Identification of predictive factors for early relapse in patients with unresectable stage III non-small cell lung cancer receiving consolidation durvalumab after concurrent chemoradiation therapy.

BACKGROUND: Patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC) receiving definitive concurrent chemoradiation therapy (CCRT) benefit from durvalumab consolidation therapy. However, predictive factors for early relapse during durvalumab maintenance have not yet been identified. METHODS: The present study included the lung cancer cohort of the Catholic Medical Centers at the Catholic University of Korea from January 2018 to December 2021. A total of 51 NSCLC patients treated with durvalumab consolidation therapy after definitive CCRT were included in the analysis. Early relapse was defined as patients experiencing relapse within 6 months of starting initial durvalumab therapy. RESULTS: Among the 51 patients, 15 (29.4%) relapsed during the study period. Median time from initial therapy of durvalumab to progression was 451.00 ± 220.87 days (95% confidence interval [CI]: 18.10-883.90) in overall patients. In multivariate analysis, younger age (adjusted odds ratio [aOR], 0.792; 95% CI: 0.642-0.977; p = 0.030), higher pack-years (aOR, 1.315; 95% CI: 1.058-1.635; p = 0.014), non-COPD (aOR, 0.004; 95% CI: 0.000-0.828; p = 0.004) and anemia (aOR, 234.30; 95% CI: 1.212-45280.24; p = 0.042), were independent predictive factors for early relapse during durvalumab consolidation therapy. CONCLUSION: Younger age, higher number of pack-years, non-COPD, and anemia were independent predictive factors for early relapse during durvalumab consolidation therapy in patients with unresectable stage III NSCLC after definitive CCRT. Careful patient selection and clinical attention are needed for high-risk individuals.

Cognitive impairment is associated with elevated serum homocysteine levels among older adults.

PURPOSE: The aim of this study was to examine the associations between the risk of cognitive impairment and the serum levels of folate, vitamin B12, and homocysteine (Hcy). METHODS: Subjects were persons aged 60-79 years who participated in the Yangpyeong Cohort study between 2011 and 2012. Cognitive impairment and normal subjects consisted of 100 pairs of old adults matched by age, sex, and education levels. Cognitive function was evaluated with the Korean version of the Mini-Mental State Examination for Dementia Screening (MMSE-DS). Pearson's partial correlation coefficients and conditional multiple logistic regression analysis were applied to determine the associations between cognitive function and the serum levels of folate, vitamin B12, and Hcy. RESULTS: Compared with the matched normal group, the cognitive impairment group had higher proportions of folate deficiency (< 3 ng/mL) and hyperhomocysteinemia (≥ 15 µmol/L). Serum Hcy concentrations were inversely associated with serum folate (r = - 0.234, p = 0.001) and MMSE-DS score (r = - 0.150, p = 0.037) after adjusting for age, sex, and education. The high Hcy group showed a higher prevalence of cognitive impairment (4th vs. 1st quartile, OR 3.30, 95% CI 1.12-9.72, p for trend = 0.014) after adjusting for exercise. CONCLUSIONS: The present findings suggest a putative protective role of high serum folate and normal Hcy against cognitive impairment among older adults.

Periodontitis Is Associated with Cognitive Impairment in Elderly Koreans: Results from the Yangpyeong Cohort Study.

OBJECTIVES: To investigate the association between periodontitis and cognitive impairment in elderly Koreans. DESIGN: Cross-sectional study with age- and sex-matched case-control selection. SETTING: The Yangpyeong cardiovascular cohort (YCC), a part of the Korean Genome Epidemiologic Study (KoGES), Yangpyeong, South Korea. PARTICIPANTS: Individuals with cognitive impairment (n=65) and cognitively normal controls (n=124) aged 60 and older from the YCC. MEASUREMENTS: Alveolar bone loss was assessed on dental panoramic radiographs to categorize the cumulative history of periodontitis (HOP) into three groups: normal, moderate periodontitis, severe periodontitis. The Mini-Mental State Examination (MMSE) was used to categorize participants as cognitively normal or cognitively impaired. Age- and sex-matched conditional logistic regression models were used for analysis. Confounders considered in the analysis were age, sex, drinking, smoking, exercise, total cholesterol, total protein, body mass index, fasting plasma glucose, intima-media thickness, hypertension medication, and depression. RESULTS: Participants with HOP were more likely to have cognitive impairment than those without (odds ratio=2.14, 95% confidence interval=1.04-4.41). The interaction effect of smoking and exercise on periodontitis highlighted the link. CONCLUSION: Periodontitis was independently associated with cognitive impairment after controlling for various confounders. Further longitudinal research is needed to determine whether periodontitis plays a role in cognitive decline in older adults.

Dietary Patterns Derived by Cluster Analysis are Associated with Cognitive Function among Korean Older Adults.

The objective of this study was to investigate major dietary patterns among older Korean adults through cluster analysis and to determine an association between dietary patterns and cognitive function. This is a cross-sectional study. The data from the Korean Multi-Rural Communities Cohort Study was used. Participants included 765 participants aged 60 years and over. A quantitative food frequency questionnaire with 106 items was used to investigate dietary intake. The Korean version of the MMSE-KC (Mini-Mental Status Examination-Korean version) was used to assess cognitive function. Two major dietary patterns were identified using K-means cluster analysis. The "MFDF" dietary pattern indicated high consumption of Multigrain rice, Fish, Dairy products, Fruits and fruit juices, while the "WNC" dietary pattern referred to higher intakes of White rice, Noodles, and Coffee. Means of the total MMSE-KC and orientation score of the participants in the MFDF dietary pattern were higher than those of the WNC dietary pattern. Compared with the WNC dietary pattern, the MFDF dietary pattern showed a lower risk of cognitive impairment after adjusting for covariates (OR 0.64, 95% CI 0.44-0.94). The MFDF dietary pattern, with high consumption of multigrain rice, fish, dairy products, and fruits may be related to better cognition among Korean older adults.

Dietary patterns and cognitive function in Korean older adults.

PURPOSE: The objectives of this study were to identify major dietary patterns and to investigate the association between dietary patterns and cognitive function in older adults. METHODS: This is a cross-sectional study. The data from the Korean Multi-Rural Communities Cohort Study, which is a part of the Korean Genome Epidemiology Study, were used. There were 806 (340 men and 466 women) subjects aged ≥ 60 years. Usual dietary intake was assessed using a quantitative food frequency questionnaire with 106 food items. Cognitive function was assessed using the Korean version Mini-Mental State Examination (MMSE-KC). We conducted factor analysis using the principal component analysis method to identify the major dietary patterns. The association between major dietary patterns and cognitive function was investigated by logistic regression analysis. RESULTS: Three major dietary patterns were identified and assigned descriptive names based on the food items with high loadings: "prudent" pattern, "bread, egg, and dairy" pattern, and "white rice only" pattern. As the white rice only pattern scores increased, a significant decreasing trend for MMSE-KC scores was observed after adjusting for covariates. The bread, egg, and dairy pattern was inversely related to the risk of cognitive impairment, and the white rice only pattern was positively associated with the risk of cognitive impairment. CONCLUSIONS: This study suggests that specific dietary patterns were significantly associated with cognitive impairment in older adults. In particular, like the white rice only pattern, a rice-centered diet without well-balanced meals may increase the risk of cognitive impairment. However, since our study is a cross-sectional design, the possibility of reverse causality should be considered.

Association between living arrangements and depressive symptoms among older women and men in South Korea.

PURPOSE: We investigated the relationship between different types of living arrangements and depressive symptoms among older Korean women and men. METHODS: Data were obtained from a nationally representative cross-sectional health survey conducted in 2009 in South Korea. A total of 60,305 participants (34,172 women and 26,133 men) aged 60 years and older were included in the analysis. The living arrangements were categorised into six types as follows: (1) living with a spouse only; (2) living with a spouse in an extended family; (3) living with a spouse in a nuclear family; (4) living alone; (5) living without a spouse in an extended family; and (6) living without a spouse in a nuclear family. The Korean version of the Center for Epidemiologic Studies Depression Scale was used as the measurement tool for depressive symptoms. We used multiple regression analysis to estimate the effects of living arrangement on depressive symptoms. RESULTS: A total of 16.8 % of the total study population showed depressive symptoms. Living with a spouse only was the most common type of living arrangement (46.3 %). Women and men living with a spouse only were the least likely to have depressive symptoms. However, living without a spouse in a nuclear family and living alone were most strongly associated with depressive symptoms in women (OR 1.81; 95 % CI 1.64-2.00) and men (OR 2.71; 95 % CI 2.43-3.03), respectively. CONCLUSIONS: The prevalence of depressive symptoms are associated with the living arrangements of elderly Koreans. There are gender differences in these associations, that may stem from the different demands of social roles and relationships in the family.

Psychosocial, physical, and autonomic correlates of depression in korean adults: results from a county-based depression screening study.

OBJECTIVE: We aimed to investigate the prevalence and psychosocial and neurophysiological correlates of depression in a large county-based cohort of Korean adults. METHODS: We recruited 2355 adults from a rural county-based health promotion program. The following psychometric scales were used: the Center for Epidemiologic Studies Depression scale (CES-D) was used to assess depression, the General Health Questionnaire (GHQ) was used to evaluate stress, and the Medical Outcome Study Social Support Survey (MOS-SSS) was used to determine perceived social support. Heart rate variability (HRV) was used to assess neurophysiological properties. The psychosocial and neurophysiological variables of adults with depression (CES-D score ≥25) and without depression (CES-D score <25) were statistically compared. A logistic regression model was constructed to identify factors independently associated with depression. RESULTS: We estimated that 17.7% of the subjects had depression, which was associated with old age, being female, being single, less religious affiliation, high education, low body mass index (BMI), low levels of aerobic exercise, low social support, and a low HRV triangular index. The explanatory factors of depression included high education, less religious affiliation, low levels of current aerobic exercise, low BMI, and low social support. CONCLUSION: Given the relatively high prevalence of overall depression, subsyndromal depression should also be regarded as an important issue in screening. The independent factors associated with depression suggest that practical psychosocial intervention, including brief psychotherapy, aerobic exercise, and other self-help methods should be considered. In addition, the HRV results suggest that further depression screening accompanied by neurophysiological features would require fine methodological modifications with proactive efforts to prevent depressive symptoms.

Prevalence and correlates of depressive symptoms in korean adults: results of a 2009 korean community health survey.

The aim of this study was to investigate the prevalence and correlates of depressive symptoms in the largest number of Korean individuals examined to date. We analyzed cross-sectional data collected from 229,595 Korean adults aged 19 yr and above who participated in a Korean Community Health Survey conducted in 2009. The Center for Epidemiologic Studies Depression Scale (CES-D) was used as the measurement tool for depressive symptoms (CES-D score over 16) and definite depression (CES-D score over 25). Multivariate logistic regression analysis was performed to identify associations between sociodemographic factors and depressive symptoms. The percentages of depressive symptoms and definite depression in the total study population were 11% (7.8% for men, 14.0% for women) and 3.7%, (2.4% for men, 5.0% for women), respectively. Female gender, older age, disrupted marital status, low education and income level, multigenerational household composition and metropolitan residence were associated with greater risk of depressive symptoms. The present study provides a valid prevalence and correlates of depressive symptoms, using the largest representative sample of the Korean general population to date. Various sociodemographic factors contribute to the prevalence and effects of depressive symptoms in Korea.

Erythrocyte α-linolenic acid is associated with the risk for mild dementia in Korean elderly.

n-3 polyunsaturated fatty acids (PUFA) play an important role in brain development and function, but there is conflicting evidence between the relationship of n-3 PUFA and dementia in the elderly. The purpose of the present study was to test the hypothesis that n-3 PUFA content of erythrocytes is associated with mild dementia in elderly Koreans. Fifty-seven elderly (age ≥65 years) patients (19 male, 38 female) were recruited, and indicators of dementia (intake, erythrocyte fatty acid composition, and Mini-Mental Status Examination-Korean Version [MMSE-K]) were evaluated. Patients were divided into groups based on their MMSE-K score: normal control group (score >21 [n = 24]) and deficit group (score ≤21 [n = 33]). Multivariate-adjusted regression analysis showed that a higher level of α-linolenic acid (ALA; 18:3n-3) significantly decreased the risk of mild dementia after adjusting for age, sex, and height. MMSE-K score was also significantly and positively associated with erythrocyte ALA and total n-3 PUFA. However, erythrocyte levels of docosahexaenoic acid (22:6n-3) and eicosapentaenoic acid (20:5n-3) were not significantly related with the risk of mild dementia and MMSE-K score. Dietary intake was also not significantly associated with the risk of mild dementia and MMSE-K score after adjusting for age, sex, height, and energy intake. In conclusion, ALA derived from plant sources of n-3 PUFA, but not eicosapentaenoic acid and docosahexaenoic acid from fish, decreased the risk for mild dementia among the Korean elderly.

Matrix metalloproteinase-9 promoter polymorphisms in Korean patients with systemic lupus erythematosus.

To investigate the association between functional promoter polymorphisms of matrix metalloproteinase-9 (MMP-9) and systemic lupus erythematosus (SLE), we analyzed MMP-9 promoter -1562 C>T and MMP-9 -90 (CA)(n) repeat polymorphisms in 135 Korean SLE patients (mean age, 34.7 years; 124 female and 11 male) and in 135 gender- and age-matched healthy controls (mean age, 35.4 years). Clinical and laboratory findings were collected during the follow-up period (mean, 63.5 months; range, 3-252 months), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Indexes were calculated. The levels of total MMP-9 were measured in sera of SLE patients and controls by enzyme-linked immunoabsorbent assay. The serum levels of MMP-9 in SLE patients were significantly lower than those of controls (mean +/- standard error of the mean, 1421.6+/-177.4 vs 3731.4+/-441.4 ng/ml, p=1.2 x 10(-5) by t test). Both functional polymorphisms were under the Hardy-Weinberg equilibrium state except (CA)(n) repeat polymorphisms in SLE patients (p=2.6 x 10(-5) by chi(2) goodness-of-fit test). The distribution of the MMP-9 promoter polymorphisms or haplotypes was not significantly different in SLE patients and controls. However the frequency of alleles with low numbers of CA repeats (n<21, 11.9% vs 7.0%, p=0.06 by the chi(2) test; odds ratio=1.78, 95% confidence interval=0.99-3.20) and the prevalence of low CA repeats homozygote tended to be higher in patients than in controls (5.2% vs 0.7%, p=0.07 by logistic regression, odds ratio=7.29, 95% confidence interval=0.88-60.10) in the recessive model. No relationship was found between MMP-9 polymorphisms and clinical features or damage as indicated by SLICC/ACR Damage Index in the study subjects. These results suggest that genetic polymorphisms of the MMP-9 promoter regions are not associated with the development of SLE in Korea.

AK2 activates a novel apoptotic pathway through formation of a complex with FADD and caspase-10.

Mitochondrial proteins function as essential regulators in apoptosis. Here, we show that mitochondrial adenylate kinase 2 (AK2) mediates mitochondrial apoptosis through the formation of an AK2-FADD-caspase-10 (AFAC10) complex. Downregulation of AK2 attenuates etoposide- or staurosporine-induced apoptosis in human cells, but not that induced by tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL) or Fas ligand (FasL). During intrinsic apoptosis, AK2 translocates to the cytoplasm, whereas this event is diminished in Apaf-1 knockdown cells and prevented by Bcl-2 or Bcl-X(L). Addition of purified AK2 protein to cell extracts first induces activation of caspase-10 via FADD and subsequently caspase-3 activation, but does not affect caspase-8. AFAC10 complexes are detected in cells undergoing intrinsic cell death and AK2 promotes the association of caspase-10 with FADD. In contrast, AFAC10 complexes are not detected in several etoposide-resistant human tumour cell lines. Taken together, these results suggest that, acting in concert with FADD and caspase-10, AK2 mediates a novel intrinsic apoptotic pathway that may be involved in tumorigenesis.

Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I/II clinical trial.

To assess the safety and therapeutic efficacy of autologous human bone marrow cell (BMC) transplantation and the administration of granulocyte macrophage-colony stimulating factor (GM-CSF), a phase I/II open-label and nonrandomized study was conducted on 35 complete spinal cord injury patients. The BMCs were transplanted by injection into the surrounding area of the spinal cord injury site within 14 injury days (n = 17), between 14 days and 8 weeks (n = 6), and at more than 8 weeks (n = 12) after injury. In the control group, all patients (n = 13) were treated only with conventional decompression and fusion surgery without BMC transplantation. The patients underwent preoperative and follow-up neurological assessment using the American Spinal Injury Association Impairment Scale (AIS), electrophysiological monitoring, and magnetic resonance imaging (MRI). The mean follow-up period was 10.4 months after injury. At 4 months, the MRI analysis showed the enlargement of spinal cords and the small enhancement of the cell implantation sites, which were not any adverse lesions such as malignant transformation, hemorrhage, new cysts, or infections. Furthermore, the BMC transplantation and GM-CSF administration were not associated with any serious adverse clinical events increasing morbidities. The AIS grade increased in 30.4% of the acute and subacute treated patients (AIS A to B or C), whereas no significant improvement was observed in the chronic treatment group. Increasing neuropathic pain during the treatment and tumor formation at the site of transplantation are still remaining to be investigated. Long-term and large scale multicenter clinical study is required to determine its precise therapeutic effect. Disclosure of potential conflicts of interest is found at the end of this article.

Fractal analysis of EEG in hypnosis and its relationship with hypnotizability.

Fractal analysis was applied to study the trends of EEG signals in the hypnotic condition. The subjects were 19 psychiatric outpatients. Hypnotizability was measured with the Hypnotic Induction Profile (HIP). Fifty-four sets of EEG data were analyzed by detrended fluctuation analysis (DFA), a well-established fractal analysis technique. The scaling exponents, which are the results of fractal analysis, are reduced toward white noise during the hypnotic condition, which differentiates the hypnotic condition from the waking condition. Further, the decrease in the scaling exponents during hypnosis was solely associated with the eye-roll sign within specific cortical areas (F3, C4, and O1/2) closely related to eye movements and attention. In conclusion, the present study has found that the application of the fractal analysis technique can demonstrate the electrophysiological correlations with hypnotic influence on cerebral activity.

The short vitamin D receptor is associated with increased risk for generalized aggressive periodontitis.

BACKGROUND: Generalized aggressive periodontitis (GAP) exhibits severe inflammation and alveolar bone loss. Vitamin D receptor (VDR) regulates both bone metabolism and inflammation-related genes, and its polymorphisms and haplotypes may affect the functional activity of the VDR protein in GAP. OBJECTIVE: We analysed the genetic effect of VDR start codon, intron, and exon polymorphisms, and their haplotypes on the development of GAP. MATERIALS AND METHODS: The VDR start codon 27823C > T (rs2228570, FokI), intron 8 60890G > A (rs154410, BsmI), and exon 9 61968T > C (rs731236, TaqI) polymorphisms were determined by using the polymerase chain reaction-restriction fragment length polymorphism analysis among 93 GAP patients and 143 healthy controls. RESULTS: The VDR start codon 27823*C/*C genotype was associated with an increased risk for GAP [odds ratio (OR) = 1.83, p = 0.028], but the intron 8 60880G > A and exon 9 61968T > C polymorphisms were not associated with GAP. The VDR haplotype homozygote ht1(C-G-T) carrying 27823*C allele was associated with a 1.8-fold increased risk of GAP (OR = 1.84, p = 0.030). CONCLUSION: These results demonstrate that the short VDR (27823*C/*C) protein may influence GAP susceptibility.

Sexual and physical abuse among Korean female inpatients with schizophrenia.

The study reports the prevalence and correlates of sexual and physical abuse in a sample of 100 female inpatients with schizophrenia in South Korea. Clinical assessment interviews consisted of the Positive and Negative Syndrome Scale, the Scale for the Assessment of Positive Symptoms, an interview assessing history of sexual and repeated physical abuse, and demographic and psychosocial factors. Lifetime prevalence of severe sexual or physical abuse was 52%. Compared with nonabused patients (n = 48), the abused patients (n = 52) showed more nonpsychotic symptoms (i.e., anxiety, depression) and higher levels of distress, but no difference in psychotic symptoms. This study failed to note significant differences in positive symptoms addressed in previous Western studies.

Cardiomyopathy associated with clozapine.

Clozapine is an atypical antipsychotic agent that is more effective than the standard neuroleptics currently used for treating refractory schizophrenia. In addition, clozapine is a drug with few extrapyramidal side effects. However, clozapine is also associated with potentially serious adverse effects, such as cardiac complications as well as agranulocytosis. Clozapine-related cardiomyopathy has not been previously reported in East Asia. This report describes a 31-year-old Korean male patient with schizophrenia who developed dilated cardiomyopathy on treatment with clozapine. The removal of clozapine caused subsequent physical improvement. However, the readministration of clozapine for managing relapse of psychosis caused a recurrence of dilated cardiomyopathy in this patient. Therefore, this is the 1st report showing that the 2nd trial of clozapine caused recurrence of cardiomyopathy associated with clozapine. Thus, this report adds important support for a causal relation between clozapine and cardiac complications. In conclusion, this report attempts to raise awareness of clozapine-related cardiomyopathy.

Clinical effectiveness of urinary human chorionic gonadotropin related protein (hCGRP) quantification for diagnosis of ectopic pregnancy.

We detected pregnancy related new molecule, human chorionic gonadotropin related protein (hCGRP) in the urine of a pregnant women by using a monoclonal antibody against the human chorionic gonadotropin (hCG). This study examined the effectiveness of urinary hCGRP quantification in diagnosing ectopic pregnancy. This study included 40 normal pregnant women and 25 patients with ectopic pregnancy. Patients' serum and urinary intact whole hCG (i-hCG) and hCGRP concentrations were measured using sandwich ELISA and the ratio of hCGRP to i-hCG was calculated. Statistical analysis was performed using statistical package for social sciences (SPSS) 10.0. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the cut-off value to discriminate ectopic pregnancies from normal intrauterine pregnancies. Urinary hCGRP and hCGRP/i-hCG ratio in ectopic pregnancy group (14 +/- 6.6 ng/mL, 4.6 +/- 1.9%, respectively) were significantly lower than those of normal pregnancy group (149 +/- 10.2 ng/mL, 29.7 +/- 1.9%, respectively; p<0.001). Based on ROC curve analysis, a cut-off point of urinary hCGRP/i-hCG ratio <16.2% discriminated between ectopic pregnancy and normal pregnancy with a sensitivity, specificity, positive predictive value and negative predictive value of 92.0%, 90.0%, 32.6%, and 99.5%, respectively. Urinary hCGRP/i-hCG ratio measurement may be effective in diagnosing ectopic pregnancy.

Phosphorylation of ERK and CREB in cultured hippocampal neurons after haloperidol and risperidone administration.

The purpose of the present paper was to determine whether the brief exposure of neurons to antipsychotic drugs is associated with the activation of extracellular signal-regulated kinases (ERK) and cyclic adenosine 3',5'-monophosphate (cAMP) response element (CRE) binding protein (CREB). The activation of ERK-1/2 and CREB can be monitored by immunoblotting with antibodies that specifically recognize p-ERK-1/2 (phosphorylated on Thr-202 and Tyr-204) and p-CREB (phosphorylated on Ser-133). In hippocampal neuron cultures at 25 days in vitro (DIV), the levels of ERK and CREB phosphorylation significantly increased after treatment with haloperidol (50 nmol/L) and risperidone (50 nmol/L), except when risperidone was administered at the p-CREB level. However, risperidone also increased the p-CREB level at an insignificant rate in the same direction. At 10 DIV, none of the antipsychotic drugs significantly increased the level of ERK and CREB phosphorylation. The difference between levels of ERK and CREB phosphorylation in response to haloperidol and risperidone at 25 DIV was also observed. Risperidone significantly increased the level of ERK-1/2 phosphorylation, but not the level of CREB phosphorylation. Haloperidol, in contrast, had a different effect. These data indicate that neuronal maturation affects the phosphorylation of ERK and CREB in response to antipsychotic drugs. Furthermore, these results demonstrate that different antipsychotic drugs could lead to different profiles of ERK and CREB phosphorylation in neurons.

Down-regulation of ARC contributes to vulnerability of hippocampal neurons to ischemia/hypoxia.

ARC is a caspase recruitment domain-containing molecule that plays an important role in the regulation of apoptosis. We examined ARC expression during neuronal cell death following ischemic injury in vivo and in vitro. After exposure to transient global ischemic conditions, the expression of ARC was substantially reduced in the CA1 region of hippocampus in a time-dependent manner with concomitant increase of TUNEL-positive cells. Quantitative analysis using Western blotting exhibited that most of ARC protein disappeared in the cultured hippocampal neurons exposed to hypoxia for 12 h and showing 60% cell viability. Forced expression of ARC in the primary cultures of hippocampal neurons or B103 neuronal cells significantly reduced hypoxia-induced cell death. Further, the C-terminal P/E rich region of ARC was effective to attenuate hypoxic insults. These results suggest that down-regulation of ARC expression in hippocampal neurons may contribute to neuronal death induced by ischemia/hypoxia.