Liver export protein synthetic rates are increased by oral meal feeding in weight-losing cancer patients

2000 ◽  
Vol 279 (3) ◽  
pp. E707-E714 ◽  
Author(s):  
Matthew D. Barber ◽  
Kenneth C. H. Fearon ◽  
Donald C. McMillan ◽  
Christine Slater ◽  
James A. Ross ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Synthesis Rate ◽  
Similar Degree ◽  
Albumin Concentration ◽  
Fibrinogen Concentration ◽  
Albumin Synthesis ◽  
Fed State ◽  
Synthetic Rate ◽  
Export Protein ◽  
Median Weight Loss

We have demonstrated previously that, in the fasting state, whereas albumin synthesis is similar in cachectic cancer patients compared with controls, fibrinogen synthesis is increased. Whether synthesis of these proteins is altered after an oral meal was examined in eight weight-losing pancreatic cancer patients and six healthy controls by use of an intravenous flooding dose of [2H5]- or [2H8]phenylalanine. Cancer patients had a median weight loss of 19%, a significantly lower serum albumin concentration, and a significantly higher plasma fibrinogen concentration than controls ( P < 0.005). Fasting albumin synthesis rates were similar between cancer patients and controls (median total synthesis rate 11.3 vs. 13.9 g/day, respectively) and rose on feeding by a similar degree (median 29 and 24%). The fasting fibrinogen total synthetic rate was significantly higher in cancer patients than in controls (median 3.3 vs. 1.0 g/day, P = 0.0019). In cancer patients in the fed state, fibrinogen synthetic rate rose by a median of 38% ( P = 0.012), whereas in controls there was no significant change. These findings demonstrate significant upregulation by feeding of acute-phase protein synthesis in cachectic cancer patients.

scholarly journals Synthesis rate of plasma albumin is a good indicator of liver albumin synthesis in sepsis

2000 ◽  
Vol 279 (2) ◽  
pp. E244-E251 ◽  
Author(s):  
Benoît Ruot ◽  
Denis Breuillé ◽  
Fabienne Rambourdin ◽  
Gerard Bayle ◽  
Pierre Capitan ◽  
...  
Keyword(s):  
Synthesis Rate ◽  
Albumin Concentration ◽  
Liver Protein ◽  
Mrna Levels ◽  
Albumin Synthesis ◽  
Plasma Albumin ◽  
Period 2 ◽  
Fractional Synthesis ◽  
Plasma Albumin Concentration

Plasma albumin is well known to decrease in response to inflammation. The rate of albumin synthesis from both liver and plasma was measured in vivo by use of a large dose ofl-[2H3-14C]valine in rats injected intravenously with live Escherichia coli and in pair-fed control rats during the acute-phase period (2 days postinfection). The plasma albumin concentration was reduced by 50% in infected rats compared with pair-fed animals. Infection induced a fall in both liver albumin mRNA levels and albumin synthesis relative to total liver protein synthesis. However, absolute liver albumin synthesis rate (ASR) was not affected by infection. In plasma, albumin fractional synthesis rate was increased by 50% in infected animals compared with pair-fed animals. The albumin ASR estimated in the plasma was similar in the two groups. These results suggest that hypoalbuminemia is not due to reduced albumin synthesis during sepsis. Moreover, liver and plasma albumin ASR were similar. Therefore, albumin synthesis measured in the plasma is a good indicator of liver albumin synthesis.

scholarly journals Biological basis of hypoalbuminemia in ESRD.

1998 ◽  
Vol 9 (12) ◽  
pp. 2368-2376 ◽  
Author(s):  
G A Kaysen
Keyword(s):  
Peritoneal Dialysis ◽  
Acute Phase ◽  
Synthesis Rate ◽  
Albumin Concentration ◽  
Albumin Synthesis ◽  
Dialysis Patients ◽  
Extravascular Space ◽  
Amyloid A ◽  
Stage Renal Disease ◽  
End Stage

Hypoalbuminemia is associated with mortality in patients with end-stage renal disease (ESRD) maintained either on peritoneal dialysis (PD) or hemodialysis (HD). Serum albumin concentration is determined by its rate of synthesis, by the catabolic rate constant (the fraction of the vascular pool catabolized per unit time), by external losses, and by redistribution from the vascular to the extravascular space. Hypoalbuminemia in dialysis patients is primarily a consequence of reduced albumin synthesis rate in both HD and PD patients, and in the case of PD patents, of transperitoneal albumin losses as well. Continuous ambulatory peritoneal dialysis patients are able to increase albumin synthesis to replace losses. Thus, ESRD does not directly suppress albumin synthesis. The rate of albumin synthesis is inversely proportional to the serum concentration of one potential acute phase protein (alpha2 macroglobulin), and albumin concentration is inversely proportional to that of either C-reactive protein or serum amyloid A in both HD and PD patients. The cause of decreased albumin synthesis is primarily a response to inflammation (the acute phase response), although it is possible that inadequate nutrition may also contribute. The cause of the inflammatory response is not immediately evident. There is no evidence that shifts of albumin to the extravascular space or that dilution of the plasma by volume expansion plays any role in causing hypoalbuminemia in ESRD patients.

Modulation of the liver export protein synthetic response to feeding by an n−3 fatty-acid-enriched nutritional supplement is associated with anabolism in cachectic cancer patients

2004 ◽  
Vol 106 (4) ◽  
pp. 359-364 ◽  
Author(s):  
Matthew D. BARBER ◽  
Tom PRESTON ◽  
Donald C. McMILLAN ◽  
Christine SLATER ◽  
James A. ROSS ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Fatty Acid ◽  
Fish Oil ◽  
Cancer Patients ◽  
Nutritional Supplement ◽  
Whole Body ◽  
Fasting State ◽  
Fed State ◽  
Export Protein ◽  
Oral Supplement

The acute-phase protein response is associated with accelerated weight loss and shortened survival in cancer. This may be due to hepatic protein synthesis increasing demand for amino acids. An n-3 fatty-acid-enriched nutritional supplement will moderate aspects of cachexia in cancer patients. The present study examined the effect of such a supplement on hepatic synthesis of albumin and fibrinogen. Albumin and fibrinogen synthesis were measured in the fed and fasting state in eight weight-losing patients with pancreatic cancer by an intravenous flooding dose technique. Tracer incorporation into proteins was measured by GC/MS. Patients were restudied after 3 weeks of oral supplement enriched with fish oil (providing 2510 kJ/day and 2 g of eicosapentaenoic acid/day). At baseline, all patients were losing weight (median, 2.4 kg/month). After 3 weeks of consumption of the fish-oil-enriched nutritional supplement, patients′ weight stabilized (median change, +1 kg; P=0.01). At baseline, albumin and fibrinogen synthesis rates were stimulated in the fed compared with the fasting state [14.2 compared with 11.3 g/day (29% rise; P=0.01) and 4.5 compared with 3.3 g/day (38% rise; P=0.01) respectively]. After 3 weeks of the supplement, this stimulation in the fed state was no longer observed for albumin and was reduced for fibrinogen [11.2 compared with 10.5 g/day (3% rise; P=0.21) and 3.7 compared with 2.9 g/day (17% rise; P=0.01) respectively]. After 3 weeks, the combined albumin plus fibrinogen synthetic rate tended to fall in the fasting state (14.7 compared with 12.3 g/day; P=0.09) and was significantly reduced in the fed state (18.7 compared with 14.6 g/day; P=0.01). Modulation of hepatic export protein synthesis with feeding may have contributed to the net whole-body anabolism observed with administration of the n-3 fatty-acid-enriched oral supplement.

The response of liver albumin synthesis to infection in rats varies with the phase of the inflammatory process

2001 ◽  
Vol 102 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Benoît RUOT ◽  
Fabienne BÉCHEREAU ◽  
Gérard BAYLE ◽  
Denis BREUILLÉ ◽  
Christiane OBLED
Keyword(s):  
Food Intake ◽  
Food Restriction ◽  
Specific Effect ◽  
Synthesis Rate ◽  
Albumin Concentration ◽  
Mrna Levels ◽  
Albumin Synthesis ◽  
Acute Response ◽  
Absolute Synthesis ◽  
Albumin Mrna

To discriminate between the effects of infection and of anorexia associated with infection, liver albumin synthesis was measured in well-fed rats, in rats injected with live Escherichia coli and in pair-fed rats at different stages of the inflammatory response (1, 6 and 10 days after infection) using a large dose of l-[1-14C]valine. Albuminaemia and albumin mRNA levels were unchanged following food restriction. However, absolute albumin synthesis was decreased in pair-fed rats compared with control animals after 1 day of food restriction, and had returned to normal values by day 10 when food intake was restored. Infection was characterized by a decrease in the plasma albumin concentration (35%, 45% and 28% as compared with pair-fed rats at 1, 6 and 10 days after infection respectively). Albumin mRNA levels and relative albumin synthesis were reduced in infected rats as compared with both control and pair-fed animals at all stages of infection. However, during the early acute response, the albumin absolute synthesis rate was similar in infected rats and pair-fed rats, indicating no specific effect of infection at this stage. Later in the course of infection, the amount of albumin synthesized by the liver was lower in infected than in pair-fed rats, and hypoalbuminaemia was probably maintained due to a lack of stimulation of synthesis despite increased food intake.

Acute Stimulation of Albumin Synthesis Rate with Oral Meal Feeding in Healthy Subjects Measured with [Ring-2H5]Phenylalanine

1995 ◽  
Vol 88 (2) ◽  
pp. 235-242 ◽  
Author(s):  
K. A. Hunter ◽  
P. E. Ballmer ◽  
S. E. Anderson ◽  
J. Broom ◽  
P. J. Garlick ◽  
...  
Keyword(s):  
Oral Feeding ◽  
Synthesis Rate ◽  
Liver Protein ◽  
Albumin Synthesis ◽  
Adult Rats ◽  
Fed State ◽  
Total Liver ◽  
Fractional Rate ◽  
Fractional Synthesis ◽  
Stimulation Of

1. The short-term effect of oral feeding on albumin synthesis rate was investigated in 12 healthy volunteers using two meal regimens. Albumin synthesis was measured over 90 min after injection of a ‘flooding’ amount (43 mg/kg body weight) of phenylalanine enriched to 7.5, 10 or 15 atoms% with the stable isotope [ring-2H5]phenylalanine. 2. In one set of subjects, consumption of five small hourly meals resulted in a consistent and significant increase (P < 0.05) in albumin fractional synthesis rate from a mean (± SEM) fasting value of 5.8 (± 0.4)%/day to 7.1 (± 0.4)%/day in the fed state. 3. A second study in which albumin synthesis was measured 30 min after consumption of a single larger meal was carried out in another set of volunteers. The fractional rate of albumin synthesis was again significantly elevated after feeding (P < 0.05), rising from 7.1 (± 0.4)%/day in the fasted state to 9.1 (± 0.6)%/day in the fed state. In both studies, similar responses were observed in the absolute rate of albumin synthesis (mg day−1 kg−1). 4. Albumin secretion time was significantly shorter (P < 0.05) after feeding in both studies, suggesting that the acute stimulation in albumin synthesis observed after feeding may in part be mediated via a post-transcriptional mechanism. 5. The response of total liver protein synthesis to oral feeding was investigated in an animal model employing adult rats studied with a flooding amount of [2,6-3H]phenylalanine. 6. The results indicated a stimulation of 20% with no difference in the proportion of albumin synthesis relative to total liver synthesis, determined from the immunoprecipitation of albumin from the liver.

Some Factors Influencing Metabolism and Distribution of Fibrinogen in Man and Rabbits

1977 ◽  
Vol 37 (02) ◽  
pp. 243-252
Author(s):  
Yi-Hsiang Chen ◽  
E. B Reeve
Keyword(s):  
Plasma Fibrinogen ◽  
Synthesis Rate ◽  
Fibrinogen Concentration ◽  
Fractional Catabolic Rate ◽  
System Parameters ◽  
Catabolic Rate ◽  
Simultaneous Decrease ◽  
Normal Males ◽  
Healthy Females ◽  
Made In

SummaryTo shed some light on the homeostatic regulation of plasma fibrinogen, metabolic studies were made in healthy females, and in normal, thyroidectomized, and thyroxine-treated rabbits. In females, compared with normal males, plasma fibrinogen concentration, plasma and interstitial fibrinogen decreased consequent to an increased fractional catabolic rate and a normal fibrinogen synthesis rate. The interstitial/plasma fibrinogen ratio remained unchanged. In normal rabbits, with increasing body weight fractional catabolic rate and catabolic rate decreased, while fibrinogen concentration and plasma fibrinogen remained constant owing to a simultaneous decrease in fibrinogen synthesis. In addition, fractional transcapillary transfer rate and transcapillary flux also decreased resulting in a shrinkage of interstitial fibrinogen. Thyroidectomy and thyroxine-injection markedly altered fibrinogen metabolism: thyroid hormone accelerated fibrinogen catabolism but also stimulated synthesis. The net result was an increase in plasma fibrinogen and fibrinogen concentration. The interstitial/plasma fibrinogen ratio decreased in thyroxine-treated, and increased in thyroidectomized animals. This study defines the variations of the fibrinogen system parameters in these physiologic and pathologic conditions, and illustrates some patterns of alterations in fibrinogen metabolism.

Effects of smoking and abstention from smoking on fibrinogen synthesis in humans

2001 ◽  
Vol 100 (4) ◽  
pp. 459-465 ◽  
Author(s):  
Kirsty A. HUNTER ◽  
Peter J. GARLICK ◽  
Iain BROOM ◽  
Susan E. ANDERSON ◽  
Margaret A. McNURLAN
Keyword(s):  
Risk Factors ◽  
Significant Risk ◽  
Plasma Fibrinogen ◽  
Fibrinogen Concentration ◽  
Primary Role ◽  
Absolute Rate ◽  
Albumin Synthesis ◽  
Plasma Albumin ◽  
Concomitant Reduction ◽  
Metabolic Mechanism

Cigarette smoking and hyperfibrinogenaemia are both significant risk factors for the development of cardiovascular disease. Two studies are described here which aimed to establish the metabolic mechanism responsible for the raised plasma fibrinogen concentration observed in smokers. Chronic smokers had a significantly elevated absolute rate of fibrinogen synthesis (ASR) compared with non-smokers (22.7±1.3 mg/kg per day versus 16.0±1.3 mg/kg per day; means±S.E.M., P < 0.01), with plasma levels of fibrinogen significantly correlated with fibrinogen synthesis (r = 0.65, P = 0.04). Unlike fibrinogen, plasma albumin concentrations were lower in smokers than in non-smokers (45±0.4 versus 47±0.7 g/l, P < 0.05), but there was no difference in rates of albumin synthesis between the two groups. Two weeks cessation from smoking by previously chronic smokers was associated with a rapid and marked fall in plasma fibrinogen concentration (from 3.06±0.11 g/l to 2.49±0.14 g/l, P < 0.001), and a significant reduction in ASR (a 33% reduction, from 24.1±1.7 to 16.1±1.0 mg/kg per day, P < 0.001). These studies suggest a primary role for increased synthesis in producing the hyperfibrinogenaemia associated with smoking. Moreover, abstention from smoking for a period of only 2 weeks induces a significant decrease in the rate of fibrinogen synthesis by the liver, with a concomitant reduction in the plasma fibrinogen concentration.

scholarly journals Systemic inflammation and nutritional insufficiency in palliative cancer patients

2021 ◽  
Vol 102 (4) ◽  
pp. 446-452
Author(s):  
O V Kurchenkova ◽  
U V Kharlamova ◽  
A V Vazhenin ◽  
A O Abdalov
Keyword(s):  
Cancer Patients ◽  
Body Mass ◽  
Systemic Inflammation ◽  
Risk Index ◽  
Nutritional Risk ◽  
Albumin Concentration ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Nutritional Risk Index ◽  
Nutritional Insufficiency

Aim. To study the relationship between the symptoms of nutritional insufficiency and systemic inflammation in cancer palliative patients. Methods. 106 palliative cancer patients were examined at Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine: 54 (50.9%) men and 52 (49.1%) women aged 61 [54; 67] years. All patients underwent laboratory and instrumental examination within the approved standards of specialized medical care. Systemic inflammation was assessed by the levels of acute phase proteins (C-reactive protein, fibrinogen). The study of integrated clinical and laboratory, somatometric parameters was carried out. The nutritional risk index was assessed. Results. Palliative cancer patients showed a statistically significant decrease in the concentration of hemoglobin, lymphocytes, and albumin. The activation of systemic inflammation that manifested by hyperfibrinogenemia and an increase in the level of C-reactive protein was revealed. The study of somatometric parameters revealed a statistically significant decrease in body mass index, shoulder circumference, subscapular skinfold thickness, and a tendency to reduce lean body mass. The nutritional risk index assessment showed mild nutritional insufficiency in 22 (20.8%) of the examined patients and severe nutritional insufficiency in 28 (26.4%) patients. The maximum diagnostic significance of the level of C-reactive protein for prediction the nutritional insufficiency was achieved at 80.4% sensitivity and 52.7% specificity (AUC=0.671, 95% confidence interval [0.573; 0.759], p=0.001), which corresponded to a C-reactive protein threshold of 31 mg/l. Conclusion. 50 (47.2%) of the examined patients showed signs of nutritional insufficiency, a statistically significant decrease in hemoglobin and albumin concentration, as well as lymphocyte count, activation of systemic inflammation, manifested by hyperfibrinogenemia, and an increase in the level of C-reactive protein; it was revealed a statistically significant relationship between C-reactive protein level and malnutrition.

Albumin synthesis in humans increases immediately following the administration of endotoxin

2002 ◽  
Vol 103 (5) ◽  
pp. 525-531 ◽  
Author(s):  
Hans BARLE ◽  
Anna JANUSZKIEWICZ ◽  
Lars HÅLLSTRÖM ◽  
Pia ESSÉN ◽  
Margaret A. MCNURLAN ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Early Phase ◽  
The Other ◽  
Synthesis Rate ◽  
Control Group ◽  
Albumin Synthesis ◽  
Fractional Synthesis Rate ◽  
Before And After ◽  
Fractional Synthesis ◽  
Absolute Synthesis

In order to investigate the immediate (i.e. within 3h) response of albumin synthesis to the administration of endotoxin, as a model of a moderate and well controlled catabolic insult, two measurements employing L-[2H5]phenylalanine were performed in 16 volunteers. One group (n = 8) received an intravenous injection of endotoxin (4ng/kg; lot EC-6) immediately after the first measurement of albumin synthesis, whereas the other group received saline. A second measurement was initiated 1h later. In the endotoxin group, the fractional synthesis rate of albumin was 6.9±0.6%/day (mean±S.D.) in the first measurement. In the second measurement, a significant increase was observed (9.6±1.2%/day; P<0.001). The corresponding values in the control group were were 6.6±0.6%/day and 7.0±0.6%/day respectively (not significant compared with first measurement and P<0.001 compared with the second measurement in the endotoxin group). The absolute synthesis rates of albumin were 148±35 and 201±49mg·kg-1·day-1 before and after endotoxin (P<0.01). In the control group, the corresponding values were 131±21 and 132±20mg·kg-1·day-1 (not significant compared with the first measurement and P<0.01 compared with the second measurement in the endotoxin group). In conclusion, these results indicate that albumin synthesis increases in the very early phase after a catabolic insult, as represented by the administration of endotoxin.

Albumin Synthesis Rate as a Measure of Liver Function in Patients with Cirrhosis

2009 ◽  
Vol 182 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Ernst Hasch ◽  
Stig Jarnum ◽  
Niels Tygstrup
Keyword(s):  
Liver Function ◽  
Synthesis Rate ◽  
Albumin Synthesis
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