Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our aim was to study the prognostic value of growth hormone (GH) -stimulated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) generation in patients with compensated [group 1 (N = 8) with a Child-Pugh (CP) score of 5-8] and decompensated postnecrotic liver cirrhosis [group 2 (N = 7) with a CP score of 9-12]. Serum levels of IGF-I, GH-binding protein (GHBP), and IGFBP-3 were measured before and 24 hr after a single subcutaneous injection of recombinant human GH (rhGH, 0.14 units/kg). Patients (mean age 56 years) were followed prospectively for three years. Six patients (40%) died during the follow-up period, of whom half had a CP score <9. Mean serum IGF-I levels 24 hr after rhGH injection (group 1 vs group 2, 17.4 +/- 6.8 vs 7.4 +/- 0.7 nmol/liter) predicted survival with 93% accuracy. Levels <10 nmol/liter portended a poor prognosis, with 15% survival at one year, whereas levels >10 nmol/liter had a 100% survival rate at one and two years, respectively. Baseline IGF-I (9.98 +/- 2.0 vs 6.38 +/- 0.8 nmol/liter), GHBP (9.2 +/- 3 vs 5.7 +/- 0.8%/50 microl), and IGFBP-3 serum levels at baseline (1.7 +/- 0.3 vs 0.86 +/- 0.2 mg/liter) and at 24 hr (2.04 +/- 0.38 vs 0.99 +/- 0.3 mg/liter) did not add to the predictive value of stimulated IGF-I levels at 24 hr and were less accurate in predicting the outcome in comparison to CP score (80%). We conclude that stimulated IGF-1 <10 nmol/liter may be a true predictor of a negative prognosis in patients with liver cirrhosis.
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PMID:Prognostic value of generation of growth hormone-stimulated insulin-like growth factor-I (IGF-I) and its binding protein-3 in patients with compensated and decompensated liver cirrhosis. 963 25

Insulin resistance is present in nearly all patients with cirrhosis, but its etiology remains unknown. Chronic hyperinsulinemia has been suspected as a potential candidate, and we therefore tested the hypothesis that, in cirrhosis, prolonged reduction of the hyperinsulinemia restores insulin sensitivity. Whole-body insulin sensitivity (euglycemic insulin-clamp technique), glucose turnover (6,6-2H2-glucose isotope dilution), glucose oxidation (indirect calorimetry), non-oxidative glucose disposal, and fractional glycogen synthase activity in muscle (biopsies) were measured in eight clinically stable patients with cirrhosis before and at the end of a 4-day continuous subcutaneous infusion of the somatostatin-analogue octreotide (200 microg/24 h) designed to continuously reduce plasma insulin levels. Baseline data were compared with results obtained in healthy individuals matched for sex, age, and weight (n = 8). During the baseline (pre-octreotide) study, patients demonstrated a significant decrease in insulin-mediated glucose uptake compared with controls (5.75 +/- 0.21 vs. 7.98 +/- 0.84 mg/kg/min; P < .03), which was entirely accounted for by an impairment in non-oxidative glucose disposal (P < .04). Four-day infusion of octreotide to cirrhotic patients: 1) reduced postabsorptive and meal-stimulated plasma insulin levels by approximately 35% to 45% without significantly affecting glucose tolerance; 2) did not significantly alter plasma free fatty acids (FFA), growth hormone, and glucagon levels in the postabsorptive state and during the meal test; 3) normalized insulin-mediated whole-body glucose disposal (7.63 +/- 0.72 mg/kg/min post-octreotide; P = not significant vs. control). Restoration of insulin-mediated glucose utilization was entirely caused by normalization of non-oxidative glucose disposal; 4) was associated with a considerably more pronounced stimulation by insulin of the fractional glycogen synthase in muscle compared with pre-octreotide results (increment above baseline pre: 0.035 +/- 0.010 vs. post: 0.060 +/- 0.023 nmol/min/mg protein; P < .04). Fractional glycogen activity significantly correlated with non-oxidative glucose disposal during insulin infusion (r = .69; P < .03). Prolonged reduction of hyperinsulinemia for 96 hours in cirrhotic patients normalizes insulin-mediated glucose uptake and glycogen synthesis in muscle. We conclude that chronic hyperinsulinemia causes insulin resistance in cirrhosis.
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PMID:Insulin resistance in cirrhosis: prolonged reduction of hyperinsulinemia normalizes insulin sensitivity. 965 6

Hepatitis C infection is common in patients receiving life-long blood transfusion therapy. Interferon-alpha induces long-term viral clearance in 25-30% of patients suffering from Cooley's anemia. Ribavirin, an orally active guanoside analogue together with interferon-alpha produces a sustained response in up to 40% of patients with cirrhosis, who had previously failed single agent treatment. Growth retardation in iron-overloaded patients is the result of growth hormone deficiency in up to 30% of patients. Height gain can be successfully achieved in these patients with growth hormone treatment. Pregnancy in women with Cooley's anemia is now a reality, and over 100 pregnancies have been documented. Conception may be spontaneous or the result of ovulation induction. Cardiomyopathy and diabetes require careful assessment in these patients before a decision is made to treat with gonadotrophins to induce ovulation.
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PMID:New approaches to the management of hepatitis and endocrine disorders in Cooley's anemia. 966 45

The intestine is an important target organ for insulin-like growth factor-I (IGF-I), an anabolic hormone synthesized in the liver upon growth hormone (GH) stimulation. Levels of IGF-I are reduced in cirrhosis, and altered GH/IGF-I axis may contribute to malnutrition in cirrhotic patients. Our aim was to study Na(+)-dependent jejunal transport of amino acids (L-leucine, L-proline, L-glutamic acid, and L-cysteine) in cirrhotic rats and to analyze the effect of IGF-I on this function. IGF-I or saline was administered for 2 wk to rats with CCl(4)-induced cirrhosis and saline was administered to healthy control rats. Transport of amino acids was assessed in brush-border membrane vesicles (BBMV) using (14)C- or (35)S-labeled amino acids, and the kinetic constants V(max) and K(t) were determined. Na(+)-independent uptake of L-leucine, L-proline, L-glutamic acid, and L-cysteine by BBMV was similar in all groups. Na(+)-dependent uptake of all four amino acids was significantly diminished in cirrhotic rats compared with both controls and IGF-I-treated cirrhotic rats. The latter two groups exhibited similar V(max) and K(t), whereas untreated cirrhotic rats had reduced V(max) and increased K(t) compared with normal controls and IGF-I-treated cirrhotic animals. In conclusion, the transport of all four tested amino acids by BBMV is impaired in cirrhotic rats, and low doses of IGF-I can correct this defect.
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PMID:Altered intestinal transport of amino acids in cirrhotic rats: the effect of insulin-like growth factor-I. 1091 40

Insulinlike growth factor-1 (IGF-1) is an anabolic hormone synthesized by the liver upon stimulation by growth hormone (GH). IGF-1 exerts important effects on renal hemodynamics and renal sodium handling. The bioactivity of this hormone is influenced by its binding proteins (BP) of which IGF-BP3 favors retention in the capillary lumen while IGF-BP1 facilitates the transport to the target tissues. IGF-BP1 modulates the actions of IGF-1 on target cells including renal tubules. Although a number of reports have dealt with disturbances of the IGF-1/IGF-BP system in cirrhosis, no studies have yet addressed the relationship between alterations in this system and renal function changes in cirrhosis. In the present study we have included 20 patients with cirrhosis and 10 healthy subjects (control group). As compared with the controls, patients showed lower circulating levels of IGF-1 and IGF-BP3, higher IGF-BP1 levels, and a tendency to higher insulinemia and GH values. The index IGF-1 x IGF-BP1/IGF-BP3 (IGF-1-IGF-BP index, reflecting the accessibility of circulating IGF-1 to target cells) was higher in patients with ascites. IGF-1 directly correlated with renal blood flow (P < 0.05), with IGF-BP3 (P < 0.001) and inversely with the Pugh's score (P < 0.02). A negative correlation was found between IGF-1-IGF-BP index and fractional sodium excretion (P < 0.01) and between IGF-BP1 and urinary sodium excretion (P < 0.02). Our findings support the hypothesis that the disturbance of the IGF-1/IGF-BP axis may be related to the degree of renal vasodilation and renal sodium retention in cirrhotic patients.
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PMID:Disturbed synthesis of insulinlike growth factor I and its binding proteins may influence renal function changes in liver cirrhosis. 1141 10

The GH-related effects are primarily mediated by insulin-like growth factor I (IGF-I), a peptide hormone almost completely produced by the liver. Liver cirrhosis is usually accompanied by a fall in protein turnover. Furthermore, an important consequence of chronic liver disease (CLD) is growth hormone/insulin-like growth factor (GH/IGF) axis modification and growth failure. Nutritional status also suffers in this condition, and IGF-I has been proposed as a marker of hepatocellular dysfunction, malnutrition and survival. CLD is characterised by alterations of various clinical biochemistry laboratory parameters. Aminotransferases, bilirubin, plasma proteins, together with prothrombin time and gamma globulins, are usually examined for laboratory diagnostic and/or monitoring purposes. These traditional parameters are also used in the perioperative liver transplantation, but an early signal of graft functioning has still not been established. The aim of the present work is a review of the possibility offered by the clinical biochemistry laboratory GH/IGF investigation in the outcome of liver transplantation.
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PMID:GH/IGF system, cirrhosis and liver transplantation. 1148 52

The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis is disturbed in cirrhosis, with elevated basal GH and low IGF-I levels relating to liver function and prognosis. In plasma, GH is bound to a high-affinity GH-binding protein (GHBP), which has been found to be slightly reduced in cirrhosis, but with huge variations. GHBP is identical to the extracellular part of the hepatic GH receptor, but other tissues may contribute to the circulating GHBP levels. The aim was therefore to measure circulating and regional concentrations of GHBP in relationship to hepatic function and body composition in patients with cirrhosis (n = 38) and controls with normal liver function (n = 29). Blood samples from the hepatic, renal, and femoral veins and the femoral artery were collected simultaneously during a hemodynamic investigation. Plasma GHBP was directly measured by a specific and sensitive fluoroimmunoassay. Circulating GHBP levels were identical in the patients and controls (mean +/- SD) 1.03 +/- 0.56 nmol/L and 1.02 +/- 0.55 nmol/L, respectively (not significant). We found no significant hepatic, renal, or peripheral arteriovenous extractions or generations of GHBP, and it did not significantly correlate to liver function. In the controls, GHBP correlated significantly with body mass index (BMI) (r =.60, P <.005), whereas this relationship was not found in the patients with cirrhosis. In conclusion, high-affinity GHBP appears to be normal in patients with cirrhosis, with no significant hepatic generation or renal extraction and no association with the severity of the liver disease. Thus, our study supports the hypothesis that tissues other than the liver, despite its abundant GH receptors, may contribute to the circulating GHBP.
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PMID:A comparison of circulating and regional growth hormone-binding protein in cirrhosis. 1169 54

Several issues have to be considered when taking care of girls and women with Turner syndrome. During childhood, short stature is the primary concern and treatment with growth hormone (GH) is now widely used, often in conjunction with the androgen, oxandrolone. Recent studies indicate that doses used previously in the treatment of short stature have been too small. Induction of puberty should be performed at an appropriate age with reference to the peers of the patient. In adulthood, female sex hormone substitution should be offered to possibly prevent the increased morbidity seen in Turner syndrome, which consists of increased risk of fractures and osteoporosis, a clustering of diseases like ischaemic heart disease, hypertension, stroke and Type 2 diabetes, the latter entities being involved in the insulin resistance syndrome. Furthermore, hypothyreosis are often seen and the risk of Type 1 diabetes may also be increased. Congenital malformations of the heart are frequently seen in Turner syndrome, possibly increasing the risk of dissecting aorta aneurism. Liver enzymes are often elevated in Turner syndrome and there may be an increased risk of cirrhosis of the liver. Mortality does seem to be increased in Turner syndrome and women with the 'pure' 45,X karyotype do seem to be most severely affected. In the clinical practice of Turner syndrome, a careful monitoring of glucose and bone metabolism, weight, thyroid function and blood pressure should be performed. A cardiovascular risk profile should be determined and the patient informed concerning risks and benefits from sex hormone replacement therapy. Based on the available literature, sex hormone replacement therapy is highly recommended, although at present there are no longitudinal data documenting the long-term positive effect of sex steroid substitution. However, hypogonadism is expected to explain at least part of the decreased lifespan found in Turner syndrome. Since general physicians encounter Turner patients infrequently, it is recommended that the care and treatment of Turner syndrome is centralised.
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PMID:Aspects of the treatment of Turner syndrome. 1182 6

We have previously shown that the administration of low doses of insulin-like growth factor-I (IGF-I) to CCl4-cirrhotic rats improves liver function and reduces fibrosis. To better understand the mechanisms behind the hepatoprotective effects of IGF-I, and to identify those genes whose expression is affected in cirrhosis and after IGF-1 treatment, we have performed differential display of mRNA analysis by means of polymerase chain reaction (PCR) in livers from control and CCl4-cirrhotic rats treated or not with IGF-I. We have identified 16 genes that were up- or down-regulated in the cirrhotic liver. IGF-I treatment partially normalized the expression of eight of these genes, including serine proteinase inhibitors such as serpin-2 and alpha-1-antichymotripsin, alpha-1-acid glycoprotein, and alpha-2u-globulin. Additionally, we show that IGF-I enhanced the regenerative activity in the cirrhotic liver, as determined by the increased expression of the proliferating cell nuclear antigen (PCNA). Finally, IGF-I treatment partially restored the expression of growth hormone receptor (GHR) and the levels of global genomic DNA methylation, which are reduced in human and experimental cirrhosis. Taken together, our observations confirm the hepatoprotective effects of IGF-I, and suggest that this action can be exerted in part through the normalization of liver gene expression, growth hormone (GH) responsiveness and global genomic DNA methylation.
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PMID:Altered liver gene expression in CCl4-cirrhotic rats is partially normalized by insulin-like growth factor-I. 1184 91

Malnutrition is a frequent complication of cirrhosis, and many studies have demonstrated the adverse influence of malnutrition on clinical outcomes in patients with cirrhosis. The coexisting complications of fluid overload and ascites may mask the severity of malnutrition, particularly in the early stages of its development. During periods of decompensation, protein and energy requirements are higher, and many patients have inadequate nutritional intake at these times. Further, protein supplementation should not be restricted ad hoc in cirrhotic patients, as for the vast majority of patients dietary protein does not precipitate hepatic encephalopathy. The impairment of hepatic glycogen storage in cirrhotic patients effects a state of accelerated starvation with catabolism of fat and protein to provide substrates for gluconeogenesis. Recent studies have demonstrated the efficacy of nocturnal nutritional supplements in improving nitrogen balance. Resistance to the actions of the anabolic growth factors insulin and growth hormone (GH) is common in cirrhosis, and recent studies have shown that GH resistance, in particular, may be overcome with exogenous GH therapy. Hypermetabolism may be observed in up to one-third of cirrhotic patients. The recent exciting observation that beta-blocker therapy can decrease energy expenditure and catecholamine levels in these patients indicates the need for further intervention studies of beta-blockers as metabolic therapy in cirrhosis.
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PMID:Issues of malnutrition and bone disease in patients with cirrhosis. 1198 28


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