Shigeto Morimoto

Traditional Chinese Medicine and Kampo: A Review from the Distant past for the Future

Traditional Chinese medicine (TCM) is a complete system of healing that developed in China about 3000 years ago, and includes herbal medicine, acupuncture, moxibustion and massage, etc. In recent decades the use of TCM has become more popular in China and throughout the world. Traditional Japanese medicine has been used for 1500 years and includes Kampo-yaku (herbal medicine), acupuncture and acupressure. Kampo is now widely practised in Japan and is fully integrated into the modern health-care system. Kampo is based on TCM but has been adapted to Japanese culture. In this paper we review the history and characteristics of TCM and traditional Japanese medicine, i.e. the selection of traditional Chinese herbal medicine treatments based on differential diagnosis, and treatment formulations specific for the ‘Sho’ (the patients symptoms at a given moment) of Japanese Kampo - and look at the prospects for these forms of medicine.

Matrix extracellular phosphoglycoprotein (MEPE) is highly expressed in osteocytes in human bone

The matrix extracellular phosphoglycoprotein (MEPE) gene is highly expressed in tumors that cause oncogenic hypophosphatemic osteomalacia (OHO). MEPE is also known as one of the bone-tooth matrix proteins and is associated with bone mineralization. We developed a rabbit polyclonal antibody directed against recombinant human MEPE (rhMEPE) after cloning its cDNA from the cDNA library of a nasal tumor tissue causing OHO. Using this antibody, we analyzed the distribution of MEPE in human bones by immunohistochemistry. In bone specimens from normal subjects, MEPE was predominantly expressed by osteocytes and not by osteoblasts. In bone specimens from patients with osteomalacia, however, MEPE was focally expressed by deeply located osteocytes. We also compared the MEPE positivity of osteocytes in mineralized bone and non-mineralized osteoid obtained from patients with osteomalacia and osteoporosis. Among osteomalacia patients, MEPE positivity was seen in 87.5 ± 8.6% of the osteocytes from mineralized bone compared with 7.8 ± 6.4% of those from osteoid. Among osteoporosis patients, MEPE positivity was found in 95.3 ± 0.5% of the osteocytes from mineralized bone compared with 4.9 ± 5.7% of those from osteoid. MEPE was mainly expressed by osteocytes embedded in the matrix of mineralized bone from patients with osteomalacia or osteoporosis. Our data provide the first histological evidence that MEPE is predominantly expressed by osteocytes in human bone, with significant expression by osteocytes within mineralized bone.

Adiponectin, T-cadherin and Tumour Necrosis Factor-α in Damaged Cardiomyocytes from Autopsy Specimens

This study determined the presence of adiponectin, T-cadherin (an adiponectin receptor) and tumour necrosis factor-α (TNF-α) in damaged myocytes from autopsied patients with acute or old myocardial infarction (MI) or dilated cardiomyopathy (DCM), using immunohistochemical staining. The enrolled patients included eight with acute MI, six with old MI and seven with DCM. Four autopsied individuals with no cardiac lesions were also enrolled as controls. Adiponectin and TNF-α were not observed in normal myocytes from control subjects, but T-cadherin was weakly detected. Immunoreactivity for adiponectin and T-cadherin was observed at the periphery of damaged myocytes from MI and DCM patients; intracellular reactivity for TNF-α was also seen. There were no statistically significant differences in the degree of reactivity for each molecule in the myocytes between the MI and DCM patients. These results suggest that the presence of adiponectin and TNF-α in damaged myocytes may contribute to the processes of myocardial injury occurring in MI and DCM.

Adiponectin Replacement Therapy Attenuates Myocardial Damage in Leptin-deficient Mice with Viral Myocarditis

The effects of adiponectin replacement therapy on myocardial damage were studied in leptin-deficient (OB) mice with acute viral myocarditis. Encephalomyocarditis virus was injected intraperitoneally into OB and wild-type (WT) mice. One subgroup of OB mice received no intervention and another subgroup received daily adiponectin replacement, simultaneously with viral inoculation. Differences in heart weight, cardiac histological score, numbers of infiltrating or apoptotic cells in the myocardium and the immunoreactivity of adiponectin receptors in myocytes were determined. The reactivity of adiponectin receptor 1 in myocytes from OB mice on day 4 and day 8 after viral inoculation was significantly decreased compared with that in myocytes from WT mice; the OB mice also had elevated cardiac weights and severe inflammatory myocardial damage. Adiponectin replacement in OB mice inhibited the development of severe myocarditis by augmenting myocyte adiponectin receptor 1 reactivity. Exogenously administered adiponectin may inhibit the progression of viral myocarditis through binding to the adiponectin receptor 1 in leptin-deficient conditions.

Brain Atrophy in a Murine Model of Chronic Fatigue Syndrome and Beneficial Effect of Hochu-ekki-to (TJ-41)

Brain-derived neurotrophic factor (BDNF) is associated with the main symptoms of chronic fatigue sydrome (CFS) and neuron apoptosis. Nevertheless, no study has been performed directly to explore the relationship between CFS, BDNF and neuron apoptosis. We induced a CFS model by six injections of killed Brucella abortus antigen in BALB/c mice and treated them with Hochu-ekki-to (TJ-41). Daily running activity, body weight (BW), ratio of cerebral weight to BW (CW/BW) and expression levels of BDNF and Bcl-2 mRNA in the hippocampus were determined. The daily activity and CW/BW decreased significantly in the CFS model. BDNF and Bcl-2 mRNA expression levels in the hippocampus were suppressed in the CFS model and TJ-41 treated mice, while no significant difference was found between them. We improved a murine model to investigate the relationship between CFS and brain dysfunction. In this model, reduced daily activity might have been associated with decreased hippocampal BDNF mRNA expression, hippocampal apoptosis and brain atrophy. TJ-41 increased the daily running activity of the model, which was independent of brain recovery.

Genome-wide response to antihypertensive medication using home blood pressure measurements: a pilot study nested within the HOMED-BP study

BACKGROUND Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were randomly allocated to first-line treatment with a calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). METHODS We recruited 265 (93 for CCB, 71 for ACEI and 101 for ARB) patients who completed the genomic study. Home blood pressure was measured for 5 days off-treatment before randomization and for 5 days after 2-4 weeks of randomized drug treatment. Genotyping was performed by 500K DNA microarray chips. The blood pressure responses to the three drugs were analyzed separately as a quantitative trait. For replication of SNPs with p < 10(-4), we used the multicenter GEANE study, in which patients were randomized to valsartan or amlodipine. RESULTS SNPs in PICALM, TANC2, NUMA1 and APCDD1 were found to be associated with CCB responses and those in ABCC9 and YIPF1 were found to be associated with ARB response with replication. CONCLUSION Our approach, the first based on high-fidelity phenotyping by home blood pressure measurement, might be a step in moving towards the personalized treatment of hypertension.

Survey on geriatricians' experiences of adverse drug reactions caused by potentially inappropriate medications: Commission report of the Japan Geriatrics Society

Aim:  The Japan Geriatrics Society (JGS) developed the guidelines for medical treatment and its safety in the elderly and the list of potentially inappropriate medication use, a Japanese version of the Beers list, in 2005. The JGS working group in collaboration with the Japan Broadcasting Corporation conducted the survey to geriatricians to investigate their experiences of adverse drug reactions (ADR) caused by potentially inappropriate medications.

Depopulation with Rapid Aging in Minamisoma City After the Fukushima Daiichi Nuclear Power Plant Accident

To the Editor: On March 11, 2011, a strong earthquake (magnitude 9.0) occurred off the Pacific coast and hit the northeast of Japan, followed by devastating tsunamis, which destroyed many coastal cities. The three operating reactors at Fukushima Daiichi nuclear power plant shut down automatically just after this earthquake, but 41 minutes later, a massive wall of rolling water burst through the plant’s defenses and inundated the reactor buildings. The tsunami flooded emergency generators, leaving the plant without power for cooling systems while radioactive decay kept heating the cores. In the control room, plant workers desperately tried to run crucial instruments, using torches and car batteries scavenged from nearby vehicles, but the last line of emergency systems failed, and the three reactors melted down several days later. This process induced release of hydrogen gas, which caused explosions in the reactor buildings. People in Fukushima mistrust the actions of the government and the Tokyo Electric Power Company because of poor provision of accurate information concerning the plant accident, even 1 year and 4 months after the disaster. Volatile radioactive chemicals including iodine-131 and cesium137 started to spread into the air and sea. Investigation of radionuclide was conducted on bamboo sampled from six sites within a 25to 980-km radius of the Fukushima plant in July to August 2011. Strikingly high concentrations of radiocesium-134 and -137 activity were detected in mature leaves from Fukushima city (65 km from the Fukushima plant), in excess of 71 and 79 kBq/kg of dry weight (DW). In Kashiwa city (195 km from the plant), sample concentrations were in excess of 3.4 and 4.3 kBq/kg DW. In Toyohashi city (440 km from the plant), concentrations were below the measurable limits of up to 4.5 Bq/kg DW. Last summer, a comprehensive public health study was established with a large budget at Fukushima Medical University. This investigation was designed to follow up on the health of some 2 million people in the region for 30 years. According to the latest data (February 20, 2012), 99.3% of 9,747 people living in towns or villages close to the plant received an accumulated effective dose of less than 10 mSv during the first 4 months after the accident. The highest dose was 23 mSv, well below the acute exposure level (100 mSv) related to a slight increase in risk of malignant diseases. In Minamisoma, there were 305 disaster-associated deaths, 298 (97.7%) of which were in elderly adults. Minamisoma Municipal General Hospital, which is located in the evacuation area 20 km from the plant, has served as a regional core institute for evacuees. Medical care providers have been performing health monitoring and medical care, including vaccination programs, for more than 4,000 victims. In April 2012, the government released newly revised guidelines regarding the evacuation zones from the plant, but wide-area evacuation still continues in Fukushima. The population of 72,000 in Minamisoma before the accident decreased to approximately 10,000 just after the accident. On March 29, 2012, it had recovered to approximately 45,000. The proportion of those aged 65 and older increased from 25.9% to 32.1% (Figure 1A). In addition, the retention rate of population according to age group has dramatically changed (Figure 1B). Many younger than 40, especially infants, children, and young parents, moved out of the communities because of fear regarding radiation exposure, causing a rapid increase in the proportion of elderly people. In addition, loss of ordinary lifestyle may inhibit activities of daily living of older adults. Elderly adults dislike moving, and many continued to live there, suggesting the breakup of communities and families. The average age of the population in Minamisoma has increased by 14 years because of the nuclear disaster, with younger people leaving, whereas older people have stayed behind, reaching the level that it had been estimated it would reach by 2025. Similar events have been observed in Futaba county and Iitate village near Minamisoma. Public attention for the nuclear plant workers and people living in Fukushima is fading rapidly. We should continue to pay attention to depopulation with rapid aging, which may make rebuilding populations in stricken areas difficult.

Incidence of adverse drug reactions in geriatric units of university hospitals

Background:  Adverse drug reactions (ADR) in elderly people are often attributed to functional decline and polypharmacy.

Outbreak of norovirus gastroenteritis in elderly evacuees after the 2007 Noto Peninsula earthquake in Japan.

Although extending life is not primary in hospice care, treatment that willfully shortens survival can be perceived as lack of regard for the life, and consequently the dignity, of the patient. Patients, family, and staff fear that palliative measures may inadvertently hasten death. Clarifying the relationship between treatment and death is critical to allaying this apprehension. We studied patients whose opioid dose increased, because this dynamic might produce complications. Significantly longer survival in patients whose opioid dose increased bolsters previous findings that intensified opioid therapy correlates with longer survival. Those investigators suggested that higher doses might identify patients with greater pain hospitalized for analgesia with less-advanced disease, but in this study, increasing opioid dose correlated with longer hospice stays in patients with relatively low ultimate dosages and in patients not receiving opioids on admission to the hospice. One might object that the survival advantage associated with increasing opioid doses is the result of sicker patients dying so soon after admission that there was no opportunity to increase their analgesic therapy. This, however, was not the case in our population. The slopes of the curves show that the rate of mortality of inpatients receiving increasing opioid doses was still slower 1 week after admission. Another survey also found that patients whose opioid dose rose more quickly survived longer, although the advantage was not significant. The possibility that adequate pain relief might prolong life, perhaps through diminished catecholamine exposure, merits scrutiny.