Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The term ''adrenergic'' originates from ''adrenaline'' and describes hormones or drugs whose effects are similar to those of epinephrine. Adrenergic stress is mediated by stimulation of adrenergic receptors and activation of post-receptor pathways. Critical illness is a potent stimulus of the sympathetic nervous system. It is undisputable that the adrenergic-driven ''fight-flight response'' is a physiologically meaningful reaction allowing humans to survive during evolution. However, in critical illness an overshooting stimulation of the sympathetic nervous system may well exceed in time and scope its beneficial effects. Comparable to the overwhelming immune response during sepsis, adrenergic stress in critical illness may get out of control and cause adverse effects. Several organ systems may be affected. The heart seems to be most susceptible to sympathetic overstimulation. Detrimental effects include impaired diastolic function, tachycardia and tachyarrhythmia, myocardial ischemia, stunning, apoptosis and necrosis. Adverse catecholamine effects have been observed in other organs such as the lungs (pulmonary edema, elevated pulmonary arterial pressures), the coagulation (hypercoagulability, thrombus formation), gastrointestinal (hypoperfusion, inhibition of peristalsis), endocrinologic (decreased prolactin, thyroid and growth hormone secretion) and immune systems (immunomodulation, stimulation of bacterial growth), and metabolism (increase in cell energy expenditure, hyperglycemia, catabolism, lipolysis, hyperlactatemia, electrolyte changes), bone marrow (anemia), and skeletal muscles (apoptosis). Potential therapeutic options to reduce excessive adrenergic stress comprise temperature and heart rate control, adequate use of sedative/analgesic drugs, and aiming for reasonable cardiovascular targets, adequate fluid therapy, use of levosimendan, hydrocortisone or supplementary arginine vasopressin.
 ...
PMID:Sympathetic overstimulation during critical illness: adverse effects of adrenergic stress. 2750 1

Activated protein C (APC) is a vitamin-K dependent natural anticoagulant protein. With its function in blood clotting reaction, APC can reduce the risk of venous thrombosis to prevent ischemic disease. A number of in vivo and in vitro studies over the past few decades have revealed that APC also exerted cytoprotective effects to decrease the mortality caused by endotoxin, sepsis, and brain ischemic stroke. The direct cytoprotective role requires APC binding to the endothelial protein C receptor (EPCR) and activating protease activated receptor-1 (PAR-1). It is now believed that the beneficial characters of APC are partially independent from its anticoagulant activity, though more studies need to be done to demonstrate the exact molecular mechanism. In this review, we have linked the cytoprotective effects of APC including the anti-inflammatory and anti-apoptosis activities to myocardial ischemic injury caused by cardiac ischemia reperfusion. Specifically, we have tried to combine the potential signaling pathways initiated by APC with the well-known adaptive signaling such as AMP-activated protein kinase (AMPK), PI3K/Akt and ERK/MAPK pathways that contribute to the cardioprotection against myocardial ischemia injury. We speculate that APC protects against cardiac ischemia injury via triggering crucial cardioprotective signaling pathways, and these effects are mostly associated with its cytoprotective activity but independent on its anticoagulant activity.
 ...
PMID:Activated protein C: a potential cardioprotective factor against ischemic injury during ischemia/reperfusion. 1995 50

For years, cardiac troponins (cTn) have been regarded as the preferred biomarkers for the diagnosis of myocardial infarction and for the risk stratification of patients with acute coronary syndromes, as well as for the selection of patients who need an early invasive strategy, and for the guidance of adjunctive pharmacological therapy. In addition, measurement of cTn has been found useful for detection of myocardial necrosis in conditions unrelated to myocardial ischemia including acute pulmonary embolism, myocarditis, heart failure, sepsis, and end-stage renal disease. In these conditions, an unfavorable prognosis is unequivocally associated with detectable concentrations of cTn.A major limitation of most currently available cTn assays is the lack of adequate precision, i.e., to measure cTn concentrations at the 99th percentile value with a coefficient of variation < 10%. As a consequence, many manufacturers have developed more sensitive cTn assays that now comply with precision criteria required by the Joint European Society of Cardiology/ American College of Cardiology/American Heart Association/World Heart Federation Task Force for the Redefinition of Acute Myocardial Infarction.Using assays with higher analytic sensitivity more patients will be seen in clinical practice with the high-sensitivity cardiac troponin T (TnThs) above the 99th percentile discriminator. The causes of these elevations may be due to acute, subacute and chronic cardiac disease such as heart failure or cardiomyopathies.
 ...
PMID:Troponins and high-sensitivity troponins as markers of necrosis in CAD and heart failure. 2002 39

Endoplasmic reticulum (ER) stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR). Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.
 ...
PMID:HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction. 2062 43

Cardiac ischemia/reperfusion (I/R) injury occurs in several important clinical contexts including percutaneous coronary interventions for acute myocardial ischemia, cardiac surgery in the setting of cardiopulmonary bypass, and cardiac transplantation. While the pathogenesis of I/R injury in these settings is multifactorial, it is clear that activation of the innate immune system and the resultant inflammatory response are important components of I/R injury. Toll-like receptor 4 (TLR4), originally identified as the sensor for bacterial lipopolysaccharide (LPS), has also been shown to serve as a sensor for endogenous molecules released from damaged or ischemic tissues. Accordingly, recent findings have demonstrated that TLR4 not only plays a central role as a mediator of cardiac dysfunction in sepsis, but also serves as a key mediator of myocardial injury and inflammation in the setting of I/R. Furthermore, TLR4 may play a role in the development of atherosclerotic lesions. Other studies have implicated TLR4 in the adverse remodeling that may occur after ischemic myocardial injury. This emerging body of literature, which is reviewed here, has provided new insight into the early molecular events that mediate myocardial injury and dysfunction in the setting of I/R injury.
 ...
PMID:Toll-like receptors and myocardial ischemia/reperfusion, inflammation, and injury. 2067 78

Procalcitonin (PCT) levels are below the detection level in healthy subjects, while pre-procalcitonin mRNA is over expressed in human medullar thyroid carcinoma, in small cell lung tumor, and occasionally in other rare neuroendocrine tumors such as phaeochromocytoma. PCT is known as a sensitive and specific biomarker for bacterial sepsis, being produced by extra-thyroidal parenchymal tissues, mainly hepatocytes. The increase in plasma level correlates with the severity of infection and the magnitude and the time course of its increase can be strictly related to the patient's outcome, and to the bacterial load. So far, data on serum PCT levels in patients with cardiogenic shock and in those with acute coronary syndromes (ACS) are scarce and controversial. While some studies report that PCT levels are increased in ACS patients on admission, other investigations document that plasma PCT concentrations are in the normal range. We recently reported that the degree of myocardial ischemia (clinically indicated by the whole spectrum of ACS, from unstable angina to cardiogenic shock following ST-elevation myocardial infarction) and the related inflammatory-induced response are better reflected by C-reactive protein (which was positive in most acute cardiac care patients of all our subgroups) than by PCT, which seems more sensitive to a higher degree of inflammatory activation, being positive only in patients with cardiogenic shock. Few studies investigated the dynamics of PCT in cardiac acute patients, and, despite the paucity of data and differences in patients' selection criteria, an increase in PCT values seems to be associated with the development of complications. In acute cardiac patients, the clinical values of procalcitonin rely not on its absolute value, but only on its kinetics over time.
 ...
PMID:Procalcitonin in acute cardiac patients. 2087 2

Reperfusion injury following hemorrhagic shock is accompanied by the development of a systemic inflammatory state that may lead to organ failure. Insulin connecting peptide (C-peptide) has been shown to exert anti-inflammatory effects in sepsis and myocardial ischemia-reperfusion injury and to ameliorate renal dysfunction in diabetic animals. Hence, we investigated the effect of C-peptide on kidney injury after hemorrhagic shock. We hypothesized that C-peptide would exert renoprotective effects by blunting inflammation. Hemorrhagic shock was induced in male rats (3-4 months old) by withdrawing blood from the femoral artery to a mean arterial pressure of 50 mmHg. Animals were kept in shock for 3 h, at which time they were rapidly resuscitated by returning their shed blood. At the time of resuscitation and every hour thereafter, one group of animals received C-peptide (280 nmol/kg), whereas another group received vehicle. Hemorrhagic shock resulted in significant rise in plasma levels of creatinine and elevated kidney neutrophil infiltration as evaluated by myeloperoxidase activity in vehicle-treated rats in comparison with sham rats, thus suggesting kidney injury. Treatment with C-peptide significantly attenuated the rise in creatinine and kidney myeloperoxidase activity when compared with vehicle group. At a molecular level, these effects of C-peptide were associated with reduced expression of the c-Fos subunit and reduced activation of the proinflammatory kinases, extracellular signal-regulated kinase 1/2 (ERK 1/2), and c-Jun N-terminal kinase and subsequently reduced DNA binding of activator protein 1 in the kidney. Thus, our data suggest that C-peptide may exert renoprotective effects after hemorrhagic shock by modulating activator protein 1 signaling.
 ...
PMID:C-peptide ameliorates kidney injury following hemorrhagic shock. 2126 84

Cardiogenic shock is characterized by inadequate tissue perfusion due to cardiac dysfunction, and it is often caused by acute myocardial infarction. The mortality rate in patients with cardiogenic shock is still very high (i.e., 50-60%). The pathophysiology of cardiogenic shock involves a vicious spiral circle: ischemia causes myocardial dysfunction, which in turn aggravates myocardial ischemia. Myocardial stunning and/or hibernating myocardium can enhance myocardial dysfunction, thus, worsening the cardiogenic shock. Low perfusion pressures with global ischemia leads to multiorgan dysfunction. Ischemia and reperfusion can result in systemic inflammation or within the first few days sepsis due to the translocation of bacteria or bacterial toxins from the intestines, which can result in increased mortality. The key to an optimal treatment of cardiogenic shock patients is a structured approach: (1) rapid diagnosis and prompt initiation of therapy to increase blood pressure and augment cardiac output with subsequently improved perfusion. (2) Rapid coronary revascularization is of critical importance. Using this approach, mortality can be reduced. In many hospitals, initial stabilization is achieved by intraaortic balloon counterpulsation (IABP). However, evidence for improved survival from randomized studies on the use of IABP in combination with PCI is lacking. (3) In order to achieve adequate perfusion, dobutamine and sometimes in combination with norepinephrine might be necessary. Recent studies have shown that the calcium sensitizer levosimendan in cardiogenic shock can be a useful addition to medical therapy. In this overview, epidemiology, pathophysiology, and guideline-oriented treatment strategies for cardiogenic shock are presented.
 ...
PMID:Pathophysiology, diagnosis, and treatment of infarction-related cardiogenic shock. 2142 45

Cardiac dysfunction is common in patients with severe sepsis and septic shock. We present a 71-year-old woman with Escherichia coli urosepsis and sepsis-induced myocardial injury masquerading as non-ST elevated myocardial ischemia. Spontaneous psoas hematoma requiring blood transfusion and intracranial hemorrhage developed after antiplatelet and anticoagulant therapies, even in therapeutic doses. The patient was managed conservatively and recovered well with minor residual hemiparesis. Bleeding complications are a common risk of antithrombotic therapy. It is therefore crucial to weigh the impact of efficacy against safety. Old age, female gender, renal insufficiency and sepsis character increased the risk of bleeding in this patient. A misinterpretation of elevated cardiac troponin I may give rise to a diagnostic dilemma and cause unnecessary morbidity.
 ...
PMID:Severe bleeding after antithrombotic therapy in urosepsis masquerading as myocardial infarction. 2146 17

Steroids and statins may facilitate the integration of anesthetic design with clinical outcome. Although steroids clearly benefit adult cardiac surgical patents, the evidence is weaker in pediatric cardiac surgery. Current large randomized trials of steroids likely will determine the future role of steroids in adult cardiac surgery. In the intensive care unit, steroid therapy is indicated in septic shock that is refractory to fluid and pressor therapy. Recent data, however, indicate that liberal steroid therapy for sepsis may have adverse outcome consequences. A 2nd concern in the intensive care unit is acute adrenal suppression secondary to bolus etomidate therapy because it may be deleterious in patients with septic shock. Possible clinical solutions include alternative induction agents, concomitant steroid therapy, and recent etomidate derivatives. Statins also reduce mortality and atrial fibrillation after cardiac surgery. Furthermore, they slow the progression of rheumatic valvular stenosis, an important consideration in the developing world. Statins also may reduce delirium, stroke, and acute renal injury after cardiac surgery, but further randomized trials are required before definitive recommendations can be formulated. Statins are essential in vascular surgery because they reduce mortality, myocardial ischemia, and acute renal injury. As a result, they have been recommended highly for outcome enhancement in recent perioperative guidelines. Although they may improve survival in sepsis, further investigation is indicated to define their therapeutic role.
 ...
PMID:Integrating outcome benefit into anesthetic design: the promise of steroids and statins. 2196 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>