Emotional and cognitive changes in chronic kidney disease

Chronic kidney disease (CKD) leads to cognitive impairment and emotional changes. However, the precise mechanism underlying the crosstalk between the kidneys and the nervous system is not fully understood. Inflammation and cerebrovascular disease can influence the development of depression in CKD. CKD is one of the strongest risk factors for cognitive impairment. Moreover, cognitive impairment occurs in CKD as patients experience the dysregulation of several brain functional domains due to damage caused to multiple cortical regions and to subcortical modulatory neurons. The differences in structural brain changes between CKD and non-CKD dementia may be attributable to the different mechanisms that occur in CKD. The kidney and brain have similar anatomical vascular systems, which may be susceptible to traditional risk factors. Vascular factors are assumed to be involved in the development of cognitive impairment in patients with CKD. Vascular injury induces white matter lesions, silent infarction, and microbleeds. Uremic toxins may also be directly related to cognitive impairment in CKD. Many uremic toxins, such as indoxyl sulfate, are likely to have an impact on the central nervous system. Further studies are required to identify therapeutic targets to prevent changes in the brain in patients with CKD.

Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Transduced Tat-aldose Reductase Protects Hippocampal Neuronal Cells against Oxidative Stress-induced Damage

Aldose reductase (AR) protein, a member of the NADPH-dependent aldo-keto reductase family, reduces a wide range of aldehydes and enhances cell survival by inhibition of oxidative stress. Oxidative stress is known as one of the major pathological factor in ischemia. Since the precise function of AR protein in ischemic injury is fully unclear, we examined the function of AR protein in hippocampal neuronal (HT-22) cells and in an animal model of ischemia in this study. Cell permeable Tat-AR protein was produced by fusion of protein transduction domain in Tat for delivery into the cells. Tat-AR protein transduced into HT-22 cells and significantly inhibited cell death and regulated the mitogen-activate protein kinases (MAPKs), Bcl-2, Bax, and Caspase-3 under oxidative stress condition. In an ischemic animal model, Tat-AR protein transduced into the brain tissues through the blood-brain barrier (BBB) and drastically decreased neuronal cell death in hippocampal CA1 region. These results indicate that transduced Tat-AR protein has protective effects against oxidative stress-induced neuronal cell death in vitro and in vivo, suggesting that Tat-AR protein could be used as potential therapeutic agent in ischemic injury.

Risk factors for latent tuberculosis in children who had close contact to households with pulmonary tuberculosis

PURPOSE: Tuberculosis (TB) is a common and possibly fatal infectious disease, and its incidence and prevalence is quite high in Korea compared to other Organization for Economic Co-operation and Development countries. Patients who have active TB can cause latent tuberculosis infection (LTBI) in children, which may progress to reactivated tuberculosis. This study was performed to analyze the risk of adult TB that affects children's LTBI. METHODS: From June 2013 to May 2014, 60 children (32 boys, 28 girls) who came into close contact with adult patients diagnosed with pulmonary TB underwent LTBI tests. The children were divided into the 2 groups: the first group was finally diagnosed to LTBI, and the second group was proven not to have LTBI. We compared the risk of adult patients with pulmonary TB between children with LTBI and those without through a medical record review. RESULTS: The number of adult patients with TB was 36 (father 68%, mother 23%, grandparents 8%). The patients who came into close contact with the LTBI group were older (47.0±12.8 years vs. 41.3±6.6 years) and had higher erythrocyte sedimentation rate (ESR) levels than those of the second group. The rate of negative acid-fast-bacilli smear with positive culture results in patients who came into contact with the LBTI group was higher than in the second group. The cutoff value of ESR for the diagnosis of LTBI was 31 mm/hr with a sensitivity of 0.75 and a specificity of 0.85 (area under curve=0.748). CONCLUSION: Adult pulmonary TB patients who are older and have higher ESR levels may be risk factors for LTBI in children coming into close contact with them.

Morphometric Analysis of the Skull by Moire Contourography / 체질인류학회지

The non-metric analysis of the skulls is very useful for estimating sex and determination of ancestry, the accuracy tends to depend on the amount of experiences of the observers, and so inter-observer errors might be happened. Many researchers are trying to find out more objective methods for determination of ancestry. The purpose of this presentation is to show the usefulness of moire contourography for analyzing the skull. The master screen that is similar to the gratings was made by steel rods, which were arranged as equally spaced parallel lines. Halogen light source was illuminated by lantern slide projector. The skeletal materials were documented crania, composed of 87 male and 47 female, from William M. Bass Donated Skeletal Collection housed at the Department of Anthropology, University of Tennessee. The skulls were placed just behind the master screen as anatomical position using cubic craniophore. The angle between the light source and camera was 65degrees, the distance between camera and the master screen was 1.2 m. Frontal view, left lateral and right lateral view were taken. From the frontal view, fringe patterns were analyzed for first five contour lines which were mainly located around the Glabella. The results were as followed; Type I for male was 53% and female was 4%; Type II for male was 29% and female was 2%; Type III for male was 2% and female was 15%; Type IV for male was 6% and female was 55%. From the lateral view, fringe patterns were analyzed for first four contour lines. However, first and second contour lines were critical to determine the shape and the results were as followed; Type I for male was 52% and female was 22%; Type II for male was 38% and female was 26%; Type III for male was 8% and female was 17%; Type IV for male was 2% and female was 35%. According to this study, different fringe patterns might be dependent on the degree of development of bone marker such as Glabella, Supercillary arch, Euryon and Mastoid process. For example, Supercillary arches were very well developed and slope of forehead above the Glabella was declined, fringe pattern showed reverse triangle shape. If Supercillary arches were poorly developed and slope of forehead above the Glabella was flat, fringe pattern showed home plate shape. The present research shows that moire contourography might be used as more objective methods for estimating sex. And it would be helpful to determine the ancestry when the lateral aspects were analyzed. In the future, continuing study need to be performed with same master screen for different ancestry.

Validation Study of Discriminating Sex using the Atlas from the Digital Korean 3D Human Body Modeling / 체질인류학회지

Estimation of biological profile for skeletal remains by forensic anthropological examination would be possible based on physical anthropological studies which were statistically analyzed. However, physical anthropological studies for Korean population are not enough to establish biological profile for Korean because there is lack of documented osteological specimens in Korea. Recent study suggested that physical anthropological examination could be possible on the three dimensional data which were reconstructed from computed tomography, instead of preparing skeletal specimen by defleshing bone. One of the aim of this study is to evaluate Digital Korean database which were composed of computed tomographic images of 100 cadavers. The other is to perform statistical analysis on morphometrics for segmented atlas whether the results could be helpful to estimate sex in Korean. We measured 100 segmentation atlases (male 51, female 49) from the Digital Korean database which were under the control of Catholic Institute for Applied Anatomy, The Catholic University of Korea. Measurements of segmented atlas were carried out by using Mimics software (Simulation module, Version 13.0, Materialise NV, Belgium), and values of measurement were performed statistical analysis by IBM(R) SPSS(R) (version 20.0, Armonk, New York). Among 19 measurements, the width of atlas showed most crucial element for estimating sex, which was consistent with the result using dried bones of atlas and hit ratio of discriminant functions was 88.0%. 76.7 was the cut-off score of discriminant functions. This results showed that morphometrics for segmented atlas could be helpful in estimating sex using the Digital Korean database. In the future, we expect that the other researchers could more actively use the Digital Korean database as a good specimen for physical and forensic anthropological study.

Two Pediatric Cases of Dengue Fever Imported from Philippines / 소아감염

Dengue fever is an important health problem for international travelers to all endemic areas. The steadily increasing numbers of tourists visiting endemic areas raise the risk of exposure, and imported dengue cases are increasingly observed in nonendemic area. Dengue has a wide spectrum of clinical presentations, often with unpredictable clinical evolution and outcome. While most patients recover following a self-limiting, non-severe clinical course, a small proportion progress to severe disease such as dengue hemorrhagic fever or dengue shock syndrome. Therefore, it is important to suspect dengue fever in every febrile patient returning from the tropics. Whenever it is suspected, a quick diagnosis and adequate managements are essential to avoid complications. We report two cases of imported dengue fever in Korean children presenting with fever, headache, nausea, and rash.

Retraction: Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury

No abstract available.

Expression of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma in the lung tissue of obese mice and the effect of rosiglitazone on proinflammatory cytokine expressions in the lung tissue / 소아과

PURPOSE: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-alpha, PPAR-gamma, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-gamma agonist. METHODS: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, PPAR-alpha and PPAR-gamma from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. RESULTS: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPARalpha and PPAR-gamma increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-alpha, and TGF-beta mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-beta expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. CONCLUSION: PPAR-alpha and PPAR-gamma expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.

A Pediatric Case of Toxic Hepatitis Induced by Hovenia Dulcis / 대한소아소화기영양학회지

Toxic hepatitis is a rare but devastating disease in children. Herbs are widely used in oriental medicine to treat various symptoms in Korea, however, several herbs have been reported to induce liver injury. We report a case of toxic hepatitis induced by Hovenia dulcis in a 3-year-old boy. He complained of nausea, abdominal discomfort, and jaundice. The patient had consumed water boiled with hovenia dulcis for about 1 year prior to presentation. A diagnosis of toxic hepatitis was made based on his history, laboratory data, viral markers, ultrasonography, and biopsied liver tissue. We administered supportive management for acute fulminant hepatitis but his symptoms and liver function progressed. He was transferred to another hospital for further evaluation and consideration for liver transplantation. Because acute liver failure due to herbs or dietary supplement taken for a long time is often fetal, it is important to make early diagnosis and stop taking the drug as soon as drug induced liver injury is suspected.

Erratum: Chlorogenic Acid Improves Neuroprotective Effect of PEP-1-Ribosomal Protein S3 Against Ischemic Insult

On page 173, the incorrect image which was not submitted by the author was mistakenly printed for Fig. 5 by a system error of the editing company.

Prevalence of Dementia and Its Correlates among Participants in the National Early Dementia Detection Program during 2006-2009

OBJECTIVE: To investigate the prevalence of dementia and its correlates among people with poor socioeconomic status, poor social support systems, and poor performance on the Korean version of the Mini-Mental Status Exam (MMSE-KC). METHODS: We used 2006-2009 data of the National Early Dementia Detection Program (NEDDP) conducted on Jeju Island. This program included all residents >65 years old who were receiving financial assistance. We examined those who performed poorly (standard deviation from the norm of <-1.5) on the MMSE-KC administered as part of the NEDDP, using age-, gender-, and education-adjusted norms for Korean elders. A total of 1708 people were included in this category. RESULTS: The prevalence of dementia in this group was 20.5%. Multivariate logistic regression analysis revealed that the following factors were statistically significantly associated with dementia: age of 80 or older, no education, nursing home residence, and depression. CONCLUSION: The prevalence of dementia is very high among those with lower MMSE-KC scores, and significant correlates include older age, no education, living in a nursing home, and depression. Enhancing lifetime education to improve individuals' cognitive reserves by providing intellectually challenging activities, encouraging living at home rather than in a nursing home, and preventing and treating depression in its early phase could reduce the prevalence of dementia in this population.

Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury

Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a dose- and time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.

Clinical Features and Treatment Outcomes of Hemangioma in a Single Institution / 임상소아혈액종양

BACKGROUND: Hemangiomas are the most common benign tumor of childhood. Uncertainties regarding their diagnosis or management often prompt life- or function-threatening complications or unnecessary treatment. The objective of this study is to analyze and understand the clinical features and treatment outcomes of hemangiomas for accurate diagnosis and treatment.METHODS: A retrospective chart review of 60 patients diagnosed as hemangioma in Kangbuk Samsung Hospital from January 2001 to January 2011 was performed.RESULTS: Hemangiomas were observed predominantly in female with the sex ratio of 1:2.2. They were present at birth in 32%, and within 2 months of age in 22% of the patients. In 45% of the patients, hemangiomas occurred on the head and neck, which were the most commonly involved site. 27% of the cases were clinically diagnosed, 40% of the cases were diagnosed after imaging studies, and 37% of cases were confirmed by histopathology. 40% of the patients were observed without treatment. 57% of the patients were treated with surgical excision, corticosteroid, interferon or propranolol. Eight patients were treated with oral propranolol, and seven of them demonstrated regression without major side effects.CONCLUSION: We confirmed that hemangiomas were preponderant in female and usually appeared in first 2 months of life, and the head and neck were the most favored site. We observed that propranolol was effective and safe for treating problematic infantile hemangiomas.

Clinical Features and Treatment Outcomes of Hemangioma in a Single Institution / 임상소아혈액종양

BACKGROUND: Hemangiomas are the most common benign tumor of childhood. Uncertainties regarding their diagnosis or management often prompt life- or function-threatening complications or unnecessary treatment. The objective of this study is to analyze and understand the clinical features and treatment outcomes of hemangiomas for accurate diagnosis and treatment. METHODS: A retrospective chart review of 60 patients diagnosed as hemangioma in Kangbuk Samsung Hospital from January 2001 to January 2011 was performed. RESULTS: Hemangiomas were observed predominantly in female with the sex ratio of 1:2.2. They were present at birth in 32%, and within 2 months of age in 22% of the patients. In 45% of the patients, hemangiomas occurred on the head and neck, which were the most commonly involved site. 27% of the cases were clinically diagnosed, 40% of the cases were diagnosed after imaging studies, and 37% of cases were confirmed by histopathology. 40% of the patients were observed without treatment. 57% of the patients were treated with surgical excision, corticosteroid, interferon or propranolol. Eight patients were treated with oral propranolol, and seven of them demonstrated regression without major side effects. CONCLUSION: We confirmed that hemangiomas were preponderant in female and usually appeared in first 2 months of life, and the head and neck were the most favored site. We observed that propranolol was effective and safe for treating problematic infantile hemangiomas.

Erratum to "Peroxisome Proliferator-Activated Receptor-Gamma Expression in the Lung Tissue of Obese Rats" by Hwang SJ, et al. (Yonsei Med J 2011;52:495-501.)

No abstract available.

Chlorogenic Acid Improves Neuroprotective Effect of PEP-1-Ribosomal Protein S3 Against Ischemic Insult

Chlorogenic acid (CGA) possesses various biological activities such as anti-oxidant, anti-inflammatory, and anti-diabetic activities. In the present study, we examined the effect of CGA on the transduction efficiency of PEP-1-ribosomal protein S3 (PEP-1-rpS3) into cells and brain tissues, and its neuroprotective potential against ischemia/reperfusion. We found that, in the presence of CGA, the transduction efficiency of PEP-1-rpS3 into astrocytes and the CA1 region of the hippocampus was enhanced, compared to its transduction in the absence of CGA. Also, cell viability data demonstrated that the sample treated with CGA + PEP-1-rpS3 exhibited improved cell viability against hydrogen peroxide (H2O2)-induced toxicity more significantly than the sample treated with PEP-1-rpS3 alone. Also, in a gerbil ischemia model, data demonstrated that following the ischemic insult, the group treated with PEP-1-rpS3 + CGA showed markedly enhanced protection of neuron cells in CA1 region of hippocampus, compared to those treated with CGA or PEP-1-rpS3 alone. Taken together, these results suggest that CGA may improve the transduction efficiency of protein transduction domain (PTD) fusion proteins into target cells or tissues, thereby enhancing their therapeutic potential against various diseases.

Peroxisome Proliferator-Activated Receptor-Gamma Expression in the Lung Tissue of Obese Rats

PURPOSE: Obesity is a risk factor for asthma and type II diabetes. Peroxisome proliferator-activated receptor (PPAR)-gamma has been suggested to regulate inflammatory responses in diabetes and asthma. We investigated whether PPAR-alpha, PPAR-gamma, adiponectin receptors (AdipoR1, AdipoR2), leptin, and tumor necrosis factor (TNF)-alpha are expressed in rat lung tissues and whether the expression differs between obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long Evans Tokushima Otsuka (LETO) rats. MATERIALS AND METHODS: Obese and lean rats were given with a high fat diet or a 30% restricted diet for 32 weeks, and their blood glucose levels and weights were monitored. After 32 weeks, mRNA levels of PPAR-alpha, PPAR-gamma, AdipoR1, AdipoR2, leptin, and TNF-alpha in lung tissues were measured using real time PCR. RESULTS: PPAR-alpha, PPAR-gamma, AdipoR1, AdipoR2, leptin, and TNF-alpha were expressed in both obese and lean rat lung tissues. Increased serum glucose levels on intraperitoneal glucose tolerance testing and a higher weight gain at 32 weeks were observed in OLETF control rats compared to OLETF diet restricted rats. PPAR-gamma expression was markedly elevated in obese control and diet restricted rats compared to lean rats, although PPAR-gamma expression in obese rats was not affected by diet restriction. Leptin was highly expressed in OLETF rats compared to LETO rats. TNF-alpha expression was enhanced in OLETF control rats compared LETO diet restricted rats, and decreased by diet restriction. PPAR-alpha, AdipoR1, and AdipoR2 expression were not significantly different between obese and lean rats. CONCLUSION: PPAR-gamma was highly expressed in the lung tissues of obese rats and may be a novel treatment target for regulating lung inflammation associated with obesity.

Impact of Environmental Tobacco Smoke Exposure and Home Environment on Asthma and Wheeze in School Children / 소아알레르기및호흡기학회지

PURPOSE: Environmental factors may increase risk for childhood asthma. The objective of this study was to investigate the association of environmental tobacco smoke (ETS) exposure and home environment with the development of wheeze and asthma. METHODS: We conducted a cross-sectional survey of 969 elementary school students. Data included questions about asthma and wheeze symptoms, exposure to tobacco smoke, and home environment including history of moving into a new house within 1 year of age after birth, use of fragrance at home, recent purchase of new furniture. Logistic regression and Pearson chi statistics were used to estimate these associations. RESULTS: ETS exposure was associated with current wheeze and nocturnal sleep disturbance. Paternal smoking over 20 cigarettes per day was associated with 4 or more episodes of wheeze during the past 1 year. However, there were no significant differences in pulmonary function, serum total IgE levels, blood eosinophil counts, and atopy between children with ETS exposure and non-exposure. Moving into a new house within 1 year of birth was associated with current asthma or wheeze. Use of fragrance at home and purchase of new furniture during the past 1 year were associated with current wheeze, current physician-diagnosed asthma, and nocturnal cough. CONCLUSION: Exposure to ETS, moving into a new house after birth, and indoor fragrance are risk factors for wheeze and asthma in schoolchildren.