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)

Sepsis, excessive inflammation, multiple organ failure and weakness prolong the need for intensive care in critically ill patients. Furthermore, the risk of death is high in the prolonged critically ill patient (20% after two weeks and 30% after 3 weeks). In prolonged critical illness, protein hypercatabolism and relative preservation of adipose tissue with fatty infiltration of vital organ systems is present. In view of the crucial role of the hypothalamus-pituitary axis for metabolic homeostasis, we have studied this endocrine organ in the context of critical illness. The initial "adaptive" neuroendocrine response to critical illness illness consists primarily of activated anterior pituitary function. In the chronic phase of critical illness, a uniformly reduced pulsatile secretion of anterior pituitary hormones has been observed, whereby impaired function of target organs. A reduced availability of thyrotropin (TSH)-releasing hormone (TRH), gonadotropin (LH)-releasing hormone (GnRH), the endogenous ligand of the growth hormone (GH)-releasing peptide (GHRP) receptor (ghrelin) and, in very long-stay critically ill men also of GH-releasing hormone (GHRH), inferrentially appears involved. Pulsatile secretion of GH, TSH and LH can be re-amplified by relevant combinations of releasing factors which also substantially increases circulating levels of insulin-like growth factor (IGF)-I, GH-dependent IGF-binding proteins, thyroxine (T4), triiodothyronine (T3) and testosterone. Anabolism is only evoked when GH-secretagogues, TRH and GnRH are administered together whereas the effect of single hormone treatment is minor and accompanied by side effects. A remarkable observation was that a high serum concentration of IGF-binding protein 1 predicts death in the ICU. This observation challenged the classical dogma of adaptive hyperglycemia during critical illness. In a large prospective randomized clinical study (1548 patients), we showed that ICU mortality was reduced by 42% with strict normalization of glycemia using exogenous insulin infusion (N Engl J Med 2001). This was due to prevention of typical ICU complications such as sepsis, multiple organ failure and need for prolonged invasive organ support and intensive care. We conclude that the new concept of reduced stimulation of pituitary function in prolonged critically ill patients opens new therapeutic perspectives to reverse the paradoxical 'wasting syndrome' but that maintenance of strict normoglycemia with insulin is crucial to also increase the chances of survival of these patients.
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PMID:Endocrinology in intensive care medicine: new insights and therapeutic consequences. 1223 41

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are the most common complications of sepsis, and the mortality of sepsis-induced ALI remains high in critically ill patients. Growth hormone releasing peptide-2 (GHRP-2), a ghrelin agonist, has been shown to exert beneficial effects on various inflammatory diseases. We therefore explored whether GHRP-2 possesses anti-inflammatory properties in the pathogenesis of lipopolysaccharide (LPS)-induced ALI. Male Sprague-Dawley rats were intratracheally instilled with LPS (2 mg/kg) to induce ALI. ALI was confirmed with lung tissue injury (histopathological examination), enhanced lung edema (wet-to-dry weight ratio), and neutrophil infiltration (myeloperoxidase activity) at 6 h after LPS exposure. The analyses of bronchoalveolar lavage fluid showed the significant increases in pulmonary permeability (total cells and protein) and the levels of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). In contrast, these lung injury indexes were attenuated in rats that received a subcutaneous injection of GHRP-2 (100 microg/kg) 0.5 h prior to LPS administration. To further explore the potential anti-inflammatory mechanism of GHRP-2 in LPS-induced ALI, we assessed of nuclear factor-kappaB (NF-kappaB) activity in lung tissues at 6 h after LPS challenge. We thus found that pretreatment with GHRP-2 markedly suppressed the activation of NF-kappaB in lung tissues. These results indicate that GHRP-2 attenuated LPS-induced ALI. Early protection appears to be mediated partly through the inhibition of NF-kappaB pathway activation. The present study indicates that GHRP-2 acts as a potential therapeutic reagent for treating ALI.
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PMID:Growth hormone releasing peptide-2, a ghrelin agonist, attenuates lipopolysaccharide-induced acute lung injury in rats. 2080 79