The influence of bile salts and mixed micelles on the pharmacokinetics of quinine in rabbits.

The bioavailability of orally administered drugs can be influenced by interactions with food components and by physico-chemical conditions in the upper gastrointestinal tract. Normally, bile salts enhance the transport of lipophilic drugs across mucosal membranes. Bile salts are able to form stable mixed micelles consisting of fatty acids and phospholipids. Conventional micellar systems are known to solubilize lipophilic drugs having a low bioavailability. The influence of bile salts and mixed micelles on the pharmacokinetics of the lipophilic drug quinine was investigated in rabbits. Female rabbits were given intraduadenally quinine (5 mg/kg body weight) without and with incorporation into the micellar or mixed micellar systems. Blood was collected every 30 min for 6 h. In plasma, concentration of quinine was measured using HPLC. The plasma concentration-time profiles of quinine were significantly lower within the first 2 h after administration in presence of both the sodium salt of glycodeoxycholic acid (above the critical micellar concentration) as well as of mixed micellar systems consisting of glycodeoxycholic acid and palmitic acid and/or lecithin. The pharmacokinetic parameters AUC (relative bioavailability) and c(max) of quinine were significantly decreased by micellar systems in rabbits. These mixed micellar systems lower and not as expected, increase the absorption of quinine in vivo. Therefore, quinine should be orally administered at least 1h before food intake, particularly before fat intake.     

Calcium-binding proteins S100A8 and S100A9 as novel diagnostic markers in human prostate cancer.

PURPOSE: S100 proteins comprise a family of calcium-modulated proteins that have recently been associated with epithelial tumors. We examined the expression of two members of this family, S100A8 and S100A9, together with the S100 receptor RAGE (receptor for advanced glycation end products) in human prostate adenocarcinomas and in prostatic intraepithelial neoplasia. EXPERIMENTAL DESIGN: Tissue specimens of 75 patients with organ-confined prostate cancer of different grades were analyzed by immunohistochemistry for expression of S100A8, S100A9, and RAGE. In addition, in situ hybridization of S100A8 and S100A9 was done for 20 cases. An ELISA was applied to determine serum concentrations of S100A9 in cancer patients compared with healthy controls or to patients with benign prostatic hyperplasia (BPH). RESULTS: S100A8, S100A9, and RAGE were up-regulated in prostatic intraepithelial neoplasia and preferentially in high-grade adenocarcinomas, whereas benign tissue was negative or showed weak expression of the proteins. There was a high degree of overlap of S100A8 and S100A9 expression patterns and of S100A8 or S100A9 and RAGE, respectively. Frequently, a gradient within the tumor tissue with an increased expression toward the invaded stroma of the prostate was observed. S100A9 serum levels were significantly elevated in cancer patients compared with BPH patients or healthy individuals. CONCLUSION: Our data suggest that enhanced expression of S100A8, S100A9, and RAGE is an early event in prostate tumorigenesis and may contribute to development and progression or extension of prostate carcinomas. Furthermore, S100A9 in serum may serve as useful marker to discriminate between prostate cancer and BPH.     

A continuous‐flow,high‐throughput,high‐pressure parahydrogen converter for hyperpolarization in a clinical setting

Pure parahydrogen (pH₂) is the prerequisite for optimal pH₂‐based hyperpolarization experiments, promising approaches to access the hidden orders of magnitude of MR signals. pH₂ production on‐site in medical research centers is vital for the proliferation of these technologies in the life sciences. However, previously suggested designs do not meet our requirements for safety or production performance (flow rate, pressure or enrichment). In this article, we present the safety concept, design and installation of a pH₂ converter, operated in a clinical setting. The apparatus produces a continuous flow of four standard liters per minute of ≈98% enriched pH₂ at a pressure maximum of 50 bar. The entire production cycle, including cleaning and cooling to 25 K, takes less than 5 h, only ≈45 min of which are required for actual pH₂ conversion. A fast and simple quantification procedure is described. The lifetimes of pH₂ in a glass vial and aluminum storage cylinder are measured to be T_1C(glass vial) = 822 ± 29 min and T_1C(Al cylinder) = 129 ± 36 days, thus providing sufficiently long storage intervals and allowing the application of pH₂ on demand. A dependence of line width on pH₂ enrichment is observed. As examples, ¹H hyperpolarization of pyridine and ¹³C hyperpolarization of hydroxyethylpropionate are presented. Copyright © 2012 John Wiley & Sons, Ltd.     

Ultrasound Bone Fracture Sensing and Data Communication: Experimental Results in a Pig Limb Sample

Approximately 6.3 million fractures occur each year in the United States alone. Accurately monitoring the progression of fracture healing is essential to be able to advise patients when it is safe to return to normal activity. The most common method used to confirm and monitor fracture healing is the acquisition of multiple radiographic images over the many months required for healing. This imaging method uses large expensive equipment and exposes patients to high levels of ionizing radiation. In the study described here, we tested another technology for monitoring fracture healing that could minimize the need for multiple radiographic images. We tested a piezoelectric transducer fixed to the surface of a bone that uses electromechanical impedance spectroscopy to measure simulated fractures and transmits the measurement data to an acoustic receiver located externally on the skin surface.     

Short-term preoperative supplementation of an immunoenriched diet does not improve clinical outcome in well-nourished patients undergoing abdominal cancer surgery

ObjectiveA recent study suggested that the anti-inflammatory effect of immunonutrition starts after only two d. We therefore investigated the effect of an immunoenriched oral diet administered for three d preoperatively.MethodsIn this prospective, randomized, double-blind, placebo-controlled study, well-nourished patients (Nutrition Risk Screening 2002 <3) with gastrointestinal cancer who were scheduled for major elective abdominal cancer surgery were randomly assigned to either 750 mL of an immunoenriched formula (IEF group) or 750 mL of an isocaloric, isonitrogenous placebo diet (Con group) for 3 consecutive d preoperatively.ResultsA total of 108 patients (IEF group: n = 55; Con group: n = 53) were randomized. The two groups were comparable for all baseline and surgical characteristics. The overall mortality was 2.8% and not significantly different between the two groups (IEF group: 3.6% vs. Con group: 1.9%, P = 1.00). Intention-to-treat analysis showed no difference for the incidence of postoperative overall (IEF group: 29% vs. Con group: 30%; P = 1.00) and infectious (IEF group: 15% vs. Con group: 17%; P = 0.79) complications. Length of hospital stay was 12 ± 4.9 d in the IEF group and 11.6 ± 5.3 d in the Con group (P = 0.68).ConclusionsPreoperative oral supplementation with an immunoenriched diet for 3 d preoperatively did not improve postoperative outcome compared with the placebo in well-nourished patients with elective gastrointestinal cancer surgery.