The influence of manure composition on emissions of odour and ammonia from finishing pigs fed different concentrations of dietary crude protein

An investigation was conducted into the influence of manure composition on the odour emission rate (OER) and the emission rate of ammonia (NH(3)), when diets containing 130, 160, 190 and 210gkg(-1) crude protein (CP) were fed to finishing pigs. A group of four boars and four gilts, housed in environmentally sealed pens, were assigned to each diet for a 23-day experimental period which was replicated three times (n=3). Ventilation air from each pen was sampled for NH(3) and odour, by olfactometry, on four days during the trial period. Simultaneous collections of manure were taken from the surface and base of each pit. The pH and the concentrations of dry matter, total Kjeldahl nitrogen (TKN), total ammoniacal nitrogen (TAN) and volatile fatty acids in the manure were measured. Manure composition differed between samples from the surface and base of the pit (P<0.05). Reducing dietary CP concentration decreased the emission of NH(3) (linear, P<0.001). The acetic acid:propionic acid ratio in manure samples was correlated to OER (r=0.79, P<0.001). There was a quadratic relationship between dietary CP concentration and OER (P<0.05). OER decreased between 210gkg(-1) and 160gkg(-1) CP and increased between 160gkg(-1) and 130gkg(-1) CP. In conclusion, reducing dietary crude protein levels could be used effectively to reduce ammonia emissions and OER, although no significant advantage was to be gained in OER from reducing crude protein level below 160gkg(-1).     

Inhibition of protein synthesis and JNK activation are not required for cell death induced by anisomycin and anisomycin analogues

Anisomycin was identified in a screen of clinical compounds as a drug that kills breast cancer cells (MDA16 cells, derived from the triple negative breast cancer cell line, MDA-MB-468) that express high levels of an efflux pump, ABCB1. We show the MDA16 cells died by a caspase-independent mechanism, while MDA-MB-468 cells died by apoptosis. There was no correlation between cell death and either protein synthesis or JNK activation, which had previously been implicated in anisomycin-induced cell death. In addition, anisomycin analogues that did not inhibit protein synthesis or activate JNK retained the ability to induce cell death. These data suggest that either a ribosome-ANS complex is a death signal in the absence of JNK activation or ANS kills cells by binding to an as yet unidentified target.     

Synthesis and evaluation of phenoxyoxazaphospholidine,phenoxyoxazaphosphinane, and benzodioxaphosphininamine sulfides and related compounds as potential anti-malarial agents

A series of phenoxyoxazaphospholidine, phenoxyoxazaphosphinane and benzodioxaphosphininamine sulfides and related cyclic organophosphorus compounds based on the lead anti-tubulin herbicides amiprophos methyl and butamifos were synthesised and evaluated for anti-malarial activity. Of these compounds, while none of the phenoxyoxazaphospholidines, phenoxyoxazaphosphinanes or benzodioxaphosphininamine sulphides were more potent than APM, phosphorothioamidate 30, a dual compound also bearing an aminoquinoline motif, showed promising activity against Plasmodium falciparum (IC₅₀ 0.038 μM) and warrants further study.     

Jasmonoyl-l-isoleucine is required for the production of a flavonoid phytoalexin but not diterpenoid phytoalexins in ultraviolet-irradiated rice leaves

Rice produces low-molecular-weight antimicrobial compounds known as phytoalexins, in response to not only pathogen attack but also abiotic stresses including ultraviolet (UV) irradiation. Rice phytoalexins are composed of diterpenoids and a flavonoid. Recent studies have indicated that endogenous jasmonyl-l-isoleucine (JA-Ile) is not necessarily required for the production of diterpenoid phytoalexins in blast-infected or CuCl₂-treated rice leaves. However, JA-Ile is required for the accumulation of the flavonoid phytoalexin, sakuranetin. Here, we investigated the roles of JA-Ile in UV-induced phytoalexin production. We showed that UV-irradiation induces the biosynthesis of JA-Ile and its precursor jasmonic acid. We also showed that rice jasmonate biosynthesis mutants produced diterpenoid phytoalexins but not sakuranetin in response to UV, indicating that JA-Ile is required for the production of sakuranetin but not diterpenoid phytoalexins in UV-irradiated rice leaves.     

Nano-Scale Pollutants: Fate in Irish Surface and Drinking Water Regulatory Systems

Nano-functionalized products such as UV protective paints additives, antimicrobial food packaging, and fuel additives offering reduced CO₂ emissions have the potential to secure a significant Irish market share in the near future. This scoping study gives a first estimation of nanomaterial surface water concentrations and population ingestional exposure through drinking water resulting from these products. As nanomaterial behavior in wastewater treatment plants (WWTPs) and water treatment plants (WTPs) is currently unclear, bridging data relating to potentially relevant materials (pharmaceuticals and metal removal efficiencies in WWTPs; pathogen removal efficiencies in WTPs) are employed in this study. Mean nanomaterial removal efficiencies of 59.8% and 70.2% were predicted for Irish WWTPs, between 96.95% and 0% for Irish WTPs. Predicted nano-scale TiO₂ concentrations in surface waters (resulting from exterior paints) were 2 orders of magnitude greater than that of Ag (resulting from food packaging) and CeO₂ (resulting from fuel additives), respectively. Predicted surface and drinking water concentrations were unlikely to pose any ecotoxicological or human health risk, although nano-scale TiO₂ and Ag may warrant monitoring as part of standard surface water monitoring schemes. Future research should be directed toward characterizing the behavior of different categories of nanomaterials within WWTP processes.     

Synthesis and evaluation of phosphoramidate and phosphorothioamidate analogues of amiprophos methyl as potential antimalarial agents

A series of phosphoramidate and phosphorothioamidate compounds based on the lead antitubulin herbicidal agents amiprophos methyl (APM) and butamifos were synthesised and evaluated for antimalarial activity. Of these compounds, phosphorothioamidates were more active than their oxo congeners and the nature of both aryl and amido substituents influenced the desired activity. The most active compound was 46, O-ethyl-O-(2-methyl-4-nitrophenyl)-N-cyclopentyl phosphorothioamidate, which was more effective than the lead compound.     

Application of quality by design principles to the development and technology transfer of a major process improvement for the manufacture of a recombinant protein

This study describes the application of quality by design (QbD) principles to the development and implementation of a major manufacturing process improvement for a commercially distributed therapeutic protein produced in Chinese hamster ovary cell culture. The intent of this article is to focus on QbD concepts, and provide guidance and understanding on how the various components combine together to deliver a robust process in keeping with the principles of QbD. A fed-batch production culture and a virus inactivation step are described as representative examples of upstream and downstream unit operations that were characterized. A systematic approach incorporating QbD principles was applied to both unit operations, involving risk assessment of potential process failure points, small-scale model qualification, design and execution of experiments, definition of operating parameter ranges and process validation acceptance criteria followed by manufacturing-scale implementation and process validation. Statistical experimental designs were applied to the execution of process characterization studies evaluating the impact of operating parameters on product quality attributes and process performance parameters. Data from process characterization experiments were used to define the proven acceptable range and classification of operating parameters for each unit operation. Analysis of variance and Monte Carlo simulation methods were used to assess the appropriateness of process design spaces. Successful implementation and validation of the process in the manufacturing facility and the subsequent manufacture of hundreds of batches of this therapeutic protein verifies the approaches taken as a suitable model for the development, scale-up and operation of any biopharmaceutical manufacturing process.     

Effect of a glucagon-like peptide 1 analog, ROSE-010, on GI motor functions in female patients with constipation-predominant irritable bowel syndrome

The glucagon-like peptide 1 (GLP-1) analog ROSE-010 reduced pain during acute exacerbations of irritable bowel syndrome (IBS). Our objective was to assess effects of ROSE-010 on several gastrointestinal (GI) motor and bowel functions in constipation-predominant IBS (IBS-C). In a single-center, randomized, parallel-group, double-blind, placebo-controlled, dose-response study, we evaluated safety, pharmacodynamics, and pharmacokinetics in female patients with IBS-C. ROSE-010 (30, 100, or 300 μg sc) or matching placebo was administered once daily for 3 consecutive days and on 1 day 2-10 days later. We measured GI and colonic transit by validated scintigraphy and gastric volumes by single-photon emission computed tomography. The primary end points were half time of gastric emptying of solids, colonic transit geometric center at 24 h, and gastric accommodation volume. Analysis included intent-to-treat principle, analysis of covariance (with body mass index as covariate), and Dunnett-Hsu test for multiple comparisons. Exposure to ROSE-010 was approximately dose-proportional across the dose range tested. Demographic data in four treatment groups of female IBS-C patients (total 46) were not different. Gastric emptying was significantly retarded by 100 and 300 μg of ROSE-010. There were no significant effects of ROSE-010 on gastric volumes, small bowel or colonic transit at 24 h, or bowel functions. The 30- and 100-μg doses accelerated colonic transit at 48 h. Adverse effects were nausea (P < 0.001 vs. placebo) and vomiting (P = 0.008 vs. placebo). Laboratory safety results were not clinically significant. In IBS-C, ROSE-010 delayed gastric emptying of solids but did not retard colonic transit or alter gastric accommodation; the accelerated colonic transit at 48 h with 30 and 100 μg of ROSE-010 suggests potential for relief of constipation in IBS-C.     

Antimicrobial Residues and Antimicrobial-Resistant Bacteria: Impact on the Microbial Environment and Risk to Human Health—A Review

Water quality has become a major environmental concern due to the presence of potentially harmful bacteria, protozoa, and chemicals. In particular, pharmaceuticals have recently gained prominence due to their potential negative effects on both the aquatic environment and on human health. The antimicrobial classes of penicillins, cephalosporins, macrolides, and fluoroquinolones are among the most frequent pharmaceuticals detected in the environment in Europe. The common route of entry of these antimicrobials into the environment is thought to be through wastewater treatment plant (WWTP) effluent. The main concern with regard to antimicrobial agents is the potential formation of antimicrobial resistance. Evidence suggests WWTPs may promote development of antimicrobial resistance. This study reviews antimicrobial residues typically found in treated water, their sources, process barriers, entry into the environment, and consequent human health concerns. The effects of WWTP on residues and the formation of antimicrobial-resistant bacteria are also discussed in addition to current risk assessment approaches for evaluating human health concerns, including development of antimicrobial resistance and resultant therapeutic failure. The uncertainty surrounding the fate and impact of different classes of antimicrobials in the environment is highlighted in addition to the lack of standardised methods to detect antimicrobials and to assess selective pressures.