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Heterogeneity in liver histopathology is associated with GSK-3β activity and mitochondrial dysfunction in end-stage diabetic rats on differential diets

  • Lee, Jun-Ho;Choi, Soo-Bong;Sung, Dong-Jun;Jin, Mingli;Lee, Ju-Han;Mun, Ji-Young;Hwang, Tae-Sook;Han, Sang-Don;Ro, Young-Tae;Kim, Sung-Young;You, Jueng-Soo;Lim, Inja;Noh, Yun-Hee
    • BMB Reports
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    • v.53 no.2
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    • pp.100-105
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    • 2020
  • While liver histopathology is heterogeneous in diabetes, the underlying mechanisms remain unclear. We investigated whether glycemic variation resulting from differential diets can induce heterogeneity in diabetic liver and the underlying molecular mechanisms. We generated end-stage non-obese diabetic model rats by subtotal-pancreatectomy in male Sprague-Dawley rats and ad libitum diet for 7 weeks (n = 33). The rats were then divided into three groups, and fed a standard- or a low-protein diet (18 or 6 kcal%, respectively), for another 7 weeks: to maintain hyperglycemia, 11 rats were fed ad libitum (18AL group); to achieve euglycemia, 11 were calorie-restricted (18R group), and 11 were both calorie- and protein-restricted with the low-protein diet (6R group). Overnight-fasted liver samples were collected after the differential diets together with sham-control (18S group), and histology and molecular changes were compared. Hyperglycemic-18AL showed glycogenic hepatopathy (GH) without steatosis, with the highest GSK-3β inactivation because of Akt activation during hyperglycemia; mitochondrial function was not impaired, compared to the 18S group. Euglycemic-18R showed neither GH nor steatosis, with intermediate GSK-3β activation and mitochondrial dysfunction. However, euglycemic-6R showed both GH and steatosis despite the highest GSK-3β activity and no molecular evidence of increased lipogenesis or decreased ApoB expression, where mitochondrial dysfunction was highest among the groups. In conclusion, heterogeneous liver histopathology developed in end-stage non-obese diabetic rats as the glycemic levels varied with differential diets, in which protein content in the diets as well as glycemic levels differentially influenced GSK-3β activity and mitochondrial function in insulin-deficient state.

Morbidity and Medical Facilities Utilization Patterns of High School Students in Urban and Rural Areas (도시(都市)와 농촌(農村), 고등학생(高等學生)의 상병(傷病) 및 의료이용(醫療利用) 양상(樣相))

  • Kim, Sung-Pha;Park, Jae Yong
    • Journal of the Korean Society of School Health
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    • v.3 no.2
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    • pp.96-108
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    • 1990
  • This study was conducted to assess the morbidity and medical facilities utilization patterns of high school students in urban and rural areas, and to contribute to establishment of school health policies. A questionnaire survey was carried out for 1,979 of one boy's and one girl's high school in Pusan and 1,315 of one boy's and one girl's high school in Kyungnam province from March 27 to April 8, 1989. The summarized result is as follows. The number of students who were sick or injured in one month period was 378.0 of 1,000 students. One sick or injured student experienced 1.2 events on the average and thus the incidence rate was 453.2 per 1,000 students for a month. The morbidity rate of the urban area (550.8) was higher than that of the rural area (306.5) while the rate for girl students (561.9) was higher than that of the boy students (328.3) (P<0.01). Especially, the girl students (740.7) in the urban area showed two times higher morbidity rate than that of the girl students in the rural area. Out of all morbidity respiratory disease for 67.6 percent in urban area and 68.5 percent in rural area and it was followed by gastrointestinal disease and nervous & sensory diseases. The morbid conditions took place at school in 37.5 percent, and at home in 59.8 percent. The absence rate due to morbidity was 4.4 percent out of all morbid students. In addition, 73.5 percent of all morbid student utilized medical treatment, of which the pharmacy accounted for 53.8 percent and 57.5 percent in the urban and rural areas, respectively. The second most common facility utilized was hospital OPD. While there was no student who utilized the school nursing room in the rural area, 1.5 percent of the sick students utilized the school nursing room in the urban area. The most important in selecting medical facility was the distance. By low medical expense was more frequent cited reason for selecting medical facility in rural area (13.6 percent) than in urban area (3.2 percent). Mild illness accounted for 70.3 percent of the reasons for no treatment and 21.8 percent was due to the conflict between school hour and clinic hour. The morbid students mostly suffered from mild respiratory and gastrointestinal disease, and its incidence was the highest rate in the school. Although there was relation between the worry of absence and no-treatment, the school nursing room utilization of students was very insufficient. Therefore, it is required to activate the operation of the high school nursing room by utilizing the specialized personnel.

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The Clinical Characteristics and Pharmacologic Treatment of Neuralgic Pain in Maxillofacial Region (악안면 신경통성 동통의 임상적 특징과 약물 치료)

  • Sung-Chang Chung;Sung-Woo Lee;Young-Ku Kim
    • Journal of Oral Medicine and Pain
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    • v.21 no.1
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    • pp.173-182
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    • 1996
  • This study was performed to provide the information on the clinical characteristics of the most common paroxysmal pain disorder in maxillofacial region, trigeminal neuralgia, and the effects and side effects of carbamazepine. The patients who visited Orofacial Pain Clinic, Dept. of Oral Diagnosis, Seoul National University Dental Hospital for treating paroxysmal pain were studied by history taking, clinical examination, and radiography. Sixty-two patients(male 20, female42) without any clinical and radiological abnormalities were Included. The change of pain, blood tests, and side effects were investigated periodically after administration of carbamazepine. The obtained results were as follows : 1. Almost all patient with trigeminal neuralgia were over the age of forties and it was more common in women. 2. Trigeminal neuralgia was more right sided and the involved nerve was in the order of maxillary n., mandibular n., and ophthalmic n. 3. The mean duration of suffering was 20.7 months. Eighty percent of patients had apparent trigger area. 4. The duration of pain attack was in the older of several seconds, 1 min. to 5 min., more than 10 min., and 5 min. to 10 min. The frequency of pain attack was in the order of more than 10 per day, 6-10 per day, and 1-5 per day. 5. The clinic the patients had visited for reducing neuralgic pain was in the order of dental clinic, neurology, oriental medicine, otolaryngology, and pharmacy. 6. Unnecessary dental treatments for reducing neuralgic pain were performed in 41.9% of the patients. Almosit all treatments were irreversible ones such as endodontic treatment and tooth extraction. 7. The initial mean VAS was 8.6, but it was decreased to 3.8 after 1 month, to 2.7 after 2 months. Almost all patients showed decreased pain with 200-600mg/day of carbamazepine to 6 months. 8. WBC counts, especially neutrophil counts, was decreased in 1 week after administration of carbamazepine but reached initial level after 1 month. SGOT, SGPT, and creatinine did not show any significant change. 9. Blood pressure was not changed significantly after administration of carbamazepine. 10. Almost patients did not show any apparent side effects, but drowsiness, dizziness, skin itching, constipation, and gastric irritation were occurred in some patients.

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Aqueous Extracts of Liriope platyphylla Are Tightly-Regulated by Insulin Secretion from Pancreatic Islets and by Increased Glucose Uptake through Glucose Transporters Expressed in Liver Hepatocytes

  • Kim, Ji-Eun;Nam, So-Hee;Choi, Sun-Il;Hwang, In-Sik;Lee, Hye-Ryun;Jang, Min-Ju;Lee, Chung-Yeol;Soon, Hong-Ju;Lee, Hee-Seob;Kim, Hae-Sung;Kang, Byeong-Cheol;Hong, Jin-Tae;Hwang, Dae-Youn
    • Biomolecules & Therapeutics
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    • v.19 no.3
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    • pp.348-356
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    • 2011
  • Liriope platyphylla is a medical herb that has long been used in Korea and China to treat cough, sputum, neurodigenerative disorders, obesity and diabetes. The aims of this study were to study the antidiabetic effects of the aqueous extract of L. platyphylla (AEtLP) through pancreatic and extrapancreatic actions. AEtLP were orally administrated to ICR mice once a day for 7 days. Of three different concentrations of AEtLP, only 10% AEtLP were low toxic to liver, based on body weight and serum biochemical analyses. However, 10% AEtLP-treated mice displayed signifi cant reduction of the glucose concentration and increased insulin concentration; no changes were noted using 5% and 15% AEtLP. Also, the increase of glucose transporter (Glut)-1 expression in liver was dependent on the concentration of AEtLP, and was regulated by the phosphorylation of Akt. The lowest expression of Glut-3 was observed in 15% AEtLP treated mice, followed by 10% AEtLP- and 5% AEtLP-treated mice. This pattern of Glut-3 expression was roughly in accord with the phosphorylation of c-Jun N-teminal kinase (JNK) in the mitogen-activated protein kinase (MAPK) pathway. Furthermore, a signifi cant rise of the superoxide dismutase activity (SOD) was detected in AEtLP-treated mice. The fi ndings suggest that AEtLP should be considered as a diabetes therapeutic candidate to induce insulin secretion from pancreatic ${\beta}$-cells and glucose uptake in liver cells.

Health Status and Health Care Utilization in a Rural Area, Nepal (네팔 도서지역 주민들의 상병상태 및 의료이용양상)

  • Lee, Myung-Ken;Kim, Myung-Ho;Lee, Myung-Sun;Park, Kyoung-Ok
    • Journal of agricultural medicine and community health
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    • v.21 no.2
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    • pp.231-241
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    • 1996
  • The estimation of medical care status and the planning of health service program should be done according to each community resident's socio-medical background and public health service. In this point, it is most necessary to be set the exact and new socio-economic statistics data in Nepal, one of the worst countries in national health status. We surveyed 668 house, 3,425 residents in Dolka area, Nepal from January 25th to February 1st, 1995. 1. In personal characteristics, the ratio of men and women was similar, the person who were below 19 years old were 28.1% and the single were 52.4%. The illeterate person were 50.3% and the lower group in economic status which had been estimated by interviewers were 46.9%. 2. In sanitational characteristics, the person who used stream water or rainwater to drink were 42.2% and the person who always boiled water to drink were only 8.3%. The person who had not toilet in their house were 67.3% and the lower group in sanitational status which had been estimated by interviewers were 61.8%. 3. The prevalence rate of illness during the last one month were 8.6% and the chronic were 26.1% and the acute were 72.5%. The distribution of sickness symptom were headache, fever and joint pain in order and the person who took no medical treatment among the sick were 37.0%. The patterns of medical utilization were public health center, hospital and pharmacy in order. 4. Illness prevalence was significantly related to sex, age, merital status and educational experience. The residents who were women, 40 years old or more, married and had not educational experience were apt to take illness. 5. Medical utilization was significantly related to educational experience, job, distance from home to medical facilities and economic status. The person who had educational experience, were officer workers or merchants, lived near by medical facilities and had higher economic status took medical treatment very well.

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Association Study in Endothelin 1 (EDN1) Gene Polymorphism and Excess or Deficiency Syndrome in Korean Asthmatic Patients (한국인 기관지 천식 허증(虛證), 실증(實證) 환자와 EDN1 유전자 다형성과의 상관성 연구)

  • Yoem, Yu-rim;Kim, Kwan-il;Baek, Hyun-jung;Kim, Mi-a;Lee, Beom-joon;Kim, Jin-ju;Kim, Su-kang;Chung, Joo-ho;Jung, Hee-jae;Jung, Sung-ki
    • The Journal of Internal Korean Medicine
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    • v.37 no.1
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    • pp.47-64
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    • 2016
  • Objectives: In the present study, a genetic analysis was conducted to investigate the association of the expression of SNPs of EDN1 gene polymorphism with the clinical phenotype in bronchial asthma patients with either excess or deficiency syndrome.Methods: Ninety-four healthy control subjects and 52 asthma patients were included in this study. The asthma patients were divided into two groups: those with deficiency syndrome and those with excess syndrome. We searched the exonic and promoter areas of the EDN1 gene in the NCBI website SNPs with <0.01 minor allele frequency (MAF) and <0.01 heterozygosity. Pro programs were performed to obtain the odds ratio, 95% confidence interval, and p-value. Multiple logistic regression models were conducted to analyze the genetic data.Results: In our genotype and allele analyses, there were significant differences in the codominant 2 model of the rs3087459 SNP genotype and also in the CGG haplotype between the control group and the asthma group. Genotype and allele analyses were conducted between the deficiency and excess syndrome group. There were significant differences in the dominant and log-additive model and also in the frequency of C-alleles of rs3087459 SNP genotype. There were significant differences in codominant 1, dominant and log-additive model and T-allele of rs5370 SNP genotype. The AGG haplotype also revealed significant differences.Conclusions: EDN1 SNPs (rs3087459, rs5370) showed a significant association with symptomatic excess syndrome in Korean asthmatic patients.

Synergistic Increase of Oxidative Stress and Tumor Markers in PAH-Exposed Workers

  • Gao, Mei-Li;Chen, Lei;Li, Yong-Fei;Xue, Xiao-Chang;Chen, Lan;Wang, Li-Na;Shah, Walayat;Kong, Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7105-7112
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    • 2014
  • In this study, we investigated oxidative stress and tumor marker levels of polycyclic aromatic hydrocarbons (PAHs) in 136 coke oven workers and in 60 control subjects, and evaluated the correlation between oxidative stress and tumor marker levels. Questionnaires on basic demographic information were also administered. Significant differences in employment time and percentages of alcohol drinkers were observed between the control and exposed groups. PAH exposure was assessed using urinary 1-hydroxy-pyrene (1-OHP) levels and was found to be significantly higher in workers than in the controls. Significant differences (P<0.001) of MDA, GST, LDH, NSE, Cyfra21-1, and of SCC and TNF-a (P<0.0001 and P<0.05, P<0.001, respectively) levels were observed among controls and coke-oven workers, except for bottom coke oven workers. Associations between age and risk of increased TNF-a, smoking and increased GST activities, and drinking with increased MDA concentrations, were marginal (P=0.055, P=0.048, P=0.057, respectively). The association between smoking with MDA (P=0.004), NSE (P=0.005), SCC (P=0.004) andTNF-a (P<0.001), and drinking with TNF-a levels was significant (P=0.012). In addition, a significant positive correlation between oxidative stress and tumor markers was found in the present study. These results suggest that a synergistic increase of oxidative stress and tumor markers induced by PAHs may play a role in toxic responses for PAHs in coke oven workers.

Intestinal Parasitic Infections and Environmental Water Contamination in a Rural Village of Northern Lao PDR

  • Ribas, Alexis;Jollivet, Chloe;Morand, Serge;Thongmalayvong, Boupha;Somphavong, Silaphet;Siew, Chern-Chiang;Ting, Pei-Jun;Suputtamongkol, Saipin;Saensombath, Viengsaene;Sanguankiat, Surapol;Tan, Boon-Huan;Paboriboune, Phimpha;Akkhavong, Kongsap;Chaisiri, Kittipong
    • Parasites, Hosts and Diseases
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    • v.55 no.5
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    • pp.523-532
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    • 2017
  • A field survey studying intestinal parasites in humans and microbial pathogen contamination at environment was performed in a Laotian rural village to identify potential risks for disease outbreaks. A parasitological investigation was conducted in Ban Lak Sip village, Luang Prabang, Lao PDR involving fecal samples from 305 inhabitants as well as water samples taken from 3 sites of the local stream. Water analysis indicated the presence of several enteric pathogens, i.e., Aeromonas spp., Vibrio spp., E. coli H7, E. coli O157: H7, verocytotoxin-producing E. coli (VTEC), Shigella spp., and enteric adenovirus. The level of microbial pathogens contamination was associated with human activity, with greater levels of contamination found at the downstream site compared to the site at the village and upstream, respectively. Regarding intestinal parasites, the prevalence of helminth and protozoan infections were 68.9% and 27.2%, respectively. Eight helminth taxa were identified in fecal samples, i.e., 2 tapeworm species (Taenia sp. and Hymenolepis diminuta), 1 trematode (Opisthorchis sp.), and 5 nematodes (Ascaris lumbricoides, Trichuris trichiura, Strongyloides stercoralis, trichostrongylids, and hookworms). Six species of intestinal protists were identified, i.e., Blastocystis hominis, Cyclospora spp., Endolimax nana, Entamoeba histolytica/E. dispar, Entamoeba coli, and Giardia lamblia. Questionnaires and interviews were also conducted to determine risk factors of infection. These analyses together with a prevailing infection level suggested that most of villagers were exposed to parasites in a similar degree due to limited socio-economic differences and sharing of similar practices. Limited access to effective public health facilities is also a significant contributing factor.

Chemical and bioactive comparison of flowers of Panax ginseng Meyer, Panax quinquefolius L., and Panax notoginseng Burk.

  • Li, Fang;Lv, Chongning;Li, Qiao;Wang, Jing;Song, Dan;Liu, Pengpeng;Zhang, Dandan;Lu, Jincai
    • Journal of Ginseng Research
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    • v.41 no.4
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    • pp.487-495
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    • 2017
  • Background: Although flowers of Panax ginseng Meyer (FPG), Panax quinquefolius L. (FPQ), and Panax notoginseng Burk. (FPN) have been historically used as both medicine and food, each is used differently in practice. Methods: To investigate the connection between components and enhancing immunity activity of FPG, FPQ, and FPN, a method based on a rapid LC coupled with quadrupole time-of-flight MS and immunomodulatory activity study evaluated by a carbon clearance test were combined. Results: According to quantitative results, the ratio of the total content of protopanaxatiol-type ginsenosides to protopanaxadiol-type ginsenosides in FPN was 0, but ranged from 1.10 to 1.32 and from 0.23 to 0.35 in FPG and FPQ, respectively. The ratio of the total content of neutral ginsenosides to the corresponding malonyl-ginsenosides in FPN ($5.52{\pm}1.33%$) was higher than FPG ($3.2{\pm}0.64%$) and FPQ ($2.39{\pm}0.57%$). The colorimetric analysis showed the content of total ginsenosides in FPQ, FPG, and FPN to be $13.75{\pm}0.60%$, $17.45{\pm}0.42%$, and $12.45{\pm}1.77%$, respectively. The carbon clearance assay indicated that the phagocytic activity of FPG and FPQ was higher than that of FPN. A clear discrimination among FPG, FPQ, and FPN was observed in the principal component analysis score plots. Seven compounds were confirmed to contribute strongly by loading plots, which may be the cause of differences in efficacy. Conclusion: This study provides basic information about the chemical and bioactive comparison of FPG, FPQ, and FPN, indicating that protopanaxtriol-type ginsenosides and malonyl-ginsenosides may play a key role in their enhancing immunity properties.

Panax ginseng as an adjuvant treatment for Alzheimer's disease

  • Kim, Hyeon-Joong;Jung, Seok-Won;Kim, Seog-Young;Cho, Ik-Hyun;Kim, Hyoung-Chun;Rhim, Hyewhon;Kim, Manho;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.42 no.4
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    • pp.401-411
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    • 2018
  • Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid ${\beta}$-protein ($A{\beta}$) formation by inhibiting ${\beta}$- and ${\gamma}$-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and $A{\beta}$-induced neurotoxicity, and decrease $A{\beta}$-induced production of reactive oxygen species and neuro-inflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates $A{\beta}$-induced cholinergic deficits in AD models. Similarly, gintonin inhibits $A{\beta}$-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce $A{\beta}$ formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.