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

Trauma, sepsis, and surgery are associated with global hypercatabolism and a negative nitrogen balance. When critical illness is prolonged the relentless loss of lean tissue becomes functionally important. Protein catabolism in the critically ill patient is associated with complex changes in the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. Many small clinical studies indicate that treatment with recombinant human (rh) GH would be a safe and effective means of limiting the deleterious effects of the catabolic response. Unexpectedly, however, two large prospective randomized controlled trials (PRCTs) demonstrated that administration of rhGH to long-stay critically ill adults increases morbidity and mortality. Some progress has been made in understanding the mechanisms underlying this observation.
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PMID:Treatment with GH and IGF-1 in critical illness. 1639 18

Intestinal failure (IF) occurs when the body is unable to sustain its energy and fluid requirements without support, due to loss of functional small bowel. Prolonged IF is seen after large intestinal resection and described as short bowel syndrome (SBS). The hallmark of the management is parental nutrition (PN), which is costly and may be associated with the well-recognized problems of parental nutrition associated liver disease (PNALD) and line related sepsis. Cessation of PN at the earliest possible stage is desirable but for this enteral autonomy has to be achieved first. Intestinal adaptation occurs when the remaining gut goes through morphological changes increasing its absorptive capacity. Factors such as intraluminal nutrients, gastrointestinal secretions and hormones facilitate adaptation. Enteral feeds are a potent stimulant to adaptation and should be started as soon as the clinical situation permits. Some drugs are thought to increase intestinal adaptation. These include glutamine, growth hormone and glucagon like peptide- 2, but there is a paucity of pediatric data to guide their use. In some cases surgical bowel lengthening procedures can be performed to increase the absorptive surface area. An isolated liver transplantation may be required if the liver has sustained irreversible damage but intestinal autonomy seems achievable. When prolonged PN is either unsustainable or associated with unacceptable side effects, small bowel transplantation should be considered as a treatment option.
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PMID:Management of intestinal failure. 1709 Sep 4

The objective of the present study was to investigate the effects of recombinant human growth hormone (rhGH) on the intestinal mucosa barrier of septic rats and explore its possible mechanism. Female Sprague-Dawley rats were randomized into three groups: control, Escherichia coli-induced sepsis (S) and treatment (T) groups. Groups S and T were subdivided into subgroups 1d and 3d, respectively. Expression of liver insulin-like growth factor-1 (IGF-1) mRNA, Bcl-2 and Bax protein levels and the intestinal Bax/Bcl-2 ratio, and plasma GH and IGF-1 levels were determined. Histological examination of the intestine was performed and bacterial translocation was determined. rhGH significantly attenuated intestinal mucosal injuries and bacterial translocation in septic rats, markedly decreased Bax protein levels, inhibited the decrease of Bcl-2 protein expression and maintained the Bax/Bcl-2 ratio in the intestine. rhGH given after sepsis significantly improved levels of plasma GH (T1d: 1.28 +/- 0.24; T3d: 2.14 +/- 0.48 microg/L vs S1d: 0.74 +/- 0.12; S3d: 0.60 +/- 0.18 microg/L; P < 0.05) and IGF-1 (T1d: 168.94 +/- 65.67; T3d: 201.56 +/- 64.98 microg/L vs S1d: 116.72 +/- 13.96; S3d: 107.50 +/- 23.53 microg/L; P < 0.05) and expression of liver IGF-1 mRNA (T1d: 0.98 +/- 0.20; T3d: 1.76 +/- 0.17 vs S1d: 0.38 +/- 0.09; S3d: 0.46 +/- 0.10; P < 0.05). These findings indicate that treatment with rhGH had beneficial effects on the maintenance of the integrity of the intestinal mucosa barrier in septic rats.
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PMID:Beneficial effect of recombinant human growth hormone on the intestinal mucosa barrier of septic rats. 1722 95

Gram-negative sepsis with release of endotoxin is a frequent cause of cachexia that develops partly because of resistance to growth hormone (GH) with reduced insulin-like growth factor-I (IGF-I) expression. We set out to more fully characterize the mechanisms for the resistance and to determine whether in addition to a defect in the janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) 5b pathway, required for GH-induced IGF-I expression, there might also be a more distal defect. Conscious rats were given endotoxin and studied 4 h later. In liver of these animals, GH-induced JAK2 and STAT5 phosphorylation was impaired and appeared to be caused, at least in part, by a marked increase in hepatic tumor necrosis factor-alpha and interleukin-6 mRNA expression accompanied by elevated levels of inhibitors of GH signaling, namely cytokine-inducible suppressors of cytokine signaling-1 and -3 and cytokine-inducible SH2 protein (CIS). Nuclear phosphorylated STAT5b levels were significantly depressed to 61% of the control values and represent a potential cause of the reduced GH-induced IGF-I expression. In addition, binding of phosphorylated STAT5b to DNA was reduced to an even greater extent and averaged 17% of the normal control value. This provides a further explanation for the impaired IGF-I gene transcription. Interestingly, when endotoxin-treated rats were treated with GH, there was a marked increase in proinflammatory cytokine gene expression in the liver. If such a response were to occur in humans, this might provide a partial explanation for the adverse effect of GH treatment reported in critically ill patients.
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PMID:Endotoxin attenuates growth hormone-induced hepatic insulin-like growth factor I expression by inhibiting JAK2/STAT5 signal transduction and STAT5b DNA binding. 1732 69

We observed the potential use of fibrin sealant as a therapeutic modality for successful resolution of gastrointestinal anastomosis dehiscence in intra-abdominal sepsis. Forty-eight patients (33 men and 15 women) suffering from intra-abdominal sepsis were subjected to prophylactic appliance of fibrin sealant during immediate primary anastomosis during the laparotomy. The perioperative management invariably involved fluid resuscitation, active suction drainage of the abdominal liquor puris, nutritional supplementation, and growth hormone. The total surgical-related success ratio was 91.7% (44/48) for primary anastomosis with fibrin sealant in intra-abdominal sepsis. Anastomotic leakage occurred in the other four patients, two of which died because of leakage complications in our hospital. The hospital stay after the operation was 30.2 +/- 12.0 days. There has been no sign of recurrence over a follow-up period of 1-15 months. It is concluded that fibrin sealant may be useful in preventing gastrointestinal anastomosis dehiscence in intra-abdominal sepsis.
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PMID:Fibrin sealant prevents gastrointestinal anastomosis dehiscence in intra-abdominal sepsis. 1739 Sep 11

Prolonged sepsis and exposure to an inflammatory milieu decreases muscle protein synthesis and reduces muscle mass. As a result of its ability to integrate diverse signals, including hormones and nutrients, the mammalian target of rapamycin (mTOR) is a dominant regulator in the translational control of protein synthesis. Under postabsorptive conditions, sepsis decreases mTOR kinase activity in muscle, as evidenced by reduced phosphorylation of both eukaryotic initiation factor (eIF)4E-binding protein (BP)-1 and ribosomal S6 kinase (S6K)1. These sepsis-induced changes, along with the redistribution of eIF4E from the active eIF4E.eIF4G complex to the inactive eIF4E.4E-BP1 complex, are preventable by neutralization of tumor necrosis factor (TNF)-alpha but not by antagonizing glucocorticoid action. Although the ability of mTOR to respond to insulin-like growth factor (IGF)-I is not disrupted by sepsis, the ability of leucine to increase 4E-BP1 and S6K1 phosphorylation is greatly attenuated. This "leucine resistance" results from a cooperative interaction between both TNF-alpha and glucocorticoids. Finally, although septic animals are not IGF-I resistant, the anabolic actions of IGF-I are nonetheless reduced because of the development of growth hormone resistance, which decreases both circulating and muscle IGF-I. Herein, we highlight recent advances in the mTOR signaling network and emphasize their connection to the atrophic response observed in skeletal muscle during sepsis. Although many unanswered questions remain, understanding the cellular basis of the sepsis-induced decrease in translational activity will contribute to the rational development of therapeutic interventions and thereby minimize the debilitating affects of the atrophic response that impairs patient recovery.
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PMID:Regulation of muscle protein synthesis during sepsis and inflammation. 1750 52

This study was devised to investigate whether fibrin glue (FG) in combination with growth hormone (GH) could have a beneficial effect at a late period (14 days) after injury. Male Wistar rats, with abdominal sepsis induced by an incomplete anastomosis, were divided into three groups. In the control group, the rats got incomplete anastomoses sutured alone; in the FG and FG/GH groups, anastomoses protection was performed with application of FG alone or in combination with GH. The anastomotic bursting pressure (ABP) was significantly higher in the FG/GH group than that of the FG group on postoperative day (POD) 5 (p < .01), while it could not be measured from POD 7 to POD 14 because of intestinal dehiscence. There was no difference between FG and FG/GH group on POD 3 and POD 5 in anastomotic tensile strength, which was significantly higher in the FG/GH group than that of the FG group from POD 7 to POD 14 (p < .001). Hydroxyproline content of the FG/GH group was significantly higher than that of the control from POD 3 and that of the FG group from POD 5 (p < .05). Combination of FG with GH had a synergistic effect to improve intestinal anastomotic healing over a limited 14-day course of observation.
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PMID:Combination of fibrin glue with growth hormone augments healing of incomplete intestinal anastomoses in a rat model of intra-abdominal sepsis: a dynamic study. 1797 18

Most of the major advances in the prevention and treatment of burn sepsis and MODS have been made within the last 20 years. Improvements have been made in gaining a better understanding of the pathophysiology of burn sepsis and MODS, in revising the definition of sepsis and MODS, and in prevention and treatment of burn shock. Additionally, improvements have been made in fluid resuscitation in patients with burn shock and in early gastrointestinal feeding to prevent translocation of endotoxins from the gut. Other achievements have been made in using recombinant human growth hormone combined with intensive insulin therapy to control hyperglycemia, and potassium chloride to prevent hypokalemia in order to accelerate protein synthesis. Additional advances include early closure and coverage of the burn wound, rational use of antibiotics, immunological modulation to combat immunological dissonance. Also, advances have been made by using early anticoagulation treatment to prevent coagulopathy. In prevention and treatment of burn sepsis and MODS, comprehensive support for all organs during the course of treatment is emphasized. Although the advances in burn treatment have been extremely encouraging over the last 50 years, burn sepsis and MODS remain the most common cause of mortality in the critical ill. To cope with extreme environmental conditions, such as armed conflict and natural disasters, research is needed to optimize the oral resuscitation regime, and more efficacious treatment strategies that are based on an indepth understanding of the pathogenesis of sepsis.
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PMID:[The present strategy and ponderation on prevention and treatment of burn sepsis and multiple organ dysfunction syndrome (MODS)]. 1910 24

Parenteral nutrition support for burn injury in China began to develop in 1970s along with improvement in burn foundational research of burn injury and the marketing of parenteral nutrition solutions manufactured by Chinese amino acids pharmaceutical industry. Up to 1980s many kinds of parenteral nutrition products were used in clinical therapy, and they were proved to be effective and safe. Meanwhile the guide for parenteral nutrition support of China was drafted to ensure standardized administration. Some problems should be called for attention in present practice of parenteral nutrition support. First, immuno nutrients have been proved to possess synergistic effect on parenteral/enteral nutrition support. But for those critical patients in sepsis/MODS period, more attention should be paid to the use of immuno nutrients in time of administration and optimal dosage because of the complicate physiopathologic reactions. Secondly, the use of growth hormone has been proved to be effective for promoting healing in patients with burn in many cases. However, the indications of growth hormone should be strictly observed and the regime of a low dose and short course should be adopted 7 days after burn for ensuring safety. Thirdly, we should pay attention to the best path of giving nutrition, whether enteral or parenteral. Parenteral nutrition support should be adopted for critical burn patients in early period with intestinal dysfunction, and enteral nutrition support should be used when intestinal functions recover partially. For patients with burn hypermetabolism, the application of enteral and parenteral nutrition support is complimentary, and it is aptly called total nutrition.
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PMID:[Review and prospect of parenteral nutrition support for burn patients in China]. 1910 29

This review aims to provide physicians with an overview of the potential of procalcitonin to guide antibiotic therapy in respiratory tract infections and in sepsis. Knowledge of the strengths and weaknesses of procalcitonin are prerequisites for a rational and safe use in clinical routine. In most infections a true gold standard for diagnosis does not exist, therefore physicians must remain sceptical towards observational studies evaluating procalcitonin. Interpretation of procalcitonin levels must always include the clinical setting and knowledge of assay characteristics, particularly the setting of specific cut-off ranges and functional assay sensitivities. Highly sensitive procalcitonin measurements, embedded in a clearly defined setting and prospectively validated with clinical algorithms were repeatedly effective in markedly reducing the (over)-utilisation of antimicrobial therapy. Today, this concept has been proven for lower respiratory tract infections and in pilot studies for meningitis and critically ill patients with sepsis. The higher the absolute risk for adverse outcome of a patient, the more cautious physicians must remain and empirical antibiotic therapies must be considered despite initial low procalcitonin levels at the initial presentation. In these patients a procalcitonin-guided shortening of antibiotic courses seems appropriate. The prognostic utility of initial procalcitonin measurement in respiratory tract infections is suboptimal. Other biomarkers including cortisol, human growth hormone and prohormones from adrenomedullin and vasopressin ("copeptin") have a superior predictive potential to estimate the risk for short and long term mortality and other adverse outcomes in different diseases. An accurate prognostic assessment has the potential to optimise the management of patients and the allocation of our limited health care resources by lowering unnecessary hospitalisations and associated cost. Future intervention studies must prove if these biomarkers indeed improve clinical decision making and thus the overall medical management of patients.
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PMID:Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections--hope for hype? 1952 89


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