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.     

Rapid brain MRI protocols result in comparable differential diagnoses versus a full brain protocol in most canine and feline cases

Evaluation of brain disease in veterinary patients uses a wide variety of MRI sequences. A shortened protocol that maintains consistency of interpretation would reduce radiologist reporting time, patient anesthetic time, and client cost. The aims of this retrospective, methods comparison, observer agreement study were to evaluate whether abbreviated MRI protocols alter differential diagnoses and recommendations compared to our institution's standard protocol; evaluate interobserver agreement on standard brain MRIs; and assess whether differential diagnoses change after postcontrast images. Normal and pathologic canine and feline brain MRIs were retrieved from hospital archives. Three protocols were created from each: a 5-sequence noncontrast enhanced Fast Brain Protocol 1 (FBP1); a 6-sequence contrast-enhanced Fast Brain Protocol 2 (FBP2); and an 11-sequence standard brain protocol (SBP). Three blinded veterinary radiologists interpreted FBP images for 98 cases (1 reader/case) and SBP images for 20 cases (3 readers/case). A fourth observer compared these interpretations to the original MRI reports (OMR). Overall agreement between FBPs and OMR was good (k = 0.75) and comparable to interobserver agreement for multiple reviews of SBP cases. Postcontrast images substantially altered conclusions in 17/97 cases (17.5%), as well as improved interobserver agreement compared to noncontrast studies. The conclusions reached with shortened brain protocols were comparable to those of a full brain study. The findings supported the use of a 6-sequence brain MRI protocol (sagittal T2-weighted [T2w] TSE; transverse T2w turbo spin echo fluid-attenuated inversion recovery, T2*-weighted gradient recalled echo, T1-weighted spin echo, and diffusion weighted imaging/apparent diffusion coefficient; and postcontrast transverse T1-weighted spin echo) for dogs and cats with suspected intracranial disease.     

The effect of strain, growth stage, and cultivating condition of Ganoderma lucidum on 5α-reductase inhibition

The inhibitory effects of 102 methanol extracts of 40 mycelia, 9 culture fluids, and 53 fruiting bodies of 40 strains of Ganoderma lucidum on 5-reductase were investigated. The methanol extract of the fruiting body of each strain was found to show the strongest 5-reductase inhibitory activity among the extracts tested.     

A split-root apparatus for examining the effects of hydraulic lift by trees on the water status of neighbouring crops

We describe a split-root system for examining the effects of hydraulic lift by trees on crop growth. In this system, upper lateral tree roots were grown in a container set on the ground through which the taproot of the tree could penetrate into the moist soil below. The container, with a radius of 0.5 m and a height of 0.20 m, consisted of two compartments divided by a waterproof barrier. A markhamia tree (Markhamia lutea (Benth.) Schumann) and upland rice (Oryza sativa (L.)) plants were planted in one compartment, with only rice plants planted in the other compartment. Irrigation of the container was ceased at the start of the experiment. The stomatal conductance of the rice plants in the associated side, in which both trees and rice plants were grown, declined more rapidly during the first drying period than in the rice-only compartment, suggesting that there was competition for water between the tree and the crop plants. However, during the later drying period, the rice plants in the associated side were green and viable, while those in the rice-only side became desiccated. Rice roots were seen intermingling with tree roots, and the soil water content in the associated site tended to be higher than in the rice-only side. It is likely that hydraulic lift occurred in the associated side and that water that had been transferred to the surface roots was released into the soil, enabling the rice plants in this compartment to remain viable. This novel system is useful for examination of the effects of hydraulic lift by trees on the growth of neighbouring crops. This revised version was published online in June 2006 with corrections to the Cover Date.     

Acorn dispersal and predation patterns of four tree species by wood mice in abandoned cut-over land

We compared patterns of acorn dispersal and predation by wood mice among four tree species (Quercus serrata, Quercus crispula, Castanea crenata, and Juglans mandshurica var. sieboldiana) that are abundant in cool temperate woodlands. We devised an acorn dispersal experiment using 400 magnet-inserted acorns and a magnetic locator in a 1.8-ha study plot, which spanned a cut-over area and an adjacent deciduous forest. Ten wire mesh baskets, each containing 40 acorns (10 acorns per species), were placed on the border between these two habitat types. About 13.0% (n = 52) of the total acorns remained in the baskets, while 77.3% (n = 309) were dispersed throughout the study plot and subsequently retrieved using the magnetic locator. Microhabitat, distance, and burial depth of transported acorns were significantly different among species. In the cut-over area, J. mandshurica var. sieboldiana acorns were dispersed under fallen trees or branches and near stumps, and were buried deeply in the soil. Dispersal distances of J. mandshurica var. sieboldiana acorns were significantly greater than those of Q. serrata acorns. The number and microhabitat of transported acorns significantly differed between habitat types. J. mandshurica var. sieboldiana acorns were dispersed in the cut-over area rather than in the forest. For all four species, the numbers of acorns delivered to fallen trees or branches, stumps, and crumbled soil with overhang under any vegetation type were greater in the cut-over area than in the forest.     

Chemical changes of kenaf core binderless boards during hot pressing (I): influence of the pressing temperature condition

Self-bonding is the main factor of the performance expression of binderless boards, and therefore its clarification is considered to be an important issue. For this purpose, a series of chemical analyses were conducted on kenaf core binderless boards and their chemical changes during the hot-pressing process are discussed in this article. First of all, binderless boards were prepared from kenaf core powder at different pressing temperatures (without steam-explosion process) and were used for chemical analyses after they were reduced into powders and extracted with methanol. To investigate their chemical changes, lignin, holocellulose, and neutral sugar contents were determined, Fourier transform infrared (FTIR) spectra were recorded, and the nitrobenzene oxidation procedure was applied. As a result, it was found that parts of lignin and hemicelullose were decomposed during the hot-pressing process; however, the contribution of the resulting fractions to selfbonding was not observed. In addition, progress of condensation reactions in lignin and the formation of chemical bonds by low molecular weight conjugated carbonyl compounds in methanol extractives were observed. Thermal softening of lignin is also suggested to play an important role in the expression of board performance.     

Manufacture and mechanical properties of binderless boards from kenaf core

Binderless boards were prepared from finely ground powders of kenaf (Hibiscus cannabinus L.) core under varying manufacturing conditions. This research was designed to investigate their mechanical properties and evaluate the various manufacturing conditions: pressing temperature and time, pressing pressure, board density, board thickness, grain size of raw materials, and addition of furfural. The mechanical properties (i.e., modulus of rupture and elasticity, internal bonding strength) of boards increased with increasing board density and met the requirement for 15 type medium-density fiberboard (MDF) by JIS A 5905-1994. Thickness swelling and water absorption of boards exceeded the maximum permitted levels for 15 type MDF and S20 grade hardboard by JIS A 5905-1994, which indicates the low water-resistant property of binderless boards. In contrast to that in usual wood-based materials, internal bonding strength showed significant correlations with other board properties: modulus of rupture and elasticity, thickness swelling, and water absorption. We confirmed experimentally that the best manufacturing conditions proved to be as follows: pressing temperature 180°C, time 10min; pressing pressure 5.3MPa; board thickness 5mm; board density 1.0g/cm³; average grain size 53µm; and powder with no furfural content.Part of this paper was presented at the 52nd Annual Meeting of the Japan Wood Research Society, Gifu, April 2002     

Plectosporium blight of monkshood caused by <Emphasis Type="Italic">Plectosporium tabacinum</Emphasis>

Severe blight of potted seedlings of monkshood caused by Plectosporium tabacinum was found in glasshouses in Kagawa Prefecture in southwest Japan in May 2001. Root rot and browning of stem bases were followed by wilting and yellowing of leaves, then blighting of leaves, flower buds and stems. A fungus was isolated from diseased plants and confirmed to cause the disease. The new disease was named “Plectosporium blight of monkshood”.     

First report of celery stunt anthracnose caused by <Emphasis Type="Italic">Colletotrichum simmondsii</Emphasis> in Japan

A new disease was found in Japan, on celery (Apium graveolens var. dulce) having severe chlorotic leaf spot, stunt, and dwarf with leaf curl. A spore suspension from the fungus isolated from affected plants induced identical symptoms 14 days after plants were sprayed. Identification and molecular characterization showed that the causal agent is Colletotrichum simmondsii. This report is the first of stunt anthracnose on celery caused by C. simmondsii. We propose the name “stunt anthracnose” for the new disease. Colletotrichum acutatum sensu lato, as reference pathogen of celery anthracnose, should be changed to C. fioriniae based on morphological and molecular characteristics.