Search

Cardiovascular disease remains a leading cause of morbidity and mortality after kidney transplantation (KT). Although statins reduce cardiovascular risk and have renal benefits in the general population, their effects on KT recipients are not well-established. We studied the effects of early statin use (within 1-year post-transplantation) on long-term outcomes in 714 KT recipients from the Korean cohort study for outcome in patients with KT. Compared with the control group, statin group recipients were significantly older, had a higher body mass index, and had a higher prevalence of diabetes mellitus. During a median follow-up of 85 months, 74 graft losses occurred (54 death-censored graft losses and 20 deaths). Early statin use was independently associated with lower mortality (hazard ratio, 0.280; 95% confidence interval 0.111–0.703) and lower death-censored graft loss (hazard ratio, 0.350; 95% confidence interval 0.198–0.616). Statin therapy significantly reduced low-density lipoprotein cholesterol levels but did not decrease the risk of major adverse cardiovascular events. Biopsy-proven rejection and graft renal function were not significantly different between statin and control groups. Our findings suggest that early statin use is an effective strategy for reducing low-density lipoprotein cholesterol and improving patient and graft survival after KT. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease influenced by a complex interplay of genetic and environmental factors. The activation of the JAK-STAT pathway increases the expression of inflammatory cytokines such as IL-4 and IL-13, further deteriorating AD. Therefore, for the treatment of AD, the JAK-STAT pathway is emerging as a significant target, alongside inflammatory cytokines. This study investigates the potential therapeutic effects of a novel herbal complex, LK5, composed of Scutellaria baicalensis, Liriope platyphylla, Sophora flavescens, Dictammus dasycarpus, and Phellodendron schneider, known for their anti-inflammatory and immune-modulating properties. We examined the anti-inflammatory and anti-AD effects of the LK5 herbal complex in HaCaT cells stimulated by LPS and IL-4/IL-13, as well as in a mouse model of AD induced by DNCB. In HaCaT cells stimulated with LPS or IL-4/IL-13, the LK5 herbal complex demonstrated anti-inflammatory effects by inhibiting the expression of inflammatory cytokines including TNF-α, IL-6, and IL-1β, and downregulating the phosphorylation of STAT proteins. In a murine AD-like model induced by DNCB, administration of the LK5 herbal complex significantly ameliorated clinical symptoms, including dermatitis, ear thickness, and TEWL. Histological analysis revealed a reduction in epidermal thickness and mast cell infiltration. The LK5 herbal complex also inhibited pruritus induced by compound 48/80. Furthermore, the LK5 herbal complex treatment significantly decreased the levels of inflammatory cytokines such as TSLP, IL-6, and IgE in plasma and ear tissue of AD-induced mice. These findings suggest that the LK5 herbal complex may modulate the immune response and alleviate AD symptoms by inhibiting STAT pathways. [ABSTRACT FROM AUTHOR]

Background: The Living Kidney Donor Profile Index (LKDPI) was developed in the United States to predict graft outcomes based on donor characteristics. However, there are significant differences in donor demographics, access to transplantation, proportion of ABO incompatibility, and posttransplant mortality in Asian countries compared with the United States. Methods: We evaluated the clinical relevance of the LKDPI score in a Korean kidney transplant cohort by analyzing 1860 patients who underwent kidney transplantation between 2000 and 2019. Patients were divided into three groups according to LKDPI score: <0, 1–19.9, and ≥20. Results: During a median follow‐up of 119 months, 232 recipients (12.5%) experienced death‐censored graft loss, and 98 recipients (5.3%) died. High LKDPI scores were significantly associated with increased risk of death‐censored graft loss independent of recipient characteristics (LKDPI 1–19.9: HR 1.389, 95% CI 1.036–1.863; LKDPI ≥20: HR 2.121, 95% CI 1.50–2.998). High LKDPI score was also significantly associated with increased risk of biopsy‐proven acute rejection and impaired graft renal function. By contrast, overall patient survival rates were comparable among the LKDPI groups. Conclusion: High LKDPI scores were associated with an increased risk of death‐censored graft loss, biopsy‐proven acute rejection, and impaired graft renal function among a Korean kidney transplant cohort. [ABSTRACT FROM AUTHOR]

Senior living is an emerging research topic among hospitality scholars. Drawing upon the theory of planned behavior, this study examines the determining factors of potential residents, Baby Boomers, moving into senior living communities. We developed a survey derived from expert interviews, and data (n = 400) were collected via Qualtrics. The results show that personal privacy and employee competency develop a positive attitude toward senior living; friends and church members are greater social influences than family members; and psychological preparation and being a decision maker improves seniors’ perception of behavioral control. The synergistic interaction indicates a sense of control over their life could further enhance the positive attitude toward Boomers’ decision to choose senior living. The managerial implications are discussed for industry practitioners. [ABSTRACT FROM AUTHOR]

Glucose utilization by visceral adipose tissue (VAT) reflects inflammatory activity, which also promotes tumor growth and carcinogenesis. The effect of metabolically active VAT on survival outcomes in breast cancer is unknown. We investigated survival outcomes in patients with breast cancer based on the standardized uptake value (SUV) of VAT (SUVmean-VAT) using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). A total of 148 patients with breast cancer were divided into high- and low groups according to their SUVmean-VAT and SUVmax-tumor. Clinical characteristics and survival outcomes were compared between the groups. High SUVmean-VAT was associated with poor recurrence-free survival (RFS; hazard ratio [HR], 2.754; 95% confidence interval [CI], 1.090–6.958, p = 0.032) and distant metastasis-free survival (DMFS; HR, 3.500; 95% CI, 1.224–10.01, p = 0.019). Multivariate analysis showed that high SUVmean-VAT was a significant factor for poor RFS and poor DMFS (p = 0.023 and 0.039, respectively). High SUVmax-tumor was significantly associated with short RFS (p = 0.0388). Tumors with a high SUV tended to have a short DMFS, although the difference was not significant (p = 0.0718). Our findings showed that upregulated glucose metabolism in the VAT measured using 18F-FDG PET/CT may be a prognostic biomarker for adverse outcomes in breast cancer. [ABSTRACT FROM AUTHOR]

Tacrolimus is the mainstay of immunosuppression in liver transplantation to prevent rejection. However, the clinical use of tacrolimus is complicated by its narrow therapeutic window and significant intra-patient variability (IPV). High tacrolimus IPV is associated with overexposure and adverse effects, including malignancy. The effects of tacrolimus IPV in liver transplant recipients with and without hepatocellular carcinoma (HCC) are unknown. We investigated the association between tacrolimus IPV and transplant outcomes in 636 liver transplant patients. Tacrolimus IPV was determined by calculating the coefficient of variance (CV) of outpatient tacrolimus trough levels from 3 to 12 months after transplantation. High tacrolimus IPV was defined as CV > 30%. Patients were grouped according to tacrolimus IPV and HCC status. Among 636 liver transplant patients, 349 had HCC and 287 had no HCC. Overall survival in HCC patients was significantly reduced with high tacrolimus IPV (P < 0.001), whereas survival of non-HCC patients was not associated with tacrolimus IPV. Multivariable analysis confirmed the independent association between high tacrolimus IPV and overall mortality in HCC patients (HR, 3.010; 95% CI, 1.084–4.918). HCC recurred in 59 patients (16.9%) post-transplantation. After adjusting for donor/recipient factors, immunosuppression, and tumor characteristics, high tacrolimus IPV was independently associated with an increased risk of HCC recurrence (HR, 2.196; 95% CI, 1.272–3.791). High tacrolimus IPV was associated with significantly increased risks of overall mortality and HCC recurrence in liver transplant recipients with HCC. [ABSTRACT FROM AUTHOR]

Tenascin-C is an extracellular matrix glycoprotein strongly expressed in coronary atherosclerotic plaque. Aptamers are single-stranded oligonucleotides that bind to specific target molecules with high affinity. This study hypothesized that tenascin-C expression at atherosclerotic plaque in vivo could be detected by tenascin-C specific aptamers using positron emission tomography (PET). This paper reports the radiosynthesis of a fluorine-18 (18F)-labeled tenascin-C aptamer for the biodistribution and PET imaging of the tenascin-C expression in apolipoprotein E-deficient (ApoE−/−) mice. The aortas ApoE−/− mice showed significantly increased positive areas of Oil red O staining than control C57BL/6 mice, and tenascin-C expression was detected in foam cells accumulated in the subendothelial lesions of ApoE−/− mice. The ex vivo biodistribution of the 18F-labeled tenascin-C aptamer showed significantly increased uptake at the aorta of ApoE−/− mice, and ex vivo autoradiography of aorta revealed the high accumulation of the 18F-labeled tenascin-C aptamer in the atherosclerotic lesions of ApoE−/− mice, which was consistent with the location of the atherosclerotic plaques detected by Oil red O staining. PET imaging of the 18F-labeled tenascin-C aptamer revealed a significantly higher mean standardized uptake in the aorta of the ApoE−/− mice than the control C57BL/6 mice. These data highlight the potential use of tenascin-C aptamer to diagnose atherosclerotic lesions in vivo. • Tenascin-C expressed in the atherosclerotic lesions of aorta obtained from ApoE−/− mice. • Accumulation and retention of 18F-labeled TNC-specific aptamer in the aorta of ApoE−/− mice is higher than that of the control C57BL/6 mice. • Ex vivo autoradiography of 18F-labeled TNC-specific aptamer visualized the atherosclerotic lesions of aorta obtained from ApoE−/− mice. • PET imaging of 18F-labeled TNC-specific aptamer revealed a higher uptake in the aorta of the ApoE−/− mice than the control C57BL/6 mice. [ABSTRACT FROM AUTHOR]

The discourse of active aging, as introduced by the WHO, aims at optimizing older adults' opportunities for health, participation, and security that could eventually enhance their social integration and quality of life. Considering that even those with frailty could strive for active aging in the given circumstances, we examined the meaning of active aging in long-term care settings and care strategies to promote it based on the WHO's framework. We conducted interviews with a total of 35 participants. The interpretative analyses revealed that the activities taken place in LTCFs have various scopes depending on older adults' physical and cognitive functional ability, and it captures the forms of activities that go beyond its lexical meaning. By defining being "active," the present findings could contribute to an understanding of how the three elements of active aging can be carried out in LTCFs. [ABSTRACT FROM AUTHOR]

The purpose of this study was to design a community-based, needs-sensitive, and culturally appropriate parenting education program that is effective for rural Malawian caregivers. With the use of the five-stage model, qualitative methods and procedures were used for developing the program. The presented program emphasized securing sustainability and community empowerment by listening to the voices of Malawian mothers, community leaders, and Malawian facilitators who are also parents. In order to ensure the cultural appropriateness and feasibility of the program, contents were provided in both English and Chichewa, and utilized Malawian folklore, well-known Malawian songs, and children's play during the home visit sessions. In the process of developing and implementing the parenting education program, Malawian caregivers' prior knowledge, cultural assets, needs and wants were honored and actively reflected, in order to make the program locally relevant and meaningful. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder primarily targeting joints, significantly impacting patients' quality of life. The introduction of tumor necrosis factor-alpha (TNF-α) inhibitors has markedly improved RA management by reducing inflammation. However, these medications are associated with adverse skin reactions, which can vary greatly among patients due to genetic differences. Objectives: This study aimed to identify risk factors associated with skin adverse events by TNF-α in RA patients. Methods: A cohort study was conducted, encompassing patients with RA who were prescribed TNF-α inhibitors. This study utilized machine learning algorithms to analyze genetic data and identify markers associated with skin-related adverse events. Various machine learning algorithms were employed to predict skin and subcutaneous tissue-related outcomes, leading to the development of a risk-scoring system. Multivariable logistic regression analysis identified independent risk factors for skin and subcutaneous tissue-related complications. Results: After adjusting for covariates, individuals with the TT genotype of rs12551103, A allele carriers of rs13265933, and C allele carriers of rs73210737 exhibited approximately 20-, 14-, and 10-fold higher incidences of skin adverse events, respectively, compared to those with the C allele, GG genotype, and TT genotype. The machine learning algorithms used for risk prediction showed excellent performance. The risk of skin adverse events among patients receiving TNF-α inhibitors varied based on the risk score: 0 points, 0.6%; 2 points, 3.6%; 3 points, 8.5%; 4 points, 18.9%; 5 points, 36.7%; 6 points, 59.2%; 8 points, 90.0%; 9 points, 95.7%; and 10 points, 98.2%. Conclusions: These findings, emerging from this preliminary study, lay the groundwork for personalized intervention strategies to prevent TNF-α inhibitor-associated skin adverse events. This approach has the potential to improve patient outcomes by minimizing the risk of adverse effects while optimizing therapeutic efficacy. [ABSTRACT FROM AUTHOR]

With the advent of live-attenuated, quadrivalent, and cell-cultured vaccines for influenza, there have been discussions on the safety of these vaccines compared to conventional vaccines (such as inactivated, trivalent, and egg-cultured vaccines) because of the development of neurological adverse events (AEs). This study aimed to compare the trends and safety signals in the AE reporting systems of the US and South Korea and, more particularly, to evaluate the association between influenza vaccination and Guillain–Barré syndrome (GBS). In total, 400,535 AE reports from the US Vaccine Adverse Event Reporting System (VAERS) and 28,766 AE reports from the Korea Adverse Event Reporting System (KAERS) between 2005 and 2017 were assessed. Disproportionality analysis was performed to detect the safety signals and examine the potential risk of GBS with influenza vaccination using the case/non-case approach. In both databases, GBS was the most frequently reported AE following influenza immunization. Using the case/non-case approach, the adjusted reporting odds ratio (ROR) of GBS was 3.57 (95% confidence interval [CI], 3.16–4.03) and 3.09 (95% CI, 0.83–11.45) in the VAERS and KAERS data, respectively. People vaccinated with live-attenuated vaccines reported 2.30 times (95% CI, 1.74–3.05) more cases of GBS than those vaccinated with other types of vaccines. Our analysis of the VAERS and KAERS reports for AEs following immunization (AEFI) for influenza shows the need for cautious monitoring regarding the development of GBS after influenza vaccination, particularly, after live-attenuated vaccination. However, owing to potential reporting bias caused by limited AEFI reports after the introduction of new types of influenza vaccines, further prospective safety studies are needed. [ABSTRACT FROM AUTHOR]

Background: Multiplicity in breast cancer is common. Studies on multiple breast cancers have revealed high concordance in biomarker status among individual lesions. However, genomic differences among multiple lesions are not well-established. We aimed to investigate the potential genomic heterogeneity of multiple breast cancer.Methods: Twenty-one patients with radiologically and histologically evident multiple breast cancer with similar histology were included. Two lesions from each of the 21 patients were selected, and biomarker status was evaluated for each lesion. Capture-based targeted next-generation sequencing was performed using a cancer gene panel consisting of 170 genes.Results: We identified discordance in intrinsic subtype in 2 (10%) of the 21 patients. Pathogenic mutations were detected in 13 of the 21 patients, of whom 11 shared oncogenic variants in the two lesions. The remaining two patients yielded different mutation results for TP53, ATM, and PIK3CA. Difference in copy number alteration was observed in 7 (33%) of the 21 patients including ERBB2 (n = 2), FGFR1 (n = 2), and FGFR2 (n = 1) genes.Conclusion: Despite similar histologic features of the individual lesions, inter-lesional genomic difference was identified in more than one-third of the patients. Inter-lesional genomic heterogeneity needs to be considered when performing a genomic test in multiple breast cancers. [ABSTRACT FROM AUTHOR]

Presents a study which examined the possibility of employing the surface treatment of sapphire using reactive ion beam pretreatment as an alternative process for GaN growth in metalorganic chemical vapor deposition. Experimental procedure; Results and discussion; Conclusions.

Background/Purpose: Aptamers are oligonucleotide or peptide molecules that bind to a target molecule with high affinity and specificity. The present study aimed to evaluate the target specificity and applicability for in vivo molecular imaging of an aptamer labeled with a radioisotope. Methods: The human epidermal growth factor receptor 2 (HER2/ErbB2) aptamer was radiolabeled with 18F-fluoride. HER2-positive tumor cell uptake of the aptamer was evaluated in comparison to negative controls by flow cytometry and confocal microscopy. Using 18F-labeled HER2-specific aptamer positron emission tomography (PET), in vivo molecular images of BT474 tumor-bearing mice were taken at 60, 90 and 120 minutes after injection. Results: In flow cytometric analysis, HER2 aptamer showed strong binding to HER2-positive BT474 cells, while binding to HER2-negative MDA-MB231 cells was quite low. Likewise, in confocal microscopic images, the aptamer was bound to HER2-positive breast cancer cells, with minimal binding to HER2-negative cells. In vivo PET molecular imaging of BT474 tumor-bearing mice revealed significant higher uptake of the 18F-labeled HER2 specific aptamer into the tumor compared to the that of HER2-negative cell tumor(p = 0.033). HER2 aptamer was able to preferentially bind to HER2-positive breast cancer cells both in vitro and in vivo, by recognizing HER2 structure on the surface of these cells. Conclusion: The 18F-labeled aptamer enabled appropriate visualization of HER2 expression by human breast cancer cells. The results suggest that a radiolabeled HER2 aptamer could potentially be applied in the development of treatment strategies or in targeted therapy against HER2-positive breast cancer cells. [ABSTRACT FROM AUTHOR]

This study examines a model linking three facets of tourist involvement (“importance & pleasure,” “sign value,” and “risk probability & consequence”) with tourist experience (TE) and environmentally responsible behavior (ERB). Data were collected with a self-administered questionnaire in a convenient sampling approach from tourists visiting Nansha Wetland Park, China. In total, 308 valid questionnaires were obtained. The structural equation modeling technique was applied to data analyses. Of three tourist involvement (TI) facets, “importance & pleasure” was found to be the most salient predictor of TE, which in turn led to ERB. “Risk probability & consequence” was shown as a potent predictor of both TE and ERB. “Sign value” did not have any effect on either TE or ERB. Basically, TE served as a full mediator between “importance & pleasure” and ERB, and a partial mediator between “risk probability & consequence” and ERB. Contributions, managerial implications, and future research directions are discussed. [ABSTRACT FROM AUTHOR]

Background: A number of symptomatic patients tend to use over-the-counter (OTC) medications and prescription medications. OTC medications can be easily obtained in pharmacies for self-treatment, but using OTC medications is not always safe and beneficial for patients. The aims of this study were to examine the use patterns of OTC medications and assess patients' perspectives regarding the use of OTC medications in Korean patients with chronic diseases. Patients and methods: A descriptive, cross-sectional survey was carried out with Korean patients who visited the community pharmacy, located at the southern region of South Korea, during September 2015. Results: A total of 345 patients participated in this survey. Approximately 64% of Korean survey respondents reported that they had used OTC drugs. The most commonly used OTC medications were antipyretics, analgesics and anti-inflammatory drugs. The perception level of Korean consumers on adverse drug reactions and drug–drug interactions from OTC medications was relatively low. Although OTC package leaflets are a main source of information about OTC medications, Korean consumers' level of reading OTC package leaflets was relatively low. Conclusion: Based on these results, this study can serve as a meaningful starting point for interventions of health care professionals regarding OTC medications in South Korea. In particular, pharmacists should inform their consumers of drug-related problems from OTC drugs during consultation with the consumers; however, information about OTC drugs should be tailored to consumer information needs with the consideration of his or her circumstance. It is somewhat difficult to generalize the results from this study to other regions of South Korea since most of the respondents were probably residents of a small rural city located in the southern region of South Korea. [ABSTRACT FROM AUTHOR]

The purpose of this study is to identify types of adaptation strategies used by unskilled migrant workers living in South Korea as they acculturated to life in the country and to determine specific characteristics by acculturation patterns. To this end, a Q methodology was used. A total of fifty-nine statements were drawn through in-depth interviews with eight migrant workers and two South Koreans working in related organizations as well as from thirteen other studies, and four factor types of acculturation patterns were identified by conducting a Q sorting on thirty-eight subjects. Interpretation of the study revealed that the subjects used four types of adaptation strategies: accepted separation, compromising integration, conflict marginalization, and harmonious assimilation. The subjects in each type showed concrete socio-psychological adaptation strategies in response to South Korea’s unique culture and policies of discriminative exclusion. [ABSTRACT FROM AUTHOR]

Recent evidence highlights a role for sex and hormonal status in regulating cellular responses to ischemic brain injury and neurodegeneration. A key pathological event in ischemic brain injury is the opening of a mitochondrial permeability transition pore (MPT) induced by excitotoxic calcium levels, which can trigger irreversible damage to mitochondria accompanied by the release of pro-apoptotic factors. However, sex differences in brain MPT modulation have not yet been explored. Here, we show that mitochondria isolated from female mouse forebrain have a lower calcium threshold for MPT than male mitochondria, and that this sex difference depends on the MPT regulator cyclophilin D (CypD). We also demonstrate that an estrogen receptor beta (ERβ) antagonist inhibits MPT and knockout of ERβ decreases the sensitivity of mitochondria to the CypD inhibitor, cyclosporine A. These results suggest a functional relationship between ERβ and CypD in modulating brain MPT. Moreover, co-immunoprecipitation studies identify several ERβ binding partners in mitochondria. Among these, we investigate the mitochondrial ATPase as a putative site of MPT regulation by ERβ. We find that previously described interaction between the oligomycin sensitivity-conferring subunit of ATPase (OSCP) and CypD is decreased by ERβ knockout, suggesting that ERβ modulates MPT by regulating CypD interaction with OSCP. Functionally, in primary neurons and hippocampal slice cultures, modulation of ERβ has protective effects against glutamate toxicity and oxygen glucose deprivation, respectively. Taken together, these results reveal a novel pathway of brain MPT regulation by ERβ that could contribute to sex differences in ischemic brain injury and neurodegeneration. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to verify the value of arterial spin labeling (ASL) collateral perfusion estimation for predicting functional outcomes in acute anterior circulation ischemic stroke. Methods: This secondary analysis of an ongoing prospective observational study included data from participants with acute ischemic stroke due to steno-occlusion of the internal carotid artery and/or the middle cerebral artery within 8 h of symptom onset. We compared the collateral map, which is a 5-phase collateral imaging derived from dynamic contrast-enhanced magnetic resonance angiography, and ASL to validate the ASL collateral perfusion estimation. Multiple logistic regression analyses were conducted to identify independent predictors of favorable functional outcomes. Results: One hundred forty-eight participants (68 ± 13 years, 96 men) were evaluated. The ASL collateral perfusion grade was positively correlated with the collateral perfusion grade of the collateral map (P <.001). Younger age (OR = 0.53, 95% CI = 0.36–0.78, P =.002), lower baseline NIHSS score (OR = 0.85, 95% CI = 0.78–0.92, P <.001), intermediate ASL collateral perfusion grade (OR = 4.02, 95% CI = 1.43–11.26, P =.008), good ASL collateral perfusion grade (OR = 26.37, 95% CI = 1.06–655.01, P =.046), and successful reperfusion (OR = 5.84, 95% CI = 2.08–16.42, P <.001) were independently associated with favorable functional outcomes. Conclusion: ASL collateral perfusion estimation provides prognostic information, which can be helpful in guiding management decisions. [ABSTRACT FROM AUTHOR]

Recent advances in automated cell counters enable us to count cells more easily with consistency. However, the wide use of the traditional vital dye trypan blue (TB) raises environmental and health concerns due to its potential teratogenic effects. To avoid this chemical hazard, it is of importance to introduce an alternative non-hazardous vital dye that is compatible with automated cell counters. Erythrosin B (EB) is a vital dye that is impermeable to biological membranes and is used as a food additive. Similarly to TB, EB stains only nonviable cells with disintegrated membranes. However, EB is less popular than TB and is seldom used with automated cell counters. We found that cell counting accuracy with EB was comparable to that with TB. EB was found to be an effective dye for accurate counting of cells with different viabilities across three different automated cell counters. In contrast to TB, EB was less toxic to cultured HL-60 cells during the cell counting process. These results indicate that replacing TB with EB for use with automated cell counters will significantly reduce the hazardous risk while producing comparable results. [ABSTRACT FROM AUTHOR]

Background and purpose We present a case of magnetic resonance imaging (MRI)-occult intracranial dural arteriovenous fistula (DAVF) with serious cervical myelopathy and review the pathophysiological background. Summary of case A 61-year-old man had suffered from progressive neurological deterioration. He had demonstrated swollen spinal cord with diffuse enhancement and no dilated vascularity on MRI. Finally, digital subtraction angiography revealed DAVF at the petrous ridge and it was successfully treated by embolization. Conclusion A slow flow DAVF is not readily recognizable on MRI. Whenever a patient presents with unexplainable progressive myelopathy, a possibility of vascular origin has to be considered. [ABSTRACT FROM AUTHOR]

Breast cancer is the major cause of cancer death in women worldwide. The most common site of metastasis is bone. Bone metastases obstruct the normal bone remodeling process and aberrantly enhance osteoclast-mediated bone resorption, which results in osteolytic lesions. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPARγ) that has anti-inflammatory and antitumor activity at micromolar concentrations through PPARγ-dependent and/or PPARγ-independent pathways. We investigated the inhibitory activity of 15d-PGJ2 on the bone loss that is associated with breast cancer bone metastasis and estrogen deficiency caused by cancer treatment. 15d-PGJ2 dose-dependently inhibited viability, migration, invasion, and parathyroid hormone-related protein (PTHrP) production in MDA-MB-231 breast cancer cells. 15d-PGJ2 suppressed receptor activator of nuclear factor kappa-B ligand (RANKL) mRNA levels and normalized osteoprotegerin (OPG) mRNA levels in hFOB1.19 osteoblastic cells treated with culture medium from MDA-MB-231 cells or PTHrP, which decreased the RANKL/OPG ratio. 15d-PGJ2 blocked RANKL-induced osteoclastogenesis and inhibited the formation of resorption pits by decreasing the activities of cathepsin K and matrix metalloproteinases, which are secreted by mature osteoclasts. 15d-PGJ2 exerted its effects on breast cancer and bone cells via PPARγ-independent pathways. In Balb/c nu/nu mice that received an intracardiac injection of MDA-MB-231 cells, subcutaneously injected 15d-PGJ2 substantially decreased metastatic progression, cancer cell-mediated bone destruction in femora, tibiae, and mandibles, and serum PTHrP levels. 15d-PGJ2 prevented the destruction of femoral trabecular structures in estrogen-deprived ICR mice as measured by bone morphometric parameters and serum biochemical data. Therefore, 15d-PGJ2 may be beneficial for the prevention and treatment of breast cancer-associated bone diseases. [ABSTRACT FROM AUTHOR]

Many osteopenic disorders, including a postmenopausal osteoporosis and lytic bone metastasis in breast and prostate cancers, are linked with a hyperosteoclast activity due to increased receptor activator of nuclear factor kappa-B ligand (RANKL) expression in osteoblastic/stromal cells. Therefore, inhibition of RANKL-induced osteoclastogenesis and osteoclast-induced bone resorption is an important approach in controlling pathophysiology of these skeletal diseases. We found that, of seven type I, II, and III saikosaponins isolated from Bupleurum falcatum, saikosaponins A and D, type I saikosaponins with an allyl oxide linkage between position 13 and 28 and two carbohydrate chains that are directly attached to the hydroxyl groups in position 3, exhibited the most potent inhibition on RANKL-induced osteoclast formation at noncytotoxic concentrations. The stereochemistry of the hydroxyl group at C16 did not affect their activity. Saikosaponins A and D inhibited the formation of resorptive pits by reducing the secreted levels of matrix metalloproteinase- (MMP-) 2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Additionally, saikosaponins A and D inhibited mRNA expression of parathyroid hormone-related protein as well as cell viability and invasion in metastatic human breast cancer cells. Thus, saikosaponins A and D can serve as a beneficial agent for the prevention and treatment of osteoporosis and cancer-induced bone loss. [ABSTRACT FROM AUTHOR]

This study was performed to produce a strong antibody against repeated peptides for a specific region of an antigen. Nine amino acids at C-terminal from human brainβ-tubulin III were selected as a target sequence since it is well known for a high conservancy of sequence and resistance to antibody production. The synthetic oligonucleotides had six bases (5′-CGAC—GT-3′, 5′-TC—CAGC-3′) appended at each end and were repeatedly linked and directly joined by ligase in the presence of restriction enzymes (AccI,AvaI) to allow for the construction of head-to-tail repeats. Ligated oligonucleotides containing more than 10-unit repeats were eluted from agarose gels and cloned into theAccI site of a modified pGEX expression vector. The cloned repeated target sequences were subsequently expressed in a bacterial system. A large amount of glutathione-S-transferase-fusion protein containing the unit repeats was purified by affinity chromatography on glutathione-agarose beads and injected into Balb/c mice to produce polyclonal and monoclonal antibodies (Abs). Total protein from several mammalian brains was extracted and utilised to test the quality of the generated Abs in immunoblot assays. The generated Abs specifically recognised the 55-kDa human brainβ-tubulin protein but not any other mammalian brainβ-tubulins. The potential uses of this system could be applied to an effective epitope generation for an antibody and to the development of a new type of subunit vaccine. [ABSTRACT FROM PUBLISHER]

A crude extract from Acanthopanax senticosus (AS) has drawn increased attention because of its potentially beneficial activities, including anti-fatigue, anti-stress, anti-gastric-ulcer, and immunoenhancing effects. We previously reported that AS crude extract exerts anti-inflammatory activity through blockade of monocytic adhesion to endothelial cells. However, the underlying mechanisms remained unknown, and so this study was designed to investigate the pathways involved. It was confirmed that AS extract inhibited lipopolysaccharide (LPS)-induced adhesion of monocytes to endothelial cells, and we found that whole extract was superior to eleutheroside E, a principal functional component of AS. A series of PCR experiments revealed that AS extract inhibited LPS-induced expression of genes encoding lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) in THP-1 cells. Consistently, protein levels and cell surface expression of LFA-1 and Mac-1 were noticeably reduced upon treatment with AS extract. This inhibitory effect was mediated by the suppression of LPS-induced degradation of IκB-α, a known inhibitor of nuclear factor-κB (NF-κB). In conclusion, AS extract exerts anti-inflammatory activity via the suppression of LFA-1 and Mac-1, lending itself as a potential therapeutic galenical for the prevention and treatment of various inflammatory diseases. [ABSTRACT FROM AUTHOR]

Abstract: Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. [Copyright &y& Elsevier]

Abstract: Mitochondrial dysfunction leading to deficits in energy production, Ca2+ uptake capacity, and free radical generation has been implicated in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) caused by mutations in Cu,Zn superoxide dismutase (SOD1). Numerous studies link UCP2, a member of the uncoupling protein family, to protection of neurons from mitochondrial dysfunction and oxidative damage in various mouse models of acute stress and neurodegeneration, including Parkinson's disease. Here, we tested the potential neuroprotective effects of UCP2 and its ability to modulate mitochondrial function, in the G93A mutant SOD1 mouse model of familial ALS. Disease phenotype, mitochondrial bioenergetics, and Ca2+ uptake capacity were investigated in the central nervous system of double transgenic mice, expressing both human mutant G93A SOD1 and human UCP2 (hUCP2). Unexpectedly, hUCP2 expression accelerated the disease course of SOD1 mutant mice. In addition, we did not observe a classical uncoupling effect of hUCP2 in G93A brain mitochondria, although we did detect a decrease in reactive oxygen species (ROS) production from mitochondria challenged with the respiratory chain inhibitors rotenone and antimycin A. We also found that mitochondrial Ca2+ uptake capacity was decreased in the double transgenic mice, as compared to G93A mice. In summary, our results indicate that the neuroprotective role of UCP2 in neurodegeneration is disease-specific and that, while a mild uncoupling by UCP2 in brain mitochondria may protect against neurodegeneration in some injury paradigms, the mitochondrial damage and the disease caused by mutant SOD1 cannot be ameliorated by UCP2 overexpression. [Copyright &y& Elsevier]

Background: Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death. Methods: We conducted a single center analysis from May 2011 through April 2012. We retrospectively analyzed 103 patients with lactic acidosis among 207 patients with metabolic acidosis. We used SOFA and APACHE II as severity scores to estimate illness severity. Multivariate logistic regression analysis and Cox regression analysis models were used to identify factors that affect mortality. Results: Of the 103 patients with a mean age of 66.1±11.4 years, eighty-three patients (80.6%) died from sepsis (61.4%), hepatic failure, cardiogenic shock and other causes. The percentage of sodium bicarbonate administration (p = 0.006), catecholamine use, ventilator care and male gender were higher in the non-survival group than the survival group. The non-survival group had significantly higher initial and follow-up lactic acid levels, lower initial albumin, higher SOFA scores and APACHE II scores than the survival group. The mortality rate was significantly higher in patients who received sodium bicarbonate. Sodium bicarbonate administration (p = 0.016) was associated with higher mortality. Independent factors that affected mortality were SOFA score (Exp (B) = 1.72, 95% CI = 1.12–2.63, p = 0.013) and sodium bicarbonate administration (Exp (B) = 6.27, 95% CI = 1.10–35.78, p = 0.039). Conclusions: Lactic acidosis, which has a high mortality rate, should be evaluated in patients with metabolic acidosis. In addition, sodium bicarbonate should be prescribed with caution in the case of lactic acidosis because sodium bicarbonate administration may affect mortality. [ABSTRACT FROM AUTHOR]

Abstract: Bone homeostasis is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Osteoporosis occurs when osteoclast activity surpasses osteoblast activity. Pro-inflammatory cytokines stimulate osteoclast differentiation and activity by increasing production of macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL). In this study, we investigated whether Magnoliae Flos (MF), one of the most commonly used Chinese medicinal herbs for managing rhinitis, sinusitis and headache, could effectively inhibit osteoporosis. In ovariectomized (OVX) mice compared to sham mice, the body weight increased and serum levels of alkaline phosphatase (ALP), tartrate resistant acid phosphatase 5b, calcium, and osteocalcin were significantly elevated. However, orally administrated MF extract substantially inhibited the increased body weight and serum levels of bone turnover markers, without any evidence of tissue toxicity. MF extract treatment significantly reversed the morphometric parameters of ovariectomy-induced bone loss, including trabecular bone volume, thickness, number, separation, and bone density, to almost the same levels of the sham mice. Furthermore, MF extract reduced the RANKL-mediated osteoclast differentiation and bone resorption by inhibiting the activities of matrix metalloproteinases (MMPs) and cathepsin K in mouse bone marrow macrophages. MF extract appeared to increase ALP activity in murine osteoblastic cells. Taken together, MF extract may be a beneficial supplement for the blockade of osteoporosis progression, particularly for the management of postmenopausal osteoporosis. [Copyright &y& Elsevier]

Abstract: Rotaviruses are important human and animal pathogens with high impact on public health and livestock industry. There is little evidence about the cross-species pathogenicity and extra-intestinal infections of animal and human reassortant rotaviruses, particularly based on all 11 genotyping data. In this study, the bovine triple reassortant KJ56-1 strain harboring two bovine-like genome segments, eight porcine-like genome segments, and one human-like genome segment was used to evaluate the cross-species pathogenicity in its parent species, calves and piglets, and to determine its abilities of causing viremia and extra-intestinal tropisms in piglets. The KJ56-1 strain isolated from a calf diarrhea fecal sample replicated without causing diarrhea and severe intestinal pathology in calves. However, piglets inoculated with this strain showed persistent severe diarrhea and marked intestinal pathology. By SYBR Green real-time RT-PCR, viral RNA was detected in the sera, mesenteric lymph node, lung, liver, choroid plexus, and cerebrospinal fluid in the experimental piglets. An immunofluorescence assay confirmed viral replication in these extra-intestinal organs and tissues. These results indicated that the bovine triple reassortant KJ56-1 strain was virulent to piglets but not to calves. Our data also demonstrated that the reassortant rotaviruses had the ability to spread to the bloodstream from the gut, enter and amplify in the mesenteric lymph node, and disseminate to the extra-intestinal organs and tissues. [Copyright &y& Elsevier]

Amyotrophic lateral sclerosis is a devastating neurodegenerative disorder that is more prevalent in males than in females. A similar gender difference has been reported in some strains of transgenic mouse models of familial amyotrophic lateral sclerosis harbouring the G93A mutation in CuZn superoxide dismutase. Mitochondrial damage caused by pathological alterations in Ca2+ accumulation is frequently involved in neurodegenerative diseases, including CuZn superoxide dismutase-related amyotrophic lateral sclerosis, but its association with gender is not firmly established. In this study, we examined the effects of genetic ablation of cyclophilin D on gender differences in mice expressing G93A mutant CuZn superoxide dismutase. Cyclophilin D is a mitochondrial protein that promotes mitochondrial damage from accumulated Ca2+. As anticipated, we found that cyclophilin D ablation markedly increased Ca2+ retention in brain mitochondria of both males and females. Surprisingly, cyclophilin D ablation completely abolished the phenotypic advantage of G93A females, with no effect on disease in males. We also found that the 17β-oestradiol decreased Ca2+ retention in brain mitochondria, and that cyclophilin D ablation abolished this effect. Furthermore, 17β-oestradiol protected G93A cortical neurons and spinal cord motor neurons against glutamate toxicity, but the protection was lost in neurons lacking cyclophilin D. Taken together, these results identify a novel mechanism of oestrogen-mediated neuroprotection in CuZn superoxide dismutase-related amyotrophic lateral sclerosis, whereby Ca2+ overload and mitochondrial damage are prevented in a cyclophilin D-dependent manner. Such a protective mechanism may contribute to the lower incidence and later onset of amyotrophic lateral sclerosis, and perhaps other chronic neurodegenerative diseases, in females. [ABSTRACT FROM AUTHOR]

Abstract: In endothelial cells, focal adhesion kinase (FAK) regulates cell proliferation, migration, adhesion, and shear-stimulated activation of MAPK. We recently found that FAK is recruited into focal adhesion (FA) sites through interactions with XIAP (X-chromosome linked inhibitor of apoptosis protein) and activated by Src kinase in response to shear stress. In this study, we examined which domain(s) of FAK is(are) important for various vascular functions such as FA recruiting, XIAP-binding and shear stress-stimulated ERK activation. Through a series of experiments, we determined that the FRNK domain is recruited into FA sites and promotes endothelial cell adhesion. Interestingly, XIAP knockdown was shown to reduce FA recruitment of FRNK and the cell adhesive effect of FRNK. In addition, we found that XIAP interacts with FRNK, suggesting cross-talk between XIAP and FRNK. We also demonstrated that FRNK inhibits endothelial cell migration and shear-stimulated ERK activation. These inhibitory effects of FRNK were reversed by XIAP knockdown. Taken together, we can conclude that XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK. [Copyright &y& Elsevier]

Abstract: Objectives: Acetazolamide-challenged perfusion magnetic resonance imaging (MRI) has been shown as a method for assessment of cerebrovascular reserve (CVR) capacity in patients with atherosclerotic steno-occlusive disease of internal carotid artery. We have assessed the feasibility of the acetazolamide-challenged perfusion MRI for evaluating CVR in symptomatic patients with severe middle cerebral artery (MCA) stenosis (≥70%) by comparison with the acetazolamide-challenged technetium-99m-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT). Methods: Seventeen prospectively enrolled patients with symptomatic unilateral MCA stenosis underwent technetium-99m-hexamethylpropyleneamine oxime SPECT and perfusion MRI without and with acetazolamide challenge, respectively. Acetazolamide-challenged SPECT and perfusion MRI were compared quantitatively by Region of interest (ROI) analysis. Results: At all ROIs, there were no significant differences in percent change between SPECT and perfusion MRI. Patients with impaired CVR showed significant decreases in the percent changes of respective cerebral blood flow (P=.016) and respective cerebral blood volume (P=.029). Conclusion: Acetazolamide-challenged perfusion MRI is feasible for evaluating CVR in symptomatic patients with severe MCA stenosis quantitatively. [Copyright &y& Elsevier]

Abstract: Despite the impact of bovine group A rotaviruses (GARVs) as economically important and zoonotic pathogens, there is a scarcity of data on cross-species pathogenicity and extra-intestinal spread of bovine reassortant GARVs. During the course of characterizing the genotypes of all 11 genomic segments of bovine GARVs isolated from diarrheic calves in South Korea, a unique G6P[7] reassortant GARV strain (KJ9-1) was isolated. The strain harbors five bovine-like gene segments (VP7: G6; VP6: I2; VP1: R2; VP3: M2; NSP2: N2, and NSP4: E2), five porcine-like gene segments (VP4: P[7]; NSP1: A1; NSP3: T1, and NSP5: H1), and one human-like gene segment (VP2: C2). To investigate if this reassortant strain possessed cross-species pathogenicity in calves and piglets, and could induce viremia and extra-intestinal spread in calves, colostrum-deprived calves and piglets were experimentally inoculated with the KJ9-1 strain. The KJ9-1 strain caused severe diarrhea in experimentally infected calves with extensive intestinal villous atrophy, but replicated without causing clinical symptoms in experimentally infected piglets. By SYBR Green real-time RT-PCR, viral RNA was detected in sera of the calves at post-inoculation day (PID) 1, reaching a peak at PID3, and then rapidly decreasing from PID4. In addition, viral RNA was detected in the mesenteric lymph node, lungs, liver, choroid plexus, and cerebrospinal fluid. An immunofluorescence assay confirmed viral replication in the extra-intestinal organs and tissues of virus-inoculated calves. The data indicates that the homologous/heterologous origin of the NSP4 gene segment (E2 genotype), may play a key role in the ability to cause diarrhea in calves and piglets. [Copyright &y& Elsevier]

Abstract: The apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1) is involved in the base excision repair of apurinic/apyrimidinic sites induced by oxidative DNA damage. APE/Ref-1 was decreased by kainic acid (KA) injury in a time-dependent manner at the level of proteins, not transcripts. We investigated whether alteration of APE/Ref-1 amounts would influence hippocampal cell fate, survival or death, after KA injury. Overexpression of APE/Ref-1 using adenovirus and restoration of APE small peptides significantly reduced KA-induced hippocampal cell death. Both silencing of APE/Ref-1 by siRNA and inhibition of endonuclease by an antibody significantly increased caspase-3 activity and apoptotic cell death triggered from the early time after exposure to KA. These findings suggest that cell death is initiated by reducing APE/Ref-1 protein and inhibiting its repair function in spite of enough protein amounts. In conclusion, APE/Ref-1 may be a regulator of cell death initiation, and APE small peptides could provide molecular mechanism-based therapies for neuroprotection in progressive excitotoxic neuronal damage. [Copyright &y& Elsevier]

Abstract: Porcine group A rotavirus (GARV) is considered to be an important animal pathogen due to their economic impact in the swine industry and its potential to cause heterologous infections in humans. This study examined 475 fecal samples from 143 farms located in 6 provinces across South Korea. RT-PCR and nested PCR utilizing primer pairs specific for the GARV VP6 gene detected GARV-positive reactions in 182 (38.3%) diarrheic fecal samples. A total of 98 porcine GARV strains isolated from the GARV-positive feces were analyzed for G and P genotyping. Based on the sequence and phylogenetic analyses, the most predominant combination of G and P genotypes was G5P[7], found in 63 GARV strains (64.3%). The other combinations of G and P genotypes were G8P[7] (16 strains [16.3%]), G9P[7] (7 strains [7.1%]), G9P[23] (2 strains [2.0%]), and G8P[1] (1 strain [1.0%]). The counterparts of G or P genotypes were not determined in three G5, five P[7], and one P[1] strains. Interestingly, phylogenetic analysis indicated that all Korean G9 strains were more closely related to lineage VI porcine and human viruses than to other lineages (I–V) of GARVs and to Korean human G9 strains (lineage III). These results show that porcine GARV infections are common in diarrheic piglets in South Korea. The infecting strains are genetically diverse, and include homologous (G5P[7]), heterologous (G8P[1]), and reassortant (G8P[7]), as well as emerging G9 GARV strains. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies demonstrate that matrix metalloproteinase-9 (MMP-9) is closely involved in the pathogenesis of epilepsy. This study investigated the role of MMP-9 in hippocampal cell death after pilocarpine-induced status epilepticus (SE). We showed that MMP-9 expression and activity significantly increased and β1-integrin levels decreased on day 3 after SE. β1-integrin degradation was also observed in hippocampal ex vivo extracts incubated with recombinant active MMP-9. Treatment with a selective MMP-9 inhibitor attenuated MMP-9 up-regulation, β1-integrin degradation, the reduction of ILK activity and Akt phosphorylation, and subsequent hippocampal damage after SE. However, co-treatment with anti-β1-integrin antibody almost completely blocked the protective effects of the MMP-9 inhibitor on both integrin-mediated survival signaling and hippocampal cell death. Our study demonstrates that MMP-9 induces apoptotic hippocampal cell death by interrupting integrin-mediated survival signaling after SE and suggests that MMP-9 may be a promising target for a neuroprotective approach to preventing seizure-induced hippocampal damage. [Copyright &y& Elsevier]

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were analyzed in freshwater fish (crucian carp) taken from 16 locations in nine rivers and a wetland in Korea, during 2000–2004. Dioxin-like polychlorinated biphenyls (DL-PCBs) were also analyzed in the same samples but over shorter period (2002–2004). Concentrations on a wet weight basis for 3 years (2002–2004) ranged from below the detection limit (DL) to 0.36pg TEQg−1 wet wt. for PCDDs, below the DL to 2.0 for PCDFs, and from 0.02 to 1.9 for DL-PCBs, with a mean of 0.07, 0.33 and 0.83pg TEQg−1 wet wt., respectively. The proportions of PCDDs, PCDFs and DL-PCBs in the total dioxin TEQ for 2002–2004 were 7%, 26% and 67%, respectively. While the temporal trend showed a significant decrease in PCDDs/DFs concentrations over the 5-year study period, DL-PCBs did not show significant change in concentration over the 3-year period. The results suggest that DL-PCBs concentrations should be determined when total dioxin TEQ is analyzed in freshwater fish. [Copyright &y& Elsevier]

Abstract: This study was carried out to investigate the chemopreventive effects of immature plum extracts. The methanol extract of immature plums (plum 1), that are picked at 20–40 days before final harvest, has remarkably inhibited the growth of hepatoma HepG2 cells. The effects of immature plum extracts on hepatotoxicity in benzo(α)pyrene (B(α)P, carcinogen)-treated mice were investigated. Male ICR mice were pretreated with immature plum extracts (2.5 or 5g/kg bw/day, for 5 days, i.p.) before treatment with B(α)P(0.5mg/kg bw, i.p., single dose). The activities of serum aminotransferase, cytochrome P450 (CYPs) and the hepatic content of lipid peroxide were increased on B(α)P-treatment group than control, but those levels were significantly decreased by the pretreatment of immature plum extracts. The primary CYPs involved in the metabolism and bioactivation of B(α)P are CYP1A1. The pretreatment of immature plum extracts inhibited the induction of CYP1A1 expression. The activities of glutathione peroxidase, superoxide dismutase and catalase were decreased by the pretreatment of immature plum extracts more than with B(α)P alone. Whereas, the hepatic content of glutathione and glutathione S-transferase activity depleted by B(α)P was significantly increased (p >0.05). These results suggest that immature plum extracts may counteract toxic effects of carcinogens, such as B(α)P, and therefore possess the chemopreventive efficacy. [Copyright &y& Elsevier]

Abstract: Chemokines are small, secreted cytokine peptides that have the ability to recruit a wide range of immune cells to sites of infection and disease. A novel CXC chemokine was obtained from Japanese flounder Paralichthys olivaceus. This chemokine cDNA contains an open reading frame of 333 nucleotides encoding 111 amino acid residues containing four conserved cysteine residues. The gene is composed of four exons and three introns as are those of mammalian and fish CXC chemokines. Results of homology and phylogenetic analysis revealed that the Japanese flounder CXC chemokine is closest to CXCL13 subgroup. The gene was expressed in immune-related organs, including head kidney, trunk kidney, spleen and peripheral blood leukocytes (PBLs). Japanese flounder CXC chemokine gene expression was observed at 3 and 6h after induction by LPS, but not at 3 and 6h after induction by poly I:C. These results suggest that the Japanese flounder CXC chemokine is probably associated with inflammatory as well as homeostatic functions. [Copyright &y& Elsevier]

Abstract: Adipogenesis inhibitory peptide was isolated and identified from black soybean (Rhynchosia volubilis Lour.) hydrolysate. An adipogenesis inhibitor was purified using consecutive methods including: ultrafiltration (MWCO; 3 and 10kDa), gel filtration chromatography (Superdex Peptide 10/300 GL column), and reverse-phase high-performance liquid chromatography (μBondapak™ C18 column). Also, the adipogenesis inhibition effect of the purified peptide was measured by observation of droplet of 3T3-L1 adipocyte by Oil Red O staining in the highest active fraction in each step. The peptide was shown to inhibit the differentiation of the 3T3-L1 pre-adipocyte, which was confirmed by morphological study. The adipogenesis inhibitory peptide was purified 71.43-fold from black soybean hydrolysate throughout a five-step purification procedure. The adipogenesis inhibitor was identified to be a tripeptide, Ile-Gln-Asn, having an IC50 value of 0.014mgprotein/ml. Furthermore, the synthetic tripeptide (Ile-Gln-Asn) exhibited the similar adipogenesis effects to the purified peptide. Thus, these results showed the potential anti-obesity effect of the purified peptide through control of adiposity. [Copyright &y& Elsevier]

Abstract: A highly efficient luminescence conversion light emitting diode (LUCO LED) was fabricated, using a commercial InGaN LED (460nm) and 4-N,N-diphenyl-9-(4-tert-butylphenyl)-1,8-naphthalimide (DBN), dispersed in epoxy as the primary light source and LUCO material, respectively. The emission of very bright white light was observed at 20mA, with CIE chromaticity coordinates of (0.32,0.33) and conversion efficiency of 82%. The luminescent output of the LUCO LED decreased rapidly, but when the LUCO LED was prepared using DNB dispersed in poly(methyl methacrylate), it only decreased to about 67% of the initial value after 19 days of continual operation at 200mA. [Copyright &y& Elsevier]

This study investigated the influence of sourcing and relatedness on the integration of events embedded in simple stories. Participants read pairs of "breaking news stories" from either 1 or 2 news agencies that were believed to be from the Internet. The stories within each pair were either related by virtue of shared situational dimensions (e.g., same protagonist, same location, causal continuity) or were unrelated to one another. One third of the participants believed the news stories were from different online news agencies and were told to remember the source of each event, one third were not instructed to remember the source, and one third thought the events only came from 1 source. Priming data from a recognition task indicated that relatedness increased integration, whereas sourcing decreased integration. The results were discussed in the context of models of discourse comprehension. [ABSTRACT FROM AUTHOR]

Abstract: Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Recently, we demonstrated that the control of cytosolic and mitochondrial redox balance and the cellular defense against oxidative damage is one of the primary functions of NADP+-dependent isocitrate dehydrogenase (ICDH) by supplying NADPH for antioxidant systems. The protective role of ICDH against heat shock-induced apoptosis in U937 cells was investigated in the control and the cells pre-treated with oxalomalate, a competitive inhibitor of ICDH. Upon exposure to heat shock, there was a distinct difference between the control cells and the cells pre-treated with 3mM oxalomalate for 3h in regard to apoptotic parameters, cellular redox status, and mitochondrial function. The oxalomalate pre-treated cells showed significant enhancement of apoptotic features such as activation of caspase-3, up-regulation of Bax, and down-regulation of Bcl-2 compared to the control cells upon exposure to heat shock. This study indicates that ICDH may play an important role in regulating the apoptosis induced by heat shock presumably through maintaining the cellular redox status. [Copyright &y& Elsevier]

Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Mitochondrial NADP + -dependent isocitrate dehydrogenase (IDPm) produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of IDPm against heat shock in HEK293 cells, an embryonic kidney cell line, was investigated in control and cells transfected with the cDNA for IDPm, where IDPm activity was 6–7 fold higher than that in the control cells carrying the vector alone. Upon exposure to heat shock, the viability was lower and the protein oxidation, lipid peroxidation and oxidative DNA damage were higher in control cells as compared to HEK293 cells in which IDPm was over-expressed. We also observed the significant difference in the cellular redox status reflected by the endogenous production of reactive oxygen species, NADPH pool and GSH recycling between two cells. The results suggest that IDPm plays an important role as an antioxidant defense enzyme in cellular defense against heat shock through the removal of reactive oxygen species. [ABSTRACT FROM AUTHOR]

For categorizing the presenting neurological symptoms in Takayasu''s arteritis (TA) and correlating to the imaging findings of cerebral angiography, we retrospectively reviewed the angiographies of 27 patients presented with stroke, transient ischemic attack (TIA), visual disturbance, and/or dizziness. Neurological manifestations of TA resulted from decreased blood flow due to a steno-occlusive lesion and/or shifting of blood flow, thromboembolism, or hypertension. The pattern analysis of neurological manifestations related to specific arterial involvement is mandatory in understanding neurological manifestations of this systemic disease. [Copyright &y& Elsevier]

Interactive Strategy Training for Active Reading and Thinking (iSTART) is a Web-based application that provides young adolescent to college-age students with high-level reading strategy training to improve comprehension of science texts, iSTART is modeled after an effective, human-delivered intervention called self-explanation reading training (SERT), which trains readers to use active reading strategies to serf-explain difficult texts more effectively. To make the training more widely available, the Web-based trainer has been developed. Transforming the training from a human-delivered application to a computer-based one has resulted in a highly interactive trainer that adapts its methods to the performance of the students. The iSTART trainer introduces the strategies in a simulated classroom setting with interaction between three animated characters—an instructor character and two student characters—and the human trainee. Thereafter, the trainee identifies the strategies in the explanations of a student character who is guided by an instructor character. Finally, the trainee practices self-explanation under the guidance of an instructor character. We describe this system and discuss how appropriate feedback is generated. [ABSTRACT FROM AUTHOR]

The article presents information on the first Asia-Pacific CHRIE (APac-CHRIE) Conference and annual meeting that was held on May 21-23, 2003 in Seoul, Korea. The conference was hosted by the Hong Kong Polytechnic University (PolyU) in collaboration with Yonsei University, Korea and organized by the Institute of Convention and Exhibition Management of Hallym University, Korea. The conference officially started with an inaugural plenary session at the Lotte Hotel in the afternoon of May 21, 2003. Dr. Kyung-Sang Kwon, Director General of Bureau of Tourism, South Korea; Professor Hai-Sik Sohn, Chairman of the Asia Pacific Tourism Association; Dr. Evangelos Christou, President of Euro-CHRIE; and Prof. Kaye Chon, President of APac-CHRIE each welcomed the delegates and stressed the goals of the APac-CHRIE conference. A 30-minute poster session began with various topics subsequent to the inaugural plenary session. Shortly after the poster presentations, the first concurrent paper sessions were held featuring four unique topics: emerging issues in hospitality education, emerging research in foodservice management, conventions and events tourism, and lodging management.

BACKGROUND. A paucity of reports exist on the use of botulinum toxin type A injections as an alternative noninvasive treatment for masseteric hypertrophy. OBJECTIVE. To evaluate the effects of botulinum toxin type A on masseteric hypertrophy using computed tomography. METHODS. Percutaneous intramuscular injections of botulinum toxin type A of 30 U per side was carried out in 11 subjects with masseteric hypertrophy. The changes in the masseteric muscle volume before and 12 weeks after injection were evaluated using computed tomography. The changes in the lower facial contours on the photographs were evaluated as excellent, good, fair, and no changes. RESULTS. Nine of the 11 subjects showed a mean reduction of approximately 22% in the masseteric muscle volume. The maximum reduction was 35.4% (range, 8.1% to 35.4%). Nine subjects showed aesthetically good results with a grade of good or excellent at 12 weeks after treatment. CONCLUSION. Botulinum toxin injections are a noninvasive alternative method for treating masseteric hypertrophy. [ABSTRACT FROM AUTHOR]

Sympathetic neurolysis is very important in treating chronic pain, especially sympathetically maintained pain. However, conventional neurolytic agents destroy nerve fibers nonselectively and may leave serious complications.Botulinum toxin type A (BTA) selectively acts on cholinergic nerves and inhibits the secretion of acetylcholines (Ach) at the involved nerve endings. Because cholinergic nerves also exist in autonomic ganglia, it is believed that BTA has pharmacological effects on sympathetic ganglia. In this study, after the administration of BTA into the superior cervical ganglion (SCG) in rabbits, the possible clinical use of BTA as a neurolytic agent was evaluated.In the normal saline-treated control group, miosis was not observed in all 12 rabbits. However, in the BTA-treated group, 15 cases of miosis were observed among 40 rabbits (37.5%). Furthermore, BTA induced miosis in a dose-dependent manner, though onset time and duration of miosis varied. Mean time of onset and duration were 1.8 days and 5.3 weeks, respectively. By eosin–hematoxylin (H&E) staining finding, no significant chronological and histological changes between the control and the experimental groups were observed.In conclusion, BTA was found to have a sympathetic ganglion blocking effect over a period of more than 1 month without causing considerable pathologic changes in the SCG, that is, this toxin may be used in the case of sympathetically maintained pain control as a sympatholytic. [Copyright &y& Elsevier]