Neopterin in renal cell carcinoma: inhalational administration of interleukin-2 is not accompanied by a rise of urinary neopterin.

Inhalational administration of interleukin-2 (IL-2) is effective in controlling renal cell carcinoma (RCC) lung metastases with minimal toxicity. Neopterin is an indicator of systemic immune activation in metastatic cancer and is increased after systemic IL-2 administration. Urinary neopterin was investigated in 13 patients with metastatic RCC and 18 controls. In seven patients, urinary neopterin was followed before and after treatment with inhalational IL-2. Neopterin was measured by high-performance liquid chromatography and creatinine was determined by Jaffé reaction. Urinary neopterin was significantly increased in patients with metastatic RCC compared to controls (257 +/- 263 micromol/mol creatinine vs. 110 +/- 41 micromol/mol creatinine; Mann-Whitney U-test, p < 0.05). Median survival was significantly longer in patients with urinary neopterin <173 micromol/mol creatinine compared to patients with neopterin > or = 173 micromol/mol creatinine (698 vs. 245 days; log-rank test, p < 0.05). No significant increase was observed after inhalational IL-2 therapy (147 +/- 101 vs. 153 +/- 54 micromol/mol creatinine). We conclude that urinary neopterin is increased in patients with metastatic RCC, and higher neopterin concentrations are indicative of poor prognosis. The absence of an increase in urinary neopterin after inhalational IL-2 therapy is in accord with the lack of significant systemic toxicity.     

The potential role of hypocortisolism in the pathophysiology of PTSD and psoriasis

Different physical, chemical and psychological stressors can provoke a unique but different endocrine response involving activation of the hypothalamo-pituitary-adrenal (HPA) axis. Inability of adequate compensatory reaction can lead to many disorders. The aim of our study was comparison of cortisol values in diseases provoked by various stressors. Our investigation included 34 posttraumatic stress disorder (PTSD) patients, as an example of disorder caused by extremely strong, acute stressful stimulus, 19 psoriatic patients, as an example of chronic stress stimulus and 17 healthy volunteers. In each patient we determined 24-hour urinary cortisol, serum cortisol at 8 a.m. and 5 p.m., and cortisol in dexamethasone suppression test by the standard radioimmunoassay (RIA) method. PTSD patients showed lower urinary 24-hour cortisol values, (361 +/- 28 nmol/24 h), "stronger" circadian rhythm of serum cortisol (595 +/- 57 nmol/l at 8 a.m. and 242 +/- 23 nmol/l at 5 p.m.) and attenuated suppression of cortisol in dexamethasone suppression test (197 +/- 45 nmol/l) in comparison to healthy volunteers (590 +/- 87 nmol/24 h urine, 590 +/- 32 nmol/l at 8 a.m., 402 +/- 31 nmol/l, and < 86 nmol/l in dexa test). Psoriatic patients showed markedly lower 24-hour cortisol values (150 +/- 98 nmol/24 h), even in comparison to PTSD patients, then serum cortisol values (404 +/- 138 nmol/l at 8 a.m., 187 +/- 80 nmol/l at 5 p.m.) and enhanced suppression of cortisol (23 +/- 5 nmol/l). The model of attenuated feedback inhibition in PTSD patients shows that they are unusually reactive to stress and represents an alternative model of acute stress reaction to extremely strong stressful stimulus. Unusually low cortisol values in psoriatic patients correlate to our hypothesis that in chronic stress-related disease, as psoriasis is, exists, by still undefined mechanism, altered HPA axis function, which is obviously incompetent to realise its immunoregulatory function, so consequentially, clinical signs of psoriasis persist.     

Urinary neopterin in malignant lymphoma.

Urinary neopterin levels were studied in 96 patients with malignant lymphomas. Twenty-eight had Hodgkin's disease and 68 non-Hodgkin's lymphoma. Neopterin excretion was significantly related to the clinical stage of the disease. Mean neopterin excretion in patients with active disease (634 +/- 527 mumol neopterin/mol creatinine) was significantly higher (p = 0.000) than in patients in complete remission (198 +/- 105 mumol neopterin/mol creatinine). Mean neopterin levels of patients in stage III-IV were higher than for patients in stage I-II. These findings were the same in patients with Hodgkin's disease and those with non-Hodgkin's lymphoma (659 +/- 593-425 +/- 316 mumol neopterin/mol creatinine), regardless of the histological subtype. A significant correlation was found between neopterin excretion, ESR (r = 0.31; p = 0.003) and hemoglobin (r = -0.40; p = 0.000). Longitudinal analysis showed a trend towards a correlation between response to therapy and neopterin excretion. These findings suggest that neopterin may be a useful prognostic marker in non-Hodgkin's lymphoma.     

The effect of shock wave lithotripsy on nitric oxide and malondialdehyde levels in plasma and urine samples

Shock wave lithotripsy (SWL) is accepted as the first treatment choice for most urinary stones, but it has adverse effects on the kidneys. The mechanisms underlying shock wave-induced renal injury have been discussed and include shear stress, thermal and cavitation effects and free radical formation. We investigated the effects of SWL on plasma and urinary nitrite, a stable metabolite of nitric oxide (NO), and malondialdehyde (MDA) concentrations. Between February and October 2004, 12 men and 8 women with renal calculi were treated using a Dornier MPL-9000 lithotriptor. The ages ranged from 22 to 45 years (average age: 33.7 years). Plasma and urinary NO and MDA levels were analysed before, immediately after, 30 and 60 min and 24 h after SWL. Plasma NO levels were higher than baseline levels immediately, and at 30, 60 min and 24 h after treatment (p = 0.016, p = 0.031, p = 0.033 and p = 0.045, respectively). Simultaneously, the mean urinary NO levels also showed significant elevation after SWL compared with baseline values, except for 24 h (p = 0.021, p = 0.023 and p = 0.048, respectively). The mean levels of plasma MDA showed statistically significant elevation immediately, and 30 and 60 min after SWL termination compared with pre-SWL values (p = 0.012, p = 0.008 and p = 0.012, respectively). Urinary MDA levels obtained immediately (p = 0.035), and 30 (p = 0.006) and 60 (p = 0.045) min after SWL were increased compared to pre-SWL values. We speculate that SWL treatment causes oxidative stress caused by renal ischemia-reperfusion (I/R) injury. Additionally, the increase of NO production may have prevented renal damage caused by vasoconstriction.     

Urinary free cortisol and cortisone excretion in healthy individuals: influence of water loading

The influence of water loading on urinary excretion of free cortisol and cortisone was investigated in healthy men. The results were as follows: water loading tests (intake of 0.25-1.5 L) in a single individual showed that a water load of 1.5 L reliably increased the excretion of urine, free cortisol and cortisone (p < 0.01). Regression analyses gave significant correlations of urine volume with free cortisol and free cortisone, and of free cortisol and free cortisone. Corresponding results were obtained when water loading tests were performed in males who ingested 1.5 L of water (n = 8): the excretion of urine, free cortisol and free cortisone were significantly augmented; correlated was urine volume with free cortisol and free cortisone, and free cortisol with free cortisone. In a third set of tests, volunteers collected one 5 h urine (10:00-15:00 h) after the intake of 3 x 0.1 or 0.5 L at 11:00, 12:00 and 14:00 h. Excretion of urine, free cortisol and free cortisone in males of the low water loading group (3 x 0.1 L) was 0.59 mL/min, and 8.2 or 15.0 microg/5 h; corresponding values in individuals ingesting 3 x 0.5 L of water were 1.5 mL/min (p < 0.01), 12.3 microg/5 h (p > 0.05) and 26.3 microg/5 h (p < 0.02). In summary, urinary free cortisol and cortisone excretion in healthy men depends on urine volume, especially during water diuresis. Thus, interpretation of free cortisol and especially of free cortisone excretion is only possible if subjects strictly control their fluid intake and if urine volume is considered an important pre-analytical parameter-otherwise, interpretation of urinary free cortisol results is difficult and of urinary free cortisone data remains tenuous at best.     

Vocal buffering of the stress response: exposure to conspecific vocalizations moderates urinary cortisol excretion in isolated marmosets

For many species, the presence of a significant social partner can lessen the behavioral and physiological responses to stressful stimuli. This study examined whether a single, individually specific, signature vocalization (phee call) could attenuate the physiological stress response that is induced in marmosets by housing them in short-term social isolation. Utilizing a repeated-measures design, adult marmosets (n=10) were temporarily isolated from their long-term pair mate and exposed to three conditions: signature vocalizations from the pair mate, phee calls from an unfamiliar opposite sex individual, or no auditory stimuli. Levels of urinary cortisol were monitored as a physiological indicator of the stress response. Urinary cortisol levels were also monitored, while subjects remained undisturbed in their home cages to provide baseline levels. Temporarily isolated marmosets showed significantly higher levels of urinary cortisol than undisturbed marmosets. However, the nature of the acoustic stimulus experienced during isolation led to differences in the excretion of urinary cortisol. Isolated marmosets exposed to a familiar pair mate's vocalization showed significantly lower levels of urinary cortisol than when exposed to unfamiliar marmoset vocalizations (P <0.04) or to no auditory stimuli (P <0.03). Neither the duration of pairing nor the quality of relationship in the pair (indexed by spatial proximity scores) predicted the magnitude of reduction in cortisol in the familiar vocalization condition. The results presented here provide the first evidence that a single, individually specific communication signal can decrease the magnitude of a physiological stress response in a manner analogous to the physical presence of a social partner, a process we term "vocal buffering."     

Characterization of leptin pulse dynamics and relationship to fat mass,growth hormone,cortisol, and insulin

To investigate the regulation of leptin secretion and pulsatility by fat mass, we performed overnight leptin sampling every 20 min for 12 h and compared leptin dynamics with total body and regional fat measurements in 20 healthy male subjects. Simultaneous growth hormone (GH), cortisol, and insulin levels were assessed to determine relatedness and synchronicity during overnight fasting. Deconvolution analyses were performed to determine simultaneous hormonal dynamics, synchronicity, and interrelatedness using cross-correlation and cross-approximate entropy (X-ApEn) analyses. Subjects demonstrated 4.7 +/- 0.4 leptin pulses/12 h. Leptin secretion correlated highly with total body fat (r = 0.78, P < 0.001) and regional fat depots. In contrast, leptin pulsatility did not correlate with total fat (r = 0.07, P = 0.785) or other measures of fat. There was synchronicity between GH and leptin (lag -39 minutes), cortisol and leptin (lag -211 min), and leptin and insulin, with leptin following insulin by 275 min. The mean random X-ApEn was significant between leptin and GH (0.854 +/- 0.030), cortisol (0.891 +/- 0.023), and insulin (0.868 +/- 0.034), demonstrating a high degree of regularity and pattern frequency. These data demonstrate differential regulation of leptin secretion and pulsatility in adipocytes and suggest that the leptin pulse generator is extrinsic to fat, whereas fat mass acts as an amplifier to modulate secretion and amplitude for a given pulsatility. We demonstrate synchronicity between leptin and GH, cortisol, and insulin. The directionality of the cross correlation suggests a temporal construct in which changes in leptin follow those of insulin but precede those of GH and cortisol during overnight fasting.     

Familiarity may buffer the adverse effects of relocation on marmosets (Callithrix kuhlii): Preliminary evidence

The relocation of exotic species is increasingly crucial for the proper management of captive populations. We investigated the effects of relocation on urinary cortisol levels and proximity behavior in four Wied's marmosets (Callithrix kuhlii). Two of the relocated marmosets constituted a well‐established pair, whereas two (the newly established pair) were introduced when they arrived at the new facility. Four adult females served as control animals in which we assessed cortisol response to pair formation in the absence of relocation. Urinary cortisol in the relocated subjects was monitored for 4 weeks before and 12 weeks after the relocation event. Urinary cortisol in the control subjects was monitored for 4 weeks before and 8 weeks after the pairs were formed. Proximity was monitored in the relocated subjects for 12 weeks following the move. After the animals were relocated, the newly established pair had significantly elevated levels of urinary cortisol compared to the well‐established pair and control females, which lasted at least 8 weeks. For both pairs, cortisol levels decreased over time across the 12 weeks following the relocation event. The members of the well‐established pair were in contact with each other for 65% of the intervals sampled in the 2 weeks immediately following relocation, compared to only 12% in the newly established pair. These preliminary findings suggest that relocation is associated with significant adverse physiological and behavioral changes that may be ameliorated by the presence of a highly familiar social partner. The study highlights the importance of future research in this field. Zoo Biol 24:93–100, 2005. © 2005 Wiley‐Liss, Inc.     

Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin, on corticosteroid metabolism in patients with heterozygous familial hypercholesterolemia.

The present study examined whether hypolipidemic therapy with a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin, influences corticosteroid metabolism in patients with heterozygous familial hypercholesterolemia (FH). Urinary excretion of tetrahydrocortisone, tetrahydrocortisol, 6 beta-hydroxycortisol and free cortisol were determined in 22 patients with heterozygous FH before and after pravastatin administration (10 mg/day for 2 months). Pravastatin induced a statistically significant decrease in serum total cholesterol in patients with heterozygous FH from 6.9 +/- 0.1 to 5.9 +/- 0.1 mmol/l (p less than 0.05). No significant changes were seen in the urinary tetrahydrocortisone, tetrahydrocortisol and free cortisol levels before and after pravastatin therapy. Urinary excretion of 6 beta-hydroxycortisol was significantly (p less than 0.05) increased after pravastatin administration. These results suggest that the hypolipidemic effect of pravastatin in patients with heterozygous FH does not influence the corticosteroid metabolism. The increase in urinary 6 beta-hydroxycortisol may be caused by pravastatin-induced hepatic microsomal 6 beta-hydroxylase induction.     

Influence of metabolic genotype GSTM1 on levels of urinary mutagens in patients treated topically with coal tar

Fifteen hospitalized, non-smoking, dermatological patients were treated with ointment containing 2% coal tar (CT) in order to assess the influence of metabolic genotype GSTM1 on urinary mutagen levels. Urinary 1-pyrenol, the main metabolite of pyrene, was used to check the high exposure to PAH of this population. The mean levels of urinary 1-pyrenol found in the 24-h urine of our patients were 467. 8+/-211.0 nmoles-24 h (range 94.6-890.1 nmoles-24 h). Mutagenicity was assessed on urine samples collected over a period of 24 h, after three consecutive days of topical application, using the bacterial mutagenesis test on Salmonella typhimurium strains TA98 and YG1024 in the presence of microsomal enzymes. The latter strain turned out to be more sensitive than the former in revealing urinary mutagens in these patients (42 693+/-30 867 vs. 6877+/-6040 net revertants-24 h). The mutagenicity on YG1024 strain and 1-pyrenol levels of urine samples were correlated (Spearman's rank correlation coefficient=0. 6678, P<0.01, z=2.795). The influence of genotype GSTM1 on urinary mutagen levels was assessed on strain YG1024. The values of urinary mutagenicity of subjects with genotype GSTM1-null (n=6) were on average higher than those of GSTM1-positive subjects (n=9) (55 498+/-45 957 vs. 34 156+/-11 933 net rev.-24 h), a non-significant statistical difference. The mean total excretion of mutagens corrected for PAH exposure (net rev./nmoles of urinary 1-pyrenol) in GSTM1-null patients was double that of GSTM1-positive ones (136. 8+/-34.7 vs. 70.8+/-23.3 net rev./nmoles of urinary 1-pyrenol; one-tailed Mann-Whitney U-test, U=11.5, P<0.05). These results indicate a greater body burden of promutagens, resulting from skin application of CT, in GSTM1-null subjects.     

Rhythms in human bone marrow and blood cells

In 24h studies of bone marrow (BM), circadian stage-dependent variations were demonstrated in the proliferative activity of BM cells from subsets of 35 healthy diurnally active men. On an average, the percentage of total BM cells in deoxyribonucleic acid (DNA) synthesis phase was 188% greater at midday than at midnight (circadian rhythm: p = 0.018; acrophase or peak time of 13: 16h). Patients with malignant disease (n = 15) and a normal cortisol circadian rhythm showed higher fractions of BM cells in S-phase at midday. Colony-forming units--granulocyte/macrophage (CFU-GM), an indicator of myeloid progenitor cells, showed the same circadian variation as DNA S-phase (average range of change or ROC = 136%; circadian rhythm: p < 0.001; acrophase of 12:09h). Deoxyribonucleic acid S-phase and CFU-GM in BM both showed a circannual rhythm (p = 0.015 and 0.008) with an identical acrophase of August 12. The daily peak in BM glutathione content, a tripeptide involved in cellular defense against cytotoxic damage, preceded BM proliferative peaks by 4-5 h (ROC = 31-90%; circadian rhythm: p = 0.05; acrophase of 08:30h). Myeloid (ROC = 57%; circadian rhythm: p = 0.056; acrophase at 08:40h) and erythroid (ROC = 26%; circadian rhythm: p = 0.01; acrophase of 13:01h) precursor cells were positively correlated (r = 0.41; p < 0.001), indicating a circadian temporal relationship and equal influence on S-phase of total BM cells. Yield of positive selected CD34+ progenitor stem cells also showed significant circadian variation (ROC = 595%; circadian rhythm: p = 0.02; acrophase of 12:40h). Thus, the temporal synchrony in cell cycling renders BM cells more sensitive at specific times to hematopoietic growth factors and cell cycle-specific cytotoxic drugs. Moreover, proper timing of BM harvesting may improve progenitor cell yield. When using marker rhythms in the blood to allow for individualized timing of BM procedures, the times of low values in white blood corpuscles, neutrophils, and lymphocytes and high values in cortisol were predictive of the times of highest BM erythroid, myeloid, and total S-phase numbers occurring in the following 12 h.     

Urinary neopterin in patients with advanced colorectal carcinoma

In previous studies, mostly in patients with early stage colorectal carcinoma, neopterin, an indicator of systemic immune activation, has been associated with poor prognosis. The aim of the present study was to evaluate urinary neopterin in patients with advanced or metastatic colorectal carcinoma treated with chemotherapy. A retrospective analysis was performed of urinary neopterin, determined by high-performance liquid chromatography, in 88 patients with advanced or metastatic colorectal carcinoma. Peripheral blood cell count and serum carcinoembryonic antigen (CEA) were determined in 72 patients before the start of chemotherapy. Urinary neopterin in colorectal carcinoma patients was significantly increased compared to controls, but lower than in patients with inflammatory bowel disease. Neopterin correlated significantly with serum CEA, age, peripheral blood leukocyte and platelet counts. The median survival of colorectal carcinoma patients with urinary neopterin below 214 micromol/mol creatinine was significantly longer compared to that of patients with higher neopterin concentrations (median 18 vs 5 months, log-rank test p=0.003). CEA and hemoglobin were also associated with survival in univariate analysis, but in multivariate analysis only urinary neopterin and serum CEA were independent predictors of survival. High urinary neopterin during follow-up was also predictive of poor prognosis.     

Do Premenopausal Women with Major Depression Have Low Bone Mineral Density? A 36-Month Prospective Study

Background

An inverse relationship between major depressive disorder (MDD) and bone mineral density (BMD) has been suggested, but prospective evaluation in premenopausal women is lacking.

Methods

Participants of this prospective study were 21 to 45 year-old premenopausal women with MDD (n = 92) and healthy controls (n = 44). We measured BMD at the anteroposterior lumbar spine, femoral neck, total hip, mid-distal radius, trochanter, and Ward''s triangle, as well as serum intact parathyroid hormone (iPTH), ionized calcium, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-hour urinary-free cortisol levels at 0, 6, 12, 24, and 36 months. 25-hydroxyvitamin D was measured at baseline.

Results

At baseline, BMD tended to be lower in women with MDD compared to controls and BMD remained stable over time in both groups. At baseline, 6, 12, and 24 months intact PTH levels were significantly higher in women with MDD vs. controls. At baseline, ionized calcium and 25-hydroxyvitamin D levels were significantly lower in women with MDD compared to controls. At baseline and 12 months, bone-specific alkaline phosphatase, a marker of bone formation, was significantly higher in women with MDD vs. controls. Plasma ACTH was also higher in women with MDD at baseline and 6 months. Serum osteocalcin, urinary N-telopeptide, serum cortisol, and urinary free cortisol levels were not different between the two groups throughout the study.

Conclusion

Women with MDD tended to have lower BMD than controls over time. Larger and longer studies are necessary to extend these observations with the possibility of prophylactic therapy for osteoporosis.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT 00006180","term_id":"NCT00006180"}}NCT 00006180     

Variable sensitivity to the glucocorticoid activity of cortisol in patients with primary adrenal insufficiency: assessment with ACTH profiles

Our aim was to investigate the usefulness of circulating levels of adrenocorticotropic hormone (ACTH) and also salivary cortisol to monitor cortisone substitution in patients with Addison's disease. 13 patients with primary adrenal insufficiency (8 women and 5 men, age 44 ± 11 years) received 12.5 mg cortisone acetate orally at 16:00 h and 25 mg at 07:00 h. Blood samples for cortisol and ACTH analysis were drawn every hour for 24 h, and also every half hour between 07:00 and 12:00 h. Samples for salivary cortisol were collected in parallel. Total ACTH levels showed large inter-individual variations and a diurnal rhythm with a nadir in the early evening at 19:00 (median 19 ng/l, range 2-434 ng/l) and high levels in the early morning, with a peak around 07:30 (median 844 ng/l, range 45-2,249 ng/l). Plasma cortisol concentrations showed 2 peaks distinct in time, but variable in height, 1-2 h after intake of cortisone. Plasma cortisol correlated significantly with ln(ACTH) at 17:00 h (r=-0.56), at 10:00 h (r=-0.51), and at 10.30 h (r=-0.57). When tested at different time points, ln(ACTH) at 10:00 to 12:00 h was negatively correlated with plasma cortisol between 08:30 and 12:00 h. Plasma cortisol was highly correlated to ln(salivary cortisol) most of the time points measured, but 30-60 min after intake of cortisone acetate the correlation disappeared. In conclusion, the large interindividual variation in ACTH levels most likely indicates varying sensitivity to cortisol with a need for individualized dosing schemes. Furthermore ACTH-determinations may be useful for dose titration of cortisol.     

Comparison of serum estradiol to urinary estrone conjugates in the rhesus macaque (Macaca mulatta)

Paired urine and serum samples were collected daily during fourteen nonconceptive (7 females) and ten conceptive (9 females) ovarian cycles from a total of 12 female rhesus monkeys (Macaca mulatta). Daily urine samples were analyzed for concentrations of estrone conjugates (Ei Conj). Serum samples were evaluated for concentrations of estradiol (E2) and progesterone (P) by radioimmunoassay (RIA), and bioactive luteinizing hormone (bLH) and monkey chorionic gonadotropin (mCG) were analyzed by a mouse Leydig cell bioassay. Linear correlation (r) between urinary E1 Conj and serum E2 (r range = -0.176-0.948) during nonconceptive cycles aligned by the preovulatory E1 Conj peak (Day 0) improved when daily hormone values were realigned to account for an approximately 24-h delay in the excretion of hormonal metabolites in urine (r range = 0.465-0.967). Similarly, correlation between urinary E1 Conj and serum E2 during conceptive cycles aligned by Day 0 (r range = 0.300-0.824) improved when values were offset by 24 h (r range = 0.408-0.876). When conceptive cycles were compared to nonconceptive cycles, serum P levels were significantly elevated over nonconceptive levels by Day +12 (p less than 0.001), and urinary E1 Conj levels by Day +13 (p less than 0.02), whereas serum E2 and bLH were both significantly elevated by Day +14 (p less than 0.0006 and p less than 0.01, respectively). In both nonconceptive and conceptive cycles, urinary E1 Conj paralleled serum E2 and demonstrated incremental increases above baseline levels, which were greater than for serum E2.     

Molybdenum in infancy: Methodical investigation of urinary excretion

PROJECT: The clinical evaluation of trace element metabolism in infancy is based on optimal pre-analytical procedures. Urinary molybdenum excretion, the major determinant of its retention, was investigated to deduce criteria for representative specimen collection. PROCEDURES: 1.) Molybdenum concentration was analyzed in 24-hour urinary specimens (n = 193) to evaluate the range in pediatric patients. 2.) In 20 children aged 0.4 to 9.3 (mean 2.3) years admitted for a micturition cystourethrogram, three urinary collection methods (catheter, spontaneous midstream samples, urinary collection bags) were compared. 3.) Diurnal variations of molybdenum concentration were assessed by fractional urinary colLection in preterm infants fed infant formula or human milk (n = 10). Analysis was performed using atomic absorption spectroscopy. RESULTS: 1.) The molybdenum concentration in 24hour specimens was 4.0 (0-123) microg Mo/l. 2.) Urine gained by catheter collection (n = 20) rendered 7.0 (0.5-60.1) microg Mo/l, midstream samples and the use of urinary collection bags showed a concentration of 21.25 (0-91) microg Mo/l (p > 0.05). 3.) Fractional collection over 72 hours rendered a significant increase in only one participant. Diurnal differences of the urinary molybdenum concentration were significant between 3-6 p.m. and 6-9 p.m.. The molybdenum/creatinine quotient differed between the time intervals 3-6 p.m. and 9-12 p.m., as well as 9-12 a.m. and 6-9 a.m. (p < 0.05). CONCLUSION: Pediatric routine procedures are suitable for the assessment of urinary molybdenum excretion. The diurnal variations assessed are of minor clinical relevance, but should be considered by respective definition of collecting times and reference values.     

Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress

In vitro studies have shown that alpha-lipoic acid (LA) is an antioxidant. There is a paucity of studies on LA supplementation in humans. Therefore, the aim of this study was to assess the effect of oral supplementation with LA alone and in combination with alpha-tocopherol (AT) on measures of oxidative stress. A total of 31 healthy adults were supplemented for 2 months either with LA (600 mg/d, n = 16), or with AT (400 IU/d, n = 15) alone, and then with the combination of both for 2 additional months. At baseline, after 2 and 4 months of supplementation, urine for F2-isoprostanes, plasma for protein carbonyl measurement and low-density lipoprotein (LDL) oxidative susceptibility was collected. Plasma oxidizability was assessed after incubation with 100 mM 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) for 4 h at 37 degrees C. LDL was subjected to copper- and AAPH-catalyzed oxidation at 37 degrees C over 5 h and the lag time was computed. LA significantly increased the lag time of LDL lipid peroxide formation for both copper-catalyzed and AAPH-induced LDL oxidalion (p < .05), decreased urinary F2-isoprostanes levels (p < .05), and plasma carbonyl levels after AAPH oxidation (p < .001). AT prolonged LDL lag time of lipid peroxide formation (p < .01 ) and conjugated dienes (p < .01) after copper-catalyzed LDL oxidation, decreased urinary F2-isoprostanes (p < .001), but had no effect on plasma carbonyls. The addition of LA to AT did not produce an additional significant improvement in the measures of oxidative stress. In conclusion, LA supplementation functions as an antioxidant, because it decreases plasma- and LDL-oxidation and urinary isoprostanes.     

Effects of age, sex and renal function on urinary insulin-like growth factor I (IGF-I) levels in adults.

Insulin-like growth factor I (IGF-I) levels in urine were measured in adults using specific RIA after extraction with acid-ammonium sulfate. Mean (+/- SD) total urine IGF-I values were 267.9 +/- 112.9 ng/day and 167.8 +/- 73.2 ng/g creatinine (Cr) in 17 normal young adults. There was a positive correlation (r = 0.785, P < 0.001) between IGF-I values in early morning urine and those of 24 h urine when they were corrected by urinary Cr. IGF-I values in early morning urine were ranged from 60 to 1,100 ng/gCr with a mean value of 309.6 ng/gCr in 178 normal adults aged 21-80 yr. There was a consistent trend towards higher urinary IGF-I values in males during aging and this trend did not reach statistical significance until the sixth and seventh decades. There was a positive correlation (r = 0.465, P < 0.005) between urinary IGF-I values and age in males but not in females. Although urinary IGF-I values were higher in females than in males of the second and third decades, no sex difference was found in older adults. Urinary IGF-I values were correlated reversely with 24 h Cr clearance (CCr) and positively with urinary beta 2-microglobulin (beta 2-MG) levels in patients with renal dysfunction. These findings indicate that urinary IGF-I levels are influenced by age, sex and renal function in adults.     

Serum lipids and urinary albumin excretion in non insulin-dependent diabetics

The increase of urinary albumin excretion has a predictive value for cardiovascular disease in insulin-dependent and non insulin-dependent diabetics. To study the relationship between urinary albumin excretion and serum lipids, 380 non insulin-dependent diabetics, 40 to 75 yr old, with urinary albumin excretion from 0 to 200 mg/l, and normal serum creatinine (less than 150 µmol/1), were surveyed. Urinary albumin excretion, was related positively to age (r² = 0.014; p = 0.02), to systolic blood pressure (r² = 0.073, p = 0.0001) and diastolic blood pressure (r² = 0.052, p = 0.0001); a negative correlation existed with HDL-cholesterol (r² = 0.043, p = 0.0001) and Apoprotein A1 (r² = 0.044, p = 0.0001). A stepwise regression analysis was performed and resulted in three independently contributing variables related to urinary albumin excretion: First systolic blood pressure (F = 36), second Apoprotein A1 (F 24), third hemoglobin AlC (F = 6). The presence of hypertension or insulin therapy did not modify these findings. In conclusion, serum lipid seems an important determinant of urinary albumin excretion in non insulin-dependent diabetics.Abbreviations UAE Urinary Albumin Excretion - IDDs Insulin-Dependent Diabetics - NIDDs Non Insulin-Dependent Diabetics - ACE Angiotensin-converting-enzyme - HDL High Density Lipoproteins - VLDL Very Low Density Lipoproteins - LDL Low Density Lipoproteins     

Diurnal rhythm of 3-methoxy-4-hydroxyphenylglycol (MHPG): relationship between plasma and urinary levels

Plasma and urinary levels of MHPG were determined in six normal volunteers. Samples were obtained at 3-hour intervals for plasma and at 12-hour intervals for urine. Acrophase, amplitude and period were determined for plasma MHPG levels. A sinusoidal pattern was obtained for diurnal plasma MHPG with a peak at 15:00 hrs. +/- 46 min. Urinary MHPG, corrected for creatinine levels, correlated with both 9 AM plasma MHPG and with baseline plasma MHPG. Furthermore, the relationship between plasma and urinary MHPG was linear when the rhythm of urinary levels was assumed to lag 6.2 hours behind the plasma rhythm. It was concluded that free MHPG is evenly distributed in the total body space and that conjugated MHPG is largely restricted to the blood.