[Protective effects of Polygonatum odoratum polysaccharides on alcohol-induced injury of HepG2 cells and its mechanisms].

Objective: To investigate the protective effects of Polygonatum odoratum polysaccharides (POP) on alcohol-induced injury of HepG2 cells and its potential molecular mechanisms. Methods: After screening the appropriate concentration of alcohol-treated HepG2 cells and the intervention concentration of POP by MTT method, HepG2 cells were divided into three groups according to different intervention concentrations (200 µg/L, 400 µg/L and 600 µg/L) of POP, and the blank group without POP. After pretreated for 1 h, HepG2 cells were treated with 4% alcohol for 24 h. The activities of intracellular alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and the levels of intracellular reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF- α) were measured. The protein expressions of Kelch-like epichlorohydrin-associated protein-1 (Keap1), phosphorylated nuclear factor E2-related factor 2 (p-Nrf2), phosphoamide adenine dinucleotide quinone oxidoreductase -1 (NQO1), B lymphocyte tumor-2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase 3 were detected. Results: Compared with the HepG2 cells treated with 4% alcohol, POP at the various concentrations could effectively down-regulate the activities of ALT and AST in HepG2 cells induced by alcohol (P＜0.05). The levels of IL-1ß and TNF-α in the 200 µg/L POP treated group were decreased significantly (P＜0.05), while the level of GSH was increased significantly (P＜0.01). The levels of ROS, MDA, IL-1ß and TNF-α in the 400 µg/L and 600 µg/L POP treated groups were decreased significantly (P＜0.05 or P＜0.01), while the GSH level was increased significantly (P＜0.01). POP effectively up-regulated the expressions of p-Nrf2 and NQO1 protein in HepG2 cells induced by alcohol, and also down-regulated the Bax/Bcl-2 index (P＜0.05), and inhibited the protein expressions of Keap1 and cleaved-caspase-3 (P＜0.05). Conclusion: POP can improve alcohol-induced oxidative stress injury in HepG2 cells by regulating the Nrf2/Keap1 pathway, thereby reducing the inflammatory index and apoptosis level of HepG2 cells. Among them, 400 µg/L and 600 µg/L POP have better intervention effects.

Pathogenic Hydrogel? A Novel-Entrapment Neuropathy Model Induced by Ultrasound-Guided Perineural Injections.

Entrapment neuropathy (EN) is a prevalent and debilitative condition caused by a complex pathogenesis that involves a chronic compression-edema-ischemia cascade and perineural adhesion that results in excessive shear stress during motion. Despite decades of research, an easily accessible and surgery-free animal model mimicking the mixed etiology is currently lacking, thus limiting our understanding of the disease and the development of effective therapies. In this proof-of-concept study, we used ultrasound-guided perineural injection of a methoxy poly(ethylene glycol)-b-Poly(lactide-co-glycoilide) carboxylic acid (mPEG-PLGA-BOX) hydrogel near the rat's sciatic nerve to induce EN, as confirmed sonographically, electrophysiologically, and histologically. The nerve that was injected with hydrogel appeared unevenly contoured and swollen proximally with slowed nerve conduction velocities across the injected segments, thus showing the compressive features of EN. Histology showed perineural cellular infiltration, deposition of irregular collagen fibers, and a possible early demyelination process, thus indicating the existence of adhesions. The novel method provides a surgery-free and cost-effective way to establish a small-animal model of EN that has mixed compression and adhesion features, thus facilitating the additional elucidation of the pathophysiology of EN and the search for promising treatments.

Activation of mGluR5 and NMDA Receptor Pathways in the Rostral Ventrolateral Medulla as a Central Mechanism for Methamphetamine-Induced Pressor Effect in Rats.

Acute hypertension produced by methamphetamine (MA) is well known, mainly by the enhancement of catecholamine release from sympathetic terminals. However, the central pressor mechanism of the blood-brain-barrier-penetrating molecule remains unclear. We used radio-telemetry and femoral artery cannulation to monitor the mean arterial pressure (MAP) in conscious free-moving and urethane-anesthetized rats, respectively. Expression of Fos protein (Fos) and phosphorylation of N-methyl-D-aspartate receptor subunit GluN1 in the rostral ventrolateral medulla (RVLM) were detected using Western blot analysis. ELISA was carried out for detection of protein kinase C (PKC) activity in the RVLM. MA-induced glutamate release in the RVLM was assayed using in vivo microdialysis and HPLC. Systemic or intracerebroventricular (i.c.v.) administration of MA augments the MAP and increases Fos expression, PKC activity, and phosphorylated GluN1-ser 896 (pGluN1-ser 896) in the RVLM. However, direct microinjection of MA into the RVLM did not change the MAP. Unilateral microinjection of a PKC inhibitor or a metabotropic glutamate receptor 5 (mGluR5) antagonist into the RVLM dose-dependently attenuated the i.c.v. MA-induced increase in MAP and pGluN1-ser 896. Our data suggested that MA may give rise to glutamate release in the RVLM further to the activation of mGluR5-PKC pathways, which would serve as a central mechanism for the MA-induced pressor effect.

Thienoisoindigo (TII)-Based Quinoidal Small Molecules for High-Performance n-Type Organic Field Effect Transistors.

A novel quinoidal thienoisoindigo (TII)-containing small molecule family with dicyanomethylene end-capping units and various alkyl chains is synthesized as n-type organic small molecules for solution-processable organic field effect transistors (OFETs). The molecular structure of the 2-hexyldecyl substituted derivative, TIIQ-b16, is determined via single-crystal X-ray diffraction and shows that the TIIQ core is planar and exhibits molecular layers stacked in a "face-to-face" arrangement with short core intermolecular distances of 3.28 Å. The very planar core structure, shortest intermolecular N···H distance (2.52 Å), existence of an intramolecular non-bonded contact between sulfur and oxygen atom (S···O) of 2.80 Å, and a very low-lying LUMO energy level of -4.16 eV suggest that TIIQ molecules should be electron transporting semiconductors. The physical, thermal, and electrochemical properties as well as OFET performance and thin film morphologies of these new TIIQs are systematically studied. Thus, air-processed TIIQ-b16 OFETs exhibit an electron mobility up to 2.54 cm2 V-1 s-1 with a current ON/OFF ratio of 105-106, which is the first demonstration of TII-based small molecules exhibiting unipolar electron transport characteristics and enhanced ambient stability. These results indicate that construction of quinoidal molecule from TII moiety is a successful approach to enhance n-type charge transport characteristics.

The Effect of the Repression of Oxidative Stress on Tenocyte Differentiation: A Preliminary Study of a Rat Cell Model Using a Novel Differential Tensile Strain Bioreactor.

Because of limitations in the current understanding of the exact pathogenesis of tendinopathy, and the lack of an optimal experimental model, effective therapy for the disease is currently unavailable. This study aims to prove that repression of oxidative stress modulates the differentiation of tendon-derived cells (TDCs) sustaining excessive tensile strains, and proposes a novel bioreactor capable of applying differential tensile strains to cultured cells simultaneously. TDCs, including tendon-derived stem cells, tenoblasts, tenocytes, and fibroblasts, were isolated from the patellar tendons of Sprague‒Dawley rats. Cyclic uniaxial stretching with 4% or 8% strain at 0.5 Hz for 8 h was applied to TDCs. TDCs subjected to 8% strain were treated with epigallocatechin gallate (EGCG), piracetam, or no medication. Genes representing non-tenocyte lineage (Pparg, Sox9, and Runx2) and type I and type III collagen were analyzed by quantitative polymerase chain reaction. The 8% strain group showed increased expression of non-tenocyte lineage genes and type III/type I collagen ratios compared with the control and 4% strain groups, and the increased expression was ameliorated with addition of EGCG and piracetam. The model developed in this work could be applied to future research on the pathophysiology of tendinopathy and development of treatment options for the disease. Repression of oxidative stress diminishes the expression of genes indicating aberrant differentiation in a rat cell model, which indicates potential therapeutic intervention of tendinopathy, the often relentlessly degenerate condition.

Is Case Management Effective for Long-Lasting Suicide Prevention?

BACKGROUND: Case management services have been implemented in suicide prevention programs. AIMS: To investigate whether case management is an effective strategy for reducing the risks of repeated suicide attempts and completed suicides in a city with high suicide rates in northern Taiwan. METHOD: The Suicide Prevention Center of Keelung City (KSPC) was established in April 2005. Subjects included a consecutive sample of individuals (N = 2,496) registered in KSPC databases between January 1, 2006, and December 31, 2011, with at least one episode of nonfatal self-harm. Subjects were tracked for the duration of the study. RESULTS: Of all the subjects, 1,013 (40.6%) received case management services; 416 (16.7%) had at least one other deliberate self-harm episode and 52 (2.1%) eventually died by suicide. No significant differences were found in the risks of repeated self-harm and completed suicides between suicide survivors who received case management and those who refused the services. However, a significant reduction in suicide rates was found after KSPC was established. CONCLUSION: Findings suggest that case management services might not reduce the risks of suicide repetition among suicide survivors during long-term follow-up. Future investigation is warranted to determine factors impacting the downward trend of suicide rates.

Switching suicide methods as a predictor of completed suicide in individuals with repeated self-harm: a community cohort study in northern Taiwan.

OBJECTIVE: Repetition of suicide attempts is common, but little is known about the relationship between switching methods of suicide attempt and the probability of completed suicide. This study aimed to determine the transition of methods chosen by individuals who repeat suicide attempts, and how the switched methods of suicide attempts influence the risk of suicide death. METHOD: All consecutive individuals (n = 2052) with an episode of non-fatal suicide attempt registered in a surveillance database provided by the Department of Health of the Keelung City Government from 1 January 2006 to 31 December 2010 were enrolled and followed up until the end of 2011. The earliest attempt recorded in the database was defined as the index attempt. Data on the time of subsequent completed suicide and methods chosen for repeated self-harm during the follow-up period were analyzed by performing a Cox proportional hazards regression. RESULTS: Of the total subjects, 374 (18.2%) had at least one other attempted suicide and 50 (2.4%) eventually died by suicide. Subjects who used highly lethal methods in the index self-harm tended to switch methods in the next suicide attempt (p<0.001). Switching to a more lethal method was a significant predictor of completed suicide (adjusted hazard ratio (aHR) 7.05, 95% confidence interval (CI) 3.52-14.14). In addition, subjects who used charcoal-burning in the index self-harm attempt had a higher risk of subsequent suicide death (aHR 3.47, 95% CI 1.57-7.68). CONCLUSIONS: The findings in this study give us some insight into the patterns of methods in repeat suicide attempters. The intent behind switching methods of suicide attempt might be considered as an important item of clinical assessment of the seriousness of suicidal behavior.

The rate of fatality and demographic characteristics associated with various suicide methods: a community-based study in Northern Taiwan.

BACKGROUND: Understanding lethality and risk factors of suicide methods is an initial step in suicide prevention. AIMS: To investigate the fatality rate and demographic characteristics of various suicide methods. METHOD: This study enrolled consecutive individuals with episodes of suicide attempts registered in a surveillance database in a city with a high rate of suicide mortality in Taiwan, from January 1, 2006, to December 31, 2010. In total, 3,089 suicide attempt events (including 2,583 nonfatal suicides and 506 completed suicides) occurred during the study period. RESULTS: Overall, the fatality rate of suicides was 16.4%. Charcoal burning accounted for the most suicide deaths (37.6%), with a fatality rate of 50.1%. Suicide by hanging carried the highest fatality rate (81.2%). Males tended to choose more lethal methods and had higher fatality rates compared with females. Elders and married persons were less likely to attempt suicide by charcoal burning. The case fatality ratio increased along with age among suicide attempts, but not in those using charcoal burning. CONCLUSION: The choice of suicide methods and lethality might be influenced by one's demographic characteristics. RESULTS from this study may provide clues for establishing suicide prevention strategies such as restricting access to common lethal suicide methods in the high-risk group.

Is suicide mortality associated with meteorological and socio-economic factors? An ecological study in a city in Taiwan with a high suicide rate.

BACKGROUND: Keelung City has the highest suicide rate in Taiwan. This study aimed to determine whether meteorological and socio-economic factors are associated with suicide mortality in Keelung City, by gender and by means of suicide. SUBJECTS AND METHODS: Data on suicides between January 2006 and December 2010 were provided by the Department of Health, Keelung City Government. The suicide victims were categorized into non-violent and violent groups, based on the International Classification of Disease, Ninth Revision. Meteorological data were obtained from the Central Weather Bureau of Taiwan. Socio-economic data were gathered from the Accounting and Statistics Office, Keelung City Government. Multiple linear regression analysis with backward elimination was performed to determine the model that was most effective in predicting dependent variables. RESULTS: During the 5-year study period, the overall suicide mortality rate was negatively associated with ambient temperature. Male suicide mortality was positively correlated with unemployment, and negatively correlated with ambient temperature, barometric pressure, rainy days, family income and number of holidays. Female suicide mortality and violent suicide mortality were not significantly correlated with any meteorological or socio-economic factors. Non-violent suicide mortality was positively correlated with unemployment, and negatively correlated with ambient temperature, barometric pressure and family income. CONCLUSIONS: Suicide is a complex psychopathological phenomenon. Further studies with individual data are warranted to confirm how meteorological and socio-economic conditions influence ones' suicidal behaviour.

Methods of suicide predict the risks and method-switching of subsequent suicide attempts: a community cohort study in Taiwan.

OBJECTIVE: Suicide is a major public health concern. This study aimed to determine the predictors of repeated suicide attempts, focusing on whether lethality level of the suicidal method predicts the risk of subsequent suicide attempts. METHODS: All consecutive individuals (N=2,070) with an episode of nonfatal self-harm registered in a surveillance database provided by the Department of Health of Keelung City Government in Taiwan from January 1, 2006 to December 31, 2010 were enrolled and followed up until the end of 2011. The earliest attempt recorded in the database was defined as the index attempt. Subjects were classified according to suicide method into low-lethal and high-lethal groups. Data on time of and methods chosen for subsequent suicide attempts during the follow-up period were analyzed. RESULTS: Of the total people screened for the study, 18.1% made a repeated suicide attempt. Subjects in the high-lethal group were more likely to be male; aged 35-64 years; and single, divorced, or widowed. Compared to other time intervals, most subsequent suicide attempts occurred within 6 months from the index attempt. The independent predictors for repeated suicide attempts were the use of low-lethal methods in the index attempt and being 35-49 years old. Using high-lethal methods and being older than 50 years were associated with changing suicide method for the second attempt. CONCLUSION: Lethality level of former suicidal method could predict repeated suicide attempts and changing of suicide methods. Further clarification is needed on whether a higher risk of repeat attempts is associated with higher rates of suicide mortality.

Association of salivary dehydroepiandrosterone levels and symptoms in patients with attention deficit hyperactivity disorder during six months of treatment with methylphenidate.

This prospective study aimed to determine whether salivary levels of dehydroepiandrosterone (DHEA) in patients with attention deficit hyperactivity disorder (ADHD) change significantly during 6 months of treatment with methylphenidate (MPH), and to investigate long-term relationship between these levels and ADHD symptoms. Fifty ADHD patients aged between 6 and 12 years, and 50 age- and gender-matched healthy subjects were recruited. ADHD patients were prescribed oral MPH with a dose range of 5-15 mg/day at the discretion of the psychiatrist. DHEA levels were determined from saliva samples collected from both ADHD patients and healthy subjects at pretreatment and 1, 3, and 6 months from pretreatment visit. ADHD symptoms were evaluated with the Swanson, Nolan, and Pelham, Version IV Scale for ADHD and the ADHD Rating Scale, and computerized Continuous Performance Test (CPT). The results showed that salivary DHEA levels significantly increased in ADHD patients during the 6-month course of methylphenidate treatment, but the DHEA levels did not significantly change in the untreated healthy group during the 6-month period of natural observation. For the longitudinal observation, among ADHD patients, the salivary DHEA levels were independently correlated with distraction and impulsivity performance in the CPT, but not correlated with inattention and hyperactivity in the clinical ADHD symptoms. Whether DHEA exerts effects on neurocognitive functions as mediators or independently of MPH warrants further investigation.

Clinical characteristics, precipitating stressors, and correlates of lethality among suicide attempters.

BACKGROUND: Given that suicide attempt is a major risk factor for suicide completion, this study investigated the clinical features, precipitating stressors, and the correlates of lethality in suicide attempters. METHODS: The sample comprised 357 people who had attempted suicide and had been sent to the emergency room in a general hospital from November 2002 to June 2005. Data collection was conducted by a consultant psychiatrist and social worker through interview. RESULTS: The proportion of females was much higher than that of males. Suicide attempts peaked at 20 to 29 years old in females, and 30 to 39 years old in males. The females reported significantly more family relationship problems than the males, while the males more commonly reported unemployment or economic problems. The most prevalent psychiatric diagnosis was affective disorders. The females had a higher rate of self-poisoning by medication than the males, while the males had a higher rate of self-poisoning by non-medicinal chemicals than the females. Those with high-lethality attempts were older than those with medium- and low-lethality attempts, and more were males. CONCLUSION: While females and young adults had higher rates of suicide attempts, males and the elderly were considered at higher risk for suicide completion.

Feasibility of human T-lymphotropic virus type I screening using pooled sera.

BACKGROUND AND PURPOSE: The human T-cell lymphotropic virus type I (HTLV-I) seroprevalence rate among volunteer blood donors in Taiwan is low. To study the feasibility of HTLV-I enzyme immunoassay (EIA) screening using pooled sera, we prospectively compared its sensitivity to that of the routine test for each donor. METHODS: HTLV-I EIA tests for each serum sample and a pooled-sera test with 50 samples from voluntary donated blood samples were performed concurrently to assess the effectiveness and cost savings of this screening method. RESULTS: Of 135,606 blood samples from volunteer donors tested for HTLV-I infection, 60 samples (0.044%) were HTLV-I EIA-positive using the routine method. Among these, the positive results were confirmed by Western blot in 22 samples (36.7%). In the pooled-sera test, 17 of 2,713 pooled samples were EIA-positive and these results were all confirmed by Western blot. Five of the 22 (22.7%) EIA-positive samples had a false-negative result in the pooled-sera test. Serial dilution in these five cases revealed that the maximum dilution before loss of sensitivity was 8-fold for two specimens and 16-fold for three specimens. CONCLUSION: In this study, the 50-pooled sera test had higher specificity (100%), but lower sensitivity (77.3%), than the routine HTLV-I screening. Our results suggest that use of a pooling method with five samples would leave a reasonable safety margin and be feasible for HTLV-I mass screening in areas with low seroprevalence for HTLV-I infection.