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.     

Carbon and nitrogen mineralization of non-composted and composted municipal solid waste in sandy soils

A sterilized, but undecomposed, organic by-product of municipal waste processing was incubated in sandy soils to compare C and N mineralization with mature municipal waste compost. Waste products were added to two soils at rates of 17.9, 35.8, 71.6, and dry weight and incubated at for 90 d. Every 30 d, nitrate and ammonium concentrations were analyzed and C mineralization was measured as total CO₂-C evolved and added total organic C. Carbon mineralization of the undecomposed waste decreased over time, was directly related to application rate and soil nutrient status, and was significantly higher than C mineralization of the compost, in which C evolution was relatively unaffected across time, soils, and application rates. Carbon mineralization, measured as percentage C added by the wastes, also indicated no differences between composted waste treatments. However, mineralization as a percentage of C added in the undecomposed waste treatments was inversely related to application rate in the more productive soil, and no rate differences were observed in the highly degraded soil. Total inorganic N concentrations were much higher in the compost- and un-amended soils than in undecomposed waste treatments. Significant N immobilization occurred in all undecomposed waste treatments. Because C mineralization of the undecomposed waste was dependant on soil nutrient status and led to significant immobilization of N, this material appears to be best suited for highly degraded soils low in organic matter where restoration of vegetation adapted to nutrient poor soils is desired.     

Beta-carotene isomer composition of sub- and supercritical carbon dioxide extracts. Antioxidant activity measurement

In the present work sub- and supercritical extraction conditions using carbon dioxide were studied in order to obtain extracts with different compositions from the green microalgae Dunaliella salina. Different compositions of beta-carotene isomers were identified in the extracts by using HPLC-DAD. Also, antioxidant activity of the extracts was measured using a TEAC assay. An experimental design was applied considering two factors, extraction pressure and temperature, in a wide range of values, trying to maximize the extraction yield. Higher yields were obtained at high pressures and low temperatures, that is, at higher CO2 densities. Attempts were made to correlate the antioxidant activity of the extracts with their chemical composition by means of principal component analysis. A certain relationship was found between their antioxidant activity and the isomeric composition of beta-carotenes. As a result, an original equation is proposed to predict the antioxidant activity of extracts from D. salina in terms of the ratio 9-cis-beta-carotene/all-trans-beta-carotene, the concentration of alpha-carotene, and, especially, the concentration of 9-cis-beta-carotene.     

Mechanisms and management of acaricide resistance for Tetranychus urticae in agroecosystems

Journal of Pest Science - The two-spotted spider mite, Tetranychus urticae Koch, is a constant threat to sustainable production of numerous economically important crops globally. Management of T....     

Atherosclerosis associated with vasculopathic lesions in a golden retriever with hypercholesterolemia

A 2-year-old neutered male golden retriever dog presented for lameness secondary to ulcerations of multiple digital paw pads was diagnosed with vasculitis and hypercholesterolemia. Despite treatment, ischemic necrosis progressed to include all distal extremities and the dog eventually expired due to myocardial infarction secondary to severe atherosclerosis. The rapid demise and the dermatologic lesions may have been secondary to cholesterol embolism syndrome which has never before been reported in a dog.     

Pilot project to investigate over-wintering of free-living gastrointestinal nematode larvae of sheep in Ontario,Canada

This study investigated the overwintering survival and infectivity of free-living gastrointestinal nematode (GIN) stages on pasture. The presence of GIN larvae was assessed on 3 sheep farms in Ontario with a reported history of clinical haemonchosis, by collecting monthly pasture samples over the winter months of 2009/2010. The infectivity of GIN larvae on spring pastures was evaluated using 16 tracer lambs. Air and soil temperature and moisture were recorded hourly. Free-living stages of Trichostrongylus spp. and Nematodirus spp. were isolated from herbage samples. Gastrointestinal nematodes were recovered from all tracer lambs on all farms; Teladorsagia sp. was the predominant species. Very low levels of Haemonchus contortus were recovered from 1 animal on 1 farm. The results suggest that Haemonchus larvae do not survive well on pasture, while Teladorsagia sp., Trichostrongylus spp. and Nematodirus spp. are able to overwinter on pasture in Ontario and are still infective for sheep in the spring.     

Adoption of milk cooling technology among smallholder dairy farmers in Kenya

Factors influencing adoption of milk cooling technology were studied with data for 90 smallholder dairy farmers who were randomly selected from seven dairy cooperative societies in Kiambu County, Kenya. Logistic regression identified the age of the household head, daily household milk consumption, freehold land ownership, fodder production area, number of female calves, cooperative membership and cooperative services as significant factors influencing farmers’ willingness to invest in milk cooling technology. These findings offer an entry point for increased interventions by policy makers and various dairy sector stakeholders in promoting milk cooling technology with the aim of significantly reducing post-harvest losses and increasing the sector’s competitiveness.     

Immune characterization of long pentraxin 3 in pigs infected with influenza virus

Long pentraxin 3 (PTX3) is a conserved pattern-recognition secreted protein and a host-defence-related component of the humoral innate immune system. The aim of the present study was to characterize swine PTX3 (SwPTX3) protein expression in influenza virus infected pigs. First, we performed in silico studies to evaluate the cross-reactivity of PTX3 human antibodies against SwPTX3. Secondly, we used in vitro analysis to detect SwPTX3 presence in swine bone marrow dendritic cells (SwBMDC) upon stimulation with different agents by Western blot and immunofluorescence. Finally, the levels of SwPTX3 were assessed in experimental infection of pigs with different strains of influenza virus. This is a novel study where the expression of SwPTX3 was evaluated in the context of a pathogen infection. The initial characterization of SwPTX3 in influenza virus infected pigs contributes to understand the role of PTX proteins in the immune response.     

Seroprevalence of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in shelter cats on the island of Newfoundland,Canada

Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are retroviruses found within domestic and wild cat populations. These viruses cause severe illnesses that eventually lead to death. Housing cats communally for long periods of time makes shelters at high risk for virus transmission among cats. We tested 548 cats from 5 different sites across the island of Newfoundland for FIV and FeLV. The overall seroprevalence was 2.2% and 6.2% for FIV and FeLV, respectively. Two sites had significantly higher seroprevalence of FeLV infection than the other 3 sites. Analysis of sequences from the FeLV env gene (envelope gene) from 6 positive cats showed that 4 fell within the FeLV subtype-A, while 2 sequences were most closely related to FeLV subtype-B and endogenous feline leukemia virus (en FeLV). Varying seroprevalence and the variation in sequences at different sites demonstrate that some shelters are at greater risk of FeLV infections and recombination can occur at sites of high seroprevalence.     

Treatment of Intraoperative Persistent Penile Erection in a Stallion

This case report describes the occurrence of persistent penile erection in a breeding stallion that occurred while the horse was under inhalant anesthesia for a carpal arthroscopy. The horse had no history of breeding problems, and no abnormalities were detected on physical examination, complete blood count, or serum chemistry tests performed prior to surgery. Anesthesia was induced with guaifenesin and ketamine after sedation with xylazine and was maintained with isoflurane in 100% oxygen. Penile erection developed approximately 35 minutes after induction and persisted for over 2 hours despite various physical and pharmacological attempts to alleviate it (massage, cold compresses, intravenous benztropine administration, and intracavernosal phenylephrine). Successful resolution of the erection was obtained by cannulation and drainage of blood from the corpus cavernosum and subsequent irrigation with heparinized sterile saline and infusion of phenylephrine in the corpus cavernosum. The detumescent penis was placed back into the sheath, and purse string sutures were placed in the sheath to ensure the penis would remain inside the sheath during recovery. The stallion's recovery from anesthesia was uneventful, the sutures were removed, and the horse was fitted with a penile sling to prevent additional edema or trauma. The stallion recovered completely from the persistent penile erection. Semen was collected 6 days after the event, and he returned to normal pasture breeding 6 weeks after surgery.