• Biomolecules & Therapeutics
• /
• v.32 no.1
• /
• pp.154-161
• /
• 2024

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that causes progressive paralysis. L-Citrulline is a nonessential neutral amino acid produced by L-arginine via nitric oxide synthase (NOS). According to previous studies, the pathogenesis of ALS entails glutamate toxicity, oxidative stress, protein misfolding, and neurofilament disruption. In addition, L-citrulline prevents neuronal cell death in brain ischemia; therefore, we investigated the change in the transport of L-citrulline under various pathological conditions in a cell line model of ALS. We examined the uptake of [¹⁴C]L-citrulline in wild-type (hSOD1wt/WT) and mutant NSC-34/ SOD1^G93A (MT) cell lines. The cell viability was determined via MTT assay. A transport study was performed to determine the uptake of [¹⁴C]L-citrulline. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to determine the expression levels of rat large neutral amino acid transported 1 (rLAT1) in ALS cell lines. Nitric oxide (NO) assay was performed using Griess reagent. L-Citrulline had a restorative effect on glutamate induced cell death, and increased [¹⁴C]L-citrulline uptake and mRNA levels of the large neutral amino acid transporter (LAT1) in the glutamate-treated ALS disease model (MT). NO levels increased significantly when MT cells were pretreated with glutamate for 24 h and restored by co-treatment with L-citrulline. Co-treatment of MT cells with L-arginine, an NO donor, increased NO levels. NSC-34 cells exposed to high glucose conditions showed a significant increase in [¹⁴C]L-citrulline uptake and LAT1 mRNA expression levels, which were restored to normal levels upon co-treatment with unlabeled L-citrulline. In contrast, exposure of the MT cell line to tumor necrosis factor alpha, lipopolysaccharides, and hypertonic condition decreased the uptake significantly which was restored to the normal level by co-treating with unlabeled L-citrulline. L-Citrulline can restore NO levels and cellular uptake in ALS-affected cells with glutamate cytotoxicity, pro-inflammatory cytokines, or other pathological states, suggesting that L-citrulline supplementation in ALS may play a key role in providing neuroprotection.

• Childhood Kidney Diseases
• /
• v.5 no.2
• /
• pp.147-155
• /
• 2001

Purpose : IgA nephropathy(IgAN) and thin glomerular basement membrane disease(TGBMD) are common glomerular diseases that cause hematuria in childhood. IgAN has characteristics of IgA deposit as the sole or predominantly localized to the mesangium Recently, it has been reported that thinning of glomerular basement membrane(GBM) is commonly accompanied with precipitation of electron dense deposits in IgAN. We performed this study to examine the frequency of thinning of GBM among children with IgAN and to analysis tile correlation between urinary abnormalities and GBM thickness and furthermore to conduct comparative analysis of the clinical and pathological features of IgAN and TGBMD. Methods : This study summarizes data collected from Department of Pediatrics, Busan Paik Hospital, Inje Medical College. Data include 51 cases who were diagnosed as IgAN from 1995 to 2000, and 26 cases who were diagnosed as TGBMD from 1990 to 2000 by percutaneous renal biopsy. Results : Males accounted for 29/51($56.9\%$) patients with IgAN and 8/26($30.8\%$) of those with TGBMD. The clinical and laboratory features between IgAN and TGBMD were significantly different regarding the incidence of proteinuria(IgAN vs TGBMD: $43.1\%\;vs\;3.8\%$, p=0.001), the incidence of co-appearance of proteinuria with hematuria ($41.2\%\;vs\;3.8\%$, p=0.001), total amount of protein in 24 hours collected urine ($808{\pm}\;mg\;vs\;251{\pm}200.7\;mg$, p=0.001) and the incidence of proteinuria more than 1 gm in 24 hours collected urine ($23.5\%\;vs\;3.8\%$, p=0.01). On the contrary, there were no significant differences in the levels of serum albumin, creatinine, BUN, and Ccr between two groups. The mean thickness of GBM in patients with IgAN was $293.0{\pm}79.2\;nm$(139.7-461.9 nm) and $180.9{\pm}35.8\;nm$(110.5-229.5 nm) in patients with TGBMD. The mean GBM thickness revealed significantly thinner in TGBMD compared than those with IgAN (P=0.0001). The frequency of thickness being less than 250 nm was $37.4{\pm}34.4\%$ in IgAN and $93.0{\pm}7.0\%$ in TGBMD (P=0.0001). But there were no correlations between urinary abnormalities and GBM thickness in patients with IgAN. Conclusion : The thinning of GBM would be one of the common pathological findings in IgAN Moreover, there is no significant correlations between urinary abnormalities and GBM thickness in patients with IgAN, However, patients with IgAN tend to have significantly higher possibilities of proteinuria, co-appearance of proteinuria with hematuria and higher total amount of protein in 24 hours collected urine compared those with TGBMD. These differences might be play all important role as progressive prognostic indicators in patients with IgAN. (J Korean Soc Pediatr Nephrol 2001;5 : 136-46)

• Radiation Oncology Journal
• /
• v.16 no.4
• /
• pp.485-495
• /
• 1998

Purpose : The major goal of the therapy in the soft tissue sarcoma is to control both local and distant tumor. However, the technique of obtaining local control has changed significantly over the past few decades from more aggressive surgery to combined therapy including conservative surgery and radiation and/or chemotherapy. We retrospectively analyzed the treatment results of the postoperative radiation therapy of soft tissue sarcoma and its prognostic factor. Materials and Methods : Between March 1983 and June 1994, 50 patients with soft tissue sarcoma were treated with surgery and postoperative radiation therapy at Kang-Nam St. Mary's hospital. Complete follow up was possible for all patients with median follow up duration 50 months (range 6-162 months). There were 28 male and 32 female patients. Their age ranged from 6 to 83 with a median of 44 years. Extremity (58$\%$) was the most frequent site of occurrence followed by trunk (20$\%$) and head and neck (12$\%$). Histologically malignant fibrous histiocytoma (23$\%$), liposarcoma (17$\%$), malignant schwannoma (12$\%$) constitute 52$\%$ of the patients. Daily radiation therapy designed to treat all areas at a risk for tumor spread upto dose of 4500-5000 cGy. A shrinking field technique was then used and total 55-65 Gy was delivered to tumor bed. Twenty-five patients (42$\%$) received chemotherapy with various regimen in the postoperative period. Results : Total 41 patients failed either with local recurrence or with distant metastasis. There were 29 patients (48$\%$) of local recurrence. Four patients (7$\%$) developed simultaneous local recurrence and distant metastasis and 8 patients (13$\%$) developed only distant metastasis. Local recurrence rate was rather higher than of other reported series. This study included patients of gross residual, recurrent cases after previous operation, trunk and head and neck Primary This feature is likely explanation for the decreased local control rate. Five of 29 Patients who failed only locally were salvaged by re-excision and/or re-irradiation and remained free of disease. Factors affecting local control include histologic type, grade, stage, extent of operation and surgical margin involvement, lymph node metastasis (p<0.05). All 21 patients who failed distantly are dead with progressive disease at the time of this report. Our overall survival results are similar to those of larger series. Actuarial 5 year overall survival and disease free survival were 60.4 $\%$, 30.6$\%$ respectively. Grade, stage (being close association with grade), residual disease (negative margin, microscopic, gross) were significant as a predictor of survival in our series (p<0.05). Conclusion : Combined surgery and postoperative radiation therapy obtained 5 year survival rate comparable to that of radical surgery.

• Journal of Life Science
• /
• v.23 no.9
• /
• pp.1096-1103
• /
• 2013

Chronic traumatic encephalopathy (CTE), which is common in athletes, is a progressive neurodegenerative disease and a long-term consequence of repetitive closed head injuries. CTE is regarded as a chronic brain syndrome due to the effects of repetitive traumatic brain injury (TBI). Because neurotrophic factors are neuroprotective in models of brain and spinal cord injuries, we examined the effects of cerebrolysin, a mixture of various neurotrophic factors, on brain pathology in a mouse model of repetitive mild TBI (rmTBI), which is a good model of CTE. Five groups were created and treated as follows: groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control. We found that p-tau expression was increased in the pyramidal layer of the cortex and hippocampus, particularly the CA3 region, but not in the CA1 region and the dentate gyrus (DG). Intra-tail vein administration of cerebrolysin ($10{\mu}l$ of 1 mg/ml) after/during rmTBI treatment reduced p-tau expression in both the cortex and hippocampus. Histological analysis revealed mild astrocyte activation (increased expression of glial fibrillary acidic protein (GFAP)) but not microglia activation (ionized calcium binding adaptor molecule 1 (iba-1) expression) and peripheral macrophage infiltration (CD45). Additionally, administration of cerebrolysin after rmTBI resulted in reduced astrocyte activation. These observations in rmTBI demonstrated that cerebrolysin treatment reduces phosphorylation of tau and astrocyte activation, attenuates brain pathology, and mitigates function deficits in TBI. Taken together, our observations suggest that cerebrolysin has potential therapeutic value in CTE.

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

• Tuberculosis and Respiratory Diseases
• /
• v.59 no.1
• /
• pp.23-29
• /
• 2005

Background : Chronic obstructive lung disease is characterized by smoke-related, gradually progressive, fixed airflow obstructions. However, some studies suggested that a reversible bronchial obstruction is common in chronic obstructive lung disease. Such reversibility persists despite the continued treatment with aerosolized bronchodilators and it appears to be related to the diminution in symptoms. The isolated volume response to a bronchodilator is defined as a remarkable increase in the FVC in response to the administration of a bronchodilator whereas the $FEV_1$ remains unchanged. This has been suggested in patients with severe emphysema. Therefore, the aim of this study was to determine the relationship between the response to a bronchodilator and the severity of an airflow obstruction in COPD patients using the GOLD classification. Methods : This study examined 124 patients with an airway obstruction. The patients underwent spirometry, and the severity of the airflow obstruction was classified by GOLD. The response groups were categorized by an improvement in the FVC or $FEV_1$ > 12%, and each group was analyzed. Results : Most subjects were men with a mean age of $65.9{\pm}8.5$ years. The mean smoking history was $41.26{\pm}20.1$ pack years. The isolated volume response group had relatively low $FEV_1$ and FVC values compared with the other groups. (p<0.001) Conclusion : In this study, an isolated volume response to a bronchodilator is a characteristic of a severe airway obstruction, which is observed in patient with a relatively poorer baseline lung function.

• Journal of Chest Surgery
• /
• v.36 no.11
• /
• pp.812-819
• /
• 2003

Background: Left ventricular dysfunction is one of the important prognostic factors of early mortality and long-term survival after valve operation. We studied the intermediate term results of mitral valve reconstruction in patients with moderate to severe left ventricular dysfunction. Material and Method: Forty four patients who underwent mitral valve reconstruction with a left ventricular ejection fraction (EF) of <45% or less (20∼45%) from April 1995 through July 2001 were reviewed retrospectively. Ages ranged from 10 to 67 years (46∼14 years) and 32 patients were in NYHA class III-IV. The mitral valve diseases were regurgitation (MR) in 28 patients, stenosis(MS) in 10, and mixed lesion in 5. The etiologies of mitral valve disease were rheumatic in 20 patients, degenerative in 14, ischemic in 5, annular dilatation in 2, congenital in 2, and endocarditis in 1. Operatively, all patients had annuloplasty and/or various valvuloplasty techniques, and a total of 52 procedures were concomitantly performed. Total cardiopulmonary bypass and aortic crossclamp time were 160$\pm$57 minutes and 112$\pm$45 minutes respectively. Result: Two operative deaths occurred as a result of left ventricular failure (4.5%). After the mean follow-up of 39 months (range, 10∼83 months), there was no late death. Transthoracic echocardiography revealed no or grade I of MR in 29 patients (72.5%) and no or mild MS in 35 patients (87.5%). The actuarial survival at 5 years was 100%. Four patients required mitral valve replacement due to progressive mitral valvular disease. The actuarial freedom from valve-related reoperation at 5 years was 84$\pm$9%. Conclusion: This study suggests that mitral valve reconstruction in patients with moderate to severe left ventricular dysfunction offers good early and intermediate survival and acceptable freedom from valve-related reoperation, and it is the strategy for effective management for these patients.

• Journal of Periodontal and Implant Science
• /
• v.30 no.4
• /
• pp.851-870
• /
• 2000

The major goals of periodontal therapy is the functional regeneration of periodontal supporting structures already destructed by periodontal disease as well as the reduction of signs and symptoms of progressive periodontal disease. There have been many efforts to develop materials and therapeutic methods to promote periodontal wound healing. There have been increasing interest on the chitosan made by chitin. Chitin is second only to cellulose as the most abundant natural biopolymer. It is a structural component of the exoskeleton of invertebrates(e.g., shrimp, crabs, lobsters), of the cell wall of fungi, and of the cuticle of insects. Chitosan is a derivative of chitin made by deacetylation of side chains. Many experiments using chitosan in various animal models have proven its beneficial effects. The aim of this study is to evaluate the osteogenesis of chitosan on the calvarial critical size defect in Sprague Dawley rats. An 8 mm surgical defect was produced with a trephine bur in the area of the midsagittal suture. The rats were divided into two groups: Untreated control group versus experimental group with 50mg of soluble chitosan gel. The animals were sacrificed at 2, 4 and 8 weeks after surgical procedure. The specimens were examined by histologic, histomorphometric and radiodensitometric analyses. The results are as follows: 1. The length of newly formed bone in the defects was $102.91{\pm}25.46{\mu}m$, $219.46{\pm}97.81{\mu}m$ at the 2 weeks, $130.95{\pm}39.24{\mu}m$, $212.39{\pm}89.22{\mu}m$ at the 4 weeks, $181.53{\pm}76.35{\mu}m$ and $257.12{\pm}51.22{\mu}m$ at the 8 weeks in the control group and experimental group respectively. At all periods, the means of experimental group was greater than those of control group. But, there was no statistically significant difference between the two groups. 2. The area of newly formed bone in the defects was $2962.06{\pm}1284.48{\mu}m^2$, $5194.88{\pm}1247.88{\mu}m^2$ at the 2 weeks, $5103.25{\pm}1375.88{\mu}m^2$, $7751.43{\pm}2228.20{\mu}m^2$ at the 4 weeks and $8046.20{\pm}818.99{\mu}m^2$, $15578.57{\pm}5606.55{\mu}m^2$ at the 8 weeks in the control group and experimental group respectively. At all periods, the means of experimental group was greater than those of control group. The experimental group showed statistically significant difference to the control group at the 2 and 8 weeks. 3. The density of newly formed bone in the defects was $14.26{\pm}6.33%$, $27.91{\pm}6.65%$ at the 2 weeks, $20.06{\pm}9.07%$, $27.86{\pm}8.20%$ at the 4 weeks and $22.99{\pm}3.76%$, $32.17{\pm}6.38%$ at the 8 weeks in the control group and experimental group respectively. At all periods, the means of experimental group was greater than those of control group. The experimental group showed statistically significant difference to the control group at the 2 and 8 weeks. These results suggest that the use of chitosan on the calvarial defects in rats has significant effect on the regeneration of bone tissue in itself

• Journal of Korean Academy of Nursing
• /
• v.21 no.3
• /
• pp.396-417
• /
• 1991

In order that nursing care an essential quality of nursing practice be acceptable and satisfying, it is necessary that client's culture be respected and that nursing practice be appropriate to that culture. Since cultural elements are an important influence on health practices and life patterns related to medical treatment, recovery from and prevention of disease, nurses need to have an understanding and knowledge of social and cultural phenomena to aid in the planning of nursing interventions. To understand the health practices surrounding health and illness, the health beliefs and practices of both folk and professional healing systems should be ascertained. Cultural data are required to provide care of high quality to clients and to reduce possible conflict between the client and the nurse. It is nursing's goal to provide clients from various cultures with quality nursing care which is satisfying and valuable. The problem addressed by this study was to identify Korean health practices which would contribute to the planning of professional caring practice with the culture : ultimately this study was intended to make a contribution to the development of the science of nursing. The concrete objectives of this study were ; 1) to identify Korean health practices, 2) to interpret the identitial health practices through traditional cultural thought, and 3) to compare the Korean health practices with those of other cultures. The investigator used the ethnosceintific approach outlined by spradly in a qualitative study. To discover ancestral wisdom and knowledge related to traditional health practeces, the subjects of this study were selected from residents of a small rural mountain village in south west Korea, a place considered to be maintaining and transmitting the traditional culture in a relatively well -preserved state because of being isolated from the modern world. The number of subjects was 18, aged 71 to 89. Research data were collected from January 8 to March 31, 1990. Five categories of health practices were identified : “Manage one's own mind”, “Moderation in all thing”, “Live in accord with nature”, “Live in mutuality with others”, and “Live to the best of one's ability”. Values derived from these ways of thinking from Confucianism, Taoism and Buddhism help fashion a traditional way of life, examplified by the saying “Benifience to all”. Korean thought and philosophy is influenced primerily by Confucianism, Confucian principles of ethics, embedded deeply in the peoples' minds, form the idea that “heaven and human being are intimately united” based on concept that “heaven is, so to speak, reason”. Twoe Gae's theory of existential subjectivity develops the concept of self which is the basis of the spirit of reverence in modern Confucian philosophy. The human md is granted from heaven out of the idea of matter, and what control the mind is the spirit of reverence. Hence the idea of “The primacy of the mind" and provided that one should control one's own mind. The precepts of duty to parents, respect for elders and worship of ancestors, and moderation in all behavior put a restraint on life which directed that one live earnestly according to Nature's laws with their neighbors. Not only Confucianism, but also Buddism and Taoism have had an important effect upon these patterns of ideas. When compared with western culture, Korean health practices tend to be more inclusive, abstract and intuitive while westerner health practices found to be mere concrete, practical and personal. Values and beliefs based and pragmatism and existentialism infuence western civilization, Ethical values may be founded on utilitarianism, which considers what is good for the persons in their circumstances as the basis of conduct and takes a serious view of their practical lives including human aspirations rather than an absolute truth. These philosophical and ethical ideas are foundations for health practices related to active, practical and progressive attitudes. This study should be enable nursing not only to understand clients as reflections of the traditional culture when planning nursing practice, but to dovelop health education corresponding to cultural requiments for the purpose of protection against disease and improvement of health, and thus promote sound health practice. Eventually it is hoped that through these processes quality nursing care as the central idea of the science of nursing will be achieved.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.5
• /
• pp.953-961
• /
• 1998

Background : In recent years, lung cancer has been one of most common cause of death in Korea. Despite many physician's high degree of pessimism about the gains made in treatment, progressive improvement in the survival of lung cancer by treatment has occurred, particulary in the early stages of the disease. However, a lot of patients refuse treatment or give up in the fight against the disease. This study was done to evaluate factors influencing the compliance to therapy and to lead in the establishment of special programs to enhance compliance in patients with lung cancer. Methods: The medical records of 903 patients, whose ECOG(Eastern Cooperative Oncology Group) performance status was 3 or less and whose medical record was relatively satisfactory, among 1141 patients diagnosed with lung cancer between January 1989 and December 1996 were reviewed retrospectively. Compliance was classified into three groups based on the degree of compliance with physicians practice guideline: (a) compliants; (b) patients who initially complied but gave up of themselves midway during the course of treatment; (c) noncompliants who refused the treatment. Results: The overall compliance rate was 63.9%, which was progressively increased from 57.3-61.3% in 1989 and 1990 to 64.2-67.5% in 1995 and 1996. Age, education level and occupation of patients bore statistically significant relationship with the compliance but sex, marital status and smoking history did not. The compliance was significantly higher in patients without symptoms than with, and was also significantly higher in patients with good performance status. The compliance was significantly high in patients with NSCLC(non-small cell lung cancer) compared to SCLC(small cell lung cancer), but after exclusion of stage I and II, among NSCLC, which had higher compliance to surgery there was no significant difference of compliance by histology. The compliance was significantly lower in advanced stage. Conclusion: To enhance the compliance, special care including education programs about therapy including complication and prognosis are necessary, especially for educationally and economically disadvantaged patients.