Neuroinflammation, Oxidative Stress, and Neurogenesis in a Mouse Model of Chronic Fatigue Syndrome, and the Treatment with Kampo Medicine.

The diagnosis of chronic fatigue syndrome (CFS) is mainly symptom-based, and the etiology is still unclear. Here, we evaluated the pathological changes in the brain of a mouse model of CFS and studied the effects of Kampo medicine. A mouse model of CFS was established through six repeated injections of Brucella abortus (BA) every two weeks for a period of 12 weeks. Neuroinflammation was measured by estimating interleukin (IL)-1ß, IL-6, and interferon-gamma (IFN-γ), and oxidative stress by nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) 6 weeks after the last injection. Hippocampal neurogenesis was evaluated through Ki-67, doublecortin (DCX), and 5-bromodeoxyuridine (BrdU) assays. The effects of Kampo medicines (Hochuekkito (TJ-41) and Hachimijiogan (TJ-7)) on neuroinflammation during CFS were studied. The wheel-running activity of mice was decreased by about 50% compared to baseline at 6 weeks after the last BA injection. The levels of IL-1ß, IL-6, 3-NT, and 4-HNE were increased in both the cortex and the hippocampus of CFS mice at 6 weeks after the last BA injection. Hippocampal neurogenesis was unchanged in CFS mice. Treatment with TJ-41 and TJ-7 reduced the expressions of IL-1ß, IL-6, and IFN-γ in the hippocampus but not in the cortex. The results of the present study indicate that neuroinflammation and oxidative stress play important roles in the pathogenesis of CFS. The data further suggest that treatment with TJ-41 and TJ-7 could help reduce the inflammation associated with CFS in the hippocampus, but failed to improve the symptoms in CFS mice.

Induction Murine Models of Chronic Fatigue Syndrome by Brucella abortus Antigen Injections: Is Anemia Induced or Not?

To investigate whether Brucella abortus (BA) antigen injections lead to anemia, and to establish an appropriate Chronic Fatigue Syndrome (CFS) animal model by BA injections, 6 repeated injections of BA antigen were fulfilled every 2 weeks. At a high dose of 1∗10(10) particles/mouse, anemia was induced within 2 weeks and then recovered a lot at the end of the research, while at a moderate dose of 1∗10(8) (3 injections) shifting to 1∗10(9)/mouse (3 injections) anemia was absent. In both groups running wheel activity remained very low even 6 weeks after the last injection.

Elevated Serum Gamma-glutamyl Transpeptidase Levels and Fatty Liver Strongly Predict the Presence of Carotid Plaque.

AIM: There is a strong relationship between carotid atherosclerosis and future cardiovascular disease (CVD). This study sought to clarify the association of fatty liver and an elevated serum gamma-glutamyl transpeptidase (GGT) level with carotid atherosclerosis. METHODS: We reviewed the medical records of subjects who underwent medical checkups at our institute. Carotid atherosclerosis and fatty liver were assessed using ultrasound (US), and predictors of increased carotid intima-media thickness (IMT) and carotid plaque were identified using a logistic regression model. RESULTS: In total, 958 subjects (564 men, 394 women; median age, 59 years) were enrolled. The median value of the mean carotid IMT was 0.713 mm, and the frequency of carotid plaque was 19.5%. For the highest quartile of the mean carotid IMT (≥ 0.863 mm), a male sex, older age, hypertension (HT), dyslipidemia (DL) and type 2 diabetes mellitus (DM) were identified as independent predictors. A male sex, older age, HT and elevated serum GGT level were found to be significant predictors of the presence of carotid plaque. In addition, fatty liver correlated with the existence of carotid plaque. When the combination of the serum GGT level and presence or absence of fatty liver was included as a variable in the analysis, a male sex, older age, HT and fatty liver with a serum GGT level of ≥ 83 IU/L (90th percentile) (odds ratio 3.21, 95% confidence interval 1.27-8.12, p=0.014)were identified to be significantly associated with carotid plaque. CONCLUSIONS: This study suggests that the simultaneous presence of an elevated serum GGT level and fatty liver is highly predictive of carotid plaque.

Role of Kampo medicine in integrative cancer therapy.

Clinical trials to date demonstrate that standard cancer treatments are currently the most efficient treatments for large numbers of cancer patients. Cancer treatments will increasingly require approaches that allow patients to live with cancer, by increasing their natural healing power and tumor immunity, as well as attenuating the progression of their cancers, instead of only attacking the cancer cells directly. Complementary and alternative medicine, including Kampo medicine, compensates for the drawbacks of western medicine by increasing patients' self-defense mechanisms. In Japan, clinicians who have studied both western medicine and Kampo treat cancer patients by fusing the two medical systems into a unitary one. The goal of the system is to assist the functional maintenance and recovery of the living body complex with the physical, mental, social, and spiritual balance, rather than addressing direct antitumor effects. In this review, we describe the usefulness of Kampo medicine, especially juzentaihoto, and outline the reports on evidence, in addition to the report on an attitudinal survey about the use of Kampo medicine in cancer treatment in Japan.

Significance of Kampo, traditional Japanese medicine, in supportive care of cancer patients.

The current standard treatment for cancer is a multidisciplinary therapy whereby various types of treatment are properly combined. Chemotherapy with multiple anticancer drugs is now common, and traditional, complementary, and alternative therapies are adopted as supportive measures. Medical care in Japan is distinguished by the ability for patients to access both Western and Kampo medical cares at the same time. There is a high degree of trust in the safety of Kampo therapies because they are practiced by medical doctors who are educated with fundamental diagnosis of Western medicine. Highly reliable clinical studies are being published, demonstrating that palliative or supportive care for cancer patients using Kampo preparations alleviates adverse effects of chemotherapy or radiotherapy. This paper reports the circumstances around cancer care in Japan where traditional therapeutic Kampo formulas are used for patients undergoing cancer treatment with cutting-edge chemotherapy, specifically to alleviate adverse effects of anticancer drugs.

Perfusable tissue index obtained by positron emission tomography as a marker of myocardial viability in patients with ischemic ventricular dysfunction.

In areas of severe asynergy, the clinically important task is to identify functionally recoverable myocardium. Fourteen patients with asynergy were investigated by H2(15O) dynamic positron emission tomography imaging before revascularization. Regional myocardial blood flow (MBF) was determined and the water-perfusable tissue fraction (PTF) for each region of interest and the total anatomical tissue fraction (ATF) were estimated. The PTF/ATF was analyzed as the water perfusable tissue index (PTI). Asynergy was defined as segments with wall motion more than 2SD below than that of a normal population. An increase of >0.8SD in anterior wall segments with asynergy and an increase of >0.6 SD in inferior wall asynergy were defined as significant improvements of wall motion indicative of viable myocardium. Fifteen segments with wall motion abnormalities less than -2SD and 10 control segments were identified; 7 segments recovered and 8 segments did not. MBF was similar in both groups of segments before revascularization (0.78 +/- 0.27 vs 0.73 +/- 0.18 ml min-(-1) x g(-1), NS). The PTI in the recovered segments was significantly higher than that in the unimproved segments (0.734 +/- 0.058 vs 0.592 +/- 0.038, p<0.0001) and was similar to that of the control segments. After revascularization, the PTI correlated with the SD of wall motion (p<0.05, r=0.58). PTI may be a good predictor of contractile recovery after revascularization.