Average Daily Excretion Research Articles

Effects of perchlorate on sodium‐iodide symporter and pendrin gene expression in deer mice

Effects of perchlorate on sodium-iodide symporter (NIS) and pendrin gene expression in deer mice kidney and stomach were investigated. This was accomplished by isolating a partial cDNA sequence of deer mice NIS gene of 425 bps, and quantitatively analyzing NIS mRNA expression in various deer mouse tissues. The highest NIS expression level was in the stomach, followed by testes, brain, and large intestine; very low expression of NIS was observed in the lung, kidney, heart, and liver. Exposure to perchlorate through drinking water for 28 days did not significantly increase NIS gene expression in the kidney and stomach, and pendrin gene expression in the kidney. In a depuration experiment in which deer mice were exposed to perchlorate for 8-h followed by an 88-h depuration period, no significant difference was observed between the low and high exposure groups in terms of NIS or pendrin gene expression in the kidney or stomach at the end of the experiment. Furthermore, no significant linear relationship was observed between gene expression (either NIS or pendrin) in the kidney and perchlorate mass excreted via urine at day 28, average daily excretion, or total excretion mass over the 28 day exposure. Several factors could influence the effect of perchlorate exposure on NIS and pendrin gene expression in the stomach and kidney, including (1) pre-exposure to trace perchlorate through food and water perhaps resulting in adaptation (or tolerance) in these animals; (2) metabolism of perchlorate in deer mice causing only 46-61% perchlorate excreted into urine. It is also possible that there is no effect of perchlorate exposure and/or urinary excretion on NIS and pendrin gene expression, particularly in the kidney.

Effect of diet composition on water consumption in growing pigs1

Concerns relating to use of water resources by the livestock industry, combined with the rising cost of manure management, have resulted in greater interest in identifying ways to reduce drinking water utilization by pigs while maintaining animal well-being and achieving satisfactory growth performance. The objective of this experiment was to determine if increasing the dietary CP or mineral concentrations increases water intake and excretion and, conversely, if reducing the dietary CP content reduces water intake and excretion. Forty-eight barrows (34.3 +/- 4.6 kg of BW; 12/treatment) were given free access to diets containing a low protein (16.9% CP), high protein (20.9% CP), or excess protein (25.7% CP) level, or a diet with excess levels of Ca, P, Na, and Cl. Water was available to each pig on an ad libitum basis via dish drinkers that were determined to waste less than 3% of total water flow. The excess CP diet tended to increase average daily water intake (ADWI) and urinary excretion (P < 0.10) and increased the water:feed ratio (P < 0.05); lowering dietary CP did not lower water intake or excretion. The excess mineral diet did not increase ADWI or urinary excretion but did increase water excretion via the feces. Daily nutrient intake and dietary nutrient concentration were poor predictors of ADWI; only daily intake of N and K were significantly correlated with ADWI (P < 0.05), and the r-values were low (0.39 and 0.32, respectively). There was no relationship between ADFI and ADWI. The average water:feed ratio was 2.6:1. Any study of water utilization is complicated by behavioral as well as nutritional and physiological influences, and isolating physiological need from so-called luxury intake is a significant experimental challenge. Because the impact of dietary treatment on water utilization was small, we conclude that factors other than dietary protein and mineral concentration and daily protein and mineral intake have a relatively large effect on water intake and excretion. Consequently, strategies to reduce water intake must recognize, understand, and manage these additional behavioral and physiological factors. Diet composition may be a part of strategies designed to reduce excessive water utilization by the pig industry but may have a limited effect if other important factors are ignored.

Pesticide Dose Estimates for Children of Iowa Farmers and Non-Farmers

SM1-PD-11 Introduction: Farm children have the potential to be exposed to pesticides. Biologic monitoring is often used to assess this exposure; however, the significance of the exposure is uncertain unless doses are estimated. Methods: In the spring and summer of 2001, 117 children (66 farm, 51 non-farm) of Iowa farm and non-farm households were recruited to participate in a study investigating potential take-home pesticide exposure. Each child provided an evening and morning urine sample at 2 visits spaced approximately 1 month apart. Estimated doses were calculated for atrazine, metolachlor, chlorpyrifos, and glyphosate from urinary concentrations derived from the spot urine samples and compared with Environmental Agency reference doses. Results: For all pesticides except glyphosate, the doses from farm children were higher than doses from the non-farm children. The difference was statistically significant for atrazine (P = 0.0001) but only marginally significant for chlorpyrifos and metolachlor (P = 0.07 and 0.1, respectively). The highest doses for atrazine, chlorpyrifos, metolachlor, and glyphosate were 0.085, 1.96, 3.16, and 0.34 μg/kg per day, respectively. None of the doses exceeded the Environmental Agency chronic reference values for atrazine, metolachlor, and glyphosate; however, all of the doses for chlorpyrifos exceeded the Environmental Agency chronic population-adjusted reference value. Doses were similar for male and female children. A trend of decreasing dose with increasing age was observed for chlorpyrifos. Discussion and Conclusions: There are several limitations in our pesticide dose estimates that are common to the estimation of doses from spot urinary concentrations. First, it was assumed that the spot urine samples were representative of average daily pesticide excretion and that the doses estimate average daily doses. Second, the merits of creatinine adjustment for spot urine samples are being debated, especially in children. Lastly, it was assumed that the amount of pesticide metabolite excreted in urine, after adjusting for the fraction of metabolite excreted, was equivalent to an absorbed pesticide dose. Estimation of pesticide dose from farm children's urine samples allows comparison to Environmental Agency reference doses and therefore provides an indication of the significance of pesticide exposure. Additional longitudinal studies that better estimate daily pesticide doses over the course of a year are needed to truly determine the health significance of pesticide exposures.

Balanço de compostos nitrogenados, produção de proteína microbiana e concentração plasmática de uréia em vacas leiteiras alimentadas com dietas à base de cana-de-açúcar

Doze vacas da raça Holandesa, puras e mestiças, foram distribuídas em três quadrados latinos 4 x 4, com o objetivo de avaliar o balanço de nitrogênio (N), a produção de proteína microbiana, a concentração de uréia no plasma e no leite e diferentes tempos de coleta de urina. As dietas foram constituídas à base de silagem de milho (SM) (AG 1051) com relação volumoso:concentrado (V:C) de 60:40, com base na matéria seca (MS), ou à base de cana-de-açúcar (CA) (RB 855536) com relação V:C de 60:40, com 0,35 ou 1% de uréia+sulfato de amônio (SA) ou V:C de 50:50 com 1% de uréia+SA. O balanço de N, para a dieta à base de SM, foi maior, 88 g N/dia, do que para as dietas com CA com 40% de concentrado, 67 ou 69 g N/dia. Entre as dietas contendo CA, não houve diferença no balanço de N. A excreção média diária total de derivados de purinas (DP), as purinas absorvidas (PA) e a estimativa de N microbiano, 221 g/dia, foram maiores para dieta à base de SM, quando comparada com as dietas à base de CA com 40% de concentrado, 180 ou 178 g N microbiano/dia. Entretanto, quando comparada à dieta contendo CA com 50% de concentrado, não houve diferença para as variáveis balanço de N, DP, PA e N microbiano. Não houve diferença na excreção média diária total de DP, PA e produção de N microbiano, entre as dietas contendo CA. Em relação aos tempos de coleta de urina de 24 ou 8 horas, ou seja, coleta total ou parcial, não houve diferença nas excreções médias diárias de creatinina (24 x 22 mg/kg de PV), uréia, alantoína (245 x 228 mmol/dia) e ácido úrico. A dieta contendo CA, corrigida com 1% de uréia+SA, com 50% de concentrado proporcionou produção de proteína microbiana semelhante à dieta à base de SM com relação V:C de 60:40, com base na MS. O N-uréia plasmático parece ser melhor indicador do metabolismo protéico em vacas leiteiras do que o N-uréia no leite.

Sodium transport antagonism reduces thrombotic microangiopathy in stroke-prone spontaneously hypertensive rats.

We examined whether amiloride, an agent that possesses epithelial sodium channel (ENaC)- and sodium/hydrogen exchange (NHE)-inhibitory activities, would exhibit renal vascular protection in saline-drinking, stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP received amiloride (1.0 mg.kg(-1).day(-1), n = 6) or deionized water (3 mg.kg(-1).day(-1), n = 6) for 5 wk starting at 61 days of age. Systolic blood pressure (SBP) did not differ among the groups, and there was no difference in the average daily urine output, sodium excretion, or potassium excretion. Terminal urinary protein excretion, blood urea nitrogen, and renal thrombotic microangiopathic lesions were markedly reduced in the amiloride group with no difference in plasma renin activity (PRA). In a survival protocol, SHRSP infused subcutaneously with benzamil (0.7 mg.kg(-1).day(-1), n = 8), a selective ENaC inhibitor, dimethylamiloride (0.7 mg.kg(-1).day(-1), n = 8), a selective NHE inhibitor, or vehicle (n = 7) had comparable SBP. Dimethylamiloride nonetheless prolonged survival of SHRSP (P < 0.005 vs. vehicle), and benzamil-treated SHRSP lived even longer (P < 0.0001 vs. vehicle; P < 0.05 vs. dimethylamiloride). In a separate series, plasma potassium concentration was elevated by dimethylamiloride (3.4 +/- 0.1 meq/l, n = 8) and benzamil (3.3 +/- 0.1 meq/l, n = 8) relative to vehicle (3.0 +/- 0.1 meq/l, n = 8) at 4 but not at 24 h after dosing. These findings suggest the involvement of a sodium transport mechanism in the development of thrombotic microangiopathy in SHRSP, unrelated to marked changes in arterial pressure, PRA, plasma potassium, or urinary water and electrolyte excretion.

Diurnal variation in the renal excretion of modified RNA catabolites in humans.

Renally excreted modified RNA catabolites [pseudouridine (psi), N (2), N (2)-dimethylguanosine (m(2)(2)G) and N (6)-threoninocarbonyladenosine (t(6)A)] are markers of whole-body rates of degradation of rRNA and tRNA, and are thought to be potential indicators of the resting metabolic rate. To investigate diurnal variations of these RNA catabolites, the amounts of psi, m(2)(2)G and t(6)A excreted were determined by HPLC of the urine from eight healthy male adults collected over 47-h periods, which were subdivided into the morning (06.00 or 09.00 to 12.00 hours), the afternoon (12.00 to 18.00 hours), the evening (18.00 to 24.00 hours) and the night (00.00 to 06.00 or 08.00 hours), under two different nutritional regimens with 100 or 50 g of protein/day. Furthermore, rates of degradation of rRNA and tRNA were calculated using values for these RNA catabolites. For comparison, the corresponding excretion of creatinine, which originates from the energy metabolism of muscle, and of 3-methylhistidine (m(3)His), which is an indicator of muscle protein degradation, was determined. Differences in excretion during the collection periods were tested using the Friedmann test. The excretion of psi, creatinine and m(3)His (micromol x h(-1) x kg(-1)) altered significantly (P <0.001) during the day. Medians were: for psi, 0.21 (morning), 0.19 (afternoon), 0.19 (evening) and 0.18 (night); for creatinine, 8.8, 8.4, 8.0 and 7.3 respectively; for m(3)His, 0.13, 0.11, 0.12 and 0.10 respectively. The excretion rates of m(2)(2)G and t(6)A (nmol x h(-1) x kg(-1)) altered, but not significantly, during the day; corresponding medians were: for m(2)(2)G, 9.0, 8.4, 8.0 and 8.4 respectively; for t(6)A, 4.3, 4.1, 3.9 and 3.9 respectively. From these results it can be concluded that, in order to assess the average daily rates of degradation of tRNA and rRNA using modified RNA catabolites, urine collection should be carried out quantitatively over 24 h periods. Likewise, the catabolites creatinine and m(3)His must be determined using 24 h urine samples when average daily excretion values are required.

Plasma, milk and faecal progesterone concentrations during the oestrous cycle of lactating dairy cows with different milk yields

The hypotheses tested in this study were that neither average progesterone (P4) concentrations in plasma and milk nor average progesterone metabolites concentrations in faeces would differ during an oestrous cycle in two groups of cows with differing daily milk yields. High producing (HP=8) and low producing (LP=8) dairy cows were selected randomly for the study. Their oestrous cycles were initially synchronised using P4 and prostaglandin F2α. Chromic oxide capsules were administered twice daily to measure total faecal output. Samples of blood, faeces and milk were taken daily throughout one oestrous cycle, plasma and milk P4, and faecal progesterone metabolites (FP4M) assayed. The average daily milk yields in the two groups were 30.8 and 21.9 l per day, respectively ( P<0.0001), although daily faecal output was similar in both the groups (HP, 7.7 versus LP, 6.9 kg DM; P=0.24). Mean plasma and milk P4 concentrations were similar in both the groups (plasma P4, 4.12 versus 4.05 ng/ml; P=0.3; milk P4, 8.2 versus 8.3; P=0.9) during dioestrus. Average daily excretion of P4 to the milk was greater in HP than LP cows (252 versus 185 μg, P=0.04). Neither concentration nor the daily yield of FP4Ms was affected by level of milk yield (concentration: 12.2 versus 11.5 μg/g; daily yield: 89.1 versus 82.9 mg per day; P>0.05). These data showed that the concentrations of P4 in plasma and milk, and the concentrations and daily yields of FP4M were not affected by the level of daily milk yields which differed by about 41% of the LP average of 21.9 l.

Pharmacokinetics of icodextrin in peritoneal dialysis patients

Pharmacokinetics of icodextrin in peritoneal dialysis patients. Icodextrin is a glucose polymer osmotic agent used to provide sustained ultrafiltration during long peritoneal dialysis (PD) dwells. A number of studies have evaluated the steady-state blood concentrations of icodextrin during repeated use; however, to date the pharmacokinetics of icodextrin have not been well studied. The current study was conducted to determine the absorption, plasma kinetics and elimination of icodextrin and metabolites following a single icodextrin exchange. Thirteen PD patients were administered 2.0 L of solution containing 7.5% icodextrin for a 12-hour dwell. Icodextrin (total of all glucose polymers) and specific polymers with degrees of polymerization ranging from two to seven (DP2 to DP7) were measured in blood, urine and dialysate during the dwell and after draining the solution from the peritoneal cavity. A median of 40.1% (60.24 g) of the total administered dose (150 g) was absorbed during the 12-hour dwell. Plasma levels of icodextrin and metabolites rose during the dwell and declined after drain, closely corresponding to the one-compartment pharmacokinetic model assuming zero-order absorption and first-order elimination. Peak plasma concentrations (median C peak = 2.23 g/L) were observed at the end of the dwell (median Tmax = 12.7 h) and were significantly correlated with patients' body weight (R2 = 0.805, P < 0.001). Plasma levels of icodextrin and metabolites returned to baseline within 3 to 7 days. Icodextrin had a plasma half-life of 14.73 hours and a median clearance of 1.09 L/h. Urinary excretion of icodextrin and metabolites was directly related to residual renal function (R2 = 0.679 vs. creatinine clearance, P < 0.01). In the nine patients with residual renal function, the average daily urinary excretion of icodextrin was 473 +/- 77 mg per mL of endogenous renal creatinine clearance. Icodextrin metabolites DP2 to DP4 were found in the dialysate of subsequent dextrose exchanges, contributing to their elimination from blood. Changes in intraperitoneal concentrations of icodextrin metabolites during the dwell revealed a dual pattern, with a progressive rise in the dialysate concentration of smaller polymers (DP2 to DP4) and a progressive decline in the dialysate concentrations of the larger polymers (DP5 to DP7), suggesting some intraperitoneal metabolism of the glucose polymers. This increase in dialysate metabolite levels, however, did not contribute significantly to dialysate osmolality. In addition, some diffusion of maltose (DP2) from blood to dialysate may have occurred. There were no changes in serum insulin or glucose levels during icodextrin administration, indicating that icodextrin does not result in hyperglycemia or hyperinsulinemia as occurs during dextrose-based dialysis. Serum sodium and chloride declined in parallel with the rise in plasma levels of icodextrin, supporting the hypothesis that these electrolyte changes are the result of the increased plasma osmolality due to the presence of icodextrin metabolites. The pharmacokinetics of icodextrin in blood following intraperitoneal administration conforms to a simple, single-compartment model that can be approximated by zero-order absorption and first-order elimination. A small amount of intraperitoneal metabolism of icodextrin occurs but does not contribute significantly to dialysate osmolality. The metabolism of absorbed icodextrin and the resultant rise in plasma levels of small glucose polymers (DP2 to DP4) do not result in hyperglycemia or hyperinsulinemia, but may result in a small decrease in serum sodium and chloride.

Progesterone clearance rate in lactating dairy cows with two levels of dry matter and metabolisable energy intakes

The aim of these studies was to determine the effect of levels of dry matter (DM) and metabolisable energy (ME) intakes on clearance rate of progesterone (P4) in dairy cows. Thirty-two lactating Holstein–Friesian cows were selected for the study and were fed indoors in individual stalls for a period of 5 weeks. They were individually offered a diet of combinations of pasture, hay and pelleted cereal grain to achieve two different levels of DM and ME. In the first trial, 16 cows were allocated to two groups: (i) high DM (HDM), and (ii) low DM (LDM) intakes, while the amount of ME intake was constant. In the second trial, 16 cows were allocated to two groups: (i) high ME, and (ii) low ME intakes with similar amount of DM intake. A GnRH-agonist (deslorelin) was initially implanted in the ear of each cow to block endogenous P4 secretion. Then 3 weeks later, a CIDR device was inserted into the vagina of each cow and left in place for 11 days. Chromic oxide (Cr 2O 3) capsules were administered to allow daily faecal output (FO) to be estimated. Daily blood, faecal and milk samples were taken during the period of the experiment for P4 and faecal P4 metabolites analyses. Trial 1: The average milk yield was similar among cows in high and LDM intake groups (26.7 versus 25.0 l per day, P=0.2). The average daily FO was 7.8 kg DM in the HDM and 5.7 in the LDM cows ( P<0.0001). Average daily DM intakes were 17.3 kg and 15.4 kg in the HDM and LDM groups, respectively ( P<0.0001). The average plasma P4 concentrations were similar between the two groups (1.56 versus 1.60 ng/ml, P=0.7) but milk P4 concentrations were higher in LDM cows (4.6 versus 3.6 ng/ml, P=0.02). The average daily excretion rate of P4 into the milk was higher in LDM cows (122.3 versus 88.5 μg, P=0.002). The concentrations of faecal P4 metabolites (FP4M) were not influenced by the level of daily DM intake (2.85 versus 2.90 μg/g, P=0.6). The average daily yields of FP4M were higher among cows in the HDM group (23.2 versus 16.3 mg, P=0.01). Trial 2: The average milk yield was 31.2 l per day in HME cows compared to 25.0 l per day in LME cows ( P<0.0001). The average daily FO was 7.8 kg DM in LME and 5.8 kg DM in HME cows ( P<0.0001), and the average DM content of faeces was higher in LME cows (15.8 versus 12.7%, P=0.01). The average daily ME intake was 213 MJ per day in HME group compared to 183 MJ per day in LME group ( P<0.0001). The average plasma and milk P4 concentrations were similar between the two groups (plasma P4=1.54 versus 1.56 ng/ml, P=0.4; milk P4: 3.7 versus 3.6 ng/ml, P=0.6). The average daily excretion rate of P4 into the milk was higher in HME cows (114 versus 88.5 μg, P=0.03). Concentrations of FP4M were not influenced by the level of daily ME intake (2.5 versus 2.85 μg/g, P=0.08). However, daily yields of FP4M were greater in the LME group (23.2 versus 14.4 mg, P=0.01). In conclusion, this study was unable to establish a relationship between the level of DM and ME in the diet with the excretion rates of FP4M metabolites and plasma P4 concentrations.

Excretion rate of progesterone in milk and faeces in lactating dairy cows with two levels of milk yield.

This study was conducted to measure the effect of the level of daily milk yield on the excretion rate of progesterone (P4) in milk and faeces in high-producing (HP) and low-producing (LP) lactating dairy cows. A GnRH-agonist was implanted to block endogenous production of P4. A CIDR device was inserted into the vagina and left in place for 11 days. The average and peak milk yields were greater in HP cows (P < 0.0001). Mean plasma concentrations of P4 were also similar in both groups (P = 0.44), even though the average mass of P4 delivered from a CIDR device was higher with HP cows (P = 0.02). Average milk P4 concentration was similar in both groups (P = 0.81), so that average daily excretion of P4 in the milk was greater with HP cows (P = 0.05). The concentrations (P = 0.83) and daily yields (P = 0.4) of total faecal progesterone metabolites were not affected by level of milk yield. These data show that the concentrations of plasma and milk P4, and the concentration and yield of P4 metabolites are not affected by the levels of daily milk yield.

Correlation between Faecal Excretion of Indium-111-Labelled Granulocytes and Calprotectin, a Granulocyte Marker Protein, in Patients with Inflammatory Bowel Disease

Background: Several studies have suggested that clinical indices of disease activity in inflammatory bowel disease (IBD) do not adequately reflect the degree of inflammation in most such patients. Faecal excretion of indium-111-labelled neutrophilic granulocytes has been suggested as the gold standard of disease activity, but its complexity and high cost and the exposure of patients to ionizing irradiation have limited the use of this technique. The aim of this study was to investigate the correlation between the faecal excretion of the granulocyte marker protein calprotectin and that of 111In-labelled granulocytes. Methods: Calprotectin in stool extracts from 19 patients with Crohn's disease (CD), 10 with ulcerative colitis (UC), and 9 presumably healthy controls was assessed with a simple enzyme-linked immunosorbent assay. Simultaneously, the faecal excretion of autologous 111In-labelled granulocytes was measured. Results: There was a strong correlation between the average daily excretion of calprotectin and that of the total 3-day excretion of 111In-labelled granulocytes (r = 0.87, P < 0.0001). Furthermore, the concentration of calprotectin, assessed in a small stool sample on day 1, also correlated well with the excretion 111In-labelled granulocytes (r = 0.80, P < 0.0001). Conclusion: The results suggest that faecal calprotectin reflects the granulocyte migration through the gut wall in patients with IBD and hence might serve as a simple, inexpensive alternative to the indium-111 technique.

Utility of creatinine excretion in body-composition studies of healthy men and women older than 60 y

This study evaluated whether aging alters the usefulness of creatinine excretion as an index of lean body mass (LBM) or muscle mass in healthy men and women. Creatinine excretion was determined while 24 young (15 men and 9 women aged < 32 y) and 38 older (23 men and 15 women aged > 60 y) healthy volunteers stayed at a clinical research center for 3 d. Total LBM was determined by 40K counting in all subjects, and cross-sectional areas of upper arm and thigh muscles were determined in some subjects (10 young, 20 old) by magnetic resonance imaging. The slopes and intercepts of the regression equations relating LBM to average daily creatinine excretion were the same in the younger and older groups, and the precision with which LBM could be determined from creatinine excretion was not diminished by aging. Creatinine excretion was closely correlated with cross-sectional areas of upper arm (r = 0.85) and thigh (r = 0.88) muscles, and the slopes and intercepts of the regression equations were not significantly affected by age. The older group had a mean LBM smaller than that of the younger group, which was accounted for entirely by a smaller muscle mass. Mean resting metabolic rate (RMR), whole-body protein turnover rate, and thigh strength were lower in the older group than in the young group. Adjustment of RMR and protein turnover for creatinine excretion or LBM eliminated the age effects. Strength was lower in the older group even after adjustment for creatinine excretion or LBM. This study indicates that creatinine excretion is useful for evaluating body composition in both young and old subjects.

Bone mass and subtle abnormalities in ovulatory function in healthy women.

Women with occasional anovulatory or short luteal phase menstrual cycles have been reported to lose bone mineral density (BMD) at a greatly accelerated rate compared to women without such abnormalities. To investigate this association, we performed a longitudinal study of BMD in a group of healthy premenopausal women enrolled in a comprehensive study of ovulatory function. Subjects had collected daily urine samples that were analyzed for estrone and progesterone metabolites by enzyme-linked immunoassay. The 53 participants collected urine for an average of 4.1 cycles. Computer algorithms identified 7 (13.2%) women with luteal phase abnormalities (> 1 anovulatory cycle or cycle with luteal phase length < or = 10 days) and 17 (32.1%) women with other menstrual abnormalities. Areal BMD (grams per cm2) was measured at the lumbar spine, hip, and whole body using dual energy x-ray absorptiometry; BMD was measured 2-3 times over an average observation period of 17.5 months. At baseline, women with luteal abnormalities had mean BMD similar to those of the 29 women with no abnormal cycles: lumbar spine, 1.06 vs. 1.09 g/cm2; total hip, 0.95 vs. 0.94 g/cm2; whole body, 1.15 vs. 1.11 g/cm2 (P > 0.10; adjusted for age and weight at baseline, parity, physical activity level, and calcium intake). When compared at follow-up to women with no abnormal cycles, women with luteal abnormalities tended to gain BMD at the spine and hip (P > 0.10). On whole body measurement, women with luteal abnormalities tended to lose BMD compared to women with no abnormal cycles (-1.1%/yr vs. 0%/yr; P = 0.08); however, the magnitude of loss was not unusual for women in this age range and was within the coefficient of variation for replicate measurements. Neither mean luteal phase length, percent time in luteal phase, nor average daily excretion of progesterone metabolites was associated with baseline BMD or percent annual change in BMD at any measurement site. Thus, we did not confirm a relationship between luteal abnormalities and accelerated bone loss in this population of healthy premenopausal women.

Response of renal orotic acid and creatinine to treatments affecting metabolic protein supply of ruminants.

90 urine samples obtained in three lamb trials and one experiment using adult wethers were analyzed for their contents of orotic acid and creatinine. The average daily excretion of orotic acid accounted for 0.5 mg to 1.5 mg (35 micrograms to 130 micrograms/W0.75) with a high individual variation. Correlation coefficients between orotic acid and other urinary constituents were low indicating an entirely different response to metabolic variations. There was only a weak relationship to live weight, protein retention and rumen fluid traits. Defaunation reduced the orotic acid excretion (significant in the adult wethers) whereas the addition of rumen-protected lysine as well as the use of different dietary carbohydrate sources were without effect. The urinary excretion of creatinine increased with live weight and age from 0.4 g/d in the 20 kg lambs to 1.7 g/d in the adult 53 kg wethers. The correlations with live weight were close whereas the apparently negative correlation with protein retention was not real as could be evaluated by calculation of the partial correlations. There was a close correlation of creatinine with total N, urea and allantoin. Neither defaunation nor rumen-protected lysine and the kind of carbohydrate source had significant effects on creatinine. The use of orotic acid and creatinine as indicators of metabolic disorders were discussed. Easy application in practical diagnosis without quantitative urine collection might be possible by the determination of orotic acid in the milk of cows and of the creatinine/N ratio in urine.

Daily excretion levels of an unidentified ketosteroid in the urine of patients with Cushing's syndrome and healthy subjects measured by a new method.

We developed a new method for measuring an unidentified ketosteroid glucuronide (US-G) detected by the method of Iwata et al. for measuring 17-ketosteroid glucuronides by reversed phase HPLC on a Capcell-Pak C8 column with three kinds of mobile phase solutions (Iwata method; Clin Chem 35: 795-799, 1989). The Iwata method inadequately separated US-G and two hydroxy 17-ketosteroides, 11 beta-hydroxyetiocholanolone and 11 beta-hydroxyandrosterone, and it exhibits insufficient sensitivity for measuring traces of US-G in the urine of healthy subjects. We solved these problems by developing a new method which measures US-G in urine, as a free type by hydrolyzing the glucuronide type enzymatically, by normal phase HPLC on a Capcell-Pak Silica column with one kind of mobile phase solution. By this method, the levels of US excreted as a glucuronide in the urine of healthy subjects and of patients with Cushing's syndrome were determined as proportions of the levels of 11 beta-hydroxyandrosterone. The average daily urinary excretion of US was 971 micrograms (125-4,995 micrograms) in patients with Cushing's syndrome (n = 22: two males and 20 females aged 26 to 65 years), and 34 micrograms (0-141 micrograms) in healthy subjects (n = 63: 49 males, and 14 females aged 21 to 54 years), and the differences were clearly significant. However, there were no differences between the urinary US levels of patients with pituitary adenoma and patients with adrenal adenoma. Furthermore, no US was detected in the urine of patients with aldosteronism (two males and eight females aged 34 to 61 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Effekte einer Hochvoltkondensatorentladungstherapie auf die Zirkadianrhythmen verschiedener physiologischer Parameter

The aim of the study was to evaluate the effects of high-voltage capacitor-discharge therapy. For this reason we studied the circadian rhythms of different physiological parameters in two groups - one with and one without high-voltage capacitor-discharge therapy - during a three-week treatment in a health resort. One remarkable finding in patients was an evident influence on the circadian rhythm of the excretion of free Cortisol in urine following high-voltage capacitor-discharge therapy. We found an obvious increase of the average daily excretion of Cortisol and a phase-acceleration of Cortisol. This could be an effect of high-voltage capacitor-discharge therapy on the adrenal cortex and could explain some effects of this therapy reported in the older literature.

Fish oil supplementation reduces excretion of 2,3-dinor-6-oxo-PGF 1α and the 11-dehydrothromboxane B 2/2,3-dinor-6-oxo-PGF 1α excretion ratio in adult men

Dietary supplementation with a fish oil concentrate (FOC) reduced the endogenous synthesis of prostacyclin (PGI 2), as measured by the excretion of its major urinary catabolite, 2,3-dinor-6-oxo-PGF 1α (PGI 2-M). Thirty-four healthy men (24–57 years old) were given controlled diets and supplements that provided 40% of the energy from fat and a minimum of 22 mg/d of α-tocopherol for two consecutive experimental periods of 10 weeks each. During the experimental periods, the men received capsules containing 15 g/d of a placebo oil (PO) (period 1) or 15 g/d of the FOC (period 2). In addition to the PO or FOC, capsules contained 1 mg of α-tocopherol per g of fat as an antioxidant. The average daily excretion of PGI 2-M during the last week of FOC supplementation (period 2) was 22% less ( P = 0.0001) than at the end of the first period. These results are at variance with those reported in comparable human studies conducted by other investigators during the middle and late 1980s. A 20% reduction ( P = 0.003) in the 11-dehydrothromboxane B 2 to 2,3-dinor-6-oxo-PGF 1α excretion ratio at the end of period 2 in this study demonstrates that a shift of the n-6 to n-3 polyunsaturated fatty acid ratio from 12.5 to 2.3 brings about a substantial modulation of the eicosanoid system.

Effect of organized general preventive administration of iodized salt on struma incidence and ioduria in 11-16-year-old children in the Jena endemic area

In 1988 and in 1991, i.e. two and five years after the introduction of a general iod salt supply (32 mg KJO2/kg salt) in our region, we investigated the frequency of goiters and the level of iodine excretion in urine in 504 and 336 school children of 11 to 16 years of age. In 1988 the assessment of goiter size was made by inspection and palpation according to the recommendation of WHO. 36% of the school children were found to have goiters of type I b or II. The average urine excretion of iodine amounted to 46.2 +/- 37.2 micrograms Iod/g creatinine (n = 353). In 1991 we selected school children with goiters by the same criteria and found frequency (34%) to be nearly unchanged compared to 1988. Furthermore we investigated these goiters with ultrasound and confirmed the diagnosis in 100 from 107 children. The average daily urine excretion of iodine was significantly higher in 1991 (57.7 +/- 24.8 micrograms/Iod/g creatinine, n = 328) than in 1988. However this value is below the level recommended by the WHO (minimum 75 micrograms Iod/g creatinine). Despite the increase of the iodine intake over the last years, the frequency of goiters in pubertal school children in the Jena region is endemic. This fact supports the demand for a general and sufficient iodine supply.

Gastrointestinal Absorption Factor for Uranium Incorporated in Diet

The gastrointestinal absorption factor (f 1 ) for uranium incorporated in diet was estimated for a group representing the urban Indian population, by studying the average daily ingestion and urinary excretion of U. The technique of neutron activation was employed to determine the concentration of 238 U in daily diet, drinking water and urine samples. The gut absorption factor was found to be 0.016

Identification of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25,26-hexol in human urine

A new bile alcohol, 5 beta-cholestanehexol, was identified in the urine of healthy humans as the glucuronide. The bile alcohol glucuronide fraction was isolated by an ion exchange chromatography on piperidinohydroxypropyl Sephadex LH-20. After enzymatic hydrolysis, the bile alcohols were converted into trimethylsilyl ether derivatives and analyzed by a combination of gas-liquid chromatography and mass spectrometry. The major bile alcohol was 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol. As minor constituents the following C26 and C27 bile alcohols were identified: 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25,26-hexol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,26-pentol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol. In addition to these bile alcohols, a new bile alcohol was identified as a sixth component of the urinary bile alcohols. The structure was assigned as (24S)-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25,26-hexol by the direct comparison of mass spectral data and chromatographic properties with synthetic standard. The average daily excretion of the new bile alcohol was 28.6 micrograms and 3.0% of the total bile alcohols. The presence of 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol and 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25,26-hexol suggests that 26-hydroxylation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol is most likely for the biosynthesis of this new bile alcohol.