ABSTRACT
In view of our recent demonstration that insulin inhibits the expression of intercellular adhesion molecule-1 (ICAM-1) and the fact that ICAM-1 expression is known to be modulated by nuclear factor-kappaB (NFkappaB), we have now investigated whether insulin inhibits intranuclear NFkappaB binding activity. We have also investigated whether insulin inhibits the pro-inflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), which attracts leucocytes to the inflamed sites and is also regulated by NFkappaB. Insulin was incubated with cultured human aortic endothelial cells (HAEC) at 0, 100 and 1000 microU/mL. Intranuclear NFkappaB binding activity was suppressed by approximately 45% at 100 microU/mL and by 60% at 1000 microU/mL (p < 0.05). MCP-1 mRNA expression was also suppressed by 47% at 100 microU/mL and by 79% at 1000 microU/mL (p < 0.05). We conclude that insulin at physiologically relevant concentrations exerts an inhibitory effect on the cardinal pro-inflammatory transcription factor NFkappaB and the pro-inflammatory chemokine MCP-1; these effects suggest an anti-inflammatory and potential anti-atherogenic effects of insulin.
Subject(s)
Aorta/metabolism , Chemokine CCL2/antagonists & inhibitors , Endothelium, Vascular/metabolism , Insulin/pharmacology , NF-kappa B/antagonists & inhibitors , Aorta/cytology , Cells, Cultured , Endothelium, Vascular/cytology , HumansABSTRACT
Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial and other cell types and participates in inflammation and atherosclerosis. It serves as a ligand for leukocyte function-associated antigen-1 on leukocytes and is partially responsible for the adhesion of lymphocytes, granulocytes, and monocytes to cytokine-stimulated endothelial cells and the subsequent transendothelial migration. Its expression on endothelial cells is increased in inflammation and atherosclerosis. As it has been suggested that insulin and hyperinsulinemia may have a role in atherogenesis, we have now investigated whether insulin has an effect on the expression of ICAM-1 on human aortic endothelial cells (HAEC). HAEC were prepared from human aortas by collagenase digestion and were grown in culture. Insulin (100 and 1000 microU/mL) caused a decrease in the expression of ICAM-1 (messenger ribonucleic acid and protein) by these cells in a dose-dependent manner after incubation for 2 days. This decrease was associated with a concomitant increase in endothelial nitric oxide synthase (NOS) expression also induced by insulin. To examine whether the insulin-induced inhibition of ICAM-1 was mediated by nitric oxide (NO) from increased endothelial NOS, HAEC were treated with N(omega)-nitro-L-arginine, a NOS inhibitor. N(omega)-Nitro-L-arginine inhibited the insulin-induced decrease in ICAM-1 expression in HAEC at the messenger ribonucleic acid and protein levels. Thus, the inhibitory effect of insulin on ICAM-1 expression is mediated by NO. We conclude that insulin reduces the expression of the proinflammatory adhesion molecule ICAM-1 through an increase in the expression of NOS and NO generation and that insulin may have a potential antiinflammatory and antiatherosclerotic effect rather than a proatherosclerotic effect.
Subject(s)
Endothelium, Vascular/metabolism , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Intercellular Adhesion Molecule-1/biosynthesis , Nitric Oxide/physiology , Aorta/cytology , Aorta/drug effects , Aorta/metabolism , Blotting, Western , Cell Separation , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Enzyme Inhibitors , Humans , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/biosynthesis , Nitric Oxide Synthase Type III , Nitroarginine/pharmacology , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
OBJECTIVES: Thrombolytic therapy is frequently used to manage vascular graft thrombosis. However, long-term patency after thrombolysis remains poor. The purpose of this study was to characterise the morphological and functional response of endothelial cells (EC) exposed to a thrombus and subsequently lytic therapy. METHODS: Human EC were exposed to human whole blood thrombus for 2, 6, 12, and 24 h. The thrombus was lysed with urokinase. Cell morphology was studied with electron microscopy. Northern blot analyses were performed with human c-DNA probes for endothelin-1, thrombomodulin, tissue factor, tissue plasminogen activator, plasminogen activator inhibitor, and triose phosphate isomerase. RESULTS: EC retraction occurred for each period of incubation. Thrombomodulin expression was increased 2.2-fold at 6 h and 2.4-fold at 24 h. t-PA expression was depressed proportionally to the duration of thrombus exposure. PAI and TF expression transiently increased 1.5-fold at 2 h of exposure and returned to baseline at 6 h. Endothelin expression remained unchanged. CONCLUSIONS: Except for a transient increase in TF expression and reversal of the tPA/PAI ratio, EC exposed to thrombus do not appear to become actively procoagulant. The increase in TM expression may reflect enhanced thromboresistance. However, EC retraction may be responsible for an increase thrombogenicity of saphenous vein graft after thrombosis and Urokinase therapy.
Subject(s)
Endothelium, Vascular/metabolism , Thrombolytic Therapy/adverse effects , Cells, Cultured , Endothelin-1/analysis , Endothelium, Vascular/drug effects , Endothelium, Vascular/ultrastructure , Graft Occlusion, Vascular/drug therapy , Humans , Microscopy, Electron, Scanning , Plasminogen Activator Inhibitor 1/analysis , Saphenous Vein , Thrombomodulin/analysis , Thromboplastin/analysis , Thrombosis/drug therapy , Tissue Plasminogen Activator/analysis , Urokinase-Type Plasminogen Activator/adverse effects , Urokinase-Type Plasminogen Activator/therapeutic useABSTRACT
Ample evidence is available on the impact of health care practices and hospital routines and procedures on breastfeeding. Good practices enhance successful initiation and establishment of breastfeeding and contribute to increased duration, just as inappropriate practices, and failure to support and encourage mothers, have the opposite effect. In 1991 the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) jointly launched the Baby-Friendly Hospital Initiative, which aims to give every baby the best start in life by ensuring a health care environment where breastfeeding is the norm. The initiative is based on the principles summarized in a joint statement issued by the two organizations in 1989 on the role of maternity services in protecting, promoting, and supporting breastfeeding. To become truly baby-friendly, hospitals and maternity wards around the world are giving practical effect to the principles described in the joint WHO/UNICEF statement that have been synthesized into Ten Steps To Successful Breastfeeding. This summary of the rationale and scientific basis for the Ten Steps is presented in the light of cumulative experience demonstrating the crucial importance of these principles for the successful initiation and establishment of breastfeeding.
Subject(s)
Breast Feeding , Health Promotion/organization & administration , Hospital Administration , Maternal Health Services/organization & administration , Female , Humans , Infant, Newborn , Mothers/education , Mothers/psychology , Organizational Policy , World Health OrganizationABSTRACT
The presence of lactational amenorrhoea cannot be fully relied upon to protect the individual mother against becoming pregnant. Nevertheless, the use of breast-feeding as a birth-spacing mechanism has important implications for global health policy. This article identifies the information that should be collected and examined as a basis for developing guidelines on how to reduce the dual protection afforded by post-partum lactational amenorrhoea and other family planning methods, and discusses when such methods should be introduced.
Subject(s)
Birth Intervals , Breast Feeding , Family Planning Services , Adult , Female , Humans , Infant , Infant, Newborn , Pregnancy , World Health OrganizationABSTRACT
No se puede confiar por completo en que la amenorrea de la lactancia prevenga el embarazo. No obstante, el empleo de la lactancia materna como mecanismo para espaciar los nacimientos tiene gran trascendencia para las políticas de salud globales. En este artículo se identifica la información que es preciso reunir y examinar como base para establecer pautas encaminadas a reducir la protección dual proporcionada después del parto por la amenorrea de la lactancia materna y otros métodos de planificación familiar, y se analiza cuándo se deben introducir esos métodos
Subject(s)
Breast Feeding , Birth Intervals , Policy Making , Family Planning Services , Colombia , Mexico , Chile , GuamABSTRACT
No se puede confiar por completo en que la amenorrea de la lactancia prevenga el embarazo. No obstante, el empleo de la lactancia materna como mecanismo para espaciar los nacimientos tiene gran trascendencia para las políticas de salud globales. En este artículo se identifica la información que es preciso reunir y examinar como base para establecer pautas encaminadas a reducir la protección dual proporcionada después del parto por la amenorrea de la lactancia materna y otros métodos de planificación familiar, y se analiza cuándo se deben introducir esos métodos
Disponible en inglés en Bull WHO 68(5), 1990
Subject(s)
Breast Feeding , Birth Intervals , Colombia , Mexico , Chile , Guam , Policy Making , Family Planning ServicesABSTRACT
The presence of lactational amenorrhoea cannot be fully relied upon to protect the individual mother against becoming pregnant. Nevertheless, the use of breast-feeding as a birth-spacing mechanism has important implications for global health policy. This article identifies the information that should be collected and examined as a basis for developing guidelines on how to reduce the dual protection afforded by postpartum lactational amenorrhoea and other family planning methods, and discusses when such methods should be introduced.
PIP: Lactational amenorrhea in many developing countries is still the most successful form of contraception, especially when modern forms of contraception are not available. In cultures where frequent or prolonged breast feeding is common, postpartum amenorrhea and suppressed ovulation are frequent and serve to space births. It is this spacing of births that leads to decreased infant and maternal morbidity and mortality. It must be remembered that lactational amenorrhea is not a completely reliable form of contraception. In fact the figures indicate that in cultures were family planning use is low, birth intervals are largely determined by the duration and intensity of breastfeeding. Studies indicate that an increase of 15% 32% in birth intervals can result from prolonged lactation. It would be to the advantage of health care planners and providers to examined more closely the causes and properties of lactational amenorrhea. Field directed education can provide women with the information necessary to help them control their child spacing. The WHO Breast-feeding Data Bank collects and analyzes information on breast-feeding and its effects on fertility regulation. Methods used to assess lactational infertility and how the information is used by the data bank are described in this article. There is a summary of relevant information gathered from published sources and post 1983 studies of the WHO. The practical implications to health policy that are associated with lactation-associated infertility are also mentioned.