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)

Severe sepsis and septic shock are still associated with high mortality rates. To improve the outcome, multidisciplinary interactions and cooperation between basic, clinical and industrial researchers are mandatory to develop new artificial or biological devices for the treatment of septic syndrome and related systemic complications. In the future, the development and validation of new biomarkers, aimed at an early diagnosis of sepsis, and the rigorous monitoring of the most significant prognostic indicators, could contribute to better understanding of the mechanisms underlying septic syndrome as well as to the timely institution of potentially effective treatments.
 ...
PMID:[Sepsis: from pathophysiology to treatment]. 1706 33

Severe sepsis is a complex syndrome often resulting in multiple organ dysfunction. This is an extremely challenging problem to manage in the intensive care unit, with mortality rates remaining at unacceptably high levels. Death of patients afflicted by this condition generally results from organ dysfunction syndromes related to hypoperfusion abnormalities. Management of patients with severe sepsis or septic shock can be very complex and challenging, utilizing a significant amount of resources. Pharmacologic support of patients with severe sepsis or septic shock primarily involves agents to support and improve perfusion at the microvascular level. It is important to understand the pharmacologic properties of the medications utilized to manage patients with these conditions. The information presented in this article is based on the best evidence currently available in order to assist the critical care nurse in understanding the pharmacologic therapy related to treatment of severe sepsis and septic shock.
 ...
PMID:Pharmacologic treatment related to severe sepsis. 1709 Oct 42

Sepsis and septic shock are not uncommon conditions in the surgical intensive care unit. Sepsis is a generalized activation of the immune system in the presence of clinically suspected or culture-proven infection. Severe sepsis is sepsis with organ system dysfunction. Septic shock is sepsis with hypotension (systolic blood pressure <90 mm Hg) without other causes. Although the incidence of sepsis is increasing, the case fatality rate is falling. This improvement in outcome is in part due to bold initiatives like the Surviving Sepsis Campaign from the Institute for Health Care Improvement. In this article the authors present the epidemiology of severe sepsis and evidence-based campaigns for its treatment, with a focus on the surgical patient.
 ...
PMID:Management of severe sepsis in the surgical patient. 1711 57

Severe sepsis remains a common cause of death in surgical patients. Eradication of the septic source and supportive care has long been the mainstay of treatment. In recent years, however, early goal-directed therapy, tighter glucose control, administration of drotrecogin alfa (activated), and steroid replacement have produced improved morbidity and mortality. In the future, a better understanding of the pathophysiology of sepsis and clinical studies may further improve outcomes from severe sepsis.
 ...
PMID:Management of sepsis. 1711 61

Severe sepsis is associated with dysfunction of the macrophage/monocyte, an important cellular effector of the innate immune system. Previous investigations suggested that probiotic components effectively enhance effector cell functions of the immune system in vivo. In this study, we produced bacteria-free, lysozyme-modified probiotic components (LzMPC) by treating the probiotic bacteria, Lactobacillus sp., with lysozyme. We showed that oral delivery of LzMPC effectively protected rats against lethality from polymicrobial sepsis induced by cecal ligation and puncture. We found that orally administrated LzMPC was engulfed by cells such as macrophages in the liver after crossing the intestinal barrier. Moreover, LzMPC-induced protection was associated with an increase in bacterial clearance in the liver. In vitro, LzMPC up-regulated the expression of cathelicidin-related antimicrobial peptide (CRAMP) in macrophages and enhanced bactericidal activity of these cells. Furthermore, we demonstrated that surgical stress or cecal ligation and puncture caused a decrease in CRAMP expression in the liver, whereas enteral administration of LzMPC restored CRAMP gene expression in these animals. Using a neutralizing Ab, we showed that protection against sepsis by LzMPC treatment required endogenous CRAMP. In addition, macrophages from LzMPC-treated rats had an enhanced capacity of cytokine production in response to LPS or LzMPC stimulation. Together, our data suggest that the protective effect of LzMPC in sepsis is related to an enhanced cathelicidin-related innate immunity in macrophages. Therefore, LzMPC, a novel probiotic product, is a potent immunomodulator for macrophages and may be beneficial for the treatment of sepsis.
 ...
PMID:Lysozyme-modified probiotic components protect rats against polymicrobial sepsis: role of macrophages and cathelicidin-related innate immunity. 1714 79

1. In recent studies, the vascular adventitia has been established as an important source of inducible nitric oxide synthase (iNOS) and subsequent nitric oxide (NO) production, even more powerful than the media in response to certain inflammatory factors, such as lipopolysaccharide (LPS). The adventitia has an independent L-arginine (L-Arg)/NOS/NO pathway and is involved in the regulation of vascular function. In the present study, we explored the changes in and the pathophysiological significance of the L-Arg/NOS/NO pathway in the adventitia of rats with sepsis. 2. Sepsis was induced by caecal ligation and puncture in order to observe changes in L-Arg transport, NOS gene expression and activity and NO generation in the vascular adventitia to determine the mechanism of activation of the L-Arg/NOS/NO pathway. 3. Severe sepsis resulted in severe disturbance of haemodynamic features, with decreased mean arterial blood pressure, brachycardia and inhibited cardiac function (decreased left ventricular +/-dP/dt(max)). Left ventricular end-diastolic pressure was elevated threefold (P < 0.01) under anaesthesia. Rats with sepsis showed severe glucopenia and lacticaemia. Plasma levels of the inflammatory factors macrophage chemoattractant protein-1 and interleukin-8 were increased five- and 29-fold, respectively (P < 0.01). 4. In the adventitia of the thoracic and abdominal aortas, the L-Arg/NO pathway was similarly characterized: the uptake of [(3)H]-L-Arg was Na(+) independent, with the peak occurring at approximately 40 min incubation. Total NOS activity was largely calcium independent (> 90%). The V(max) of L-Arg transport in the sepsis group was increased by 83.5% (P < 0.01), but the K(m) value was not significantly different compared with controls. 5. The mRNA levels of cationic amino acid transporter (CAT)-1 and CAT-2B in the sepsis group were increased by 86 and 62%, respectively (both P < 0.01). Inducible NOS activity was increased 2.8-fold compared with controls (P < 0.01) and iNOS mRNA levels were elevated approximately sixfold (P < 0.01). The NO levels in the plasma and incubation media (incubation for 40 min) in the sepsis group were increased by 144 and 273%, respectively (both P < 0.01). 6. The Arg/NOS/NO pathway was activated in the vascular adventitia of rats with sepsis shock. The L-Arg/NOS/NO pathway in the aortic adventitia may play an important role in the pathogenesis of sepsis and septic shock.
 ...
PMID:Altered L-arginine/nitric oxide synthase/nitric oxide pathway in the vascular adventitia of rats with sepsis. 1718 2

Severe sepsis and septic shock are common causes of morbidity and mortality of intensive care unit (ICU) patients. There are an estimated 751,000 cases of severe sepsis each year in the US, with a mortality of 20%-63% and an annual health care cost of US$16.7 billion. Worldwide, 18 million cases of severe sepsis occur annually, killing approximately 1,400 people each day and a health care cost of US$9.4 billion in Europe alone. Despite advances in medical science, the overall mortality for severe sepsis and septic shock has been slightly improved only with passage of time. Although there are no solid statistics, it is a conjecture that the morbidity and mortality and health cure cost of severe sepsis and septic shock are quite high in China. Septic shock is primarily a form of distributional shock and usually characterized by high cardiac output and low systemic vascular resistance. In septic shock, patients can have both hypotension resulting from decreased systemic vascular resistance, and sequestration of blood in the microcirculation resulting in compromised tissue perfusion. It is important to outline a guideline for hemodynamic monitor and support in severe sepsis and septic shock patients to maintain adequate perfusion of organs and cellular oxygen uptake. A group of 9 critical care experts in the diagnosis and management of severe sepsis and septic shock, representing members of the Chinese Society of Critical Care Medicine (Chinese Medical Association), gathered together to develop this hemodynamic monitor and support guidelines to enable the bedside clinician to follow for the sake of improving the outcome in severe sepsis and septic shock patients. The recommendations, totally 21 items, are graded based on a modified Delphi methodology.
 ...
PMID:[Guidelines of hemodynamic monitor and support in adult patients with severe sepsis and septic shock (draft)]. 1737 62

Severe sepsis, a leading cause of death in hospitalized patients, is one of the most dramatic examples of the pathological potential of inflammation. Since inflammation contributes to multiple clinical scenarios, it may not be surprising that diverse infectious and inflammatory disorders converge in the pathogenesis of severe sepsis. The physiological regulation of the immune responses by the nervous system represents effective anti-inflammatory mechanisms that can be exploited against inflammatory disorders. Recent studies indicate that acetylcholine, the principal cholinergic neurotransmitter, also functions as an immune cytokine that prevents macrophage activation through a 'nicotinic anti-inflammatory pathway'. Nicotine is more efficient than acetylcholine at inhibiting the NF-kappaB pathway and attenuating the production of pro-inflammatory cytokines from macrophages through a mechanism dependent on the alpha7-nicotinic acetylcholine receptor (alpha7n AChR). Treatment with nicotinic agonists attenuated systemic inflammation and improved survival in experimental sepsis in a clinically relevant time frame. Nicotine has already been used in clinical trials, but its clinical potential is limited by its collateral toxicity. Similar to the development of selective agonists for adrenergic receptors, selective nicotinic agonists for the alpha7nAChR may represent a promising pharmacological strategy against infectious and inflammatory diseases.
 ...
PMID:The neuronal strategy for inflammation. 1738 Jul 97

Acute kidney injury (AKI) is a common complication of severe sepsis. Severe sepsis is the most common cause of AKI in ICU. The widely accepted and practiced initial cornerstone of treatment for septic AKI is fluid resuscitation. The biological rationale for fluid resuscitation in septic AKI is based on the assumption that septic AKI is an ischemic form of AKI and that increasing renal perfusion and oxygen delivery by means of fluid resuscitation will protect the kidney. Whether this is true, however, remains uncertain. In this paper, we discuss salient pathophysiological aspects of AKI, review the evidence available on the need for fluid resuscitation, the amount and the type of fluid that might be best suited to AKI and discuss all major aspects of fluid resuscitation for septic AKI in humans and experimental animals.
 ...
PMID:Fluid resuscitation and the septic kidney: the evidence. 1746 24

Severe sepsis is a systemic inflammatory response to infection resulting in acute organ dysfunction. Vascular perfusion abnormalities are implicated in the pathology of organ failure, but studies of microvascular function in human sepsis are limited. We hypothesized that impaired microvascular responses to reactive hyperemia lead to impaired oxygen delivery relative to the needs of tissue and that these impairments would be associated with organ failure in sepsis. We studied 24 severe sepsis subjects 24 h after recognition of organ dysfunction; 15 healthy subjects served as controls. Near-infrared spectroscopy (NIRS) was used to measure tissue 1) microvascular hemoglobin signal strength and 2) oxygen saturation of microvascular hemoglobin (StO2). Both values were measured in thenar skeletal muscle before and after 5 min of forearm stagnant ischemia. At baseline, skeletal muscle microvascular hemoglobin was lower in septic than control subjects. Microvascular hemoglobin increased during reactive hyperemia in both groups, but less so in sepsis. StO2 at baseline and throughout ischemia was similar between the two groups; however, the rate of tissue oxygen consumption was significantly slower in septic subjects than in controls. The rate of increase in StO2 during reactive hyperemia was significantly slower in septic subjects than in controls; this impairment was accentuated in those with more organ failure. We conclude that organ dysfunction in severe sepsis is associated with dysregulation of microvascular oxygen balance. NIRS measurements of skeletal muscle microvascular perfusion and reactivity may provide important information about sepsis and serve as endpoints in future therapeutic interventions aimed at improving the microcirculation.
 ...
PMID:Impairments in microvascular reactivity are related to organ failure in human sepsis. 1748 35


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