A large potentiation effect of serum on the in vitro potency of tulathromycin against Mannheimia haemolytica and Pasteurella multocida

The antimicrobial properties of tulathromycin were investigated for M.haemolytica and P.multocida. Three invitro indices of antimicrobial activity, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves, were established for six isolates of each organism. Each index was measured in two growth media: Mueller-Hinton broth (MHB) and calf serum. It was shown that MICs and MBCs were markedly lower in serum than in MHB. MHB:serum ratios for MIC were 47:1 (M.haemolytica) and 53:1 (P.multocida). For both serum and MHB, adjustment of pH led to greater potency at alkaline compared to acid pH. Tulathromycin MIC was influenced by size of inoculum count, being 4.0- to 7.7-fold greater for high compared to low initial counts. It was concluded that for the purpose of determining dosages for therapeutic use, pharmacodynamic data for tulathromycin should be derived in biological fluids such as serum. It is hypothesized that invitro measurement of MIC in broth, conducted according to internationally recommended standards, may be misleading as a basis for estimating the invivo potency of tulathromycin

Parthenogenetic flatworms have more symbionts than their coexisting, sexual conspecifics, but does this support the Red Queen?

The Red Queen hypothesis predicts that sexuality is favoured when virulent parasites adapt quickly to host genotypes. We studied a population of the flatworm Schmidtea polychroa in which obligate sexual and parthenogenetic individuals coexist. Infection rates by an amoeboid protozoan were consistently higher in parthenogens than in sexuals. Allozyme analysis showed that infection was genotype specific, with the second most common clone most infected. A laboratory measurement of fitness components failed to reveal high infection costs as required for the Red Queen. Although fertility was lower in more infected parthenogens, this effect can also be explained by the accumulation of mutations. We discuss these and other characteristics of our model system that may explain how a parasite with low virulence can show this pattern

A Study on the Tendency of the Environmental Education in Geography Text-book of the World

1.帝国書院から翻訳出版された世界地理教科書全30巻を通読し, そのなかから国情の差と世界全域を網羅することを考慮して23ヶ国を選び, 地理教育における環境教育の一側面を捉える試みを行った.2.対象とした各国の教科書は, それぞれの国の教育制度, 教育年限, 教育事情が異なるため, 対象年令が若干異なっているが, 一部を除き大半は中等教育以上の教科書である.次代を教育する教科書という共通の基盤にたつものと理解して, 以下の調査を行い若干の知見を得た.3.各国の地理教科書から環境と人間活動とに係る環境問題に関する記述を抽出してまず記述量を把握し, 次いで記述の対象について13項目に分け, さらに42の細目に分類整理した.その結果は第1図, 第2表, 第4表に示した.4.抽出した記述量は全体で566記述, 単純な一国平均は25記述となり, 最高記述国は56記述のアメリカ合衆国であった.5.さらに記述量が多い項目第1位と第2位を基にして, 各国の特色を把握し第3表のような5グループに分類した.6. 42種に細分した記述からは, 各国それぞれの環境問題に対する関心の領域の広狭をうかがうことができるが, 最も広範にわたって記述している国は記述量でも多いアメリカ合衆国であった.7.記述量と記述細目数とを基にすると地理教育の分野で, 環境教育問題に関心を寄せている国とさほどではない国とに分かれる.関心が高い国と察知されるのは, アメリカ合衆国, フランス, オーストラリアなど10ヶ国であった.8.環境教育問題は, 執筆形式にもよるが, 単元 (章) や節を直接設けている関心が高い国は, 第5表のとおり10ヶ国見られた.9.環境教育の方法, 環境問題の中心に取り上げられている課題あるいは視点は, 国情によってIn this study, we made it clear that tendency of environmental education in the geography textbook of the world. We used textbooks in Japanese translation of each country languages and these textbooks timely published by the Teikoku-Shoin from 1979 to 1980. The method of study is as follows. The environmental problems such as natural conservation and environment, various field of industry, various kinds of industrial pollution, living environment, outdoor recreation and other things are extracted from the discription in textbooks. We counted out the number of extracted data each country and matters for investigation and made a surveyed of its character in the same time. These data was classified into thirteen groups according to the same factor and subdivided into forty two items such as protection and conservation area, pollution, natural resources, living environment, municipal waste, land development and other things. A summary of the survey is shown below. 1) The count of environmental discription in each country range from the most fifty three in U. S. A. to the lowest five in Mexco and Brazil and its average twenty five. 2) As we cannot easily compare with that each country has its own writing style of textbook, it was ten countries that take up a environmental problems by chapter or section on the textbook. 3) Each country it different from politic and economic situation, framework of society, standard of land development and living and so on. The character of each country from a point of view environmental problems and its education can be broadly classified into five group. 4) Moreover, we was classified by character of environmental education as developed country and developing country and the former may be divied into a narrow, overpopulated old country and a wide, abundant in natural resources newer country

Comparison of standardised versus non-standardised methods for testing the in vitro potency of oxytetracycline against mannheimia haemolytica and pasteurella multocida

The in vitro pharmacodynamics of oxytetracycline was established for six isolates of each of the calf pneumonia pathogens Mannheimia haemolytica and Pasteurella multocida. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and bacterial time-kill curves were determined in two matrices, Mueller Hinton broth (MHB) and calf serum. Geometric mean MIC ratios, serum:MHB, were 25.2:1 (M. haemolytica) and 27.4:1 (P. multocida). The degree of binding of oxytetracycline to serum protein was 52.4%. Differences between serum and broth MICs could not be accounted for by oxytetracycline binding to serum protein. In vitro time-kill data suggested a co-dependent killing action of oxytetracycline. The in vitro data indicate inhibition of the killing action of oxytetracycline by serum factor(s). The nature of the inhibition requires further study. The outcome of treatment with oxytetracycline of respiratory tract infections in calves caused by M. haemolytica and P. multocida may not be related solely to a direct killing action

Comparison between the immunoassay and high performance liquid chromatography for therapeutic monitoring of carbamazepine and phenytoine

Objective: To investigate the correlation of the immunoassay and chromatography method for quantitative measurement of two antiepileptic drugs (AED), carbamazepine (CBZ) and phenytoin (PHT) and determination of relation between the CBZ and it\u27s metabolite carbamazepine 10,11-epoxide (CBZ-E). Additionally we investigated whether there is a difference in the determination of serum concentration of CBZ and PHT when measured in two different labs by high performance liquid chromatography (HPLC). Materials and methods: This study was carried out on 102 blood samples (72 CBZ and 30 PHT) collected from epileptic outpatients. Plasma concentrations of CBZ and PHT were determined by validated HPLC (Shimadzu and Agilent) and the CEDIA-immunoassay method. Results: The correlations of serum concentrations of CBZ between CEDIA and HPLC1 and between CEDIA and HPLC2 were good (R = 0.97 for both techniques). Even better correlation was found between concentrations of CBZ measured by the two HPLC systems (R = 0.99). Similar, for PHT, we found good correlation between CEDIA and the two systems of HPLC (HPLC1 and HPLC2, R = 0.98) and between the two systems of HPLC of R =0.98. The moderate correlation coefficient was found between serum concentrations of CBZ and its metabolite CBZ-E, measured in two labs by different HPLC (R = 0.49 and 0.43, respectively; P < 0.001). Conclusion: We observed good correlation for estimation of CBZ and PHT concentration obtained by means the immunoassay and two different HPLC. The possibility of measurement of CBZ-E could be advantage of chromatography in comparison with immunoassay

Intradiscal pharmacokinetics of oral antibiotics to treat Chronic Lower Back Pain

Oral coamoxiclav and amoxicillin, for extended dose regimens of up to 100 days, have shown benefit in the treatment of Chronic Lower Back Pain (CLBP) associated with vertebral bone oedema, known as Modic type 1 changes, which may be caused by a bacterial infection, but the magnitude of clinical improvement has been variable. The objectives of this review were to use sparse data from the literature to estimate the exposure of amoxicillin in the intervertebral disc, and to determine whether adequate antimicrobial exposure may have been achieved. Exposure to amoxicillin in herniated disc tissue was approximately 6.5% of the serum concentration. Dosing of oral amoxicillin, Q12h, at doses of up to 1,000 mg is unlikely to lead to effective exposure in disc tissue. Mean exposure to 500 mg or 750 mg of oral Q8h amoxicillin may reach the efficacy target for ~50% of Cutibacterium acnes strains, but not for 90% of C. acnes strains. Mean exposure to 1,000 mg of oral amoxicillin Q8h may reach the target exposure for 90% of strains. Oral amoxicillin CLBP studies may all be underdosed. More than 1400 patients with CLBP and Modic type 1 changes have been exposed to oral amoxicillin for up to 100 days, with no apparent evaluation of systemic or intradiscal pharmacokinetics. Additional clinical evaluations of amoxicillin and alternative antibiotics, their dose regimens, and intradiscal pharmacokinetics are warranted to optimize treatment for this indication. Expertise in antibacterial pharmacokinetics and pharmacodynamics should be included in the design and execution of future studies

The positive transcriptional elongation factor (P-TEFb) is required for neural crest specification

Regulation of gene expression at the level of transcriptional elongation has been shown to be important in stem cells and tumour cells, but its role in the whole animal is only now being fully explored. Neural crest cells (NCCs) are a multipotent population of cells that migrate during early development from the dorsal neural tube throughout the embryo where they differentiate into a variety of cell types including pigment cells, cranio-facial skeleton and sensory neurons. Specification of NCCs is both spatially and temporally regulated during embryonic development. Here we show that components of the transcriptional elongation regulatory machinery, CDK9 and CYCLINT1 of the P-TEFb complex, are required to regulate neural crest specification. In particular, we show that expression of the proto-oncogene c-Myc and c-Myc responsive genes are affected. Our data suggest that P-TEFb is crucial to drive expression of c-Myc, which acts as a ‘gate-keeper’ for the correct temporal and spatial development of the neural crest

Chromatin signature of embryonic pluripotency is established during genome activation

available in PMC 2011 April 8.After fertilization the embryonic genome is inactive until transcription is initiated during the maternal–zygotic transition. This transition coincides with the formation of pluripotent cells, which in mammals can be used to generate embryonic stem cells. To study the changes in chromatin structure that accompany pluripotency and genome activation, we mapped the genomic locations of histone H3 molecules bearing lysine trimethylation modifications before and after the maternal–zygotic transition in zebrafish. Histone H3 lysine 27 trimethylation (H3K27me3), which is repressive, and H3K4me3, which is activating, were not detected before the transition. After genome activation, more than 80% of genes were marked by H3K4me3, including many inactive developmental regulatory genes that were also marked by H3K27me3. Sequential chromatin immunoprecipitation demonstrated that the same promoter regions had both trimethylation marks. Such bivalent chromatin domains also exist in embryonic stem cells and are thought to poise genes for activation while keeping them repressed. Furthermore, we found many inactive genes that were uniquely marked by H3K4me3. Despite this activating modification, these monovalent genes were neither expressed nor stably bound by RNA polymerase II. Inspection of published data sets revealed similar monovalent domains in embryonic stem cells. Moreover, H3K4me3 marks could form in the absence of both sequence-specific transcriptional activators and stable association of RNA polymerase II, as indicated by the analysis of an inducible transgene. These results indicate that bivalent and monovalent domains might poise embryonic genes for activation and that the chromatin profile associated with pluripotency is established during the maternal–zygotic transition.National Institutes of Health (U.S.) (grant 1R01 HG004069)National Institutes of Health (U.S.) (grant 5R01 GM56211)Human Frontier Science Program (Strasbourg, France) (LT-00090/2007)European Molecular Biology Organization (fellowship