RESUMO
Cleft lip and cleft palate also known as orofacial cleft is a congenital malformation involving the partial or total lack of anatomical continuity of craniofacial tissue. The most common environmental factors that may cause orofacial clefts include pharmaceuticals, alcohol, addictive drugs, and tobacco smoke. Living in the area of industrial factories, garbage, ironworks, crematoria, wastewater treatment plants, and plastic waste landfills also has a significant impact on the development of the craniofacial defects. Some of the main factors causing the formation of congenital craniofacial defects are dioxins, of which emission to the environment is an important environmental and health problem. Dioxins are a diverse group of organic chemical compounds, derivatives of oxanthrene and fumarates, which are organoleptically imperceptible. Acting mainly through induction of inflammation, they influence a number of metabolic processes, including the process of bone mineralization and embryonic development. In this work, we highlight the problem of orofacial cleft including the impact of dioxin on development of this defect and the recommended prevention.
Assuntos
Fenda Labial/etiologia , Fissura Palatina/etiologia , Dioxinas/toxicidade , Poluentes Ambientais/toxicidade , Fenda Labial/prevenção & controle , Fissura Palatina/prevenção & controle , Feminino , Humanos , GravidezRESUMO
Acquired drug resistance to mycotic infections is rapidly emerging as a major medical problem. Opportunistic fungal infections create therapeutic challenges, particularly in high risk immunocompromised patients with AIDS, cancer, and those undergoing transplantation. Higher mortality and/or morbidity rates due to invasive mycosis have been increasing over the last 20 years, and in light of growing resistance to commonly used antibiotics, novel antifungal drugs and approaches are required. Currently there is considerable interest in antifungal peptides that are ubiquitous in plant and animal kingdoms. These small cationic peptides may have specific targets or may be multifunctional in their mechanism of action. On the basis of recent advances in protein engineering and solid phase syntheses, the utility and potential of selected peptides as efficient antifungal drugs with acceptable toxicity profiles are being realized. This review will discuss recent advances in peptide therapy for opportunistic fungal infections.
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Cytokines and chemokines govern leukocyte trafficking, thus regulating inflammatory responses. In this study, the anti-inflammatory effects of low dose 17 beta-estradiol were evaluated on chemokine, chemokine receptor, and cytokine expression in the spinal cords (SC) of BV8S2 transgenic female mice during acute and recovery phases of experimental autoimmune encephalomyelitis (EAE). In EAE protected mice, 17 beta-estradiol strongly inhibited mRNA expression of the chemokines RANTES, MIP-1 alpha, MIP-2, IP-10, and MCP-1, and of the chemokine receptors CCR1, CCR2 and CCR5 at both time points. Conversely, ovariectomy, which abrogated basal 17 beta-estradiol levels and increased the severity of EAE, enhanced the expression of MIP-1 alpha and MIP-2 that were over-expressed by inflammatory mononuclear cells in SC. 17 beta-estradiol inhibited expression of LT-beta, TNF-alpha, and IFN-gamma in SC, but had no effect on IL-4 or IL-10, indicating reduced inflammation but no deviation toward a Th2 response. Interestingly, elevated expression of CCR1 and CCR5 by lymph node cells was also inhibited in 17 beta-estradiol treated mice with EAE. Low doses of 17 beta-estradiol added in vitro to lymphocyte cultures had no direct effect on the activation of MBP-Ac1-11 specific T cells, and only at high doses diminished production of IFN-gamma, but not IL-12 or IL-10. These results suggest that the beneficial effects of 17 beta-estradiol are mediated in part by strong inhibition of recruited inflammatory cells, resulting in reduced production of inflammatory chemokines and cytokines in CNS, with modest effects on encephalitogenic T cells that seem to be relatively 17 beta-estradiol insensitive.
Assuntos
Quimiocinas/genética , Citocinas/genética , Encefalomielite Autoimune Experimental/tratamento farmacológico , Estradiol/farmacologia , RNA Mensageiro/efeitos dos fármacos , Receptores de Quimiocinas/genética , Medula Espinal/efeitos dos fármacos , Animais , Movimento Celular/imunologia , Células Cultivadas/citologia , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/imunologia , Quimiocina CCL4 , Quimiocina CXCL2 , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/imunologia , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/fisiopatologia , Feminino , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Linfonodos/citologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Proteínas Inflamatórias de Macrófagos/genética , Camundongos , Camundongos Transgênicos , Ovariectomia , RNA Mensageiro/metabolismo , Receptores CCR1 , Receptores CCR5/efeitos dos fármacos , Receptores CCR5/imunologia , Receptores CCR5/metabolismo , Receptores de Quimiocinas/efeitos dos fármacos , Receptores de Quimiocinas/imunologia , Receptores de Quimiocinas/metabolismo , Medula Espinal/imunologia , Medula Espinal/metabolismo , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Células Th1/citologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/citologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Resultado do TratamentoRESUMO
A shift toward Th2 cytokine production has been demonstrated during pregnancy and high dose estrogen therapy and is thought to be the primary mechanism by which estrogen suppresses the development of experimental autoimmune encephalomyelitis. However, low dose estrogen treatment is equally protective in the absence of a significant shift in cytokine production. In this study cytokine-deficient mice were treated with estrogen to determine whether a shift in Th2 cytokine production was required for the protective effects of hormone therapy. Estrogen effectively suppressed the development of experimental autoimmune encephalomyelitis in IL-4 and IL-10 knockout mice and in wild type littermate mice with a similar potency of protection. Significant disease suppression was also seen in IFN-gamma-deficient mice. The decrease in disease severity was accompanied by a concomitant reduction in the number of proinflammatory cytokine- and chemokine-producing cells in the CNS. Although there was no apparent increase in compensatory Th2 cytokine production in cytokine-deficient mice, there was a profound decrease in the frequency of TNF-alpha-producing cells in the CNS and the periphery. Therefore, we propose that one mechanism by which estrogen protects females from the development of cell-mediated autoimmunity is through a hormone-dependent regulation of TNF-alpha production.
Assuntos
Citocinas/deficiência , Citocinas/genética , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Encefalomielite Autoimune Experimental/prevenção & controle , Estradiol/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese , Sequência de Aminoácidos , Animais , Moléculas de Adesão Celular/biossíntese , Quimiocinas/antagonistas & inibidores , Quimiocinas/biossíntese , Quimiocinas/genética , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Implantes de Medicamento , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Estradiol/administração & dosagem , Feminino , Interferon gama/deficiência , Interferon gama/genética , Interleucina-10/deficiência , Interleucina-10/genética , Interleucina-4/deficiência , Interleucina-4/genética , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Dados de Sequência Molecular , RNA Mensageiro/biossíntese , Receptores de Quimiocinas/antagonistas & inibidores , Receptores de Quimiocinas/biossíntese , Receptores de Quimiocinas/genética , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Medula Espinal/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The perivascular transmigration and accumulation of macrophages and T lymphocytes in the CNS of mice with experimental autoimmune encephalomyelitis (EAE) may be partly regulated by low m.w. chemotactic cytokines. Using the RNase protection assay and ELISA, we quantified expression of chemokines and chemokine receptors in the spinal cord (SC), brain, and lymph nodes of BV8S2 transgenic mice that developed or were protected from EAE by vaccination with BV8S2 protein. In paralyzed control mice, the SC had increased cellular infiltration and strong expression of the chemokines RANTES, IFN-inducible 10-kDa protein, and monocyte chemoattractant protein-1 and the cognate chemokine receptors CCR1, CCR2, and CCR5, with lower expression of macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, and MIP-2; whereas brain had less infiltration and a lower expression of a different pattern of chemokines and receptors. In TCR-protected mice, there was a decrease in the number of inflammatory cells in both SC and brain. In SC, the reduced cellular infiltrate afforded by TCR vaccination was commensurate with profoundly reduced expression of chemokines and their cognate chemokine receptors. In brain, however, TCR vaccination did not produce significant changes in chemokine expression but resulted in an increased expression of CCR3 and CCR4 usually associated with Th2 cells. In contrast to CNS, lymph nodes of protected mice had a significant increase in expression of MIP-2 and MIP-1beta but no change in expression of chemokine receptors. These results demonstrate that TCR vaccination results in selective reduction of inflammatory chemokines and chemokine receptors in SC, the target organ most affected during EAE.
Assuntos
Quimiocinas/biossíntese , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/uso terapêutico , Receptores de Quimiocinas/biossíntese , Medula Espinal/imunologia , Medula Espinal/metabolismo , Animais , Encéfalo/imunologia , Encéfalo/metabolismo , Movimento Celular/imunologia , Quimiocinas/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/prevenção & controle , Feminino , Expressão Gênica/imunologia , Linfonodos/imunologia , Linfonodos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores de Quimiocinas/genética , VacinaçãoRESUMO
Lectins are structurally and functionally diverse group of proteins or protein domains capable of specific binding of oligosaccharide structures present on cell surfaces, the extracellular matrix, and secreted glycoproteins. Animals lectins are classified into six groups: C-type lectins, S-type lectins (galectins), I-type lectins, P-type lectins, pentraxins, and others. In this review, the basic knowledge regarding structure and function of animal lectins is presented.
Assuntos
Lectinas/classificação , Lectinas/fisiologia , Animais , Endocitose/fisiologia , Lectinas/química , Selectinas/classificação , Selectinas/fisiologiaAssuntos
Adenocarcinoma/secundário , Antígenos de Neoplasias/análise , Neoplasias do Colo/patologia , Antígenos do Grupo Sanguíneo de Lewis/análise , Metástase Neoplásica , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Animais , Neoplasias do Colo/imunologia , Células HT29 , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Fatores de Risco , Transplante HeterólogoRESUMO
Aberrant glycosylation is a common phenomenon accompanying colon carcinoma progression. The changes observed include increased expression of Lewis blood group family antigens, particularly Lex, sialyl Lex and sialyl Lexa. Recently it was shown that these antigenic epitopes may play an important role in cell-cell homotypic as well as heterotypic adhesive interactions. This work presents a phenotypic characteristic of 11 human colon carcinoma cell lines of different degree of differentiation. Expression of potential ligands for endogenous cellular lectins: Lewis antigens, CEA and CD44v6 antigens was evaluated by cytofluorimetry. The aim of the work is to select adhesive and invasive colon carcinoma cells with specified cell surface antigen pattern, for studies on adhesive interactions with endothelial cells, occurring during early steps of metastasis.