Ensuring the safety of animal feed

A general outline is presented of measures for the production of safe animal feed. This is based on the setting of so-called ‘feed safety objectives’ which make use of principles that relate to animal health, animal welfare, legal aspects of farm practices and human food safety objectives for products of animal origin. Particular emphasis will be put on the types of feed used in relation to feedborne animal diseases caused by infectious and chemical agents and on the relationship between animal feed and zoonotic foodborne diseases. In addition the influence of feed on animal welfare will be discussed. To produce safe animal feed, a pro-active control system is advocated. This approach has been very successful in relation to human food and involves the use of ‘good manufacturing practices’ (GMP) and the ‘hazard analysis critical control point’ (HACCP) concept as the main tools. However, it has been shown that the HACCP-system has certain shortcomings. To counteract these shortcomings, product traceability and hazard early-warning systems have been developed and will also be presented

Chronic instability of the anterior tibiofibular syndesmosis of the ankle. Arthroscopic findings and results of anatomical reconstruction

<p>Abstract</p> <p>Background</p> <p>The arthroscopic findings in patients with chronic anterior syndesmotic instability that need reconstructive surgery have never been described extensively.</p> <p>Methods</p> <p>In 12 patients the clinical suspicion of chronic instability of the syndesmosis was confirmed during arthroscopy of the ankle. All findings during the arthroscopy were scored. Anatomical reconstruction of the anterior tibiofibular syndesmosis was performed in all patients. The AOFAS score was assessed to evaluate the result of the reconstruction. At an average of 43 months after the reconstruction all patients were seen for follow-up.</p> <p>Results</p> <p>The syndesmosis being easily accessible for the 3 mm transverse end of probe which could be rotated around its longitudinal axis in all cases during arthroscopy of the ankle joint, confirmed the diagnosis. Cartilage damage was seen in 8 ankles, of which in 7 patients the damage was situated at the medial side of the ankle joint. The intraarticular part of anterior tibiofibular ligament was visibly damaged in 5 patients. Synovitis was seen in all but one ankle joint. After surgical reconstruction the AOFAS score improved from an average of 72 pre-operatively to 92 post-operatively.</p> <p>Conclusions</p> <p>To confirm the clinical suspicion, the final diagnosis of chronic instability of the anterior syndesmosis can be made during arthroscopy of the ankle. Cartilage damage to the medial side of the tibiotalar joint is often seen and might be the result of syndesmotic instability. Good results are achieved by anatomic reconstruction of the anterior syndesmosis, and all patients in this study would undergo the surgery again if necessary.</p

Interobserver and intraobserver variability in the radiological assessment of sialolithiasis using cone beam computed tomography

BACKGROUND: Data regarding the inter- and intraobserver variability in the radiological assessment of sialolithiasis using cone beam computed tomography are missing in the current literature. This study assessed the inter- and intraobserver variability in the radiological assessment of sialolithiasis using cone beam computed tomography (CBCT). MATERIAL AND METHODS: In 107 patients, 130 salivary glands (65 parotid and 65 submandibular) with clinical signs of obstruction were assessed by four independent observers; 2 residents OMFS and 2 experienced OMFS. The observers analyzed the CBCT images and determined the absence or presence of one or more salivary stones in the affected gland. This procedure was repeated after three months. RESULTS: Interobserver agreements showed kappa values of 0.84 for the parotid gland, and 0.93 for the submandibular gland. Intraobserver agreements for the whole group reported kappa values between 0.83 - 0.95. There was no significant difference between residents and experienced OMFS. CONCLUSIONS: Due to the good inter- and intraobserver agreement, CBCT appears to be a reproducible imaging modality for detecting salivary stones in patients with signs and symptoms of obstructed parotid and submandibular glands. Key words:Salivary gland calculi, cone-beam computed tomography, observer variation

Effect of age on the pharmacokinetics of busulfan in patients undergoing hematopoietic cell transplantation; an alliance study (CALGB 10503, 19808, and 100103)

Older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome have often been excluded from myeloablative-conditioning regimens containing busulfan because of non-disease-related morbidity and mortality. We hypothesized that busulfan clearance (BuCL) in older patients (\u3e 60 years) would be reduced compared to that in younger patients, potentially explaining observed differences in busulfan tolerability. AML patients in three CALGB hematopoietic cell transplantation studies were treated with a conditioning regimen using IV busulfan, dosed at 0.8 mg/kg. Plasma busulfan concentrations were determined by LC-MS and analyzed by non-compartmental methods. BuCL was normalized to actual (ABW), ideal (IBW), or corrected (CBW) body weight (kg). Differences in BuCL between age groups were examined using the Wilcoxon rank sum test. One hundred and eighty-five patients were accrued; 174 provided useable pharmacokinetic data. Twenty-nine patients a parts per thousand yen60 years old (median 66; range 60-74) had a significantly higher BuCL versus those \u3c 60 years old (median 50; range 18-60): BuCL 236 versus 168 mL/min, p = 0.0002; BuCL/ABW 3.0 versus 2.1 mL/min/kg, p = 0.0001; BuCL/IBW 3.8 versus 2.6 mL/min/kg, p = 0.0035; BuCL/CBW 3.4 versus 2.6 mL/min/kg, p = 0.0005. Inter-patient variability in clearance (CV %) was up to 48 % in both age groups. Phenytoin administration, a potential confounder, did not affect BuCL, regardless of weight normalization (p \u3e 0.34). Contrary to our hypothesis, BuCL was significantly higher in older patients compared to younger patients in these studies and does not explain the previously reported increase in busulfan toxicity observed in older patients

Human mass balance study of the novel anticancer agent ixabepilone using accelerator mass spectrometry

Ixabepilone (BMS-247550) is a semi-synthetic, microtubule stabilizing epothilone B analogue which is more potent than taxanes and has displayed activity in taxane-resistant patients. The human plasma pharmacokinetics of ixabepilone have been described. However, the excretory pathways and contribution of metabolism to ixabepilone elimination have not been determined. To investigate the elimination pathways of ixabepilone we initiated a mass balance study in cancer patients. Due to autoradiolysis, ixabepilone proved to be very unstable when labeled with conventional [14C]-levels (100 μCi in a typical human radio-tracer study). This necessitated the use of much lower levels of [14C]-labeling and an ultra-sensitive detection method, Accelerator Mass Spectrometry (AMS). Eight patients with advanced cancer (3 males, 5 females; median age 54.5 y; performance status 0–2) received an intravenous dose of 70 mg, 80 nCi of [14C]ixabepilone over 3 h. Plasma, urine and faeces were collected up to 7 days after administration and total radioactivity (TRA) was determined using AMS. Ixabepilone in plasma and urine was quantitated using a validated LC-MS/MS method. Mean recovery of ixabepilone-derived radioactivity was 77.3% of dose. Fecal excretion was 52.2% and urinary excretion was 25.1%. Only a minor part of TRA is accounted for by unchanged ixabepilone in both plasma and urine, which indicates that metabolism is a major elimination mechanism for this drug. Future studies should focus on structural elucidation of ixabepilone metabolites and characterization of their activities

Detection of Squamous Cell Carcinoma and Corresponding Biomarkers Using Optical Spectroscopy

1) Investigate the use of optical reflectance spectroscopy to differentiate malignant and non-malignant tissues in head and neck lesions; 2) Characterize corresponding oxygen tissue biomarkers that are associated with pathologic diagnosi

On the interplay between hypothermia and reproduction in a high arctic ungulate

For free-ranging animals living in seasonal environments, hypometabolism (lowered metabolic rate) and hypothermia (lowered body temperature) can be effective physiological strategies to conserve energy when forage resources are low. To what extent such strategies are adopted by large mammals living under extreme conditions, as those encountered in the high Arctic, is largely unknown, especially for species where the gestation period overlaps with the period of lowest resource availability (i.e. winter). Here we investigated for the first time the level to which high arctic muskoxen (Ovibos moschatus) adopt hypothermia and tested the hypothesis that individual plasticity in the use of hypothermia depends on reproductive status. We measured core body temperature over most of the gestation period in both free-ranging muskox females in Greenland and captive female muskoxen in Alaska. We found divergent overwintering strategies according to reproductive status, where pregnant females maintained stable body temperatures during winter, while non-pregnant females exhibited a temporary decrease in their winter body temperature. These results show that muskox females use hypothermia during periods of resource scarcity, but also that the use of this strategy may be limited to non-reproducing females. Our findings suggest a trade-of between metabolically driven energy conservation during winter and sustaining foetal growth, which may also apply to other large herbivores living in highly seasonal environments elsewhere.publishedVersio

Tetrahydrouridine Inhibits Cell Proliferation through Cell Cycle Regulation Regardless of Cytidine Deaminase Expression Levels

Tetrahydrouridine (THU) is a well characterized and potent inhibitor of cytidine deaminase (CDA). Highly expressed CDA catalyzes and inactivates cytidine analogues, ultimately contributing to increased gemcitabine resistance. Therefore, a combination therapy of THU and gemcitabine is considered to be a potential and promising treatment for tumors with highly expressed CDA. In this study, we found that THU has an alternative mechanism for inhibiting cell growth which is independent of CDA expression. Three different carcinoma cell lines (MIAPaCa-2, H441, and H1299) exhibited decreased cell proliferation after sole administration of THU, while being unaffected by knocking down CDA. To investigate the mechanism of THU-induced cell growth inhibition, cell cycle analysis using flow cytometry was performed. This analysis revealed that THU caused an increased rate of G1-phase occurrence while S-phase occurrence was diminished. Similarly, Ki-67 staining further supported that THU reduces cell proliferation. We also found that THU regulates cell cycle progression at the G1/S checkpoint by suppressing E2F1. As a result, a combination regimen of THU and gemcitabine might be a more effective therapy than previously believed for pancreatic carcinoma since THU works as a CDA inhibitor, as well as an inhibitor of cell growth in some types of pancreatic carcinoma cells

Praktijkervaringen met waterberging en natuur in een beekdal : achtergrondrapport : Beerze

Hoofddoel van het pilotprogramma is waterbeheerders, terreinbeherende instanties en provincies te ondersteunen in hun activiteiten een koppeling tot stand te brengen tussen waterberging en - buffering en natuurbehoud en -ontwikkeling. Eén van de geselecteerde pilots uit het pilotprogramma ligt langs de Beerze. De Beerze is representatief voor de huidige situatie in veel Brabantse beekdalen: er is sprake van een waterkwantiteitsprobleem, en (tijdelijke) berging van het beekwater in natuurgebieden stuit op problemen, vooral vanwege de (eutrofe) waterkwaliteit. Tegelijkertijd speelt verdroging van natuurgebieden een rol. De pilot Beerze ligt in het traject Logtse Baan - Logtse Velden - Smalbroeken. De onderzoeksperiode van deze pilot besloeg 2004 tot medio 200

W::Neo: A Novel Dual-Selection Marker for High Efficiency Gene Targeting in Drosophila

We have recently developed a so-called genomic engineering approach that allows for directed, efficient and versatile modifications of Drosophila genome by combining the homologous recombination (HR)-based gene targeting with site-specific DNA integration. In genomic engineering and several similar approaches, a “founder” knock-out line must be generated first through HR-based gene targeting, which can still be a potentially time and resource intensive process. To significantly improve the efficiency and success rate of HR-based gene targeting in Drosophila, we have generated a new dual-selection marker termed W::Neo, which is a direct fusion between proteins of eye color marker White (W) and neomycin resistance (Neo). In HR-based gene targeting experiments, mutants carrying W::Neo as the selection marker can be enriched as much as fifty times by taking advantage of the antibiotic selection in Drosophila larvae. We have successfully carried out three independent gene targeting experiments using the W::Neo to generate genomic engineering founder knock-out lines in Drosophila