Phytosterols have an unfavourable effect on bacterial activity and no evident protective effect on colon carcinogenesis.

The effects of physiological dietary phytosterol supplements on intestinal microflora activity and faecal sterols and their capacity to protect rats fed a normal or high saturated fatty-acid diet against tumour development were studied. A group of 80 female Wistar rats were fed an 8% lipid diet for 4 weeks (adaptation period) and then randomly assigned in a factorial experimental design study to diets containing 8% or 24% hydrogenated coconut oil, with or without a 24-mg/day/rat phytosterol supplement. They were instilled intrarectally with saline or methyl-nitroso-urea (MNU). Faecal sterol output was analysed for one week each month. Pathological analysis was done at the end of the 30-week experiment. Animals treated with MNU and given phytosterol supplements had tumour frequencies (8/20) similar to those not fed phytosterols (11/20). The fat-supplemented diet had no significant influence. Colonic glands were found in area of lymphoid follicles in all the groups, but were more frequent in rats on high-fat diets (P < 0.01). The coprostanol and the cholesterol excretion of the phytosterol-supplemented rats was significantly enhanced. Therefore phytosterols have an unfavourable effect on bacterial activity. These data confirm the capacity of phytosterols to decrease cholesterol absorption, but indicate that a large excess of phytosterol must be avoided until further research on its effects on carcinogenesis has been done.

Influence of a high-calcium carbonate diet on the incidence of experimental colon cancer in rats.

This study was done to determine whether a high dietary calcium carbonate concentration could protect against colon tumors in rats. Female Wistar rats were randomly assigned to one of four groups and maintained on an 8% lipid diet for an adaptation period of four weeks. All groups were then fed a 24% lipid diet (sunflower oil), with (Groups 2 and 4) or without (Groups 1 and 3) a 1.5% calcium carbonate supplement. They were intrarectally instilled with saline (Groups 1 and 2) or nitrosomethylurea (NMU) (Groups 3 and 4). Fecal sterol output and pH were analyzed for one week each month. Histological analysis was done at the end of the 32-week experiment. No tumors were found in the non-NMU-treated animals. The NMU-treated rats had tumors: 31% in Group 3 and 30% in Group 4. The calcium carbonate supplement had no effect on this incidence. The lipid and cholesterol excretions of the calcium carbonate-supplemented rats were significantly enhanced. The coprostanol output was not altered, although its fecal concentration of the calcium-supplemented rats was decreased. Although neither lipid overload nor NMU treatment altered the fecal pH, it was significantly increased in both calcium carbonate-supplemented groups. These findings suggest that additional calcium as carbonate has no effect on colon tumor incidence, although the fecal composition is altered. The increased pH of the feces due to the carbonate could have the opposite effect to calcium.

Effect of egg consumption in healthy volunteers: influence of yolk, white or whole-egg on gastric emptying and on glycemic and hormonal responses.

The effects of the ingestion of 2 whole eggs (E), 2 egg whites, 2 egg yolks (Y), or no eggs with a standard breakfast on gastric emptying, glycemic and hormonal responses have been studied in 12 healthy young males. E and Y induce a significant delay of gastric emptying, together with reduced blood glucose and insulin peaks (Y). Egg ingestion, whatever the part, increases gastric inhibitory peptide level in blood. Cholecystokinin is enhanced after E or Y ingestion. The results indicate that egg ingestion, especially yolk ingestion, may be of interest in regulating metabolic variables of glucose metabolism.

Dietary calcium salts as protective agents and laminin P1 as a biochemical marker in chemically induced colon carcinogenesis in rats.

To evaluate the protective effect of different calcium forms against colon carcinogenesis, Wistar rats fed a high-fat diet (24%) were supplemented with different chemical forms of dietary calcium and were intrarectally instilled with N-methyl-N-nitrosourea (NMU). Supplemental calcium was administered at 1.5% mineral (w/w of total diet) complexed with either carbonate, gluconate, or lactate in Groups 2, 3, and 4, respectively. The tumor incidence of colon cancer was compared with a control group (Group 1), fed the same diet without supplemental calcium. Colon carcinoma incidence was 31, 33, 13, and 7% in Groups 1, 2, 3, and 4, respectively. Calcium had a significant protective effect against carcinogenesis, and the maximum protective effect was observed with gluconate and lactate forms. Laminin P1 blood level was measured as a tumor marker. Laminin P1 results were compared with the reference group (Group T), fed a standard diet and not NMU instilled. The serum laminin P1 level was significantly higher (p = 0.0001) in NMU-instilled Groups 1, 2, 3, and 4 (0.24 +/- 0.03, 0.93 +/- 1.43, 0.84 +/- 1.33, and 0.41 +/- 0.34 mU/ml respectively) than in the Reference Group T (0.10 +/- 0.05 mU/ml).

Potential teratogenic and neurodevelopmental consequences of coffee and caffeine exposure: a review on human and animal data.

The teratogenic effect of caffeine has been clearly demonstrated in rodents. The sensitivity of different animals species is variable. Malformations have been demonstrated in mice at 50-75 mg/kg of caffeine, whereas the lowest dose usually needed to induce malformations is 80 mg/kg in rats. However, when caffeine is administered in fractioned amounts during the day, 330 mg/kg/day are necessary to reach teratogenicity in rats. In rodents, the most frequently observed malformations are those of the limbs and digits, ectrodactyly, craniofacial malformations (labial and palatal clefts) and delays in ossification of limbs, jaw and sternum. Nevertheless, even in rodents, caffeine can be considered as a weak teratogenic agent, given the quite large quantities of caffeine necessary to induce malformations and the small number of animals affected. In humans, caffeine does not present any teratogenic risk. The increased risk of the most common congenital malformations entailed by moderate consumption of caffeine is very slight. However, caffeine potentiates the teratogenic effect of other substances, such as tobacco, alcohol, and acts synergistically with ergotamine and propranolol to induce materno-fetal vasoconstrictions leading to malformations induced by ischemia. Therefore, even though caffeine does not seem to be harmful to the human fetus when intake is moderate and spread out over the day, some associations, especially with alcohol, tobacco, and vasoconstrictive or anti-migraine medications should be avoided. Maternal consumption of caffeine affects brain composition, especially in case of a low-protein diet and also seems to interfere with zinc fixation in brain. Maternal exposure to caffeine induces also long-term consequences on sleep, locomotion, learning abilities, emotivity, and anxiety in rat offspring, whereas in humans, more studies are needed to ascertain long-term behavioral effects of caffeine ingestion by pregnant mothers.

Caffeine and sports activity: a review.

Potential ergogenic effects of caffeine at the cellular level are mediated by three main mechanisms of action which are: intracellular mobilization of calcium from sarcoplasmic reticulum and increased sensitivity of myofibrilles to calcium; inhibition of phosphodiesterases leading to an increase in cyclic-3',5'-adenosine monophosphate (cAMP) in various tissues including muscle; and the antagonism at the level of adenosine receptors, mainly in the central nervous system. The main mechanism of action of caffeine at the level usually encountered in vivo after the ingestion of a few cups of coffee is undoubtedly linked to the antagonism of caffeine at adenosine receptors. Caffeine also increases production of plasma catecholamines that allow the body to adapt to the stress created by physical exercise. Catecholamine production increases probably, in turn, the availability of free fatty acids as muscle substrates during work, thus allowing glycogen sparing. Caffeine is able to increase muscle contractility, has no ergogenic effect on intense exercise of brief duration, but can improve the time before exhaustion. Caffeine is also able to improve physical performance and endurance during prolonged activity of submaximal intensity. Glycogen sparing resulting from increased rate of lipolysis could contribute to the prolonged time to exhaustion. Finally, tolerance to the methylxanthine should be taken into account when an athlete wants to draw any benefit from caffeine absorption prior to a sports event.

Potential genotoxic, mutagenic and antimutagenic effects of coffee: a review.

Coffee and caffeine are mutagenic to bacteria and fungi, and in high concentrations they are also mutagenic to mammalian cells in culture. However, the mutagenic effects of coffee disappear when bacteria or mammalian cells are cultured in the presence of liver extracts which contain detoxifying enzymes. In vivo, coffee and caffeine are devoid of mutagenic effects. Coffee and caffeine are able to interact with many other mutagens and their effects are synergistic with X-rays, ultraviolet light and some chemical agents. Caffeine seems to potentiate rather than to induce chromosomal aberrations and also to transform sublethal damage of mutagenic agents into lethal damage. Conversely, coffee and caffeine are also able to inhibit the mutagenic effects of numerous chemicals. These antimutagenic effects depend on the time of administration of coffee as compared to the acting time of the mutagenic agent. In that case, caffeine seems to be able to restore the normal cycle of mitosis and phosphorylation in irradiated cells. Finally, the potential genotoxic and mutagenic effects of the most important constituents of coffee are reviewed. Mutagenicity of caffeine is mainly attributed to chemically reactive components such as aliphatic dicarbonyls. The latter compounds, formed during the roasting process, are mutagenic to bacteria but less to mammalian cells. Hydrogen peroxide is not very active but seems to considerably enhance mutagenic properties of methylglyoxal. Phenolic compounds are not mutagenic but rather anticarcinogenic. Benzopyrene and mutagens formed during pyrolysis are not mutagenic whereas roasting of coffee beans at high temperature generates mutagenic heterocyclic amines. In conclusion, the mutagenic potential of coffee and caffeine has been demonstrated in lower organisms, but usually at doses several orders of magnitude greater than the estimated lethal dose for caffeine in humans. Therefore, the chances of coffee and caffeine consumption in moderate to normal amounts to induce mutagenic effects in humans are almost nonexistent.

Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects.

Caffeine is the most widely consumed central-nervous-system stimulant. Three main mechanisms of action of caffeine on the central nervous system have been described. Mobilization of intracellular calcium and inhibition of specific phosphodiesterases only occur at high non-physiological concentrations of caffeine. The only likely mechanism of action of the methylxanthine is the antagonism at the level of adenosine receptors. Caffeine increases energy metabolism throughout the brain but decreases at the same time cerebral blood flow, inducing a relative brain hypoperfusion. Caffeine activates noradrenaline neurons and seems to affect the local release of dopamine. Many of the alerting effects of caffeine may be related to the action of the methylxanthine on serotonin neurons. The methylxanthine induces dose-response increases in locomotor activity in animals. Its psychostimulant action on man is, however, often subtle and not very easy to detect. The effects of caffeine on learning, memory, performance and coordination are rather related to the methylxanthine action on arousal, vigilance and fatigue. Caffeine exerts obvious effects on anxiety and sleep which vary according to individual sensitivity to the methylxanthine. However, children in general do not appear more sensitive to methylxanthine effects than adults. The central nervous system does not seem to develop a great tolerance to the effects of caffeine although dependence and withdrawal symptoms are reported.

[Effects of coffee on the respiratory system]. / Les effets du café sur l'appareil respiratoire.

The consumption of coffee is a very old and popular habit. It is possible that it may have an effect on the respiratory system and on the regulation of respiration. Apart from the manifestations of hypersensitivity linked to the handling of green coffee, the consumption of coffee can have different effects. On the one hand it has a beneficial effect on bronchospasm. On the other hand its consumption has been suspected of contributing to the development of chronic airflow obstruction (COPD) and also in the genesis of bronchial cancer, without, however, its responsibility being proven in a clear fashion. In fact, in these two latter pathological circumstances, the causal relationship is probably indirectly linked to the fact that there is a strong positive correlation between the consumption of coffee and of tobacco. Finally the consumption of coffee increases ventilatory frequency in normal subjects and also in the course of COPD, and if taken in large quantities by pregnant women, there is an increased risk of neonatal apnoea in the newborn, by an abrupt cessation in the caffeine level.

Evaluation of (13C)ethanol incorporation into very-low-density lipoprotein triglycerides using gas chromatography/isotope ratio mass spectrometry coupling.

Gas chromatography/isotope ratio mass spectrometry (GC/IRMS) coupling was used to evaluate (13C)ethanol incorporation into plasmatic very-low-density lipoprotein (VLDL) triglycerides of three healthy human volunteers. After the perfusion of 13C-enriched alcohol, VLDL triglyceride fractions were extracted from plasma samples and prepared for the analysis of (13C)fatty acid methyl esters. The GC/IRMS coupling line, the analytical procedure and the data collection are described. The results show that ethanol itself may be used as a substrate for lipogenesis, though to a small extent: less than 10% of VLDL triglycerides may be derived from this metabolic pathway. Ethanol incorporates predominantly into myristic and palmitic acid. The small amount of sample material required for analysis, which minimizes the amount of isotope-labelled substrate required, makes this technique a valuable tool for metabolic investigations in human subjects.

[Diet peculiarities. Vegetarianism, veganism, crudivorism, macrobiotism]. / Les particularités diététiques. Végétarisme, végétalisme, crudivorisme, macrobiotisme.

People who refuse to eat meat animal products mostly adhere to vegetarianism, veganism, crudivorism or macrobiotism, But these food habits are only one part of life-style chosen for spiritual, ethic or hygienic and healthy motivations. Except vitamin B12 deficiencies these regimens do not produce other deficiencies if they are correctly followed and if the energy intake is in agreement with the RDA'S. They reduce the risks of metabolic diseases, coronaropathies, arterial hypertension, colon cancer, diverticular disease of the colon, kidney and gallstones. Nevertheless crudivorism and macrobiotism are associated with high risks of deficiencies especially in children and pregnant women.

[Effect of ornithine oxoglutarate on the duration and quality of wound healing in extensive reparative and plastic surgical methods]. / Incidence de l'oxoglutarate d'ornithine sur la durée et la qualité de la cicatrisation au cours des grands décollements de la chirurgie réparatrice et plastique.

Fifty-two overweight female patients hospitalized for a major plastic surgical procedure were included in a therapeutic trial designed to evaluate wound healing. Twenty-seven patients were randomized to a placebo and 25 to ornithine oxoglutarate (Cetornan). There were no statistical differences between patients concerning age, type of plasty, extent of detachment, or overall evaluation of physical condition at the time of randomisation. Evaluation was based mainly on clinical criteria, including duration and quality of healing, and type of complications. Results showed a significant improvement in time to healing in the Cetornan group (18 +/- 1 day) as compared to the placebo group (26 +/- 3 days) (p less than 0.01). Complications occurred in nine of the 27 patients under placebo (30%) and in three of the 25 patients under Cetornan (12%) (p = 0.07). Clinical and biological tolerance was outstanding. No patient was excluded during the trial.

[Plasma insulin and glucagon after ingestion of meal enriched with increased doses of pectin in healthy man]. / Insulin et glucagon plasmatiques après ingestion d'un repas enrichi par des doses croissantes de pectine chez l'homme sain.

The effects of three doses of pectin (5, 10 and 15 g) included in a solid-liquid meal on the postprandial plasma insulin and glucagon responses were studied in 12 healthy men. The mean plasma glucagon level was significantly smaller with 5 g of pectin than the control values at 150 min (p less than 0.05) whereas plasma insulin values did not vary. No change in mean plasma glucagon and insulin levels was noted with 10 g and 15 g of pectin although the mean blood glucose levels were significantly higher than the control values at 180 min (p less than 0.05). Addition of pectin to a meal, even if the doses were relatively important, had little or no effect on the postprandial hormonal responses in healthy men. However, pectin could be of renewed interest because of the possibility of its action of satiety by means of sustained late blood glucose levels.

Morphometric study of human hepatic cell modifications induced by fenofibrate.

We have studied liver biopsies obtained in 12 hyperlipoproteinemic (HLP) patients (type II, 6; type IV, 6) treated with diet and fenofibrate, and in 15 patients (type II, 11; type IV, 4) receiving diet only. Electron microscopy of liver biopsies and the morphometric analysis according to the method of Weibel and Rohr showed mitrochondrial changes in patients treated with fenofibrate, these changes depending on the type of hyperlipoproteinemia. In type II HLP, we found a decreased volume of normal mitochondria (fenofibrate, 125.72 +/- 17.04 X 10(-3) cm3/cm3; diet only, 185.84 +/- 8.96 10(-3), P less than .05). In type IV HLP we found a decreased number of giant mitochondria (fenofibrate, 0.08 +/- 0.03 X 10(10) cm-3; diet only, 0.32 +/- 0.08 X 10(10) cm-3, P less than .05) and a decreased volume of altered mitochondria (fenofibrate, 6.00 +/- 1.44 X 10(-3) cm3/cm3; diet only, 13.61 +/- 1.17 X 10(-3), P less than .05). In contrast with the rodent studies, the present study shows no change in the number of volume of peroxisomes.

Hypertrophy of liver peroxisomes in type II and type IV hyperlipoproteinemia.

A morphometric study on liver biopsies from patients with primary hyperlipoproteinemia (IIa n = 4, IIb n = 7, IV n = 7) and in controls (n = 7) was performed by light and electron microscopy. We found hypertrophy of peroxisomes in all subjects with hyperlipoproteinemia. As none of our patients had been given lipid-lowering drugs, this increase in volume seems to be due to hyperlipoproteinemia. Hypertrophy of peroxisomes in hyperlipoproteinemia may constitute a response of the hepatocyte to a disturbed metabolic state. Alterations of peroxisomes in hyperlipoproteinemia may thus occur prior to any lipid-lowering therapy.

Long-term influence of a wheat-bran supplemented diet on secretion of gastrointestinal hormones and on nutrient absorption in healthy man.

Responses of gastric inhibitory polypeptide (GIP), gastrin and vasoactive intestinal polypeptide (VIP) to a test meal and also nutrient absorption were measured in five healthy men before and after 1, 3 and 7 weeks of daily ingestion of 20 g of wheat bran added to a normal balanced diet. Basal levels of the three hormones were not affected by bran ingestion. Bran ingestion induced a progressive decrease of GIP response to the test meal which became significant after 7 weeks at 30 min (373.9 +/- 71.4 vs 231.1 +/- 47.8 pg/ml, mean +/- s.e.m., P less than 0.05) and at 180 min (389.4 +/- 43.9 vs 262.2 +/- 37.9 pg/ml, P less than 0.01). Gastrin release did not change except for a slight but not significant decrease after 3 weeks. There was no VIP secretion after meal ingestion and addition of bran caused no change. Blood glucose response decreased with time with the greatest effects during the third week with fibre at 30 min (5.00 +/- 0.50 vs 7.38 +/- 0.05 mmol/l before bran), and at 60 min (3.88 +/- 0.34 vs 5.94 +/- 0.27 mmol/l before bran, P less than 0.05). Wet and dry weight of faeces increased by at least 60 per cent from the first week with bran onwards. Faecal nitrogen and fat also increased from 1.77 +/- 0.16 to 2.44 +/- 0.13 g/d for nitrogen (P less than 0.02) and threefold for fat (from 3.78 +/- 0.58 to 10.35 +/- 0.67 per cent dry weight, P less than 0.005) at the third week. Fat and nitrogen contents remained higher until the end of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

The hepatocyte and type IIA and IIB hyperlipoproteinemia. A morphometric study.

We obtained liver biopsies in 4 patients with type IIA and 7 patients with type IIB hyperlipoproteinemia, and also in 7 healthy controls. A morphometric analysis of liver tissue was carried out by light and electron microscopy. Structural alterations of the hepatocyte and its organelles in type IIA and IIB hyperlipoproteinemia seem to fall into different categories: smaller nuclei, enlarged peroxisomes and altered mitochondria are found in both types of hyperlipoproteinemia, while an increase in the volume of hepatocytes is found only in type IIA. The enlargement of liver peroxisomes in untreated hyperlipoproteinemia is noteworthy, since it has been considered as a marker of the liver toxicity of lipid-lowering drugs.