The effect of selenium source on the oxidative status and performance of broilers reared at standard and high ambient temperatures.

1. This study investigated the oxidative status of broilers fed diets containing selenium (Se) from 14 to 35 d of age and reared at two different constant temperatures. Measurements of oxidative status included blood glutathione peroxidase (GSH-Px) and plasma total antioxidant status (TAS). Other variables included feed intake (FI), weight gain (WG), feed conversion ratio (FCR), Se levels in breast and liver tissue, jejunal villus morphometry, percentage weight of organs in relation to body weight; apparent metabolisable energy adjusted for nitrogen (AMEn); dry matter retention (DMR); fat retention (FR) and nitrogen retention (NR).2. The experiment started at 14 d of age, when 240 birds were randomly allocated to 48 pens (12 pens in four rooms). Treatments included a control diet 1 (SFC; 209.4 g/kg CP and 12.98 MJ/kg ME and no added Se containing saturated fat); diet 2 (SFSe) the control plus 12.605 mg/kg Se additive; diet 3 (USFC) was a second control diet (208.2 g/kg CP and 13.10 MJ/kg ME with no added Se containing unsaturated fat as rapeseed oil); diet 4 (USFSe) was the latter control plus 12.605 mg/kg Se additive. Two rooms were kept at a standard temperature of 20°C (ST) and two rooms were kept at high temperature of 35°C (HT).3. A temperature x Se interaction existed for GSH-Px in birds reared at ST (P < 0.05), and these birds had the highest levels of Se in liver tissue (P < 0.05). Fat x Se interactions were evident in breast tissue with highest levels in USFSe (P < 0.05). Adding Se improved jejunal VH: CD in USFSe fed birds (P < 0.001).4. Birds reared at ST had higher FI and WG than those reared at HT (P < 0.001), and had lower FCR than those reared at HT (P < 0.05). AMEn (MJ/kg DM) and FR were higher in birds fed USF diets, and lowest in birds fed SF (P < 0.50 and P < 0.001 respectively). NR was highest in birds raised at ST (P < 0.50).5. Broiler growth performance was reduced by HT. Oxidative status and Se in liver tissue was improved by adding Se in both diets.

The effect of feeding different sources and levels of selenium on growth performance and antioxidant status of broilers raised at two different temperatures.

1. This study examined the effects of different dietary sources and levels of selenium (Se) on growth performance, hepatic and breast meat Se content, glutathione peroxidase (GSH-Px) activity and total antioxidant status (TAS) in blood, when fed to broilers from 14 to 35 d of age and reared at two different temperatures (20°C and 35°C). 2. Five hundred and sixty male Ross 308 broilers were reared in a single floor pen and fed the same proprietary starter diet from 0 to 14 d age (229.9 g/kg CP and 12.67 MJ/kg ME, without Se supplementation). 3. The experiment started at 14 d age, and the birds randomly assigned to 112 raised-floor pens (0.36 m2 area, 5 birds/pen). Each of the seven experimental diets were offered to birds in 16 pens within four rooms. Two rooms were at 20°C and two rooms were maintained at 35°C. The experimental diets were fed from 14 to 35 d age and contained 214.9 g/kg CP and 13.11 MJ/kg ME. The experimental diets were as follows; control diet containing background Se only (0.189 mg/kg; C); low level sodium selenite (0.376 mg/kg; LSS): high level sodium selenite (0.558 mg/kg; HSS); low level commercial B Traxim® Se (0.244 mg/kg) (LBT); high level B Traxim® Se (0.448 mg/kg; HBT); low level selenised yeast (0.290 mg/kg; LSY); high level selenised yeast (0.487 mg/kg; HSY). 4. Birds consumed more when raised at 20°C compared to birds reared at 35°C (P ≤ 0.05). Birds fed lower Se level reared at 35°C had higher weight gain versus those fed higher Se level (P < 0.05). Birds fed SY had the lowest feed intake, weight gain and FCE (P < 0.05). The greatest GSH-Px activity was observed in birds fed SS diets (P < 0.001). There were interactions between diet x level for TAS, which were highest in birds fed LBT compared to birds fed HBT (P < 0.05). Breast Se content was higher in birds fed HSY compared to LSY (P < 0.001). The highest hepatic Se was seen in birds fed SY and lowest in C (P < 0.001). 5. Birds fed BT diets showed similar levels of Se to those birds fed inorganic Se, and similar levels of GSH-Px to birds fed SY. Further comparative work with broilers fed BT and other Se supplemented diets may elucidate the findings from this report.

Effect of feeding different sources of selenium on growth performance and antioxidant status of broilers.

1. This study was conducted to determine the effect of different sources of selenium (Se) on breast and liver tissue deposition, apparent metabolisable energy (AME), growth performance and antioxidant status of broilers, measured as Se content in liver and breast tissues and glutathione peroxidase (GSH-Px) in blood, when used in 0-35 d broiler chicken diets. 2. A total of 200 male Ross 308 broilers were used in the feeding trial, which comprised two dietary phases, a starter from 0 to 21 d and finisher from 21 to 35 d of age. Four treatments with 10 replications each were used. A control diet (C) was formulated that was sufficient in protein and energy (230 and 215 g/kg of crude protein and 12.67 and 13.11 MJ/kg of metabolisable energy, respectively), for both phases, but contained background Se only from the feed ingredients. Diet 2 (IS) was supplemented with 10.35 g/t inorganic, elemental source of Se. Diet 3 (SY) was supplemented with 136.36 g/t selenised yeast, an organic source derived from Saccharomyces cerevisiae. Diet 4 (SS) was supplemented with 0.666 g/t sodium selenite, an inorganic source. 3. Birds fed the SY diet consumed less and weighed less than those fed IS or C (P < 0.05; 0-35 d of age), but there was no difference compared to birds fed SS diets. There were no differences in FCR or dietary AME between broilers fed different Se sources. All diets containing supplementary Se increased concentrations in the liver and breast muscle, and for GSH-Px levels in blood compared to birds fed the C diet (P < 0.001). Birds fed SY diets had greater Se levels in liver and breast tissues compared to birds fed any of the other diets (P < 0.001). 4. Diets supplemented with Se had variable effects on broiler growth performances and antioxidant status. Feeding Se from a yeast source has higher transfer into breast tissues. Feeding different sources and levels of Se to birds in a more challenging situation to induce oxidative stress may bring more conclusive results.

Harnessing drug/radiation interaction through daily routine practice: Leverage medical and methodological point of view (MORSE 02-17 study).

BACKGROUND: Safety profile of the interaction between anticancer drugs and radiation is a recurrent question. However, there are little data regarding the non-anticancer treatment (NACT)/radiation combinations. The aim of the present study was to investigate concomitant NACTs in patients undergoing radiotherapy in a French comprehensive cancer center. METHODS: A prospective cross-sectional study was conducted. All cancer patients undergoing a palliative or curative radiotherapy were consecutively screened for six weeks in 2016. Data on NACTs were collected. RESULTS: Out of 214 included patients, a NACT was concomitantly prescribed to 155 patients (72%), with a median number of 5 NACTs per patient (range: 1-12). The most prescribed drugs were anti-hypertensive drugs (101 patients, 47.2%), psychotropic drugs (n = 74, 34.6%), analgesics (n = 78, 36.4%), hypolipidemic drugs (n = 57, 26.6%), proton pump inhibitors (n = 46, 21.5%) and antiplatelet drugs (n = 38, 17.8%). Although 833 different molecules were reported, only 20 possible modifiers of cancer biological pathways (prescribed to 74 patients (34.5%)) were identified. Eight out of the 833 molecules (0.9%), belonging to six drug families, have been investigated in 28 ongoing or published clinical trials in combo with radiotherapy. They were prescribed to 63 patients (29.4%). CONCLUSION: Drug-radiation interaction remains a subject of major interest, not only for conventional anticancer drugs, but also for NACTs. New trial designs are thus required.

Rehabilitation and leucine supplementation as possible contributors to an athlete's muscle strength in the reathletization phase following anterior cruciate ligament surgery.

OBJECTIVES: To determine the interest of a muscle rehabilitation program following anterior cruciate ligament reconstruction (ligamentoplasty) and the influence of leucine supplementation on the muscle strength of athletes undergoing reathletization. MATERIAL AND METHODS: The authors have analyzed prospectively, in double blind, two groups of athletes (22 versus 23) who had randomly received either leucine supplementation or a placebo. Muscle strength was measured at the beginning and the end of the program In terms of thigh perimeter, isokinetic testing results, single-leg test and percentage of body fat. The reathletization program was identical in the two groups for an average of 2.7weeks. RESULTS: By the end of the program, both groups had increased their thigh perimeter at 10 and 15cm from the patella (respectively 1.2cm and 1.3cm, P<0.0001). Fat mass had decreased by 1.28% (P=0.017). Values of isokinetic muscle strength for the injured limb improved by 13 to 55% with highly significant differences. The leucine group generally showed more improved muscle parameters than the placebo group, with only one significant positive result with regard to thigh muscle perimeter at 10cm from the patella (P=0.009). CONCLUSION: With or without leucine, the rehabilitation program leads to improved muscle quality. Taking leucine appears to promote muscle recovery of the injured limb with regard to a single parameter (thigh muscle perimeter at 10cm from the patella), while the other parameters showed no significant improvement. A complementary study associating the recovery phase with other dietary supplements might help to optimize these preliminary results.

Validation of cytochrome P450 time-dependent inhibition assays: a two-time point IC50 shift approach facilitates kinact assay design.

1. Recent guidance from the US Food and Drug Administration (USFDA) has advocated testing of time-dependent inhibition of cytochrome P450 (CYP), which can be addressed by performing IC(50) shift as well as K(I)/k(inact) determinations. 2. Direct (IC(50), K(i)) and time-dependent inhibition (IC(50) shift, K(I)/k(inact)) assays were validated in human liver microsomes with liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis for the following enzyme/substrate/inhibitor combinations: CYP1A2/phenacetin/alpha-naphthoflavone/furafylline, CYP2C8/amodiaquine/montelukast/gemfibrozil-1-O-beta-glucuronide, CYP2C9/diclofenac/sulfaphenazole/tienilic acid, CYP2C19/S-mephenytoin/S-benzylnirvanol/S-fluoxetine, CYP2D6/dextromethorphan/quinidine/paroxetine, and CYP3A4/midazolam/testosterone/ketoconazole/azamulin/verapamil/diltiazem. IC(50) shift assays were performed with two pre-incubation time points (10 and 30 min) to facilitate k(inact) assay design. 3. Data obtained show good agreement with literature values. For rapid acting inhibitors, such as azamulin/CYP3A4 and tienilic acid/CYP2C9, the IC(50) shifts were similar at both time points suggesting a short maximum pre-incubation time with closely spaced time points for the K(I)/k(inact) assay. Slow acting inhibitors (such as verapamil/CYP3A4 or S-fluoxetine/CYP2C19) showed an increase in IC(50) shift between 10 and 30 min suggesting a longer maximum pre-incubation time with wider spacing of time points for K(I)/k(inact). 4. The two-time point IC(50) shift experiment proved to be an excellent method for the selection of appropriate K(I)/k(inact) assay parameters and is suitable for the routine analysis of P450 inhibition by drug candidates.

Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer.

We describe a flexible system for gene expression profiling using arrays of tens of thousands of oligonucleotides synthesized in situ by an ink-jet printing method employing standard phosphoramidite chemistry. We have characterized the dependence of hybridization specificity and sensitivity on parameters including oligonucleotide length, hybridization stringency, sequence identity, sample abundance, and sample preparation method. We find that 60-mer oligonucleotides reliably detect transcript ratios at one copy per cell in complex biological samples, and that ink-jet arrays are compatible with several different sample amplification and labeling techniques. Furthermore, results using only a single carefully selected oligonucleotide per gene correlate closely with those obtained using complementary DNA (cDNA) arrays. Most of the genes for which measurements differ are members of gene families that can only be distinguished by oligonucleotides. Because different oligonucleotide sequences can be specified for each array, we anticipate that ink-jet oligonucleotide array technology will be useful in a wide variety of DNA microarray applications.

Fluorometric high-throughput screening for inhibitors of cytochrome P450.

Rapid screening for cytochrome P450 inhibitors is part of the current paradigm for avoiding development of drugs likely to give clinical pharmacokinetic drug-drug interactions and associated toxicities. We have developed microtiter plate-based, direct, fluorometric assays for the activities of the principal human drug-metabolizing enzymes, CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, as well as for CYP2A6, which is an important enzyme in environmental toxicology. These assays are rapid and compatible with existing high-throughput assay instrumentation. For CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2D6, the potency of enzyme inhibition (IC50) is consistent regardless of the probe substrate or assay method employed. In contrast, CYP3A4 inhibition for an individual inhibitor shows significant differences in potency (>300-fold) depending on the probe substrate being used. We have investigated these differences through the use of several structurally distinct fluorescent substrates for CYP3A4 and several classical substrate probes (e.g., testosterone, nifedipine, and midazolam), with a panel of known, clinically significant, CYP3A4 inhibitors. The use of multiple probe substrates appears to be needed to characterize the inhibition potential of xenobiotics for CYP3A4.

Mortality in a recent oil refinery cohort.

A retrospective cohort mortality study of 10,763 Amoco Corporation oil refinery workers employed between 1970 and 1980 showed low overall mortality; the standardized mortality ratio for all causes of death was 73 for white males and 68 for black males. White male mortality was examined by several exposure classifications devised for group cohort members by potential for exposure to refinery processes and exposure to two components of petroleum (light aromatic hydrocarbons and heavy oils). Statistically significant elevations were found in various exposure groups for skin cancers, digestive system cancers, and benign neoplasms. Of these, skin cancer mortality appeared to increase with increasing exposure.

Health insurance claims of petrochemical company employees.

This paper describes a morbidity data base for epidemiologic studies which uses information from health insurance claims. Strengths of the data base include completeness and relatively low cost. A limitation is the length of time needed for all claims to be received and processed: rates generated using current information are lower than they will be after all claims are processed. Nevertheless, internal comparisons can presently be made using such rates. Examples illustrate differences in claims experience according to employees' smoking habits and according to kind of job.

Determining exposure categories for a refinery retrospective cohort mortality study.

This paper describes and compares two methods used to assign exposure categories to 10,766 petroleum refinery employees included in an epidemiological study. The first scheme grouped individuals into six organization (OR) job groups: Administrative, Maintenance, Operations, Laboratory, General and Other. This scheme used "most common administrative department," as determined by computerized job histories. For the second classification scheme, "most common job title" and "most common plant location" were used to group individuals in four ways (IH codes): 1)job type (administrative, maintenance, operations and unknown); 2) contact with refinery processes; 3) exposure to light aromatics; and 4) exposure to heavy oils. Exposure categories for the latter three were none, occasional, routine and unknown. Comparison of the two schemes showed that OR job groups developed from administrative job histories were sometimes useful in classifying employees according to refinery exposures. While OR job groups were acceptable for employees clearly in managerial, maintenance or operations positions, IH codes provided more precise exposure profiles for these three relatively homogeneous groups. For individuals in laboratory positions and those with vague or unspecified department codes (23% of this cohort), the IH classification codes were necessary to group employees by job and exposure.

Smoking habits of oil refinery employees.

Smoking habits of White male employees of a large oil company were analyzed. There were only slight differences in smoking habits between refinery and nonrefinery employees. Salaried employees, both at refineries and elsewhere, smoked much less than hourly employees.