Hepatic Albumin Synthesis Research Articles

Clinical significance of the latency period of abnormal ammonia metabolism in chronic liver disease: Proposal of a new concept.

The liver is a key organ in regulating metabolism, and chronic liver disease is associated with several metabolic disorders. In the later stages of liver cirrhosis, the urea cycle is impaired, which disrupts of ammonia detoxification and eventually causes hyperammonemia and hepatic encephalopathy. Although hyperammonemia is not detected during the period between the late stage of chronic hepatitis and the early stage of liver cirrhosis, hepatic albumin synthesis capacity decreases as the fibrosis progresses. Increased ammonia levels are associated with a decreased capacity of the liver to synthesize albumin as well as activation of hepatic stellate cells, which promote fibrosis. Herein, we discuss the possibility that abnormal ammonia metabolism might play an important role in the pathogenesis of liver diseases even without hyperammonemia. We consider the disease period without hyperammonemia as the latency period of abnormal ammonia metabolism and discuss its clinical significance.

Biochemical Assessment As Markers For Diagnosis And Evaluation Hepatitis B Virus (HBV)

Abstract 
 This paper summarizes assessment biochemical markers of the development of hepatitis B viruses (HBV), in which any possible connection between certain biochemical parameters and chronic hepatitis was identified. Liver function tests are helpful in diagnosing liver disease and dysfunction, assessing severity, tracking treatment, and determining prognosis. According to the findings of biochemical studies, chronic patients have higher levels of ALP, GPT, GOT, and TSB than carriers. The rise in liver enzymes strongly indicates hepatocellular damage, despite the fact that ALP, GPT, GOT, and TSB levels in the carrier group were all within normal parameters as compared to the reference group. Testing liver function in terms of protein level, albumin, and globulin, the concentration of protein profiles in chronic patients is clearly decreasing as compared to the carrier group. In severe or long-lasting liver disease, the significant decreasing profile of serum proteins is evident in some conditions, the release of tumor necrosis factor hampers the synthesis of albumin, however, induce the synthesis of the acute phase response, hypoalbuminemia is multifactorial, while the hepatic synthesis of albumin is decreased in liver disease.

Oral exposure of pigs to the mycotoxin deoxynivalenol does not modulate the hepatic albumin synthesis during a LPS-induced acute-phase reaction.

The sensitivity of pigs to deoxynivalenol (DON) might be influenced by systemic inflammation (SI) which impacts liver. Besides following acute-phase proteins, our aim was to investigate both the hepatic fractional albumin (ALB) synthesis rate (FSR) and the ALB concentration as indicators of ALB metabolism in presence and absence of SI induced by LPS via pre- or post-hepatic venous route. Each infusion group was pre-conditioned either with a control diet (CON, 0.12 mg DON/kg diet) or with a DON-contaminated diet (DON, 4.59 mg DON/kg diet) for 4 wk. A depression of ALB FSR was observed 195 min after LPS challenge, independent of feeding group or LPS application route, which was not paralleled by a down-regulated ALB mRNA expression but by a reduced availability of free cysteine. The drop in ALB FSR only partly explained the plasma ALB concentrations which were more depressed in the DON-pre-exposed groups, suggesting that ALB levels are influenced by further mechanisms. The abundances of haptoglobin, C-reactive protein, serum amyloid A, pig major acute-phase protein, fibrinogen and LPS-binding protein mRNA were up-regulated upon LPS stimulation but not accompanied by increases in the plasma concentrations of these proteins, pointing at an imbalance between synthesis and consumption.

31-Year-Old Woman With Jaundice and Abdominal Pain

31-Year-Old Woman With Jaundice and Abdominal Pain

Molecular Scale Optimum Hydrophobicity To Establish an Enhanced Probe-Protein Interaction: Near-Infrared Imaging of Albumin Biosynthesis Modulation.

Albumin is the most abundant serum protein and shows variation in its synthesis rate in different physiological and pathophysiological conditions. Thus, there might be an association expected between serum albumin concentration and body health. A library of NIR probes engineered with the optimum hydrophobicity has been developed and characterized using spectroscopy techniques and was employed to understand the variation of hepatic albumin synthesis rates on physiological and pathophysiological states. Given the importance of hydrophobicity in rendering an effective interaction of small molecules with biomolecules, strategic structure interaction relationship studies led us toward the development of a potent emissive molecular probe through chemical library development. By exploration of these newly developed molecular probes, our study elegantly showed how a pathophysiological condition like the hyperinsulinemic state significantly downregulates albumin biosynthesis in HepG2 cells using fluorescence microscopy as a tool. An excellent correlation between the albumin transcript level and fluorescence intensity inside the cells has been observed. The key role of hydrophobicity resulting in an effective interaction of the probes with albumin, thus leading to strong optical signals, has been experimentally demonstrated in this report. Also, a siRNA interference technique has been utilized to establish the excellent selectivity of the developed probes with excitation as well as emission in the NIR region. We therefore have established through our experimental findings that suitable cell permeable emissive molecular markers with a high degree of albumin specificity can be used as a good optical tool for studying the effect of hyperinsulinemia on albumin biosynthesis modulation.

Albumin Turnover in Peritoneal and Hemodialysis.

The turnover of albumin is increased in both peritoneal dialysis (PD) and hemodialysis (HD) due to increased external losses, normally leading to compensatory increases in the hepatic albumin synthesis. The normal rate of albumin synthesis is on the order of 12 g/day corresponding to an equally large albumin fractional catabolic rate of ~4% daily. Most albumin catabolism is assumed to occur in the endothelium, but there is also renal and hepatic catabolism and leakage into the gastrointestinal tract. In PD the daily losses are on the order of 5 g/day. There are also external albumin losses in HD, particularly when high-performance membranes are used, the losses per session ranging between 1 and 8 g (or more). The dialytic albumin losses cannot be detected by assessing the transcapillary escape rate of albumin from the plasma compartment to the interstitium. In PD, tracer albumin that has been injected into the peritoneal fluid is absorbed to the tissues surrounding the peritoneal cavity without much edema formation, due to the process of "volume recirculation". A small fraction of the dialysate albumin tracer (0.2-0.3 ml/minute) is directly reabsorbed to the plasma via the lymphatics. A significant portion of dialysis patients are affected by chronic inflammation, such as in the malnutrition inflammation and atherosclerosis syndrome, which is also associated with cardiovascular mortality and fluid overload. These patients usually have a reduced ability to compensate for external losses of albumin, which may result in hypoalbuminemia. Reduced plasma albumin levels in dialysis patients may thus be regarded as a sign of chronic inflammation rather than reflecting malnutrition.

Albumin synthesis in very low birth weight infants is enhanced by early parenteral lipid and high-dose amino acid administration

Albumin is one of the most important plasma proteins and plays a key role in many physiologic processes, such as preserving colloid osmotic pressure, scavenging radicals, and binding and transporting bilirubin, hormones, and drugs. However, albumin concentrations are often low in preterm infants during the first days of life. We hypothesized that early parenteral lipid and high-dose amino acid (AA) administration to very low birth weight (VLBW) infants from birth onwards increases hepatic albumin synthesis rates. Inborn VLBW infants were randomized to receive from birth onwards either 2.4g amino acids/(kg(·)d) (control group), 2.4g amino acids/(kg(·)d) plus 2g lipids/(kg(·)d) (AA+lipid group), or 3.6g amino acids/(kg(·)d) plus 2g lipids/(kg(·)d) (high AA+lipid group). On postnatal day 2, infants received a primed continuous infusion of [U-(13)C6,(15)N]leucine. Mass spectrometry was used to determine the fractional and absolute albumin synthesis rates (FSR and ASR, respectively). In total, 28 infants (median gestational age 27 weeks (IQR 25-28), median birth weight 810g (IQR 679-998) were studied. The median FSR was 6.5%/d in the control group, 10.6%/d in the AA group, and 12.3%/d in the high AA+lipid group, while the median was 84 mg/(kg(·)d) in the control group, 138 mg/(kg(·)d) in the AA group, and 160 mg/(kg(·)d) in the high AA+lipid group. A group of VLBW infants given parenteral nutrition containing lipids and high-dose amino acids showed a higher rate of albumin synthesis compared to infants receiving no lipids and standard amounts of amino acids during the first two days of life.

Tying up PGE2 with albumin to relieve immunosuppression in cirrhosis.

The function of the innate immune system is suppressed in patients with acutely decompensated cirrhosis and predisposes these patients to bacterial infections. A new study shows that increased synthesis of the immunosuppressive prostaglandin PGE2 by circulating monocytes and resident macrophages and impaired hepatic synthesis of human serum albumin (HSA) are major contributors to immune suppression in cirrhosis (pages 518–523). The authors' data suggests a new avenue for therapy in acute decompensation of cirrhosis.

Differential Changes in Hepatic Synthesis of Albumin and Fibrinogen After Severe Hemorrhagic Shock in Pigs

Changes of plasma albumin and fibrinogen after various insults have been described as acute phase responses. This study investigated the acute changes of hepatic synthesis of albumin and fibrinogen after hemorrhage and resuscitation with lactated Ringer's (LR) solution or normal saline (NS) in pigs. Twenty anesthetized pigs were randomized into control (n = 6), LR solution (n = 7), and NS (n = 7) groups. Hemorrhage of 60% estimated blood volume was induced in the LR and NS groups by removing blood from the left femoral artery with a computer-controlled pump, followed by resuscitation with either LR solution at three times the bled volume, or NS to reach the same mean arterial pressure as in the LR group. Stable isotope 1-C-phenylalanine was infused for 6 h with hourly blood sampling and subsequent gas chromatography and mass spectrometry analysis to quantify hepatic protein synthesis. Hemorrhage decreased mean arterial pressure and increased heart rate. Resuscitation with LR solution or NS corrected these changes. Compared with baseline, hemorrhage and resuscitation decreased albumin levels to 49% ± 2% and 44% ± 3% and fibrinogen levels to 50% ± 2% and 53% ± 2% in LR solution and NS (all P < 0.05), respectively. Albumin synthesis was impaired from 8.8 ± 1.4 mg/kg per hour (control) to 5.3 ± 0.8 mg/kg per hour in LR solution and 3.9 ± 0.6 mg/kg per hour in NS (both P < 0.05). No changes were observed in fibrinogen synthesis after hemorrhage and resuscitation with LR solution (4.4 ± 0.7 mg/kg per hour) or NS (3.3 ± 0.4 mg/kg per hour), compared with the control (3.5 ± 0.3mg/kg per hour). Hemorrhage and resuscitation compromised albumin synthesis, but not fibrinogen synthesis. There were no differences in hepatic synthesis of albumin or fibrinogen between LR solution and NS resuscitation.

356 Albumin Synthesis Rates in VLBW Infants - Effects of High dose Amino Acid and Lipid Administration from Birth Onwards

IntroductionAlbumin is one of the most important proteins in plasma and plays a key role in physiological processes like preservation of colloid osmotic pressure and binding of bilirubin and drugs....

Cyclosporin A Inhibits Albumin Synthesis in Huh7 Cells

Background/AimsHypoalbuminemia occurs frequently in renal transplant recipients immediately after renal transplantation. We studied the regulation of hepatic albumin synthesis by cyclosporin A (CsA) in Huh7 cells.MethodsHuh7 cells were incubated with various concentrations of CsA for 4, 8, 16, and 24 hours. Albumin was measured in Huh7 cell-conditioned medium by sandwich enzyme-linked immunosorbent assay and Western blot. Albumin mRNA expression was analyzed by Northern blotting in CsA-treated cells.ResultsCsA (10-7-10-4 M) inhibited albumin synthesis in Huh7 cells in a dose- dependent manner. A Western blot analysis for albumin in the conditioned medium released from CsA-treated (10-7-10-5 M) cells also showed significant inhibition of albumin synthesis in a dose-dependent manner. Vehicle (olive oil) did not affect albumin synthesis. In contrast, a Northern blot analysis revealed no inhibition of albumin mRNA expression by CsA at any time point from 1-24 hours, indicating that the inhibition of albumin synthesis occurred at the translational level.ConclusionsOur results suggest that inhibition of hepatic albumin synthesis by high dose CsA contributes to the hypoalbuminemia in renal transplant recipients.

Adaptations to high-intensity intermittent exercise in rodents

In humans, exercise-induced plasma volume (PV) expansion is typically associated with an increase in plasma albumin content, due in part to an increase in hepatic albumin synthesis. We tested the ability of a 12-day high-intensity intermittent exercise protocol to induce an increase in PV in rodents. Since albumin synthesis is transcriptionally regulated, we tested the hypothesis that exercise training would induce an increase in hepatic albumin gene expression. Fifty adult male Sprague-Dawley rats weighing between 245 and 350 g were randomly assigned to one of five groups: cage control (CC), sham exercise (sham), continuous moderate-intensity exercise training (MI), high-intensity intermittent exercise training (HI), or a single day of HI training (1-HI). Twenty-four hours after the last training session, rats were anesthetized. PV was determined, and the liver was removed, flash frozen, and stored for later analysis. Citrate synthase (CS) activity of the red quadriceps muscle, a marker of aerobic adaptation, increased with training (MI and HI) and in response to 1-HI (P < 0.05). We did not see a significant exercise-induced PV expansion as PV averaged 23.6 +/- 2.7 ml/kg body wt in the CC group and 26.6 +/- 1.3 ml/kg body wt in the HI group (P > 0.05). However, hepatic albumin mRNA expression, as determined by real-time PCR, increased 2.9 +/- 0.4- and 4.1 +/- 0.4-fold after MI and HI, respectively, compared with CC. A single bout of HI (1-HI) did not alter hepatic albumin mRNA expression. These data demonstrate an increase in both CS activity and hepatic albumin gene expression with 12 days of aerobic exercise training in the rodent with a rapid (within 24 h) adaptation in the skeletal muscle to high-intensity intermittent exercise.

Anticatabolic Effects of Avoiding Preoperative Fasting by Intravenous Hypocaloric Nutrition

We tested the hypothesis that the avoidance of preoperative fasting by hypocaloric nutrition attenuates protein catabolism after surgery. Prolonged fasting before major abdominal procedures has been demonstrated to accentuate the catabolic response to surgery. Twenty-two patients undergoing colorectal cancer surgery were randomly assigned to receive glucose and amino acids intravenously starting either 20 hours before the operation or with surgical skin incision. Nutrition was administered until the second postoperative day, with glucose providing 50% and amino acids 20% of each patient's measured resting energy expenditure. Whole body leucine and glucose kinetics were assessed by L-[1-(13)C]leucine and [6,6-(2)H(2)]glucose before and after surgery. Fractional synthesis rates of muscle protein, albumin, and fibrinogen were determined using primed continuous infusions of L-[(2)H(5)]phenylalanine postoperatively, whereas the expression of mRNA of proteolytic genes in muscle (Mafbx/atrogin-1, ubiquitin, Murf 1) was determined by quantitative RT-PCR. Circulating concentrations of glucose, lactate, amino acids, insulin, glucagon, and cortisol were also measured. This study has been registered at ClinicalTrials.gov (Identifier: NCT00614133). Preoperative feeding inhibited endogenous protein breakdown (fasting group: 128 +/- 23 micromol . kg(-1) . h(-1); nutrition group: 96 +/- 22 micromol . kg(-1) . h(-1); P = 0.02) and blunted the increase in amino acid oxidation (fasting group: 27 +/- 5 micromol . kg(-1) . h(-1); nutrition group: 20 +/- 5 micromol . kg(-1) . h(-1); P = 0.03), resulting in positive whole-body protein balance after surgery (fasting group: -10 +/- 4 micromol . kg(-1) . h(-1); nutrition group: 1 +/- 3 micromol . kg(-1) . h(-1); P < 0.001). This anabolic response was associated with decreased muscle proteolytic gene expression and increased hepatic albumin synthesis. Total plasma protein, fibrinogen, and muscle protein synthesis were not affected. Hypocaloric nutrition decreases protein catabolism, with a contribution from the ubiquitin pathway in muscle, and stimulates albumin synthesis after colorectal surgery if initiated 1 day before the operation.

Albumin and whole-body protein synthesis respond differently to intraperitoneal and oral amino acids

Patients with peritoneal dialysis are at risk for malnutrition and hypoalbuminemia, which are indicators of poor outcome. Recently, it was shown that dialysis solutions containing amino acids (AAs) and glucose improve protein anabolism in peritoneal dialysis patients. We determined if the same solutions could increase the fractional synthesis rate of albumin along with whole-body protein synthesis. Changes in the fractional albumin synthetic rate reflect acute change in hepatic albumin synthesis. A random-order cross-over study compared the effects of Nutrineal (AA source) plus Physioneal (glucose) dialysate with Physioneal alone dialysate. Eight patients in the overnight fasting state were compared to 12 patients in the daytime-fed state. Fractional albumin synthetic rate and whole-body protein synthesis were determined simultaneously using a primed-continuous infusion of L-[1-(13)C]-leucine. Fractional albumin synthesis on AAs plus glucose dialysis did not differ significantly from that on glucose alone in the fasting or the fed state. Protein intake by itself (fed versus fasting) failed to induce a significant increase in the fractional synthetic rate of albumin. Conversely, the oral protein brought about a significant stimulation of whole-body protein synthesis. Our findings show that the supply of AAs has different effects on whole-body protein synthesis and the fractional synthetic rate of albumin.

Effect of tacrolimus and cyclosporine A on suppression of albumin secretion induced by inflammatory cytokines in cultured human hepatocytes

To investigate the effect of tacrolimus (FK506) and cyclosporine A (CSA) on albumin secretion and on the IL-6 -induced suppression of albumin synthesis in cultured human hepatocytes. HepG2 cells were cultured separately with IL-6, IL-10 (0-10 ng/ml) and FK506, CSA (0-100 ng/ml) for 48 h. In another experiment, HepG2 cells were incubated with different amounts of FK506 and CSA (0-10 ng/ml) in the presence of IL-6 (5 ng/ml). The albumin levels in these groups of hepatic cultures were measured by radioimmunoassay. The concentration of LDH secreted by cells stimulated with FK506 and CSA was detected by spectrophotometry. IL-6 decreased the levels of albumin in a dose-dependent manner (P < 0.01), maximal inhibition was observed at 5 ng/ml. Neither IL-10 nor FK506 modulated albumin production. However, FK506 decreased LDH levels in the supernatant of cells (P < 0.05) and prevented the IL-6-induced suppression of albumin synthesis (P < 0.01) in a dose dependent manner. In contrast, CSA caused only a slight decrease in albumin levels (P < 0.05). In addition, CSA slightly increased the amount of LDH in HepG2 cells and did not interfere with the IL-6-induced decrease in albumin synthesis. These findings suggest that IL-6, but not IL- 10, may play an important role in the suppression of hepatic albumin secretion. FK506 but not CSA protects against the suppression of hepatic albumin synthesis caused by IL-6.

Counter-regulatory effects of procalcitonin and indoxyl sulphate on net albumin secretion by cultured rat hepatocytes.

Although hypoalbuminaemia is a significant predictor of mortality in haemodialysis (HD) patients, the pathophysiological mechanisms involved remain to be determined. Albumin is a negative acute-phase reactant and many proinflammatory substances are elevated in HD patients. We investigated factors that may affect liver albumin synthesis. Hepatocytes were isolated from rat livers and were cultured with interleukin (IL)-4, IL-6, IL-12, tumor necrosis factor (TNF)-alpha, procalcitonin (PCT), a sensitive marker of infection, and indoxyl sulphate (IS), a uraemic toxin. Albumin levels in the supernatant were measured by enzyme-linked immunosorbent assay. Albumin mRNA expression was determined by reverse transcriptase polymerase chain reaction. IL-6 and TNF-alpha significantly decreased albumin levels in a dose-dependent manner (P<0.01 and P<0.05, respectively). In contrast, IL-4 and IL-12 did not modulate albumin production. PCT and IS significantly and dose-dependently increased albumin levels (both P<0.01). PCT increased albumin mRNA expression in the hepatocytes (P = 0.05) and dose-dependently abrogated IL-6-induced suppression of albumin synthesis (P<0.01). IS also blocked the IL-6-induced decrease in net albumin secretion (P<0.01). Our findings indicate that PCT and IS protect against suppression of hepatic albumin synthesis caused by proinflammatory cytokines, suggesting their potential role in preventing hypoalbuminaemia in HD patients.

Insights into the Abnormalities of Chronic Renal Disease Attributed to Malnutrition

ABSTRACT. Low values of serum proteins and loss of lean body mass are commonly found in patients with chronic renal insufficiency (CRI) and especially in dialysis patients. These abnormalities have been attributed to malnutrition (i.e., an inadequate diet), but available evidence indicates that this is not the principal cause. In contrast, there is persuasive evidence that secondary factors associated with the CRI condition cause abnormalities in protein turnover and ultimately result in low serum protein levels and loss of lean body mass. Recent reports have identified some factors that could interfere with the control of protein turnover in CRI patients, including acidosis, inflammation, and/or resistance to anabolic hormones. Each of these stimulates protein breakdown in muscle and activates a common proteolytic pathway, the ubiquitin-proteasome pathway. Moreover, acidosis or inflammation suppress hepatic albumin synthesis. Understanding the biochemical mechanisms that regulate the ubiquitin-proteasome and other catabolic pathways are required to identify new strategies for preventing protein deficits that are associated with CRI.

Metabolic effects of restoring partial beta-cell function after islet allotransplantation in type 1 diabetic patients.

Successful intraportal islet transplantation normalizes glucose metabolism in diabetic humans. To date, full function is not routinely achieved after islet transplantation in humans, with most grafts being characterized by only partial function. Moreover, the duration of full function is variable and cannot be sufficiently predicted with available methods. In contrast, most grafts retain partial function for a long time. We hypothesized that partial function can restore normal protein and lipid metabolism in diabetic individuals. We studied 45 diabetic patients after islet transplantation. Labeled glucose and leucine were infused to assess whole-body glucose and protein turnover in 1) 6 type 1 diabetic patients with full function after intraportal islet transplantation (FF group; C-peptide > 0.6 nmol/l; daily insulin dosage 0.03 +/- 0.02 U x kg(-1) body wt x day(-1); fasting plasma glucose < 7.7 mmol/l; HbA1c < or = 6.5%), 2) 17 patients with partial function (PF group; C-peptide > 0.16 nmol/l; insulin dosage < 0.4 U x kg(-1) body wt x day(-1)), 3) 9 patients with no function (NF group; C-peptide < 0.16 nmol/l; insulin dosage > 0.4 U x kg(-1) body wt x day(-1)), and 4) 6 patients with chronic uveitis as control subjects (CU group). Hepatic albumin synthesis was assessed in an additional five PF and five healthy volunteers by means of a primed-continuous infusion of [3,3,3-2H3]leucine. The insulin requirement was 97% lower than pretransplant levels for the FF group and 57% lower than pretransplant levels for the PF group. In the basal state, the PF group had a plasma glucose concentration slightly higher than that of the FF (P = 0.249) and CU groups (P = 0.08), but was improved with respect to the NF group (P < 0.01). Plasma leucine (101.1 +/- 5.9 micromol/l) and branched-chain amino acids (337.6 +/- 16.6 micromol/l) were similar in the PF, FF, and CU groups, and significantly lower than in the NF group (P < 0.01). During insulin infusion, the metabolic clearance rate of glucose was defective in the NF group versus in the other groups (P < 0.01). Both the basal and insulin-stimulated proteolytic and proteosynthetic rates were comparable in the PF, FF, and CU groups, but significantly higher in the NF group (P = 0.05). In addition, the PF group had a normal hepatic albumin synthesis. Plasma free fatty acid concentrations in the PF and FF groups were similar to those of the CU group, but the NF group showed a reduced insulin-dependent suppression during the clamp. We concluded that the restoration of approximately 60% of endogenous insulin secretion is capable of normalizing the alterations of protein and lipid metabolism in type 1 diabetic kidney recipients, notwithstanding chronic immunosuppressive therapy. The results of the present study indicate that "success" of islet transplantation may be best defined by a number of metabolic criteria, not just glucose concentration/metabolism alone.

IGF-I levels rise and GH responses to GHRH decrease during long-term prednisone treatment in man.

Glucocorticoid excess is associated with a blunted GH response to GHRH. IGF-I levels in hypercortisolism are controversial and have been reported as low, normal or high. The aim of this study was to evaluate longitudinally time-dependent changes in the GH response to GHRH, IGF-I, IGFBP-3 and albumin values in patients during corticotherapy. Six patients received GHRH before and after one week and one month of prednisone administration (20-60 mg/d, orally). IGF-I, IGFBP-3 and albumin were determined in each test, at time 0. Ten normal controls were also evaluated in one occasion. There were no differences in basal GH values, GH response to GHRH, IGF-I and IGFBP-3 levels between controls and patients before starting corticotherapy. Albumin (g/l; mean+/-SE) values were lower in patients before treatment (31+/-4) than in controls (43+/-1). After one week of prednisone administration there was a significant decrease in peak GH (microg/l) levels (before: 18.8+/-7.4; 1 week: 5.0+/-1.3), which was maintained after one month (8.1+/-3.5). IGF-I (microg/l) levels increased significantly, from 145+/-23 to 205+/-52 after one week of therapy, reaching levels of 262+/-32 after one month. IGFBP-3 (mg/l) values did not increase significantly (before: 2.1+/-0.2; 1 week: 2.5+/-0.3; 1 month: 2.8+/-0.2). Albumin levels showed a significant rise both after one week (36+/-4) and one month (42+/-3) of corticotherapy. In summary, we observed a marked decrease in the GH response to GHRH after one week and one month of prednisone administration associated with an increase in circulating IGF-I and albumin values. The physiological implications of these findings are still uncertain. It is possible that glucocorticoids increase hepatic IGF-I and albumin synthesis, although other mechanisms may have a role.

Albumin synthesis after intense intermittent exercise in human subjects.

We measured hepatic albumin synthesis in five volunteers (4 men and 1 woman) at 3 and 6 h after recovery from intense exercise. A primed-constant infusion of a stable isotopic tracer of phenylalanine was used to determine hepatic fractional synthetic rate (FSR) and absolute synthetic rate (ASR) of albumin from the enrichment of phenylalanine in albumin. The infusion of the stable isotope tracer began 2 h after upright exercise or upright rest. Albumin FSR and ASR were 6.39 +/- 0.48%/day and 120 +/- 9 mg.kg body wt-1.day-1, respectively, 3-6 h after recovery from exercise; the FSR and ASR on the time control study day were 5.94 +/- 0.47%/day and 104 +/- 9 mg.kg body wt-1.day-1, respectively. The 6 and 16% increases (P < 0.05) in FSR and ASR after exercise were associated with an elevated plasma albumin content at 5 and 6 h of recovery (P < 0.05), an increased total protein content throughout recovery (P < 0.05), and a negative free water clearance (P < 0.05) at 2, 3, and 6.5 h of recovery compared with baseline values; these variables were unchanged from their baselines on the time control study day. Increased albumin content and reduced free water clearance contribute to a retention of fluid within the circulation after intense exercise. The measured increase in albumin synthesis could not account for the entire increase in albumin content at 6 h of recovery from exercise. However, we estimate that if the increased activity was maintained for the next 18 h, it could account for the expected increase in albumin content at 24 h of recovery.