decreased in all patients with SLE, especially in the clinically inactive patients. D1+ and D9+ cells were also decreased in all patients. CONCLUSION: The finding of quantitative abnormalities in the cell-mediated immunity of the intestinal mucosa may reflect systemic defects of the immune system in SLE.
Assuntos
Jejuno/imunologia , Jejuno/patologia , Lúpus Eritematoso Sistêmico/patologia , Adolescente , Adulto , Biópsia , Feminino , Humanos , Imunidade nas Mucosas , Imuno-Histoquímica , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Leucócitos Mononucleares , Lúpus Eritematoso Sistêmico/fisiopatologia , Pessoa de Meia-Idade , Fenótipo , Estatísticas não ParamétricasRESUMO
OBJECTIVE: The objective of this study was to examine mononuclear cell subpopulations and evidence of cellular activation in unaffected jejunal mucosa in Crohn's disease. DESIGN: A cross-sectional study was performed in patients with Crohn's disease from the ambulatory unity of the University Hospital, UFRJ. METHODS: Mucosal samples from 20 patients with Crohn's colitis or ileitis were obtained by peroral jejunal biopsy. Patients with jejunal involvement or pregnant women were excluded from the study. Specimens were analysed histologically and by indirect immunoperoxidase method using anti-monoclonal antibodies to CD2, CD4, CD8, CD25, CD45RO, RFDR1, RFD1 and RFD7 by two 'blind' observers. Seven patients with non-inflammatory bowel disorders and two healthy volunteers were studied as controls. RESULTS: Lamina propria CD2-positive (CD2+) cells were reduced in Crohn's disease (P < 0.004) whether clinically active (P < 0.02) or clinically inactive (P < 0.008). CD4+ and CD8+ cells were also reduced in Crohn's disease (P < 0.003), whereas the CD4:CD8 ratio did not differ from that in controls. CD25+, CD45RO+ and HLA-DR+ cells were not significantly increased in patients with Crohn's disease. RFD7+ cells were decreased in Crohn's disease (P < 0.02), whereas RFD1+ cells were not significantly different from the control group. CONCLUSION: No evidence of cellular activation was found in the unaffected mucosa of Crohn's disease. The reduction in T-cell and macrophage-like cell numbers may result from cell migration to inflamed areas. It is also possible that this finding represents a primary defect which may have a role in the pathogenesis of Crohn's disease.