How does the Selection of Laboratory Mice Affect the Results of Physiological Distribution of Radiopharmaceuticals?

BACKGROUND: The choice of mice strain can significantly influence the physiological distribution and may lead to an inadequate assessment of the radiopharmaceutical properties. OBJECTIVE: This work aims to present how the legal requirements that apply to radiopharmaceuticals contained in the various guidelines determine the choice of the mouse strain for quality control and preclinical studies and affect the results of physiological distribution. METHODS: Swiss and BALB/c mice were chosen as commonly used strains in experiments for research and quality control purposes. Radiopharmaceuticals, i.e., preparations containing one or more radioactive isotopes in their composition, are subject to the same legal regulations at every stage of the research, development and routine quality control as all other medicines. Therefore, in vivo experiments are to be carried out to confirm the pharmacological properties and safety. Moreover, if a radiopharmaceutical's chemical structure is unknown or complex and impossible to be determined by physicochemical methods, an analysis of physiological distribution in a rodent animal model needs to be performed. RESULTS: In our studies, thirty-six mice (Swiss n=18, BALB/c n=18) were randomly divided into six groups and injected with the following radiopharmaceuticals: [99mTc]Tc-Colloid, [99mTc]Tc-DTPA and [99mTc]Tc-EHIDA. Measurement of physiological distribution was conducted following the requirements of European Pharmacopoeia (Ph. Eur.) monograph 0689, internal instructions and the United States Pharmacopeia (USP) monograph. Additionally, at preclinical studies, ten mice (Swiss n=5, BALB/c n=5) were injected with the new tracer [99mTc]Tc-PSMA-T4, and its physiological distribution has been compared. The p-value <0.05 proved the statistical significance of the radiopharmaceutical physiological distribution. CONCLUSION: We claim that mice strain choice can significantly influence the physiological distribution and may lead to inaccurate quality control results and incomprehensible interpretation of the results from preclinical in vivo studies of a new radiopharmaceutical.

Impact of colostrum and plasma immunoglobulin intake on hippocampus structure during early postnatal development in pigs.

The first milk, colostrum, is an important source of nutrients and an exclusive source of immunoglobulins (Ig), essential for the growth and protection from infection of newborn pigs. Colostrum intake has also been shown to affect the vitality and behaviour of neonatal pigs. The objective of this study was to evaluate the effects of feeding colostrum and plasma immunoglobulin on brain development in neonatal pigs. Positive correlations were found between growth, levels of total protein and IgG in blood plasma and hippocampus development in sow-reared piglets during the first 3 postnatal days. In piglets fed an elemental diet (ED) for 24h, a reduced body weight, a lower plasma protein level and a decreased level of astrocyte specific protein in the hippocampus was observed, as compared to those that were sow-reared. The latter was coincident with a reduced microgliogenesis and an essentially diminished number of neurons in the CA1 area of the hippocampus after 72h. Supplementation of the ED with purified plasma Ig, improved the gliogenesis and supported the trophic and immune status of the hippocampus. The data obtained indicate that the development of the hippocampus structure is improved by colostrum or an Ig-supplemented elemental diet in order to stimulate brain protein synthesis and its development during the early postnatal period.

[Biological role of obestatin in physiology and pathophysiology]. / Biologiczna rola obestatyny w fizjologii I patofizjologii.

Obestatin is a 23 amino acid peptide encoded by the same gene as ghrelin and synthetized in the gastrointestinal tract. The first results of the investigations on the physiological function of obestatin pointed to its role in the reduction of appetite, delay of stomach emptying and decrease of body weight gains which may testify the fact that this peptide is an endogenous antagonist for ghrelin. The results of the last 5 years investigations on the physiological role of obestatin presented in this paper contradict such a statement and prove that obestatin is an independent hormone, participating in many physiological processes in the organism which may include the development of the gastrointestinal tract in the early postnatal period.