Well-differentiated liposarcoma of the tongue. A case report.

Liposarcoma of the oral cavity is very rare. The difficulty in clinical and histopatologic differentiation of these oral lipomatous lesions have been recognized by several authors. The aim of this article is to present a case report of a well-differentiated lipoma-like liposarcoma of the tongue, in a 36-year-old woman, and to review the existing literature.

Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens.

Isoflavonoid phytoestrogens and lignans in plants are known to be constituents of animal and human food and recently they have been found in human urine and other biological materials. These compounds have received increasing attention because of their interesting biological properties and possible role in human cancer and other diseases. The present study demonstrates that the main mammalian lignan enterolactone (trans-2,3-bis[(3-hydroxyphenyl)methyl]-butyrolactone) and some other diphenols are moderate or weak inhibitors of human estrogen synthetase (aromatase) and that this lignan binds to or near the substrate region of the active site of the P-450 enzyme. The inhibition is competitive with respect to testosterone and androstenedione, and the lignan affinity is 1/75-1/300 that of these natural substrates. It is suggested that the high concentration of lignans in vegetarians, by inhibiting aromatase in peripheral and/or cancer cells and lowering estrogen levels, may play a protective role as antipromotional compounds during growth of estrogen-dependent cancers.

Identification of the isoflavonic phytoestrogen daidzein in human urine.

The identification by gas chromatography-mass spectrometry of the isoflavonic phytoestrogen daidzein [7-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one] for the first time in human urine is described. The metabolism and effect on reproduction of isoflavones in animals and the possible significance of phytoestrogens in man is discussed. Preliminary results on the quantitative excretion of daidzein in female subjects consuming different diets are also reported.

Detection and identification of the plant lignans lariciresinol, isolariciresinol and secoisolariciresinol in human urine.

The mammalian lignans enterolactone and enterodiol are regular constituents of human urine and are excreted daily in mumol amounts. They are produced by metabolic action of intestinal bacteria from natural plant lignan precursors which are constituents of various food plants. However, natural plant lignans seem to occur very seldom in detectable amounts in human urine. The present investigation shows that only in 5% of the 150 diphenolic fractions extracted from the urine of women plant lignans other than the previously identified matairesinol could be found. The lignans lariciresinol, isolariciresinol and secoisolariciresinol were identified for the first time by comparison of their GC characteristics and mass spectra with the corresponding results of authentic synthesized reference compounds. Secoisolariciresinol is one natural precursor of the mammalian lignan enterodiol. Of the two other plant lignans, no animal or human metabolic products are known. The occurrence of chemically unchanged plant lignans in some cases in human urine could be a result of an insufficient metabolic capacity of intestinal bacteria, resulting in a decreased detoxification of phenolic plant products.

Isotope dilution gas chromatographic-mass spectrometric method for the determination of lignans and isoflavonoids in human urine, including identification of genistein.

We describe an isotope dilution gas chromatographic-mass spectrometric method for the quantitative determination of the lignans enterolactone, enterodiol and matairesinol and the isoflavonoids daidzein, equol, O-desmethylangolensin and genistein in urine. Furthermore we present the gas chromatographic/mass spectrometer identification of genistein. Urine samples were extracted on Sep-Pak cartridges, conjugated fractions were isolated by chromatography on the acetate form of DEAE-Sephadex and deuterated internal standards of all seven compounds were added to the samples before hydrolysis. The hydrolysate was extracted on a Sep-Pak cartridge and following chromatography on the acetate form of QAE-Sephadex two fractions were obtained: Fraction 1 contained equol, enterolactone, enterodiol, matairesinol and all estrogens and fraction 2 contained O-desmethylangolensin, daidzein and genistein. The latter was ready for gas chromatography/mass spectrometry, but the first one was further purified to eliminate the estrogens by chromatography on the carbonate form of QAE-Sephadex. Following silylation, the samples were analyzed by combined capillary column gas chromatography/mass spectrometry in the selective ion monitoring mode. The within-assay imprecision varied from 0.8-15.2% (mean 8.7%) and the between-assay imprecision from 4.1-13.9% (mean 9.3%), depending on compound and concentration level. The mean recovery of authentic standards added to urine extracts before hydrolysis varied from 96.6 to 105.5%. Values obtained from 10 Finnish omnivorous men are presented. Individual values for matairesinol (excretion range 3.3-59.9 nmol/24 h) and genistein (range 21.8-1180 nmol/24 h) in human urine have never been published before.

Identification of lignans and phytoestrogens in urine of chimpanzees.

It was recently observed that the urinary excretion of animal lignans is low in postmenopausal breast cancer patients compared to normal omnivorous and vegetarian women. In addition, the mean excretion of the isoflavonic phytoestrogen equol tended to be lower. Because nonhuman primates appear to be remarkably resistant to the carcinogenic effect of estrogens, we investigated the possible occurrence of lignans and phytoestrogens in the urine of chimpanzees on their regular diet. Five major diphenols were isolated and identified by capillary gas chromatography and mass spectrometry by comparison with synthesized authentic reference compounds. Three of these compounds, the phytoestrogen equol and its precursor daidzein, the lignan enterolactone, were according to preliminary assays excreted in very large amounts. In addition, the lignan enterodiol and the daidzein metabolite O-desmethylangolensin were identified. It is concluded that the chimpanzee excretes both isoflavonic phytoestrogens and lignans in urine, apparently in high concentrations. It is suggested that these compounds may play a role in the maintenance of the resistance against carcinogenic effects of estrogens, which nonhuman primates possess, because both equol and enterolactone have been shown to have antiestrogenic properties in animals. However, much further work is necessary before the possible biological role of these compounds may be established.

Effect of diet on lignans and isoflavonoid phytoestrogens in chimpanzees.

Diphenolic compounds belonging to the classes of lignans and isoflavonoids have been identified in urine of man and animals, including the chimpanzee. Some of these compounds, formed by intestinal bacteria from plant lignans and phytoestrogens, have been shown in animal studies to exhibit biological activities that suggest they could function as cancer-protective compounds. The effect of diet on urinary excretion of these compounds in the adult male chimpanzee has been studied. It was found that the chimpanzees consuming their regular food excreted large amounts of the isoflavonoid phytoestrogens, equol (mean +/- SE) (127.5 +/- 34.0 nmol/mg cr.) and daidzein (20.7 +/- 9.0 nmol/mg cr.) and the lignan, enterolactone (14.1 + 3.5 nmol/mg cr.). Small amounts of the lignan, enterodiol, (0.4 +/- 0.2 nmol/mg cr.) were also excreted. On all other four test diets (high protein, high carbohydrate, high vegetable, and high fat), the excretion was less, particularly on a high fat diet where the excretion of all diphenolic compounds was reduced by more than 90% to a level observed in omnivorous human subjects or women with breast cancer. These results suggest that diet profoundly influences the excretion of both animal lignans and phytoestrogens in urine. Because non-human primates are particularly resistant to mammary and genital carcinoma on estrogen treatment, the present data suggest that the very high levels of phytoestrogens and lignans as found during exposure to the regular diet may partially account for why these primates are so resistant to hormonal manipulations to induce cancer.

Inhibitory effect of silibinin on tumour necrosis factor-alpha and hydrogen peroxide production by human monocytes.

Silibinin is a chemically defined flavonoid and the main active component of silymarin, a polyphenolic complex from Silybum marianum, which has anti-inflammatory, hepatoprotective and anticarcinogenic properties. Monocytes obtained from healthy individuals were incubated with silibinin to evaluate cell viability, hydrogen peroxide (H(2)O(2)) release and tumour necrosis factor-alpha (TNF-α) production by these cells. The duration of treatment and different silibinin concentrations had no significant effect on cell viability. Monocytes showed a dose-dependent inhibitory effect on H(2)O(2) release by phorbol myristate acetate-stimulated monocytes in silibinin concentrations ranging from 6.25 to 50 µg mL(-1). Significant inhibition of TNF-α production by lipopolysaccharide-stimulated monocytes was observed at concentrations of 12.5, 50 and 100 µg mL(-1) of silibinin. These results suggest that silibinin exerts antioxidant and anti-inflammatory properties on human monocytes through an inhibitory effect on H(2)O(2) release and on TNF-α production, respectively.

Anatomical distribution of exogenous 14C-oxalate in the rat by macroautoradiography.

A single dose of 14C-oxalate was given to a group of laboratory rats using a gastric tube. The animals were then killed at intervals of 1/2, 2, 5, 24 and 72 h following oxalate administration and the oxalate distribution was determined using the technique of macroautoradiography. The results showed that a large proportion of the absorbed oxalate was already excreted in the bladder 30 min after administration. The non-absorbed oxalate was found eliminated with the faeces after 24 h. At the same time, 14C-oxalate was demonstrated in the bones; whereas 72 h later no radioactivity could be found anymore. It is conceivable, therefore, that the rapid renal excretion of exogenous oxalate may lead to a short-term oxalate peak in the urine. More importantly, the occurrence of such a urinary oxalate peak could in turn be responsible for crystalluria and stone formation.

Absorption of oxalic acid in rats by means of a 14C method.

13 rats received a daily dose of 0.5 ml of a 1% solution of 14C-marked sodium oxalate (specific activity 29 nCi/ml) administered in one application with a throat probe. Feces and urine were collected every 24 h and the amount of 14C-oxalate was determined by liquid scintillation counting. The average distribution for 13 rats during 7 days showed 25.2% of 14C-oxalate in the urine and 73.4% in the feces. The rate of absorption is considerably higher than values given in literature (2.6--12% urine). These results indicate that in the pathogenesis of calcium oxalate stone formation some possible significance must be attributed to the exogenic oxalate.

Isolated biotin-resistant deficiency of 3-methylcrotonyl-CoA carboxylase presenting as a clinically severe form in a newborn with fatal outcome.

The son of Kurdish, consanguineous parents (cousin marriage) presented from the first day of life with initially focal and later generalized attacks of epileptic seizures and a severe generalized muscular hypotonia. Urinary excretion of 3-hydroxyisovalerate and of 3-methylcrotonylglycine was persistently increased. Diagnosis of isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency was confirmed in cultured fibroblasts. Psychomotor retardation was progressive, seizures and marked EEG abnormalities persisted. Treatment with leucine and protein-resistricted diet under hospital control did not significantly improve these conditions. The patient died from a cardiac and circulatory failure after a prolonged epileptic attack, with bronchial aspiration. The non-responsiveness of our patient to therapy and the fatal outcome indicate the existence of a severe neonatal variant of this otherwise rather benign genetic enzyme deficiency.

Identification of the phyto-oestrogen 3',7-dihydroxyisoflavan, an isomer of equol, in human urine and cow's milk.

The isoflavonoid diphenol 3',7-dihydroxyisoflavan, an isomer of the known compound equol (4',7-dihydroxyisoflavan), has been identified in human urine and in cow's milk. The compound was isolated as the glucuronide, purified by column chromatography and identified after hydrolysis to the aglycon. The trimethylsilyl ether derivative was characterized by comparison of its mass spectrum and chromatographic properties with those of synthesized silylated isomers of equol.

Urinary estrogen profile determination in young Finnish vegetarian and omnivorous women.

For a long time it has been postulated that diet may influence estrogen metabolism and in this way affect breast cancer risk. In order to investigate possible effects of variations of dietary fiber intake on estrogen metabolism, the urinary estrogen profile (13 estrogens), including the catecholestrogens, was determined in one 72-h summer and one winter sample collected in the midfollicular phase of the menstrual cycle by 11 lactovegetarian and 12 omnivorous young Finnish women. Urinary estrogens were purified by ion-exchange chromatography and the quantitative determination was carried out by capillary gas chromatography-mass spectrometry. Detailed records of the subjects' diet during one 5-day period in summer and one in winter were obtained and dietary fiber intake calculated. The mean difference with regard to intake of total fiber in the two dietary groups was 3 g/day in the summer (not significant) and 5 g/day in the winter (P less than 0.05), the mean (geometric) consumption being 23 and 19 g/day by the vegetarian and omnivorous women, respectively. Within the groups we found seasonal variation in fiber intake only for the omnivorous women. During winter, compared to summer, the omnivorous women consumed significantly less grain (P less than 0.001), vegetable (P less than 0.02) and total fiber (P less than 0.02). The excretion of 13 estrogens was remarkably constant in the omnivoric group but a significant seasonal variation of total and individual catecholestrogens and of estrone was observed in the vegetarians (P less than 0.05-0.005). The quantitatively most important estrogen was 2-hydroxyestrone, followed by estrone, estriol, 2-hydroxyestradiol, 4-hydroxyestrone and estradiol, the three latter being excreted in similar amounts. Between the dietary groups there were no significant differences in excretion of total or individual urinary estrogens in any season or between the mean values for both seasons. However, numerous significant (P less than 0.05-0.01) negative correlations between dietary intake of total or grain fiber/kg body weight and the excretion of individual estrogens were found. These correlations disappeared if the fiber intake was not related to body weight. We conclude that dietary fiber intake significantly affects estrogen metabolism by reducing estrogen excretion in urine and that grain fiber seems to be most important in that respect. One of the mechanisms involved is a partial interruption of the enterohepatic circulation of the estrogens, due to alterations of the intestinal metabolism and reabsorption of these steroids, caused by the fiber.

Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets.

Recently two groups of compounds with diphenolic structure, the lignans and the isoflavonic phytoestrogens, were detected and identified in human urine and other biological fluids. These compounds are of great biological interest because they exhibit both in vitro and in vivo weak estrogenic and sometimes also antiestrogenic activities and many plant lignans have been shown to have anticarcinogenic, antiviral, antifungal and other interesting biological effects. The compounds found in relatively large amounts (10-1000 times more than estrogens) in urine are modified by intestinal bacteria from plant lignans and phytoestrogens, which are present in fiber-rich food such as grain and beans. They bind with low affinity to estrogen receptors and preliminary results suggest that they may induce production of sex hormone binding globulin (SHBG) in the liver and in this way may influence sex hormone metabolism and biological effects. Five compounds, the lignans enterolactone (Enl), enterodiol (End) and the isoflavonic phytoestrogen metabolites daidzein (Da), equol (Eq) and O-desmethylangolensin (O-Dma) were measured in urine by gas chromatography-mass spectrometry (selected ion monitoring) using deuterated internal standards in 5 groups of women (total number 53). The members of three dietary groups (omnivores, lactovegetarians and macrobiotics) were living in Boston and of two groups in Helsinki (omnivores and lactovegetarians). Until now measurements have been carried out in 94 72-h samples. The highest mean excretion of the most abundant compound, enterolactone, was found in the macrobiotic group and the lowest in the omnivoric groups. Total mean 24-h excretion of enterolactone was 17,680 nmol in the macrobiotics, 4,170 nmol in the Boston lactovegetarians, 3,650 nmol in the Helsinki lactovegetarians, 2,460 nmol in the Helsinki omnivores and 2,050 nmol in the Boston omnivores. The other diphenols followed approximately the same pattern. In an earlier study the lowest excretion of enterolactone (1,040 nmol/24 h) was found in a group of postmenopausal apparently healthy breast cancer patients living in Boston. It is concluded that further studies are necessary to elucidate the possible role of these compounds in cancer and other diseases. However, the evidence obtained until now seems to justify the conclusion that these compounds may be among the dietary factors affording protection against hormone-dependent cancers in vegetarians and semivegetarians.

Effect of dietary components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of estrogens and on sex hormone binding globulin (SHBG).

A brief account of our present knowledge on the enterohepatic metabolism of estrogens and on the origin, metabolism and biological effects of mammalian lignans and phytoestrogens is undertaken. Furthermore, recently published results on the effects of dietary fiber, fat and carbohydrates on estrogen metabolism are reviewed. New preliminary results are presented on quantitative assays of lignans and phytoestrogens in urine of women belonging to various dietary and population groups and in a group of chimpanzees. The highest values of lignans and phytoestrogens were found in the non-human primates, and in macrobiotic, lactovegetarian and Japanese women, all groups considered having a low risk for the development of breast and other hormone-dependent cancer. New results on correlations between intake of various fibers, lignan and phytoestrogen excretion and plasma levels of estrogens, free testosterone and SHBG in women are presented. There is a significant positive correlation between the intake of fiber and urinary excretion of lignans and phytoestrogens, and the concentration of plasma SHBG. Fiber intake and urinary excretion of lignans and equol correlated negatively with plasma percentage free estradiol. Enterolactone excretion correlated negatively with plasma free testosterone. It is concluded that dietary macro- and micronutrients seem to play an important role in estrogen metabolism.

Reduction of exogenous oxalate in urine of rats by binding with aluminium-oxyhydrate (Andursil) and an anion-exchanger (Colestid) in the intestinal tract.

The influence of calcium carbonate, aluminium oxyhydrate (Andursil) and an anion exchanger (Colestid) on the absorption of oxalate from the intestine in rats was investigated. The animals were administered daily doses of 15mg oxalate as a 14C-sodium-oxalate solution by means of a throat probe, and the substances of interest were mixed with the food. The intake of food and the 14C-activity in the urine were measured during four urine-collecting periods of 3 days each. The quantity of the enterally administered oxalate excreted with urine has a negative correlation to the amount of the investigated test substances ingested with food.

[Test of efficacy of an oxalate-binding anion exchanger Colestid in healthy subjects for use in idiopathic calcium-oxalate urolithiasis]. / Prüfung der Wirksamkeit eines oxalatbindenden Anionenaustauschers Colestid an gesunden Probanden zum Einsatz bei der idiopathischen Calcium-Oxalat-Urolithiasis.

Sodium oxalate (402 mg) was administered in a single dose to 10 healthy volunteers receiving a controlled diet. Half the group received 3 times 10 g Colestid and the other half 4 times 2 g Andursil. On the 5th day the oxalate load was repeated. Urine was collected within 32 hours following oxalate application in 8 fractions. In each fraction the levels of oxalate, calcium, phosphate and uric acid were determined. The amount of oxalate, phosphate and uric acid measured in the group receiving Colestid was lower in all fractions. Peak excretions of oxalate found in unmedicated volunteers were suppressed following oxalate load. In the group receiving Andursil, only the excretion of phosphate was decreased. The results presented suggest that Colestid may be promising in the prevention of calcium-oxalate-urolithiasis.

[Modification of urinary pH through ascorbic acid]. / Beeinflussung des Urin-pH durch Ascorbinsäure.

The influence of orally administered ascorbic acid on the urinary pH of 10 healthy volunteers and 10 patients with infected urine was investigated. During a four-day period of investigation urinary pH and the concentration of ascorbic acid in the respective urines were measured five times a day. On the second and third day three times a dose of 2 g ascorbic acid was given, while the diet was under control all four days. A correlation between pH decrease and ascorbic acid concentration is only observed if the concentration of the latter is higher than 200 mg%. The mean decrease in urinary pH between days with ascorbic acid supply and days without is -0,16 pH units for the volunteers respectively -0,18 pH units for the patients. Therefore, vitamin C can not be recommended to lower the pH of alkaline urines.

Localization of exogenous 14C-oxalate in rats determined by whole-body- and microautoradiography.

A single dose of 14C-oxalate was given to Wistar rats using a throat probe. The animals were sacrificed and the oxalate distribution was determined using whole-body-autoradiography. The results showed that a large portion of the absorbed oxalate had reached the bladder 30 min after administration. It is possible that this rapid renal excretion could lead to a short-term oxalate peak in the urine. The oxalate also showed a great affinity for bone. This suggests that there is a deep compartment for oxalate in bone. At the light microscopic level, the localization of 14C-oxalate in bone and in the gastric wall was demonstrated using microautoradiography. This appears to show that there is gastric excretion of absorbed oxalate. Further pharmacokinetic investigations are necessary to confirm this conclusion.

Diet and urinary estrogen profile in premenopausal omnivorous and vegetarian women and in premenopausal women with breast cancer.

The urinary estrogen profile was studied in the midfollicular phase twice, and diet four times during 1 yr in 10 premenopausal breast cancer (BC) patients consuming an omnivorous normal Finnish diet and in two control groups, one consuming an omnivorous (n = 12) and the other a lactovegetarian (n = 11) diet. Total fat intake in relation to caloric intake was almost identical in all three groups. Only with regard to grain fiber intake did the BC patients differ significantly from both other groups. No differences were found between the groups with regard to urinary excretion of 13 individual estrogens and total estrogens, with the exception of 4-hydroxyestrone (4-OH-E1), which was significantly lower (P less than 0.05) in the BC group than in the vegetarians. A high carbohydrate to protein ratio in the diet had a negative correlation with the excretion of 2-hydroxyestrogens and 2-hydroxyesterone (2-OH-E1) to 4-OH-E1 ratio. The BC group had significantly higher urinary 2-OH-E1 to E1 ratio (P less than 0.05) compared to the vegetarians. The 2-OH-E1 to 4-OH-E1 ratio was highest in the BC group (= 7.1) and differed significantly from that of the omnivores (= 4.3; P less than 0.02) and vegetarians (= 3.6; P less than 0.005). This ratio showed a negative correlation with intake of carbohydrates, starch, total and grain fiber. Urinary excretion of 4-OH-E1 correlated positively with total and grain fiber intake and plasma SHBG. Protein intake correlated positively with urinary 2-methoxy-E1 excretion, and retinol intake positively with catechol estrogen, E1 and E2 excretion. It is concluded that estrogen production and urinary estrogen profile in premenopausal breast cancer patients is normal with the exception of a low 4-OH-E1 excretion and high urinary 2-OH-E1 to 4-OH-E1 ratio. This ratio, which seems to depend on diet, is the only urinary estrogen parameter separating premenopausal BC patients from the control omnivorous and lactovegetarian women.