Claustral MeCP2 Regulates Methamphetamine-induced Conditioned Place Preference in Cynomolgus Monkey

The claustrum, a brain nucleus located between the cortex and the striatum, has recently been highlighted in drug-related reward processing. Methyl CpG-binding protein-2 (MeCP2) is a transcriptional regulator that represses or activates the expression of the target gene and has been known to have an important role in the regulation of drug addiction in the dopaminergic reward system. The claustrum is an important region for regulating reward processing where most neurons receive dopamine input; additionally, in this region, MeCP2 is also abundantly expressed. Therefore, here, we hypothesized that MeCP2 would be involved in drug addiction control in the Claustrum as well and investigated how claustral MeCP2 regulates drug addiction. To better understand the function of human claustral MeCP2, we established a non-human primate model of methamphetamine (METH) - induced conditioned place preference (CPP). After a habituation of two days and conditioning of ten days, the CPP test was conducted for three days. Interestingly, we confirmed that virus-mediated overexpression of MECP2 in the claustrum showed a significant reduction of METH-induced CPP in the three consecutive days during the testing period. Moreover, they showed a decrease in visit scores (frequency for visit) for the METH-paired room compared to the control group although the scores were statistically marginal. Taken together, we suggest that the claustrum is an important brain region associated with drug addiction, in which MeCP2 may function as a mediator in regulating the response to addictive drugs.

Methyl-CpG Binding Protein 2 in Alzheimer Dementia / 대한배뇨장애요실금학회지

Despite decades of research on Alzheimer disease, understanding the complexity of the genetic and molecular interactions involved in its pathogenesis remains far from our grasp. Methyl-CpG Binding Protein 2 (MeCP2) is an important epigenetic regulator enriched in the brain, and recent findings have implicated MeCP2 as a crucial player in Alzheimer disease. Here, we provide comprehensive insights into the pathophysiological roles of MeCP2 in Alzheimer disease. In particular, we focus on how the alteration of MeCP2 expression can impact Alzheimer disease through risk genes, amyloid-β and tau pathology, cell death and neurodegeneration, and cellular senescence. We suggest that Alzheimer disease can be adversely affected by upregulated MeCP2-dependent repression of risk genes (MEF2C, ADAM10, and PM20D1), increased tau accumulation, and neurodegeneration through neuronal cell death (excitotoxicity and apoptosis). In addition, we propose that the progression of Alzheimer disease could be caused by reduced MeCP2-mediated enhancement of astrocytic and microglial senescence and consequent glial SASP (senescence-associated secretory phenotype)-dependent neuroinflammation. We surmise that any imbalance in MeCP2 function would accelerate or cause Alzheimer disease pathogenesis, implying that MeCP2 may be a potential drug target for the treatment and prevention of Alzheimer disease.

The effects of surface grinding and polishing on the phase transformation and flexural strength of zirconia

PURPOSE: The purpose of this in vitro study was to evaluate the effect of surface grinding and polishing procedures using high speed zirconia diamond burs with different grit sizes on the phase transformation and flexural strength of zirconia.

Comprehensive MicroRNAome Analysis of the Relationship Between Alzheimer Disease and Cancer in PSEN Double-Knockout Mice / 대한배뇨장애요실금학회지

PURPOSE: Presenilins are functionally important components of γ-secretase, which cleaves a number of transmembrane proteins. Manipulations of PSEN1 and PSEN2 have been separately studied in Alzheimer disease (AD) and cancer because both involve substrates of γ-secretase. However, numerous clinical studies have reported an inverse correlation between AD and cancer. Interestingly, AD is a neurodegenerative disorder, whereas cancer is characterized by the proliferation of malignant cells. However, this inverse correlation in the PSEN double-knockout (PSEN dKO) mouse model of AD has been not elucidated, although doing so would shed light onto the relationship between AD and cancer. METHODS: To investigate the inverse relationship of AD and cancer under conditions of PSEN loss, we used the hippocampus of 7-month-old and 18-month-old PSEN dKO mice for a microRNA (miRNA) microarray analysis, and explored the tumorsuppressive or oncogenic role of differentially-expressed miRNAs. RESULTS: The total number of miRNAs that showed changes in expression level was greater at 18 months of age than at 7 months. Most of the putative target genes of the differentially-expressed miRNAs involved Cancer pathways. CONCLUSIONS: Based on literature reviews, many of the miRNAs involved in Cancer pathways were found to be known tumorsuppressive miRNAs, and their target genes were known or putative oncogenes. In conclusion, the expression levels of known tumor-suppressive miRNAs increased at 7 and 18 months, in the PSEN dKO mouse model of AD, supporting the negative correlation between AD and cancer.

Drug Abuse and Psychosis: New Insights into Drug-induced Psychosis

Addictive drug use or prescribed medicine abuse can cause psychosis. Some representative symptoms frequently elicited by patients with psychosis are hallucination, anhedonia, and disrupted executive functions. These psychoses are categorized into three classifications of symptoms: positive, negative, and cognitive. The symptoms of DIP are not different from the symptoms of schizophrenia, and it is difficult to distinguish between them. Due to this ambiguity of distinction between the DIP and schizophrenia, the DIP animal model has been frequently used as the schizophrenia animal model. However, although the symptoms may be the same, its causes are clearly different in that DIP is acquired and schizophrenia is heritable. Therefore, in this review, we cover several DIP models such as of amphetamine, PCP/ketamine, scopolamine, and LSD, and then we also address three schizophrenia models through a genetic approach with a new perspective that distinguishes DIP from schizophrenia.

Pathophysiological Role of Neuroinflammation in Neurodegenerative Diseases and Psychiatric Disorders / 대한배뇨장애요실금학회지

Brain diseases and disorders such as Alzheimer disease, Parkinson disease, depression, schizophrenia, autism, and addiction lead to reduced quality of daily life through abnormal thoughts, perceptions, emotional states, and behavior. While the underlying mechanisms remain poorly understood, human and animal studies have supported a role of neuroinflammation in the etiology of these diseases. In the central nervous system, an increased inflammatory response is capable of activating microglial cells, leading to the release of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. In turn, the pro-inflammatory cytokines aggravate and propagate neuroinflammation, degenerating healthy neurons and impairing brain functions. Therefore, activated microglia may play a key role in neuroinflammatory processes contributing to the pathogenesis of psychiatric disorders and neurodegeneration.

Analysis of current nursing homes in Korea and to assess the role and prospect of dentists in comparison to Japanese long term care insurance system / 대한치과보철학회지

STATEMENT OF PROBLEM: The introduction of "The Long-term Care Insurance System"(a public nursing care insurance scheme) is scheduled from July in 2008. Lately, the importance of oral health care had increased. Introduction and establishment of the methodology (nursing care procedure) based on professional dental knowledge is inevitable. PURPOSE: The purpose of this study was to rouse recognition of the importance of dental care in the long term elderly care in nursing homes, with implementation of the new insurance law. MATERIAL AND METHODS: Visited two institutions for the elderly, Yudang Village and Sungjiwon located in Suwon city to investigate the present conditions in terms of (1) the detailsof the institution, (2) the activities concerning with dental care in the institution, and (3) the consciousness and recognition regarding dental care of the staffs. RESULTS: In two institutions, under the present conditions, oral cleaning (including the cleaning of denture) for residents was operated with no professional advices and limited professional dental care. It was found that there was very little awareness of aspiration pneumonia. The members of staff however, did recognizethe necessity of professional maintenance and management of oral care in daily nursing care, and that many residents hold dental problems. They were very eager in introducing the methodology (nursing care procedure) in dental care in nursing homes.

Baicalein Protects 6-OHDA-induced Neuronal Damage by Suppressing Oxidative Stress

The protective effects of baicalein, one of the flavonoids in Scutellaria baicalensis Georgi, were evaluated against 6-hydroxydopamine (6-OHDA)-induced neuronal damage in mice and cultured human neuroblastoma cells. Nigrostriatal damage was induced by stereotaxically injecting 6-OHDA into the right striatum. Baicalein was administered intraperitoneally 30 min before and 90 min after lesion induction. Animals received a further daily injection of baicalein for 3 consecutive days. Two weeks after 6-OHDA injection, contralateral rotational asymmetry was observed by apomorphine challenge in lesioned mice. Tyrosine hydroxylase (TH) immunohistochemistry revealed a significant loss of terminals in lesioned striatum and the reduction of the numbers of TH-positive cell in the ipsilateral substantia nigra (SN). In addition, the levels of dopamine (DA) and DA metabolites were reduced and lipid peroxidation was increased in lesioned striatum. However, baicalein treatment reduced apomorphine-induced rotational behavior in 6-OHDA-lesioned mice, and increased TH immunoreactivity in the striatum and SN, and DA levels in lesioned striatum. Lipid peroxidation induced by 6-OHDA was also inhibited by baicalein treatment. Furthermore, when SH-SY5Y human neuroblastoma cells were treated with baicalein, 6-OHDA-induced cytotoxicity and reactive oxygen species (ROS) production were significantly reduced. These results indicate that baicalein effectively protects 6-OHDA-induced neuronal damage through antioxidant action.

An Epidemiological Study of Hip Fracture in Jeju Island, Korea / 대한정형외과학회잡지

PURPOSE: This prospective study conducted to estimate incidence of hip fracture among persons over 50 years of age, in Jeju island, Korea during the year 2002. MATERIALS AND METHODS: Patients over 50 years of age who lived in Jeju island and sustained a femoral neck or intertrochanteric fracture during the year 2002 (from January 1st 2002 to December 31th 2002) were investigated. The information collected from the hospital records for each patient included age, sex, the nature of injury, the day of injury, location, the method of treatment, and the degree of osteoporosis. The population figures were derived from the National Statistical Office. RESULTS: There were 151 fractures of the neck or intertrochanteric region of the femur (36 in men, 115 in women) in population over 50 years of age. The incidence was 12.8/10, 000 for total patients (7.3/10, 000 for men, 16.8/10, 000 for women). The standardized incidence rate against the 1985 U.S. population was 119/100, 000 for men and 187/100, 000 population for women. The incidence rate showed seasonal variations, being highest in fall. The mean age of patients was 77.1 years (range 50 -98 years). The most common cause of injury was a simple fall (131/151, 86.8%). There were 92 (60.9%) fractures of the neck and 59 (39.1%) of the intertrochanteric fracture. One hundred twenty six patients (83.4%) showed definite osteoporosis (Singh index, Grade I-III). CONCLUSION: The incidence rate of hip fracture increased 3.8 times in 2002 data (12.8/10, 000) in Jeju island when compared with 1991 data (3.4/10, 000) in Honam area. To have more accurate trend and estimate of incidence rate of osteoporotic fractures in the elderly, further longitudinal study need to be conducted.

Effects of Fetal Mesencephalic Cell Grafts on the Intrastriatal 6-hydroxydoapmine Lesioned Rats

The effects of fetal mesencephalic cell grafts on the restoration of nigrostriatal dopaminergic function were studied in the intrastriatal 6-hydroxydopamine-lesioned rats. Four weeks after lesioning, transplantation of ventral mesencephalic cells from embryonic day 14 fetuses showed the number of tyrosine hydroxylase (TH) positive cells and fiber outgrowth in the grafted striatum, and significantly ameliorated symptomatic motor behavior of the animals, as determined by apomorphine-induced rotation. Furthermore, in substantia nigra pars compacta (SNc), the numbers of TH cells and fibers were markedly restored. Dopamine content of ipsilateral SNc was close to that of contralateral SNc (91.9 9.8%) in the transplanted animals, while the ratio was approximately 32% in sham-grafted animals. These results indicate that grafted cells restored the activity for the dopaminergic neurons located in SNc, although they were transplanted into striatum. In addition, we showed that the implanted fetal cells expressed high level of glial cell line-derived neurotrophic factor (GDNF), suggesting that the transplanted fetal cells might serve as a dopamine producer and a reservoir of neurotrophic factors. These results may be helpful in consideration of the therapeutic transplantation at early stage of PD.

Involvement of Oxidative Stress and Poly (ADP-ribose) Polymerase Activation in 3-Nitropropionic Acid-induced Cytotoxicity in Human Neuroblastoma Cells

3-Nitropropionic acid (3-NP) inhibits electron transport in mitochondria, leading to a metabolic failure. In order to elucidate the mechanism underlying this toxicity, we examined a few biochemical changes possibly involved in the process, such as metabolic inhibition, generation of reactive oxygen species (ROS), DNA strand breakage, and activation of Poly (ADP-ribose) polymerase (PARP). Exposure of SK-N-BE (2) C neuroblastoma cells to 3-NP for 48 h caused actual cell death, while inhibition of mitochondrial function was readily observed when exposed for 24 h to low concentrations (0.2~2 mM) of 3-NP. The earliest biochemical change detected with low concentration of 3-NP was an accumulation of ROS (4 h after 3-NP exposure) followed by degradation of DNA. PARP activation by damaged DNA was also detectable, but at a later time. The accumulation of ROS and DNA strand breakage were suppressed by the addition of glutathione or N-acetyl-L-cysteine (NAC), which also partially restored mitochondrial function and cell viability. In addition, inhibition of PARP also reduced the 3-NP-induced DNA strand breakage and cytotoxicity. These results suggest that oxidative stress and activation of PARP are the major factors in 3-NP-induced cytotoxicity, and that the inhibition of these factors may be useful in protecting neuroblastoma cells from 3-NP-induced toxicity.

Identification of Fastidious Mycobacteria other than M. tuberculosis ( MOTT ) by Comparative Sequence Analysis of rpoB and 16S rDNA

Conventional tests for the identification of mycobacteria may frequently result in erroneous identification and underestimate the diversity within the genus Mycobacterium. However, this problem can be overcome by molecular approach like as 16S rRNA gene (rDNA) or RNA polymerase gene (rpoB) sequence analysis. In this study, a molecular approach analyzing partial sequence of 16S rDNA and rpoB gene was applied to mycobacteria other than M tuberculosis (MOTT) isolates that had not been definitely identified by conventional physical and biochemical tests. Among the eighteen isolates included in this study, twelve isolates could be identified to the species level and six were identified to the complex level. Compared with the results by 16S rDNA analysis, the rpoB analysis could di6erentiate some of the strains into the subspecies level.

Ceramide is Involved in MPP+ -induced Cytotoxicity in Human Neuroblastoma Cells

To understand the cytotoxic mechanism of MPP+, we examined the involvement of ceramide in MPP+ -induced cytotoxicity to human neuroblastoma SH-SY5Y cells. When SH-SY5Y cells were exposed to MPP+, MPP+ induced dose-dependent cytotoxicity accompanied by 2-fold elevation of intracellular ceramide levels in SH-SY5Y cells. Three methods were used to test the hypothesis that the elevated intracellular ceramide is related to MPP+ -induced cytotoxicity: C2-ceramide was directly applied to cells, sphingomyelinase (SMase) was exogenously added, and oleoylethanolamine (OE) was used to inhibit degradation of ceramide. Furthermore, inhibition of ceramide-activated protein phosphatase (CAPP), the effector of ceramide, using okadaic acid (OA) attenuated cell death but treatment of fumonisin B1, the ceramide synthase inhibitor, did not alter the cytotoxic effect of MPP+. Based on these, we suggest that the elevation of intracellular ceramide is one of the important mediators in MPP+ -induced cell death.

Impairment Grading in Orthopedic Certificates / 대한정형외과학회잡지

In orthopedic practice, patients sometimes ask certain kinds of medical documents certifying their disability grading. But many orthopedic surgeons are not accustomed to issue such medical certificates. So we want to review the way of evaluation and grading of disabilities for such different kinds of medical certificates(for examples: disability grading certificate for use in traffic accident, industrial accident, liability of national compensation, private insurance, the handicapped, military service and others) and compare the differences between them.

Tibia Fracture on Removal of Interlocking Medullary Nail: A report of 3 cases / 대한정형외과학회잡지

Interlocking medullary nails have been widely used in the treatment of long bone fractures especially in tibia and femur. But with increasing use of nails, many preoperative, intra-operative and post-operative complications have been reported. We have experienced 3 cases of very rare complication, fracture of tibia shaft which occurred during removal of interlocking medullary nail after complete healing of original tibial fracture. We report these rare complications with literature review.

Diganostic Values of Bone Scan Followed by CT Scan in Undetected Pelvic bone Fracture / 대한정형외과학회잡지

Pelvic bone is complex in its shape, so we often miss to find the fractures in cases with unclear fracture line. We studied 25 patients who were suspected to have occult fractures in pelvic area. We were able to find lots of occult fractures with bone scan followed by CT scan. The results were as follows; 1. There were 31 unexpected hot spots in 25 patients in bone scan. 2. Six cases (19.3%j of new injuries were found on re-evaluation of plain film or additionally rechecked plain films. 3. Twenty-one new fractures (67.7%) were found on CT film study. 4. Total 27 additional fractures (89.1%) were found after bone scan followed CT scan. In conclusion Bone Scan followed by CT is a effective method of detecting occult fracture in pelvic area.

Treatment of Radial Neck Fractures in Children / 대한정형외과학회잡지

In children, the radial neck fractures are treated in various ways, including long arm cast without closed reduction, long arm cast following C/R by Patterson's or Pesudo's method, open reduction with or without K-wire fixation. We treated 25 children with radial neck fracture who visited DaeDong General Hospital from March 1992 to February 1995, and followed up average 17.4 months (from 13 months to 27 months). The results of clinical analysis are as follows: l. Age distribution was from 3 to 15 years old, and the mean was 9.4 years old. 2. Twelve cases showing less than 30degrees initial angulation were treated with long arm cast without reduction, and all of them resulted in excellent result. 3. Patterson s C/R method was useful in cases with angulation between 30degrees ~45degrees. In patients with more than 45degreesangulation, Pesudo method was more effective. 4. 3 cases with 90 angulation were treated by open reduction and internal fixation, and all of them showed unexpected excellent results. 5. Premature epiphyseal closure was present in 2 cases but both of them revealed good functional result.

Radial Neck Fracture with 90° Complete Displacement: Report of 3 Cases / 대한정형외과학회잡지

Complete fractures of radial neck or proximal radial epiphysis with 90° displacement are very rare, and only several cases were reported in the literatures. We have experienced 2 cases of radial neck fracture with 90° posterior displacement and one case with anterior displacement. All of them were treated operatively. We followed up these 3 cases more than 15 months and report the results with review of literatures.

Glomus Tumor: 4 cases Report / 대한정형외과학회잡지

Glomus tumor is well recognized and documented lesion which usually presents as painful dermal nodules in fingers. The tumor results from hypertrophy of a glomus, which is a normal structure of the skin, a coiled arterioyenous shunt regulating body temperature. Glomus tumor may occur at any age but is most frequent in the middle age of life. Pain, tenderness and cold sensitivity are the classic triad of symptoms. Complete surgical exision is the treatment of choice for glomus tumors. Successful removal of tumor leads to complete relief of pain and return to normal function. We report 4 cases of subungual glomus tumor successfully treated by complete exision with review of literatures.

Problems in issuing medical certificate in orthopedic field / 대한정형외과학회잡지

No abstract available.