Impact of feed glyphosate residues on broiler breeder egg production and egg hatchability.

Glyphosate is the active substance in glyphosate-based herbicides, e.g. Roundup. Its widespread application on feed crops leaves residues in the feed. Glyphosate has antimicrobial and mineral chelating properties and we investigated whether there is an association between feed residues of glyphosate on the one side and broiler breeder egg laying percent and egg hatchability on the other side. Twenty-six feed samples from five conventional flocks producing hatching eggs were analysed for glyphosate. Data on laying percent and egg hatchability from periods following each feed sampling were then associated with feed residues of glyphosate. The average glyphosate residue level was 0.09 mg/kg, maximum was 0.19 and minimum was 0.004 mg/kg. Average laying percent over observation days was 65% (SD = 5.4%) and average hatchability was 79% (SD = 5.8%). We found a negative association between feed glyphosate residue level and hatchability (P = 0.03) when adjusted for breeder age, storage time of eggs on farm before delivery and storage time at hatchery before incubation start. No association was found with laying percent (P = 0.59) adjusted for breeder age. The range of glyphosate concentrations in feed was narrow and should be kept in mind when interpreting both significant and non-significant associations with glyphosate residue concentrations. In nine of 24 analysed conventional eggs the concentration of glyphosate in yolk was above the detection limit however below the quantification limit indicating that traces of glyphosate are common in conventional eggs.

Efficacy of ixazomib for the treatment of relapsed/refractory multiple myeloma: A protocol of systematic review and meta-analysis.

BACKGROUND: Over the past years, ixazomib has been increasingly explored for the treatment of relapsed/refractory multiple myeloma (RRMM). However, its results are still contradictory. This study will explore the efficacy and safety of ixazomib for patients with RRMM. METHODS: A systematic records search of Cochrane Library, PUBMED, EMBASE, CINAHL, ACMD, PsycINFO, WANGFANG, and China National Knowledge Infrastructure will be carried out from their origin to March 31, 2020 with no limitations of language and publication status. Trials will be selected by titles/abstracts, and full manuscripts by 2 independent authors. Data collection will be carried out from eligible trials based on the previous designed criteria. Study quality will be checked using Cochrane risk of bias, and statistical analysis will be administered by RevMan 5.3 software. RESULTS: This study will summarize the current high-quality trials investigating the efficacy and safety of ixazomib for the treatment of patients with RRMM. CONCLUSION: The results of this study may provide convinced evidence on the evidence-based medicine level, and guidance for clinical practice and future studies. INPLASY REGISTRATION NUMBER: INPLASY202040027.

Why Regulators Lost Track and Control of Pesticide Risks: Lessons From the Case of Glyphosate-Based Herbicides and Genetically Engineered-Crop Technology.

PURPOSE OF REVIEW: The approval of genetically engineered (GE) crops in the late 1990s triggered dramatic changes in corn, soybean, and cotton pest management systems, as well as complex, novel regulatory challenges. Lessons learned are reviewed and solutions described. RECENT FINDINGS: Government-imposed resistance management provisions can work and adapt to changing circumstances, but within the private sector, pressures to gain and hold market share have thus far trumped the widely recognized need for resistance management. Risks arising from the use of formulated pesticides often exceed by a wide margin those in regulatory risk assessments based on data derived from studies on nearly 100% pure active ingredients. Innovative policy changes are needed in four problem areas: excessive faith in the accuracy of pre-market risk assessments and regulatory thresholds; post-approval monitoring of actual impacts; risk arising from formulated pesticides, rather than just pure active ingredient; challenges inherent in assessing and mitigating the combined impacts of all GE traits and associated pesticides on agroecosystems, as opposed to each trait or pesticide alone; and, tools to deal with failing pest management systems.

Improved synthesis of glycine, taurine and sulfate conjugated bile acids as reference compounds and internal standards for ESI-MS/MS urinary profiling of inborn errors of bile acid synthesis.

Bile acid synthesis defects are rare genetic disorders characterized by a failure to produce normal bile acids (BAs), and by an accumulation of unusual and intermediary cholanoids. Measurements of cholanoids in urine samples by mass spectrometry are a gold standard for the diagnosis of these diseases. In this work improved methods for the chemical synthesis of 30 BAs conjugated with glycine, taurine and sulfate were developed. Diethyl phosphorocyanidate (DEPC) and diphenyl phosphoryl azide (DPPA) were used as coupling reagents for glycine and taurine conjugation. Sulfated BAs were obtained by sulfur trioxide-triethylamine complex (SO3-TEA) as sulfating agent and thereafter conjugated with glycine and taurine. All products were characterized by NMR, IR spectroscopy and high resolution mass spectrometry (HRMS). The use of these compounds as internal standards allows an improved accuracy of both identification and quantification of urinary bile acids.

Calibration strategies for the determination of stable carbon absolute isotope ratios in a glycine candidate reference material by elemental analyser-isotope ratio mass spectrometry.

We report a methodology for the determination of the stable carbon absolute isotope ratio of a glycine candidate reference material with natural carbon isotopic composition using EA-IRMS. For the first time, stable carbon absolute isotope ratios have been reported using continuous flow rather than dual inlet isotope ratio mass spectrometry. Also for the first time, a calibration strategy based on the use of synthetic mixtures gravimetrically prepared from well characterised, highly (13)C-enriched and (13)C-depleted glycines was developed for EA-IRMS calibration and generation of absolute carbon isotope ratio values traceable to the SI through calibration standards of known purity. A second calibration strategy based on converting the more typically determined delta values on the Vienna PeeDee Belemnite (VPDB) scale using literature values for the absolute carbon isotope ratio of VPDB itself was used for comparison. Both calibration approaches provided results consistent with those previously reported for the same natural glycine using MC-ICP-MS; absolute carbon ratios of 10,649 × 10(-6) with an expanded uncertainty (k = 2) of 24 × 10(-6) and 10,646 × 10(-6) with an expanded uncertainty (k = 2) of 88 × 10(-6) were obtained, respectively. The absolute carbon isotope ratio of the VPDB standard was found to be 11,115 × 10(-6) with an expanded uncertainty (k = 2) of 27 × 10(-6), which is in excellent agreement with previously published values.

Quantitative determination of guanidinoacetate and creatine in dried blood spot by flow injection analysis-electrospray tandem mass spectrometry.

BACKGROUND: Guanidinoacetate (GAA) and creatine (Cr) are reliable biochemical markers of primary creatine disorders. The aim of this study was to develop and validate a method for the determination of GAA and Cr in dried blood spot through the use of stable isotope dilution and flow injection analysis (FIA)-ESI-MS/MS. METHODS: Dried blood spots were extracted using methanol-water solution containing D3-Cr. After evaporation and formation of butyl esters, samples were analyzed using multiple reaction monitoring mode (m/z 174.2-->101.1 for GAA, 188.3-->90.1 for Cr and 191.3-->93.1 for D3-Cr). RESULTS: The analysis was very fast (1 min). The detection limits were 0.34 micromol/l of blood and 0.30 micromol/l of blood for Cr and GAA, respectively, and the response was linear over the range 0.25-12.5 micromol/l of blood for GAA and 3.57-624.7 micromol/l of blood for Cr. Recovery range was 93-101% for Cr and 94-105% for GAA and between-run CVs were 5.3% for GAA and 4.5% for Cr. Ion suppression effect was also studied. The method was applied to spots obtained from two patients affected by GAMT deficiency, four patients affected by AGAT deficiency (including a newborn) as well as 282 healthy subjects. CONCLUSIONS: The detection of GAA in dried blood spot by FIA-ESI-MS/MS is a highly reliable and high throughput method for the diagnosis of GAMT and AGAT deficiencies and a possible tool for newborn screening of both these tractable disorders.

Supplemental nutrition with ornithine alpha-ketoglutarate in rats with cancer-associated cachexia: surgical treatment of the tumor improves efficacy of nutritional support.

We investigated the use of ornithine alpha-ketoglutarate in treatment of rats bearing Morris hepatoma 7777. Rats received diets containing either ornithine alpha-ketoglutarate, which has been used in other catabolic states (i.e. injury, sepsis), or an isonitrogenous, isocaloric diet containing glycine. Untreated tumors grew to a mass of 11 g/100 g body weight over the 3-wk period after implantation and induced progressive anorexia, negative nitrogen balance, and body and tissue wasting. Compared with glycine, ornithine alpha-ketoglutarate had no effect on tumor growth, but also did not alter the catabolic effects of the tumor on its host. We hypothesized that capture of amino acids by the tumor limited the efficacy of supplemental nutrition here and in published reports in which tumor burden comprised 4-30% of body weight. This is supported by our observation that a 3-wk of implantation the rate of protein deposition plus amino acid oxidation by the tumor was equivalent to approximately 70% of the host's daily protein intake. To parallel the clinical situation in which tumor burden is small at diagnosis and initiation of treatment, the same diets were tested in rats treated by excision of the tumor at a limited stage of the disease. Rats received 3 d preoperative nutrition with ornithine alpha-ketoglutarate or glycine, and continued on the same diets for 3 or 6 d postoperatively. Compared with glycine-fed rats, ornithine alpha-ketoglutarate-fed rats showed a more positive nitrogen balance, higher concentrations of glutamine and branched-chain amino acids in muscle, and accelerated protein deposition in small intestine (P < 0.05). Our results explain the lack of success of nutritional support in untreated cancer and underline the need for clinically relevant animal models for further studies.

Safety and efficacy of a 1,5% glycine solution as an irrigation medium in prostatic surgery.

The safety and efficacy of irrigation with a 1,5% glycine solution during transurethral resection of the prostate gland for benign hyperplasia were studied in 21 patients. Absorption of the irrigation solution during the procedure resulted in raised plasma glycine levels immediately after the operation, but these had virtually returned to normal within 24 hours. No adverse effects were noted and all the patients recovered uneventfully. This study demonstrates that glycine is well tolerated as an irrigation medium and appears to be free of complications.

Preparation of a stable intravenous gamma-globulin: process design and scale-up.

Intravenous gamma-globulin has been prepared on a pilot scale by the process of reduction with dithiothreitol and alkylation with iodoacetamide. The spent reagents are removed by diafiltration followed by ultrafiltration. The product is stabilized with maltose to minimize precipitation. Process design concepts as well as product characteristics are discussed.

Influence of inorganic phosphate on the activity determination of isoenzymes of alkaline phosphatase in various buffer systems.

The inhibitory effect of inorganic phosphate on the activity determination of isoenzymes of alkaline phosphatase (AP) in diethanolamine (DEA), glycine and 2-amino-2-methyl-1,3-propandiol (AMPD) buffer was studied. This effect depends on the buffer used and isoenzyme investigated. Especially the placental isoenzyme is inhibited; the inhibitory effect in DEA buffer is stronger than in the other buffers used. The requirement of purity for 4-nitrophenylphosphate with respect to its content of inorganic phosphate and conclusions for using control sera enriched with AP isoenzymes are discussed.