The koala is a specialist feeder with a diet consisting almost exclusively of potentially toxic eucalypt leaves. Monoterpenes, an abundant class of plant secondary metabolites in eucalypts, are highly lipophilic. Chronic absorption and systemic exposure can be anticipated for the koala, causing health effects in various ways when consumed in high amounts, but particularly causing alterations in immune function in this species. Therefore, careful leaf selection, efficient detoxification pathways, and other specialist adaptations are required to protect animals from acute intoxication. This is the first paper providing insight into the systemic exposure of koalas to these compounds. Profiles of six selected major monoterpenes were investigated in the ingesta of deceased koalas from four different regions of NSW and South-East Queensland. Concentrations of the same compounds were measured in lymphoid tissues of deceased koalas and in the blood of live koalas from other regions of NSW. Analytical methods included liquid extraction and solid-phase micro-extraction, followed by gas-chromatography/ mass-spectrometry. Concentrations in the ingesta of individual animals vary remarkably, though the average proportions of individual monoterpenes in the ingesta of animals from the four different regions are highly comparable. Blood concentrations of the selected monoterpenes also varied considerably. The highest blood concentrations were found for 1,8-cineole, up to 971 ng/ml. There was similarity between circulating monoterpene profiles and ingesta profiles. Based on the observed lack of similarity between blood and lymph tissue concentrations, individual monoterpenes either exhibit different affinities for lymphatic tissue compared to blood or their accumulation in blood and lymph tissue differs temporally. In general, blood monoterpene concentrations found in koalas were low compared to those reported in other marsupial eucalypt feeders, but significant concentrations of monoterpenes were detected in all samples analysed. This data on blood and lymphatic tissue monoterpene concentrations builds the fundamental groundwork for future research into the effects of dietary monoterpenes on various biological processes of specialist herbivores and into the significance of these animals' metabolic and behavioural strategies for coping with these compounds. We have shown that the systemic exposure of koalas to potentially anti-inflammatory eucalypt monoterpenes is continuous, and we provide data on physiological concentrations which will allow realistic future studies of the effects of monoterpenes on immune cell function.
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http://dx.doi.org/10.1007/s10886-019-01097-x | DOI Listing |
Inn Med (Heidelb)
January 2025
Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU Klinikum München, München, Deutschland.
Celiac disease is one of the most common lifelong autoimmune disorders and is currently understood as a genetically determined immune intolerance to gluten. In genetically predisposed individuals, the consumption of gluten, along with additional environmental factors, triggers an immunological reaction in the small intestinal epithelium, leading to the destruction of the mucosal architecture with villous atrophy. This can be asymptomatic, but may also cause a wide range of symptoms and lead to systemic complications, such as osteoporosis or infertility.
View Article and Find Full Text PDFClin Cancer Res
January 2025
The Wistar Institute, Philadelphia, PA, United States.
Purpose: A first-in-human phase one study was conducted in nasopharyngeal carcinoma (NPC) patients to assess the safety and tolerability of VK-2019, a small molecule selective inhibitor of Epstein-Barr virus Nuclear Antigen 1 (EBNA1).
Patients And Methods: Pharmacokinetic and pharmacodynamic studies, including circulating tumor EBV DNA plasma levels, were performed. Twenty-three patients received VK-2019 orally once daily at doses ranging from 60 to 1800 mg using an accelerated titration design, with cohort expansion at 1800 mg.
Background & Aims: Hepatic insulin resistance is a fundamental phenomenon observed in both Type 2 diabetes (T2D) and metabolic (dysfunction) associated fatty liver disease (MAFLD). The relative contributions of nutrients, hyperinsulinemia, hormones, inflammation, and other cues are difficult to parse as they are convoluted by interplay between the local and systemic events. Here, we used a well-established human liver microphysiological system (MPS) to establish a physiologically-relevant insulin-responsive metabolic baseline and probe how primary human hepatocytes respond to controlled perturbations in insulin, glucose, and free fatty acids (FFAs).
View Article and Find Full Text PDFVet World
November 2024
Department of Anatomy, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Background And Aim: Bacterial lipopolysaccharide (LPS)-induced neuroinflammation can be the most dependable animal model for studying neurodegeneration mechanisms driven by systemic inflammation-induced neuroinflammation. Hence, this study aimed to standardize the LPS model of neuroinflammation by comparing the effect of relatively low-dose LPS administered for different durations on the induction of neurodegeneration in Wistar rats.
Materials And Methods: Six groups of six adult Wistar rats per group were used in the study.
Clin Pharmacol Drug Dev
January 2025
Department of Pathology, Xianning Central Hospital, The First Affiliated Hosptial of Hubei University of Science and Technology, Xianning, Hubei, P.R. China.
Bosentan is a dual endothelin receptor antagonist widely used in the treatment of pulmonary artery hypertension. However, there are few reports on the pharmacokinetics (PK) and bioequivalence of bosentan dispersible tablets (32 mg) in the Chinese population. This study aimed to evaluate the PK characteristics and bioequivalence of the test and reference formulations of bosentan dispersible tablets in healthy Chinese volunteers under fasting and fed conditions.
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