Compound K, which was produced from ginsenosides of Panax ginseng in intestine, could protect liver injury.
BackgroundLiver cirrhosis is a diffuse hepatic fibrosis and nodule formation. The transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) are very important cytokines in hepatic fibrogenesis. The aim of this study was to examine the relationship between the changes of the serum cytokines and morphological changes following common bile duct ligation in experimental rats.MethodsCommon bile ducts of fifty male Sprague-Dawley rats were ligated and seven male rats were set aside as controls. Five rats each were sacrificed in 1, 2, 4, 6, 8, and 10 experimental weeks. Light microscopic studies and liver function tests were performed during the above experimental weeks. The levels of serum TGF-β1 and IL-10 were analyzed by ELISA. Also, alpha smooth muscle actin (α-SMA) immunohistochemical stains were performed.ResultsOn the eighth week after common bile duct ligation, most hepatic lobular areas had been replaced by proliferated bile ducts and fibrous tissue (typical biliary cirrhosis). Serum TGF-β1 levels between the control group and the common bile duct ligation group showed statistically significant changes. The α-SMA was stained at proliferated bile ducts. These findings were correlated with each other.ConclusionThus, this experiment may clarify our understanding of the mechanism in liver fibrogenesis. Also, indicated is a need to explore the therapeutic potential of these cytokines as anti-fibrotic agents.
BackgroundThe requirement for subsequent cholecystectomy in patients with gallbladder in situ after endoscopic removal of stones from the common bile duct (CBD) is controversial. The aims of this study were to assess the requirement for subsequent cholecystectomy for gallbladder-related symptoms, and to identify the patients who develop symptoms after the endoscopic removal of CBD stones.MethodsOf 241 patients with gallbladder in situ following endoscopic removal of stones from the CBD, 146 patients (78 men and 68 women; mean age 69±13 years, range 20–93) with a follow-up time of more than three months without elective cholecystectomy were enrolled in the study. Fifty-nine patients had gallbladder stones (single stones in 27 and multiple stones in 32) and 87 patients had gallbladder in situ without stones. The time from entry to the occurrences of death or cholecystectomy was evaluated retrospectively. Cox regression analysis was used to evaluate the risk factors associated with these events.ResultsThe mean duration of follow-up was 24.1±18.0 months (range 3–70 months). During follow-up, seven patients (4.8%) underwent cholecystectomy, on average 18.4 months after CBD stone removal, as the result of acute cholecystitis in four cases, biliary pain in two cases and acute pancreatitis in one case. Laparoscopic cholecystectomy was performed in four patients and open cholecystectomy in three patients. Post-operative morbidity occurred in two patients, with improvement after conservative management. Nine patients (6.2%) died as the result of unrelated biliary disease. Age, sex, presence of gallbladder stones, multiplicity of gallbladder stones and underlying disease did not correlate with subsequent cholecystectomy by Cox regression analysis.ConclusionElective cholecystectomy is not warranted in patients with bile duct stones when the common duct can be cleared of stones by endoscopic sphincterotomy. We could not find any clinical predictors of further symptoms or complications arising from the retained gallbladder.
Information on the molecular mechanisms of drug action is essential for the development of any potential chemotherapeutic. In this context, several cancer drugs have been shown to induce apoptosis in tumor cells.1) Apoptosis, known as programmed cell death, is a highly organized cell death process that is characterized by distinct morphological features, such as, cell shrinkage, chromatin condensation, plasma membrane blebbing, DNA fragmentation, and the breakdown of cells into smaller units (apoptotic bodies). 2)Many investigators have demonstrated that apoptosis is regulated by two major pathways. [3][4][5] The first pathway occurs via death receptors on the cell surface, such as, TNFR1 (tumor necrosis factor receptor 1) and Fas, the latter of which can directly activate procaspase-8 by DISC (death-inducing signaling complex), which includes the cytoplasmic tails of Fas receptors and procaspase-8.4) Caspase-8, in turn, activates the proteolytic caspase cascade that transmits and amplifies death signals by activating apoptotic executioner caspases like caspase-3 and -7. These executioner caspases then cleave several substrate proteins including poly (ADP-ribose) polymerase-1 (PARP-1), which results in the self-destruction of cells.6) Furthermore, interaction between Fas and FasL induces apoptotic cell death and altered levels of Fas/FasL expression have been implicated in the pathogenesis of diseases associated with immune regulation. 7,8) The second pathway regulates the apoptotic cascade via a convergence of signaling at mitochondria, such as, those signals mediated by Bcl-2 family proteins. This pathway involves altered mitochondrial membrane potentials, the release of cytochrome c into the cytosol, and the activation of procaspase-9, which is followed by the activations of effector caspases like caspase-3 and -7.5) The mitochondrial pathway, driven by Bcl-2 family proteins, may involves anti-apoptotic (Bcl-2 and Bcl-xL) or pro-apoptotic (Bax, Bak, and Bid), and regulates cell death by controlling mitochondrial membrane permeability during apoptosis. 9)Triterpenoids derived from plants are used for medicinal purposes in many Asian countries and some have been reported to have anti-tumor activity.10) Moreover, it was recently found that the novel synthetic triterpenoid methyl-2-cyano-3,12-dioxooleane-1,9-dien-28-oate potently induces caspase-mediated apoptosis in human lung cancer cells. 11)Furthermore, it is also known that the phytoterpenoid 3-oxoolean-12-en-27-oic acid (3-OA, a pentacyclic compound) is present in Aceriphyllum rossii ENGLER (Saxifragaceae), which grows in scant amounts in damp rocky areas in valleys in the central northern region of Korea.12) During recent years, pharmacological characterizations of 3-OA have concluded that it has several biological activities, which include; the protein tyrosine phosphatase 1B inhibitory activity, 13) acylCoA:cholesterol acyltransferase (ACAT) inhibitory activity, 12) and anti-complementary activity. 14) Furthermore, it has been demonstrated that 3-OA is c...
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