Responses to the Standard for Exchange of Nonclinical Data (SEND) in non-US countries

The Standard for the Exchange of Nonclinical Data (SEND), adopted by the US FDA, is part of a set of regulations and guidances requiring the submission of standardized electronic study data for nonclinical and clinical data submissions. SEND is the nonclinical implementation of SDTM (Study Data Tabulation Model), the standard electronic format for clinical regulatory submissions to FDA. SEND, SDTM, and the associated Controlled Terminology have been developed by CDISC (Clinical Data Interchange Standards Consortium). In order to successfully implement SEND, interdisciplinary contributions between sponsors and CROs, need a model for task allocation. This is being undertaken by the Pharmaceutical Users Software Exchange (PhUSE). Because SEND is currently the preferred submission format of the US FDA only and will become required by it starting in December 2016, only American academic societies and companies are actively involved. An exception to this is the INHAND initiative, which leads the way in standardizing terminology for toxicological pathology. On the other hand, international globalization of other clinical and nonclinical practices is not feasible because there are substantial differences between the US and non-US countries in CRO involvement in drug development. Thus, non-US countries must consider and develop approaches to SEND that meet their needs. This paper summarizes the activities of the major organizations involved in SEND development and implementation, discusses the effective use of SEND, and details a compliance scheme (research material of the Showa University School of Medicine) illustrating how pharmaceutical companies can complete a large amount of work up to an FDA application with the effective utilization of CROs and solution providers.     

Assessment of water quality in small agricultural ponds in Nara,Japan

Paddy and Water Environment - In Japan, since ancient times, numerous small- to medium-size agricultural ponds have been constructed to irrigate paddy rice fields. Economic growth and urbanization...     

Criterion for estimating humidity control capacity of materials in a room

As a measure of estimating humidity control capacity of materials in an airtight room under sinusoidal temperature variation, we used the Cb value, which is the ratio of the range of variation in relative humidity in a steel box lined with the material of interest to the range in an empty steel box. In order to clarify the factors that affect the Cb value, we focused on both the temperature variation rate and the area that is lined in the box. It was found that changing the rate of temperature variation over one period strongly affected the Cb value, although the amplitude of temperature variation did not. We further noticed that the difference between the time when peak temperature was reached and the time when peak absolute humidity was reached (peak time difference), was found to be useful for estimating the humidity control capacity of materials. Knowing the difference between the phase when peak temperature was reached and the phase when peak absolute humidity was reached (phase angle difference) was also useful. Because the Cb value was affected by both the variation period and the lined area in the box, we can draw a contour diagram of the period and the lined area for materials to give an overview of the humidity control capacity of a material. The materials of primary interest in this study were Japanese cedar and porous ceramics.     

Effect of cropping systems and crop successions on fumonisin levels in corn from Northern Paraná State,Brazil

In this study the effect of different cropping systems and crop successions was evaluated on natural Fusarium sp. contamination and fumonisin levels in corn. The cropping systems consisted of a conventional and no-tillage area cultivated with corn in the summer following either oats or fallow in the winter (2006 and 2007 growing seasons). In addition, the effect of applying nitrogen fertilizer (0, 22.5, 45.0, 90.0 and 90.0 kg ha⁻¹ nitrogen supplemented with potassium oxide) on fumonisin contamination was evaluated in the 2006 growing season. Fusarium sp. was detected in 90% samples in 2006 and in 100% samples in 2007. In both growing seasons, no-till corn following oats showed the highest mean fumonisin levels and differed significantly (P < 0.05) from all the others (2006) and from conventional till corn following either oats or fallow in the winter (2007). Fumonisin levels ranged from 0.13 to 19.52 μg g⁻¹ (mean 6.97 μg g⁻¹) and from 3.70 to 7.75 μg g⁻¹ (mean 6.29 μg g⁻¹) in no-till corn following oats from the 2006 and 2007 growing seasons, respectively. Plots treated with 0 kg ha⁻¹ and 22.5 kg ha⁻¹ nitrogen showed the highest mean fumonisin levels and differed significantly from those with 45.0 and 90 kg ha⁻¹ nitrogen. Fumonisin levels correlated negatively (P < 0.05) with the nitrogen fertilization rates. Although no-till is advantageous from a soil conservation standpoint, it may enhance the potential for fumonisin contamination in corn.     

Anthocyanin composition and antioxidant activity of the Crowberry (Empetrum nigrum) and other berries

The anthocyanin composition and antioxidant activity of the crowberry ( Empetrum nigrum) were studied. High-performance liquid chromatography (HPLC) combined with a diode array detector and electrospray ionization mass spectrometry were used for identification and quantification of individual anthocyanins. Freeze-dried crowberry powder was extracted with 80% methanol containing 0.5% acetic acid and subjected to HPLC. Thirteen kinds of anthocyanins were identified. The major anthocyanins were cyanidin-3-galactoside and delphinidin-3-galactoside, at 8.04 and 8.62 mg/g extract, respectively. The HPLC profile of crowberry extract was similar to bilberry and blueberry. The total content of anthocyanins in crowberry was 41.8 mg/g extract, higher than the other nine major berry species (2.5-38.8 mg/g extract). The antioxidant activity was also evaluated using the 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis(3-ethybenzothiazoline-6-sulfonic acid) radical quenching assays and the ferric reducing activity power assy. Crowberry extract exerted the strongest antioxidant activity. In conclusion, individual anthocyanins in crowberry were identified and then quantified in this study. Additionally, crowberry is suggested to be associated with a reduction in the risk of developing chronic diseases because of its strong antioxidant activity.     

Development of an enzyme-linked immunosorbent assay to detect an immunomodulatory alpha-D-glucan-protein complex, MPG-1, in basidiomycete Tricholoma matsutake and related processed foods

We previously isolated a novel immunomodulatory alpha-(1,4)(1,6)(1,2)- d-glucan-protein complex (MPG-1) from mycelia of Tricholoma matsutake in basidiomycetes. In the present study, we raised a polyclonal antibody by immunizing rabbits with MPG-1 and constructed a sandwich enzyme-linked immunosorbent assay (ELISA) system to examine the distribution of MPG-1 among edible mushrooms and related processed foods. The system detected MPG-1 quantitatively at concentrations of more than 10 ng/mL, with a coefficient of variation of less than 10% by intra-assay and interassay precision. Analysis with the system of chemically modified MPG-1 suggested that the sugar moiety was mainly involved in the detection. The system detected MPG-1 in the extracts of the fruiting bodies of T. matsutake but not in those of 34 other basidiomycete species. Moreover, a significant amount of MPG-1 was detected in the extracts of their cultured mycelia. The antigenic structure of MPG-1 was relatively stable in terms of pH and temperature. MPG-1 was detected in processed foods supplemented with T. matsutake. These results suggest that MPG-1 is distributed predominantly in T. matsutake species and that the ELISA system can detect it in processed foods supplemented with T. matsutake.     

Impact of introduced honey bees on native pollination interactions of the endemic Echium wildpretii (Boraginaceae) on Tenerife, Canary Islands

The aim of this study was to investigate effects of introduced honey bees (Apis mellifera) on native pollination interactions of Echium wildpretii ssp. wildpretii in the sub-alpine desert of Tenerife. We selected two study populations, one dominated by honey bees, while the other was visited by many native insects. During peak activity period of insects, nectar was nearly completely depleted in flowers of the first, but not the latter population. Thus, a high abundance of honey bees may have suppressed visitation by native animals due to exploitative competition. Honey bees stayed longer and visited more flowers on the same inflorescence than native bees, thus potentially promoting self-pollination of the plants. Level of seed set and viability was similar in the two study populations. However, we cannot rule out long-term changes in genetic population structure due to changes in gene-flow patterns caused by foraging behaviour of honey bees vs. native flower-visitors.     

Vertical Distribution of Trace Metals in Natural Soil Horizons from Japan Part 2: Effects of Organic Components in Soil

The association of Al, Mn, Fe, Ba, Zn, Cr, Ni, Co and Pb withsoil organic matter (SOM) was investigated in three Japanesesoils. Organically bound metals were assayed by elementalanalysis of a fraction extracted with acidified hydrogenperoxide (H₂O₂) and the humic acid extracted withalkaline reagent, from soil sampled at various depths of solums.A Dystric Cambisol showed higher extractability with acidifiedH₂O₂ for most of the metals than a Humic Andosol and an Orthic Acrisol. A Humic Andosol had more metals associated with humicacid than the other two soils.Cu showed high extractability with acidified H₂O₂ andalso significant association with humic acid, while Pb showedhigh extractability with acidified H₂O₂ but itsassociation with humic acid was relatively low among the metalsinvestigated. As humic acid is highly resistant to weathering,retention of Cu with SOM may last longer than that of Pb.The binding of metals with SOM probably has contributed to theaccumulation of some metals in organic-rich shallow horizons of soil. Such metals were Zn, Cu, Ni and Pb in a Dystric Cambisol,Cu in a Humic Andosol, and Pb and Cu in an Orthic Arisol.     

Improvement of the bitter taste of amino acids through the transpeptidation reaction of bacterial gamma-glutamyltranspeptidase.

The tastes of several bitter amino acids and their gamma-glutamyl derivatives were compared. The bitterness of Phe, Val, Leu, and His was reduced, sourness was produced, and preferences were increased by gamma-glutamylization. Because the effect of gamma-glutamylization of bitter amino acids was most obvious for Phe, which is an atypical bitter amino acid, an enzymatic method for the synthesis of gamma-glutamylphenylalanine (gamma-Glu-Phe) involving bacterial gamma-glutamyltranspeptidase was developed. The optimum reaction conditions were 200 mM Gln, 200 mM Phe, and 0.5 unit/mL GGT, pH 10.4. After 1.5-h of incubation at 37 degrees C, 140 mM gamma-Glu-Phe was obtained, the yield being 70%. gamma-Glu-Phe was purified on a Dowex 1x8 column and then identified by NMR.