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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Septic shock is an important cause of mortality in children with sepsis. The incidence of septic shock is 2-4% of admissions in western pediatric intensive care units and 40%-67% for Indian PICUs. Early goal-directed resuscitation that includes aggressive fluid resuscitation of up to 60 mL/kg as boluses of 20 mL/kg by IV push, to achieve desired heart rates and blood pressure, has emerged as mainstay of treatment in the initial stage. Crystalloids are the preferred fluids, while colloids may be used in some situations. Fluid refractory shock warrants use of vasoactive drugs. Dopamine is the first choice. Dobutamine and low dose epinephrine are the preferred inotropic drugs while nor-epinephrine is a vasopressor. Children with cold shock and normal blood pressure may benefit from nitrosodilators like nitroprusside and nitroglycerine. Inodilators such as milrinone are also useful in this situation. Targeting clinical therapeutic end-points assists the management. Good supportive care is also essential for improving the outcomes.
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PMID:Management of septic shock. 2154 46

Previous anti-inflammatory strategies against sepsis, a leading cause of death in hospitals, had limited efficacy in clinical trials, in part because they targeted single cytokines and the experimental models failed to mimic clinical settings. Neuronal networks represent physiological mechanisms, selected by evolution to control inflammation, that can be exploited for the treatment of inflammatory and infectious disorders. Here, we report that sciatic nerve activation with electroacupuncture controls systemic inflammation and rescues mice from polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls systemic inflammation by inducing vagal activation of aromatic L-amino acid decarboxylase, leading to the production of dopamine in the adrenal medulla. Experimental models with adrenolectomized mice mimic clinical adrenal insufficiency, increase the susceptibility to sepsis and prevent the anti-inflammatory effects of electroacupuncture. Dopamine inhibits cytokine production via dopamine type 1 (D1) receptors. D1 receptor agonists suppress systemic inflammation and rescue mice with adrenal insufficiency from polymicrobial peritonitis. Our results suggest a new anti-inflammatory mechanism mediated by the sciatic and vagus nerves that modulates the production of catecholamines in the adrenal glands. From a pharmacological perspective, the effects of selective dopamine agonists mimic the anti-inflammatory effects of electroacupuncture and can provide therapeutic advantages to control inflammation in infectious and inflammatory disorders.
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PMID:Dopamine mediates vagal modulation of the immune system by electroacupuncture. 2460 93

We have recently shown that the catecholamine dopamine regulates cellular iron homeostasis in macrophages. As iron is an essential nutrient for microbes, and intracellular iron availability affects the growth of intracellular bacteria, we studied whether dopamine administration impacts the course of Salmonella infections. Dopamine was found to promote the growth of Salmonella both in culture and within bone marrow-derived macrophages, which was dependent on increased bacterial iron acquisition. Dopamine administration to mice infected with Salmonella enterica serovar Typhimurium resulted in significantly increased bacterial burdens in liver and spleen, as well as reduced survival. The promotion of bacterial growth by dopamine was independent of the siderophore-binding host peptide lipocalin-2. Rather, dopamine enhancement of iron uptake requires both the histidine sensor kinase QseC and bacterial iron transporters, in particular SitABCD, and may also involve the increased expression of bacterial iron uptake genes. Deletion or pharmacological blockade of QseC reduced but did not abolish the growth-promoting effects of dopamine. Dopamine also modulated systemic iron homeostasis by increasing hepcidin expression and depleting macrophages of the iron exporter ferroportin, which enhanced intracellular bacterial growth. Salmonella lacking all central iron uptake pathways failed to benefit from dopamine treatment. These observations are potentially relevant to critically ill patients, in whom the pharmacological administration of catecholamines to improve circulatory performance may exacerbate the course of infection with siderophilic bacteria.IMPORTANCE Here we show that dopamine increases bacterial iron incorporation and promotes Salmonella Typhimurium growth both in vitro and in vivo These observations suggest the potential hazards of pharmacological catecholamine administration in patients with bacterial sepsis but also suggest that the inhibition of bacterial iron acquisition might provide a useful approach to antimicrobial therapy.
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PMID:Dopamine Is a Siderophore-Like Iron Chelator That Promotes Salmonella enterica Serovar Typhimurium Virulence in Mice. 3072 25

The prevention and treatment of sepsis associated encephalopathy (SAE) remains challenging in clinic. Besides the anti-infection treatments and goal-directed supportive treatments, no specific method is reported for the prevention and treatment of SAE. This study tried to investigate the effects and underlying mechanisms of small dose of L-dopa/Benserazide hydrochloride (L-DA) on SAE. We found that L-DA administration (i.p.) at early stage of sepsis, but not at late stage, improved learning and memory of sepsis surviving mice in Cecal ligation and perforation (CLP) model. Corresponding to the improvement of learning and memory in CLP model, L-DA administration limited neuroinflammation, improved neuroplasticity, reversed sepsis-induced decrease of hippocampal dopamine level, but had no obvious effects on the survival and body weight recovery. Further studies showed that specific inhibitors of dopamine D1 or D2 receptors both partly reduced the protective effect of L-DA on the learning and memory of lipopolysaccharides (LPS) treated mice. D1 receptor specific inhibitor significantly blocked the anti-neuroinflammation effects of L-DA in LPS treated mice, but D2 receptor inhibitor did not. All these suggest that L-DA administration could prevent and treat SAE via dopamine D1 and D2 receptors. Dopamine D1 receptor is a potential target of anti-neuroinflammation.
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PMID:Small dose of L-dopa/Benserazide hydrochloride improved sepsis-induced neuroinflammation and long-term cognitive dysfunction in sepsis mice. 3220 48


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