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)

Inflammatory cytokines may mediate the host response to infection via central nervous system, endocrine, and/or paracrine/autocrine signaling mechanisms. Previous studies have shown that intravenous administration of interleukin (IL)-1 beta alters the concentration of the anabolic hormone insulin-like growth factor (IGF)-I in plasma and various tissues. The purpose of the present study was to determine 1) whether the intracerebroventricular injection of IL-1 beta can influence peripheral IGF-I levels in control animals and 2) whether the central administration of a IL-1 receptor antagonist (IL-1ra) can prevent the changes in peripheral IGF-I induced by endotoxin [lipopolysaccharide (LPS)] or sepsis produced by cecal ligation and puncture. In the first experiment, injection of IL-1 beta (100 ng/rat) decreased IGF-I levels in plasma, liver, and gastrocnemius muscle 28-36% by 1.5 h in conscious fasted rats. IGF-I levels remained reduced at 3 h, but returned to baseline by 6 h. IGF-I content was not altered in soleus, kidney, spleen, intestine, or whole brain after IL-1 beta. In the second series of experiments, LPS injected intravenously decreased IGF-I levels in plasma, liver, and gastrocnemius at 1.5 h, and levels were even further reduced at 3 and 6 h in these tissues (59, 57, and 48%, respectively). Moreover, the IGF-I content was also decreased in soleus (30-35%) and increased in kidney (2- to 3-fold) after LPS. In the third experiment, changes in IGF-I levels in plasma and tissues, similar to those seen in LPS-treated rats, were detected 24 h after induction of peritonitis. Intracerebroventricular infusion of IL-1ra did not alter any of the changes in IGF-I produced by either LPS or sepsis, although it did attenuate the concomitant changes in growth hormone levels. These data suggest that, although central IL-1 beta is capable of modulating peripheral IGF-I levels, central administration of IL-1ra was unable to modulate the changes in peripheral IGF-I in blood and tissues produced by either endotoxemia or peritonitis.
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PMID:Role of central IL-1 in regulating peripheral IGF-I during endotoxemia and sepsis. 957 56

The hypercatabolic response to trauma, extensive surgery and sepsis is characterized by an increased metabolic rate, severe muscle wasting and a negative nitrogen balance. This process of 'autocannibalism' may be in part a consequence of a disordered growth hormone (GH)/insulin-like growth factor (IGF) axis. In this chapter the normal physiology of the GH/IGF axis is first briefly reviewed. This is followed by a discussion of the changes that accompany fasting and catabolic illness, the effects of IGF-1 administration in health and disease and a comparison of the effects of IGF-1, GH and insulin on catabolism. Although initial investigations of IGF-1 administration in animals and human volunteers have often been encouraging, studies in catabolic patients have so far proved disappointing. Combined treatment with GH, IGF-1 (and insulin) or with IGF-1 and its major binding protein, may prove more effective, especially when used in conjunction with nutritional supplements such as glutamine.
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PMID:The role of IGFs in catabolism. 958 77

Characteristic responses to surgery, trauma, and sepsis are catabolism and immunodepression. Nutritional therapy is important for managing patients with severe surgical stress. Conventional nutritional support, however, has not been successful in reducing morbidity and mortality rates. New nutritional support strategies have been aimed at enhancing protein metabolism and immunity. This review focuses on glutamine and growth hormone as nutritional support strategies for patients experiencing surgical stress. Glutamine is important in several key metabolic processes in critical illness. Exogenous glutamine also augments the functions of lymphocytes, macrophages, and neutrophils. Growth hormone has potent anabolic actions. Moreover, the peptides have immunostimulatory effects. These new modalities may be beneficial for the treatment of surgical patients.
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PMID:[Glutamine and growth hormone for the surgical nutritional support]. 961 98

Both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are potent anabolic agents. Exogenous GH improves nitrogen metabolism in patients undergoing surgery; however, the anabolic effects of GH in cases of multiple injury, burn, and sepsis are equivocal. Moreover, few data are available concerning the effects of GH in organ failures. Exogenous IGF-1 attenuates catabolism in animal trauma models. A clinical trial, however, did not confirm the anabolic actions of IGF-1. Further knowledge of the interaction between the GH/IGF-1 axis in critical illness is essential for GH and IGF-1 therapy. Theoretically, the improved nitrogen metabolism achieved with exogenous anabolic agents may provide functional benefits. However, only a few studies have confirmed the beneficial effects of GH on body function in trauma and sepsis. GH treatment decreases the postoperative depression of hand grip strength. GH also stimulates wound healing. Both GH and IGF-1 exert their effects on immune system, suggesting that these anabolic agents are potentially beneficial for the prevention and treatment of sepsis. On the contrary, inhibition of polymorphonuclear neutrophil apoptosis and the potentiation of PMNs by GH may have harmful effects on the systemic responses. Further studies are required to determine the safety and clinical benefits of GH administration in critical illness.
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PMID:Anabolic agents in trauma and sepsis: repleting body mass and function. 964 2

In patients with severe head injury, hypothalamohypophyseal impairment with subsequent hormone abnormalities has been well documented. Stress ulcer is another commonly encountered problem in such patients. However, little has been reported in the literature about the alterations of pituitary hormones in acute head-injured patients with stress ulcer. Forty consecutive male patients with head injury were studied. The other criteria for eligibility were: 1) Glasgow coma scale 4 to 10; 2) within 24 hours after head injury; 3) not in shock or sepsis; and 4) no past history of peptic ulcer. Stress ulcer was confirmed by endoscopic examination. The basal serum levels of pituitary hormones were measured and the response of pituitary to the provocative testing with thyrotropin-releasing hormone and gonadotropin-releasing hormone was also evaluated. Twenty-seven (67.5%) of forty patients showed evidence of stress ulcer by endoscope. In the patients without stress ulcer, the basal serum levels of thyroid-stimulating hormone (TSH), prolactin (PRL), growth hormone (GH), luetinizing hormone (LH), and follicle-stimulating hormone (FSH) were found to be within normal range. However, the basal levels of PRL in the patients with stress ulcer were abnormally elevated and significantly higher than those in the patients without stress ulcer (p < 0.001). The basal levels of TSH and GH were significantly lower in the patients with stress ulcer than those without stress ulcer (p < 0.001). In the patients with stress ulcer, significant increases (p < 0.001) of serum levels of TSH, PRL, LH and FSH after thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone (GnRH) provocation were identified. Hypothalamohypophyseal dysfunction and stress ulcer may occur in severely head-injured patients. In patients with stress ulcer, the abnormalities of pituitary hormones and provocative response of the pituitary with TRH and GnRH revealed normal pituitary function with hypothalamic insufficiency. Our study suggested that stress ulcers in acute head-injured patients were associated with hypothalamic damage.
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PMID:Hypothalamic dysfunction in acute head-injured patients with stress ulcer. 979 99

Evaluation of growth hormone therapy in burns is limited and none is reported from developing countries where burns still carry high mortality. We analysed serial observations on the clinical and biochemical profiles in 13 patients with second and third degree burns who received recombinant human growth hormone (rhGH) (0.5 IU/kg body wt) for 2 weeks in addition to standard conservative treatment and in 9 patients who were managed with standard conservative treatment only. The two groups of patients had burns, comparable in extent and severity. Additional rhGH treatment resulted in improved wound healing (p < 0.001), delayed separation of eschars (p < 0.01), increase in haemoglobin (p < 0.05), serum albumin (p < 0.01), calcium (p < 0.05), phosphorus (p < 0.001), glomerular filtration rate (p < 0.05) and 7 fold elevation in IGF-1. Also, a reduction in weight loss (p < 0.01), nitrogen production rate (p < 0.05), catabolic index (p < 0.01), duration of sepsis (p < 0.01) and hospital stay by 40% (p < 0.01) was noted with rhGH therapy. Transient hypercalcemia (3 patients), albuminuria (2 patients) and elevated blood glucose (one patient) were noted in the rhGH treated group not necessitating any specific therapy. Mortality in rhGH treatment group was 8.3% compared to 44.5% in the "no rhGH" treatment group. These observations suggest significant benefits of short term rhGH treatment in burn patients on conservative management.
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PMID:Effect of growth hormone therapy in burn patients on conservative treatment. 991 74

Sepsis induces a state of growth hormone (GH) resistance associated with a decrease of circulating insulin-like growth factor (IGF) I, a GH-dependent anabolic hormone mainly produced by the liver. To address the mechanisms that might trigger GH insensitivity in sepsis, we investigated the regulation of liver GH receptor (GHR) and its gene expression by endotoxin. Endotoxin injection in rats decreased serum IGF-I and liver GH-binding sites after 10 h. In contrast to liver GHR, circulating GH-binding protein (GHBP) levels were not significantly reduced after endotoxin injection. The parallel decrease in IGF-I and GHR and in their corresponding liver mRNAs suggests that decreased serum IGF-I and liver GHR were likely to result from decreased liver synthesis. Although GH administration in control animals significantly enhanced serum IGF-I, it did fail to prevent the decline in serum IGF-I and liver GH-binding sites in endotoxemic rats. In this study, we showed that endotoxin injection induces a state of GH insensitivity associated with decreased liver GHR. This decline in GHR, which cannot be prevented by exogenous GH, might contribute to the GH insensitivity observed in sepsis.
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PMID:GH insensitivity induced by endotoxin injection is associated with decreased liver GH receptors. 1007 25

Acquired growth hormone resistance (AGHR) may be defined as the combination of a raised serum growth hormone (GH) concentration, low serum insulin-like growth factor-1 (IGF-1) concentration and a reduced anabolic response to exogenous GH. A wide range of conditions exhibit the syndrome to a variable degree, including sepsis, trauma, burns, AIDS, cancer, and renal or liver failure. The primary defect seems to be a reduction in IGF-1 concentration which then leads to increased GH concentration by a loss of negative feedback. It is not clear whether IGF-1 concentration falls because of decreased production or increased clearance from the circulation, or both. Treatment to reverse the biochemical defect by restoring IGF-1 levels, either by the administration of GH or IGF-1, has resulted in improvements in a wide range of metabolic parameters and, more recently, to definite clinical benefit in well-defined groups, such as patients with AIDS. These results cannot be extrapolated to other groups with AGHR as a recent unpublished report suggested increased mortality in critically ill patients treated with GH. Research needs to focus on the molecular basis of AGHR if we are to develop therapies for catabolism.
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PMID:Acquired growth hormone resistance in adults. 1008 99

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.
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PMID:The role of insulin and other hormones in the regulation of amino acid and protein metabolism in humans. 1021 37

Albumin mRNA expression was studied by the use of reverse transcriptional polymerase chain reaction (RT-PCR) to determine the molecular mechanism in peritoneal infection. Albumin mRNA content markedly decreased. Endotoxin inhibited albumin mRNA expression in vivo probably by stimulating TNF,IL-1, and IL-6 production. Changes of the hormone levels were not the cause of hypoalbuminemia in infection. Reconbined growth hormone and astragalus polysaccharides alleviated inhibition albumin synthesis inhibition increasing albumin serum concentration in rats with peritoneal infection. The results suggested that hypoalbuminemia is associated with endotoxemia during sepsis, which inhibites hepatocytes albumin synthesis probably by stimulating nonparenchymal cells to produce TNF, IL-1, and IL-6.
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PMID:[Molecular mechanism and therapy of hypoalbuminemia in peritoneal infection]. 1037 87


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