Changes In Urinary Excretion Research Articles

A simple LC-MS/MS method for quantitative analysis of underivatized neurotransmitters in rats urine: assay development, validation and application in the CUMS rat model.

Many amino acid neurotransmitters in urine are associated with chronic stress as well as major depressive disorders. To better understand depression, an analytical LC-MS/MS method for the simultaneous determination of 11 underivatized neurotransmitters (4-aminohippurate, 5-HIAA, glutamate, glutamine, hippurate, pimelate, proline, tryptophan, tyramine, tyrosine and valine) in a single analytical run was developed. The advantage of this method is the simple preparation in that there is no need to deconjugate the urine samples. The quantification range was 25-12,800 ng mL(-1) with >85.8% recovery for all analytes. The nocturnal urine concentrations of the 11 neurotransmitters in chronic unpredictable mild stress (CUMS) model rats and control group (n = 12) were analyzed. A series of significant changes in urinary excretion of neurotransmitters could be detected: the urinary glutamate, glutamine, hippurate and tyramine concentrations were significantly lower in the CUMS group. In addition, the urinary concentrations of tryptophan as well as tyrosine were significantly higher in chronically stressed rats. This method allows the assessment of the neurotransmitters associated with CUMS in rat urine in a single analytical run, making it suitable for implementation as a routine technique in depression research.

Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment.

To quantify changes in urinary excretion of aquaporin2 water channels (u-AQP2), the sodium-potassium-chloride co-transporter (u-NKCC2) and the epithelial sodium channels (u-ENaC) during treatment with bendroflumethiazide (BFTZ), amiloride and placebo. In a randomized, double-blinded, placebo-controlled, 3-way crossover study we examined 23 healthy subjects on a standardized diet and fluid intake. The subjects were treated with amiloride 5 mg, BFTZ 1.25 mg or placebo twice a day for 4.5 d before each examination day. On the examination day, glomerular filtration rate was measured by the constant infusion clearance technique with (51)Cr-EDTA as reference substance. To estimate the changes in water transport via AQP2 and sodium transport via NKCC2 and ENaC, u-NKCC2, the gamma fraction of ENaC (u-ENaCγ), and u-AQP2 were measured at baseline and after infusion with 3% hypertonic saline. U-NKCC2, u-ENaCγ, u-AQP2 and plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensin II (p-ANG II) and aldosterone (p-Aldo) were measured, by radioimmunoassay. Central blood pressure was estimated by applanation tonometry and body fluid volumes were estimated by bio-impedance spectroscopy. General linear model with repeated measures or related samples Friedman's two-way analysis was used to compare differences. Post hoc Bonferroni correction was used for multiple comparisons of post infusion periods to baseline within each treatment group. At baseline there were no differences in u-NKCC2, u-ENaCγ and u-AQP2. PRC, p-Ang II and p-Aldo were increased during active treatments (P < 0.001). After hypertonic saline, u-NKCC2 increased during amiloride (6% ± 34%; P = 0.081) and increased significantly during placebo (17% ± 24%; P = 0.010). U-AQP2 increased significantly during amiloride (31% ± 22%; P < 0.001) and placebo (34% ± 27%; P < 0.001), while u-NKCC2 and u-AQP2 did not change significantly during BFTZ (-7% ± 28%; P = 0.257 and 5% ± 16%; P = 0.261). U- ENaCγ increased in all three groups (P < 0.050). PRC, AngII and p-Aldo decreased to the same extent, while AVP increased, but to a smaller degree during BFTZ (P = 0.048). cDBP decreased significantly during BFTZ (P < 0.001), but not during amiloride or placebo. There were no significant differences in body fluid volumes. After hypertonic saline, u-NKCC2 and u-AQP2 increased during amiloride, but not during BFTZ. Lower p-AVP during BFTZ potentially caused less stimulation of NKCC2 and AQP2 and subsequent lower reabsorption of water and sodium.

Validation of urinary calcium isotope excretion from bone for screening anabolic therapies for osteoporosis.

Urinary excretion of calcium tracers in labeled individuals decreases in response to antiresorptive therapy, providing a tool to rapidly screen potential therapies. Using teriparatide, we demonstrate in this study that anabolic therapy also decreases tracer excretion, confirming that this method can also be used to screen potential anabolic therapies. Changes in urinary excretion of calcium tracers from a labeled skeleton may be a rapid and sensitive method to screen potential therapies for osteoporosis. This method has been used to screen antiresorptive therapies, but the effect of anabolic therapies on tracer excretion is unknown. Eight-month-old female Sprague Dawley rats (n = 11) were given 50 μCi (45)Ca iv. After a 1-month equilibration period, baseline urinary (45)Ca excretion and total bone mineral content (BMC) were measured. Rats were then treated with 30 μg/kg teriparatide sc per day, a bone anabolic agent, for 80 days. Urine was collected throughout the study and analyzed for (45)Ca and total Ca, and BMC was measured at the beginning and end of the study. Teriparatide decreased urinary (45)Ca excretion by 52.1 % and increased BMC by 21.7 %. The change in bone calcium retention as determined by the ratio of (45)Ca to total Ca excretion in urine from day 6 through 15 of teriparatide treatment was significantly correlated (p = 0.036) with the change in BMC after 80 days of teriparatide treatment. Urinary excretion of calcium tracers from labeled bone is an effective method to rapidly screen potential anabolic therapies for osteoporosis.

EVALUATION OF DIURETIC ACTIVITY OF MILK EXTRACT OF SEMECARPUS ANACARDIUM NUT

Semi carpus anacardium ‘Marketing Nut’ is a tropical flowering plant widely distributed in India. Semicarpus anacardium are widely used for its therapeutic potential as immunomodulatory and in folklore the plant material is reported in the treatment of diureti c. Since, the diuretic activity of these plant materials has not been investigated in scientifically controlled studies; the aim of the present study was to evaluate the diuretic potenti al of milk extracts of Semicarpus anacardium seed in normal rats after acute and sub - chronic oral administration. Milk extracts of Semicarpus anacardium seed (150 and 300 mg/kg) along with the reference drug, furosemide (10 mg/kg) were administrated orally to male Wistar rats for 8 subsequent days and their urine output was quantitated at several intervals of time after the dose. Several other parameters such as urinary electrolyte concentration, plasma electrolyte conc entration and creatinine clearance were also measured by flame spectrophotometry and Jaffe alkaline picrate method. After administration of single dose of the milk extracts of Semicarpus anacardium seed, urine output significantly showed equivalent increment at all time points, and at 24 h after the dose, the total volume of urine excreted was highest in furosem ide followed by plant extracts and control group. Both extracts increased the urinary levels of Na + and K + , to about the same extent, while furosemide increased urinary levels of only Na + and decreased urinary K + . Despite changes in urinary excretion of t he electrolytes, plasma Na + and K + levels were not affected by any of the substances. The present study supports the ethnomedical use of Semicarpus anacardium seed for their diuretic effect

PP094. A comparison of gestational changes in urinary excretion of magnesium with those of calcium

Magnesium is one of the essential minerals required in various cellular functions. Some investigators have postulated that some aspects of pathophysiology in preeclampsia could be associated with alteration in regulatory mechanisms of the mineral. However, gestational changes in absorption, excretion and blood concentration of magnesium have remained less elucidated compared with those of calcium, which is another important mineral forming a divalent cation. The purpose of this study was to clarify if urinary excretion of magnesium during pregnancy might be altered compared with those of calcium. Sixty specimens of 24h urine and 586 samples of spot urine were collected from healthy pregnant women who gave consent. Determination of the minerals were according to Orthocresol-phthalein complexone method for calcium, and xylidyl blue method for magnesium. Urinary creatinine was determined by Jaffe Method. Daily excretions of magnesium determined with 24h samples were 60, 70, 81, 65, and 102mg in 1st, 2nd, and early 3rd trimesters, term, and postpartum 4weeks, respectively. There were no statistical differences among the values. Those of calcium were 174, 186, 139, 52, and 40mg, respectively. The values in term and in postpartum were significantly lower than those in 1st through early 3rd trimesters. The Mg/Cr ratios (mg/mg Cr) determined with spot urine samples were 0.064, 0.071, 0.066, 0.067, and 0.086, in 1st, 2nd, and early 3rd trimesters, term, and postpartum 4weeks, respectively. The value of Mg/Cr in postpartum was significantly higher than the values in pregnant period. The Ca/Cr ratios (mg/mg Cr) were 0.164, 0.163, 0.135, 0.118, and 0.090, respectively. There was a trend of decreasing pattern in changes of Ca/Cr from 2nd trimester to postpartum. It is suggested that there is a mechanism of preservation of calcium in the late phase of pregnancy or puerperal period by reducing urinary excretion of the mineral. However, human pregnancy does not seem to show such a function controlling magnesium metabolism.

A Prospective Study for the Prediction of Preeclampsia with Urinary Calcium Level

To assess the efficacy of calciuria as a diagnostic test for the prediction of preeclampsia, and also to determine the changes in urinary excretion of calcium in preeclampsia and normotensive women. A prospective study was conducted on 60 primi mothers in the age group of 20-30years, and all were enrolled at 16weeks of gestation with clinical follow up by 4weeks and 24h urinary calcium and creatinine estimation. Ten mothers developed preeclampsia (study groups) and fifty remained normotensive (control groups). By means of Receiver-operator curve, a cut-off level of urinary calcium in 24h was chosen for predicting preeclampsia. Preeclamptic women excreted significantly less total urine calcium (87.0±3.59mg/24h) than normotensive women (303.68±17.699mg/24h) (p<0.0001) at 40weeks of gestation. Urinary calcium and calcium/creatinine (Ca:Cr) ratio decreases progressively from 28weeks to 40weeks in the study group when compared to normotensive group. Preeclamptic women excrete less calcium than normotensive women. This parameter would predict preeclampsia earlier in pregnancy.

Mathematical model gives insights into vitamin B6 and kynurenine metabolism

Vitamin B6 deficiency and oral contraceptive (OC) use have been associated with impaired tryptophan (trp) metabolism. To investigate the underlying mechanism, we developed a mathematical model of trp metabolism via the kynurenine pathway. The model includes kinetics from gut to liver, muscle and brain as well as trp concentrations in portal and peripheral circulation. Regulatory mechanisms and inhibition of relevant enzymes were included. Changes in urinary excretion of trp catabolites were observed as a function of vitamin B6 status using our model. Excretions of kynurenine, 3‐hydroxykynurenine and xanthurenic acid were increased in vitamin B6 deficiency as reported in the literature. Predicted effects of a trp load alone or concurrent with vitamin B6 deficiency also were consistent with experimental data. Dynamic variations of trp and trp metabolites were observed after simulation of trp input due to meals. Changes in trp metabolites concentrations were seen after induction of tryptophan 2,3‐dioxygenase alone or in combination with impaired B6 status as reported in OC users. Our findings support the use of this mathematical model as a tool to test trp metabolism in different conditions to complement, clarify and provide new insights into the associations of altered trp metabolism with OC use and vitamin B6 deficiency. Supported by NIH grant DK072398, and NSF grants DMS‐061670 (MR, HFN), EF‐1038593 (HFN. MR).

Diuretic and potassium-sparing effect of isoquercitrin—An active flavonoid of Tropaeolum majus L.

Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic effects supporting the ethnopharmacological use of this plant as diuretic. In the present work, phytochemical investigation, guided by bio-assay in spontaneously hypertensive rats (SHR), was carried out in order to identify the compounds responsible for diuretic action. Chromatographic fractionation of the hydroethanolic extract yielded an active fraction (TMLR) rich in isoquercitrin. TMLR (25-100mg/kg) and isoquercitrin (5-10mg/kg), as well the reference drug hydrochlorothiazide (10mg/kg) were orally administered in a single dose or daily for 7 days to SHR. The urine excretion rate, pH, density, conductivity and content of sodium (Na(+)) and potassium (K(+)) electrolytes were measured in the urine of saline-loaded animals. The urinary excretion rate was dose-dependently increased in both TMLR and isoquercitrin groups, as well as Na(+). Despite the changes in urinary excretion of electrolytes, the plasmatic levels of Na(+) and K(+) had not been changed. In addition, we did not find any evidence of renal toxicity or other adverse effects in these animals, even after prolonged treatment with TMLR or isoquercitrin. This research supports and extends the ethnomedicinal use of T. majus as diuretic. This activity seems to be associated to the presence of the flavonol isoquercitrin.

Acid-base conditions regulate calcium and magnesium homeostasis

Previous experimental studies demonstrate that the acid-base balance influences mineral homeostasis by regulating the absorption of calcium and magnesium in the kidneys. No intervention studies are available on population samples. To study the urinary excretion of calcium and magnesium before and after an intervention with the aim of decreasing the acid load. Healthy subjects aged 50-75 years were recruited by advertising. Urinary calcium, magnesium and urea as well as blood pressure were measured before and after the intervention. This comprised taking tablets containing potassium hydrogen carbonate or potassium chloride (placebo) during 7-10 days. There were significant relationships between the urinary excretion of urea and magnesium and calcium before the intervention. Comparing before and after intervention, the change in urinary excretion of urea was related to a change in urinary excretion of calcium and magnesium. There was a significant decrease in systolic as well as diastolic blood pressure both after administration of potassium hydrogen carbonate and citrate. The results confirm previous studies showing a relation between acid conditions in the body and the excretion of calcium and add new data on magnesium. A blood pressure decrease after potassium has been found in previous studies. This suggests an alternative for the treatment of moderately increased levels of blood pressure that should be further explored.

Diurnal Changes in Urinary Excretion of IgG, Transferrin, and Ceruloplasmin Depend on Diurnal Changes in Systemic Blood Pressure in Normotensive, Normoalbuminuric Type 2 Diabetic Patients

Previous studies of diabetic patients indicate that increased urinary excretion of certain plasma proteins (molecular radii <55 A), such as IgG, transferrin, and ceruloplasmin, precede the development of microalbuminuria. Moreover, increases in these urinary proteins predict future development of microalbuminuria. To clarify whether blood pressure changes influence urinary excretion of these proteins, we examined relationships between diurnal blood pressure changes measured by ambulatory blood pressure monitoring and urinary excretion of IgG, transferrin, ceruloplasmin, alpha2-macroglobulin (88 A) and albumin (36 A) measured separately during the day and night in 20 healthy controls and 26 normotensive, normoalbuminuric diabetic patients. Diurnal change in systolic blood pressure was not correlated to urinary excretion of either albumin or alpha2-macroglobulin in either diabetic patients or controls. However, statistically significant correlations between diurnal changes in systolic blood pressure and those of urinary excretion of IgG, transferrin and ceruloplasmin were found in diabetic patients but not in controls. The present findings suggest that urinary excretion of IgG, transferrin, and ceruloplasmin are more easily affected than albuminuria by systemic blood pressure changes in normoalbuminuric diabetic patients. This is supported by our previous finding that urinary excretion of IgG, transferrin and ceruloplasmin increased while albuminuria did not following enhanced glomerular filtration rate after acute protein loading, which causes increased glomerular capillary pressure due to afferent arterioles dilation, mimicking diabetic intra-renal hemodynamics. Taken together, these findings suggest that urinary excretion of IgG, transferrin, and ceruloplasmin may be more sensitive indicators of glomerular capillary pressure change than albuminuria in normoalbuminuric diabetic patients.

Effects of endotoxin derived from Escherichia coli lipopolysaccharide on the pharmacokinetics of drugs

Lipopolysaccharide (LPS) endotoxin is an active component in the outer membrane of Gram-negative bacteria. LPS is usually used as an animal model of chronic inflammation such as sepsis. During inflammation, development of diarrhea, and changes in the plasma protein bindings, in the hepatic and/or intestinal microsomal cytochrome P450 (CYP) isozymes, and in the renal excretion of drugs have been reported. Thus, in rats pretreated with lipopolysaccharide endotoxin isolated from Escherichia Coli (ECLPS rats), the absorption, the distribution, the metabolism, and the excretion of drugs could be expected to alter. Interestingly, in ECLPS rats, the time-dependent effects on the hepatic CYP isozymes have been reported. Thus, in ECLPS rats, the pharmacokinetics of drugs which are mainly metabolized via hepatic CYP isozymes could be expected to be time-dependent. In this review, an attempt to explain changes in the pharmacokinetics of drugs reported in the literature was made in terms of hepatic CYP isozyme changes or urinary excretion changes in ECLPS rats.

Effect of Acarbose on the Increased Plasma Concentration of Uric Acid Induced by Sucrose Ingestion

Sucrose is converted fructose and glucose, which may increase plasma uric acid concentration (pUA) through increased purine degradation and/or decreased uric acid (UA) excretion. To investigate effects of acarbose, an inhibitor of alpha-glucosidase, on the increased pUA from sucrose administration, we measured pUA and urinary UA excretion in 6 healthy subjects before and after administering sucrose, with and without co-administration of acarbose. Sucrose raised pUA by 10% (p < 0.01). However, excretion and fractional clearance of UA were unchanged. Sucrose and acarbose coadministration also increased pUA, but less than did sucrose alone (sucrose: 4.9 to 5.4 mg/dl; sucrose + acarbose, 4.7 to 4.9 mg/dl, p < 0.05) without changes in urinary excretion and fractional clearance of UA. Acarbose appears to attenuate the rise in pUA by sucrose ingestion by inhibiting sucrose absorption.

Effects of hepatic injury or kidney injury on the tryptophan–niacin metabolism in rats

Abstract Hepatic α-amino-β-carboxymuconate-e-semialdehyde decarboxylase (ACMSD) plays a key role in regulating NAD biosynthesis. In normal rats, ACMSD has been generally detectable only in the liver and kidneys. Therefore, there is a possibility that liver or kidney injury affects tryptophan–niacin metabolism. We previously reported the significant change of tryptophan–niacin metabolism in rats with liver cirrhosis or in rats with d -galactosamine injected liver injury. In this experiment, we investigated the change of tryptophan–niacin metabolism in rats treated with puromycin aminonucleoside (PAN)-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan–niacin conversion. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. The reduction of urinary excretion of niacin in nephrotic rats may be due to the reduction of blood tryptophan concentration. The role of the kidney ACMSD may be insignificant concerning tryptophan–niacin conversion under this experimental condition.

Observation of changes in urinary excretion of thorium in humans following ingestion of a therapeutic soil

The study investigated the changes in urinary thorium excretion by humans following ingestion of a therapeutic soil, which contains about 10 ppm of thorium. This well-known healing earth in Germany has been considered as an alternative medicine for diarrhoea and gastric hyper-acidity. Six adult volunteers ingested this therapeutic soil in varying quantities for 1–15 days at levels approximating those described in the package insert of the medicine (10–60 g of soil per day). The subjects ingested about 0.1–0.6 mg of thorium daily, which is 100–600 times higher than the normal daily intake of about 1 μg thorium in Germany. All 24-h urine samples collected from the subjects during pre-ingestion, ingestion and post-ingestion periods of the soil were analyzed for 232Th using inductively coupled plasma mass spectrometry (ICP-MS). The measured excretion values varied in a wide range. Apparently, the high thorium amounts administered did not increase the 232Th excretion in urine as expected, suggesting that this soil ingestion will not result in a considerably higher and harmful uptake of thorium into the human body.

A reduction in alcohol consumption is associated with reduced plasma F 2-isoprostanes and urinary 20-HETE excretion in men

There is considerable evidence that chronic moderate-to-high alcohol consumption increases blood pressure. The mechanisms by which this occurs are not clear. Alcohol consumption can induce oxidative stress and cytochrome P450 (CYP450) isoforms that are associated with oxidative stress and may influence vascular tone. To study the role of such mechanisms we examined whether reducing alcohol intake in moderate-to-heavy drinkers (40–110 g/day) resulted in changes in urinary excretion of 20-HETE, a CYP450 metabolite of arachidonic acid, and plasma and urinary F 2-isoprostanes as markers of lipid peroxidation. After a 4-week run-in period during which healthy men maintained their usual drinking pattern they were randomized to a two-way crossover intervention study. In each of the 4-week treatment periods subjects either substituted their usual alcohol intake with a 0.9% alcohol beer or maintained their usual alcohol intake. Plasma and urinary F 2-isoprostanes and urinary 20-HETE were measured by gas chromatography mass spectrometry, and serum γ-glutamyl transpeptidase (γ-GT) was measured as a biomarker of alcohol consumption, at the end of each study period. Sixteen healthy men age 51.0 ± 2.7 years and with a BMI of 26.4 ± 0.61 kg/m 2 completed the study. The reductions in alcohol intake (72.4 ± 5.0 vs 7.9 ± 1.6 g/day, p < 0.001) and serum γ-GT (geometric mean 24.4 U/L (95% CI 19.7, 30.2) vs 18.6 U/L (95% CI 15.5, 22.2, p < 0.01) were accompanied by a significant fall in blood pressure as well as urinary 20-HETE excretion (158 ± 23 vs 109 ± 19 pmol/mmol creatinine, p < 0.001) and plasma F 2-isoprostanes (3438 ± 158 vs 2929 ± 145 pmol/L, p = 0.01). A substantial reduction in alcohol consumption in healthy men lowered plasma F 2-isoprostanes and urinary 20-HETE. Increased oxidative stress and 20-HETE production may be linked, at least in part, to the pathogenesis of alcohol-related hypertension.

Effect of Docosahexaenoic Acid Ingestion on Temporal Change in Urinary Excretion of Mercapturic Acid in ODS Rats.

We hypothesized a suppressive mechanism for docosahexaenoic acid (22:6n-3; DHA)-induced tissue lipid peroxidation in which the degradation products, especially aldehydic compounds, are conjugated with glutathione through catalysis by glutathione S-transferases, and then excreted into urine as mercapturic acids. In the present study, ascorbic acid-requiring ODS rats were fed a diet containing DHA (3.6% of total energy) for 31 days. Lipid peroxides including degradation products and their scavengers in the liver and kidney were determined, and the temporal change in the urinary excretion of mercapturic acids was also measured. The activity of aldehyde dehydrogenase, which catalyzes the oxidation and detoxification of aldehydes, tended to be higher in the liver of DHA-fed rats. The levels of lipid peroxides as measured by thiobarbituric acid-reactive substances and aldehydic compounds were higher and that of α-tocopherol was lower in the liver, and the pattern of temporal changes in the urinary excretion of mercapturic acids was also different between the n-6 linoleic acid and DHA-fed rats. Accordingly, we presume from these results that after dietary DHA-induced lipid peroxidation, a proportion of the lipid peroxidation-derived aldehydic degradation products is excreted into urine as mercapturic acids.

Water pH and urinary excretion in silver catfish Rhamdia quelen

The effect of acute exposure to different water pH levels on urinary excretion and plasma ion levels in silver catfish Rhamdia quelen was analysed. Fish were exposed to pH 4·0, 5·0, 7·5, 8·0, and 9·0 for 4 days and urine was collected. Other specimens were also exposed to the experimental pH for 24 h and blood was sampled. Urine flow rate, urine and plasma pH showed a significant trend to increase with the increase of water pH. Urinary Na+ excretion rate also increased and ammonia urinary excretion rate decreased with the increase of water pH. There was a significant trend to decrease volume, ammonia, Cl− and Na+ urinary excretion rate with increasing mass in fish exposed to all pH levels studied. Plasma ammonia levels showed a slight decrease in fish exposed to water pH from 4·0 to 8·0, but those exposed to water pH 9·0 presented the highest ammonia levels. Most plasma ions and urinary excretion changes observed in silver catfish exposed to acidic or alkaline water were similar to those already detected in rainbow trout Oncorhynchus mykiss. In addition, the kidney and urinary bladder might participate on acid–base balance in silver catfish, since urine pH changed according to plasma pH.

Urinary phytoestrogen excretion of rats bearing methylnitrosourea-induced mammary carcinoma in response to treatment with 2-methoxyestradiol

The effect of treating mammary tumor-bearing rats with 2-methoxyestradiol (2-MeE2) on the urinary excretion of 12 phytoestrogens was investigated and compared with the changes in urinary excretion of estradiol metabolites. Alterations of excretion were registered for isoflavonoids, lignans and coumestans. However, due to large variations statistical significant differences were found only for two lignans, i.e. significant increases of enterodiol and matairesinol. Since the single components of phytoestrogens showed diverse alterations, excretions were expressed also by the ratio of total isoflavonoids to total lignans and compared with the estrogen ratios 2-hydroxyestrone to 16α-hydroxyestrone and A-ring to D-ring metabolites. The ratio of isoflavonoids to lignans was consistently decreased, whereas both ratios of estradiol metabolites were highly increased. The latter effect is probably due to demethylation of 2-methoxyestrone resulting in high catechol estrogen levels in urine. These results suggest that the high levels of catechol estrogens, produced by 2-MeE2 treatment, may have influenced the urinary excretion pattern of phytoestrogens.

Diuretic activity of the aqueous extracts of Carum carvi and Tanacetum vulgare in normal rats

In the Moroccan traditional medicine, the ripe fruits of Carum carvi L . (Apiaceae) and the leaves of Tanacetum vulgare L . (Asteraceae/Compositae), two widely available plant materials, are used as diuretics. Since, the diuretic activity of these substances has not been investigated in scientifically controlled studies, the aim of the present study was to evaluate the diuretic potential of aqueous extracts of Carum carvi fruit (caraway) and the leaves of Tanacetum vulgare (tansy) in normal rats after acute and sub-chronic oral administration. Water extracts of Carum carvi and Tanacetum vulgare (100 mg/kg) or the reference drug, furosemide (10 mg/kg) were administrated orally to male Wistar rats and their urine output was quantitated at several intervals of time after the dose. After single doses of the extracts of both caraway seeds and tansy leaves, urine output was significantly increased at all time points, and at 24 h after the dose, the total volume of urine excreted was similar for the plant extracts and furosemide. Both extracts increased urinary levels of Na + and K +, to about the same extent, while furosemide increased urinary levels of only Na + and decreased urinary K +. Despite changes in urinary excretion of the electrolytes, plasma Na + and K + levels were not affected by any of the three substances. In the 8-day sub-chronic study, all three substances induced significant diuresis and natriuresis; only tansy increased urinary potassium excretion. The plant extracts did not appear to have renal toxicity or any other adverse effects during the study period. In conclusion, water extracts of both Carum carvi and Tanacetum vulgare have strong diuretic action confirming their ethnopharmacological use. From the pattern of excretion of water, sodium and potassium, it may be deduced that there are atleast two types of active principals present in these extracts, one having a furosemide-like activity and the other a thiazide-like activity.

Age-related and menopause-related changes of urinary excretion of C- and N-terminal cross-linked telopeptides of type I collagen and the relationships thereof with menopause-related bone loss

To study the age-related and menopause-related changes of urinary excretion of C- and N-terminal cross-linked telopeptides of type I collagen (uCTX/Cr and uNTX/Cr) and the relationships thereof with menopause state, years after menopause, bone mineral density (BMD), and menopause-related bone loss in healthy women. ELISA was used to examine the uCTX/Cr and uNTX/Cr of 659 female volunteers aged 20 - 80 in Changsha. Dual energy X-ray absorptiometry (DXA) was used to measure the BMD of various skeletal sites, including the lumbar vertebrae (L1 - L4) at anteroposterior (AP) position, L(2) - L(4) at lateral (LAT) position, hip, and forearm. 339 postmenopausal women among the 659 subjects were divided into 3 groups, osteoporotic, osteopenic, and normal groups according to the WHO criteria of osteoporosis diagnosis. (1) Both the curves of uCTX/Cr and uNTX/Cr with age were fit the best by regression analysis of cubic equation. The coefficients of determination (R(2)) were 0.139 for uCTX/Cr and 0.149 for uNTX/Cr. The levels of uCTX/Cr and uNTX/Cr of the women aged > 35 increased with age. (2) The values of uCTX/Cr and uNTX/Cr were 253 mg/mol +/- 101 mg/mol Cr and 63 nmol +/- 34 nmol BCE/mmol Cr respectively in the postmenopausal women, remarkably higher than those of the premenopausal women (149 mg/mol +/- 80 mg/mol Cr and 33 nmol +/- 17 nmol BCE/mmol Cr respectively), increased by 69.5% and 93.4% respectively. The annual change rates of uCTX/Cr and uNTX/Cr were the highest within the first 5 years after menopause, and these increases were in agreement with the significant decrease of BMD at most skeletal sites by 10.8% approximately 27.6%. (3) After controlled for age and body weight, both uCTX/Cr and uNTX/Cr showed significant negative correlation with BMD (r = -0.078 to -0.283, P < 0.05 or 0.01), and there was a significant positive correlation between uCTX/Cr and uNTX/Cr. (4) The elevation of the levels of uCTX/Cr and uNTX/Cr in the osteoporotic and osteopenic postmenopausal subgroups were significantly higher than those in the postmenopausal women with normal BMD (P < 0.05 or 0.01). For example, the uCTX/Cr levels of the osteoporotic, osteopenic, and normal BMD subgroups according to the DXA results at the anteroposterior lumbar spine were 189 +/- 87, 272 +/- 108, and 366 +/- 135 mg/mol Cr respectively, while the uNTX/Cr levels were 52 +/- 22, 68 +/- 34 and 108 +/- 41 nmol BCE/mmol Cr respectively. uCTX/Cr and uNTX/Cr can be used as sensitive markers to determine the bone turnover status, which is changeable with age and menopausal status in women. They present a significantly negative correlation with BMD, and increase significantly in the postmenopausal women with osteopenia or osteoporosis, which indicates that measuring uCTX/Cr and uNTX/Cr can predict age-related and menopause-related bone loss in women.