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 - Clinical Medicine (Core Departments) - Clinical Sciences for Surgical Stresses
The original purpose of anesthesiology was reduction of surgery-induced pain. However, the present goal of anesthesiology is control of excessive biological responses induced by a variety of stresses and protection of patients from stress-induced complications. Clinical activity of this department is divided into anesthesia in the operation theater, pain control for a variety of diseases and critical care medicine. We aim to protect a living body from stresses including surgical stresses, pain, injuries and inflammation for the benefit of patients. Our ultimate goal is elucidation of mechanism for stress responses and development of treatment and care for suppression of excessive stress responses.

  Kazuhiko Fukuda, M.D., Ph.D.
Research and Education
The goal of research in this department is to elucidate mechanisms of responses induced by a variety of stresses and to develop management to control stress responses. Anesthetics and opioids have long been used to suppress stress responses induced by surgical stresses, and are clinically indispensable drugs today. However, the mechanisms of action of these drugs have not been completely understood. We are analyzing actions of anesthetics and opioids from many aspects. To analyze pharmacological actions of opioids at the molecular level, we have cloned cDNAs of opioid receptors, and have analyzed intracellular signal transduction mechanisms activated by opioids. Using genetically engineered mice, we are testing the role of the opioid receptor family in the pharmacological actions of inhaled anesthetics, and have demonstrated the possible involvement of the nociceptin receptor and the kappa-opioid receptor in the analgesic action of nitrous oxide. We have shown that benzodiazepines and local anesthetics potentiate corticotropin releasing factor-induced transcription of the proopiomelanocortin gene. During perioperative period, oxygen supply is often reduced by anemia and changes in the cardio-respiratory system, and organs are exposed to hypoxia, which induces hypoxic responses at the organ, cellular and molecular levels. We have analyzed hypoxia-inducible factor (HIF), which plays important roles in cellular hypoxic responses, and demonstrated that perioperatively used drugs and hypothermia can change cellular hypoxic responses by affecting HIF activity and gene expression controlled by HIF. The clinical research group in this department is attempting to develop comfortable anesthetic care for ambulatory surgery and automatic control of intravenous anesthesia.
This department is responsible for instruction and clinical training of anesthesiology and critical care medicine for undergraduate and postgraduate students. Residents are trained to obtain the basic capability of life support and anesthetic care in the operation room. Doctors aiming to be board certified anesthesiologists are trained for anesthetic management of special operations, intensive care for various systemic diseases and control of pain caused by various diseases.

Professor Kazuhiko Fukuda

Toshiyuki Arai

Hajime Segawa,
Kiichi Hirota,
Jiro Kurata

Masahiro Kakuyama,
Hidekatsu Furutani,
Hisanari Ishii,
Takehiro Shoda,
Hiroshi Tsujikawa,
Keiji Tanimoto,
Taizo Hisano,
Tomoharu Tanaka,
Toshiyuki Mizota,
Masami Sato,
Katsunori Yokoyama
Makiko Ikeura,
Tomohiro Koyama,
Toshie Habara
TEL +81-75-751-3433
FAX +81-75-752-3259
Predicted structure of the opioid receptors.
Cloning of the cDNAs and determination of the amino acid sequences demonstrated that the opioid receptors belong to the seven transmembrane receptor family.
Intracellular signal transduction mechanism mediated by the opioid
Activation of the opioid receptors induces a variety of cellular responses, including inhibition of adenylate cyclase, activation of the inwardly rectifier K+ channel and inhibition of the voltage-dependent Ca2+ channel, via activation of the G-protein. Furthermore, activation of mitogen-activated protein kinases by the opioid receptors leads to changes in gene expression and activation of phospholipase A2.
Effects of anesthetics on the hypoxia-inducible factor (HIF).
Propofol, an intravenous anesthetic, inhibits lipopolysaccharide-induced HIF-1 activation and changes in glucose metabolism in macrophage, by suppressing translation of HIF-1alpha from mRNA.
Clinical anesthesia in the operating theater
Staffs of the department of anesthesia perform anesthetic management and teach residents in the operating theater.
Recent Publications
1. Koyama, T., Mayahara, T., Wakamatsu, T., Sora, I. and Fukuda, K.: Deletion of mu-opioid receptor in mice does not affect the minimum alveolar concentration of volatile anesthetics and nitrous oxide-induced analgesia. Br. J. Anaesth. 103, 744-749 (2009).
2. Tsujikawa, H., Shoda, T., Mizota, T. and Fukuda, K.: Morphine induces DNA damage and P53 activation in CD3+ T cells. Biochim. Biophys. Acta 1790, 791-799 (2009).
3. Tanaka, T., Wakamatsu, T., Daijo, H., Oda, S., Kai, S., Adachi, T., Kizaka-Kondoh, S., Fukuda, K. and Hirota, K.: Persisting mild hypothermia suppresses hypoxia-inducible factor 1a protein synthesis and HIF-1-mediated gene expression. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298, R661-671 (2010).
4. Tanaka, T., Takabuchi, S., Nishi, K., Oda, S., Wakamatsu, T., Daijo, H., Fukuda, K. and Hirota, K.: The intravenous anesthetic propofol inhibits lipopolysaccharide-induced hypoxia-inducible factor 1 activation and suppresses the glucose metabolism in macrophages. J. Anesth. 24, 54-60 (2010).
5. Koyama, T. and Fukuda, K.: Involvement of the k-opioid receptor in nitrous oxide-
induced analgesia in mice. J. Anesth. 24, 297-299 (2010).