A case-control study on the association of mineral elements exposure and thyroid tumor and goiter.

Thyroid tumor and thyroid goiter are prevalent disease around the world. In this case-control study, we investigated the association between exposure to a total of twelve mineral elements and thyroid disease as well as thyroid functions. Participants with thyroid tumor or goiter (N = 197) were matched with a healthy population (N = 197) by age (± 2 years old) and same sex. Questionnaires were used to collect data about the demographic characteristics and information of subjects. Serum and urine samples were collected simultaneously for each of the subjects. Mineral elements, iodine level of urine and levels of the total seven thyroid function indexes in serum were detected respectively. Conditional logistic regression was applied to estimate the associations between mineral elements and the risk of thyroid tumor and goiter through single-element models and multiple-element models. Multiple linear regression was used to evaluate relationships between mineral elements and percentage changes of thyroid functions. Higher concentrations of mineral elements in the recruited population were found in this study than other comparable studies, and the levels of chromium (Cr), manganese (Mn), nickel (Ni), arsenic (As), cadmium (Cd), selenium (Se), antimony (Sb), thallium (Tl) and lead (Pb) in the case group were lower than the control group. According to the single-element models, Cr, Mn, Ni, Sb and Tl showed significant negative associations with the risk of thyroid tumor and goiter, and, Cd showed nonmonotonic dose response. Cd and mercury (Hg) showed a nonmonotonic percentage change with T4, while Tl was associated with the increased FT4 in the control group. Therefore, Cd, Hg and Tl may disturb the balance of thyroid function to some extent, and Cr, Mn, Ni, Cd, Sb, and Tl may become potential influencing factors for the risk of thyroid tumor and goiter.

Dexlansoprazole and Esomeprazole Do Not Affect Bone Homeostasis in Healthy Postmenopausal Women.

BACKGROUND & AIMS: Epidemiological studies have associated proton pump inhibitor (PPI) therapy with osteoporotic fractures, but it is not clear if PPIs directly cause osteoporosis. We evaluated the effect of dexlansoprazole and esomeprazole on bone turnover, bone mineral density (BMD), true fractional calcium absorption (TFCA), serum and urine levels of minerals, and levels of parathyroid hormone (PTH) in healthy postmenopausal women. METHODS: We performed a prospective, multicenter, double-blind study of 115 healthy, postmenopausal women (45 to 75 years of age) from November 4, 2010, through August 7, 2014. Women were randomly assigned to groups given dexlansoprazole (60 mg), esomeprazole (40 mg), or placebo daily for 26 weeks. We measured plasma levels of procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) at 0 (baseline), 13, and 26 weeks. Primary outcomes were percent change in P1NP and CTX between weeks 0 and 26. We also measured changes in serum and urine levels of mineral, BMD, PTH (all subjects), and TFCA (n = 30). RESULTS: Between baseline and week 26, there were no significant within-group differences in markers of bone turnover; there was a nonsignificant increase in CTX levels in the dexlansoprazole group (0.12 ng/mL). The esomeprazole and dexlansoprazole groups had significantly increased levels of P1NP (18.2% and 19.2%, respectively) and CTX (22.0% and 27.4%, respectively) at week 26 compared with the placebo group, although these values remained within normal ranges. There were no statistically significant differences between groups in serum or urine levels of minerals, BMD, or PTH at week 26. PPI therapy did not reduce TFCA. CONCLUSIONS: In a prospective study of postmenopausal women, we found significant increases in markers of bone turnover in women given PPI therapy compared with women given placebo, but levels remained within the normal reference range. We found no significant differences among groups in changes in BMD, PTH, serum or urine levels of minerals, or TFCA. Our findings indicate that 26 weeks of treatment with a PPI has no clinically meaningful effects on bone homeostasis. Clinicaltrials.gov no: NCT01216293.

The ACE-2/Ang1-7/Mas cascade enhances bone structure and metabolism following angiotensin-II type 1 receptor blockade.

The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p.o.) for 6 weeks. A specific Mas receptor blocker (A-779) was delivered via mini-osmotic pumps during the losartan treatment period. Serum and urine bone metabolism biomarker levels were measured. Bone trabecular and cortical morphometry were quantified in distal femurs, whereas mineral contents were estimated in ashed bones, serum and urine. Finally, the expression of RAS components, the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) was determined. Losartan significantly improved the elevated bone metabolism marker levels and altered trabecular and cortical structures in OVX animals, and restored normal urinary and skeletal mineral levels. Mas receptor inhibition significantly abolished all osteo-protective effects of losartan and enhanced the deleterious effects of OVX. Losartan enhanced OVX-induced up-regulation of ACE-1, AngII, angiotensin type 1 (AT1) receptor and RANKL expression, and increased ACE-2, Ang1-7, Mas and OPG expression in OVX animals. However, A-779 significantly eradicated the effects of losartan on RAS components and RANKL/OPG expression. Thus, Ang1-7 are involved in the osteo-preservative effects of losartan via Mas receptor, which may add therapeutic value to this well-known antihypertensive agent.

Reproducibility of urinary biomarkers in multiple 24-h urine samples.

BACKGROUND: Limited knowledge regarding the reproducibility of biomarkers in 24-h urine samples has hindered the collection and use of the samples in epidemiologic studies. OBJECTIVE: We aimed to evaluate the reproducibility of various markers in repeat 24-h urine samples. DESIGN: We calculated intraclass correlation coefficients (ICCs) of biomarkers measured in 24-h urine samples that were collected in 3168 participants in the NHS (Nurses' Health Study), NHSII (Nurses' Health Study II), and Health Professionals Follow-Up Study. RESULTS: In 742 women with 4 samples each collected over the course of 1 y, ICCs for sodium were 0.32 in the NHS and 0.34 in the NHSII. In 2439 men and women with 2 samples each collected over 1 wk to ≥1 mo, the ICCs ranged from 0.33 to 0.68 for sodium at various intervals between collections. The urinary excretion of potassium, calcium, magnesium, phosphate, sulfate, and other urinary markers showed generally higher reproducibility (ICCs >0.4). In 47 women with two 24-h urine samples, ICCs ranged from 0.15 (catechin) to 0.75 (enterolactone) for polyphenol metabolites. For phthalates, ICCs were generally ≤0.26 except for monobenzyl phthalate (ICC: 0.55), whereas the ICC was 0.39 for bisphenol A (BPA). We further estimated that, for the large majority of the biomarkers, the mean of three 24-h urine samples could provide a correlation of ≥0.8 with true long-term urinary excretion. CONCLUSIONS: These data suggest that the urinary excretion of various biomarkers, such as minerals, electrolytes, most polyphenols, and BPA, is reasonably reproducible in 24-h urine samples that are collected within a few days or ≤1 y. Our findings show that three 24-h samples are sufficient for the measurement of long-term exposure status in epidemiologic studies.

Translocation of mineralo-organic nanoparticles from blood to urine: a new mechanism for the formation of kidney stones?

Recent studies indicate that mineralo-organic nanoparticles form in various human body fluids, including blood and urine. These nanoparticles may form within renal tubules and increase in size in supersaturated urine, eventually leading to the formation of kidney stones. Here, we present observations suggesting that mineralo-organic nanoparticles found in blood may induce kidney stone formation via an alternative mechanism in which the particles translocate through endothelial and renal epithelial cells to reach urine. We propose that this alternative mechanism of kidney stone formation and the study of mineralo-organic nanoparticles in general may provide novel strategies for the early detection and treatment of ectopic calcifications and kidney stones.

[Long-term effect of environmental cadmium exposure on human body's mineral metabolic balance].

OBJECTIVE: To investigate the effect of long-term exposure to environmental cadmium on eight mineral element's metabolic balance of human body. METHODS: To choose a high cadmium area polluted by smelting and mining north of Guangdong province and a cadmium-free area with a similar economic level, and living and eating habit of residents as a contrast from April 2011 to August 2012. Stratified random sampling and clustered sampling method were adopted to choose the non-occupationally cadmium-exposed respondents who have lived in local area for more than 15 years, older than 40 years, having local rice and vegetable as the main dietary source, with simple and relatively stable diet, and without diabetes, kidney disease, thyroid disease, liver disease or other history of chronic disease. This study included 298 respondents, of whom 155 were in cadmium exposure group and 143 in control group. Questionnaires was used to acquire their health status and their morning urine samples were collected. Electrolytically coupled plasma mass spectrometry (ICP-MS) was used to test the concentrations of sodium(Na), magnesium (Mg), phosphorus (P), potassium (K), calcium (Ca), copper (Cu), zinc (Zn) and iodine (I). The Mann-Whitney U test method was used to compare the differences of concentrations of urinary cadmium, Na, Mg, P, K, Ca, Cu, Zn, I, and the ratio of Na to K (Na/K), Ca to P (Ca/P) between exposed group and control group.χ(2) test was used to compare the abnormal rate of urinary cadmium between exposed group and control group. Pearson correlation and multiple regression method were used to investigate the relationship between urinary cadmium levels, gender, age, smoking, passive smoking, and minerals. RESULTS: The urinary cadmium level P50 (P25-P75) in exposed group was 5.45 (2.62-10.68) µg/g·cr, which was higher than that of the control group, which was 1.69 (1.22-2.36) µg/g·cr (Z=-10.49,P<0.001). The abnormal rate of urinary cadmium was 51.6% (80/155), which was higher than that of the control group (2.8 %(4/143)) (χ(2)= 87.56, P<0.001). The urinary Ca, Cu, Zn, and I level P50 (P25-P75) of exposed group were 173.80 (114.40-251.70), 20.55 (14.95-28.44), 520.23 (390.25-647.15), and 246.94 (203.65-342.97) µg/g·cr, which were higher than those in control group (142.42 (96.87-179.11), 15.44 (12.26-20.98), 430.09 (309.85-568.78) and 213.85 (156.70-281.63) µg/g·cr, respectively) (Z values were-4.33,-5.04,-3.47 and-4.24, all P values <0.001). The urinary P, K level P50 (P25-P75) of exposed group were 582.50 (463.20-742.8), 890.10(666.00-1 305.40) µg/g·cr, which were lower than control group (694.50 (546.20-851.17), 1 098.58(904.53-1 479.18) µg/g·cr) (Z values were-3.36,-4.02, all P values <0.001). on Based the results of Pearson correlation analysis, urinary cadmium was positively correlated with urinary Ca, Cu, Zn, and I, and the correlation coefficients were 0.31, 0.61, 0.38, and 0.25, respectively (all P values <0.05). Based on the results of multiple regression analysis, urinary cadmium levels contributed most to the metabolic balance of urinary Ca, Cu, Zn and I. The standardized regression coefficients were 0.31, 0.59, 0.39, and 0.24, respectively (all P values<0.001). CONCLUSION: Long-term environmental exposure to cadmium affected the metabolic balance of Ca, Cu, Zn and I in human body.

Application of Market Basket Analysis for the Visualization of Transaction Data Based on Human Lifestyle and Spectroscopic Measurements.

With the innovation of high-throughput metabolic profiling methods such as nuclear magnetic resonance (NMR), data mining techniques that can reveal valuable information from substantial data sets are constantly desired in this field. In particular, for the analytical assessment of various human lifestyles, advanced computational methods are ultimately needed. In this study, we applied market basket analysis, which is generally applied in social sciences such as marketing, and used transaction data derived from dietary intake information and urinary chemical data generated using NMR and inductively coupled plasma optical emission spectrometry measurements. The analysis revealed several relationships, such as fish diets with high trimethylamine N-oxide excretion and N-methylnicotinamide excreted at higher levels in the morning and produced from a protein that was consumed one day prior. Therefore, market basket analysis can be applied to metabolic profiling to effectively understand the relationships between metabolites and lifestyle.

Effect of dietary mineral sources and oil content on calcium utilization and kidney calcification in female Fischer rats fed low-protein diets.

We studied the effects of dietary mineral source and oil intake on kidney calcification in 4-wk-old female Fischer rats after consuming the AIN-76 purified diet (AIN-76). A modified AIN-76 mineral mixture was used, although the original calcium (Ca)/phosphorus (P) molar ratio remained unchanged. Rats were fed the modified diets for a period of 40 d before their kidneys were removed on the last day. Ca balance tests were performed on days 31 to 36 and biochemical analysis of urine was also studied. Kidney Ca, P, and magnesium (Mg) in the standard diet group (20% protein and 5% oil) were not affected by the mineral source. Kidney Ca, P, and Mg in the low-protein (10% protein) diet group, were found to be influenced by the dietary oil content and mineral source. In particular, the different mineral sources differentially increased kidney mineral accumulation. Pathological examination of the kidney showed that the degree of kidney calcification was proportional to the dietary oil content in the 10% dietary protein group, reflecting the calcium content of the kidney. The information gathered on mineral sources in this study will help future researchers studying the influence of dietary Ca/P molar ratios, and histological changes in the kidney.

A comparison of parathyroid hormone-related protein (1-36) and parathyroid hormone (1-34) on markers of bone turnover and bone density in postmenopausal women: the PrOP study.

Parathyroid hormone-related protein (PTHrP)(1-36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but it has not been directly compared with parathyroid hormone (PTH)(1-34). We performed a 3-month randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis, comparing daily subcutaneous injections of PTHrP(1-36) to PTH(1-34). Thirty-five women were randomized to each of three groups: PTHrP(1-36) 400 µg/day; PTHrP(1-36) 600 µg/day; and PTH(1-34) 20 µg/day. The primary outcome measures were changes in amino-terminal telopeptides of procollagen 1 (PINP) and carboxy-terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)2 vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1-34) (92%) (p < 0.005) was greater than for PTHrP(1-36) (30%) (p < 0.05). PTH(1-34) also increased bone formation (PINP) (171%) (p < 0.0005) more than either dose of PTHrP(1-36) (46% and 87%). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all three groups. LS BMD increased equivalently in each group (p < 0.05 for all). Total hip (TH) and femoral neck (FN) BMD increased equivalently in each group but were only significant for the two doses of PTHrP(1-36) (p < 0.05) at the TH and for PTHrP(1-36) 400 (p < 0.05) at the FN. PTHrP(1-36) 400 induced mild, transient (day 15) hypercalcemia. PTHrP(1-36) 600 required a dose reduction for hypercalcemia in three subjects. PTH(1-34) was not associated with hypercalcemia. Each peptide induced a marked biphasic increase in 1,25(OH)2 D. Adverse events (AE) were similar among the three groups. This study demonstrates that PTHrP(1-36) and PTH(1-34) cause similar increases in LS BMD. PTHrP(1-36) also increased hip BMD. PTH(1-34) induced greater changes in bone turnover than PTHrP(1-36). PTHrP(1-36) was associated with mild transient hypercalcemia. Longer-term studies using lower doses of PTHrP(1-36) are needed to define both the optimal dose and full clinical benefits of PTHrP. © 2013 American Society for Bone and Mineral Research.

Comparative effect of green tea, chokeberry and honeysuckle polyphenols on nutrients and mineral absorption and digestibility in rats.

BACKGROUND/AIMS: Natural polyphenols are chemically and biologically active. This study aimed at examining the physiological effects of high doses of polyphenol extracts from green tea and new polyphenol-rich sources (chokeberry and honeysuckle fruits) on nutrient absorption. METHODS: 32 male Wistar rats were divided into four groups and fed a diet supplemented with one of the three polyphenolic extracts (at 0.4%) or a control diet for 4 weeks. A perfusion technique was used to study the effects at intestinal level. Pure polyphenols from the three sources were introduced into perfusion fluid at a concentration of 0.4% and allowed to cross the intestinal tract in 1.5 h. RESULTS: In the perfusion experiment, addition of the extracts caused a strong and statistically significant reduction in absorption of the selected nutrients (water, glucose, cholesterol, amino acids and minerals) compared to control animals. In the nutritional experiment, we recorded a slight decrease in diet utilization and growth in rats on polyphenolic diets relative to control group. In the same experiment, we observed a reduction of Zn and Cu absorption, but this was not accompanied by diminished concentrations in the bone femur. CONCLUSIONS: The presence of the polyphenolic extracts in the perfusion liquids significantly reduced absorption from the small intestine, but the nutritional experiment did not confirm deleterious consequences of the consumption of high extract doses.

Fetal and postnatal bone development: reviewing the role of mechanical stimuli and nutrition.

Fetal and postnatal bone development is by tradition viewed as a process of bone mineral accretion or an increase in bone mass. Accordingly, previous approaches to bone development in neonatology and early childhood have emphasized the determinants of peak bone mass and their relationship to osteopenia, osteoporosis and fractures in later life. This suggests that the neonatal period and early childhood is an important period for bone mineral accrual, and that peak bone mass may be correlated with subsequent skeletal health. Nevertheless, describing fetal and postnatal bone development just in terms of changes in mass or density means looking at bones as if they were amorphous heaps of calcium and phosphorus. In reality, of course, bones are complex three-dimensional structures. It is therefore important to create conditions that stimulate bones to become more stable. We suggest that functional bone physiology can be used to explain fetal and postnatal bone development and to devise strategies for improved bone development in both premature infants and neonates.

Tissue iron distribution and urinary mineral excretion vary depending on the form of iron (FeSO4 or NaFeEDTA) and the route of administration (oral or subcutaneous) in rats given high doses of iron.

Sodium iron ethylenediaminetetraacetate (NaFeEDTA) has considerable promise as an iron fortificant in food. However, effects of administering high levels of NaFeEDTA on tissue iron distribution and mineral excretion are not well understood. The objectives of this study were to assess nonheme iron distribution in the body and urinary excretion of Ca, Mg, Cu, Fe, and Zn after daily administration of high levels of iron to rats over 21 days. Iron was either given orally with food or injected subcutaneously, as either FeSO 4 or NaFeEDTA. Selected tissues were collected for nonheme iron analysis. Estimated total body nonheme iron levels were similar in rats fed NaFeEDTA or FeSO 4, but the tissue distribution was different: it was 53% lower in the liver and 86% higher in the kidneys among rats fed NaFeEDTA than among those fed FeSO 4. In contrast, body nonheme iron was 3.2-fold higher in rats injected with FeSO 4 than in rats injected with NaFeEDTA. Administering NaFeEDTA orally elevated urinary Cu, Fe, and Zn excretion compared with FeSO 4 (1.41-, 11.9-, and 13.9-fold higher, respectively). We conclude that iron is dissociated from the EDTA complex prior to or during intestinal absorption. A portion of intact FeEDTA may be absorbed via a paracellular route at high levels of intake but is mostly excreted in the urine. Metal-free EDTA may be absorbed and cause elevated urinary excretion of Fe, Cu, and Zn.

Hydromineral balance in the marine gulf toadfish (Opsanus beta) exposed to waterborne or infused nickel.

The effects of acute Ni exposure on the marine gulf toadfish (Opsanus beta) were investigated via separate exposures to waterborne nickel (Ni) and arterially infused Ni. Of the plasma electrolytes measured after 72 h of waterborne exposure (215.3 and 606.1 microM Ni in SW (salinity of 34)), only plasma [Ca2+] was significantly impacted (approximately 55% decrease at both exposure concentrations). At both exposure concentrations, plasma [Ni] was regulated for 24h, after which a linear accumulation over time occurred. Accumulation of Ni in the plasma, and in tissues in direct contact with seawater (gill, stomach, and intestine), was roughly proportional to the Ni concentration of the exposure water. Hydromineral balance in the intestinal fluid (IF) was markedly impacted, with Na(+), Cl(-), SO(4)(2-), K+, and Mg2+ concentrations elevated after 72 h of exposure to waterborne Ni. Following arterial Ni infusion (0.40 micromolNikg(-1)h(-1)), perturbation of hydromineral balance of the intestinal fluid was specific only to Na+ (significantly elevated by Ni infusion) and Mg2+ (significantly decreased by Ni infusion). Nitrogen excretion was not significantly impacted by Ni infusion. In all tissues save the kidney, Ni accumulation via infusion was only a fraction of that observed during waterborne exposures. Remarkably, the kidney Ni burden following infusion was almost identical to that resulting from both waterborne exposures, suggesting homeostatic control. Ni excretion, dominated at 24 h by extrarenal routes, was primarily a function of renal excretion by 72 h of infusion. The sum excretion from infused toadfish was relatively efficient, accounting for over 40% of the infused dose by 72 h. Mechanistic knowledge of the mechanisms of toxicity of waterborne Ni in marine systems is a critical component to the development of physiologically based modeling approaches to accurately predict Ni toxicity in marine and estuarine ecosystems.

Dietary intake in male and female smokers, ex-smokers, and never smokers: the INTERMAP study.

This report examines dietary intakes in smokers, ex-smokers, and never smokers in INTERMAP. The 4680 participants aged 40-59 years-from 17 population samples in four countries (China, Japan, UK, USA)-provided four 24-h recalls to assess nutrient intakes and two 24-h urine collections to assess excretion of urea, sodium (Na), potassium (K), etc. Compared to never smokers, current smokers generally consumed more energy from alcohol and saturated fats (SFA), less energy from vegetable protein and carbohydrates, less dietary fibre, vitamin E, beta carotene, vitamin C, thiamine, riboflavin, folate, vitamin B6, calcium, iron, phosphorus, magnesium (Mg), and K per 1000 kcal, excreted less K and urea (marker of dietary protein), had a lower ratio of polyunsaturated fat (PFA) to SFA intake, higher Keys dietary lipid score, and higher dietary and urinary Na/K. There were few differences between smokers and never smokers for total energy intake, energy from total and animal protein, monounsaturated fats, PFA, omega 3 and omega 6 PFA, dietary cholesterol, total vitamin A, retinol, vitamin D, vitamin B12, and urinary and dietary Na. Compared to ex-smokers, smokers generally consumed less energy from vegetable protein, omega 3 PFA, carbohydrates, less dietary fibre, beta carotene, vitamin E, vitamin C, thiamine, riboflavin, folate, vitamin B6, iron, phosphorus, Mg, had lower PFA/SFA, and excreted less urea and K. In conclusion, INTERMAP results are consistent with other reports indicating that smokers have less healthful diets than nonsmokers. Public health interventions in smokers should focus not only on helping them to quit smoking but also on improving their diets to further reduce cancer and cardiovascular disease risks.

[Analysis of vitamin and mineral sufficiency in children using data of consumption with food and urinary excretion]. / Otsenka obespechennosti detei vitaminami i mineral'nymi veshchestvami po dannym o postuplenii ikh s pishchei i ékskretsii s mochoi.

It has been shown that vitamin C and B2, calcium and phosphorus daily intake strongly correlated with their urinary excretion in children 5-8 years old (Moscow) from the decreased bone mineral density risk group. Hour urinary calcium, phosphorus, creatinine excretion values for adequately supplied children has been determined. Vitamin and mineral status evaluation by means of estimation of vitamins and minerals consumption and urinary level (except vitamin B2) give relatively coincided results. Difference between these methods of nutritive status assessment attains 8-25 per cent. Thus these methods are substituted for group nutritive status evaluation.

Role of urinary physiology and chemistry in bladder carcinogenesis.

Urine is a complex mixture of numerous substances, only some of which are described above. Literally thousands of substances have been identified in normal urine, including a variety of ions, non-ionic substances and macromolecules. Their presence and concentrations are highly variable, dependent on fluid intake and on nutritional, physiological and biochemical influences. Marked diurnal variations exist. Methodologies involved in the collection and analysis of these components can greatly influence the interpretation of the results. The influence of these various parameters in the urine on bladder carcinogenicity can be either direct or indirect. A major difficulty in studying this aspect of urothelial carcinogenesis is that it is essentially impossible to alter only one variable in the urine at a time. Alteration of any one variable results in physiological alteration of several other of the constituents in the urine. In addition, the processes involved in urothelial carcinogenesis frequently involve a complex interaction of multiple variables, such as volume, osmolality, cationic concentration, anionic concentration, quantitative and qualitative differences in protein, and generation of precipitate, crystals or calculi. Thus, it is likely that the actual mechanisms involved in the carcinogenic process with many of these chemicals, particularly those that are non-genotoxic, will involve a complex interaction of several constituents of the urine. Although this poses a formidable obstacle to our understanding in experimental situations as well as in extrapolating to humans, the role of specific factors appears to be discernible and should offer insight into the risk assessment process (Cohen and Ellwein, 1991 a,b and 1992).

A prospective study of several potential biologic markers for early prediction of the development of preeclampsia.

OBJECTIVE: The purpose of this study was to prospectively evaluate the predictive performance of several potential biologic markers of preeclampsia used alone or in combination. STUDY DESIGN: A prospective cohort of 1366 nulliparous women was followed up longitudinally on three occasions during pregnancy. The predictive performance of the tests, used either alone or in combination (stepwise multiple logistic regression), was assessed and compared with that of the mean arterial pressure. RESULTS: Preeclampsia occurred in 109 of the pregnant women. At a specificity of 80% the sensitivity and the positive and negative predictive values for mean arterial pressure (at a threshold of 87 mm Hg) were 46.6%, 23.5%, and 92.0%, respectively, and the corresponding values for a multiple logistic model at 15 to 24 weeks that included some biologic markers, as well as the mean arterial pressure, were 57.1%, 26.9%, and 93.7%, respectively. CONCLUSION: Preeclampsia can be predicted by a combination of simple biologic tests with a performance similar to second-trimester mean arterial pressure. However, this procedure is insufficient in terms of clinical usefulness.

Caffeine, urinary calcium, calcium metabolism and bone.

Oral doses of caffeine increase the urinary excretion of calcium, magnesium, sodium and chloride for at least 3 h after consumption. The hypercalciuric effect can be blocked by adenosine receptor agonists. The effect is proportional to dose per lean body mass and no adaptation to the urinary losses occurs with continuing consumption of caffeine. Uncompensated losses of calcium would be a risk factor for development of osteoporosis. Risks of osteoporosis due to caffeine consumption are reviewed. Comparison of data from epidemiological surveys and animal and human studies suggests that for younger adult women consuming adequate calcium, moderate caffeine intakes may have little or no deleterious effects. Increased urinary and intestinal losses may be compensated for by increased intestinal calcium absorption. However older women do not seem to compensate adequately to maintain their former calcium balance, especially when calcium intakes are below recommendations.

[The diagnosis of metabolic bone diseases]. / La diagnostica delle malattie metaboliche dell'osso.

Physical semeiotics, the laboratory, radiology and histology represent the diagnostic tools for metabolic bone diseases. Past medical history and a full objective examination form the basis for every type of diagnostic and therapeutic approach. Familial patterns, the range of drugs used by the patient, the concomitance of diseases affecting mineral metabolism, and the presence of deformities or typical characteristics of some clinical conditions allow the clinician to orientate his diagnosis. Some laboratory tests (serum calcium and phosphate, calciuria) are useful for screening, whereas others (parathyroid hormone and other calciotrophic hormones, biochemical parameters of bone remodeling) must be carried out only for precise diagnostic purposes. In addition to highlighting and characterizing fractures, plane radiology is indicated for the differential diagnosis of focal bone diseases. In the latter diagnosis is facilitated by bone scintigraphy which reveals areas of accelerated bone remodelling. The quantitative evaluation of bone mass using non-invasive methods is of fundamental importance in osteopenic syndromes. Of all the techniques evolved in the past, only quantitative computerized tomography and X-ray computerized mineralometry are used today in the diagnosis and management of osteoporotic patients. The choice of one or other technique should be based on the clinical necessity and on their respective accuracy and reproducibility. Histomorphometric bone biopsy is indicated only in cases of rapid bone loss with uncertain biochemical conditions and for the diagnosis of mineralization disorders.

Mineral balance (iron, aluminum, copper, zinc) after high-dose intravenous Desferal in a child with hemoglobin Hammersmith and Turner's syndrome.

A 12-day balance study with measurements of urine and stool excretion was undertaken to determine the effects of intravenous (i.v.) Desferal (293 mg/kg/24 h x 2) on iron, aluminum, copper, and zinc in a child with Hemoglobin Hammersmith and Turner's syndrome treated as a thalassemia major patient because of symptoms of anemia and ineffective erythropoiesis. Iron balance was positive, 34 mg/3 days baseline. The Desferal infusion induced iron excretion of 117 mg over 48 h, almost equally in stool and urine. This child receives approximately 20 transfusion/i.v. Desferal treatments yearly. If iron excretion is roughly the same with each treatment, it would equal 2,340 mg or 47% of her annual iron intake from transfusion. The i.v. infusions are an important part of this patient's therapy and may also be useful for other chronic transfusion patients for whom subcutaneous Desferal is inadequate for preventing continued iron accumulation. Some patients have successfully received their i.v. Desferal therapy at home, thereby decreasing hospitalization time and cost. Desferal induced moderate aluminum excretion in urine but had no effect on copper or zinc excretion.