Medium-chain fatty acids (MCFAs) are found at higher levels in milk lipids of many animal species and in the oil fraction of several plants, including coconuts, palm kernels and certain Cuphea species. Medium-chain triglycerides (MCTs) and fatty acids are efficiently absorbed and metabolized and are therefore used for piglet nutrition. They may provide instant energy and also have physiological benefits beyond their energetic value contributing to several findings of improved performance in piglet-feeding trials. MCTs are effectively hydrolyzed by gastric and pancreatic lipases in the newborn and suckling young, allowing rapid provision of energy for both enterocytes and intermediary hepatic metabolism. MCFAs affect the composition of the intestinal microbiota and have inhibitory effects on bacterial concentrations in the digesta, mainly on Salmonella and coliforms. However, most studies have been performed in vitro up to now and in vivo data in pigs are still scarce. Effects on the gut-associated and general immune function have been described in several animal species, but they have been less studied in pigs. The addition of up to 8% of a non-esterified MCFA mixture in feed has been described, but due to the sensory properties this can have a negative impact on feed intake. This may be overcome by using MCTs, allowing dietary inclusion rates up to 15%. Feeding sows with diets containing 15% MCTs resulted in a lower mortality of newborns and better development, particularly of underweight piglets. In conclusion, MCFAs and MCTs offer advantages for the improvement of energy supply and performance of piglets and may stabilize the intestinal microbiota, expanding the spectrum of feed additives supporting piglet health in the post-weaning period.

Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical translation. Because these strategies require immunosuppression in most cases, immunosuppressive protocols are a key element in transplantation experiments. However, standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species. Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation. This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects. It also summarizes contemporary knowledge of novel immunomodulatory strategies, such as the use of mesenchymal stem cells or antibodies. Thus, this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies.

Organic short and medium chain fatty acids are used in diets for piglets because they have an impact on the digestive processes and the intestinal microbiota. In this study, 48 pens (2 piglets/pen) were assigned randomly to 4 diets, without additive (control), with organic acids (OA; 0.416% fumaric and 0.328% lactic acid), with medium chain fatty acids (MCFA; 0.15% caprylic and capric acid), and a combination of OA and MCFA, to assess changes in the gastrointestinal microbiota with 12 pens per diet. Eight to nine piglets from each group were euthanized after 4 wk. Organic acids, MCFA, and pH in the digesta were determined and the intestinal microbiota was quantified by real-time PCR. The different diets had no effect on the growth performance. Concentration of added fumaric acid was below the detection limit in the upper small intestine whereas the concentration of lactic acid in the digesta was not affected by the treatments. The added MCFA was recovered in the MCFA treated groups in the stomach, but the concentrations declined in the upper small intestine. Concentration of short chain fatty acids was reduced in the colon digesta in piglets fed diets with OA compared with those fed unsupplemented diets (P = 0.029). The MCFA resulted in a pH reduction of the digesta, likely because of the effect on bacterial acid production. The addition of OA increased cell counts of Bacteroides-Porphyromonas-Prevotella group and clostridial clusters XIVa, I, and IV in the stomach, the clostridial cluster XIVa in the jejunum, and Bacteroides-Porphyromonas-Prevotella in the ileum and reduced counts of Streptococcus spp. in the colon (P < 0.05). The MCFA induced only minor changes in the gastrointestinal microbiota but increased cell counts for the Escherichia-Hafnia-Shigella group in the jejunum and the clostridial cluster XIVa in the colon digesta (P < 0.05). In the colon of piglets fed diets with organic OA, reduced mean cell counts of STb (est-II) positive Escherichia coli were found. In conclusion, OA and MCFA had effects on the intestinal microecology in piglets. The decrease of the intestinal pH and the reduction of E. coli virulence genes by OA could make the combination of short chain fatty acids and MCFA as interesting gut flora modifiers, which can eventually prevent postweaning diarrhea.

Translation of acute ischemic stroke research to the clinical setting remains limited over the last few decades with only one drug, recombinant tissue-type plasminogen activator, successfully completing the path from experimental study to clinical practice. To improve the selection of experimental treatments before testing in clinical studies, the use of large gyrencephalic animal models of acute ischemic stroke has been recommended. Currently, these models include, among others, dogs, swine, sheep, and nonhuman primates that closely emulate aspects of the human setting of brain ischemia and reperfusion. Species-specific characteristics, such as the cerebrovascular architecture or pathophysiology of thrombotic/ischemic processes, significantly influence the suitability of a model to address specific research questions. In this article, we review key characteristics of the main large animal models used in translational studies of acute ischemic stroke, regarding (1) anatomy and physiology of the cerebral vasculature, including brain morphology, coagulation characteristics, and immune function; (2) ischemic stroke modeling, including vessel occlusion approaches, reproducibility of infarct size, procedural complications, and functional outcome assessment; and (3) implementation aspects, including ethics, logistics, and costs. This review specifically aims to facilitate the selection of the appropriate large animal model for studies on acute ischemic stroke, based on specific research questions and large animal model characteristics.