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Middle age is not associated with altered fibrinogen concentration and production in males.
No full textWhether ageing is associated with increased fibrinogen concentration and production remains unclear. We measured fibrinogen fractional (FSR) and absolute synthesis (ASR) rates in male volunteers, of either young (mean age: 28 years, range: 22-34) or middle age (mean age: 57 years, range: 38-72), using a leucine-tracer isotope dilution technique. In the middle-age group, neither fibrinogen FSR (20.8 +/- 1.6%/day) nor ASR (1.8 +/- 0.1 g/day), or concentration (274 +/- 15 mg/dl), were different from those of the younger group (FSR: 20.2 +/- 1.4; ASR: 1.7 +/- 0.2; concentration: 265 +/- 8, respectively). Leucine Ra, an index of endogenous proteolysis, was approximately 20% lower in the older than in the younger group (P < 0.02). Thus, middle age in males is not associated with increased fibrinogen concentration and turnover, whereas endogenous protein breakdown in decreased. Factor(s) different from age per se are likely to be involved in the dysfibrinogenemia possibly occurring with ageing. Protein turnover is already reduced in middle-age males
Diabetic nephropathy is associated with increased albumin and fibrinogen production in patients with type 2 diabetes
No full textHyperfibrinogenaemia and albuminuria are cardiovascular risk factors, often coexisting in diabetic and non-diabetic people. Albuminuria in turn is associated with a compensatory albumin overproduction in non-diabetic patients. It is not known whether the presence of albuminuria in patients with type 2 diabetes mellitus is associated with greater albumin and fibrinogen production rates than in normoalbuminuric patients.
Using leucine isotope methods, we measured fractional and absolute synthesis rates (FSR, ASR) of albumin and fibrinogen in post-absorptive type 2 diabetic patients with either normal (n=11) or increased (n=10) urinary albumin excretion.
In albuminuric patients, albumin FSR (16.2 +/- 1.5%/day) and ASR (20.5 +/- 1.9 g/day) were greater (p < 0.02 and p < 0.05, respectively) than in normoalbuminuric patients (FSR=11.5 +/- 1.1%/day; ASR=15.7 +/- 1.2 g/day). Fibrinogen FSR was similar between patients with normal and increased albumin excretion, but concentration, the circulating pool and ASR of fibrinogen were 40 to 50% greater (p < 0.035) in patients with albuminuria. Albuminuria was positively correlated with albumin ASR, with fibrinogen concentration, the fibrinogen pool and ASR, whereas albumin synthesis was inversely correlated with calculated oncotic pressure.
Synthesis of albumin and fibrinogen is upregulated in type 2 diabetic patients with increased urinary albumin excretion. Albuminuria is associated with enhanced fibrinogen and albumin synthesis
Effect of liver cirrhosis on phenylalanine and tyrosine metabolism
No full textPURPOSE OF REVIEW: Phenylalanine conversion to tyrosine (i.e., 'hydroxylation') is the first irreversible step in phenylalanine catabolism and a source of circulating tyrosine. The purpose of the present review is both to examine hydroxylation from a biochemical standpoint and to report data measured in vivo under physiological conditions, as well as in liver and kidney disease.
RECENT FINDINGS: The simultaneous infusion of phenylalanine and tyrosine tracers in humans allows us to determine the hydroxylation rate in vivo. Hydroxylation accounts for a minor ( approximately 10-20%) although significant portion of tyrosine flux. The liver and the kidney are the key organs accounting for virtually the whole-body hydroxylation rates. It is regulated by substrate availability, being acutely stimulated by mixed meal ingestion and by dietary adaptation to high phenylalanine intakes. Theoretically, it may be impaired in advanced liver and kidney disease. Nevertheless, in compensated liver cirrhosis, hydroxylation as well as tyrosine flux are not decreased but rather increased. Only in end stage liver disease hydroxylation may be impaired and is corrected by transplantation. Hydroxylation is also reduced in end stage renal disease.
SUMMARY: Phenylalanine hydroxylation in vivo appears to represent a regulatory step of phenylalanine disposal and tyrosine production under acute and/or extreme conditions
A fast high-performance liquid chromatographic method for the measurement of plasma concentration and specific activity of phenylalanine.
No full textA fast high-performance liquid chromatographic (HPLC) method for the measurement in plasma of phenylalanine concentration and specific activity is reported. One-to-two mL of acidified plasma are applied to an ion-exchange resin. The eluted amino acids are enzymatically converted into the corresponding alpha-ketoacids, i.e. phenylalanine is converted into phenylpyruvic acid. After a two-step extraction, phenylpyruvic acid is separated by reverse phase chromatography within 8-10 min. The use of an internal standard allows precise quantitation of plasma concentrations. The radioactivity eluted from the HPLC is divided by the amount injected to yield the specific activity. Concentration and rate of appearance of phenylalanine in man, calculated with the L-[2,6-H-3]phenylalanine tracer, are in the range of published data
Protein degradation and synthesis measured with multiple amino acid tracers in post-absorptive and protein-anabolic conditions.
No full textIF: 3.62
Roles of insulin, age, and asymmetric dimethylarginine, on nitric oxide synthesis in vivo.
No full textWe tested the effects of insulin, on production of NO-related substances (nitrites and nitrates, NOx) following 15N-arginine iv infusion, and on ADMA and SDMA concentrations, in conditions reportedly associated with altered NO availability, i.e. ageing, hypertension, hypercholesterolemia, and Type-2 Diabetes (T2DM). A total of 26 male subjects (age: 23-71 yrs, BMI: 23-33 kg/m2), some of them affected by mixed pathologic features, were enrolled. NOx fractional synthesis rate (FSR) was lower in elderly (p<0.015) and T2DM subjects p<0.03), than in matched controls. Hyperinsulinemia generally increased both NOx FSR and ASR (Absolute Synthesis Rate), and reduced NOx, ADMA and SDMA concentrations. Insulin-sensitivity was impaired only in T2DM. Using simple linear regression analysis across all subjects, age was inversely correlated with both NOx FSR (R2 = 0.23, p<0.015) and ASR (R2 = 0.21, p<0.02). NOx FSR inversely correlated with both ADMA and SDMA. Using multiple regression analysis and various models, NOx FSR remained inversely associated with age and ADMA, whereas ASR was inversely associated with age and diabetes. No association with insulin sensitivity was found. We conclude that whole-body NOx production is decreased in ageing and T2DM. Age, ADMA concentration and T2DM, but not insulin-resistance, appear as negative regulators of whole-body NOx production
Effects of chronic metabolic acidosis on splanchnic protein turnover and oxygen consumption in human beings.
No full textBACKGROUND & AIMS: Although metabolic acidosis stimulates protein catabolism, its effects on splanchnic protein turnover and energy expenditure have not been measured in human beings. We investigated the effects of chronic metabolic acidosis (CMA) on splanchnic protein dynamics and oxygen consumption in human beings by using a leucine tracer and mass-balance techniques.
METHODS: Five subjects were studied after 6 days of HCl-, CaCl(2)-, and NH(4)Cl-induced acidosis; 8 subjects served as controls. Blood samples were collected from the radial artery and the hepatic veins. Measurements were performed on plasma and whole-blood samples.
RESULTS: Based on plasma measurements, subjects who had undergone CMA had lower rates of splanchnic proteolysis (-35%) and protein synthesis (-50%; P < .05) than controls, as well as a negative leucine kinetic balance (-6.81 +/- 2.48 micromol/kg/min/1.73 m(2) body surface [BS](-1)), compared with the neutral balance in control plasma samples (0.76 +/- 2.11 micromol/kg/min/1.73; P < .05 between groups). Based on measurements from whole blood, splanchnic proteolysis and protein synthesis did not differ significantly between CMA and control samples, and the net leucine kinetic balance was neutral in both groups (CMA, -0.69 +/- 1.57; controls, -0.74 +/- 3.45 micromol/kg/min/1.73). In CMA whole-blood measurements, splanchnic oxygen consumption (44.8 +/- 4.3 mL/min/1.73 m(2) BS) was slightly lower than in controls (57.5 +/- 8.4 mL/min/1.73 m(2) BS; P = NS). Splanchnic protein synthesis correlated with oxygen consumption (r = 0.82; P < .001).
CONCLUSIONS: CMA reduces splanchnic protein turnover and results in a negative leucine balance--an effect that apparently is offset by the contribution of blood cells to organ leucine (and protein) dynamics. Protein synthesis is a major contributor (about 67%) to energy expenditure in splanchnic organ
Decreased Homocysteine Trans-Sulfuration in Hypertension With Hyperhomocysteinemia: Relationship With Insulin Resistance
No full textHomocysteine is an independent cardiovascular risk factor and is elevated in essential hypertension. Insulin stimulates homocysteine catabolism in healthy individuals. However, the mechanisms of hyperhomocysteinemia and its relationship with insulin resistance in essential hypertension are unknown
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