Water extract of guibi-tang (GB), a traditional Chinese, Japanese, and Korean herbal medicine, is used to treat memory impairment, insomnia, and peptic ulcers. The aim of this study was to investigate the protective effects of GB on pulmonary inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). C57BL/6 mice were used to develop a pulmonary inflammation model by exposing them to CS for 1 h per day for 7 days. LPS was intranasally administered to mice under mild anesthesia on day 5. GB was administered 1 h before CS exposure at doses of 50 or 100 mg/kg for 7 days. Our results showed that GB suppressed the CS and LPS induced elevation in inflammatory cell counts in the bronchoalveolar lavage fluid (BALF), with significant reductions in protein, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels. Histological studies revealed that GB decreased the inflammatory cell infiltration into lung tissue caused by CS- and LPS-exposure. GB also significantly decreased the CS and LPS-induced expression of inducible nitric oxide synthase (iNOS) in the lung tissue. Taken together, GB effectively attenuated airway inflammation caused by CS and LPS. These results indicate that GB is a potential therapeutic herbal formula for pulmonary inflammatory disease.
Anesthesia ; Animals ; Asian Continental Ancestry Group ; Bronchoalveolar Lavage Fluid ; Cell Count ; Herbal Medicine ; Humans ; Inflammation ; Interleukins ; Lung ; Memory ; Mice ; Nitric Oxide Synthase Type II ; Peptic Ulcer ; Pneumonia* ; Sleep Initiation and Maintenance Disorders ; Smoke* ; Tobacco Products* ; Tumor Necrosis Factor-alpha ; Water*

BACKGROUND: Ozone is well known as an important component of ambient air pollutants. Ozone can aggravate respiratory symptoms in patients with bronchial asthma, but, not in healthy person. We hypothesized asthma itself may show different response to ozone compared to nonasthma. OBJECTIVE: This study was performed to evaluate the differences of response to ozone between normal and asthmatic mice model in terms of status of oxidant injury and antioxidant activity. METHODS: Three parts per million of ozone was exposed to ovalbumin (OVA)-induced murine asthma model for 3 hours at 3, 7, 14, 21 days after completion of asthma model. Airway responsiveness to methacholine was measured after completion of asthma model. Bronchoalveolar lavage (BAL), protein extraction from lung for Western blot and immunohistochemistry of 4-hydroxy-2-nonenal (4-HNE), proliferating cell nuclear antigen (PCNA), NF-E2 related factor 2 (Nrf-2), and activity of glutathione were performed at before and each ozone exposure day. RESULTS: Airway hyper-responsiveness and increased eosinophils in BAL fluid were observed in asthma model. In asthma model, the expression of 4-HNE already more increased at baseline (without ozone) compared to those in sham model. This increased expression is more enhanced at 3 days after ozone exposure. The expression of PCNA was significantly increased in OVA-model compared to those in sham model. The expression of Nrf-2 was observed at baseline, and 3 and 7 days after exposure ozone in asthma model, but not in sham model. The activity of glutathione increased significantly after exposure of ozone, but not in sham model. CONCLUSION: Murine asthma model has enhanced oxygen toxicity and antioxidant activity response to ozone.
Air Pollutants ; Animals ; Antioxidants ; Asthma ; Blotting, Western ; Bronchoalveolar Lavage ; Eosinophils ; Glutathione ; Humans ; Immunohistochemistry ; Lung ; Methacholine Chloride ; Mice ; Ovalbumin ; Oxidants ; Oxygen ; Ozone ; Proliferating Cell Nuclear Antigen ; Respiratory Hypersensitivity

This study investigated the protective effects of diallyl disulfide (DADS) against acetaminophen (AAP)-induced acute renal injury in male rats. We also investigated the effects of DADS on kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), which are novel biomarkers of nephrotoxicity in renal tissues, in response to AAP treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) AAP (1,000 mg/kg), (3) AAP&DADS, and (4) DADS (50 mg/kg/day). AAP treatment caused acute kidney injury evidenced by increased serum blood urea nitrogen (BUN) levels and histopathological alterations. Additionally, Western blot and immunohistochemistry analysis showed increased expression of KIM-1 and NGAL proteins in renal tissues of AAP-treated rats. In contrast, DADS pretreatment significantly attenuated the AAP-induced nephrotoxic effects, including serum BUN level and expression of KIM-1 and NGAL proteins. Histopathological studies confirmed the renoprotective effect of DADS. The results suggest that DADS prevents AAP-induced acute nephrotoxicity, and that KIM-1 and NGAL may be useful biomarkers for the detection and monitoring of acute kidney injury associated with AAP exposure.
Acetaminophen ; Acute Kidney Injury ; Animals ; Biomarkers ; Blood Urea Nitrogen ; Blotting, Western ; Humans ; Immunohistochemistry ; Kidney ; Lipocalins ; Male ; Neutrophils ; Rats*

Despite a remarkable increase of deceased donors, organ shortage is the main hurdle of organ transplantation in Korea. Therefore, liver transplantation priority is a major issue of liver allocation. We confront a situation that needs to change in order to achieve more adequate and objective allocation of the system. We considered the MELD system as an alternative to the CTP score and Status system. For application of the MELD system, comparison between two systems is required; and a national-based retrospective review of liver transplantation candidates (waiting list) was conducted as a multi-center collaborative study. Eleven transplant centers participated in this national study. From 2009 to 2012, 2,702 waiting lists were enrolled. After mean 349+/-412 days follow-up, 967 patients (35.8%) of liver transplantation, 750 patients (27.8%) of drop-out/mortality, and 719 patients (26.6%) on waiting were identified. In analysis of patient mortality during waiting time, status system showed significant difference of waiting mortality by status at registration. However, differences of waiting mortality by MELD system were more prominent and discriminate. In comparisons by MELD score in exclusive Status 2A waiting patients, there was a significant difference of waiting mortality by MELD score. This means that the MELD system is a good predictor of short-term survival after listing compared with status system with CTP score. Korean national-based retrospective study showed the superiority of the MELD system in prediction of short-term mortality and usefulness as a determinant for allocation priority.
Cytidine Triphosphate ; Emergencies* ; End Stage Liver Disease ; Follow-Up Studies ; Humans ; Korea ; Liver Transplantation* ; Liver* ; Mortality ; Organ Transplantation ; Resource Allocation ; Retrospective Studies ; Survival Analysis* ; Tissue Donors* ; Transplants ; Waiting Lists

Panax ginseng, also known as Korean ginseng, has long been used as a broad tonic in Oriental medicine to augment vitality, health, and longevity, particularly in older people. This study investigated the effects of Korean red ginseng (RG) on bone loss in ovariectomized (OVX) mice. C3H/HeN mice (10-weeks-old) were divided into sham and OVX groups. OVX mice were treated with vehicle, 17beta-estradiol (E2), RG (oral administration, 250 mg/kg/day), or RG (intraperitoneal administration, 50 mg/kg/every other day) for 6 weeks. Serum E2 concentration and alkaline phosphatase (ALP) activity were measured. Tibiae were analyzed using microcomputed tomography. Biomechanical properties and osteoclast surface level were measured. There was no significant difference in the degree of grip strength, body weight, uterine weight, mechanical property, tibiae length, or tibiae weight between the OVX and RG-treated groups. Compared with the OVX group, the serum ALP level was significantly lower in the RG-treated groups. Serum E2 levels and osteoclast surface levels did not change between the OVX and RG-treated groups. RG could not preserve trabecular bone volume, trabecular bone number, trabecular separation, trabecular thickness, structure model index, or bone mineral density of the proximal tibiae metaphysic. In conclusion, there was no definite effect of RG on OVX-induced bone loss in C3H/HeN mice.
Alkaline Phosphatase ; Animals ; Body Weight ; Bone Density ; Female ; Hand Strength ; Longevity ; Medicine, East Asian Traditional ; Metaphysics ; Mice* ; Osteoclasts ; Osteoporosis ; Ovariectomy ; Panax* ; Tibia ; X-Ray Microtomography

Bone changes are common sequela of radiation therapy for cancer. The purpose of this study was to establish an experimental model of radiation-induced bone loss in adult mice using micro-computed tomography (microCT). The extent of changes following 2 Gy gamma irradiation (2 Gy/min) was studied at 4, 8, 12 or 16 weeks after exposure. Adult mice that received 1, 2, 4 or 6 Gy of gamma-rays were examined 12 weeks after irradiation. Tibiae were analyzed using microCT. Serum markers and biomechanical properties were measured and the osteoclast surface was examined. A significant loss of trabecular bone in tibiae was evident 12 weeks after exposure. Measurements performed after irradiation showed a dose-related decrease in trabecular bone volume fraction (BV/TV) and bone mineral density (BMD), respectively. The best-fitting dose-response curves were linear-quadratic. Taking the controls into accounts, the lines of best fit were as follows: BV/TV (%)= -0.071D2-1.799D+18.835 (r2=0.968, D=dose in Gy) and BMD (mg/cm3) = -3.547D2-14.8D+359.07 (r2=0.986, D=dose in Gy). Grip strength and body weight did not differ among the groups. No dose-dependent differences were apparent among the groups with regard to mechanical and anatomical properties of tibia, serum biochemical markers and osteoclast activity. The findings provide the basis required for better understanding of the results that will be obtained in any further studies of radiation-induced bone responses.
Adult ; Animals ; Biomarkers ; Body Weight ; Bone Density ; Hand Strength ; Humans ; Mice ; Models, Theoretical ; Osteoclasts ; Tibia ; X-Ray Microtomography

Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.
Animals ; Cranial Irradiation ; *Fast Neutrons ; Hippocampus/metabolism/physiology/*radiation effects ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Male ; Memory/physiology/*radiation effects ; Mice ; Mice, Inbred C57BL ; Microtubule-Associated Proteins/metabolism ; Neurogenesis/physiology/*radiation effects ; Neuropeptides/metabolism

Although peroxisome proliferator receptor (PPAR)-alpha and PPAR-gamma agonist have been developed as chemical tools to uncover biological roles for the PPARs such as lipid and carbohydrate metabolism, PPAR-delta has not been fully investigated. In this study, we examined the effects of the PPAR-delta agonist GW0742 on fatty liver changes and inflammatory markers. We investigated the effects of PPAR-delta agonist GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents and expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and monocyte chemo-attractant protein-1 (MCP-1) and also, PPAR-gamma coactivator (PGC)-1alpha gene were evaluated in liver tissues of OLETF rats and HepG2 cells after GW0742 treatment. The level of TNF-alpha and MCP-1 was also examined in supernatant of Raw264. 7 cell culture. To address the effects of GW0742 on insulin signaling, we performed in vitro study with AML12 mouse hepatocytes. Rats treated with GW0742 (10 mg/kg/day) from 26 to 36 weeks showed improvement in fatty infiltration of the liver. In liver tissues, mRNA expressions of TNF-alpha, MCP-1, and PGC-1alpha were significantly decreased in diabetic rats treated with GW0742 compared to diabetic control rats. We also observed that GW0742 had inhibitory effects on palmitic acid-induced fatty accumulation and inflammatory markers in HepG2 and Raw264.7 cells. The expression level of Akt and IRS-1 was significantly increased by treatment with GW0742. The PPAR-delta agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1alpha gene expression, and improvement of insulin signaling.
Animals ; Anti-Inflammatory Agents/*pharmacology/therapeutic use ; Blood Glucose ; Cytokines/genetics/metabolism ; Diabetes Mellitus/blood/immunology/metabolism ; Fatty Liver/blood/*drug therapy/immunology ; Glucose Tolerance Test ; Hep G2 Cells ; Humans ; Insulin Resistance ; Liver/metabolism ; Male ; PPAR delta/*agonists/metabolism ; Rats ; Rats, Long-Evans ; Thiazoles/*pharmacology/therapeutic use ; Triglycerides/metabolism

Since laparoscopic liver resection was first introduced in 2001, Korean surgeons have chosen a laparoscopic procedure as one of the treatment options for benign or malignant liver disease. We distributed and analyzed a nationwide questionnaire to members of the Korean Laparoscopic Liver Surgery Study Group (KLLSG) in order to evaluate the current status of laparoscopic liver resection in Korea. Questionnaires were sent to 24 centers of KLLSG. The questionnaire consisted of operative procedure, histological diagnosis of liver lesions, indications for resection, causes of conversion to open surgery, and postoperative outcomes. A laparoscopic liver resection was performed in 416 patients from 2001 to 2008. Of 416 patients, 59.6% had malignant tumors, and 40.4% had benign diseases. A total laparoscopic approach was performed in 88.7%. Anatomical laparoscopic liver resection was more commonly performed than non-anatomical resection (59.9% vs 40.1%). The anatomical laparoscopic liver resection procedures consisted of a left lateral sectionectomy (29.3%), left hemihepatectomy (19.2%), right hemihepatectomy (6%), right posterior sectionectomy (4.3%), central bisectionectomy (0.5%), and caudate lobectomy (0.5%). Laparoscopy-related serious complications occurred in 12 (2.8%) patients. The present study findings provide data in terms of indication, type and method of liver resection, and current status of laparoscopic liver resection in Korea.
*Hepatectomy/statistics & numerical data ; Humans ; *Laparoscopy/statistics & numerical data ; Liver/*surgery ; Liver Diseases/pathology/surgery ; Liver Neoplasms/pathology/surgery ; Postoperative Complications/epidemiology ; Questionnaires ; Republic of Korea

BACKGROUND: Vitamin D can translocate a vitamin D receptor (VDR) from the nucleus to the cell membranes. The meaning of this translocation is not elucidated in terms of a role in pathogenesis of chronic obstructive pulmonary disease (COPD) till now. VDR deficient mice are prone to develop emphysema, suggesting that abnormal function of VDR might influence a generation of COPD. The blood levels of vitamin D have known to be well correlated with that of lung function in patients with COPD, and smoking is the most important risk factor in development of COPD. This study was performed to investigate whether cigarette smoke extracts (CSE) can inhibit the translocation of VDR and whether mitogen activated protein kinases (MAPKs) are involved in this inhibition. METHODS: Human alveolar basal epithelial cell line (A549) was used in this study. 1,25-(OH2)D3 and/or MAPKs inhibitors and antioxidants were pre-incubated before stimulation with 10% CSE, and then nucleus and microsomal proteins were extracted for a Western blot of VDR. RESULTS: Five minutes treatment of 1,25-(OH2)D3 induced translocation of VDR from nucleus to microsomes by a dose-dependent manner. CSE inhibited 1,25-(OH2)D3-induced translocation of VDR in both concentrations of 10% and 20%. All MAPKs inhibitors did not suppress the inhibitory effects of CSE on the 1,25-(OH2)D3-induced translocation of VDR. Quercetin suppressed the inhibitory effects of CSE on the 1,25-(OH2)D3-induced translocation of VDR, but not in n-acetylcysteine. CONCLUSION: CSE has an ability to inhibit vitamin D-induced VDR translocation, but MAPKs are not involved in this inhibition.
Animals ; Antioxidants ; Blotting, Western ; Cell Membrane ; Emphysema ; Epithelial Cells ; Humans ; Lung ; Mice ; Microsomes ; Mitogen-Activated Protein Kinases ; Proteins ; Pulmonary Disease, Chronic Obstructive ; Quercetin ; Receptors, Calcitriol ; Risk Factors ; Smoke ; Smoking ; Tobacco Products ; Vitamin D ; Vitamins