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.     

Predation by scavenging amphipods to injured hatchery-raised juvenile Japanese flounder Paralichthys olivaceus under laboratory conditions

ABSTRACT:   The attacking potential of the scavenging amphipod Scopelocheirus onagawae on artificially injured hatchery-raised Japanese flounder Paralichthys olivaceus juveniles was investigated in relation to the degree of injury on the fish. All injured flounder juveniles were attacked by amphipods regardless of the degree of injury, while non-injured juveniles were not attacked. The attack by amphipods on the juveniles generally depended on the amount of glycine, a main feeding stimulant for the amphipod, released from the injury opening. The swimming ability of flounder juveniles was important to avoid the attack of amphipods. Furthermore, an area of injury allowing the amphipods to cling to the fish affects to the vulnerability of juveniles against the predation of amphipods. This study suggests that scavenging amphipods are potentially involved in the rapid reduction of the number of hatchery-raised juveniles.     

The effect of the observation time on turbulent diffusion in the atmosphere

Turbulent diffusion from a fixed point-source is classified according to the length of the observation time with the aid of modern diffusion theory. The diffusion zone in the downwind is shown to consist of the linear, cuspidal, and parabolic zones. The effect of the observation time on the diffusivity coefficients and plume spreading is also discussed.     

Estimation of rubberwood production in Cambodia

We estimated the production of rubberwood from 1996 to 2011 in Cambodia. We employed data from interview surveys with three rubberwood processing companies and statistics from estate rubber plantations and wood retailing companies. The result was that the end use of rubberwood in Cambodia was the sawntimber products, being exported to Vietnam and China. The yield rate from rubberwood stumpage into sawn timber was between 11.6 and 14.9%, closely matching the rates of Malaysia and Thailand. The average production of rubberwood roundwood from 1996 to 2011 was 254,697 m³/year, of which sawn timber as well as residuals in secondary processing was 84,559 and 170,138 m³/year, respectively. Although the timber production of Cambodia has declined sharply due to the strict restriction of natural forest logging, rubberwood could explain more than 60% of the domestic industrial roundwood production from 2000. We suggest the necessity of monitoring the expansion of rubber plantations in new rubber producing countries and linking the rubberwood production with the regional wood resource management.     

Nitrogen-fixing activity in decomposing litter of three tree species at a watershed in eastern Japan

Nitrogen fixation during litter decomposition was studied for 34 months using litterbags containing newly fallen litter of coniferous species Cryptomeria japonica and Pinus densiflora and that of deciduous species Quercus serrata. Litterbags were set in contact with the forest floor in a deciduous broad-leaved forest near the top of a slope and in a C. japonica stand at the middle of the slope at a watershed in eastern Japan. Nitrogen-fixing activity, estimated by acetylene reduction after 16 and 19 months of incubation, was 62.65–3.86 nmoles C₂H₄ h⁻¹ g⁻¹ DW in Cryptomeria litter, but only 1.07–0.09 in Pinus and 0.72–0.04 in Quercus. The rate of N increase in decomposing litter was highest in Cryptomeria. Fungal biomass in decomposing litter, estimated by ergosterol content, increased during the initial 16 months of incubation in Cryptomeria and Quercus, and during the initial 19 months of incubation in Pinus. The litter decomposition rate was highest in Cryptomeria among the three species, due to increased N content and fungal biomass in Cryptomeria litter. Thus, N increase in decomposing Cryptomeria litter affects the subsequent N dynamics and decomposition pattern.     

Effect of sesame seeds rich in sesamin and sesamolin on fatty acid oxidation in rat liver

Activities of enzymes involved in hepatic fatty acid oxidation and synthesis among rats fed sesame (Sesamum indicum L.) differing in lignan content (sesamin and sesamolin) were compared. Sesame seeds rich in lignans from two lines, 0730 and 0732, lines established in this laborary, and those from a conventional cultivar (Masekin) were employed. Seeds from the 0730 and 0732 lines contained sesamin and sesamolin at amounts twice those from Masekin. Sesame seeds were added at levels of 200 g/kg to the experimental diets. Sesame increased both the hepatic mitochondrial and the peroxisomal fatty acid oxidation rate. Increases were greater with sesame rich in lignans than with Maskin. Noticeably, peroxisomal activity levels were >3 times higher in rats fed diets containing sesame seeds from the 0730 and 0732 lines than in those fed a control diet without sesame. The diet containing Masekin seed caused only a 50% increase in the value, however. Diets containing seeds from the 0730 and 0732 lines, compared to the control and Masekin diets, also significantly increased the activity of hepatic fatty acid oxidation enzymes including acyl-CoA oxidase, carnitine palmitoyltranferase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase. In contrast, diets containing sesame lowered the activity of enzymes involved in fatty acid synthesis including fatty acid synthase, glucose-6-phosphate dehydrogenase, ATP-citrate lyase, and pyruvate kinase. No significant differences in enzyme activities were, however, seen among diets containing sesame from Masekin cultivar and lines 0730 and 0732. Serum triacylglycerol concentrations were lower in rats fed diets containing sesame from lines 0730 and 0732 than in those fed the control or Masekin diet. It is apparent that sesame rich in lignans more profoundly affects hepatic fatty acid oxidation and serum triacylglycerol levels. Therefore, consumption of sesame rich in lignans results in physiological activity to alter lipid metabolism in a potentially beneficial manner.     

Avian reovirus antibody assay by indirect immunofluorescence using plastic microculture plates.

An indirect fluorescent antibody test was developed to detect serum antibody to avian reovirus strain WVU2937. This test employed small multiple well plastic plates (8 x 5.5 cm) which readily fitted into the standard mechanical stage mechanism of an incident light fluorescence microscope. The small wells of the plates required minimal (10 muL) volumes of reagents. In tests on 18 sera in which the indirect fluorescent antibody, agar gel precipitin and plaque reduction methods were compared sera which gave negative results in the agar gel precipitin test were sometimes positive in the indirect fluorescent antibody and plaque reduction test, but indirect fluorescent antibody titers were lower than plaque reduction test titers. No false positive reactions were detected in 46 sera from uninoculated specific pathogen free chicks of up to eight weeks of age.