Development of a dietary supplement database

Data describing the composition of dietary supplements are not readily available to the public health community. As a result, intake from dietary supplements is generally not considered in most dietary surveys and, hence, little is known about the significance of supplement intake in relation to total diet or disease risk. To enable a more comprehensive analysis of dietary data, a database of the composition of various dietary supplements has been compiled. Active ingredients of all dietary supplements sold in Australia are included in the Australian Register of Therapeutic Goods (ARTG), maintained by the Therapeutic Goods Administration. Products included in the database were restricted to those vitamin, mineral and other supplements identified in dietary data collected from studies conducted in southeast Queensland and New South Wales (850 supplements). Conversion factors from ingredients compounds to active elements were compiled from standard sources. No account has been made for bioavailability, consistent with current practice for food composition databases. The database can be queried by ARTG identification number, brand, product title, or a variety of other fields. Expected future developments include development of standard formulations for use when supplements are incompletely specified, and expansion of products included for more widespread use.

The treatment of tardive dyskinesia: A systematic review and meta-analysis

This systematic review aimed to collate randomized controlled trials (RCTs) of various interventions used to treat tardive dyskinesia (TD) and, where appropriate, to combine the data for mete-analysis, Clinical trials were identified by electronic searches, handsearches and contact with principal investigators. Data were extracted independently by two reviewers, for outcomes related to improvement, deterioration, side-effects and drop out rates. Data were pooled using the Mantel-Haenzel Odds Ratio (fixed effect model). For treatments that had significant effects, the number needed to treat (NNT) was calculated. From 296 controlled clinical trials, data were extracted from 47 trials. For most interventions, we could identify no RCT-derived evidence of efficacy. A meta-analysis showed that baclofen, deanol and diazepam were no more effective than a placebo. Single RCTs demonstrated a lack of evidence of any effect for bromocriptine, ceruletide, clonidine, estrogen, gamma linolenic acid, hydergine, lecithin, lithium, progabide, seligiline and tetrahydroisoxazolopyridinol. The meta-analysis found that five interventions were effective: L-dopa, oxypertine, sodium valproate, tiapride and vitamin E; neuroleptic reduction was marginally significant. Data from single RCTs revealed that insulin, alpha methyl dopa and reserpine were more effective than a placebo. There was a significantly increased risk of adverse events associated with baclofen, deanol, L-dopa, oxypertine and reserpine. Metaanalysis of the impact of placebo (n=485) showed that 37.3% of participants showed an improvement. Interpretation of this systematic review requires caution as the individual trials identified tended to have small sample sizes. For many compounds, data from only one trial were available, and where meta-analyses were possible, these were based on a small number of trials. Despite these concerns, the review facilitated the interpretation of the large and diverse range of treatments used for TD. Clinical recommendations for the treatment of TD are made, based on the availability of RCT-derived evidence, the strength of that evidence and the presence of adverse effects. (C) 1999 Elsevier Science B.V. All rights reserved.

Mutational analysis of the cystathionine beta-synthase gene: A splicing mutation, two missense mutations and an insertion in patients with homocystinuria

RT-PCR and direct sequence analyses were used to define mutations in the cystathionine beta-synthase (CBS) gene in two unrelated male patients with vitamin B6 nonresponsive homocystinuria. Both patients were compound heterozygotes for CBS alleles containing point mutations. One patient had a maternally derived G-->A transition in the splice-donor site of intron 1, resulting in aberrant splicing of CBS mRNA. The other allele contained a missense mutation resulting in the previously reported E144K mutant CBS protein. The second patient had a maternally derived 4 bp insertion in exon 17, predicted to cause a CBS peptide of altered amino acid sequence. A 494G-->A transition was found in exon 4 of the other allele, predicting a C165Y substitution. Expression of recombinant CBS protein, containing the C165Y mutation, had no detectable catalytic activity. Each mutation was confirmed in genomic DNA. (C) 1998 Wiley-Liss, Inc.

Between-year fluctuations in schizophrenia birth rate and associations with the Southern Oscillation Index, cloud cover and sunshine

Our group have recently proposed that low prenatal vitamin D may be a risk-modifying factor for schizophrenia. Climate variability impacts on vitamin D levels in a population via fluctuations in the amount of available UV radiation. In order to explore this hypothesis, we examined fluctuations in the birthrates for people with schizophrenia born between 1920 and 1967 and three sets of variables strongly associated with UV radiation. These included: (a) the Southern Oscillation Index (SOI), a marker of El Nino which is the most prominent meteorological factor that influences Queensland weather: (b) measures of cloud cover and (c) measures of sunshine. Schizophrenia births were extracted from the Queensland Mental Health register and corrected for background population birth rates. Schizophrenia birth rates had several apparently non-random features in common with the SO1. The prominent SO1 fluctuation event that occurred between 1937 and 1943 is congruent with the most prominent fluctuation in schizophrenia birth rates. The relatively flat profile of SOI activity between 1927 and 1936 also corresponds to the flattest period in the schizophrenia time series. Both time series have prominent oscillations in the 3 ~, year range between 1946 and 1960. Significant associations between schizophrenia birth rates and measures of both sunshine and cloud cover were identified,and all three time series shared periodicity in the 3-4 year range. The analyses suggest that the risk of schizophrenia is higher for those born during times of increased cloud cover,reduced sunshine and positive SO1. These ecological analyses provide initial support for the vitamin D hypothesis, however alternative non-genetic candidate exposures also need to be considered. Other sites with year-to-year fluctuations in cloud cover and sunshine should examine patterns of association between these climate variables and schizophrenia birth rates. The Stanley Foundation supported this project.

Calcium absorption in postmenopausal osteoporosis: Benefit of HRT plus calcitriol, but not HRT alone, in both malabsorbers and normal absorbers

In a randomized trial involving 71 postmenopausal osteoporotic women with vertebral compression fractures, radiocalcium absorption studies using the Ca-45 single isotope method (alpha) were performed at baseline and after 8 months of treatment with either continuous combined hormone replacement therapy (HRT, as piperazine estrone sulfate 0.625-0.937mg daily +/- medroxyprogesterone acetate 2.5 mg daily depending on uterine status) or HRT plus calcitriol 0.25 mu g twice daily. A calcium supplement of 600 mg nocte was given to only those women who had a daily calcium intake of less than 1 g per day at baseline, as assessed by recalled dietary intake. There was a significant decrease 0.74 (+/- 0.35 SD) to 0.58 (+/- 0.22), Delta alpha = -0.17 (+/- 0.26), p<0.0005] in alpha at 8 months compared with baseline in the HRT-treated group, but a significant increase [0.68 (+/- 0.31) to 0.84 (+/- 0.27), Delta alpha = +0.16 (+/- 0.30), p<0.003] in the HRT-plus-calcitriol treated patients, resulting in alpha being significantly higher after 8 months in the latter group than in the HRT-only group. Although 72% of the patients had been supplemented with calcium between the first and second studies, separate analyses revealed that the change in calcium intake had not affected the result. Further breakdown of the groups into baseline 'normal' absorbers (alpha greater than or equal to 0.55) and 'malabsorbers' (alpha <0.55) revealed that alpha decreased with HRT treatment only in the normal absorbers, and remained stable in the malabsorbers. Conversely, following HRT plus calcitriol treatment, alpha increased only in the malabsorbers, the normal absorbers in this group remaining unchanged. In conclusion, our data show that HRT, of the type and dose used in this study, did not produce an increase in absorption efficiency; it was in fact associated with a fall. increased absorption efficiency cannot be achieved unless calcitriol is used concurrently, and then only in patients with malabsorption. Calcitriol also had a significant effect in normal absorbers in that it prevented the decline in alpha seen with HRT alone, and thus should be considered in all patients with postmenopausal osteoporosis treated with HRT.

Effect of coinfection with STDs and of STD treatment on HIV shedding in genital-tract secretions - Systematic review and data synthesis

Objective: To determine whether coinfection with sexually transmitted diseases (STD) increases HIV shedding in genital-tract secretions, and whether STD treatment reduces this shedding. Design: Systematic review and data synthesis of cross-sectional and cohort studies meeting. predefined quality criteria. Main Outcome Measures: Proportion of patients with and without a STD who had detectable HIV in genital secretions, HIV toad in genital secretions, or change following STD treatment. Results: Of 48 identified studies, three cross-sectional and three cohort studies were included. HIV was detected significantly more frequently in participants infected with Neisseria gonorrhoeae (125 of 309 participants, 41%) than in those without N gonorrhoeae infection (311 of 988 participants, 32%; P = 0.004). HIV was not significantly more frequently detected in persons infected with Chlamydia trachomatis (28 of 67 participants, 42%) than in those without C trachomatis infection (375 of 1149 participants, 33%; P = 0.13). Median HIV load reported in only one study was greater in men with urethritis (12.4 x 10(4) versus 1.51 x 10(4) copies/ml; P = 0.04). In the only cohort study in which this could be fully assessed, treatment of women with any STD reduced the proportion of those with detectable HIV from 39% to 29% (P = 0.05), whereas this proportion remained stable among controls (15-17%), A second cohort study reported fully on HIV load; among men with urethritis, viral load fell from 12.4 to 4.12 x 10(4) copies/ml 2 weeks posttreatment, whereas viral load remained stable in those without urethritis. Conclusion: Few high-quality studies were found. HIV is detected moderately more frequently in genital secretions of men and women with a STD, and HIV load is substantially increased among men with urethritis, Successful STD treatment reduces both of these parameters, but not to control levels. More high-quality studies are needed to explore this important relationship further.

Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: The Health, Aging, and Body Composition Study

Two factors generally reported to influence bone density are body composition and muscle strength. However, it is unclear if these relationships are consistent across race and sex, especially in older persons. If differences do exist by race and/or sex, then strategies to maintain bone mass or minimize bone loss in older adults may need to be modified accordingly. Therefore, we examined the independent effects of bone mineral-free lean mass (LM), fat mass (FM), and muscle strength on regional and whole body bone mineral density (BMD) in a cohort of 2619 well-functioning older adults participating in the Health, Aging, and Body Composition (Health ABC) Study with complete measures. Participants included 738 white women, 599 black women, 827 white men, and 455 black men aged 70-79 years. BMD (g/cm(2)) of the femoral neck, whole body, upper and lower limb, and whole body and upper limb bone mineral-free LM and FM was assessed by dual-energy X-ray absorptiometry (DXA). Handgrip strength and knee extensor torque were determined by dynamometry. In analyses stratified by race and sex and adjusted for a number of confounders, LM was a significant (p < 0.001) determinant of BMD, except in white women for the lower limb and whole body. In women, FM also was an independent contributor to BMD at the femoral neck, and both PM and muscle strength contributed to limb BMD. The following were the respective Beta-weights (regression coefficients for standardized data, Std beta) and percent difference in BMD per unit (7.5 kg) LM: femoral neck, 0.202-0.386 and 4.7-6.9 %; lower limb,.0.209-0.357 and 2.9-3.5%; whole body, 0.239-0.484 and 3.0-4.7 %; and upper limb (unit = 0.5 kg), 0.231-0.407 and 3.1-3.4%. Adjusting for bone size (bone mineral apparent density [BMAD]) or body size BMD/height) diminished the importance of LM, and the contributory effect of FM became more pronounced. These results indicate that LM and FM were associated with bone mineral depending on the bone site and bone index used. Where differences did occur, they were primarily by sex not race. To preserve BMD, maintaining or increasing LM in the elderly would appear to be an appropriate strategy, regardless of race or sex.

The VITATOPS (vitamins to prevent stroke) Trial: Rationale and design of an international, large, simple, randomised trial of homocysteine-lowering multivitamin therapy in patients with recent transient ischaemic attack or stroke

Background: Epidemiological studies suggest that raised plasma concentrations of total homocysteine (tHcy) may be a common, causal and treatable risk factor for atherothromboembolic ischaemic stroke. Although tHcy can be lowered effectively with small doses of folic acid, vitamin B-12 and vitamin B-6, it is not known whether lowering tHcy, by means of multivitamin therapy, can prevent stroke and other major atherothromboembolic vascular events. Purpose: To determine whether vitamin supplements (folic acid 2 mg, B-6 25 Mg, B-12 500 mug) reduce the risk of stroke, and other serious vascular events, in patients with recent stroke or transient ischaemic attacks of the brain or eye (TIA). Methods: An international, multi-centre, randomised, double-blind, placebo-controlled clinical trial. Results: As of November 2001, more than 1,400 patients have been randomised from 10 countries in four continents. Conclusion: VITATOPS aims to recruit and follow up 8,000 patients between 2000 and 2004, and provide a reliable estimate of the safety and effectiveness of dietary supplementation with folic acid, vitamin B-12, and vitamin B-6 in reducing recurrent serious vascular events among a wide range of patients with TIA and stroke. Copyright (C) 2002 S. Karger AG, Basel.

A Randomized Trial of Sodium Fluoride (60 mg) ± Estrogen in Postmenopausal Osteoporotic Vertebral Fractures

Postmenopausal Caucasian women aged less than 80 years (n = 99) with one or more atraumatic vertebral fracture and no hip fractures, were treated by cyclical administration of enteric coated sodium fluoride (NaF) or no NaF for 27 months, with precautions to prevent excessive stimulation of bone turnover. In the first study 65 women, unexposed to estrogen (-E study), age 70.8 +/- 0.8 years (mean SEM) were all treated with calcium (Ca) 1.0-1.2 g daily and ergocalciferol (D) 0.25 mg per 25 kg once weekly and were randomly assigned to cyclical NaF (6 months on. 3 months off, initial dose 60 mg/day; group F CaD, n = 34) or no NaF (group CaD, n = 3 1). In the second study 34 patients. age 65.5 +/- 1.2 years, on hormone replacement therapy (E) at baseline, had this standardized, and were all treated with Ca and D and similarly randomized (FE CaD, n = 17, E CaD, n = 17) (+E study). The patients were stratified according to E status and subsequently assigned randomly to NaF. Seventy-five patients completed the trial. Both groups treated with NaF showed an increase in lumbar spinal density (by DXA) above baseline by 27 months: FE CaD + 16.2% and F CaD +9.3% (both p = 0.0001). In neither group CaD nor E CaD did lumbar spinal density increase. Peripheral bone loss occurred at most sites in the F CaD group at 27 months: tibia/fibula shaft -7.3% (p = 0.005); femoral shaft -7.1% (p = 0.004); distal forearm -4.0% (p = 0.004); total hip -4.1% (p = 0. 003); and femoral neck -3.5% (p = 0.006). No significant loss occurred in group FE CaD. Differences between the two NaF groups were greatest at the total hip at 27 months but were not significant [p < 0.05; in view of the multiple bone mineral density (BMD) sites, an alpha of 0.01 was employed to denote significance in BMD changes throughout this paper]. Using Cox's proportional hazards model, in the -E study there were significantly more patients with first fresh vertebral fractures in those treated with NaF than in those not so treated (RR = 24.2, p = 0.008, 95% CI 2.3-255). Patients developing first fresh fractures in the first 9 months were markedly different between groups: -23% of F CaD, 0 of CaD, 29% of FE CaD and 0 of E CaD. The incidence of incomplete (stress) fractures was similar in the two NaF-treated groups. Complete nonvertebral fractures did not occur in the two +E groups, there were no differences between groups F CaD and CaD. Baseline BMD (spine and femoral neck) was related to incident vertebral fractures in the control groups (no NaF), but not in the two NaF groups. Our results and a literature review indicate that fluoride salts. if used, should be at low dosage, with pretreatment and co-treatment with a bone resorption inhibitor.

Coaxial flattening at deep levels of orogenic belts: evidence from blueschists and eclogites on Syros and Sifnos (Cyclades, Greece)

This work presents new Structural data from a high-pressure/low-temperature (HP/LT) metamorphic terrane exposed on the islands of Syros and Sifnos (Cyclades, Greece). The structure and the metamorphism of a relatively coherent HP/LT rock section were studied in order to elucidate how strain was accommodated at deep crustal levels during the formation and exhumation of HP/LT rocks. At least three deformation phases associated with eclogite- and blueschist-facies conditions (P = 8-15 kbar; T = 400-550 degreesC) were recognised. The earliest deformation fabric (S1), preserved as inclusion trails within garnet porphyroblasts, is aligned to define a sub-vertical schistosity (at present orientation), which is frequently orthogonal to the flat matrix schistosity (S2), and may indicate that deep crustal thickening involved upright folding. The currently dominant fabric in the HP rock section, S2, is Usually moderately dipping and locally contains NW-trending glaucophane lineations, symmetric pressure-shadows and eclogitic boudins. The symmetric structures associated with this fabric seem to indicate coaxial vertical thinning, although the existence of non-coaxial structures out of the study area cannot be excluded. Glaucophane-bearing shear bands (S3), with top-to-NW sense of shearing, locally crosscut the earlier structures. The latest recognised fabric (D4) is scarce and often absent within the HP rocks. It is associated with top-to-NE kinematic criteria that formed at greenschist-facies conditions (P = 4-7 kbar; T = 400-450 degreesC). Based on these observations, it is suggested that partitioning of strain occurred at different crustal levels and at different times. Deep crustal deformation was governed by thickening via upright folding followed by coaxial vertical thinning, whereas non-coaxial shearing occurred when the rocks were already exhumed to relatively shallow crustal levels. The earliest fabrics (D1 to D3) pertain to Alpine orogenesis and possibly to syn-orogenic extension, whereas the latest correspond to whole-crust back-are extension. (C) 2002 Elsevier Science Ltd. All rights reserved.

A randomized trial comparing hormone replacement therapy (HRT) and HRT plus calcitriol in the treatment of postmenopausal osteoporosis with vertebral fractures: Benefit of the combination on total body and hip density

We report a prospective, randomized, multi-center, open-label 2-year trial of 81 postmenopausal women aged 53-79 years with at least one minimal-trauma vertebral fracture (VF) and low (T-score below 2) lumbar bone mineral density (BMD). Group HRT received piperazine estrone sulfate (PES) 0.625 - 1.25 mg/d +/- medroxyprogesterone acetate (MPA) 2.5 - 5 mg/d,- group HRT/D received HRT plus calcitriol 0.25 mug bd. All with a baseline dietary calcium (Ca) of < I g/d received Ca carbonate 0.6 g nocte. Final data were on 66 - 70 patients. On HRT/D, significant (P < 0.001) BNID increases from baseline by DXA were at total body - head, trochanter, Ward's, total hip, inter-trochanter and femoral shaft (% group mean Delta 4.2, 6.1, 9.3. 3.7. 3.3 and 3.3%, respectively). On HRT, at these significant Deltas were restricted to the trochanter and sites. si Wards. Significant advantages of HRT/D over HRT were in BMD of total body (- head), total hip and trochanter (all P = 0.01). The differences in mean Delta at these sites were 1.3, 2.6 and 3.9%. At the following, both groups Improved significantly -lumbar spine (AP and lateral), forearm shaft and ultradistal tibia/fibula. The weightbearing, site - specific benefits of the combination associated with significant suppression of parathyroid hormone-suggest a beneficial effect on cortical bone. Suppression of bone turnover was significantly greater on HRT/D (serum osteocalcin P = 0.024 and urinary hydroxyproline/creatinine ratio P = 0.035). There was no significant difference in the number of patients who developed fresh VFs during the trial (HRT 8/36, 22%; HRT/D 4/34, 12% - intention to treat); likewise in the number who developed incident nonvertebral fractures. This Is the first study comparing the 2 treatments in a fracture population. The results indicate a significant benefit of calcitriol combined with HRT on total body BMD and on BNID at the hip, the major site of osteoporotic fracture.

Anticlastogenic and antigenotoxic effects of selenomethionine on doxorubicin-induced damage in vitro in human lymphocytes

The use of antioxidants during chemotherapy has been shown to reduce or prevent the undesirable effects experienced by healthy cells. Micronutrient selenium is well known for its antioxidant properties; however, selenium exhibits a bimodal nature in that both its beneficial and toxic properties lie within a limited and narrow dose range. The present study investigated the possible protective effects of selenomethionine (SM) on the cytotoxicity, genotoxicity and clastogenicity of the chemotherapic doxorubicin (DXR), a key chemotherapic used in cancer treatment. Human peripheral lymphocytes were treated in vitro with varying concentrations of SM (0.25 mu M, 0.5 mu M, 1.0 mu M and 2.0 mu M), tested in combination with DXR (0.15 mu g/mL). SM alone was not cytotoxic and when combined with DXR treatment, reduced the DNA damage index significantly, the frequency of chromosomal aberrations, the number of aberrant metaphases and the frequency of apoptotic cells. The mechanism of chemoprotection of SM may be related to its antioxidant properties as well as its ability to interfere with DNA repair pathways. Therefore this study showed that SM is effective in reducing the genetic damage induced by the antitumoral agent DXR. (C) 2007 Elsevier Ltd. All rights reserved.

Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke - a randomized substudy

Background and Purpose - Epidemiological and laboratory studies suggest that increasing concentrations of plasma homocysteine ( total homocysteine [tHcy]) accelerate cardiovascular disease by promoting vascular inflammation, endothelial dysfunction, and hypercoagulability. Methods - We conducted a randomized controlled trial in 285 patients with recent transient ischemic attack or stroke to examine the effect of lowering tHcy with folic acid 2 mg, vitamin B-12 0.5 mg, and vitamin B-6 25 mg compared with placebo on laboratory markers of vascular inflammation, endothelial dysfunction, and hypercoagulability. Results - At 6 months after randomization, there was no significant difference in blood concentrations of markers of vascular inflammation (high-sensitivity C-reactive protein [P = 0.32]; soluble CD40L [ P = 0.33]; IL-6 [P = 0.77]), endothelial dysfunction ( vascular cell adhesion molecule-1 [P = 0.27]; intercellular adhesion molecule-1 [P = 0.08]; von Willebrand factor [P = 0.92]), and hypercoagulability (P-selectin [P = 0.33]; prothrombin fragment 1 and 2 [P = 0.81]; D-dimer [P = 0.88]) among patients assigned vitamin therapy compared with placebo despite a 3.7-mumol/L (95% CI, 2.7 to 4.7) reduction in total homocysteine (tHcy). Conclusions - Lowering tHcy by 3.7 mumol/L with folic acid-based multivitamin therapy does not significantly reduce blood concentrations of the biomarkers of inflammation, endothelial dysfunction, or hypercoagulability measured in our study. The possible explanations for our findings are: ( 1) these biomarkers are not sensitive to the effects of lowering tHcy (eg, multiple risk factor interventions may be required); ( 2) elevated tHcy causes cardiovascular disease by mechanisms other than the biomarkers measured; or ( 3) elevated tHcy is a noncausal marker of increased vascular risk.

Changes in inflammatory mediators following eccentric exercise of the elbow flexors

The aims of this study were to examine the plasma concentrations of inflammatory mediators including cytokines induced by a single bout of eccentric exercise and again 4 weeks later by a second bout of eccentric exercise of the same muscle group. Ten untrained male subjects performed two bouts of the eccentric exercise involving the elbow flexors (6 sets of 5 repetitions) separated by four weeks. Changes in muscle soreness, swelling, and function following exercise were compared between the bouts. Blood was sampled before, immediately after, 1 h, 3 h, 6 h, 24 h (1 d), 48 h (2 d), 72 h (3 d), 96 h (4 d) following exercise bout to measure plasma creatine kinase (CK) activity, plasma concentrations of myoglobin (Mb), interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1ra), IL-4, IL-6, IL-8, IL-10, IL-12p40, tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), myeloperoxidase (MPO), prostaglandin E-2 (PGE(2)), heat shock protein (HSP) 60 and 70. After the first bout, muscle soreness increased significantly, and there was also significant increase in upper arm circumference; muscle function decreased and plasma CK activity and Mb concentration increased significantly. These changes were significantly smaller after the second bout compared to the first bout, indicating muscle adaptation to the repeated bouts of the eccentric exercise. Despite the evidence of greater muscle damage after the first bout, the changes in cytokines and other inflammatory mediators were quite minor, and considerably smaller than that following endurance exercise. These results suggest that eccentric exercise-induced muscle damage is not associated with the significant release of cytokines into the systemic circulation. After the first bout, plasma G-CSF concentration showed a small but significant increase, whereas TNF-alpha and IL-8 showed significant decreases compared to the pre-exercise values. After the second bout, there was a significant increase in IL-10, and a significant decrease in IL-8. In conclusion, although there was evidence of severe muscle damage after the eccentric exercise, this muscle damage was not accompanied by any large changes in plasma cytokine concentrations. The minor changes in systemic cytokine concentration found in this study might reflect more rapid clearance from the circulation, or a lack of any significant metabolic or oxidative demands during this particular mode of exercise. In relation to the adaptation to the muscle damage, the anti-inflammatory cytokine IL-10 might work as one of the underlying mechanisms of action.

Early Control of PTH and FGF23 in Normophosphatemic CKD Patients: A New Target in CKD-MBD Therapy?

Background and objectives: Levels of parathyroid hormone (PTH) and the phosphaturic hormone FGF23, a fibroblast growth factor (FGF) family member, increase early in chronic kidney disease (CKD) before the occurrence of hyperphosphatemia. This short-term 6-wk dose titration study evaluated the effect of two phosphate binders on PTH and FGF23 levels in patients with CKD stages 3 to 4. Design, setting, participants, and measurements: Patients were randomized to receive over a 6-wk period either calcium acetate (n = 19) or sevelamer hydrochloride (n = 21). Results: At baseline, patients presented with elevated fractional excretion of phosphate, serum PTH, and FGF23. During treatment with both phosphate binders there was a progressive decline in serum PTH and urinary phosphate, but no change in serum calcium or serum phosphate. Significant changes were observed for FGF23 only in sevelamer-treated patients. Conclusions: This study confirms the positive effects of early prescription of phosphate binders on PTH control. Prospective and long-term studies are necessary to confirm the effects of sevelamer on serum FGF23 and the benefits of this decrease on outcomes. Clin J Am Soc Nephrol 5: 286-291, 2010. doi: 10.2215/CJN.05420709