Chinese medicines as a resource for liver fibrosis treatment

Liver fibrosis is a condition of abnormal proliferation of connective tissue due to various types of chronic liver injury often caused by viral infection and chemicals. Effective therapies against liver fibrosis are still limited. In this review, we focus on research on Chinese medicines against liver fibrosis in three categories, namely pure compounds, composite formulae and combination treatment using single compounds with composite formulae or conventional medicines. Action mechanisms of the anti-fibrosis Chinese medicines, clinical application, herbal adverse events and quality control are also reviewed. Evidence indicates that some Chinese medicines are clinically effective on liver fibrosis. Strict quality control such as research to identify and monitor the manufacturing of Chinese medicines enables reliable pharmacological, clinical and in-depth mechanism studies. Further experiments and clinical trials should be carried out on the platforms that conform to international standards

岡山大学における核燃料物質の安全管理のための劣化ウランと天然ウランの鑑別について

In Japan, the Law for the Regulation of Nuclear Source Materials, Nuclear Fuel Materials and Reactors (Regulation Law) controls the nuclear fuel materials such as thorium (Th), uranium (U) and plutonium (Pu). Under the Regulation Law, all related materials and reactors are needed to register to the Government. In Okayama University, many nuclear fuel materials, mainly uranium compounds, are registered and stored in 11 departments, separately. Discrimination between depleted uranium and natural uranium is important for the observance of the Regulation Law and the safety management of the nuclear fuel materials in the Okayama University. However, the discrimination of the two kind of uranium has poorly analyzed. In this study, we analyzed several uranium compounds by using γ-ray spectrometry to determine whether the depleted uranium or not

Contrast-enhanced ultrasonography for the management of portal hypertension in cirrhosis

Portal hypertension is a major pathophysiological condition in patients with cirrhosis. This accounts for the occurrence and severity of the various manifestations. The degree is determined by the portal pressure or hepatic venous pressure gradients, both of which are obtained by invasive interventional radiological procedures. Ultrasound (US) is a simple and minimally invasive imaging modality for the diagnosis of liver diseases. Owing to the availability of microbubble-based contrast agents and the development of imaging modes corresponding to contrast effects, contrast-enhanced US (CEUS) has become popular worldwide for the detailed evaluation of hepatic hemodynamics, diffuse liver disease, and focal hepatic lesions. Recent advancements in digital technology have enabled contrast-based demonstrations with improved resolution, leading to a wider range of applications. This review article describes the current role, benefits, and limitations of CEUS in the management of portal hypertension

Imaging analysis reveals mechanistic differences between first- and second-phase insulin exocytosis

The mechanism of glucose-induced biphasic insulin release is unknown. We used total internal reflection fluorescence (TIRF) imaging analysis to reveal the process of first- and second-phase insulin exocytosis in pancreatic β cells. This analysis showed that previously docked insulin granules fused at the site of syntaxin (Synt)1A clusters during the first phase; however, the newcomers fused during the second phase external to the Synt1A clusters. To reveal the function of Synt1A in phasic insulin exocytosis, we generated Synt1A-knockout (Synt1A−/−) mice. Synt1A−/− β cells showed fewer previously docked granules with no fusion during the first phase; second-phase fusion from newcomers was preserved. Rescue experiments restoring Synt1A expression demonstrated restoration of granule docking status and fusion events. Inhibition of other syntaxins, Synt3 and Synt4, did not affect second-phase insulin exocytosis. We conclude that the first phase is Synt1A dependent but the second phase is not. This indicates that the two phases of insulin exocytosis differ spatially and mechanistically

Bordetella evades the host immune system by inducing IL-10 through a type III effector, BopN

The inflammatory response is one of several host alert mechanisms that recruit neutrophils from the circulation to the area of infection. We demonstrate that Bordetella, a bacterial pathogen, exploits an antiinflammatory cytokine, interleukin-10 (IL-10), to evade the host immune system. We identified a Bordetella effector, BopN, that is translocated into the host cell via the type III secretion system, where it induces enhanced production of IL-10. Interestingly, the BopN effector translocates itself into the nucleus and is involved in the down-regulation of mitogen-activated protein kinases. Using pharmacological blockade, we demonstrated that BopN-induced IL-10 production is mediated, at least in part, by its ability to block the extracellular signal-regulated kinase pathway. We also showed that BopN blocks nuclear translocation of nuclear factor κB p65 (NF-κBp65) but, in contrast, promotes nuclear translocation of NF-κBp50. A BopN-deficient strain was unable to induce IL-10 production in mice, resulting in the elimination of bacteria via neutrophil infiltration into the pulmonary alveoli. Furthermore, IL-10–deficient mice effectively eliminated wild-type as well as BopN mutant bacteria. Thus, Bordetella exploits BopN as a stealth strategy to shut off the host inflammatory reaction. These results explain the ability of Bordetella species to avoid induction of the inflammatory response

Deletion of CDKAL1 Affects Mitochondrial ATP Generation and First-Phase Insulin Exocytosis

A variant of the CDKAL1 gene was reported to be associated with type 2 diabetes and reduced insulin release in humans; however, the role of CDKAL1 in β cells is largely unknown. Therefore, to determine the role of CDKAL1 in insulin release from β cells, we studied insulin release profiles in CDKAL1 gene knockout (CDKAL1 KO) mice.Total internal reflection fluorescence imaging of CDKAL1 KO β cells showed that the number of fusion events during first-phase insulin release was reduced. However, there was no significant difference in the number of fusion events during second-phase release or high K(+)-induced release between WT and KO cells. CDKAL1 deletion resulted in a delayed and slow increase in cytosolic free Ca(2+) concentration during high glucose stimulation. Patch-clamp experiments revealed that the responsiveness of ATP-sensitive K(+) (K(ATP)) channels to glucose was blunted in KO cells. In addition, glucose-induced ATP generation was impaired. Although CDKAL1 is homologous to cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1, there was no difference in the kinase activity of CDK5 between WT and CDKAL1 KO islets.We provide the first report describing the function of CDKAL1 in β cells. Our results indicate that CDKAL1 controls first-phase insulin exocytosis in β cells by facilitating ATP generation, K(ATP) channel responsiveness and the subsequent activity of Ca(2+) channels through pathways other than CDK5-mediated regulation

Bear bile: dilemma of traditional medicinal use and animal protection

Bear bile has been used in Traditional Chinese Medicine (TCM) for thousands of years. Modern investigations showed that it has a wide range of pharmacological actions with little toxicological side effect and the pure compounds have been used for curing hepatic and biliary disorders for decades. However, extensive consumption of bear bile made bears endangered species. In the 1980's, bear farming was established in China to extract bear bile from living bears with "Free-dripping Fistula Technique". Bear farming is extremely inhumane and many bears died of illness such as chronic infections and liver cancer. Efforts are now given by non-governmental organizations, mass media and Chinese government to end bear farming ultimately. At the same time, systematic research has to be done to find an alternative for bear bile. In this review, we focused on the literature, laboratory and clinical results related to bear bile and its substitutes or alternative in English and Chinese databases. We examined the substitutes or alternative of bear bile from three aspects: pure compounds derived from bear bile, biles from other animals and herbs from TCM. We then discussed the strategy for stopping the trading of bear bile and issues of bear bile related to potential alternative candidates, existing problems in alternative research and work to be done in the future

Volume Reduction by the Incineration of the Combustible Radioactive Solid Samples from Radioisotope Usage at the Utilization Facility : Estimation of the Distribution of Low Energy β-Emitter Using the Imaging Plate

We want to establish a system of volume reduction by the incineration of the combustible radioactive solid wastes from radioisotope usage at the utilization facility. We have been performing experiments using an experimental incineration system to examine the distribution of radionuclides during incineration and to collect basic data. To reproduce the realistic conditions of incineration of low-level radioactive wastes in an experimental system, we adopted new incineration methods in this study. Low level radioactive samples (LLRS) were set up in a mesh container of stainless steel and incinerated at high temperature (over 800•Ž) generated by two sets of high calorie gas burners. Low energy ƒÀ-emitters 35S, 45Ca, 33P, and a high energy ƒÀ-emitter 32P were used for the experiment. Their translocation percentages in exhaust air and dust were estimated using the Imaging Plate. Distribution of radionuclides during the incineration was similar to that estimated by conventional methods by our study or to that reported in incineration of liquid scintillation cocktail waste. We concluded that the use of the Imaging Plates is a simple and reliable method for estimation of the distribution of low energy ƒÀ-emitters in incineration gas and ash

Volume Reduction by the Incineration of the Combustible Radioactive Solid Samples from Radioisotope Usage at the Utilization Facility : Estimation of the Distribution of Low Energy β-Emitter Using the Imaging Plate

We want to establish a system of volume reduction by the incineration of the combustible radioactive solid wastes from radioisotope usage at the utilization facility. We have been performing experiments using an experimental incineration system to examine the distribution of radionuclides during incineration and to collect basic data. To reproduce the realistic conditions of incineration of low-level radioactive wastes in an experimental system, we adopted new incineration methods in this study. Low level radioactive samples (LLRS) were set up in a mesh container of stainless steel and incinerated at high temperature (over 800•Ž) generated by two sets of high calorie gas burners. Low energy ƒÀ-emitters 35S, 45Ca, 33P, and a high energy ƒÀ-emitter 32P were used for the experiment. Their translocation percentages in exhaust air and dust were estimated using the Imaging Plate. Distribution of radionuclides during the incineration was similar to that estimated by conventional methods by our study or to that reported in incineration of liquid scintillation cocktail waste. We concluded that the use of the Imaging Plates is a simple and reliable method for estimation of the distribution of low energy ƒÀ-emitters in incineration gas and ash