Looking at calcimimetics impact on hypercalcemia of immobilization: hypotheses and a case study

For the treatment of secondary hyperparathyroidism (HPTH-II) in dialysis patients and hypercalcemia in patients with parathyroid carcinoma. Calcimimetics are a new class of drugs approved in the European Community and the United States by the Food and Drug Administration that were designed to suppress parathyroid hormone (PTH) levels with a simultaneous reduction in serum calcium and phosphorus levels, and calcium phosphorus product (Ca x P). Hypocalcemia is a frequent finding during the correction phase of the HPTH-II with calcimimetics. By contrast, the appearance of a hypercalcemia has yet to be described. In this paper, we report a case of severe hypercalcemia of immobilization in a 40-year-old hemodialyzed woman treated by cinacalcet HCl for a severe HPTH-II (PTH>1,000 pg/mL). A kidney transplantation recipient 1983 to 1995, she was diagnosed with Charcot-Marie Tooth disease in 1991. She had multiple orthopedic interventions for kidney-related osteoarticular problems probably favored by the kidney graft and the immunosuppressive treatment. While she was receiving the maximum dose of 180 mg/day of cinacalcet HCl and PTH at 443 pg/mL, she needed to be hospitalized for a right hip prothesis. Two weeks after the intervention she developed a symptomatic hypercalcemia of 3.57 mmol/L which was resistant to several measures including lowering the calcium concentration in the dialysate, withdrawing all vitamin D and calcium supplementation and the administration of calcitonin. Her serum calcium level was finally stabilized in the 2.37-2.95 mmol/L by administration of a single intravenous dose of pamidronate. This observation illustrates that the pharmacological activation of the parathyroid CaR and other putative CaR on bone cells by calcimimetics did not protect against the occurrence of hypercalcemia of immobilization favored by a severe HPTH-II in a hemodialysis patient.     

Modulation of Starch Digestibility in Breakfast Cereals Consumed by Subjects with Metabolic Risk: Impact on Markers of Oxidative Stress and Inflammation during Fasting and the Postprandial Period

Scope : Decreasing postprandial glycaemic excursions may have a beneficial effect on inflammatory and oxidative stress profiles. In this study, we investigated the impact of carbohydrate digestibility modulation per se, as a means of reducing the glycaemic response, on metabolic and inflammatory responses in subjects with metabolic risk factors. Methods and results : Twenty healthy subjects with metabolic risk consumed a cereal product either high in Slowly Digestible Starch (HSDS) or low in SDS (LSDS) at breakfast daily for 3 weeks, in a cross‐over design. Following each 3‐week session, postprandial glycaemia, insulinaemia, the lipid profile, inflammation and oxidative stress markers were assessed and compared to those induced by ingestion of a glucose solution (as a reference). The 2‐h glycaemic and insulinaemic responses were significantly lower following the HSDS breakfast compared with the LSDS breakfast or glucose. No significant differences between the products were observed in terms of the lipid profile, C‐reactive protein, IL‐6 and tumour necrosis factor alpha. We observed a slight increase in fasting lipid peroxidation markers, including an increase in plasma malondialdehyde (MDA) and a decrease in whole blood glutathione (GSH), without significant alteration of urinary F2‐isoprostanes or plasma glutathione peroxidase (GPx) activity. Conclusion : Consumption of HSDS products for 3 weeks significantly altered both postprandial glycaemia and insulinaemia, but was not sufficient to modify the inflammatory profile. Consumption of both cereal products was associated with a slightly higher fasting oxidative stress profile.     

Herbivore-Mediated Effects of Glucosinolates on Different Natural Enemies of a Specialist Aphid

The cabbage aphid Brevicoryne brassicae is a specialist herbivore that sequesters glucosinolates from its host plant as a defense against its predators. It is unknown to what extent parasitoids are affected by this sequestration. We investigated herbivore-mediated effects of glucosinolates on the parasitoid wasp Diaeretiella rapae and the predator Episyrphus balteatus. We reared B. brassicae on three ecotypes of Arabidopsis thaliana that differ in glucosinolate content and on one genetically transformed line with modified concentrations of aliphatic glucosinolates. We tested aphid performance and the performance and behavior of both natural enemies. We correlated this with phloem and aphid glucosinolate concentrations and emission of volatiles. Brevicoryne brassicae performance correlated positively with concentrations of both aliphatic and indole glucosinolates in the phloem. Aphids selectively sequestered glucosinolates. Glucosinolate concentration in B. brassicae correlated negatively with performance of the predator, but positively with performance of the parasitoid, possibly because the aphids with the highest glucosinolate concentrations had a higher body weight. Both natural enemies showed a positive performance-preference correlation. The predator preferred the ecotype with the lowest emission of volatile glucosinolate breakdown products in each test combination, whereas the parasitoid wasp preferred the A. thaliana ecotype with the highest emission of these volatiles. The study shows that there are differential herbivore-mediated effects of glucosinolates on a predator and a parasitoid of a specialist aphid that selectively sequesters glucosinolates from its host plant.     

Effects of Pulsed Electric Fields on Cabernet Sauvignon Grape Berries and on the Characteristics of Wines

The treatment of Cabernet Sauvignon red grapes by pulsed electric fields (PEFs) is performed prior to vinification in order to enhance the extraction of polyphenols. PEF treatments of the longest duration and of the highest energy (E?= 0.7 kV/cm, t _PEF?=?200 ms, W?=?31 Wh/kg) changed the structure of grape skins and produced a wine that was richer in tannins (34 %), while treatment of the highest strength (E?=?4 kV/cm, t _PEF?=?1 ms, W =?4 Wh/kg) altered the visual appearance of phenolic compounds in the skins and led to greater extraction of the anthocyanins (19 %). The PEF treatments caused the depolymerization of skin tannins, improving the diffusion of these decondensed tannins which are smaller. The PEF treatment of longest duration and of the highest energy had more impact on the parietal tannins and the cell walls of the skins while treatment of the highest strength modified more the vacuolar tannins. Changes in the operating parameters of the PEF treatment (E?=?0.7 to 4 kV/cm, t _PEF?=?1 to 200 ms, W?=?4 to 31 Wh/kg) did not affect alcohol content, total acidity nor volatile acidity in finished wines compared to the values of the control wine, but seemed to cause a slight increase in pH (1–2 %).     

RAB10 Interacts with ABCB4 and Regulates Its Intracellular Traffic

ABCB4 (ATP-binding cassette subfamily B member 4) is an ABC transporter expressed at the canalicular membrane of hepatocytes where it ensures phosphatidylcholine secretion into bile. Genetic variations of ABCB4 are associated with several rare cholestatic diseases. The available treatments are not efficient for a significant proportion of patients with ABCB4-related diseases and liver transplantation is often required. The development of novel therapies requires a deep understanding of the molecular mechanisms regulating ABCB4 expression, intracellular traffic, and function. Using an immunoprecipitation approach combined with mass spectrometry analyses, we have identified the small GTPase RAB10 as a novel molecular partner of ABCB4. Our results indicate that the overexpression of wild type RAB10 or its dominant-active mutant significantly increases the amount of ABCB4 at the plasma membrane expression and its phosphatidylcholine floppase function. Contrariwise, RAB10 silencing induces the intracellular retention of ABCB4 and then indirectly diminishes its secretory function. Taken together, our findings suggest that RAB10 regulates the plasma membrane targeting of ABCB4 and consequently its capacity to mediate phosphatidylcholine secretion.     

Prevalence and risk factors for Salmonella and Campylobacter spp. carcass contamination in broiler chickens slaughtered in Quebec, Canada

An observational study was conducted to estimate prevalence and risk factors for Salmonella and Campylobacter spp. carcass contamination in broiler chickens. Eighty-two lots were sampled in four slaughterhouses located in the province of Québec, Canada, over a 10-month period. Carcass contamination was evaluated by the carcass rinse technique for about 30 birds per lot. Exposure to potential risk factors was evaluated based on data from questionnaires, meteorology, and cecal cultures. Multivariable binomial negative regression models were used for risk factor analysis at the lot level. The prevalence of Salmonella-positive carcasses was 21.2% (95% confidence interval: 15.7 to 26.7%). Significant risk factors (P < 0.05) associated with a higher proportion of positive carcasses within lots were Salmonella-positive cecal culture, low rainfall during transportation to the slaughterhouse, temperature of > or = 0 degree C during transportation to the slaughterhouse, and a > or = 4-h waiting period in shipping crates before slaughtering. The prevalence of Campylobacter-positive carcasses was 35.8% (95% confidence interval: 27.1 to 44.5%). Lots containing birds with Campylobacter-positive cecal culture results, lots of birds that were slaughtered at the end of the week, and lots with at least 20% of birds with digestive contents detected in the jejunum at time of slaughtering had a significantly higher proportion (P < 0.05) of contaminated carcasses. These results support the importance of preharvest control measures implemented during rearing to reduce contamination of the final product. Weather during transportation to slaughter and the day of the week that birds were slaughtered also were associated with carcass contamination; further studies are needed to determine the underlying mechanisms by which these factors influence carcass contamination.     

Superheated Steam Drying: An Overview of Pilot and Industrial Dryers with a Focus on Energy Efficiency

According to the principle of sustainability, modern industry should preserve nonrenewable energy sources and develop more efficient processes, especially in terms of energy consumption. The depletion of fossil energy reserves, the environmental impact of greenhouse gases, and the possible threats of environmental taxes are the main reasons to develop new processes in general, and new drying processes in particular, for the existing industries. Using superheated steam as a drying medium instead of hot air can improve the energy efficiency by reusing the energy from exhausted steam and prevent gas emission into the atmosphere by condensation. The present review is focused on both lab-scale pilots—including impingement jet, fluid bed, kiln, fixed bed, and flash drying—described in the literature and existing industrial facilities, with a specific analysis focused on energy efficiency. The usefulness of superheated steam drying pilots for experimental research and for the design of industrial dryers is analyzed. The impact on quality specifications of the dried product for different operating conditions is also presented. Documentation on industrial superheated steam dryers is very rare. Nevertheless, this work presents and analyses the key data available for superheated steam drying of beet, alfalfa, industrial pulp, and paint sludge. Energy recovery and process integration, with a focus on specific technological challenges for industrial dryer implementation, are also presented. This document will result in a discussion of some new ideas for possible R&D in superheated steam drying.     

Dissolution,Transport and Reaction at a DICY/DGEBA Interface

The curing of an epoxy consisting of the solid hardener dicyandiamide (DICY) and the resin diglycidyl ether of bisphenol A (DGEBA) is studied in a system consisting of a tablet of DICY embedded in liquid DGEBA. Dissolution of DICY within the liquid DGEBA in combination with the transport of dissolved DICY from the tablet border into DGEBA and the chemical reaction of both reactants is studied by scanning Brillouin microscopy and infrared spectroscopy. Scanning Brillouin microscopy demonstrates the spatial and temporal evolution of the static and dynamic hypersonic properties in the course of curing in the vicinity of the DICY tablet. Infrared spectroscopy performed on epoxy pieces extracted from the final sample at different distances from the tablet surface give information about the spatial evolution of the curing process. The results achieved by both techniques are finally combined to yield a better understanding of the curing of DICY-based epoxies, which transform upon curing from strongly heterogeneous systems towards increasingly homogeneous systems.