• Childhood Kidney Diseases
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• v.2 no.2
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• pp.125-132
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• 1998

Purpose : To study whether a low protein diet increase the efficacy of antihypertensive therapy on the progression of renal failure, we conducted an experimental study using 5/6 nephrectomized rats(n=63). Methods : At 7 days after surgery, rats were randomly assigned to three groups according to receiving antihypertensive drug: no antihypertensive drug (U), enalapril (E), and nicardipine (N), respectively and fed a low protein diet (6$\%$ protein). Proteinuria, mesangial matrix expansion score and glomerular volume were assessed at 4, 12 and 16 weeks after renal ablation. Results : Group U rats on a low protein diet developed progressive hypertension ($140{\pm}8,\;162{\pm}5,\;171{\pm}5\;and\;184{\pm}11\;mmHg$ at 4, 8, 12 and 16 weeks) which were controlled by E and N. Group U rats on a low protein diet developed proteinuria ($74{\pm}15\;mg/day$ at 16 weeks) which were decreased by E ($42{\pm}12 mg/day$) or N ($48{\pm}8 mg/day$) (p<0.05). Mesangial matrix expansion score and glomerular volume were not different between groups U, E and N on a low protein diet regardless of the antihypertensive drugs administered. Conclusion : A low protein diet did not affect blood pressure. Enalapril and nicardipine-treated rats on a low protein diet did not have different mesangial matrix expansion and glomerular volumes from rats on a low protein diet at 12 weeks and 16 weeks, in spite of the better controlling of systemic hypertension and lessening of proteinuria. Thus, combined treatment with a low protein diet and antihypertensive drugs didn't appear to show any addition,11 effects to attenuate glomerular injury.

• Clinical and Experimental Pediatrics
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• v.51 no.8
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• pp.874-878
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• 2008

Purpose : This study was undertaken to develop an animal model of periventricular leukomalacia (PVL) induced by in utero clamping of pregnant rat aorta in fetal rats. Methods : A timed pregnanct Sprague-Dawley rat on embryonic day 21 just prior to delivery was sedated and anesthetized, and a Harvard ventilator for small animals was applied. Following laparotomy, the maternal aorta was clamped reversibly for 40 minutes using a surgical clip. The fetal rats were then delivered by Cesarean section, resuscitated if necessary, and reared by a surrogate mother rat until postnatal day 21 to obtain the brain specimen. After systemic perfusion and fixation, $10{\mu}m$ thick serial brain sections were obtained and stained for pathologic examination and assessment of ventriculomegaly. Ventriculomegaly was assessed by the measured ventricle to total brain volume ratio. Results : Eight out of eleven fetal rats (73%) survived in the ischemia group after induction of in utero ischemia by clamping maternal rat aorta, and all ten survived in the control group. Body and brain weights measured at postnatal day 21 were significantly lower in the ischemia group compared to the control group. In pathologic findings, significant ventriculomagaly ($3.67{\pm}1.21%$ vs. $0.23{\pm}0.06%$) was observed in the ischemia group compared to the control group; although cystic lesion was not observed, mild (n=6) and moderate (n=2) rerefaction of the brain tissue was observed. Conclusion : A fetal rat model of PVL induced by in utero clamping of pregnant rat aorta was developed.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.487-499
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• 2000

Background : Acute lung injury is an hypoxic respiratory failure resulting from damage to the alveolar-capillary membrane, which can be developed by a variety of systemic inflammatory diseases. In this study the therapeutic effects of intra-tracheal pulmonary surfactant instillation was evaluated in the intratracheal endotoxin induced acute lung injury model of a rat. Methods : Twenty Sprague-Dawley rats were divided into 4 groups, and normal saline (2 ml/kg, for group 1) or LPS (5 mg/kg, for group 2, 3, and 4) was instilled into the trachea respectively. Either normal saline (2 ml/kg, for group 1 & 2, 30 min later) or bovine surfactant (15 mg/kg, 30 min later for group 3, 5 hr later for group 5) was instilled into the trachea. The therapeutic effect of intratracheal surfactant therapy was evaluated with one chamber body plethysmography (respiratory frequency, tidal volume and enhanced pause), ABGA, BAL fluid analysis (cell count with differential, protein concentration) and pathologic examination of the lung. Results : Intratracheal endotoxin instillation increased the respiration rate decreased the tidal volume and int creased the Penh in all group of rats. Intratracheal instillation of surfactant decreased Penh, increased arterial oxygen tension, decreased protein concentration of BAL fluid and decreased lung inflammation at both times of administration (30 minute and 5 hour after endotoxin instillation). Conclusion : Intratracheal instillation of surfactant can be a beneficial therapeutic modality as discovered in the acute lung injury model of rats induced by intratracheal LPS intillation. It deserves to be evaluated for treatment of human acute lung injury.

• Tuberculosis and Respiratory Diseases
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• v.60 no.6
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• pp.663-672
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• 2006

Background: $PM_{10}$(Particulate matter with a diameter ($<10{\mu}m$), which is characterized by different environmental conditions, is a complex mixture of organic and inorganic compounds. The Asian dust event caused by meteorological phenomena can also produce unique particulate matter in affected areas. This study investigated the cytokine produced by A549 epithelial cells exposed to particles collected during both the Asian dust pfenomenon and ambient air particles in a non-dusty period. Method: Air samples were collected using a high volume air sampler(Sibata Model HV500F) with an air flow at $500{\ell}/min$ for at least 6 hours. The cytokine messenger RNA(mRNA) was measured using a reverse transcriptase polymerase chain reaction(RT-PCR). The A549 cells were exposed to 10 to $500{\mu}g/m{\ell}$ of a suspension containing $PM_{10}$ for 24 hours. Each was compared with those in the non-exposed control cells. Result: The mRNA levels of interleukin(IL)-$1{\alpha}$, $IL-I{\beta}$, IL-8, and the granulocyte macrophage colony stimulating factor(GM-CSF) increased after veing exposed to $PM_{10}$ in the ambient air particles, compared with those in the non-exposed control cells. The increase in $IL-1{\alpha}$ and IL-8 were dose dependent at a $PM_{10}$ concentration between $100{\mu}g/m{\ell}$ and $500{\mu}g/m{\ell}$. The mRNA level of IL-8 in the A549 epithelial cells was higher during the in the Asian dust period($500{\mu}g/m{\ell}$) than during the non dust period. Conclusion: A549 cells exposed to the $PM_{10}$ collected during the Asian dust period produce more proinflammatory cytokine than during non-dusty period. This cytokine enhances the local inflammatory response in the airways and can also contribute to the systemic component of this inflammatory process.

• Journal of Life Science
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• v.29 no.6
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• pp.747-753
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• 2019

Cognitive decline is characterized by reduced long-/short-term memory and attention span, and increased depression and anxiety. Such decline is associated with various degenerative brain disorders, especially Alzheimer's disease (AD) and Parkinson's disease (PD). The increases in elderly populations suffering from cognitive decline create social problems and impose economic burdens, and also pose safety threats; all of these problems have been extensively researched over the past several decades. Possible causes of cognitive decline include metabolic and hormone imbalance, infection, medication abuse, and neuronal changes associated with aging. However, no treatment for cognitive decline is available. In neurodegenerative diseases, changes in the gut microbiota and gut metabolites can alter molecular expression and neurobehavioral symptoms. Changes in the gut microbiota affect memory loss in AD via the downregulation of NMDA receptor expression and increased glutamate levels. Furthermore, the use of probiotics resulted in neurological improvement in an AD model. PD and gut microbiota dysbiosis are linked directly. This interrelationship affected the development of constipation, a secondary symptom in PD. In a PD model, the administration of probiotics prevented neuron death by increasing butyrate levels. Dysfunction of the blood-brain barrier (BBB) has been identified in AD and PD. Increased BBB permeability is also associated with gut microbiota dysbiosis, which led to the destruction of microtubules via systemic inflammation. Notably, metabolites of the gut microbiota may trigger either the development or attenuation of neurodegenerative disease. Here, we discuss the correlation between cognitive decline and the gut microbiota.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.210-222
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• 2000

Background: Endothelin(ET) is the most potent vasoconstrictor and bronchoconstrictor. The plasma ET-1 level is elevated in patients with acute pulmonary thromboembolism(APTE). This finding suggest that ET-1 may be an important mediator in the cardiopulmonary derangement of APTE. But whether ET-1 is a pathogenic mediator or a simple marker of APTE is not known. The role of ET-1 in the pathogenesis of cardiopulmonary dysfunction in APTE(delete) was investigated through an evaluation of the effects of $ET_A$-receptor antagonist on APTE. The increase in local levels of preproET-1 mRNA and ET-1 peptide in the embolized lung was also demonstrated. Methods: In a canine autologous blood clot pulmonary embolism model, $ET_A$-receptor antagonist(10 mg/kg intravenously, n=6) was administered one hour after the onset of the embolism. Hemodynamic measurements, blood gas tensions and plasma levels of ET-1 immunoreactivity in this treatment group were compared with those in the control group(n=5). After the experiment., preproET-1 mRNA expression(using Northern blot analysis) and the distribution of ET-1(by immunohistochemical analysis) in the lung tissues were examined. Results: The increases in pulmonary arterial pressure and pulmonary vascular resistance of the treatment group were less than those of the control group. Decrease in cardiac output was also less in the treatment group. Complications such as systemic arterial hypotension and hypoxemia did not occur with the administration of $ET_A$-receptor antagonist The plasma level of ET-1 like(ED: what does 'like' mean?) immunoreactivity was increased after embolization in both groups but was significantly higher in the treatment group. The preproET-1 mRNA and ET-1 peptide expressions were increased in the embolized lung. Conclusion: ET-1 synthesis increases with embolization in the lung and may plays play an important role in the pathophysiology of cardiopulmonary derangement of APTE. Furthermore, $ET_A$-receptor antagonist attenuates cardiopulmonary alterations seen in APTE, suggesting a potential benefit of this therapy.

• Development and Reproduction
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• v.12 no.1
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• pp.97-105
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• 2008

Vinclozolin (VCZ) is a systemic fungicide commonly used in fruits, vegetables and the wine industry. VCZ and its metabolites, butenoic acid (M1) and enanilide (M2) derivatives, act as anti-androgens through actions on the androgen receptor. Although there is growing body of evidence that VCZ's action as an endocrine disrupting chemical (EDC) in male reproductive physiology and pathphysiology, no evidence on the VCZ's EDC action in female is available yet. Previously we found that the prepubertal VCZ exposures could effectively delay the onset of puberty in female rats, suggesting the postponed or weakened activities of hypothalamus-pituitary-ovary (H-P-O) reproductive hormonal axis. The present study was performed to examine whether the VCZ administration affects the transcriptional activities of reproductive hormone-related genes in the same animal model. VCZ (10 mg/kg/day) was administered daily from postnatal day 21 (PND 21) through the day when the first vaginal opening (V.O.) was observed. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus and pituitary, total RNAs were extracted and applied to the semiquantitative reverse transcription polymerase chain reaction (RT-PCR). As a result, treatment with VCZ significantly lowered the transcriptional activity of nitric oxide synthase-2 (NOS-2) which is known to adjust gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus (p<0.01). Similarly, the mRNA levels of KiSS-1, G protein-coupled receptor 54 (GPR54) and GnRH were significantly decreased in hypothalamus (p<0.01) from VCZ-treated group. As expected, the transcriptional activities of luteinizing hormone-${\beta}$ (LH-${\beta}$) and follicle stimulating hormone-${\beta}$ (FSH-${\beta}$) in the anterior pituitary from VCZ-treated group were also significantly lower than those from the control group. The present study indicates that(i) the inhibitory effect of VCZ exposure on the onset of puberty in immature female rats could be derived from the reduced transcriptional activities of gonadotropin subunits and their upstream modulators such as GnRH and KiSS-1 in hypothalamus-pituitary neuroendocrine axis, and (ii) these inhibitory effects could be mediated by NO signaling pathway.

• Journal of Preventive Medicine and Public Health
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• v.40 no.5
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• pp.363-370
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• 2007

Objectives: The principal objective of this study was to determine the relationship between maternal exposure to air pollution and low birth weight and to propose a possible environmental health surveillance system for low birth weight. Methods: We acquired air monitoring data for Seoul from the Ministry of Environment, the meteorological data from the Korean Meteorological Administration, the exposure assessments from the National Institute of Environmental Research, and the birth data from the Korean National Statistical Office between January 1, 2002 and December 31, 2003. The final birth data were limited to singletons within $37{\sim}44$ weeks of gestational age. We defined the Low Birth Weight (LBW) group as infants with birth weights of less than 2500g and calculated the annual LBW rate by district. The air monitoring data were measured for $CO,\;SO_2,\;NO_2,\;and\;PM_{10}$ concentrations at 27 monitoring stations in Seoul. We utilized two models to evaluate the effects of air pollution on low birth weight: the first was the relationship between the annual concentration of air pollution and low birth weight (LBW) by individual and district, and the second involved a GIS exposure model constructed by Arc View 3.1. Results: LBW risk (by Gu, or district) was significantly increased to $1.113(95%\;CI=1.111{\sim}1.116)\;for\;CO,\;1.004(95%\;CI=1.003{\sim}1.005)\;for\;NO_2,\;1.202(95%\;CI=1.199{\sim}1.206\;for\;SO_2,\;and\;1.077(95%\;CI=1.075{\sim}1.078)\;\;for\;PM_{10}$ with each interquartile range change. Personal LBW risk was significantly increased to $1.081(95%\;CI=1.002{\sim}1.166)\;for\;CO,\;1.145(95%\;CI=1.036{\sim}1.267)\;for\;SO_2,\;and\;1.053(95%\;CI=1.002{\sim}1.108)\;for\;PM_{10}$ with each interquartile range change. Personal LBW risk was increased to $1.003(95%\;CI=0.954{\sim}1.055)\;for\;NO_2$, but this was not statistically significant. The air pollution concentrations predicted by GIS positively correlated with the numbers of low birth weights, particularly in highly polluted regions. Conclusions: Environmental health surveillance is a systemic, ongoing collection effort including the analysis of data correlated with environmentally-associated diseases and exposures. In addition. environmental health surveillance allows for a timely dissemination of information to those who require that information in order to take effective action. GIS modeling is crucially important for this purpose, and thus we attempted to develop a GIS-based environmental surveillance system for low birth weight.

• Journal of Nutrition and Health
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• v.41 no.8
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• pp.733-741
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• 2008

In the present study, we comprehensively examined the associations of plasma levels of total adiponectin and high molecular weight (HMW) adiponectin with the features of cardiometabolic risks including body fat distribution, dyslipidemia, insulin resistance and inflammatory markers in a cross-sectional study of 110 treated hypertensive patients. Blood lipid profiles, high sensitivity C-reactive protein (hsCRP) and homeostasis model assessment of insulin resistance (HOMA- IR) derived from fasting glucose and insulin concentrations were determined. Plasma levels of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were analyzed using ELISA. The results showed that plasma levels of HMW-adiponectin were negatively associated with body mass index (BMI, r = - 0.203, p < 0.05) and waist circumference (r = -0.307, p < 0.01), which was not shown in total adiponectin. Plasma levels of HMW-adiponectin were negatively associated with triglyceride (r = -0.223, p < 0.05) and positively associated with HDL-cholesterol (r = 0.228, p < 0.05). Plasma levels of adiponectin were positively associated with HDL-cholesterol (r = 0.224, p < 0.05). Plasma levels of HMW-adiponectin were negatively associated with hsCRP (r = -0.276, p < 0.01) and IL-6 (r = -0.272, p < 0.01). In addition, there were weak associations between plasma levels of HMWadiponectin and TNF-${\alpha}$ (r = -0.163, p = 0.07) and ICAM-1 (r = -0.158, p = 0.09). However, there were no significant associations of total adiponectin with inflammatory markers except hsCRP (r = -0.203, p < 0.05). Stepwise multiple linear regression analysis showed that only plasma levels of HMW-adiponectin was an independent factor influencing serum levels of hsCRP, a marker of systemic low grade inflammation, after adjusting for age, gender, BMI, waist circumference, alcohol intake, smoking status, blood lipids, total adiponectin and drug use (p < 0.01). These results suggest that HMW-adiponectin, rather than total adiponectin, is likely to be closely associated with the features of cardiometabolic risks in treated hypertensive patients and might be effective biomarker for the prediction of cardiovascular disease.

• Journal of Life Science
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• v.21 no.11
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• pp.1518-1525
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• 2011

Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.