• Journal of Life Science
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• v.32 no.8
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• pp.611-621
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• 2022

Dimethyl sulfoxide (DMSO) is commonly used as control or vehicle solvent in preclinical research of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) due to its ability to dissolve lipophilic compounds and cross the blood brain barrier. However, the biochemical effects of DMSO on the outcomes of preclinical research are often overlooked. In the present study, we investigated whether the long-term oral administration of 5% DMSO affects the neurological, functional, and histological disease phenotype of the copper/zinc superoxide dismutase glycine 93 to alanine mutation (SOD1-G93A) mouse model of amyotrophic lateral sclerosis. SOD1-G93A transgenic mice showed shortened survival time and reduced motor function. We found that administration with DMSO led to increased mean survival time, reduced neurological scores, and improved motor performance tested using the rotarod and grip strength tests. On the other hand, DMSO treatment did not attenuate motor neuron loss in the spinal cord and denervation of neuromuscular junctions in the skeletal muscle. These results suggest that DMSO administration could improve the quality of life of the SOD1-G93A mouse model of ALS without affecting motor neuron denervation. In conclusion, the use of DMSO as control or vehicle solvent in preclinical research may affect the behavioral outcomes in the SOD1-G93A mouse model. The effect of the vehicle should be thoroughly considered when interpreting therapeutic efficacy of candidate drugs in preclinical research.

• The Korea Journal of Herbology
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• v.24 no.4
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• pp.127-135
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• 2009

Objectives : Gagam-Gongjin-dan (GGD) composited with Cervi parvum Cornu, Corni Fructus, Angelica gigantis Radix, Lycii Fructus, Dioscoreae Rhizoma, Citri Pericarpium, Gastrodiae Rihzoma, Agastachis Herba, Cassiae cortkex, Scutellariae Radix, Schisandrae Fructus has been traditionally used for chronic diseases or weakness after illness in oriental countries. However, little is known about the effects of methanol extract of GGD on immune responses to ovalbumin (OVA) plus alum. Therefore, the purpose of this study was to investigate the effects of GGD on immune responses to ovalbumin plus alum in Balb/c mice. Methods : In this study, the extract of GGD was prepared by extracting with methanol for 7 days. The extract was freeze-dried following filtration through vacuum distillation system. Mice were orally administrated with or without GGD extract of different doses (50-200 mg/kg/day) for 30 days. We examined the effects of GGD extract on the serum levels of total IgE, OVA-specific IgE, IgG1, IgG2a, and CTACK/CCL27 production and CCR10 expression in lymph node cells and body weight change and foot pad swelling responses in ovalbumin treated Balb/c. Results : The oral administration of GGD dose-dependently reduced the serum levels of total IgE, OVA-specific immunoglobulin (IgE, IgG1 and IgG2b) and CTACK/CCL27 production in ovalbumin treated BALB/c mice. The levels of CCR10 expression from lymph node cells of OVA treated mice were markedly suppressed by treatment with GGD in a concentration dependent manner. Furthermore, foot pad swelling responses were also markedly suppressed by GGD. However, body weight were significantly increased dose dependently by GGD treatment. Conclusions : These results suggest that GGD treatment suppresses immune responses to ovalbumin, and these properties may contribute to allergic disease care.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.4
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• pp.125-133
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• 2023

Purpose : This study aimed to analyze the antibacterial activity of Liriope platyphylla ethanol extract (LPEE) against Streptococcus mutans and Porphyromonas gingivalis and to validate its potential for the prevention and treatment of dental caries, gingivitis, and periodontal disease. Methods : To verify the antibacterial effect of L. pulsatilla ethanolic extract (LPEE) against S. mutans and P. gingivalis, the disk diffusion method was used to determine the inhibition zones at concentrations of 50, 100, 200, and 300 mg/㎖. To determine the minimum inhibition concentration (MIC), the final dose of LPEE was .2, .4, .8, 1.6, 2.5, and 5.0 mg/㎖, and the minimum bactericidal concentration (MBC) was determined based on the MIC results. To confirm the growth inhibitory effect of LPEE on both pathogens, the absorbance was measured at 600 nm after each incubation for 0, 3, 6, 12, and 24 hr at concentrations of .8, 1.6, 2.5, and 5.0 mg/㎖. Results : The cytotoxicity of LPEE was evaluated and the cell viability was more than 70 % at 400 mg/㎖. Therefore, concentrations of 50, 100, 200, and 300 mg/㎖ were used in this study. The antimicrobial effect against S. mutans was seen at 100 mg/㎖ and grew in a concentration-dependent manner, while P. gingivalis was effective at 50 mg/㎖ with the dose dependency. The MIC was .8 mg/㎖ for both strains, and the MBC was 1.6 mg/㎖ with the same results. The growth inhibitory effect of LPEE on S. mutans and P. gingivalis was observed, even at low concentrations. Conclusion : The antibacterial effect of LPEE was evaluated through the analysis of MIC, MBC, and growth inhibition effect on S. mutans and P. gingivalis, which suggests LPEE might have the possibility of utilization as a preventive and therapeutic composition for oral diseases.

• Korean Journal of Psychosomatic Medicine
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• v.32 no.1
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• pp.1-9
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• 2024

Frailty is a clinical syndrome as an increased vulnerability to stressors, leading to a decrease in physiologic reserves and a decline in the ability to maintain a good homeostasis. This condition leads to an increased risk of hospitalization, disability and mortality. Frailty occurs due to various causes and requires a multidimensional approach. It is also important to detect and manage it early. Frailty is also deeply related to neuropsychiatric problems such as pain and depression. In evaluating frailty, it is desirable to comprehensively consider not only physical areas such as disease, nutrition, movement, and sensory functions, but also psychosocial areas, and representative scales include Fried's physical frailty phenotype and Rockwood's frailty index. Physical activity and appropriate protein intake are important for frailty management, and inappropriate drug use should be reduced and oral care, cognitive function, and falls should also be noted. Frailty and pain can affect each other, and pain can promote frailty. Evidence has been published that hormone and protein abnormalities, immune system activity and inflammatory response, and epigenetic mechanisms work in common in the field of frailty and pain. More extensive and high-quality research should be conducted in the future, and the quality of life will be improved if the results are applied to the suppression and treatment of old age and pain.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.481-491
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• 2024

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (M^pro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in M^pro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the M^pro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC₅₀ values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

• Childhood Kidney Diseases
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• v.8 no.2
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• pp.176-185
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• 2004

Purpose: Rapidly progressive glomerulonephritis (RPGN) is a clinicopathologic entity characterized by extensive crescent formation and rapid deterioration of renal function within few months. For better understanding of its clinical course and designing better treatment strategies, a clinicopathological study of childhood RPGN was performed. Methods: The clinical manifestations and pathological findings were reviewed retrospectively in 12 children who were diagnosed as having RPGN by clinical manifestations and renal biopsy during a period from 1991 to 2003. Several clinicopathological parameters were analyzed as prognostic factors. Results: Among a total of 12 patients, 4 were male and 8 were female. The median onset age was 11.5 years(range 5.5-14.6 years), and the median period of follow-up was 25 months(range 7 months-6.6 years). According to the pathological classification, 10 patients (83%) were type II RPGN(immune-complex mediated glomerulonephritis), 2 patients were type III RPGN(pauci-immune glomerulonephritis), and none was type I RPGN(anti-glomerular basement membrane nephritis). All patients were treated with oral steroid in various combinations with methylprednisolone pulse therapy(10 patients, 83%), cyclophosphamide(8 patients, 67%), or plasmapheresis(4 patients, 33%). Clinical outcomes of 12 patients were complete remission in 1(8%), end-stage renal disease in 2(17%), chronic renal insufficiency with persistent proteinuria in 2(17%), and normal renal function with persistent proteinuria in 7(58%) at the last follow-up. Poor prognosis is associated with increased serum creatinine level, severe anemia and younger age at the time of diagnosis. Conclusion: Immune-complex mediated glomerulonephritis is the major cause RPGN in children and most cases showed improvement of renal function with aggressive management. For better understanding of this rare disease, a prospective multicenter study should be done.

• Journal of Life Science
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• v.21 no.5
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• pp.647-655
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• 2011

The neurotoxicity of aggregated amyloid ${\beta}$ ($A{\beta}$) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). It can cause neurotoxicity in AD by evoking a cascade of apoptosis to neuron. Here, we investigated the neuroprotective effects of cilostazol, which acts as a phosphodiesterase III inhibitor, on $A{\beta}_{25-35}$-induced cytotoxicity in mouse neuronal cells and cognitive decline in the C57BL/6J AD mouse model via peroxisome proliferator-activated receptor (PPAR)-${\gamma}$ activation. $A{\beta}_{25-35}$ significantly reduced cell viability and increased the number of apoptotic-like cells. Cilostazol treatment recovered cells from $A{\beta}$-induced cell death as well as rosiglitazone, a PPAR-${\gamma}$ activator. These effects were suppressed by GW9662, an antagonist of PPAR-${\gamma}$ activity, indicative of a PPAR-${\gamma}$-mediated signaling. In addition, cilostazol and rosiglitazone also restored PPAR-${\gamma}$ activity levels that had been altered as a result of $A{\beta}_{25-35}$ treatment, which were antagonized by GW9662. Furthermore, cilostazol also markedly decreased the number of apoptotic-like cells and decreased the Bax/Bcl-2 ratio. Intracerebroventricular injection of $A{\beta}_{25-35}$ in C57BL/6J mice resulted in impaired cognitive function. Oral administration of cilostazol (20 mg/kg) for 2 weeks before $A{\beta}_{25-35}$ injection and once a day for 4 weeks post-surgery almost completely prevented the $A{\beta}_{25-35}$-induced cognitive deficits, as did rosiglitazone. Taken together, our findings suggest that cilostazol could attenuate $A{\beta}_{25-35}$-induced neuronal cell injury and apoptosis as well as promote the survival of neuronal cells, subsequently improving cognitive decline in AD, partly because of PPAR-${\gamma}$ activation. The phosphodiesterase III inhibitor cilostazol may be the basis of a novel strategy for the therapy of AD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.1
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• pp.12-20
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• 2008

Purpose: Chronic pulmonary disease may be caused by aspiration of gastric contents secondary to gastroesophageal reflux. At present, there is no gold standard for documenting pulmonary aspiration. The purpose of this study was to investigate the usefulness of radionuclide scintigraphy in the detection of gastroesophageal reflux and pulmonary aspiration. Methods: Thirty-five patients with suspected aspiration pneumonia, and five normal control subjects, were included in the study. All subjects underwent gastroesophageal reflux scintigraphy after the ingestion of a $^{99m}Tc$-tin colloid mixture. Dynamic images to detect gastroesophageal reflux were obtained for 1 hour. Additional static images of the chest, to detect lung aspiration, were obtained at 6 and 24 hours after oral ingestion of the tin colloid. In addition to visual analysis, pulmonary aspiration was quantitated by counting the number of pixels labeled with radioactive isotope in the region of interest (ROI) of both lung fields. Aspiration index (AI) was obtained by subtracting the pixel counts of the background from the pixel counts of the ROI. Results: Among 35 patients with suspected aspiration pneumonia, 23 proved to have gastroesophageal reflux by scintigraphy. One patient showed definite pulmonary accumulation of activity by visual analysis of the 6-hour image. Thirty of 35 (85.7%) patients showed higher AI beyond the upper limit of AI in the healthy controls. When we compared the reflux group with the non-reflux group, there was a significantly higher AI at 6 hours in the reflux group (p<0.05). Conclusion: The results suggest that radionuclide scintigraphy is useful in detecting small pulmonary aspiration in patients with suspected aspiration pneumonia secondary to reflux.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7367-7369
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• 2013

Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-${\beta}$) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

• Clinical and Experimental Pediatrics
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• v.46 no.12
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• pp.1217-1223
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• 2003

Purpose : This study was conducted to assess clinical practices related to the evaluation and treatment of patients with acute gastrointestinal infection(AGI) in infants and children. This survey also evaluated the current opinion regarding the use of rotavirus vaccine. Methods : This survey was conducted using a self-administered questionnaire provided to 82 pediatricians in private clinics of Jeonbuk province. From April to June, 2002, 63 of 82 pediatricians(76.8 %) responded to the survey. Results : The annual proportion of patients with AGI was 13%. The highest proportion of patients with diarrhea were reported for the months of October through December. For the treatment of diarrhea, pediatricians preferred to prescribe lactobacillus products, oral rehydration solution, enzyme products, anti-emetics, anti-diarrheal formula, nothing by mouth(NPO) and bowel movement inhibitors in descending order of frequency. Most pediatricians(79.4%) prescribed antibiotics in less than 20% of patients with AGI. Amoxicillin was the most commonly prescribed antibiotics followed by trimethoprim/sulfamethoxazole(TMP/SMX) and amoxicillin/clavulanate. Clinical manifestations that pediatricians considered as important factors in prescribing antibiotics were bloody diarrhea, mucoid diarrhea, high fever, persisting disease and abdominal pain. Diagnostic procedures that pediatricians preferred for AGI patients were stool examination(rotavirus antigen, RBC, WBC), abdominal X-ray, and serum electrolytes. Pediatricians had a strong interest in rotavirus vaccine(71.4%). Conclusion : Acute gastrointestinal illness remains a common problem, especially during the winter months in Korea. AGI manifesting as watery diarrhea is appropriately treated with commonly available agents but pediatricians appear ready to consider additional approaches to decrease the sizable disease burden of AGI among children in Korea.