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21.
22.
Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans 总被引:3,自引:0,他引:3
Granowitz EV; Porat R; Mier JW; Orencole SF; Callahan MV; Cannon JG; Lynch EA; Ye K; Poutsiaka DD; Vannier E 《Blood》1993,82(10):2985-2990
Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra. 相似文献
23.
The balance of tissue-type plasminogen activator (t-PA) production and degradation determines its concentration in blood and tissues. Disturbance of this balance may result in either increased or decreased proteolysis. In the present study, we identified the receptor systems involved in the degradation of t-PA by human monocytes/macrophages in culture. Monocytes were cultured and became macrophages within 2 days. At 4 degrees C, 125I-t-PA bound to macrophages with high (apparent dissociation constant [kd], 1 to 5 nmol/L) and low affinity (kd > 350 nmol/L). At 37 degrees C, the cells internalized and degraded t-PA via the high affinity binding sites, which were partially inhibited by mannan. The low affinity binding sites were 6-aminohexanoic acid- inhibitable and not involved in t-PA degradation. Degradation of t-PA was upregulated during differentiation of monocytes to macrophages. Dexamethasone further upregulated the mannan-inhibitable t-PA degradation. Lipopolysaccharide downregulated both mannan-inhibitable and non-mannan-inhibitable t-PA degradation. Non-mannan-inhibitable degradation was completely blocked by recombinant 39-kD receptor- associated protein (RAP, inhibitor of lipoprotein receptor-related protein [LRP]), whereas mannan-inhibitable degradation was blocked by the addition of a monoclonal antibody against the mannose receptor. No differences between the degradation of t-PA and functionally inactivated t-PA were observed. We conclude that human monocyte-derived macrophages are able to bind, internalize, and degrade t-PA. Degradation of t-PA does not require complex formation with plasminogen activator inhibitors. The macrophages use two independently regulated receptors, namely, the mannose receptor and LRP, for the uptake and degradation of t-PA. 相似文献
24.
Systemic non‐biologic agents have long been in clinical use in medicine – often with considerable efficacy, albeit with some adverse effects – as with all medications. With the advent of biologic agents, all of which currently are restricted to systemic use, there is a growing need to ensure which agents have the better therapeutic ratio. The non‐biologic agents (NBAs) include a range of agents, most especially the corticosteroids (corticosteroids). This study reviews the corticosteroids in systemic use in management of orofacial mucocutaneous diseases; subsequent studies discuss corticosteroid‐sparing agents used in the management of orofacial diseases, such as calcineurin inhibitors used to produce immunosuppression; purine synthetase inhibitors; and cytotoxic and other immunomodulatory agents. 相似文献
25.
26.
Kirsti Krohn Garns Trude Elvebakk
yvind Salvesen Signe Nilssen Stafne Siv Mrkved Kjell smund Salvesen Trine Moholdt 《Nutrients》2022,14(1)
Women with obesity have increased risk for hyperglycemia during pregnancy, with negative health consequences for mother and child. We aimed to investigate adherence to nutritional recommendations in early pregnancy and to examine associations between early pregnancy dietary intake and late pregnancy glycemia among women with obesity. We included 120 women with pre-pregnancy body mass index (BMI) ≥30 kg/m2 who participated in one of two randomized controlled trials. The participants completed a food frequency questionnaire in early pregnancy (gestational weeks 12–22). Fasting and 120 min glucose tolerance after ingestion of 75 g glucose were assessed in late pregnancy (gestational weeks 32–37). About 90% of the participants reported early pregnancy diary intake within the recommendations. Average intakes of vitamin D, iron, and folate were below recommended levels. High intakes of dairy products and protein in early pregnancy were associated with lower fasting glucose in late pregnancy, whereas high intake of bread was associated with lower 120 min glucose. There were no clear associations between single dietary variables and gestational diabetes mellitus (GDM) diagnosis in late pregnancy. In conclusion, some early pregnancy dietary variables were associated with late pregnancy glycemia. Potential causality of these findings should be investigated in future studies. 相似文献
27.
J Komulainen R Lounamaa M Knip EA Kaprio HK Akerblom 《Archives of disease in childhood》1996,75(5):410-415
The determinants of the degree of metabolic decompensation at the diagnosis of type 1 (insulin dependent) diabetes mellitus (IDDM) and the possible role of diabetic ketoacidosis in the preservation and recovery of residual beta cell function were examined in 745 Finnish children and adolescents. Children younger than 2 years or older than 10 years of age were found to be more susceptible to diabetic ketoacidosis than children between 2 and 10 years of age (< 2 years: 53.3%; 2-10 years: 16.9%; > 10 years: 33.3%). Children from families with poor parental educational level had ketoacidosis more often than those from families with high parental educational level (24.4% v 16.9%). A serum C peptide concentration of 0.10 nmol/l or more was associated with a favourable metabolic situation. Low serum C peptide concentrations, high requirement of exogenous insulin, low prevalence of remission, and high glycated haemoglobin concentrations were observed during the follow up in the group of probands having diabetic ketoacidosis at the diagnosis of IDDM. Thus diabetic ketoacidosis at diagnosis is related to a decreased capacity for beta cell recovery after the clinical manifestation of IDDM in children. 相似文献
28.
Bacterial endocarditis is an uncommon diagnosis in childhood with significant morbidity and mortality. Aortic aneurysm as a complication is well described in adults but there are few reports in the paediatric literature. Two children with bacterial endocarditis are described, whose illnesses were complicated by aortic aneurysm formation requiring surgical intervention. 相似文献
29.
Role of bacterial translocation in necrotizing enterocolitis 总被引:1,自引:0,他引:1
EA Deitch 《Acta paediatrica (Oslo, Norway : 1992)》1994,83(S396):33-36
The intestinal mucosa functions as a major local defense barrier preventing bacteria that colonize the gut from invading organs and tissues. Under certain circumstances, bacteria colonizing the gastrointestinal tract can cross the gut mucosal barrier to infect the mesenteric lymph node and systemic organs via a process termed bacterial translocation. Factors that promote the translocation of bacteria or endotoxin from the gut include bacterial overgrowth with gram-negative enteric bacilli, impaired host immune defenses and injury to the gut mucosa resulting in increased intestinal permeability. These same promoting factors are present in patients at increased risk of developing necrotizing enterocolitis. Consequently, this review focuses on the potential role of bacterial and endotoxin translocation from the gut in the pathogenesis of necrotizing enterocolitis. 相似文献
30.
MB Viana M Murao G Ramos HM Oliveira RI de Carvalho M de Bastos EA Colosimo WS Silvestrini 《Archives of disease in childhood》1994,71(4):304-310
One hundred and twenty eight Brazilian children with lymphoblastic leukaemia were intensively treated with a Berlin-Frankfurt-Munich based protocol. More children had a white cell count above 50 x 10(9)/l (31%) then observed in developed countries. After a median follow up of 31 months (11-58 months), the estimated probability of relapse free survival was 41% (7%) for the whole group. After adjustment in the Cox's multivariate model, malnutrition was the most significant adverse factor affecting duration of complete remission. Age above 8 years and high peripheral white cell count were also significant adverse factors. Among the nutritional indices, the height for age and weight for age z scores were both significant, whether the cut off points of z-2 or z = -1.28 were chosen to define malnutrition. A strong statistical association between the two indices was found; the contribution of height for age z score to the prediction of relapse free survival was more significant. Children with height for age z score < -2 had a relapse risk of 8.2 (95% confidence interval 3.1 to 21.9) relative to children with z score > -2. The results of this study suggest that socioeconomic and nutritional factors should be considered in the prognostic evaluation of children with leukaemia in developing countries. 相似文献