Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats

From studies on different species and in cell culture systems, it has been suggested that vitamin D metabolites might affect themetabolism and elimination of xenobiotics. Although most studies performed on rodents and cell cultures report an upregulationof respective enzymes and transporters, data from the literature are inconsistent. Especially results obtained with sheep differ fromthese observations. As vitamin D metabolites are widely used as feed additives or therapeutics in livestock animals, we aimed toassess whether these differences indicate species-specific responses or occurred due to the very high dosages used in the rodentstudies. -erefore, we applied treatment protocols to rats that had been used previously in sheep or cattle. Forty-eight female ratswere divided into three treatment and corresponding placebo groups: (1) a single intraperitoneal injection of 1,25-(OH)2D3 orplacebo 12 h before sacrifice; (2) daily supplementation with 25-OHD3 by oral gavage or placebo for 10 days; and (3) a singleintramuscular injection of vitamin D3 10 days before sacrifice. In contrast to a previous study using sheep, treatment of rats with1,25-dihydroxyvitamin D3 did not result in an upregulation of cytochrome P450 3A isoenzymes (CYP3A), but a decrease wasfound in hepatic and intestinal expressions. In addition, a downregulation of P-glycoprotein (P-gp) and breast cancer resistanceprotein was found in the brain. Taken together, the stimulating effects of vitamin D metabolites on the expression of genesinvolved in the metabolism and elimination of xenobiotics reported previously for rodents and sheep could not be reproduced. Incontrast, we even observed a negative impact on the expression of CYP3A enzymes and their most important regulator, thepregnane X receptor. Most interestingly, we could demonstrate an effect of treatment with 25-hydroxyvitamin D3 and vitamin D3on the functional activity of ileal P-glycoprotein (P-gp) using the Ussing chamber technique.Fil: Klumpp, Karoline. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Lange, Frauke. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Muscher-Banse, Alexandra S.. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Schnepel, Nadine. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Hansen, Kathrin. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Maté, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Wilkens, Mirja. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemani

Amending Contracts for Choreographies

Distributed interactions can be suitably designed in terms of choreographies. Such abstractions can be thought of as global descriptions of the coordination of several distributed parties. Global assertions define contracts for choreographies by annotating multiparty session types with logical formulae to validate the content of the exchanged messages. The introduction of such constraints is a critical design issue as it may be hard to specify contracts that allow each party to be able to progress without violating the contract. In this paper, we propose three methods that automatically correct inconsistent global assertions. The methods are compared by discussing their applicability and the relationships between the amended global assertions and the original (inconsistent) ones.Comment: In Proceedings ICE 2011, arXiv:1108.014

Chronotrope Inkompetenz als kardiovaskulärer Risikofaktor – Vorkommen bei Patienten mit chronischer Niereninsuffizienz

Untersucht wurde das Vorkommen von Chronotroper Inkompetenz(CI) an Patienten mit chronischer Nierenerkrankung. Als Kriterien zur Beurteilung der Herzfrequenz während Belastung(Fahrradergometrie)wurden herangezogen: Erreichen der alters- und geschlechtsspezifischen Sollherzfrequenz, Steigerung der Herzfrequenz von Ruhe zu Belastung und Berechnung der chronotropen Reaktion(CR). Nach allen drei Methoden sprachen die Ergebnisse für das vermehrte Vorkommen einer CI bei chronisch Nierenkranken im Vergleich zum gesunden Kollektiv. Niereninsuffiziente erreichten seltener die Sollherzfrequenz, zeigten eine geringere Herzfrequenzspanne von Ruhe zur Maximalbelastung und der CR-Wert entsprach häufiger einer chronotropen Schwäche als in der Kontrollgruppe. Die höchste Prävalenz zeigte sich bei dialysepflichtigen Patienten, Nierentransplantierte zeigten geringfügig bessere Ergebnisse und die Gruppe mit chronischer Niereninsuffizienz in kompensierter Retention zeigte eine Neigung zur CI

“Greening up”: A Multistep Synthetic Transformation

Green Chemistry is an experimental design theory that aims to reduce the use and generation of hazardous substances in order to address problems we face in the world today like water contamination, global warming, ozone depletion, and pollution. When hazardous substances are replaced with less hazardous substances, both risk and cost can be reduced. Teaching the importance and relevance of green chemistry is imperative to the future of chemistry and the environment. Since most useful organic chemical targets require more than one synthetic step, it is important that undergraduate organic chemistry students be exposed to labs that require multiple transformations. This will allow students to understand how reactions work after observing them first-hand. Additionally, since the ‘traditional’ synthesis of most chemical substances utilizes solvents, reagents, and conditions that are harmful and hazardous to the environment, students had to propose their own green alternatives by completing a 3-step synthesis and determining a greener route. The products were purified, characterized and then a metric system was used to compare the greenness of the reactions. A reaction was considered more green if there were relative decreases in the combination of factors that include cost, environmental toxicity, and waste produced. In total, 22 different targets were attempted to be synthesized

Heat capacities of TiO2-bearing silicate liquids: Evidence for anomalous changes in configurational entropy with temperature

The heat capacities of several TiO2-bearing silicate glasses and liquids containing Cs2O, Rb2O, Na2O, K2O, CaO, MgO, or BaO have been measured to 1100 K using a differential scanning calorimeter and to 1800 K using a Setaram HT-1500 calorimeter in step-scanning mode. The results for liquids of M2O-TiO2-2SiO2 composition (M -- Na, K, Cs) are compared to those for liquids of M2O-3SiO2 composition. The presence of TiO2 has a profound influence on the heat capacity of simple three-component silicate liquids over the temperature range 900-1300 K. Specifically, replacement of Si4+ by Ti4+ leads to doubling of the magnitude of the jump in Cp at the glass transion (Tg); this is followed by a progressive decrease in liquid Cp for over 400 K, until Cp eventually becomes constant and similar to that in Ti-free systems. The large heat capacity step at Tg in the TiO2-bearing melts suggests significant configurational rearrangements in the liquid that are not available to TiO2-free silicates. In addition, these "extra" configurational changes apparently saturate as temperature increases, implying the completion of whatever process is responsible for them, or the attainment of a random distribution of structural states. Above 1400 K, however, where the heat capacities of TiO2-bearing and TiO2-free alkali silicate liquids are similar, their configurational entropies differ by ~3.5 J/g.f.w.-K. The larger configurational entropy of the TiO2-bearing alkali silicate liquids relative to the TiO2-free liquids is energetically equivalent to raising the liquid temperature by more than 300 degrees. This result clearly demonstrates the energetic magnitude of the configurational changes apparent in the supercooled liquid region and their impact on the thermodynamic properties of the stable liquid. Consideration of both density measurements on liquids and spectroscopic data on quenched glasses (from the literature) suggests that the anomalous configurational rearrangements may involve the breakdown of alkali and alkaline earth titanate complexes and changes in Ti4+ coordination.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30728/1/0000377.pd

Exercise hemodynamics of bovine versus porcine bioprostheses: A prospective randomized comparison of the mosaic and perimount aortic valves

ObjectiveThis prospective randomized study compares a porcine with a bovine bioprosthesis in the aortic position with regard to hemodynamic performance during exercise.MethodsBetween August of 2000 and December of 2002, 136 patients underwent aortic valve replacement with the porcine Medtronic Mosaic (n = 66) or the bovine Carpentier-Edwards Perimount (n = 70) bioprosthesis. Transthoracic echocardiography was performed to assess hemodynamic and dimensional data preoperatively and 10 months postoperatively; the latter follow-up included stress echocardiography with treadmill exercise.ResultsAt rest and during exercise (25 and 50 W), there was a significant difference in mean pressure gradient between the bovine and the porcine valves with labeled sizes 21 and 23, with superiority of the Perimount prosthesis. There was no difference in effective orifice area and incidence of patient-prosthesis mismatch among all sizes. The left ventricular mass index decreased significantly within 10 months postoperatively in the size 23 bovine group and the size 25 porcine group.ConclusionsOur data show a significant superiority of pressure gradients for the bovine bioprosthesis, especially with small valve sizes, when compared with the porcine device, which is more distinctive during exercise

Oral bacteria in infective endocarditis requiring surgery: a retrospective analysis of 134 patients.

OBJECTIVES It has been reported that bacteria associated with infective endocarditis originate from the oral cavity in 26-45% of cases. However, little is known on the counts and species of periodontal microbiota in infected heart valves. The aim of this study was to identify these aspects of periodontal microbiota in infective endocarditis and to potentially initiate a dental extraction concept for periodontally compromised teeth concerning patients requiring heart valve surgery. MATERIALS AND METHODS The retrospective study group consisted of tissue samples from infected heart valves of 683 patients who had undergone heart valve surgery. Before patients had undergone cardiac surgery, the following laboratory tests confirmed the occurrence of endocarditis in all patients: blood cultures, echocardiography, electrocardiography, chest X-ray, and electrophoresis of the serum proteins. The specimens were aseptically obtained and deep frozen immediately following surgery. Microbiological diagnosis included proof of germs (dichotomous), species of germs, and source of germs (oral versus other). RESULTS Microbiota was detected in 134 (31.2%) out of 430 enrolled patients. Oral cavity was supposed to be the source in 10.4% of cases, whereas microbiota of the skin (57.5%) and gastrointestinal tract (GIT, 24.6%) were detected considerably more frequently. Moreover, periodontal bacteria belonged mostly to the Streptococci species and the yellow complex. None of the detected bacteria belonged to the red complex. CONCLUSION Most frequently, the skin and GIT represented the site of origin of the microbiota. Nevertheless, the oral cavity represented the source of IE in up to 10%. Consequently, it needs to be emphasized that a good level of oral hygiene is strongly recommended in all patients undergoing heart valve surgery in order to reduce the bacterial load in the oral cavity, thereby minimizing the hematogenous spread of oral microbiota. The prerequisites for conservative dental treatment versus radical tooth extraction must always be based on the patient's cooperation, and the clinical intraoral status on a sense of proportion in view of the overall clinical situation due to the underlying cardiac disease. CLINICAL RELEVANCE The oral cavity is a source of oral microbiota on infected heart valves. Patients requiring heart valve surgery should always undergo a critical evaluation of dental treatment affecting periodontally compromised teeth, favoring a systematic, conservative-leaning recall

Rheological behavior of a commercial milk-based sauce

• The acceptation of semisolid foods by consumers is greatly determined by their rheological properties. • Sauces are semisolid foods and, in general, show viscoplastic and shear-thinning viscous flow behaviours. On the other hand, viscoelastic properties are specifically significant in the handling and quality control tasks. • As temperature changes cause alterations in physical and chemical properties of food components, which influence in texture, stability, taste, etc., a better understanding of the influence of this parameter on milk-based sauces would allow improve product quality.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Health benefits of supplementing nursery pig diets with microalgae or fish oil

Weaning stress can negatively impact a pig’s performance; dietary supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFA) reduces inflammatory stress and promotes nursery pig’s health and growth. Fish oil (FO) is a major source of n-3 PUFA; however, microalgae (AL) may provide an alternative source of n-3 PUFA. The aim of this study was to assess the health benefits of supplementing a plant protein-based nursery diet with 3.12% AL or 1.25% FO providing equal total n-3 PUFA compared to a control (CON) diet. Seventy-two pigs were fed experimental diets for three weeks (phases 1 and 2), followed by a common standard diet for three weeks (phase 3). Following phase 2, 8 pigs per treatment underwent a lipopolysaccharide (LPS) immune stress challenge to assess the acute-phase response and 8 pigs per treatment were vaccinated with novel antigens to assess acquired immunity. No significant differences in piglets’ growth were observed, despite decreased feed intake in FO piglets compared to AL piglets in phase 3. AL supplementation tended to reduce, and FO supplementation significantly reduced the LPS-induced fever response. The AL pigs had significantly reduced cortisol responses, increased cytokine concentrations, and increased chromogranin A concentrations compared to FO and CON pigs following LPS challenge. Results suggest that AL or FO supplementation in nursery diets differentially modulate the acute-phase response, possibly due to different n-3 PUFA profiles between the two ingredients