SUSCEPTIBILITY ARTIFACTS ON T2*‐WEIGHTED MAGNETIC RESONANCE IMAGING OF THE CANINE AND FELINE SPINE

The T2*‐weighted gradient recalled echo sequence is a sensitive means to detect blood degradation products. While not a routine sequence in magnetic resonance imaging of the spine in small animals, it can provide additional valuable information in select cases. The goal of this retrospective, cross‐sectional study was to describe findings when acquiring this sequence during magnetic resonance imaging examination of the spine in small animals. The University of Tennessee's veterinary radiology database was searched for dogs and cats that underwent magnetic resonance imaging for suspect spinal disease in which a T2*‐weighted gradient recalled echo sequence was acquired and susceptibility artifact was identified. The following information was recorded: signalment, clinical signs, location and appearance of susceptibility artifact, and final diagnosis. Thirty‐nine cases were included in the study. Extradural susceptibility artifacts were observed in cases of intervertebral disc herniation with or without associated hemorrhage (n = 28), extradural hemorrhage associated with spinal trauma (n = 2), hemophilia (n = 1), and in a cystic extradural mass (n = 1). Remaining lesions displaying susceptibility artifact were intramedullary and included presumptive acute noncompressive nucleus pulposus extrusion (n = 2), hematoma (n = 1), hemangiosarcoma metastasis (n = 1), intramedullary disc extrusion (n = 1), presumptive meningomyelitis (n = 1), and a mass of undetermined etiology (n = 1). Inclusion of a T2*‐weighted gradient recalled echo sequence may be helpful in spinal magnetic resonance imaging when standard imaging sequences are ambiguous or intramedullary lesions are observed.     

Pre-operative fibrous osteodystrophy and severe,refractory, post-operative hypocalcemia following parathyroidectomy in a dog

A 13-year-old dog exhibited dramatic, radiographic osteopenia consistent with fibrous osteodystrophy secondary to primary hyperparathyroidism. Following parathyroidectomy, the dog developed severe, prolonged hypocalcemia, but was successfully treated and discharged 32 d after surgery. A variety of factors may have contributed to this dog’s hypocalcemia including hypoparathyroidism and hungry bone syndrome.     

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.     

Biochemical fluorometric method for the determination of riboflavin in milk

Methods of analysis of vitamin B2 in foods generally consist of the extraction of the sample, followed by enzymatic hydrolysis and quantitative measurement of the analyte, typically through RP-HPLC. The scope of our work here is to present a soft method to measure the free riboflavin content of a nontransparent and nonhomogeneous matrix such as milk, avoiding any extraction and separation of phases that are required in any published method for determination of the free RBF content in foods. We combine the front-face (FF) measurement of the light emission of milk with the ability of the apo-form of the riboflavin-binding protein (RBP) from chicken egg white to quench the riboflavin fluorescence. Thus, we titrate the RBF present in milk by gradually adding a solution of RBP to the milk sample and measuring, upon each addition, the FF residual emission due to uncomplexed RBF. The RBP binding capability has been measured in the same matrix of the analyte. Our results indicate a concentration of free RBF practically co-incident with the certified value for total B2 vitamin content in reference milk CRM 421. Keywords: Front-face fluorescence; riboflavin; apo-riboflavin-binding protein; milk fluorescence.     

Permeability profile estimation of flavonoids and other phenolic compounds by biopartitioning micellar capillary chromatography

This paper points out the usefulness of biopartitioning micellar chromatography (BMC) using capillary columns as a high-throughput primary screening tool providing key information about the oral absorption, skin permeability, and brain-blood distribution coefficients of 15 polyphenols (6 flavones, 2 flavonols, a flavanone, 2 flavan-3-ols, 3 phenolic acids, and a phloroglucinol) in a simple and economical way. For the compounds studied, except vicenin-2, rutin, chlorogenic acid, p-hydroxycinnamic acid, and 4-hydroxybenzoic acid, maximal oral absorption (>90%) can be expected, if there are not solubility problems or metabolic processes. On the other hand, the most retained compounds in BMC, that is, 5-hydroxyflavone, flavone, and flavanone, show the highest brain-blood distribution coefficients and skin permeability coefficients.