To explore the potential function of interleukin-13 (IL-13), lipopolysaccharide (LPS) or PBS as a control was unilaterally microinjected into striatum of rat brain. Seven days after LPS injection, there was a significant loss of neurons and microglial activation in the striatum, visualized by immunohistochemical staining against neuronal nuclei (NeuN) and the OX-42 (complement receptor type 3, CR3), respectively. In parallel, IL-13 immunoreactivity was increased as early as 3 days and sustained up to 7 days post LPS injection, compared to PBS-injected control and detected exclusively within microglia. Moreover, GFAP immunostaining and blood brain barrier (BBB) permeability evaluation showed the loss of astrocytes and disruption of BBB, respectively. By contrast, treatment with IL-13 neutralizing antibody (IL-13NA) protects NeuN + neurons against LPSinduced neurotoxicity in vivo . Accompanying neuroprotection, IL-13NA reduced loss of GFAP + astrocytes and damage of BBB in LPS-injected striatum. Intriguingly, treatment with IL-13NA produced neurotrophic factors (NTFs) on survived astrocytes in LPS-injected rat striatum. Taken together, the present study suggests that LPS induces expression of IL-13 on microglia, which contributes to neurodegeneration via damage on astrocytes and BBB disruption in the striatum in vivo.

Nilotinib is used for treating patients with imatinib-sensitive or -resistant chronic myeloid leukemia (CML); however, nilotinib-resistant cases have been observed in recent years. In addition, a considerable number of patients receiving nilotinib developed diabetes. Metformin is a front-line drug for the treatment of type 2 diabetes, and several studies have shown that diabetes patients treated with metformin have reduced incidence of cancer. This study aimed to define the effect of metformin on CML cells to determine whether metformin overcomes nilotinib resistance, and to identify novel targets for the treatment of nilotinib resistance. Methods: We observed the effects of metformin and nilotinib on K562 and KU812 human CML cell lines. Nilotinib-resistant CML cell lines were generated by exposing cells to gradually increasing doses of nilotinib. Then, we investigated the driving force that makes resistance to nilotinib and the effect of metformin on the driving force. Results: Sub-toxic doses of metformin enhanced nilotinib efficacy by reducing Bcl-xL expression, which induces apoptosis in CML cells. Next, we generated nilotinib-resistant K562 and KU812 cell lines that overexpressed the c-Jun N-terminal kinase (JNK) gene. JNK silencing by a JNK inhibitor restored sensitivity to nilotinib. Furthermore, metformin was effective in decreasing phosphorylated JNK levels, restoring nilotinib sensitivity. Combined treatment with nilotinib and metformin was more effective than combined treatment with nilotinib and a JNK inhibitor in terms of cell proliferation inhibition. Conclusions: This study suggested that combination therapy with metformin and nilotinib may have clinical benefits of enhancing antileukemia efficacy and overcoming resistance to nilotinib.

Transient receptor potential vanilloid subtype 1 (TRPV1) on astrocytes prevents ongoing degeneration of nigrostriatal dopamine (DA) neurons in MPP⁺-lesioned rats via ciliary neurotrophic factor (CNTF). The present study determined whether such a beneficial effect of astrocytic TRPV1 could be achieved after completion of injury of DA neurons, rather than ongoing injury, which seems more relevant to therapeutics. To test this, the MPP⁺-lesioned rat model utilized here exhibited approximately 70~80% degeneration of nigrostriatal DA neurons that was completed at 2 weeks post medial forebrain bundle injection of MPP⁺. TRPV1 agonist, capsaicin (CAP), was intraperitoneally administered. CNTF receptor alpha neutralizing antibody (CNTFRαNAb) was nigral injected to evaluate the role of CNTF endogenously produced by astrocyte through TRPV1 activation on DA neurons. Delayed treatment of CAP produced a significant reduction in amphetamine-induced rotational asymmetry. Accompanying this behavioral recovery, CAP treatment increased CNTF levels and tyrosine hydroxylase (TH) activity in the substantia nigra pars compacta (SNpc), and levels of DA and its metabolites in the striatum compared to controls. Interestingly, behavioral recovery and increases in biochemical indices were not reflected in trophic changes of the DA system. Instead, behavioral recovery was temporal and dependent on the continuous presence of CAP treatment. The results suggest that delayed treatment of CAP increases nigral TH enzyme activity and striatal levels of DA and its metabolites by CNTF endogenously derived from CAP-activated astrocytes through TRPV1, leading to functional recovery. Consequently, these findings may be useful in the treatment of DA imbalances associated with Parkinson's disease.
Animals ; Antibodies, Neutralizing ; Astrocytes ; Capsaicin ; Ciliary Neurotrophic Factor ; Dopamine ; Dopaminergic Neurons ; Medial Forebrain Bundle ; Models, Animal ; Neurons ; Parkinson Disease ; Pars Compacta ; Rats ; Receptor, Ciliary Neurotrophic Factor ; Tyrosine 3-Monooxygenase

PURPOSE: Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. Nutrition risk screening aims to increase awareness and allow early recognition and treatment of cancer cachexia. Therefore, screenings should be brief, inexpensive, highly sensitive, and have good specificity. Simplified Nutritional Appetite Questionnaire (SNAQ) is a simple screening tool including four questions, and validated to predict weight loss within 6 months in community-dwelling adults and nursing home residents. Our study aimed to translate the SNAQ into Korean, and to assess the validity and reliability of the translated screening tool in advanced cancer patients. MATERIALS AND METHODS: The SNAQ was translated into Korean according to linguistic validation. The internal consistency of the SNAQ was evaluated by Cronbach's alpha coefficient. Test-retest reliability was evaluated using the intraclass correlation coefficient. Concurrent validity was evaluated by measuring the Pearson's correlation coefficient between the SNAQ and Mini-Nutritional Assessment (MNA) and Patient-Generated Subjective Global Assessment (PG-SGA). RESULTS: In the 194 patients included in full analysis set, cancer stage was predominantly metastatic (98.5%), the mean age was 60 years (range, 23 to 81 years), and the mean body mass index was 24 kg/m² (range, 15.6 to 39.6 kg/m²). According to MNA score ≤ 11, 57 patients (29.4%) were malnourished. The mean score (±standard deviation) of the Korean version of the SNAQ was 13.8±2.5 with a range of 6-19. Cronbach's alpha coefficient was 0.737, and intraclass correlation coefficient was 0.869. The SNAQ was moderately correlated with MNA (r=0.404, p < 0.001) and PG-SGA (r=–0.530, p < 0.001). A significant weight loss of > 5% of the original bodyweightwithin 6 months occurred in 46 of the 186 patients (24.7%). SNAQ score ≤ 14 predicted > 5% weight loss with a sensitivity of 56.5% and a specificity of 44.3%. CONCLUSION: The Korean version of the SNAQ had high validity and reliability. SNAQ is useful for the screening tool for advanced cancer patients. The SNAQ had a limitation to predict impending weight loss in advanced cancer patients.
Adult ; Appetite ; Body Mass Index ; Cachexia ; Humans ; Linguistics ; Longitudinal Studies ; Malnutrition ; Mass Screening ; Nursing Homes ; Nutrition Assessment ; Reproducibility of Results ; Sensitivity and Specificity ; Weight Loss

BACKGROUND: The shortage of human hearts for allotransplantation makes xenotransplantation a possible option for controllable organ providers. To detect acute xenograft rejection, invasive biopsy seems inevitable; however, this occasionally results in poor incision wound healing or infection. To date, no method of noninvasive imaging for early detection of xenograft rejection has been established. We hypothesized that ultrasound speckle tracking would better detect xenograft failure than routine left ventricular ejection fractions (EF). METHODS: From August 2013 to July 2015, a total of six cardiac heterotopic xenotransplants (α 1, 3-galactosyltransferase gene-knockout porcine heart) into cynomolgus monkeys were monitored with echocardiography every 3 to 7 days. M-mode and two-dimensional (2D)-EF measurements and myocardial strain analyses were performed. Cardiac xenograft pathology was reviewed from the immediate postoperative biopsy, as well as the necropsy. RESULTS: Myocardial speckle tracking analysis was feasible in all six cases. The longest survival was 43 days. Only one pathology-proven immunologic rejection occurred. Cardiac xenograft failure appeared as two types: a dilated pattern with decreased EF or a myocardial-thickening pattern with preserved EF. Both antibody-mediated rejection (n=1) and sepsis-induced myocardial dysfunction (n=2) revealed decreased radial or circumferential strains, but normal-range EF. Xenograft functional decline was significant with respect to radial or circumferential strain (P=0.028), but not to conventional M-mode or 2D-EFs (P=0.600, P=0.340, respectively). CONCLUSIONS: Radial and circumferential strains were significantly decreased in both types of xenograft failure, regardless of EF. Further studies are warranted to correlate the strain analysis and immunopathological details.
Biopsy ; Echocardiography ; Heart ; Heart Transplantation ; Heterografts ; Humans ; Macaca fascicularis ; Methods ; Pathology ; Stroke Volume ; Transplantation, Heterologous* ; Transplants* ; Ultrasonography ; Wound Healing

Autochthonous hepatitis E virus (HEV) is an emerging pathogen in developed countries, and several cases of acute HEV infection have been reported in South Korea. However, there have been no reports on HEV-associated Guillain-Barré syndrome (GBS) in Korea. We recently experienced the case of a 58-year-old Korean male with acute HEV infection after ingesting raw deer meat. Persistent cholestasis was resolved by the administration of prednisolone. At 2.5 months after the clinical presentation of HEV infection, the patient developed weakness of the lower limbs, and was diagnosed with GBS associated with acute hepatitis E. To our knowledge, this is the second report on supportive steroid therapy for persistent cholestasis due to hepatitis E, and the first report of GBS in a Korean patient with acute HEV infection.
Acute Disease ; Alanine Transaminase/blood ; Antibodies, Viral/blood ; Aspartate Aminotransferases/blood ; Bilirubin/analysis ; Cholestasis/*drug therapy ; Guillain-Barre Syndrome/complications/*diagnosis ; Hepatitis E/*diagnosis/etiology ; Hepatitis E virus/immunology ; Humans ; Immunoglobulin M/blood ; Liver/pathology ; Male ; Middle Aged ; Prednisolone/therapeutic use ; Republic of Korea ; Steroids/*therapeutic use

An endoscopic mucosal resection (EMR) is an effective and safe therapeutic technique for treating a patient with a laterally-spreading tumor (LST). Colonoscopic-procedure-related complications are noted to be about 2.8% worldwide, and a perforation is the most common. Most colon perforations cause pneumoperitoneum. However, a perforation within the retroperitoneal portion of the colon (rectum and some of sigmoid colon) may cause an extraperitoneal perforation, and the leaking free air may induce pneumoretroperitoneum, pneumomediastinum, and subcutaneous emphysema, depending on the amount of discharged air. Herein, we present the case of a patient with an extraperitoneal colon microperforation which manifested as pneumoretroperitoneum, pneumomediastinum, and subcutaneous emphysema after an EMR for a sigmoid LST, which was successfully treated with medical treatment and endoscopic clipping.
Colon ; Colon, Sigmoid ; Colonoscopy ; Humans ; Mediastinal Emphysema* ; Pneumoperitoneum ; Retropneumoperitoneum* ; Subcutaneous Emphysema*

BACKGROUND/AIMS: Providers may be hesitant to perform double-balloon enteroscopy (DBE) in the elderly because the increased number of co-morbidities in this population poses a greater risk of complications resulting from sedation. There are limited data on the use of DBE in the elderly. Here, we assessed the safety and efficacy of DBE in the elderly compared to those in younger patients. METHODS: We retrospectively analyzed the medical records of 158 patients who underwent 218 DBEs. Patients were divided into an elderly group (age > or =65 years; mean 71.4+/-5.4; n=34; 41 DBEs) and a younger group (age <65 years; mean 39.5+/-13.5; n=124; 177 DBEs). RESULTS: In both groups, the most common indication for DBE was obscure gastrointestinal bleeding. Mucosal lesions (33.3% vs. 60.9%; P=0.002) were the most common finding in both groups, followed by tumors (30.8% vs. 14.1%; P=0.036). The elderly were more likely to receive interventional therapy (51.3% vs. 23.5%; P=0.001). The diagnostic yield of DBE was slightly higher in the elderly group (92.3% vs. 86.5%; P=0.422), but was not statistically significant. The therapeutic success rate of DBE was 100% in the elderly group compared to 87.5% in the younger group (P=0.536). The overall DBE complication rate was 1.8% overall, and this rate did not differ significantly between the groups (2.6% vs. 1.7%; P=0.548). CONCLUSIONS: DBE is safe and effective in the elderly, and has a high diagnostic yield and high therapeutic success rate.
Aged* ; Double-Balloon Enteroscopy* ; Hemorrhage ; Humans ; Medical Records ; Retrospective Studies

Recently, increasingly invasive therapeutic endoscopic procedures and more complex gastrointestinal surgeries such as endoscopic mucosal resection, endoscopic submucosal dissection, and novel laparoscopic approaches have resulted in endoscopists being confronted more frequently with perforations, fistulas, and anastomotic leakages, for which nonsurgical closure is desired. In this article, we present our experiences with the use of over-the-scope clip (OTSC) for natural orifice transluminal endoscopic surgery (NOTES) closure, prevention of perforation, anastomotic leakages, and fistula closures. The OTSC is a valuable device for closing intestinal perforations and fistulas, for NOTES closure, and for the prevention of perforation after the excision of a tumor from the proper muscle layer. Furthermore, it seems to be quite safe to perform, even by endoscopists with little experience of the technique.
Anastomotic Leak ; Fistula ; Gastrointestinal Tract* ; Intestinal Perforation ; Natural Orifice Endoscopic Surgery ; Tertiary Care Centers*

Procedural sedation and analgesia (below PSA), which is used for induction of appropriate sedation and elimination of pain during many procedures, is particularly essential for children. Many other countries have pediatric PSA guidelines. PSA guidelines are also needed in Korea. We have developed pediatric PSA guidelines for Korea by reference review of pediatric PSA for standard and safe PSA practice in Korea. Pharmacologic and non-pharmacologic methods could be used for performance of ideal pediatric PSA. Pre sedation phase included assessment of patients, with accompanying personnel who have adequate knowledge and experience, and informed consent. For sedation phase, the route of medication should be determined, along with monitoring of patients and evaluation of the depth of sedation. This phase also included writing all of the PSA process, adverse events, and intervention. Considering the pain of the procedures, the time of procedures, necessity for immobilization, and characteristics of PSA medication, we decided on the PSA method. Procedures were categorized into three types according to the level of pain, anxiety, and immobilization. The first type was radiologic imaging, which requires immobilization. The second type of procedure involves a high level of anxiety and a low level of pain, such as simple suturing and lumbar puncture. The third type of procedure involves a high level of anxiety and a high level of pain, such as reduction of fracture and dislocation. After performance of the procedure, patients must be observed and monitored at a location where oxygen and airway management can be applied until they reach full recovery. Discharge information should be provided to competent parents. The main characteristics of Korean guidelines for pediatric PSA were as follows: 1. We emphasized assessment and monitoring of patients during and after PSA. 2. We suggested selection of medication by categorization of procedures according to the level of pain and anxiety. 3. We suggest that PSA be performed by two healthcare personnel; one should have adequate knowledge and experience in performance of PSA. More equipment, locations, and specialized personnel are needed for conduct of safe pediatric PSA practice in Korea.
Airway Management ; Analgesia ; Anxiety ; Child ; Conscious Sedation ; Delivery of Health Care ; Dislocations ; Humans ; Immobilization ; Informed Consent ; Korea ; Oxygen ; Parents ; Pediatrics ; Spinal Puncture ; Writing