T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays

Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an overview of the development of the field over the last two decades.

Amendment to Section 15a, Interstate Commerce Act (rule of ratemaking) : hearings before the Committee on Commerce, United States Senate, Eighty-seventh Congress, first session on S. 1197.

Hearings held May 11 - August 11, 1961.

Lessons from the Terra Preta de Índios of the Amazon region for the utilisation of charcoal for soil amendment

The potential of charcoal and of partially combusted organic waste to mimic the soil organic matter of the Terras Pretas de Índios (Amazonian Dark Earths) from the Amazon Region is discussed. These materials serve as soil conditioners and as sequesterers of carbon in recalcitrant and in reactive forms. Studies carried out by Brazilian and by international groups have contributed to the emergence of an awareness of the compositions and of the uses of these materials. In this contribution we report on chemical studies that are leading to the development of a scientific and technological awareness, and of innovations that will have value in finding novel uses in applications to soil of chars from organic wastes such as those from the biofuel industry, and from metallurgical and various coal plant residues.

Effects of sewage sludge amendment on the properties of two Brazilian oxisols and their humic acids

The effect of sewage sludge (SS) amendment on the general properties of the top layers of a sandy and a clayey oxisols and on the nature of their humic acid (HA) fractions was evaluated by chemical and physico-chemical techniques. The amended soils, especially the sandy soil, benefited of SS amendment by increasing their pH to above neutrality and enhancing the contents of C, N, P, and Ca and cation exchange capacity. The SS-HA-like sample showed larger H and N contents and a greater aliphatic character and humification degree than the HAs isolated from non-amerided soils. The composition and structure of amended soil HAs were affected by SS application as a function of soil type and layer. In particular, N-containing groups and aliphatic structures of SS-HA-like sample appears to be partially incorporated in the amended soil HAs, and these effects were more evident in the HAs from the sandy oxisol. (C) 2007 Elsevier Ltd. All rights reserved.

Nutrient accumulation and biomass production of alfafa after soil amendment with silicates

Studies on the use of silicate correctives in agriculture show that they have great potential to improve soil chemical characteristics, however, little information is available on the reactivity rates of their particle-size fractions. This study investigated whether the reactivity rates obtained experimentally could be considered in the calculation of ECC (effective calcium carbonate) for soil liming, promoting adequate development of alfalfa plants. Six treatments were evaluated in the experiment, consisting of two slag types applied in two rates. The experimental ECC was used to calculate one of the rates and the ECC determined in the laboratory was used to calculate the other. Rates of limestone and wollastonite were based on the ECC determined in laboratory. The rates of each soil acidity corretive were calculated to increase the base saturation to 80%. The treatments were applied to a Rhodic Hapludox and an Alfisol Ferrudalfs. The methods for ECC determination established for lime can be applied to steel slag. The application of slag corrected soil acidity with consequent accumulation of Ca, P, and Si in alfalfa, favoring DM production.

Molecular Basis of Ribotype Variation in the Seventh Pandemic Clone and its O139 Variant of Vibrio cholerae

Ribotyping has been widely used to characterise the seventh pandemic clone including South American and O139 variants which appeared in 1991 and 1992 respectively. To reveal the molecular basis of ribotype variation we analysed the rrn operons and their flanking regions. All but one variation detected by BglI, the most discriminatory enzyme, was found to be due to changes within the rrn operons, resulting from recombination between operons. The recombinants are detected because of the presence of a BglI site in the 16S gene in three of the nine rrn operons and/or changes of intergenic spacer types of which four variants were identified. As the frequency of rrn recombination is high, ribotyping becomes a less useful tool for evolutionary studies and long term monitoring of the pathogenic clones of Vibrio cholerae as variation could undergo precise reversion by the same recombination event.

Child Care (Pre School Services) Regulations 1996 and Child Care (Pre School Services) (Amendment) Regulations 1997

The purpose of this Guide is to offer guidance on the Child Care (Pre- School Services) Regulations, 1996. It is written for persons charged with responsibility for implementing the legislation and for anyone affected by its provisions, in particular persons who are carrying on or proposing to carry on a pre-school service. The Regulations and the Explanatory Guide expand on the provisions of Part VII of the Child Care Act, 1991 Download the Report here

Limiting the Exposure of Young People to Alcohol Advertising - Seventh Annual Report 2012

The task of the Monitoring Body is to oversee the implementation of and adherence to Voluntary Codes of Practice to limit the exposure of young people, under the age of 18 years, to alcohol advertising.  The Monitoring Body is chaired by Mr Peter Cassells  Download the seventh annual report here

Journal of the State Convention on Repeal of the Eighteenth Amendment, July 10, 1933

Proposing an amendment to the constitution of the United States. Resolved by the Senate and House of Representatives of the United States of America in Congress assembled (two-thirds of each House concurring therein), That the following article is hereby proposed as an amendment to the Constitution of the United States, which shall be valid to all intents and purposes as part of the Constitution when ratified by conventions in three-fourths of the several states. "Article-"Section 1. The eighteenth article of amendment to the Constitutionof the United States is hereby repealed. "Sec. 2. The transportation or importation into any State, Territory, or possession of the United States for delivery or use therein of intoxicating liquors, in violation of the laws thereof, is hereby prohibited. "Sec. 3. This article shall be inoperative unless it shall have been ratified as an amendment to the Constitution by conventions in the several States, as provided in the Constitution, within seven yearsfrom the date of the submission hereof to the States by the Congress.” Jno. Garner, Speaker of the House of Representatives. Charles Curtis, Vice President of the United States and President of the Senate

Seventh Report of the Iowa Library Commission Made to the Governor of Iowa, 1912-1914

1912-1914 Iowa Library Commission Report made to the Governor of Iowa.

The determination of sinigrin in Brassica, and investigations into the use of allyl-isothiocyanate as a nematicide

The goal of this thesis was to study factors related to the development of Brassica juncea as a sustainable nematicide. Brassica juncea is characterized by the glycoside (glucosinolate) sinigrin. Various methods were developed for the determination of sinigrin in Brassica juncea tissue extracts. Sinigrin concentrations in plant tissues at various stages of growth were monitored. Sinigrin enzymatically breaks down into allylisothiocyanate (AITC). AITC is unstable in aqueous solution and degradation was studied in water and in soil. Finally, the toxicity of AITC against the root-lesion nematode (Pratylenchus penetrans) was determined. A method was developed to extract sinigrin from whole Brassica j uncea tissues. The optimal time of extraction wi th boiling phosphate buffer (0.7mM, pH=6.38) and methanol/water (70:30 v/v) solutions were both 25 minutes. Methanol/water extracted 13% greater amount of sinigrin than phosphate buffer solution. Degradation of sinigrin in boiling phosphate buffer solution (0.13%/minute) was similar to the loss of sinigrin during the extraction procedure. The loss of sinigrin from boiling methanol/water was estimated to be O.Ol%/minute. Brassica juncea extract clean up was accomplished by an ion-pair solid phase extraction (SPE) method. The recovery of sinigrin was 92.6% and coextractive impurities were not detected in the cleaned up extract. Several high performance liquid chromatography (HPLC) methods were developed for the determination of sinigrin. All the developed methods employed an isocratic mobile phase system wi th a low concentration of phosphate buffer solution, ammonium acetate solution or an ion-pair reagent solution. A step gradient system was also developed. The method involved preconditioning the analytical column with phosphate buffer solution and then switching the mobile phase to 100% water after sample injection.Sinigrin and benzyl-glucosinolate were both studied by HPLC particle beam negative chemical ionization mass spectrometry (HPLCPB- NCI-MS). Comparison of the mass spectra revealed the presence of fragments arising from the ~hioglucose moiety and glucosinolate side-chain. Variation in the slnlgrin concentration within Brassica juncea plants was studied (Domo and Cutlass cuItivars). The sinigrin concentration in the top three leaves was studied during growth of each cultivar. For Cutlass, the minimum (200~100~g/g) and maximum (1300~200~g/g) concentrations were observed at the third and seventh week after planting, respectively. For Domo, the minimum (190~70~g/g) and maximum (1100~400~g/g) concentrations were observed at the fourth and eighth week after planting, respectively. The highest sinigrin concentration was observed in flower tissues 2050±90~g/g and 2300±100~g/g for Cutlass and Domo cultivars, respectively. Physical properties of AITC were studied. The solubility of AITC in water was determined to be approximately 1290~g/ml at 24°C. An HPLC method was developed for the separation of degradation compounds from aqueous AITC sample solutions. Some of the degradation compounds identified have not been reported in the literature: allyl-thiourea, allyl-thiocyanate and diallyl-sulfide. In water, AITC degradation to' diallyl-thiourea was favored at basic pH (9.07) and degradation to diallyl-sulfide was favored at acidic pH (4 . 97). It wap necessary to amend the aqueous AITC sample solution with acetonitrile ?efore injection into the HPLC system. The acetonitrile amendment considerably improved AITC recovery and the reproducibility of the results. The half-life of aqueous AITC degradation at room temperature did not follow first-order kinetics. Beginning with a 1084~g/ml solution, the half-life was 633 hours. Wi th an ini tial AITC concentration of 335~g/ml the half-life was 865 hours. At 35°C the half-life AITC was 76+4 hours essentially independent of the iiisolution pH over the range of pH=4.97 to 9.07 (1000~g/ml). AITC degradation was also studied in soil at 35°C; after 24 hours approximately 75% of the initial AITC addition was unrecoverable by water extraction. The ECso of aqueous AITC against the root-lesion nematode (Pratylenchus penetrans) was determined to be approximately 20~g/ml at one hour exposure of the nematode to the test solution. The toxicological study was also performed with a myrosinase treated Brassica juncea extract. Myrosinase treatment of the Brassica juncea extract gave nearly quantitative conversion of sinigrin into AITC. The myrosinase treated extract was of the same efficacy as an aqueous AITC solution of equivalent concentration. The work of this thesis was focused upon understanding parameters relevant to the development of Brassica juncea as a sustainable nematicide. The broad range of experiments were undertaken in support of a research priority at Agriculture and Agri-Food Canada.