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Biomedical subjects

R van der Meer

Publications and source records attributed to R van der Meer.

47 records · Page 3Linked to original sources

Fecal steroid excretion in relation to the development of casein-induced hypercholesterolemia in rabbits.

Two groups of nine rabbits fed a purified diet containing soy protein were injected intravenously with [4-14C]cholesterol. One group was fed the same diet for 78 d while the other group was fed a diet containing casein. The feces of the rabbits were collected and analyzed for radioactivity present in the neutral steroid and bile acid fractions. The excretion of neutral steroids and bile acids was lowered within 3 d after soy protein was replaced by casein and before the serum cholesterol concentration was increased. However, in the casein-fed rabbits the specific radioactivity of the bile acids was greater, whereas the amount of excreted bile acids was lower than in the soy protein-fed rabbits. After the serum cholesterol level in the casein-fed animals became constant (d 35), a further injection of [4-14C]cholesterol was given to all animals. Kinetic parameters of cholesterol metabolism according to a two-pool model were estimated from the die-away curve of [4-14C]cholesterol in serum. The size of the rapidly exchangeable pool (pool A) was greater in the casein-fed rabbits than in the soy protein-fed rabbits, whereas the size of pool B was similar in the two groups. The partial turnover rate of pool A was lower, as was the partial turnover of the slowly exchangeable pool (pool B), and the production rate of cholesterol was significantly lower on the casein-fed rabbits than in the soy protein-fed rabbits. This study suggests that the reduced excretion of steroids in casein-fed rabbits could be the cause of the hypercholesterolemia and is not the result of it.

Animals↗

Quantification of the contribution of various steps to the control of mitochondrial respiration.

Using principles developed by Kacser and Burns ((1973) in Rate Control of Biological Processes (Davies, D. D., ed) pp. 65-104, Cambridge University Press, London) and Heinrich and Rapoport ((1974) Eur. J. Biochem. 42, 97-105), inhibitor titration studies were carried out in order to quantify the amount of control (control strength) exerted by different steps in oxidative phosphorylation on the rate of mitochondrial oxygen uptake. In the resting state of respiration, nearly all control is exerted by the passive permeability of the mitochondrial inner membrane to protons. In the intermediate states and even in the active state of respiration, control is distributed among different steps including the adenine nucleotide translocator and cytochrome c oxidase. It is therefore not possible to speak of the rate-limiting step in oxidative phosphorylation. Since both the adenine nucleotide translocator and cytochrome c oxidase appear to be rate-controlling, hypotheses suggesting that respiration is fully controlled by either of these two steps alone need to be modified.

Animals↗

Control mechanisms of energy-dependent metabolic pathways in hepatocytes.

The control of respiration was studied in isolated rat-liver cells and isolated rat-liver mitochondria. When isolated rat-liver cells are perfused with different concentrations of lactate at a constant lactate/pyruvate ratio, the rate of mitochondrial respiration is a linear function of the affinity for the respiratory chain; the affinity term contains the intramitochondrial redox state and the extramitochondrial phosphate potential. However, when the cells are perfused with ammonia in addition to lactate (+ pyruvate), the stimulation of the oxygen uptake is not accompanied by an increase in the affinity. In order to obtain further insight into the relationship between oxygen uptake and intramitochondrial and extramitochondrial phosphate potential, experiments were also carried out with isolate rat-liver mitochondria incubated with an extramitochondrial ATP-utilizing system (glucose plus hexokinase) or an intramitochondrial ATP-utilizing system (citrulline synthesis). The results suggest that the rate of oxygen consumption is controlled by the intramitochondrial phosphate potential.

Adenosine Triphosphate↗

The role of hydrogen translocating shuttles during ethanol oxidation in hepatocytes from euthyroid and hyperthyroid rats.

A quantitative study of the contribution of the malate-aspartate and glycerol-3-phosphate cycles to the translocation of reducing equivalents from cytosol to mitochondria during ethanol oxidation has been made in hepatocytes from euthyroid and hyperthyroid rats. 1. In hepatocytes from euthyroid rats both cycles have an almost equal capacity and their relative contribution to total hydrogen transport to the mitochondria depends on the conditions chosen. 2. In hepatocytes from hyperthyroid rats maximal rates of ethanol oxidation were significantly lower than in hepatocytes from euthyroid rats, even though the capacity of the glycerol-3-phosphate cycle was increased. This was due to a decreased activity of alcohol dehydrogenase.

Alcohol Oxidoreductases↗

Calcium and vitamin D: possible protective agents against colorectal cancer?

Nutritional factors are important determinants of colorectal cancer risk. Diets high in fat and/or low in fibre are especially recognised to increase risk. Dietary calcium and vitamin D have been suggested to be protective against colorectal cancer. With respect to calcium, its possible effect is thought to be mediated at least in part through intraluminal precipitation of hydrophobic, cytotoxic substances, in particular fatty and bile acids, which can promote colorectal cancer development. Data from studies in vitro and in animals support a protective effect of calcium, but studies in humans, both epidemiological and interventional, have given inconclusive results. With respect to vitamin D, data from only a small number of studies are available. Results suggest a protective effect by inhibition of cell proliferation, mediated through specific receptors. It is concluded that there are currently insufficient reasons to supplement subjects at increased colon cancer risk with calcium or vitamin D, especially when dietary intake of these substances is in agreement with general guidelines.

Animals↗

Calcium supplementation as prophylaxis against colon cancer?

Dietary factors are major determinants of colorectal cancer risk. Especially a diet high in fat and low in fiber is recognized to be a risk factor. Dietary calcium has been suggested to be protective against colorectal cancer through the binding of intraluminal fatty acids and bile acids. Because of their cell-damaging properties these substances may stimulate colorectal epithelial cell proliferation and so promote colorectal cancer development. In this article data from in vitro, animal and human studies on the intraluminal effects of calcium, on its effects on colorectal epithelium and on the association between calcium intake and colorectal cancer are reviewed. It is concluded that at present it should be advised to bring dietary calcium intake into agreement with general dietary guidelines, but that high expectations of extra calcium as an effective mode of colon cancer prevention should not be encouraged.

Animals↗