Injury to brain transforms resting astrocytes to their reactive form, the hallmark of which is an increase in glial fibrillary acidic protein (GFAP), the major intermediate filament protein of their cell type. The overall glial response after brain injury is referred to as reactive gliosis. Glial-neuronal interaction is important for neuronal migration, neurite outgrowth and axonal guidance during ontogenic development. Although much attention has been given to glial regulation of neuronal development and regeneration, evidences also suggest a neuronal influence on glial cell differentiation, maturation and function. The aim of the present study was to analyze the effects of glial-hippocampal neuronal co-culture on GFAP expression in the co-cultured astrocytes. The following antibodies were used for double immunostaining chemistry; mouse monoclonal antibodies for confirm neuronal cells, rabbit anti GFAP antibodies for confirm astrocytes. Primary cultured astrocytes showed the typical flat polygonal morphology in culture and expressed strong GFAP and vimentin. Co-cultured hippocampal neurons on astrocytes had phase bright cell body and well branched neurites. About half of co-cultured astrocytes expressed negative or weak GFAP and vimentin. After 2 hour glutamate (0.5 mM) exposure of glial-neuronal co-culture, neuronal cells lost their neurites and most of astrocytes expressed strong GFAP and vimentin. In Western blot analysis, total GFAP and vimentin contents in co-cultured astrocytes were lower than those of primary cultured astrocytes. After glutamate exposure of glial-neuronal co-culture, GFAP and vimentin contents in astrocytes were increased to the level of primary cultured astrocytes. These results suggest that neuronal cell decrease GFAP expression in co-cultured astrocytes and hippocampal neuronal-glial co-culture can be used as a reactive gliosis model in vitro for studying GFAP expression of astrocytes.
Animals ; Antibodies ; Antibodies, Monoclonal ; Astrocytes* ; Axons ; Blotting, Western ; Brain ; Brain Injuries ; Chemistry ; Coculture Techniques* ; Glial Fibrillary Acidic Protein ; Gliosis ; Glutamic Acid ; Intermediate Filaments ; Mice ; Neurites ; Neuroglia ; Neurons ; Regeneration ; Vimentin

Purpose: Treatment for epilepsy primarily involves antiseizure medications (ASMs), which can be characterized using the clinical data warehouse (CDW) database. In this study, we compared retention rates and time to successful treatment for various ASMs to reflect both efficacy and adverse effects in patients with newly diagnosed epilepsy. Materials and Methods: We identified newly diagnosed epilepsy patients with ASM treatment for more than 12 months using CDW of a tertiary referral hospital. Clinical characteristics were compared between groups with successful and unsuccessful treatment. Cox regression analysis was performed to evaluate independent variables of age, sex, comorbidities, and attributes of ASM regimens. Results: Of 2515 eligible participants, 46.2% were successfully treated with the first ASM regimen, and 74.7% with all ASM regimens with the median time-to-treatment success of 14 months. Participants with second-generation ASM as the first ASM were more likely to be successfully treated with the first regimen compared to those with first-generation ASM (51.6% vs. 42.3%, p<0.001) and more successfully treated [hazard ratio (HR)=1.26; 95% confidence interval (CI): 1.15–1.39]. Overall, valproic acid was the most common ASM across a wide range of ages under 65 years, while levetiracetam in patients aged over 65 years or lamotrigine in female adult patients. Clinical factors associated with less favorable treatment outcomes included renal disease (HR=0.78; 95% CI: 0.66–0.92), liver disease (HR=0.65; 95% CI: 0.52–0.81), depression (HR=0.70; 95% CI: 0.57–0.84), and mechanical ventilation (HR=0.58; 95% CI: 0.50–0.67). Conclusion Second-generation ASMs have the advantage of more successful treatment with fewer ASM regimen changes compared with first-generation drugs. Various comorbid conditions as well as age and sex should be considered when selecting ASMs.

To evaluate the incidence of delayed enteral nutrition (EN) and identify avoidable causes of delay, we retrospectively reviewed medical records of 200 children (median age [range]; 37.5 [1-216] months) who stayed in the intensive care unit (ICU) for a minimum of 3 days. Among 200 children, 115 received EN following ICU admission with a median time of EN initiation of 5 days after admission. Of these, only 22 patients achieved the estimated energy requirement. A significant decrease in the final z score of weight for age from the initial assessment was observed in the non-EN group only (-1.3+/-2.17 to -1.57+/-2.35, P<0.001). More survivors than non-survivors received EN during their ICU stay (61.2% vs 30.0%, P=0.001) and received EN within 72 hr of ICU admission (19.8% vs 3.3%, P=0.033). The most common reason for delayed EN was gastrointestinal (GI) bleeding, followed by altered GI motility and hemodynamic instability. Only eight cases of GI bleeding and one case of altered GI motility were diagnosed as active GI bleeding and ileus, respectively. This study showed that the strategies to reduce avoidable withholding EN are necessary to improve the nutrition status of critically ill children.
Adolescent ; Child ; Child, Preschool ; Critical Illness ; Energy Intake ; Enteral Nutrition/*statistics & numerical data ; Female ; Gastrointestinal Hemorrhage/*diagnosis ; Gastrointestinal Motility ; Humans ; Ileus/*diagnosis ; Infant ; Intensive Care Units ; Male ; Nutritional Status ; Retrospective Studies ; Treatment Outcome ; Withholding Treatment/*statistics & numerical data

The causes and attributing factors of drug-induced liver injury (DILI) remain unclear as a result of exclusion-based diagnosis and low incidence. The aim of this study was to explore and evaluate potential drug-related causes and factors associated with DILI. Using electronic medical records (EMR) from the Seoul National University Bundang Hospital from 2003 to 2014, patients with DILI events were identified based on liver function test results. All patients with hepatic or biliary diseases were excluded. Patient characteristics, including demographics, clinical patterns, and severity of DILI were summarized and their associations were evaluated. Drugs frequently prescribed to patients exhibiting DILI within the month before their first DILI event compared to the total patient population were identified and the probabilities of hepatotoxicity associated with their use were assessed through examination of available reports. Among the 1,835 patients with laboratory test results, 1,023 were male and 1,053 were 65 years of age or older. Moderate DILI was dominant in older or male patients and cholestatic DILI tended to be more frequently identified in older patients of either sex. Cytarabine was the most frequently prescribed drug in DILI patients, followed by aprotinin and dopamine. Among the 30 most frequently prescribed drugs in DILI patients, 15 (50%) were identified as known hepatotoxic agents. In conclusion, this study evaluated differences in features of DILI among groups based on demographics and explored candidate drugs with possible associations with DILI, which has potential value reflecting real-world clinical practice.
Aprotinin ; Cytarabine ; Demography ; Diagnosis ; Dopamine ; Drug-Induced Liver Injury* ; Electronic Health Records* ; Humans ; Incidence ; Liver Function Tests ; Male ; Seoul

This retrospective study was conducted to determine whether increased length of hospital stay (LOS) and mortality are associated with nutritional risk upon hospital admission in gastrointestinal cancer patients, using a computerized screening tool developed by a university hospital. We included adult gastrointestinal cancer patients whose hospital stays ranged from 24 hours to 90 days. The sample included 4,345 patients. The average age of the patients was 60.5 +/- 11.4 years and 2,959 (68.1%) were males. The mean of LOS was 8.2 +/- 8.2 days and the mortality rate was 3.4% (n = 146). The majority of the patients were at low risk (LG) (n = 3,102 [71.4%]), while 779 patients (17.9%) were at moderate risk (MG), and 464 (10.7%) were at high risk (HG). In comparing the three groups based on nutritional risk, hospital LOS was significantly longer in the HG (11.4 +/- 11.4 days) than it was in the LG (7.7 +/- 7.9 days) and the MG (7.9 +/- 7.9 days) (p < 0.0001). Significant differences were found in the hospital mortality rate, which was the highest in the HG (13.6%) and the lowest in the LG (1.5%) (p < 0.0001). In the multiple logistic regression analysis, moderate-to-severe nutritional risk, increased age, and emergency admission were selected as significant variables for increased LOS and mortality. Further research is needed to evaluate the benefits of nutritional screening and intervention and their effect on outcomes in various disease populations.
Adult ; Emergencies ; Gastrointestinal Neoplasms* ; Hospital Mortality ; Humans ; Length of Stay* ; Logistic Models ; Male ; Mass Screening ; Mortality* ; Retrospective Studies

To determine blood alcohol concentration (BAC) by extrapolation, an understanding of basal pharmacokinetics is indispensable. Breath alcohol concentration (BrAC) has been used for the determination of body alcohol concentration replaced by BAC in Korea. Therefore, the determination of BAC/BrAC ratio is a key problem in alcohol pharmacokinetics. Among several factors, the ingested dose of alcohol and the allelic variation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) are the most significant factors influencing the pharmacokinetic parameters, particularly in the absorption and elimination phases. This study shows a detailed pharmacokinetic analysis of BAC and BrAC associated with genetic polymorphism including ALDH2 in 42 healthy Korean men. The change in the alcohol dose ingested influenced the maximum concentration (C(max)), the time to reach C(max) (T(max)), the absorption rate constant (K(01)), the area under the concentration-time curve (AUC(last)), and the hourly elimination rate. The conversion of wild-type 487Glu (ALDH2*1) to 487Lys (ALDH2*2) in human ALDH2 resulted in changes in C(max) (ALDH2*1/*1, 0.03+/-0.01 g/dL [+/-standard deviation] vs. ALDH2*1/*2, 0.05+/-0.004 g/dL [P<0.01]), AUC(last) (ALDH2*1/*1, 4.48+/-2.19 g.min/dL vs. ALDH2*1/*2, 7.52+/-1.26 g.min/dL [P<0.05]), and the BAC elimination rate (ALDH2*1/*1, 0.05+/-0.02 g/L/hr vs. ALDH2*1/*2, 0.09+/-0.01 g/L/hr [P<0.05]). Moreover, the comparison of BAC and BrAC by Bland-Altman plot showed good agreement, suggesting that the measurement of BrAC can be a good alternative for the determination of BAC, particularly in the post-absorption phase. These results provide fundamental information about the pharmacokinetics of alcohol and the determination of BAC in forensics.
Absorption ; Alcohols ; Aldehyde Dehydrogenase ; Forensic Sciences ; Humans ; Korea ; Male ; Pharmacokinetics* ; Polymorphism, Genetic