Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epinephrine has been found to inhibit the production of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha and to enhance the production of anti-inflammatory cytokine interleukin (IL)-10. To determine the effect of epinephrine on IL-1 beta production, the following experiments were performed: 1) blood obtained from subjects at 4-21 h after the start of a continuous infusion of epinephrine (30 ng.kg-1.min-1) produced less IL-1 beta after ex vivo stimulation with lipopolysaccharide (LPS), compared with blood drawn from subjects infused with saline; 2) in whole blood in vitro, epinephrine caused a dose-dependent decrease in LPS-induced IL-1 beta production, which was likely mediated via adrenergic receptors; and 3) inhibition of TNF and enhancement of IL-10 both contributed to epinephrine-induced inhibition of IL-1 beta production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may attenuate excessive activity of proinflammatory cytokines early in the course of systemic infection.
 ...
PMID:Epinephrine inhibits endotoxin-induced IL-1 beta production: roles of tumor necrosis factor-alpha and IL-10. 943 41

Tissue hypoxia, especially in the splanchnic area, is still considered to be an important cofactor in the pathogenesis of multiple organ failure. Thus, in the treatment of septic shock the specific effects of ino-tropic drugs on the splanchnic perfusion are of particular interest. To give strict recommendations for monitoring and for therapeutic strategies in the treatment of gastrointestinal failure in patients with sepsis is difficult not only due to the lack of data on clinical outcome and organ dysfunction, but also due to some limitations in the methods applied to assess splanchnic perfusion and oxygenation. A reasonable approach in the management of splanchnic underperfusion in septic patients includes: Measurement of gastric mucosal pH or CO2-gap because it is the only method for the assessment of splanchnic perfusion which can be useful in the clinical routine. Adequate volume loading likely is the most important step in the supportive treatment of patients with septic shock. Unfortunately, what kind of fluids, endpoints, and monitoring techniques should be used is still controversial. Nevertheless, techniques allowing us to achieve and tightly control volume loading and regional perfusion, e.g. the measurement of pHi or CO2-gap, may be helpful. Patients with high DO2 have had better outcome. However, measurement of parameters assessing global and regional oxygenation may be superior than to guide therapy by DO2. To maximize DO2 by the use of very high dosages of catecholamines can be harmful. The recommendation to use dobutamine as catecholamine of first choice seems to be justified. In critically ill patients, no negative effects of norepinephrine on regional perfusion have been demonstrated provided the patient is adequately volume resuscitated and the DO2 is normal or slightly elevated. Therefore, after volume resuscitation and treatment with dobutamine, norepinephrine should be used for achieving an adequate perfusion pressure. Epinephrine and dopamine should be avoided because they seem to restribute blood flow away from the splanchnic region. There are no convincing data yet to support the routine use of low dose dopamine or dopexamine in patients with sepsis. These recommendations are limited by the lack of outcome studies and optimal methods for the assessment of splanchnic perfusion/oxygenation.
 ...
PMID:[Aspects in monitoring and treatment of gastrointestinal underperfusion in sepsis. Diagnosis and therapy of gastrointestinal underperfusion in sepsis]. 968 8

While realizing the difficulties with the various methods used to study hormonal control of protein metabolism, there appear to be clear effects of both rapid-acting and slower-acting hormones. Moreover, some of these hormones affect protein metabolism in a dose dependent manner. Insulin and IGF-I appear to have differing effects at lower doses, with insulin primarily inhibiting protein degradation and IGF-I stimulating protein synthesis. At higher doses, infusions of insulin and IGF-I both seem to inhibit protein degradation and stimulate protein synthesis. Epinephrine primarily inhibits protein degradation whereas growth hormone primarily increases protein synthesis. Infusion of amino acids themselves can also increase protein synthesis. Thyroid hormone excess increases protein synthesis and protein degradation, with the latter effect predominating. Sex steroids appear to increase protein synthesis. To date, most interventions studying the metabolic effects of these hormones on protein metabolism have involved varying the concentration of one hormone at a time. In the complex milieu of many pathologic states (e.g. sepsis, renal failure or even the transition from fasting to feeding) multiple hormones change simultaneously. How interactions among these factors determine the overall response of body and muscle protein remains to be defined.
 ...
PMID:The role of insulin and other hormones in the regulation of amino acid and protein metabolism in humans. 1021 37

Adequate volume loading may be the most important step in the treatment of patients with septic shock. Techniques allowing us to achieve and tightly control volume loading and regional perfusion are considered to be helpful. An elevated oxygen delivery may be beneficial in some patients but the increase of oxygen delivery should be guided by the measurement of parameters assessing global and regional oxygenation. Forcing an increase in oxygen delivery by the use of very high dosages of catecholamines can be harmful. Vasopressors should be used for achieving an adequate perfusion pressure. For norepinephrine, no negative effects on regional perfusion have been demonstrated. Epinephrine and dopamine should be avoided because they seem to redistribute blood flow away from the splanchnic region. There are no convincing data yet to support the routine use of low dose dopamine or dopexamine in patients with sepsis. Neither low dose dopamine nor dopexamine has been proven to prevent renal failure in septic patients. Furthermore, there is evidence that low dose dopamine may reduce mucosal perfusion in the gut in some patients. There is some suggestion that dopexamine can improve splanchnic perfusion but since these effects remain somewhat controversial, there is no reason for a general recommendation for dopexamine in septic patients.
 ...
PMID:Supportive therapy of the sepsis syndrome. 1035 80

Tissue hypoxia, especially in the splanchnic area, is still considered to be an important cofactor in the pathogenesis of multiple organ failure. Therefore, the specific effects of the various therapeutic interventions on splanchnic perfusion and oxygenation are of particular interest. Restoring and maintaining oxygen transport and tissue oxygenation is the most important step in the supportive treatment of patients with sepsis and impaired gut perfusion. Therefore, supportive treatment should be focused on an adequate volume resuscitation and appropriate use of vasoactive drugs. Adequate volume loading may be the most important step in the treatment of patients with septic shock. An elevated oxygen delivery may be beneficial in some patients, but the increase of oxygen delivery should be guided by the measurement of parameters assessing global and regional oxygenation. Forcing an elevation in oxygen delivery by the use of very high dosages of catecholamines can be harmful. Vasopressors should be used for achieving an adequate perfusion pressure. For norepinephrine, no negative effects on gut perfusion have been demonstrated. Epinephrine and dopamine should be avoided because they seem to redistribute blood flow away from the splanchnic region. There are no convincing data yet to support the routine use of low-dose dopamine or dopexamine to improve an impaired gut perfusion. There is even evidence that low-dose dopamine may reduce the mucosal perfusion in the gut in some patients. It has been suggested that dopexamine can improve splanchnic perfusion, but because these effects remain somewhat controversial, a general recommendation for dopexamine to improve gut perfusion is not justified.
 ...
PMID:Therapeutic options for the treatment of impaired gut function. 1125 Oct 35

The effect of sepsis on the minimum alveolar concentration of desflurane (MAC(DES)) in humans and other animals has not been reported previously. The aim of this study was to test the hypothesis that sepsis might alter MAC(DES) in a normotensive septic porcine model. Twenty-four young healthy pigs were premedicated with ketamine 10 mg kg(-1 )i.m and then anaesthesia was established with propofol 3 mg kg(-1) and the trachea was intubated. Baseline MAC(DES) in each pig was evaluated by pinching with a haemostat applied for 1 min to a rear dewclaw. MAC(DES) was determined by changing desflurane concentrations stepwise until purposeful movement appeared. Pigs were randomly assigned to two groups of 12 animals: the saline group received a 1 h i.v. infusion of saline solution while the sepsis group received a 1 h i.v. infusion of live Pseudomonas aeruginosa. Epinephrine and hydroxyethylstarch were used to maintain normotensive and normovolaemic haemodynamic status. In both groups, MAC(DES) was evaluated 5 h after infusion. Significant increases in heart rate, cardiac output, mean pulmonary artery pressure and pulmonary vascular resistance occurred in the sepsis group. MAC(DES) was 9.2% (95% confidence interval (CI) 6.8-10.6%) for the saline group and 6.7% (95% CI: 4.7-10.4) for the sepsis group (P<0.05). These data indicate that MAC(DES) is significantly decreased in this normotensive hyperkinetic septic porcine model.
 ...
PMID:Influence of sepsis on minimum alveolar concentration of desflurane in a porcine model. 1149 2

Sevoflurane is widely used in anaesthetic protocols for patients undergoing surgical procedures. However, there are no reports on the influence of sepsis on minimum alveolar concentration of sevoflurane (MAC(SEV)) in animals or in humans. The aim of this study was to test the hypothesis that sepsis could alter the MAC(SEV) in a normotensive septic pig model. Twenty young, healthy pigs were used. After they had received 10 mg kg(-1) of ketamine i.m. for premedication, anaesthesia was established with propofol 3 mg kg(-1) and the trachea was intubated. Sevoflurane was used as the sole anaesthetic agent. Baseline haemodynamic recording included electrocardiography, carotid artery blood pressure and a pulmonary thermodilution catheter. Baseline MAC(SEV) in each pig was evaluated by pinching with a haemostat applied for 1 min to a rear dewclaw. MAC(SEV) was determined using incremental changes in sevoflurane concentration until purposeful movement appeared. Pigs were assigned randomly to two groups: the saline group (n = 10) received a 1-h i.v. infusion of sterile saline solution while the sepsis group (n = 10) received a 1-h i.v. infusion of live Pseudomonas aeruginosa. Epinephrine and hydroxyethylstarch were used to maintain normotensive and normovolemic haemodynamic status. In both groups, MAC(SEV) was evaluated 5 h after infusion. Significant increases in mean artery pulmonary pressure, filling, epinephrine and vascular pulmonary resistances occurred in the sepsis group. MAC(SEV) for the saline group was 2.4% [95% confidence interval (CI) 2.1-2.55%] and the MAC(SEV) for the sepsis group was 1.35% (95% CI 1.2-1.45%, P<0.05). These data indicate that MAC(SEV) is significantly decreased in this normotensive septic pig model.
 ...
PMID:Influence of sepsis on sevoflurane minimum alveolar concentration in a porcine model. 1157 78

Intraosseous (IO) puncture is considered for the administration of drugs and fluids when vascular access cannot be achieved rapidly. Adrenaline/epinephrine, adenosine, crystalloids, colloids and blood products can be applied and administered effectively using this route during resuscitation of children. This technique is relatively simple with complications of <1%. These may include tibial fracture, lower extremity compartment syndrome and osteomyelitis. A case is described in which a 3-month-old male infant presented for emergency resuscitation requiring IO infusion utilising both tibial bones. High doses of adrenaline (1:1000; 0.1 mg/kg) were administered in the right tibial epiphysis only after the standard initial concentration (1:10000; 0.01 mg/kg) had minimal effect. A local inflammatory reaction was noted 24 h later in the right tibial region, which developed into cutaneous necrosis, and was eventually resected. Radiologically, no osseous lesion could be demonstrated, however, a bone scintigram revealed osteomyelitis. Upon surgical revision, purulent destruction was evident requiring removal of the epiphysis and part of the metaphysis. Although osteomyelitis is a rare complication which may be caused by sepsis, or contamination during insertion, we speculate that adrenaline in high concentrations may promote the development of osteomyelitis and the drug should be applied cautiously in more diluted concentrations.
 ...
PMID:Osteomyelitis at the injection site of adrenalin through an intraosseous needle in a 3-month-old infant. 1206 48

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has an important role in the development of inflammatory responses during infection by regulating leukocyte trafficking and function. Our study was conducted to investigate the effect of adrenaline on lipopolysaccharide (LPS)-induced MIP-1 alpha production by human peripheral blood monocytes and human monocytic THP-1 cells. Monocytes were incubated in vitro with LPS for 4 h at 37 degrees C in the presence and absence of adrenaline and/or specific alpha- and beta-adrenergic receptor antagonists and agonists. The effects of adrenaline on MIP-1 alpha synthesis were studied at the protein level by using enzyme-linked immunosorbent assays and at the messenger RNA level by using reverse transcriptase-polymerase chain reaction. Adrenaline inhibited LPS-induced MIP-1 alpha production in a dose-dependent manner. The suppressive effect could be completely prevented by propranolol, but not by phentolamine. The specific beta-adrenergic agonist isoproterenol produced the same inhibitory effect on LPS-induced MIP-1 alpha production, whereas the alpha-adrenergic agonist phenylephrine had a minimal effect. In addition, suppression of MIP-1 alpha production was associated with an increase of intracellular cyclic adenosine monophosphate (cAMP) by the cell membrane-permeable cAMP analog dibutyryl-cAMP. Furthermore, we found that adrenaline inhibited LPS-induced MIP-1 alpha messenger RNA expression. These findings suggest that adrenaline can modulate MIP-1 alpha production in inflammatory diseases and sepsis.
 ...
PMID:Adrenaline inhibits lipopolysaccharide-induced macrophage inflammatory protein-1 alpha in human monocytes: the role of beta-adrenergic receptors. 1253 6

Epinephrine is known to be rapidly oxidized during sepsis. Ischemia and acidosis, which often accompany sepsis, are associated with the release of weakly bound cupric ions from plasma proteins. We investigated whether copper promotes oxidation of epinephrine at both physiological and acidic pH and whether D-Asp-D-Ala-D-His-D-Lys (D-DAHK), a human albumin (HSA) N-terminus synthetic peptide with a high affinity for cupric ions, attenuates this oxidation. Epinephrine alone [100 microM] or with CuCl(2) [10 microM], and with CuCl(2) [10 microM] and D-DAHK [20 microM] at pH 7.4, 7.0, 6.5, and 6.0 were incubated for 1h at 37 degrees C. Epinephrine oxidation was measured by the spectrophotometric quantification of its oxidation product, adrenochrome. We found that adrenochrome increased, suggesting copper-induced oxidation of epinephrine. At pH 7.4, 7.0, 6.5, and 6.0, adrenochrome increased by 47%, 53%, 24%, and 6% above baseline, respectively. D-DAHK attenuated the copper-induced oxidation of epinephrine to baseline levels. These in vitro results indicate that copper-induced epinephrine oxidation is greatest at the physiological pH 7.4 as well as in severe acidosis, pH 7.0, and that D-DAHK completely inhibits this oxidation.
 ...
PMID:Copper-induced oxidation of epinephrine: protective effect of D-DAHK, a synthetic analogue of the high affinity copper binding site of human albumin. 1272 20


<< Previous 1 2 3 4 Next >>