BNP response during Berlin Heart® support in child: a case report.

A five-year-old boy is presented to Necker hospital for a dilated hypertrophic cardiomyopathy. The implantation of the Berlin Heart Excor® ventricular assist device was performed. This pediatric-sized Berlin Heart® device provides mechanical support for young infants and children of all ages to sustain the failing cardiac circulation over several months, until either recovery of myocardial function or heart transplantation. It remains difficult to identify patients with sufficient recovery and the right time for explantation of the Berlin Heart®. Currently, the decision as to whether a patient should be weaned from the system is mainly based on echocardiographic data. Humoral biomarker, associated to echocardiographic features, would be helpful to identify children who might recover without heart transplantation. We observed that our young patient presented highly elevated BNP plasma levels before mechanical support, and a significant decrease during Berlin Heart® support. Monitoring levels of BNP can be helpful to detect appropriate unloading of the heart as a precondition for recovery. During pump-stop maneuvers, BNP should be regarded in combination with clinical and hemodynamic status of the patients, associated with echocardiographic data.

Mycophenolate Mofetil and Rapamycin Induce Apoptosis in the Human Monocytic U937 Cell Line Through Two Different Pathways.

Transplant vasculopathy may be considered as an accelerated form of atherosclerosis resulting in chronic rejection of vascularized allografts. After organ transplantation, a diffuse intimal thickening is observed, leading to the development of an atherosclerosis plaque due to a significant monocyte infiltration. This results from a chronic inflammatory process induced by the immune response. In this study, we investigated the impact of two immunosuppressive drugs used in therapy initiated after organ transplantation, mycophenolate mofetil, and rapamycin, on the apoptotic response of monocytes induced or not by oxidized LDL. Here we show the pro-apoptotic effect of these two drugs through two distinct signaling pathways and we highlight a synergistic effect of rapamycin on apoptosis induced by oxidized LDL. In conclusion, since immunosuppressive therapy using mycophenolate mofetil or rapamycin can increase the cell death in a monocyte cell line, this treatment could exert similar effects on human monocytes in transplant patients, and thus, prevent transplant vasculopathy, atherosclerosis development, and chronic allograft rejection. J. Cell. Biochem. 118: 3480-3487, 2017. © 2017 Wiley Periodicals, Inc.

Farnesyltransferase inhibitor R115777 protects against vascular disease in uremic mice.

BACKGROUND: Atherosclerosis and vascular calcification are major contributors to cardiovascular morbidity and mortality among chronic kidney disease patients. The mevalonate pathway may play a role in this vascular pathology. Farnesyltransferase inhibitors such as R115777 block one branch of mevalonate pathway. We studied the effects of farnesyltransferase inhibitor R115777 on vascular disease in apolipoprotein E deficient mice with chronic renal failure and on mineral deposition in vitro. METHODS AND RESULTS: Female uremic and non-uremic apolipoprotein E deficient mice were randomly assigned to four groups and treated with either farnesyltransferase inhibitor R115777 or vehicle. Farnesyltransferase inhibitor R115777 inhibited protein prenylation in mice with chronic renal failure. It decreased aortic atheromatous lesion area and calcification in these animals, and reduced vascular nitrotyrosine expression and total collagen as well as collagen type I content. Proteomic analysis revealed that farnesyltransferase inhibitor corrected the chronic renal failure-associated increase in serum apolipoprotein IV and α globin, and the chronic renal failure-associated decrease in serum fetuin A. Farnesyltransferase inhibitor further inhibited type I collagen synthesis and reduced mineral deposition in vascular smooth muscle cells in vitro, probably involving Ras-Raf pathway. CONCLUSIONS: We show for the first time that farnesyltransferase inhibition slows vascular disease progression in chronic renal failure by both indirect systemic and direct local actions. This beneficial effect was mediated via a reduction in oxidative stress and favorable changes in vasoprotective peptides.

Circulating trophoblastic cells provide genetic diagnosis in 63 fetuses at risk for cystic fibrosis or spinal muscular atrophy.

This study sought to determine whether a reliable non-invasive prenatal diagnosis (NI-PND) of cystic fibrosis (CF) or spinal muscular atrophy (SMA) can be achieved through analysis of circulating fetal trophoblastic cells (CFTC). The kinetics of CFTC circulation were also studied. CFTC were isolated by isolation by size of epithelial tumour/trophoblastic cells at 9-11 weeks of gestation, before chorionic villus sampling (CVS), from the blood of 63 pregnant women at 25% risk for having a child affected by either CF (n=32) or SMA (n=31). Collected cells were laser-microdissected, short tandem repeat-genotyped to determine fetal origin and blindly assessed for mutation analysis. CFTC were independently analysed weekly (4-12 weeks of gestation) in 14 women who achieved pregnancy following IVF. Diagnostic results were compared with those obtained by CVS. All seven CF and seven SMA pregnancies carrying an affected fetus were correctly identified as well as non-affected pregnancies. CFTC provided 100% diagnostic sensitivity (95% CI 76.8-100%) and specificity (95% CI 92.7-100%) in these 63 consecutive pregnancies at risk for CF or SMA. CFTC were found to circulate from 5 weeks of gestation and can be used to develop an early and reliable approach for NI-PND. We sought to determine whether a reliable non-invasive prenatal diagnosis (NI-PND) of two rare genetic diseases - cystic fibrosis (CF) and spinal muscular atrophy (SMA) - can be achieved through analysis of circulating fetal trophoblastic cells (CFTC) in blood of pregnant women. We also studied the time of appearance and circulation of CFTC in maternal blood. CFTC were isolated from maternal blood by isolation by size of epithelial tumour/trophoblastic cells (ISET; an approach for cell isolation from blood) at 9-11 weeks of gestation before chorionic villus sampling (CVS) from the blood of 63 pregnant women at 25% risk for having a child affected by either CF (n=32) or SMA (n=31). Collected cells were analysed by genetic test to determine fetal origin and blindly assessed for mutation analysis. We independently analysed CFTC in maternal blood samples taken weekly (4-12 weeks of gestation) from 14 women who achieved pregnancy following IVF. Diagnostic results were compared with those obtained by CVS. All seven CF and seven SMA pregnancies carrying an affected fetus were correctly identified as well as non-affected pregnancies. CFTC provided 100% diagnostic sensitivity and specificity in these 63 consecutive pregnancies at risk for CF or SMA. CFTC were found to circulate from 5 weeks of gestation and can be used to develop an early and reliable approach for NI-PND.

Decontamination of sugar syrup by pulsed light.

The pulsed light produced by xenon flash lamps was applied to 65 to 67 °Brix sugar syrups artificially contaminated with suspensions of Saccharomyces cerevisiae and with spores of Bacillus subtilis, Geobacillus stearothermophilus, Alicyclobacillus acidoterrestris, and Aspergillus niger. The emitted pulsed light contained 18.5 % UV radiation. At least 3-log reductions of S. cerevisiae, B. subtilis, G. stearothermophilus, and A. acidoterrestris suspended in 3-mm-deep volumes of sugar syrup were obtained with a fluence of the incident pulsed light equal to or less than 1.8 J/cm(2), and the same results were obtained for B. subtilis and A. acidoterrestris suspended in 10-mm-deep volumes of sugar syrup. A. niger spores would require a more intense treatment; for instance, the maximal log reduction was close to 1 with a fluence of the incident pulsed light of 1.2 J/cm(2). A flowthrough reactor with a flow rate of 320 ml/min and a flow gap of 2.15 mm was designed for pulsed light treatment of sugar syrup. Using this device, a 3-log reduction of A. acidoterrestris spores was obtained with 3 to 4 pulses of incident pulsed light at 0.91 J/cm(2) per sugar syrup volume.

Randomized trial of oral versus sequential IV/oral antibiotic for acute pyelonephritis in children.

OBJECTIVE: To confirm whether oral antibiotic treatment is as efficacious as sequential intravenous/oral antibiotic treatment in the prevention of renal scarring in children with acute pyelonephritis and scintigraphy-documented acute lesions. METHODS: In a prospective multicenter trial, children aged 1 to 36 months with their first case of acute pyelonephritis, a serum procalcitonin concentration ≥0.5 ng/mL, no known uropathy, and a normal ultrasound exam were randomized into 2 treatment groups. They received either oral cefixime for 10 days or intravenous ceftriaxone for 4 days followed by oral cefixime for 6 days. Patients with acute renal lesions detected on early dimercaptosuccinic acid scintigraphy underwent a follow-up scintigraphy 6 to 8 months later. RESULTS: The study included 171 infants and children. There were no significant differences between the 2 groups in any clinical characteristic. Initial scintigraphy results were abnormal for 119 children. Ninety-six children were measured for renal scarring at the follow-up scintigraphy (per protocol analysis population). The incidence of renal scarring was 30.8% in the oral treatment group and 27.3% for children who received the sequential treatment. CONCLUSIONS: Although this trial does not statistically demonstrate the noninferiority of oral treatment compared with the sequential treatment, our study confirmed the results of previously published reports and therefore supports the use of an oral antibiotic treatment of primary episodes of acute pyelonephritis in infants and young children.

Lanthanum carbonate, like sevelamer-HCl, retards the progression of vascular calcification and atherosclerosis in uremic apolipoprotein E-deficient mice.

BACKGROUND: Atherosclerosis and vascular calcification (VC) progression in chronic kidney disease is favored by disturbances of mineral metabolism. We compared the effect of phosphate binder lanthanum (La) carbonate with sevelamer-HCl on atherosclerosis, VC and bone structure and function in mice with chronic renal failure (CRF). METHODS: Apolipoprotein E-deficient (apoE(-/-)) mice were randomized to one non-CRF and three CRF groups, fed with standard diet (one non-CRF and one CRF) or diet supplemented with either 3% lanthanum carbonate (La3%) or 3% sevelamer-HCl (Sev3%). RESULTS: Both La3% and Sev3% supplemented CRF mice displayed a decrease of serum phosphorus, calcification at both intimal and medial aortic sites and atherosclerosis. This was associated with a reduction of plaque Type I collagen expression by both binders and of positive nitrotyrosine staining in response to sevelamer-HCl only. Increased mineral apposition and bone formation rates in unsupplemented CRF mice were reduced by Sev3% but not by La3%. CONCLUSIONS: The beneficial effects of La carbonate and sevelamer-HCl on the progression of VC and atherosclerosis in CRF mice could be mainly due to a decrease in phosphate retention and likewise a reduction of arterial Type I collagen expression. The effect of La carbonate differed from that of sevelamer-HCl in that it did not appear to exert its vascular effects via changes in oxidative stress or bone remodeling in the present model.

Relevant factors affecting microbial surface decontamination by pulsed light.

Pulsed Light (PL) uses intense flashes of white light rich in ultraviolet (UV) light for decontamination. A log-reduction higher than 5 was obtained in one flash and at fluences lower than 1.8J/cm(2) on spores of a range of spore-forming bacteria, of vegetative cells of non-spore-forming bacteria and on yeasts spread on agar media. Vegetative cells were more sensitive than spores. The inactivation by PL of Bacillus subtilis, B. atrophaeus, B. cereus, Geobacillus stearothermophilus, and Aspergillus niger spores sprayed on polystyrene was similar. The inactivation by PL of B. subtilis and A. niger spores sprayed on glass was slightly lower than on polystyrene. No alteration of the spore structures was detected by scanning electron microscopy for both PL treated B. subtilis and A. niger spores. The inactivation of spores of B. subtilis, B. atrophaeus, B. cereus and B. pumilus by PL or by continuous UV-C at identical fluences was not different, and was much higher by PL for A. niger spores. The increase in the input voltage of the lamps (which also increases the UV-C %) resulted in a higher inactivation. There was no correlation between the resistance to heat and the resistance to PL. The relative effect of UV-C radiations and light thermal energy on PL inactivation was discussed.

[Multicenter evaluation of the reliability of five blood glucose monitoring systems]. / Évaluation multicentrique de la fiabilité de cinq lecteurs de glycémie.

As part of a tender AP-HP Paris Hospitals, an assessment of the reliability record of five blood glucose monitoring systems (BGMSs) (Optium Xceed (Abbott), Contour TS (Bayer), One Touch Ultra (Lifescan), Stat Strip Xpress (Nova) and Accu Check (Roche) and an evaluation of their sensitivity to changes in hematocrit were conducted in 4 hospitals of Paris. In terms of inaccuracy, all BGMSs have submitted CV repetability under the limits of acceptability. One BGMS (Lifescan) presented a CV of reproducibility outside limit of acceptability (13.1%). The inaccuracy was measured by a comparison method on multiparameter analyser relative to the hexokinase method for two sites, the glucose oxidase for the two others. The coefficients of correlation varied from 0.8405 to 0.9303. However, according to both defined acceptability criteria (absolute value difference between the result acquired on analyzer and those determined with the BGMS), the percentage of results outside acceptability was above 20% for two BGMSs (Abbott and Lifescan). Similarly, a net effect of changes in hematocrit was observed on the results of those two BGMSs. BGMS Nova was the most reliable, because of the correction device for hematocrit and blank substractions owed to interferences. In terms of expertise, BGMSs Nova and Roche have been selected with the best analytical performance and practicability satisfactory. In the future, accreditation with standard NF/EN 22870 requested for point of care testing, will require a close collaboration between biologists and clinicians to establish a system of strict quality control to detect deviations of these BGMSs.

Impact of polyunsaturated fatty acids on oxidized low density lipoprotein-induced U937 cell apoptosis.

AIM: Dietary supplements in polyunsaturated fatty acids (PUFA), particularly omega-3, are well known for their beneficial effects in preventing cardiovascular diseases (CVD). The aim of this study was to determine the role of PUFA on the modulation of apoptosis induced by hypochlorous acidoxidized LDL (HOCl-oxLDL) in U937 cells. METHODS: We tested the effect of monocyte cell line U937 supplementation with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (ARA) or oleic acid (OA) on the modulation of HOCl-oxLDL-induced apoptosis. RESULTS: First, we showed the incorporation of fatty acids in the cellular membrane in U937 cells. Then, we showed that both EPA and ARA exerted a pro-apoptotic effect through the intrinsic mitochondrial apoptotic pathway including the dissipation of mitochondrial membrane potential followed by cardiolipin depletion, the downstream activation of caspase-3 and the increase in DNA fragmentation. The pro-apoptotic effect of EPA or ARA was completely blocked in U937/Bcl-2 cells. CONCLUSIONS: A new mechanism of dietary supplements in PUFA with likely consequences in apoptosis could be suggested through the mitochondrial pathway in monocytes.

Vitamin A, E, B12, and folic acid in end-stage renal disease Tunisian patients: status and predictive value for overall mortality and cardiovascular events.

BACKGROUND: Vitamin status and role in end stage renal disease (ESRD) is controversial. This study was aimed at assessing vitamin A, E, B12, and folic acid status in Tunisian ESRD patients and testing their predictive value for overall mortality and cardiovascular events (CVE). METHODS: We examined plasma vitamin A, E, B12, and folic acid in 115 ESRD patients and looked for any correlation with all-cause mortality and CVE after a six year follow-up. Vitamin A and E were determined by HPLC and vitamin B12 and folic acid were determined by enzyme immunoassay. RESULTS: At enrolment, plasma vitamin A was higher in patients than controls, while plasma vitamin B12 was higher in HD patients. No significant differences were observed for plasma vitamin E and folic acid concentrations between patients and controls. Folic acid and vitamin B12 levels were higher in supplemented patients. During the follow-up period, 17 patients were lost, 15 died, and 36 presented a CVE. Survival analysis showed that mortality and/or CVE trend to be lower for high folic acid levels (Log Rank = 0.098). Cox's regression analysis showed that high levels of folic acid are inversely related to all-cause mortality and/or CVE [Hazard ratio (95% confidence interval), 0.255 (0.08 - 0.740); p = 0.012]. CONCLUSIONS: Plasma vitamins A, E, B12, and folic acid concentrations are usually normal in Tunisian ESRD patients. High folic acid levels are associated with fewer CVE and better survival. However, as uremia could be associated with functional vitamin deficiency, maintaining high plasma vitamin levels by adequate nutrition and tolerable supplementation would be beneficial in ESRD patients.

Chronic kidney disease bone and mineral disorder (CKD-MBD) in apolipoprotein E-deficient mice with chronic renal failure.

BACKGROUND: Chronic kidney disease (CKD) is associated with disorders of mineral and bone metabolism (MBD) which include renal osteodystrophy and vascular calcifications. This is of clinical concern because the high risk of cardiovascular (CVD) complications observed in uremic patients may be linked with bone disease. In this context, our aim was to characterize the bone lesions in CKD-apolipoprotein E-deficient mice (apoE(-/-)) and analyze their relationships with the vascular calcifications which these animals develop rapidly in this model. With ApoE being also involved in bone metabolism, we compared the effects of CRF on the bone of apoE(-/-) mice to those observed in wild type mice (WT) of the same genetic background, C57/BL6. METHODS: After CRF creation or sham surgery, 10 week-old female apoE(-/-) and WT mice were randomized to 4 groups (n=10-14/group) and fed with standard diet. Eight weeks later, animals were euthanized. Serum, aorta and femur were sampled. Femurs were imaged with 3-dimensional microtomography (microCT) and processed for bone histomorphometry (BHM). Additional quantitative histology was performed on atherosclerotic and calcified lesions in the aortas of apoE(-/-) mice. RESULTS: First, apoE(-/-) mice exhibited higher cortical (10%) and trabecular (31%) bone mass than WT. CRF led to a further increase in trabecular BV/TV in WT and in apoE(-/-) mice (10.2% and 77.2%, respectively). We observed a similar increase in osteoid surface and osteoblastic parameters in CRF mice of both genotypes while resorption parameters were less augmented by CRF in apoE(-/-) mice. Finally, based on either BHM or microCT we found positive correlations between the extent of atherosclerotic lesions and bone volume parameters, and between the size of plaque calcification and osteoclast parameters in apoE(-/-) mice. CONCLUSION: ApoE deficiency is associated with an increase in bone mass and volumetric mineral density in 20 week-old female mice. Bone mass is further increased, whereas bone mineral density is decreased, in response to CRF in association with histological features of osteitis fibrosa. Finally, our findings of correlations between changes in bone and aortic lesions in apoE(-/-) mice, are compatible with the hypothesis of a link between bone and vascular disease and require further study.

Tissue accumulation of lanthanum as compared to aluminum in rats with chronic renal failure--possible harmful effects after long-term exposure.

BACKGROUND: Lanthanum (La) carbonate is a new treatment for hyperphosphatemia. We tested the effects of oral La carbonate and aluminum hydroxide, respectively, on tissue accumulation and liver function in rats with chronic renal failure (CRF). METHODS: Adult male non-CRF and CRF rats were randomly assigned to 3 groups receiving either standard diet (St.D), or the same diet supplemented with 3% La carbonate (non-CRF La vs. CRF La) or 3% aluminum hydroxide (non-CRF Al vs. CRF Al). RESULTS: After 12 weeks, serum phosphorus was decreased in both CRF La and Al groups. Urinary La and Al excretion was increased in these two groups, and so was liver and bone La content, and liver Al content. Both total body and liver weight were decreased in CRF La and CRF Al rats. Liver cell proliferation was decreased in these groups, while plasma total alkaline phosphatases and alanine aminotransferase were increased. Hepatic total cytochrome p450 content was reduced in CRF La, but not in CRF Al rats. CONCLUSION: Long-term oral La overload in rats with CRF was associated with a decrease in liver (and total body) weight and mild alterations of liver function, as was Al overload, possibly as a consequence of trace element accumulation.

Differential apoptotic pathways activated in response to Cu-induced or HOCl-induced LDL oxidation in U937 monocytic cell line.

We compared the apoptotic mechanism involved in U937 human monocytic cell line in presence of oxidized low-density lipoproteins (oxLDL) obtained after treatment with hypochlorous acid (HOCl) or copper (Cu). Both types of oxLDL induced U937 apoptotic cell death via the mitochondrial pathway. In contrast to HOCl-oxLDL, Cu-oxLDL induced apoptosis via a caspase-independent mechanism, with no activation of pro-caspase-3, but via the release of apoptosis inducing factor (AIF) from mitochondria. The apoptotic program of the monocyte differs depending on the mode of LDL oxidation, based on differences in the oxidatively modified components of the two oxLDL types.

Can procalcitonin measurement help the diagnosis of osteomyelitis and septic arthritis? A prospective trial.

OBJECTIVES: Procalcitonin (PCT) is an accurate marker for differentiating bacterial infection from non-infective causes of inflammation or viral infection. However, there is only one study in children which tested procalcitonin as a diagnostic aid in skeletal infections. With this study we sought to evaluate the sensitivity, specificity and predictive values of procalcitonin for identifying bone and joint infection in children evaluated in the emergency department for non traumatic decreased active motion of a skeletal segment. METHODS: Patients aged 1 month to 14 years were prospectively included in the emergency department when suspected for osteomyelitis or septic arthritis. Procalcitonin levels, C reactiv protein, white blood cell count were measured and bacteriological samples were collected before initiation of antibiotic treatment. Patients were assigned to 3 groups according to the degree of suspected infection: group 1 confirmed infection, group 2 presumed infection and group 3 non infected patients. RESULTS: Three hundred thirty nine patients were included (118 girls and 221 boys). Group 1 comprised 8 patients (2 had PCT levels > 0.5 ng/ml). Two had osteomyelitis and 6 septic arthritis. Forty children were incuded in group 2 (4 had PCT levels > 0.5 ng/ml). Eighteen had presumed osteomyelitis and 22 presumed septic arthritis. Group 3 comprised 291 children (9 PCT levels > 0.5 ng/ml) who recovered without antibiotic treatment. The specificity of the PCT as a marker of bacterial infection (comparing Group 1 and Group 3) was 96.9% [95% CI, 94.2-98.6], the sensitivity 25% [95% CI, 3.2-65.1], the positive predictive value (PPV) 18.2% [95% CI, 2.3-51.8] and the negative predictive value (NPV) 97.9% [95% CI, 95.5-99.2]. CONCLUSION: PCT is not a good screening test for identifying skeletal infection in children. Larger studies are needed to evaluate still more the place of PCT measurements in the diagnosis of osteomyelitis and septic arthritis.

Protective effects of EPA and deleterious effects of DHA on eNOS activity in Ea hy 926 cultured with lysophosphatidylcholine.

Oxidized low density lipoprotein (Ox-LDL) is a well-established risk factor in atherosclerosis and lysophosphatidylcholine (LysoPtdCho) is considered to be one of the major atherogenic component of Ox-LDL. The purpose of this work was to investigate the effects of two membrane n-3 long chain polyunsaturated fatty acids (n-3 PUFAs), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) compared to n-6 PUFA, ARA (arachidonic acid), on the activation of endothelial NO synthase (eNOS) by histamine in Ea hy 926 endothelial cells incubated during 24 h in the presence or the absence of LysoPtdCho. DHA (50 muM) produced a ROS induction in cells and aggravated the LysoPtdCho-induced oxidative stress. It did not modify the basal eNOS activity but impaired the stimulation of eNOS induced by histamine and was unable to correct the deleterious effect of LysoPtdCho on histamine-stimulated eNOS activity or phosphorylation of Ser 1177. In contrast, EPA (90 muM) did not modify the ROS level produced in the presence or absence of LysoPtdCho or basal eNOS activity and the stimulating effect of histamine on eNOS. However, it diminished the deleterious effect of LysoPtdCho as well as on the histamine-stimulated eNOS activity on the phosphorylation on Ser 1177 of eNOS. The beneficial effect of EPA but not DHA on endothelial eNOS activity in Ea hy 926 could be also partially due to a slight decrease in membrane DHA content in EPA-treated cells. Consequently, the equilibrium between NO generated by eNOS and ROS due to oxidative stress could explain, in part, the beneficial effect of EPA on the development of cardiovascular diseases. By contrast ARA an n-6 PUFA was devoid of any effect on ROS generation or eNOS activity in the basal state or after histamine-induced stimulation. In vivo experiments should be undertaken to confirm these results.

The calcimimetic R-568 retards uremia-enhanced vascular calcification and atherosclerosis in apolipoprotein E deficient (apoE-/-) mice.

OBJECTIVE: Secondary hyperparathyroidism of chronic kidney disease promotes vascular calcification. Calcimimetics reduce serum parathyroid hormone, calcium (Ca), and phosphorus by calcium-sensing receptor (CaR) activation. Here we examined possible effects of the calcimimetic R-568 (R-568) on the progression of aortic calcification and atherosclerosis in apoE(-/-) mice with chronic renal failure (CRF) and the potential implication of aortic smooth muscle cell CaR. METHODS AND RESULTS: ApoE(-/-) mice were assigned to 3 CRF groups and 1 non-CRF group receiving daily gavage with R-568, calcitriol, or vehicle. Serum Ca and phosphorus and parathyroid gland volume of CRF mice were decreased by R-568, whereas elevated serum FGF23 and total cholesterol remained unchanged. Both aortic plaque and non-plaque calcification was lower in R-568 mice, and so was atherosclerotic plaque area fraction. In vitro, R-568 induced a decrease in smooth muscle cell calcification when cultured in high phosphate medium. This decrease was abolished in CaR-SiRNA-transfected cells. CONCLUSIONS: The calcimimetic R-568 delayed the progression of both aortic calcification and atherosclerosis in uremic apoE(-/-) mice. This effect was mediated via a better control of hyperparathyroidism including serum Ca and phosphorus. Direct vascular CaR activation also could have played a role in the observed effects.

Predictors for cardiovascular morbidity and overall mortality in Tunisian ESRD patients: a six year prospective study.

OBJECTIVES: The study was aimed to test the predictive value of several potential cardiovascular factors and markers for non fatal cardiovascular events (CVE) and overall mortality in Tunisian patients with renal failure. SUBJECTS AND METHODS: One hundred and fifteen renal failure patients were followed-up from 2000 to 2006. At enrollment, each patient underwent clinical examination and blood collection for analysis of lipid parameters, albumin, C reactive protein (CRP), parathyroid hormone (PTH), homocysteine and hemoglobin. Multivariate Cox regression models were applied to identify the predictors for non fatal CVE and overall mortality. RESULTS: During the follow up, seventeen patients were lost. Among the 98 remaining patients, 29 presented a non fatal CVE (21.5%) and 15 were deceased (11.1%). In univariate analyses, non fatal CVE were more frequent in smokers and in patients with high PTH concentrations and low HDL levels. Moreover, low albumin concentrations were univariately associated with overall mortality. In the multivariate analysis, non fatal CVE was significantly and independently associated with age [hazard ratio (95% confidence interval), 1.04 (1.01-1.08); p=0.028] and the upper quartile of PTH concentrations [2.68 (1.24-5.81); p=0.013]. Overall mortality was independently predicted by the bottom quartile of albumin concentrations [5.62 (2.02-15.6); p=0.001] and the upper quartile of CRP concentrations [3.20 (1.14-8.79); p=0.027]. CONCLUSION: Advanced age and high PTH levels are the main predictors of CVE, whereas low albumin and high CRP concentrations are the independent predictors of death in Tunisian renal patients. A better control of these factors would greatly increase the patient's survival rates.

Glutathione S-transferases related to P. aeruginosa lung infection in cystic fibrosis children: preliminary study.

OBJECTIVES: In cystic fibrosis (CF) children, we investigated the predictive impact of glutathione S-transferases (GST) activity and genotypes P1, M1 and T1, and antioxidant levels on stage-severity of Pseudomonas aeruginosa lung infection. METHODS: GST activity was determined in whole blood by spectrophotometry, and GST genotypes by multiplex PCR RFLP for 36 CF and 9 control children. Levels of glutathione in erythrocyte and vitamins A, E and C in plasma were measured by HPLC. RESULTS: No difference in GST activity and no relationship between GST activity and antioxidant levels were observed in CF children as compared to controls. However, GST activity was lower in CF children with severe clinical status and infection, and the frequency of GSTP1 wild type genotype AA, prevalent in uninfected CF children (75%), decreased in infected ones (33%). CONCLUSION: GST activity and genotype could play an important role in modulating P. aeruginosa lung infection in CF patients.

Effects of increasing docosahexaenoic acid intake in human healthy volunteers on lymphocyte activation and monocyte apoptosis.

Dietary intake of long-chain n-3 PUFA has been reported to decrease several markers of lymphocyte activation and modulate monocyte susceptibility to apoptosis. However, most human studies examined the combined effect of DHA and EPA using relatively high daily amounts of n-3 PUFA. The present study investigated the effects of increasing doses of DHA added to the regular diet of human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL. Eight subjects were supplemented with increasing daily doses of DHA (200, 400, 800, 1600 mg) in a TAG form containing DHA as the only PUFA, for 2 weeks each dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear cell phospholipids, the augmentation being significant after 400 mg DHA/d. The tetradecanoylphorbol acetate plus ionomycin-stimulated IL-2 mRNA level started to increase after ingestion of 400 mg DHA/d, with a maximum after 800 mg intake, and was positively correlated (P < 0.003) with DHA enrichment in cell phospholipids. The treatment of monocytes by oxidized LDL before DHA supplementation drastically reduced mitochondrial membrane potential as compared with native LDL treatment. Oxidized LDL apoptotic effect was significantly attenuated after 400 mg DHA/d and the protective effect was maintained throughout the experiment, although to a lesser extent at higher doses. The present results show that supplementation of the human diet with low DHA dosages improves lymphocyte activability. It also increases monocyte resistance to oxidized LDL-induced apoptosis, which may be beneficial in the prevention of atherosclerosis.