Biomedical subjects

Ruud Berger

Publications and source records attributed to Ruud Berger.

25 records · Page 2Linked to original sources

PubMed2003

Hypertriglyceridemia in patients with chronic renal failure: possible mechanisms.

Cardiovascular disease (CVD) is a major cause of mortality in patients with chronic renal failure (CRF) caused by numerous factors defined as traditional and uremia-related risk factors. One of these risk factors, dyslipidemia, is often observed in patients with CRF, resulting in abnormal concentrations and composition of plasma lipoproteins. The prominent features of uremic dyslipidemia are an increase in plasma triglycerides and cholesterol in nearly all lipoproteins, and a reduction in high-density lipoprotein (HDL) cholesterol. Because of its direct contact with the circulating blood, the endothelium is preferentially subjected to the modulatory effects of these altered lipoproteins. Little is known about the mechanisms for hypertriglyceridemia in CRF. This review highlights several studies over the past years that have contributed to knowledge of hypertriglyceridemia, especially in combination with renal diseases and their dialysis treatment. The underlying mechanisms behind hypertriglyceridemia have not been fully clarified and may indeed be multifactorial. Hypertriglyceridemia may contribute to the progression of atherosclerosis. Therefore, it is essential to study the putative mechanisms for uremic dyslipidemia, since optimal treatment is essential for the prevention or delay of cardiovascular complications in patients with CRF.

Humans↗

PubMed2002

Biochemical characterization and subcellular localization of human copper transporter 1 (hCTR1).

The human copper transporter 1 gene (hCTR1) was previously identified by functional complementation in ctr1-deficient yeast. Overexpression of hCTR1 in wild-type yeast leads to increased sensitivity to copper toxicity, and mice with a homozygous disruption at the Ctr1 locus die early during embryogenesis. It is proposed that hCTR1 is responsible for high-affinity copper uptake into human cells, but the underlying molecular mechanisms are unknown. To begin to investigate the biochemical characteristics of hCTR1, a polyclonal antiserum was raised against recombinant hCTR1-fusion peptides. Biosynthetic studies using this antiserum revealed that hCTR1 was synthesized as a precursor protein of 28 kDa containing N-linked oligosaccharides, and is then converted to a mature protein of approx. 35 kDa, which is ubiquitously expressed. Immunofluorescence studies showed that subcellular hCTR1 localization differed markedly between cell types. In some cell lines, hCTR1 was located predominantly in an intracellular vesicular perinuclear compartment, and in others hCTR1 was located predominantly at the plasma membrane. In contrast with the copper export P-type ATPases mutated in Wilson disease and Menkes disease, the localization of hCTR1 was not influenced by copper concentrations. Inhibition of endocytosis by methyl-beta-cyclodextrin caused a partial redistribution of hCTR1 to the cell surface of HeLa cells. Taken together, the results in this study suggest a cell-specific control of copper uptake, which involves subcellular localization of the hCTR1 protein.

Base Sequence↗

PubMed2002

Idiopathic hypoalbuminemia explained by reduced synthesis rate and an increased catabolic rate.

OBJECTIVE: To determine the contribution of albumin synthetic and catabolic rates to steady state levels in a patient with idiopathic hypoalbuminemia. METHODS: Using L-[1-(13)C] valine, both FSR (fractional synthesis rate) as well as FCR (fractional catabolic rate) were studied. Human albumin cDNA analysis and determination of the exact albumin mass by electrospray mass spectrometry were performed. RESULTS: Compared with controls, plasma albumin concentration in the patient was reduced (6.7 vs. 37.0 +/- 2.6 g/L). Albumin FSR (= FCR in steady state) was increased compared to controls. The ASR (absolute synthesis rate) of albumin was decreased based on the enrichment in plasma valine and KIV, but estimated to be normal based on VLDL apoB100 at plateau compared to controls. Direct estimation of albumin FCR rejected the latter. No mutation was found in the transcribed region of albumin gene. The exact mass of albumin (66.493 Da) was not different from controls. CONCLUSION: The hypoalbuminemia was a result of accelerated clearance of albumin from plasma in addition to defective albumin synthesis. This study also shows that the chosen method of the precursor pool could lead to misinterpretation of data in hepatic protein synthesis.

Adult↗

PubMed2002

Triacylglycerol infusion does not improve hyperlactemia in resting patients with mitochondrial myopathy due to complex I deficiency.

BACKGROUND: A high-fat diet has been recommended for correction of biochemical abnormalities and muscle energy state in patients with complex I (NADH dehydrogenase) deficiency (CID). OBJECTIVE: This study evaluated the effects of intravenous infusion of isoenergetic amounts of triacylglycerol or glucose on substrate oxidation, glycolytic carbohydrate metabolism, and energy state in patients with CID. DESIGN: Four CID patients and 15 matched control subjects were infused with triacylglycerol (1.85 mg x kg(-1) x min(-1)) or glucose (5 mg x kg(-1) x min(-1)) while at rest. Respiratory calorimetry was used to evaluate mitochondrial substrate oxidation. Metabolism of glycolytic carbohydrate was determined on the basis of the rates of appearance and concentrations of plasma lactate from dilution of [1-(13)C]lactate measurements. In addition, high-energy phosphate metabolism was measured in forearm muscle by (31)P magnetic resonance spectroscopy. RESULTS: Whole-body oxygen consumption rates were higher in the patients than in the control subjects (P < 0.05). Oxygen consumption and high-energy phosphate metabolism in forearm muscle were not significantly different between the 2 infusion groups. The rates of appearance and concentrations of plasma lactate were higher in each of the 4 patients than in the control subjects (P < 0.05) and were lower during the triacylglycerol infusion than during the glucose infusion (P < 0.05); the differences were comparable in the patients and control subjects. CONCLUSIONS: We conclude that triacylglycerol infusion, relative to glucose infusion, does not improve the oxidation of substrates or the energy state of skeletal muscle and does not lower the rates of appearance and concentrations of plasma lactate to normal values in CID patients at rest.

Adolescent↗

PubMed2002

Triacylglycerol infusion improves exercise endurance in patients with mitochondrial myopathy due to complex I deficiency.

BACKGROUND: A high-fat diet has been recommended for the treatment of patients with mitochondrial myopathy due to complex I (NADH dehydrogenase) deficiency (CID). OBJECTIVE: This study evaluated the effects of intravenous infusion of isoenergetic amounts of triacylglycerol or glucose on substrate oxidation, glycolytic carbohydrate metabolism, and exercise endurance time and energy state of muscle in CID patients. DESIGN: Four CID patients and 15 control subjects were infused with triacylglycerol (3.7 mg x kg(-1) x min(-1)) or glucose (10 mg x kg(-1) x min(-1)) during low-intensity leg exercise. Respiratory calorimetry was used to evaluate mitochondrial substrate oxidation. The concentration and rate of appearance of plasma lactate (from dilution of [1-(13)C]lactate) were used to evaluate glycolytic carbohydrate metabolism. (31)P magnetic resonance spectroscopy was used to determine ratios of phosphocreatine to inorganic o-phosphate in forearm muscle during exercise. RESULTS: In 3 patients, leg exercise endurance time was better during the triacylglycerol infusion than during the glucose infusion. In all 4 patients, whole-body oxygen consumption rates during exercise were higher during triacylglycerol infusion than during the glucose infusion. In 3 patients, the concentration and rate of appearance of plasma lactate were lower during triacylglycerol infusion than during the glucose infusion. Ratios of phosphocreatine to inorganic o-phosphate during exercise were not significantly different between the 2 infusion studies or between the patients and control subjects. CONCLUSIONS: Triacylglycerol infusion is associated with a greater oxidation of substrates, lower rates of appearance and concentrations of plasma lactate, and greater leg exercise endurance time in myopathic CID patients than is glucose infusion. The energy state of muscle during exercise, however, was not significantly different after infusion of triacylglycerol or glucose.

Adolescent↗

PubMed2002

Lactate disposal via gluconeogenesis is increased during exercise in patients with mitochondrial myopathy due to complex I deficiency.

This study evaluated lactate disposal via gluconeogenesis as well as effects of FFA availability on gluconeogenesis via pyruvate (GNG(PYR)) in patients with mitochondrial myopathy due to complex I deficiency (CID). The rates of GNG(PYR) were measured in three CID patients and six healthy controls at rest and during 90 min cycle exercise, using the deuterium-labeled water method. All subjects served as their own control: on one occasion they were studied in the fasting state, and on the second occasion they received an infusion of triacylglycerol plus heparin. At rest, the fractional rate of gluconeogenesis from pyruvate was higher in patients than in controls in the fasting state. Triacylglycerol infusion was associated with increased rates of GNG(PYR) at rest in controls (p < 0.05) but not in patients. Circulating lactate and pyruvate levels were increased 3-fold during exercise in the CID patients. During exercise, GNG(PYR) increased in the CID patients (p < 0.01) and remained unchanged in controls, resulting in 85% and 72% higher absolute rates of GNG(PYR) in the patients than in the controls during fasting and triacylglycerol infusion, respectively. During exercise, rates of GNG(PYR) were not different between fasting and triacylglycerol infusion within both groups. Our data show that 1) GNG(PYR) is increased during exercise in CID patients; 2) increased pyruvate availability contributes to the higher rates of GNG(PYR) in the CID patients; and 3) exogenous infusion of fatty acids is not associated with increased rates of GNG(PYR) in CID patients at rest or during exercise. GNG(PYR) is a significant mechanism of lactate disposal in exercising CID patients, but triglyceride infusion does not enhance their lactate disposal through this mechanism.

Adolescent↗

PubMed2001

Transferrin synthesis is increased in nephrotic patients insufficiently to replace urinary losses.

The urinary loss of transferrin is sufficient to reduce plasma transferrin concentrations in the nephrotic syndrome. Hypotransferrinemia may lead to iron loss and microcytic anemia. The mechanism responsible for the hypotransferrinemia in the nephrotic syndrome is, however, unknown. In the present study, synthesis rate of transferrin was measured in vivo in nephrotic patients (n = 7) compared with control subjects (n = 6) using L-[1-(13)C]-valine. Plasma transferrin and iron concentration in the patients were significantly lower than in control subjects (transferrin, 1.39 +/- 0.08 versus 2.57 +/- 0.11 g/L, P < 0.0001; iron, 10.2 +/- 0.8 versus 21.1 +/- 4.5 micromol/L, P = 0.02). Furthermore, albuminuria correlated with transferrinuria (r(2) = 0.901, P = 0.001). The absolute synthesis rate of transferrin was increased in the patients (10.0 +/- 1.1 versus 7.4 +/- 0.7 mg/kg per d, P = 0.07), although this value failed to achieve significance. C-reactive protein, plasma iron, and proteinuria did not correlate with transferrin synthesis. In contrast, transferrin synthesis correlated with albumin synthesis (r(2) = 0.648, P = 0.03; n = 7). The present study indicates that increased transferrin synthesis occurs in nephrotic patients but is insufficient to compensate for urinary losses. Because, overall, no significant relationship was found between transferrin synthesis and either C-reactive protein or iron, it is unlikely that inflammation suppresses or that iron deficiency stimulates increased transferrin synthesis in these patients. The correlation between transferrin synthesis and albumin synthesis suggests that transferrin synthesis is a component of a general response in hepatic protein synthesis in the nephrotic syndrome. This suggests that a therapeutic approach to maximize plasma transferrin concentrations in nephrotic patients should be aimed primarily at reducing urinary protein excretion.

Adult↗