Toxicity and toxicokinetic study of RPh201 in Sprague-Dawley rats.

Mastic gum is used for health products and in the food industry, and is being tested for several clinical indications. Nevertheless, information on its safety is scarce. Our aim was to test the local and systemic toxicity of RPh201, a botanical extract of gum mastic, and to assess the toxicokinetic profile of the mastic gum constituents masticadienonic acid (MDA) and isomasticadienonic acid (IMDA). 340 Sprague-Dawley rats were administered twice weekly subcutaneously with placebo or different doses of RPh201 for 6 months with an interim group at 3 months and a 4-week recovery group. No systemic toxicity was observed with RPh201. Local injection site reactions were observed in all animals, with comparable severity and frequency in the placebo and high dose groups. However, given the relative increase in tissue reaction in the high dose group, these changes were attributed to RPh201 administration. Nevertheless, considering the minor local irritation effects and clear trend for reversibility, the effects were not judged to be adverse. The toxicokinetic study revealed that the MDA and IMDA exposure increased with dose and the increase was supra-proportional on all days. This study supports a "no observed adverse effect level" (NOAEL) of 300 mg/kg body weight in Sprague-Dawley rats.

International recommendations for training future toxicologic pathologists participating in regulatory-type, nonclinical toxicity studies.

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type - nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job "apprenticeship," at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A nonclinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one's understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies.

International recommendations for training future toxicologic pathologists participating in regulatory-type, nonclinical toxicity studies.

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type, nonclinical toxicology studies. Optimally, trainees should undertake a scientific curriculum of at least five years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain four or more years of intensive pathology practice during a residency and/or on-the-job "apprenticeship," at least two years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A nonclinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one's understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies.

International recommendations for training future toxicologic pathologists participating in regulatory-type, nonclinical toxicity studies.

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job "apprenticeship," at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A non-clinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one's understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies.

Neuroanatomical mapping of rabies nucleocapsid viral antigen distribution and apoptosis in pathogenesis in street dog rabies--an immunohistochemical study.

AIM: To date, there is no study from Asian countries describing the pathology and topographic distribution of virulent, "street" rabies viral infection in the canine brain. In the present study, neuroanatomical distribution of rabies viral antigen in the brains of rabid street dogs, by immunohistochemical techniques is documented and the role of apoptosis in pathogenesis of rabies in natural hosts especially canines infected with street virus is studied. MATERIALS AND METHODS: 10 brains of adult street dogs from urban areas of Bangalore, South Central India, infected with rabies were collected. The diagnosis was confirmed by immunofluorescent study. The pathomorphological features and the neuroanatomic distribution of the viral antigen by immunohistochemistry were studied. The ability of the virus to activate apoptosis in nerve cells if any, was studied by determining the DNA fragmentation and TUNEL technique in infected canine brains. RESULTS: The viral antigen was mostly localized to the neuronal perikaryon extending along the dendrites, while occasional astrocytes were also labeled. In the brain, the limbic areas, thalamus and the reticular formation of the brain stem, the trigeminal and the vagal nuclei were involved, corresponding to areas of cholinergic innervation. It is proposed that the preferential involvement of these cholinergic zones could explain some of the clinical features of rabies in canines. The extensive involvement of thalamus and immunolocalization of the rabies viral antigen in the axons are the unusual features noted in a dog's brain in contrast to murine experimental studies with "fixed virus". Characteristic DNA fragmentation forming 180-200 bp, leading to laddering was not seen, indicating apoptosis is not involved in the evolution of lesions in rabies in adult dogs infected by street virus.