In this study, we explored the potentiality of human arginine decarboxylase (ADC) to enhance the survival of mesenchymal stem cells (MSCs) against unfavorable milieu of host tissues as the low survival of MSCs is the issue in cell transplantation therapy. To address this, human MSCs overexpressing human ADC were treated with H2O2 and the resultant intracellular events were examined. First, we examined whether human ADC is overexpressed in human MSCs. Then, we investigated cell survival or death related events. We found that the overexpression of human ADC increases formazan production and reduces caspase 3 activation and the numbers of FITC, hoechst, or propidium iodide positive cells in human MSCs exposed to H2O2. To elucidate the factors underlying these phenomena, AKT, CREB, and BDNF were examined. We found that the overexpression of human ADC phosphorylates AKT and CREB and increases BDNF level in human MSCs exposed to H2O2. The changes of these proteins are possibly relevant to the elevation of agmatine. Collectively, our data demonstrate that the overexpression of human ADC stimulates pro-survival factors to protect human MSCs against H2O2 toxicity. In conclusion, the present findings support that ADC can enhance the survival of MSCs against hostile environment of host tissues.
Apoptosis/*drug effects ; Brain-Derived Neurotrophic Factor/metabolism ; Carboxy-Lyases/genetics/*metabolism ; Caspase 3/metabolism ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein/metabolism ; Humans ; Hydrogen Peroxide/*toxicity ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/cytology/drug effects/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism

PURPOSE: Paraquat is a lethal herbicide and induces acute renal failure, hepatic dysfunction, and progressive respiratory failure. The aims of this study are to investigate the correlation between plasma paraquat concentrations and initial laboratory data at Emergency Medical Center and to investigate whether initial laboratory data is useful for predicting outcomes of paraquat-poisoned patients. METHODS: A retrospective analysis by chart review was done on 83 patients who ingested paraquat and who had presented to Emergency center of within 24 hours. Plasma paraquat concentrations, urine dithionite test and initial laboratory parameters including white blood cell count, urine pH, and AST, ALT, BUN, Creatinine, Amylase, Glucose, pH, PaCO2, PaO2, HCO3. Base Excess, Na, K, Cl were obtained at the time of Emergency Center visit. We compared urine dithionite test, plasma paraquat concentrations and Severity Index of Paraquat Pisoning (SSPI) of the survival group to those of the dead group. The patients were divided into four subgroups based on the level of plasma paraquat concentration, their initial laboratory data was compared and analyzed. RESULTS: The mean plasma paraquat concentration in the mortality group was higher than that in the survival group (88.44+/-81.56 vs. 1.32+/-1.72 microgram/mL). Among the initial laboratory data of four subgroups, WBC, Glucose, Cr, pH, HCO3, Bass excess were significantly different between the group of low level of plasma paraquat concentration and higher group. ANCOVA analysis revealed that WBC, HCO3, Bass excess correlated with the level of plasma paraquat concentration significantly. CONCLUSION: The plasma paraquat concentration and SIPP were higher in the mortality group significantly. Initial laboratory data including WBC, Glucose, Cr, pH, HCO3, Bass excess were proven to be significant prognostic factors. Especially WBC, HCO3, Bass excess can be used to predict the outcome of paraquat poisoning.
Acute Kidney Injury ; Amylases ; Bass ; Creatinine ; Dithionite ; Emergencies ; Glucose ; Humans ; Hydrogen-Ion Concentration ; Leukocyte Count ; Paraquat ; Plasma ; Prognosis ; Respiratory Insufficiency ; Retrospective Studies

Objective: This study investigated the effect of TNF-α rs1800629 polymorphism on white matter integrity and memory function in patients with schizophrenia. Methods: Fifty-five participants with schizophrenia were enrolled in this study. They were genotyped for TNF-α rs1800629 polymorphism and underwent diffusion tensor imaging. Memory function was assessed using the Rey–Kim memory test. Participants with schizophrenia were grouped into GG homozygotes and A-allele carriers. Results: Compared to GG homozygotes, A-allele carriers had significantly lower scores for immediate and delayed recall and recognition of verbal memory and showed significantly lower fractional anisotropy in extensive brain regions. Lower total scores in immediate and delayed recall of verbal memory, immediate recall of visual memory, and figure copy of visual memory were significantly correlated with decreased mean fractional anisotropy in the white matter tracts of the corresponding brain regions. Conclusion Our findings suggest that the A-allele, which is associated with higher levels of TNF-α expression, correlates with lower connectivity of the fronto-temporal white matter compared to that in GG homozygotes. Impaired fronto-temporal connectivity may be associated with genetic vulnerability to schizophrenia, leading to verbal and visual memory deficits in patients with schizophrenia.

PURPOSE: A classic approach to abdominal stab wounds has been a routine laparotomy for the purpose of diagnosis or treatment. However, management protocols for abdominal stab wounds are still contentious in most trauma centers. We examined the relationship between the character of the stab wound and the injured intraabdominal organs by retrospectively analyzing the medical records of patients with abdominal stab wounds admitted to Gil hospital, and the findings for our patients are then confronted with a review of the literature. We aimed to propose proper management protocols to approach abdominal stab wounds. METHODS: The medical records of all 80 patients sustaining abdominal stab wounds, admitted at the Department of Surgery, Gil Hospital, Gachon Medical School, from January 2004 to December 2008 were retrospectively reviewed. All the abdominal stab wounds were collated based on the site and the character of the injury, investigations performed on admission, results of investigations, operations performed and findings at the time of the operation. RESULTS: The most prevalent age group was patients in their forties and the average age of the patients was 41 years for both genders. The stab wounds were most commonly located at the periumbilical area (16.9%), followed by the epigastric area (15.6%), and 18.2% of the patients had multiple wounds. The most commonly eviscerated organ was the omentum (9 out of 16 cases); 61.7% of non-eviscerated patients underwent a therapeutic laparotomy while 81.3% of eviscerated patients underwent a therapeutic laparotomy. The small bowel was the most commonly injured organ (22.7%, 17 out of 75 injuries). The review revealed a relatively common diaphragmatic injury in abdominal stab wound patients (8 cases, 10.5%). The average hospital stay was 11 days. CONCLUSION: This review revealed commonly eviscerated and injured intraabdominal organs in abdominal stab wound patients and their relationship with a therapeutic laparotomy. Although the management is still controversial, the authors suggest indications for an immediate laparotomy and a protocol for managing abdominal stab wounds. Hemodynamic instability and peritoneal irritation signs are definite indicators for an immediate laparotomy, but the review revealed intraabdominal organ evisceration alone not to be a statistically significant factor. In addition, the authors suggest that abnormal CT findings can be valuable for making a decision on management of hemodynamically stable stab wound patients. Further study may clarify a role for a more selective approach to operative intervention and for a more extensive use of selective observation.
Hemodynamics ; Humans ; Laparotomy ; Length of Stay ; Medical Records ; Multiple Trauma ; Omentum ; Retrospective Studies ; Schools, Medical ; Trauma Centers ; Wounds, Stab

PURPOSE: Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. MATERIALS AND METHODS: We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 microL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. RESULTS: Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and gamma-glutamyl cysteine synthetase, in the STZ-Agm group. CONCLUSION: Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD.
Agmatine/*therapeutic use ; Alzheimer Disease/*chemically induced/*drug therapy ; Animals ; Cognition Disorders/*chemically induced/*drug therapy ; Disease Models, Animal ; Male ; Rats ; Streptozocin/*toxicity

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are common and can be fatal. However, it is difficult to predict the in-hospital mortality, severity and prognosis of patients. Prognostic tools are needed to assess exacerbations of COPD in the emergency department. Towards this end, we compared DECAF (dyspnea, eosinopenia, consolidation, acidemia, atrial fibrillation) score with other prognostic tools available in the emergency department. METHODS: Consecutive patients admitted to the emergency department with exacerbations of COPD were recruited. We compared the DECAF score to CAPS (chronic obstructive pulmonary disease and asthma physiology score), BAP (blood urea nitrogen, altered mental status, pulse)-65 class and CURB (confusion, urea, respiratory rate, blood pressure)-65 score and assessed in-hospital mortality, endotracheal intubation, admission to the intensive care unit and admission to the hospital. RESULTS: The in-hospital mortality rate was 4.9%. The DECAF score showed excellent discrimination for in-hospital mortality (AUROC = 0.72, p = 0.002), endotracheal intubation (AUROC = 0.92, p < 0.001), admission to the intensive care unit (AUROC = 0.90, p < 0.001) and admission to the hospital (AUROC = 0.83, p < 0.001). CONCLUSIONS: The DECAF score is a simple and effective prognostic tool for assessing cases involving exacerbation of COPD in the emergency department. Emergency physicians should consider hospital admission if the DECAF score is more than 1 and consider admission to the intensive care unit and endotracheal intubation if the DECAF score is more than 3.
Asthma ; Discrimination (Psychology) ; Emergencies* ; Hospital Mortality ; Humans ; Intensive Care Units ; Intubation, Intratracheal ; Lung Diseases ; Lung Diseases, Obstructive ; Nitrogen ; Physiology ; Prognosis ; Pulmonary Disease, Chronic Obstructive* ; Respiratory Rate ; Urea

Animals ; Bone and Bones ; Bone Marrow ; Bone Regeneration ; Hydrogel ; Hydrogels ; Mesenchymal Stromal Cells ; Osteoblasts ; Osteogenesis ; Polyesters ; Polyethylene Glycols ; Rats ; Transplants

Fexuprazan (DWP14012), a potassium-competitive acid blocker, is a medical formulation prescribed to inhibit the secretion of gastric acid. The present study encompasses a comparative evaluation of pharmacokinetic (PK) analysis between the previous (reference) and size-reduced (test) formulation of fexuprazan 20 mg in healthy subjects. The study employed a randomized, open-label, single-dose, 2-sequence, 2-period, crossover design with a 7-day wash-out between periods. A total of 24 subjects were enrolled in this randomized study. During each period, the 21 subjects received either the test or reference formulation. Blood samples were collected at multiple time point ranging from 0 (pre-dose) to 48 hours post-dosing for PK analysis. The calculated PK parameters were considered bioequivalent when the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) were within the bioequivalence limit of 0.8–1.25. Safety and tolerability were included in the evaluation. A total of 20 subjects completed the study. Point estimates (90% CIs) of the GMRs were 1.1014 (0.9892–1.2265) for the maximum plasma concentration and 1.0530 (0.9611–1.1536) for the area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration, between the test and reference formulations.The reference and size-reduced test formulations of fexuprazan were well tolerated with no reports of serious adverse events. In conclusion, size-reduced and previous formulations of fexuprazan 20 mg were bioequivalent with regard to PKs, safety and tolerability.

Background: There is an incomplete understanding of the natural course of mild to moderate aortic stenosis (AS). We aimed to evaluate the natural course of patients with mild to moderate AS and its association with coronary artery disease (CAD). Methods: We retrospectively analyzed 787 patients diagnosed with mild to moderate AS using echocardiography between 2004 and 2010. Cardiac death and aortic valve replacement (AVR) for AS were assessed. Results: A median follow-up period was 92 months. Compared to the general population, patients with mild to moderate AS had a higher risk of cardiac death (hazard ratio [HR], 17.16; 95% confidence interval [CI], 13.65–21.59; P < 0.001). Established CAD was detected in 22.4% and associated with a significantly higher risk of cardiac mortality (adjusted HR, 1.62; 95% CI, 1.04–2.53; P = 0.033). The risk of cardiac death was lower when patients were taking statin (adjusted HR, 0.64; 95% CI, 0.41–0.98; P = 0.041), which was clear only after 7 years. Both patients with CAD and on statin tended to undergo more AVR, but the difference was not statistically significant (the presence of established CAD; adjusted HR, 1.63; 95% CI, 0.51–3.51; P = 0.214 and the use of statin; adjusted HR, 1.86; 95% CI, 0.76–4.58; P = 0.177). Conclusion Mild to moderate AS does not have a benign course. The presence of CAD and statin use may affect the long-term prognosis of patients with mild to moderate AS.

Background: There is an incomplete understanding of the natural course of mild to moderate aortic stenosis (AS). We aimed to evaluate the natural course of patients with mild to moderate AS and its association with coronary artery disease (CAD). Methods: We retrospectively analyzed 787 patients diagnosed with mild to moderate AS using echocardiography between 2004 and 2010. Cardiac death and aortic valve replacement (AVR) for AS were assessed. Results: A median follow-up period was 92 months. Compared to the general population, patients with mild to moderate AS had a higher risk of cardiac death (hazard ratio [HR], 17.16; 95% confidence interval [CI], 13.65–21.59; P < 0.001). Established CAD was detected in 22.4% and associated with a significantly higher risk of cardiac mortality (adjusted HR, 1.62; 95% CI, 1.04–2.53; P = 0.033). The risk of cardiac death was lower when patients were taking statin (adjusted HR, 0.64; 95% CI, 0.41–0.98; P = 0.041), which was clear only after 7 years. Both patients with CAD and on statin tended to undergo more AVR, but the difference was not statistically significant (the presence of established CAD; adjusted HR, 1.63; 95% CI, 0.51–3.51; P = 0.214 and the use of statin; adjusted HR, 1.86; 95% CI, 0.76–4.58; P = 0.177). Conclusion Mild to moderate AS does not have a benign course. The presence of CAD and statin use may affect the long-term prognosis of patients with mild to moderate AS.