Reference interval of pregnancy-associated plasma protein-A in healthy men and non-pregnant women

ObjectiveThe serum pregnancy-associated plasma protein-A (PAPP-A) concentration is a predictor of ischemic cardiac events and renal impairment. However, the reference interval of PAPP-A has not been determined. This study determined the reference interval of PAPP-A in men and non-pregnant women.MethodsThe study enrolled 126 apparently healthy individuals (52 males and 74 females). The mean age of the men and women was 34.7 (range 20–66) years and 34.6 (range 18–65) years, respectively. Serum PAPP-A concentrations were determined using an ultrasensitive enzyme-linked immunoassay kit. Reference intervals were calculated using the bootstrap method.ResultsThe results for three subjects were outliers, so the reference interval of PAPP-A was calculated using the data for 123 subjects. PAPP-A was undetectable in 26 subjects. The reference interval of PAPP-A for men and women (with the 90% confidence interval) was <22.9 ng/mL (19.7–23.3) and <33.6 ng/mL (25.2–36.7), respectively. In male subjects, serum PAPP-A levels of smokers [3.10 (UD, 7.30) ng/mL] were significantly lower than that of non-smokers [11.00 (UD, 24.4) ng/mL] (p < 0.001) and there was a positive correlation between serum PAPP-A levels and subjects’ age (r = 0.439; p < 0.001).ConclusionsThe reference interval of PAPP-A differed for men and non-pregnant women. In clinical practice, <22.9 ng/mL for men and <33.6 ng/mL for non-pregnant women may be used as reference intervals for PAPP-A.     

Effects of continuous daily administration of 0.03 mg of d-norgestrel on the plasma levels of progesterone and the urinary excretion of oestrogens

Daily determinations of the plasma level of progesterone and the urinary excretion of estrogens were performed in 5 subjects during 1 control cycle followed by 3 months of treatment with .03 mg of d-norgestrel. The control cycles were ovulatory according to the parameters investigated, although 1 of the women showed a monophasic basal body temperature. During treatment there was a tendency to a decrease of the estrogen excretion. 3 of the women showed 1 or several cycles with low progesterone levels. It is believed that this was due to a defective function of the corpus luteum. It seems that the effect of the present drug on the corpus luteum activity was about equal to that of chlormadinone acetate .5 mg daily, while .3 and .5 mg of norethindrone depressed the function more markedly.     

Relationship between plasma uridine and urinary urea excretion

To investigate whether the concentration of uridine in plasma is related to the urinary excretion of urea, 45 healthy male subjects with normouricemia and normal blood pressure were studied after providing informed consent. Immediately after collection of 24-hour urine, blood samples were drawn after an overnight fast except for water. The contents of ingested foods during the 24-hour urine collection period were described by the subjects and analyzed by a dietician. Simple regression analysis showed that plasma uridine was correlated with the urinary excretions of urea (R = 0.41, P < .01), uric acid (R = 0.36, P < .05), and uridine (R = 0.30, P < .05), as well as uric acid clearance (R = 0.35, P < .05) and purine intake (R = 0.30, P < .05). In contrast, multiple regression analysis showed a positive relationship only between plasma uridine and urinary excretion of urea. These results suggest that an increase in de novo pyrimidine synthesis leads to an increased concentration of uridine in plasma via nitrogen catabolism in healthy subjects with normouricemia and normal blood pressure.     

Relationships of urinary phyto-oestrogen excretion to BMD in postmenopausal women

OBJECTIVE: Phyto-oestrogens are plant compounds with both oestrogenic and anti-oestrogenic properties. However, it is not known whether natural phyto-oestrogens are beneficial or harmful in human osteoporosis. This study was performed to investigate the relationships between urinary phyto-oestrogens and bone mineral density (BMD) in Korean postmenopausal women. DESIGN: The subjects were classified into osteoporotic, osteopenic and normal groups according to their BMD as defined by WHO criteria. We compared the urinary phyto-oestrogens of each group and studied whether urinary phyto-oestrogens correlate with BMD. PATIENTS: The subjects were 75 Korean postmenopausal women with ages ranging from 52 to 65 years (mean 58 +/- 1.1 years). Mean number of years after menopause was 7.3 +/- 1.3. MEASUREMENTS: Twenty-four-hour urinary phyto-oestrogens were measured by gas chromatography-mass spectrometry (GCMS) and BMD by dual-energy X-ray absorptiometry (DXA, Lunar Expert-XL, Lunar Co., WI, USA). RESULTS: In Korean postmenopausal women, urinary enterolactone (1.46 +/- 1.11 micromol/day) was lower and daidzein (2.59 +/- 3.25 micromol/day) was higher than in western women, and both levels were comparable to those in Japanese women. Daily urinary excretion of genistein and apigenin were 1.09 +/- 0.912 and 0.48 +/- 0.40 micromol/day, respectively. In subjects with osteoporosis, urinary enterolactone was lower (P < 0.05) but apigenin was significantly higher (P < 0.05) than in the controls. BMD of L2-L4 correlated positively with urinary enterolactone (r = 0.388, P < 0.01), and BMD of the femoral neck and Ward's triangle correlated positively with urinary enterolactone (r = 0.271, P < 0.05 and r = 0.322, P < 0.05) but negatively with apigenin (r = -0.412, P < 0.01 and r = -0.395, P < 0.01). By multiple stepwise regression, the variables associated with spinal BMD were age, the amount of urinary apigenin and body mass index (BMI). The variables associated with femoral neck BMD were age and urinary apigenin. CONCLUSIONS: From these results, we conclude that urinary phyto-oestrogens, especially enterolactone and apigenin, are related to BMD in Korean postmenopausal women. Our results also suggest the possibility that phyto-oestrogens have differential effects on bone density. Further studies are needed to clarify the exact biological roles of phyto-oestrogenic components on bone metabolism.     

Human plasma pharmacokinetics and urinary excretion of thiotepa and its metabolites

Thiotepa has been used clinically for greater than 30 years but its pharmacokinetics remain poorly defined. We determined the plasma pharmacokinetics and urinary excretion of thiotepa and its metabolites in 21 patients with breast cancer who received 25 courses of iv bolus thiotepa (12 mg/m2) as part of combination chemotherapy. Plasma samples were obtained before injection: at 5, 10, 15, 30, 45, 60, 90, and 120 minutes; and, when possible, 180 and 240 minutes after injection. In eight courses, urine was collected as 4-hour aliquots for 24 hours after therapy. All samples were analyzed for thiotepa and tepa by gas-liquid chromatography. Urinary alkylating activity was assessed spectrophotometrically after reaction with 4-(p-nitrobenzyl)-pyridine. Plasma concentrations of thiotepa declined in a biexponential fashion with an alpha-half-life of 7.7 +/- 1.2 minutes and a beta-half-life of 125 +/- 21 minutes. Total-body clearance of thiotepa was 186 +/- 20 ml/minute/m2. The volume of the central compartment was calculated as 0.25 +/- 0.04 L/kg, and the steady-state volume of distribution was calculated as 0.70 +/- 0.11 L/kg. Tepa was detectable in plasma by 5 minutes after the injection of thiotepa. Tepa concentrations increased from 0.093 +/- 0.068 to 0.127 +/- 0.11 micrograms/ml over the 240-minute collection period. By 120 minutes, the concentration of tepa equaled that of thiotepa, and tepa persisted longer in the plasma than did thiotepa. During the first 24 hours after injection, urinary excretion of thiotepa, tepa, and alkylating activity accounted for 1.5%, 4.2%, and 23.5% of the administered dose, respectively. These results extend our laboratory's previous animal studies of thiotepa and argue for metabolism of thiotepa to tepa as a major mechanism of clearance of this compound. Further metabolism or breakdown of both compounds may explain the urinary excretion of alkylating materials other than parent compound and tepa.     

HRT does not improve urinary albumin excretion in postmenopausal diabetic women

The effect of 6 months combined, continuous hormone replacement therapy (HRT) with conjugated equine oestrogen (0.625 mg) and medroxyprogesterone acetate (2.5 mg) on albumin/creatinine ratio (ACR) was determined in postmenopausal diabetic women in a randomised, controlled study. Mean (interquartile range) change in plasma ACR was not (P=0.96) different in women receiving HRT [2 (-11, 21) mg/g, n=20] compared with those randomised to placebo [2 (-1, 14) mg/g, n=27]. Also, the proportion of women with microalbuminuria did not change (P=0.75) during HRT (baseline, 0.45; end of study, 0.53). Furthermore, several risk factors for microalbuminuria including systolic blood pressure (SBP), fasting blood glucose, glycated haemoglobin (HbA1c) and adiposity did not vary significantly during HRT. These data suggest that 6 months HRT does not reverse microalbuminuria caused by prolonged hyperglycaemia and other risk factors that underlie leakage of albumin into the urine in postmenopausal women with type 2 diabetes.