Abstract Background and Aim: Low levels of serum adiponectin have been reported to be associated with obesity, diabetes, and non‐alcoholic steatohepatitis (NASH), as well as several malignancies. Adiponectin knockout (KO) mice have been reported to cause insulin resistance and neointimal formation of the artery. We used adiponectin KO mice fed a high fat (HF) diet, and investigated the effect of adiponectin on the progression of steatohepatitis and carcinogenesis in vivo . Methods: Adiponectin KO mice and wild type (WT) mice were fed a HF diet or normal chow for the periods of 24 and 48 weeks. The HF diet contained 60% of calories from fat. Results: The adiponectin KO mice on the HF diet showed obesity, marked elevation of serum transaminase levels, and hyperlipidemia. At 24 weeks, hepatic expression of tumor necrosis factor‐α and procollagen α (I) was higher in KO mice as compared with WT mice. At 48 weeks, liver triglyceride contents in KO mice on normal chow were significantly higher than those in WT mice. Hepatocyte ballooning, spotty necrosis, and pericellular fibrosis around central veins were observed in KO mice on the HF diet. The pericellular fibrosis was more severe in KO mice on the HF diet than that in WT mice (1.62% vs 1.16%, P = 0.033). Liver adenoma and hyperplastic nodules developed in a KO mouse on the HF diet at 48 weeks (12.5%, n = 1/8), whereas no tumor was detected in WT mice ( n = 10). Conclusions: Adiponectin may play a protective role in the progression of NASH in the early stages by suppressing tumor necrosis factor‐α expression and liver fibrosis.
Abstract Protective effects of an aged garlic extract on the cardiotoxicity of doxorubicin (DOX) was evaluated using the mouse. DOX (1.5 mg/kg body wt ip) was administered three times per week for 40 days. An aged garlic extract, WG‐1 (a preserved stock solution; Wakunaga Pharmaceutical) was administered intraperitoneally six times weekly. DOX caused changes in the electrocardiogram. In the control mice, the width of the QRS complex was 20 ± 2.8 milliseconds, the R‐R interval was 130 ± 2.8 milliseconds, and the P‐Q interval was 30 ± 1.4 milliseconds. In mice treated with DOX for 40 days, the width of the QRS complex was 50 ± 10 milliseconds (p < 0.05), the R‐R interval was 240 ± 30 milliseconds (p < 0.05), and the P‐Q interval was 45 ± 1.0 milliseconds (p < 0.01). These values were significantly smaller in mice treated with WG‐1 + DOX than in mice treated with DOX. The width of the QRS complex was 29.3 ±5.8 milliseconds (p < 0.05), the R‐R interval was 145.8 ± 17.9 milliseconds (p < 0.01), and the P‐Q interval was 37.8 ± 3.5 milliseconds (p < 0.05). The lipid peroxidation in the heart homogenates prepared from DOX‐treated mice, as measured by thiobarbituric acid‐reactive substance (TBARS, nmol malondialdehyde/100 mg protein) was 332.5 ± 67.0, which was significantly larger than that in the control mice (186.6 ± 42.2) (p < 0.05). WG‐1 decreased the level of TBARS in DOX‐treated mice significantly. In the mice treated with WG‐1 + DOX, TBARS was 221.3 ± 31.6, which was significantly smaller than that of DOX‐treated mice (p < 0.05). Histological study demonstrated that the heart treated with DOX had vacuolization in muscle cells, disrupted myofibrils, and swollen mitochondria. Mice that received WG‐1 + DOX had no significant pathological lesions in the heart.
Ninety-two consecutive patients with unresectable hepatocellular carcinoma (HCC) greater than 2 cm and less than 5 cm in diameter were treated by transcatheter arterial chemoembolization using autologous blood clot as an embolizing agent (Short-TAE; S-TAE). Survival, patency of hepatic arteries and side effects were retrospectively analyzed. The median follow-up interval was 42 months. The median size of the main tumor was 3.4 cm in diameter. All tumors were determined to be inoperable because of intrahepatic spread of tumors and/or poor hepatic functional reserves. S-TAE was performed by injecting a mixture of iodized oil and anticancer drugs followed by embolization of hepatic arteries with autologous blood clot. Embolization with clots maintained patency of hepatic arteries in all the patients. The overall survival rates for 92 HCC patients at 1, 3, 5, 7 and 8 years were estimated by the Kaplan-Meier method to be 100, 52, 34, 12 and 6%, respectively, which were better compared with prior records for conventional method with gelfoam. S-TAE was successfully performed in 16 patients with Childs class C liver cirrhosis presenting icterus and ascitis. The survival rates for Childs class C patients at 1, 2 and 3 years were 100, 66 and 32%, respectively. The Cox proportional hazard model was used to assess influence of each pretreatment parameter (age, gender, virus marker, stage of cirrhosis, number of tumor) on survival. The univariate analysis demonstrated that both the stage of cirrhosis and the multiplicity of tumor were significant factors predicting survival (p=0.003 and 0.046, respectively). The multivariate analysis showed the stage of cirrhosis to be the sole factor which significantly affected prognosis of HCC patients (p=0.005). In conclusion, chemoembolization with autologous blood clot is an effective and safe therapeutic option for unresectable HCC smaller than 5 cm. The hepatic functional reserves play a key role in determining prognosis of HCC patients.
This is my response to the commentary written by Mr James Flowers with the title of 'What is Qi?' in the issue 4 of Vol.3 (2006) of eCAM. I will explain my opinions regarding the importance of Ki research, philosophical aspects of Ki and a possible role of Ki now and in the future.
'Ki-energy', which can be enhanced through the practice of Nishino Breathing Method, was reported to have beneficial health effects. Although Ki-energy can play an important role in complementary and alternative medicine (CAM), as yet it is unknown how Ki-energy is generated, transmitted through air and received by another individual. We previously proposed that Ki-energy may include near-infrared radiation, and that the wavelength was between 800 and 2700 nm. Since Ki-energy is reflected by a mirror, we believe that the 'Ki-beam' has a small divergence angle. It can also be guided in a desired direction. The acrylic mirror reflection experiment suggests that the wavelength may be between 800 and 1600 nm. Using a linear variable interference filter, we found that Ki-energy may have a peak around 1000 nm. We have also observed that 'sensitive' practitioners responded to Ki sent from a distance of 100 m. All of these results suggest that (i) Ki-energy can be guided as a directional 'beam' with a small divergence angle; (ii) the beam can be reflected by a mirror and (iii) Ki-energy may have a specific wavelength. Since these properties are characteristics of the laser radiation, we propose a quantum physics-based mechanism of 'Light Amplification by the Stimulated Emission of Radiation' (i.e. LASER) for the generation of Ki-energy. Volunteers responded to Ki even with a blindfold. This suggests that the skin must be detecting Ki-energy. We propose that the detector at the skin level may also have the stimulated emission mechanism, which amplifies the weak incident infrared radiation.
Antithymocyte globulin (ATG) is an effective immunosuppressive therapy for aplastic anemia (AA). We administered ATG combined with cyclosporine (CyA), to 9 patients (4 men and 5 women; median age, 55 years). AA was severe in 8 patients and moderate in 1. The ATG and CyA regimen was the initial treatment for 3 patients, but sequential treatment for the other 6, who were refractory to other agents. Peripheral T lymphocytes, including CD4-positive and CD8-positive cells, decreased rapidly after treatment. Although 1 patient died of pulmonary hemorrhage during the 6-month period following treatment with this combined regimen, 3 showed a favorable response, 2 moderate response, and 3 no response at all. Adverse drug reactions, including transient fever and rash, were not severe. These findings suggested that ATG and CyA in combination are a safe and effective immunosuppressive regimen for initial and refractory patients with AA.
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