Bempedoic acid (Nexletol®) is a novel cholesterol-lowering agent that is converted to its active CoA ester by very long-chain acyl-CoA synthetase 1 (ACSVL1), an enzyme selectively expressed in hepatocytes. The active metabolite selectively inhibits ATP citrate lyase (ACL), leading to a reduction in cytosolic acetyl-CoA levels and subsequent activation of SREBP2. This results in increased expression of LDL receptors and enhanced clearance of LDL cholesterol (LDL-C). Because ACSVL1 is not expressed in skeletal muscle, bempedoic acid is not activated in muscle tissue and is therefore less likely to cause muscle-related toxicity. Nonclinical studies have demonstrated direct ACL inhibition, suppression of hepatic lipid synthesis, and LDL-C-lowering effects with attenuation of atherosclerotic lesion progression in multiple animal models. In domestic and international clinical studies, bempedoic acid reduced LDL-C levels in patients with elevated LDL-C, regardless of their response to statin therapy. The LDL-C-lowering effect was observed from the first scheduled assessment after treatment initiation. With respect to safety, no significant safety concerns requiring special consideration were identified, and bempedoic acid was generally well tolerated. In addition, an international Phase III trial in patients with hypercholesterolemia who were statin-intolerant and had established cardiovascular disease or were at high cardiovascular risk demonstrated that bempedoic acid not only reduced and sustained reductions in LDL-C levels but also significantly reduced the risk of cardiovascular events, the primary endpoint of the study.
Anatomy is fundamental to medical education, providing the basis for understanding normal human structure and function and for learning clinical medicine. Cadaveric dissection plays a central role in anatomy education and remains the only opportunity for medical students to obtain information directly from the human body. During dissection practice, students face cadavers with sincerity and get information from the cadavers. The educational goal is not merely the memorization of anatomical knowledge, but the construction of a three-dimensional understanding of the human body and the development of scientific observational skills. Anatomy dissection practice is possible thanks to the noble spirit of Kentai donors, who donate their bodies to contribute to medical education. As such, dissection practice also provides an important opportunity for students to express respect and gratitude toward donors, to reflect on the dignity of life, and to cultivate medical ethics and professionalism. At our university, new dissection programs have been introduced in collaboration with clinical departments. These include the use of soft-embalmed cadavers for surgical training, enabling students to learn anatomy while experiencing basic clinical procedures such as tracheal intubation. Surgeons also provide special lectures with surgical videos, explaining how anatomical knowledge is useful in their fields. In addition, integrated education combining cadaveric dissection with medical image interpretation, including CT and MRI, has been implemented to enhance students' three-dimensional anatomical understanding from early medical education. Despite recent advances in virtual reality-based teaching tools, cadaveric dissection continues to be an essential cornerstone of anatomy curricula.
Pharmacology is one of the fundamental academic disciplines in the educational courses of Schools of Pharmaceutical Sciences, and practical training of pharmacology provides profound educational effects. On the other hand, the contents of practical training are increasingly forced to make several changes, which is motivated by several factors such as limitation in budget, concerns on animal welfare and experience of COVID-19 crisis. In Kumamoto University School of Pharmacy, the content of practical training of pharmacology and anatomy has been changed recently to diminish the usage of experimental animals to minimum necessary. For example, experiments on the effects of drugs on blood pressure in rats have been replaced by practical training with software-based simulations. Experiments on the effects of drugs on contraction responses of small intestines have also incorporated software-based simulations, but in addition, students have a chance to observe contraction of mouse small intestines in Magnus preparations. Several movies of pharmacological experiments using animals and isolated organs are provided to students via e-learning system. The other sets of experiments involve drug treatments and surgical operations in mice, and students are encouraged to handle mice by themselves in these experiments. We should continue efforts for improving the contents of practical training, while considering several factors including educational effects benefited from animal experiments and a purpose of Schools of Pharmaceutical Sciences in developing human resources for basic research of pharmaceutical sciences and life sciences.
During mammalian evolution, the cerebrum underwent remarkable changes: the brain surface expanded, and cortical folding increased. Neurons and astrocytes have increased in number and have acquired greater morphological complexity and functional diversity. Mice transplanted with human astrocytes show improved memory and learning abilities, suggesting that astrocyte functions were enhanced during evolution. Recently, human astrocytes have been shown to exhibit a larger cellular territory as well as morphological diversity. These findings suggest that evolutionary changes in astrocyte number, morphology, and function play an important role in the emergence of higher brain functions. However, research on astrocytes in enlarged, highly folded brains remains limited. To address this issue, we are investigating the molecular mechanisms that regulate astrocyte changes during evolution and their functional significance, using the ferret as a model system because of its well-developed brain structure. In this article, we provide an overview of our findings, focusing on the regulation of astrocyte number and its role in cortical folding.
Pharmacology department in medical schools performs an introductory practical training program where medical students first experience the medical practice of using drugs in a university setting. However, recent university budget cuts have led to a shortage of human resources, insufficient funding for practical training, and the simplification or promotion of online training due to the COVID-19 pandemic, as well as changes in student attitudes, creating a significant turning point. In this symposium, I presented the results of a survey on the current state of pharmacology laboratory courses at medical schools nationwide, discussed the challenges and difficulties faced by universities across the country. While new forms of practical training, such as joint role-play with other universities and VR practical training that is more accessible to students, have been identified, on the other hand, fewer universities are conducting practical training using animals to cultivate an understanding of the dangers of actual drugs, the importance of life, and the uncertainty of drug administration and the ability to respond to it. Reasons include the decreasing number of staff capable of conducting such experiments, the rising costs of experimental animals, and the limited participation of only some students. However, the educational and ethical benefits of such experiments remain high. Some universities show implementing various innovative training programs. It is essential to gather such insights and collaborate nationwide to develop training formats that, while efficient and rational for faculty, also benefit students in terms of ethical and humanistic development.
