Induction of liver transplant immune tolerance in an outbred rat strain model using tacrolimus / 한국실험동물학회지

Background@#Orthotopic liver transplantation is the only option for patients with end-stage liver disease and hepatocellular carcinoma. Post-transplant immunosuppressive therapy is important to prevent graft failure. We investigated the effectiveness of tacrolimus (FK506) and their mechanisms for liver transplant immune tolerance in an outbred rat LT model. @*Results@#To investigate the therapeutic effect of the FK506 on outbred rat LT model, FK506 and postoperative therapy were administered subcutaneously once or twice daily to transplanted rats. Histopathological and immunohistochemical analyses were conducted for all groups. The regulation of inflammatory cytokine signaling in the spleen was analyzed by flow cytometry. FK506 attenuated allograft rejection and increased survival in rat orthotopic liver transplantation models. The FK506-treated group had reduced serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Furthermore, FK506 decreased the expression of inflammatory cytokines and the activation of pathogenic Th1 and Th17 cells in the liver. @*Conclusions@#Taken together, we revealed that FK506 ameliorated strong allograft rejection in outbred liver transplantation model by anti-inflammatory effect and inhibitory peroperty of pathogenic T cells.

Metformin ameliorates experimental-obesity-associated autoimmune arthritis by inducing FGF21 expression and brown adipocyte differentiation

Rheumatoid arthritis (RA) is a systemic autoimmune disease involving excessive inflammation. Recently, RA associated with a metabolic disorder was revealed to be non-responsive to RA medications. Metformin has been reported to have a therapeutic effect on RA and obesity. The aim of this investigation was to study the therapeutic effect and the underlying mechanism of metformin's action in an experimental model of collagen-induced arthritis (CIA) associated with obesity. Metformin was administered daily for 13 weeks to mice with CIA that had been fed a high-fat diet. Metformin ameliorated the development of CIA in obese mice by reducing autoantibody expression and joint inflammation. Furthermore, metformin decreased the expression levels of pSTAT3 and pmTOR and had a small normalizing effect on the metabolic profile of obese CIA mice. In addition, metformin increased the production of pAMPK and FGF21. Metformin also induced the differentiation of brown adipose tissue (BAT), which led to a reciprocal balance between T helper (Th) 17 and regulatory T (Treg) cells in vitro and in vivo. These results suggest that metformin can dampen the development of CIA in obese mice and reduce metabolic dysfunction by inducing BAT differentiation. Thus, metformin could be a therapeutic candidate for non-responsive RA.

The Usefulness of Endoscopic Subtumoral Dissection for En-bloc Resection of Upper Gastrointestinal Submucosal Tumor / 대한소화기내시경학회지

BACKGROUND/AIMS: The removal of esophageal and gastric submucosal tumors is difficult using conventional endoscopic mucosal resection methods. This study examined the usefulness of an endoscopic subtumoral dissection for an en-bloc resection of submucosal tumors. METHODS: An endoscopic subtumoral dissection was attempted for an en-bloc resection in 15 submucosal tumors (M: F=10 : 5, 13 stomach, 2 esophagus). Before the procedures, endoscopic ultrasonography was performed in all cases. The procedure was carried out using various electrosurgical knives, such as an endoscopic submucosal dissection. RESULTS: Pathological and immunohistochemical studies confirmed a gastrointestinal stromal tumor in 6 cases. Other pathological diagnoses were made in 9 patients with submucosal lesions: leiomyoma (4), ectopic pancreas (3), lipoma (1), and hemangioma (1). An en-bloc resection was performed in 13 of the 15 tumors (86.7%). The mean specimen size was 29.5x21.1 mm. The mean procedure time was 49.4 minutes (range: 8~103 minutes). Gastric perforation was a complication in 2 cases with GIST. However, the two perforated cases were treated with endoscopic closure using endoclips and recovered without the need for surgery. CONCLUSIONS: An endoscopic subtumoral dissection technique is useful for an en-bloc resection of esophageal and gastric submucosal tumors. However, sufficient attention should be paid to the detection of perforations in the case of tumors with a proper muscle origin.

Safety and efficacy of propofol for sedative endoscopy in patients with compensated liver cirrhosis / 대한내과학회지

BACKGROUND/AIMS: Propofol is widely used for sedation during endoscopy. Because propofol may cause hepatic encephalopathy, hemodynamic compromise, and respiratory depression, cautious use is required in patients with liver cirrhosis. We evaluated the safety and efficacy of propofol in compensated cirrhosis during endoscopic examination. METHODS: Thirty-nine cirrhotic patients (19 and 20 cases of Child Pugh classes A and B, respectively) and 56 control subjects were included. The initial dose of propofol (40 mg) was increased by 20-mg increments until moderate sedation was achieved. The number connection test, flapping tremor test, blood pressure, heart rate, oxygen saturation, liver enzymes, and prothrombin time were evaluated before and after endoscopy. RESULTS: No significant change was observed in any parameter compared to baseline in either group. The mean dose of propofol was significantly lower in cirrhotic versus control subjects (49.7+/-15.8 versus 65.0+/-17.9 mg, respectively; p<0.001). Scores based on a visual analog scale evaluating patient satisfaction did not differ between groups (72+/-27 versus 64+/-26, respectively; p=0.196), nor did mean recovery time (16.4+/-9.8 versus 14.2+/-6.7 min, respectively; p=0.186). CONCLUSION: Propofol is safe and effective for moderate sedation in compensated liver cirrhosis.

Eradication Rate of First-line and Second-line Therapy for Helicobacter pylori Infection, and Reinfection Rate after Successful Eradication / 대한소화기학회지

BACKGROUND/AIMS: The increasing trend of antibiotic resistance emphasizes the need for the assessment of eradication rate of first and second-line therapy for Helicobacter pylori (H. pylori) infection. The reinfection rate depends on the geographical, national, or socioeconomic status of the patients. The aim of this study was to evaluate the recent 5-year changes of eradication rates and the reinfection rates after the successful eradication of Helicobacter pylori infection for 3-years follow-up in Bucheon, Korea. METHODS: From February 2001 to August 2006, 3,267 patients with H. pylori-positive peptic ulcer disease received the first-line therapy for 7 days. The 317 patients who failed to the first-line therapy received the second-line therapy for 7 days. The 167 patients with 3-years follow-up after the successful eradication were included. (13)C-urea breath tests or rapid urease tests and histologies were assessed to determine the H. pylori status after the eradication. RESULTS: The eradication rate of first-line therapy was 83.7% in 2001, 83.4% in 2002, 83.7% in 2003, 85.9% in 2004, 87.2% in 2005, and 81.8% in 2006 by per protocol analysis (PP), respectively. The eradication rate of second-line therapy was 80.0% in 2002, 86.8% in 2003, 89.7% in 2004, 98.0% in 2005, and 78.8% in 2006 by PP. The cumulative reinfection rate was 6.0%. The annual reinfection rate was 2.0%. The recurrence rate of peptic ulcer was 17.2% in the patients without reinfection and 50% with reinfection. CONCLUSIONS: The eradication rate for H. pylori have not changed in the recent 5-years. The annual reinfection rate was low. The successful eradication of H. pylori was effective for preventing the recurrence of peptic ulcers.

Effectiveness and Tolerance of Duodenoscopic Bowel Preparation for Colonoscopy / 대한소화기학회지

BACKGROUND/AIMS: Bowel preparation for colonoscopy remains an unpleasant experience because oral solutions have unpleasant tastes and may provoke abdominal pain, nausea, vomiting, and sleep disturbance. Duodenoscopic bowel preparation is an alternative method for patients who are unwilling to take oral preparation solution or for those who are supposed to have both gastroscopic and colonoscopic examination on the same day. We assessed the effectiveness and tolerance of duodenoscopic bowel preparation. METHODS: Patients in group OA (orally administered) ingested 45 mL of sodium phosphate (NaP) in the evening before the day of procedure and in the morning on the day of colonoscopy, whereas patients in group EA (endoscopically administered) were prepared for the procedure by duodenoscopic infusion of 90 mL of NaP diluted with 180 mL of water into the second portion of the duodenum. After 4 hours, we assessed the overall quality of colonic cleansing, using a range of excellent to inadequate. The patients completed a questionnaire on their preparation-associated symptoms, tolerance, and preference. RESULTS: In group EA, sleep disturbance (p<0.05) and nausea (p<0.05) occurred less frequently than in group OA. Overall, the tolerance rating for preparation was higher in group EA. However, the quality of colonic cleansing and cecum intubation time was not different between the two groups. Patients in group EA who had ingested NaP in the past preferred duodenoscopic bowel preparation. CONCLUSIONS: Duodenoscopic bowel preparation may play a role in colonic cleansing especially for patients who are scheduled to undergo gastroscopic and colonoscopic examination on the same day and for those who are unwilling to ingest NaP.

Effectiveness and Tolerance of Duodenoscopic Bowel Preparation for Colonoscopy / 대한소화기학회지

BACKGROUND/AIMS: Bowel preparation for colonoscopy remains an unpleasant experience because oral solutions have unpleasant tastes and may provoke abdominal pain, nausea, vomiting, and sleep disturbance. Duodenoscopic bowel preparation is an alternative method for patients who are unwilling to take oral preparation solution or for those who are supposed to have both gastroscopic and colonoscopic examination on the same day. We assessed the effectiveness and tolerance of duodenoscopic bowel preparation. METHODS: Patients in group OA (orally administered) ingested 45 mL of sodium phosphate (NaP) in the evening before the day of procedure and in the morning on the day of colonoscopy, whereas patients in group EA (endoscopically administered) were prepared for the procedure by duodenoscopic infusion of 90 mL of NaP diluted with 180 mL of water into the second portion of the duodenum. After 4 hours, we assessed the overall quality of colonic cleansing, using a range of excellent to inadequate. The patients completed a questionnaire on their preparation-associated symptoms, tolerance, and preference. RESULTS: In group EA, sleep disturbance (p<0.05) and nausea (p<0.05) occurred less frequently than in group OA. Overall, the tolerance rating for preparation was higher in group EA. However, the quality of colonic cleansing and cecum intubation time was not different between the two groups. Patients in group EA who had ingested NaP in the past preferred duodenoscopic bowel preparation. CONCLUSIONS: Duodenoscopic bowel preparation may play a role in colonic cleansing especially for patients who are scheduled to undergo gastroscopic and colonoscopic examination on the same day and for those who are unwilling to ingest NaP.

Two Cases of Severe Hyperglycemia after Overdose of Amlodipine / 대한신장학회잡지

Amlodipine, a calcium channel blocker (CCB) belonging to the group of dihydropyridines, is characterized by a slower onset of action (6-8h), a longer duration of action (24-72h), a greater vascular, cardiac effect, and hyperglycemia. Case of intoxication with 300 mg of amlodipine in a 69-year-old female patient and with 450 mg of amlodipine and 120 mg of glimepride in a 64-year-old female patient caused severe hypotension and hyperglycemia. They were initially treated with fluids, dopamine and norepinephrine, but these therapy were ineffective. Then, the patients were given a bolus injection of insulin and continuous infusion of insulin. The former patient's hyperglycemia was not controlled. She expired in 47 hours. The latter one's hyperglycemia was controlled and then her hypotension improved. In conclusion, it is suggested that hyperinsulinemia-euglycemia therapy be considered as a first-line therapy in calcium channel blocker intoxication.

A Case of Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Trachea and Colon / 결핵및호흡기질환

The 64-year-old female patient with cough and intermittent hemoptysis of six months duration visited our hospital. On chest computed tomography, a small, ovoid, 1.3cm sized and well enhanced lesion was detected on the distal trachea. Two multiple lobulated lesions on the sigmoid and transverse colon were revealed on the colonoscopy. The histological findings showed small and medium sized lymphocytes infiltration, CD20 and CD79a positive staining and multiple lymphoepithelial lesions on the distal trachea and colon tissues. Herein, a case of primary MALT lymphoma, with involvement of the trachea and colon, which was treated with rituximab (CD20 anti-monoclonal antibody), cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP regimen), is reported.

A Case of Pulmonary Sequestration Treated with Arterial Embolization / 결핵및호흡기질환

Pulmonary sequestration is a very rare congenital malformation in which a mass of pulmonary tissue is detached from the normal lung and receives its blood supply from a systemic artery. It may be clinically asymptomatic or it has a wide spectrum of various clinical manifestations. The clinical therapeutic approach is to resect the sequestered lobe to prevent frequent complication such as infection. The arterial embolization of feeding artery is a new technique and a less invasive treatment than conventional surgical removal. We have experienced a 17- year-old male with pulmonary sequestration whose complaints were pain in left lower chest. He was diagnosed by computed tomography and aortography and successfully treated with embolization of feeding artery. We report a case of pulmonary sequestration treated with arterial embolization instead of surgery.