Prescribing patterns of antidepressants, antipsychotics and mood stabilizers in bipolar patients misdiagnosed with major depressive disorder in China

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94515/1/hup2262.pd

Serological Evidence of Subclinical Transmission of the 2009 Pandemic H1N1 Influenza Virus Outside of Mexico

Background: Relying on surveillance of clinical cases limits the ability to understand the full impact and severity of an epidemic, especially when subclinical cases are more likely to be present in the early stages. Little is known of the infection and transmissibility of the 2009 H1N1 pandemic influenza (pH1N1) virus outside of Mexico prior to clinical cases being reported, and of the knowledge pertaining to immunity and incidence of infection during April-June, which is essential for understanding the nature of viral transmissibility as well as for planning surveillance and intervention of future pandemics. Methodology/Principal Findings: Starting in the fall of 2008, 306 persons from households with schoolchildren in central Taiwan were followed sequentially and serum samples were taken in three sampling periods for haemagglutination inhibition (HI) assay. Age-specific incidence rates were calculated based on seroconversion of antibodies to the pH1N1 virus with an HI titre of 1: 40 or more during two periods: April-June and September-October in 2009. The earliest time period with HI titer greater than 40, as well as a four-fold increase of the neutralization titer, was during April 26-May 3. The incidence rates during the pre-epidemic phase (April-June) and the first wave (July-October) of the pandemic were 14.1% and 29.7%, respectively. The transmissibility of the pH1N1 virus during the early phase of the epidemic, as measured by the effective reproductive number R(0), was 1.16 (95% confidence interval (CI): 0.98-1.34). Conclusions: Approximately one in every ten persons was infected with the 2009 pH1N1 virus during the pre-epidemic phase in April-June. The lack of age-pattern in seropositivity is unexpected, perhaps highlighting the importance of children as asymptomatic transmitters of influenza in households. Although without virological confirmation, our data raise the question of whether there was substantial pH1N1 transmission in Taiwan before June, when clinical cases were first detected by the surveillance network

Role of the CCAAT-Binding Protein NFY in SCA17 Pathogenesis

Spinocerebellar ataxia 17 (SCA17) is caused by expansion of the polyglutamine (polyQ) tract in human TATA-box binding protein (TBP) that is ubiquitously expressed in both central nervous system and peripheral tissues. The spectrum of SCA17 clinical presentation is broad. The precise pathogenic mechanism in SCA17 remains unclear. Previously proteomics study using a cellular model of SCA17 has revealed reduced expression of heat shock 70 kDa protein 5 (HSPA5) and heat shock 70 kDa protein 8 (HSPA8), suggesting that impaired protein folding may contribute to the cell dysfunction of SCA17 (Lee et al., 2009). In lymphoblastoid cells, HSPA5 and HSPA8 expression levels in cells with mutant TBP were also significantly lower than that of the control cells (Chen et al., 2010). As nuclear transcription factor Y (NFY) has been reported to regulate HSPA5 transcription, we focused on if NFY activity and HSPA5 expression in SCA17 cells are altered. Here, we show that TBP interacts with NFY subunit A (NFYA) in HEK-293 cells and NFYA incorporated into mutant TBP aggregates. In both HEK-293 and SH-SY5Y cells expressing TBP/Q61∼79, the level of soluble NFYA was significantly reduced. In vitro binding assay revealed that the interaction between TBP and NFYA is direct. HSPA5 luciferase reporter assay and endogenous HSPA5 expression analysis in NFYA cDNA and siRNA transfection cells further clarified the important role of NFYA in regulating HSPA5 transcription. In SCA17 cells, HSPA5 promoter activity was activated as a compensatory response before aggregate formation. NFYA dysfunction was indicated in SCA17 cells as HSPA5 promoter activity reduced along with TBP aggregate formation. Because essential roles of HSPA5 in protection from neuronal apoptosis have been shown in a mouse model, NFYA could be a target of mutant TBP in SCA17

A proposed prognostic 7-day survival formula for patients with terminal cancer

<p>Abstract</p> <p>Background</p> <p>The ability to identify patients for hospice care results in better end-of-life care. To develop a validated prognostic scale for 7-day survival prediction, a prospective observational cohort study was made of patients with terminal cancer.</p> <p>Methods</p> <p>Patient data gathered within 24 hours of hospital admission included demographics, clinical signs and symptoms and their severity, laboratory test results, and subsequent survival data. Of 727 patients enrolled, data from 374 (training group) was used to develop a prognostic tool, with the other 353 serving as the validation group.</p> <p>Results</p> <p>Five predictors identified by multivariate logistic regression analysis included patient's cognitive status, edema, ECOG performance status, BUN and respiratory rate. A formula of the predictor model based on those five predictors was constructed. When probability was >0.2, death within 7 days was predicted in the training group and validation group, with sensitivity of 80.9% and 71.0%, specificity of 65.9% and 57.7%, positive predictive value of 42.6% and 26.8%, and negative predictive value (NPV) of 91.7% and 90.1%, respectively.</p> <p>Conclusion</p> <p>This predictor model showed a relatively high sensitivity and NPV for predicting 7-day survival among terminal cancer patients, and could increase patient satisfaction by improving end-of-life care.</p

Bidirectional cross-regulation between the eNOS and ß-catenin signalling pathways

AIMS: β-catenin has been shown to be regulated by inducible nitric oxide synthase (NOS) in endothelial cells. We investigated here whether β-catenin interacts with and regulates endothelial NOS (eNOS) and whether eNOS activation promotes β-catenin signalling. METHODS AND RESULTS: We identified β-catenin as a novel eNOS binding protein in human umbilical vein endothelial cells (HUVECs) by mass spectroscopy and western blot analyses of β-catenin and eNOS immunoprecipitates. This was confirmed by in situ proximity ligation assay. eNOS activity, assessed by cGMP production and eNOS phosphorylation (Ser1177), was enhanced in β-catenin(-/-) mouse pulmonary endothelial cells (MPECs) relative to wild-type MPECs. eNOS activation (using adenosine, salbutamol, thrombin, or histamine), or application of an NO donor (spermine NONOate) or cGMP-analogue (8-bromo-cGMP) caused nuclear translocation of β-catenin in HUVEC as shown by western blotting of nuclear extracts. Exposure to spermine NONOate, 8-bromo-cGMP, or sildenafil (a phosphodiesterase type 5 inhibitor) also increased the expression of β-catenin-dependent transcripts, IL-8, and cyclin D1. Stimulation of wild-type MPECs with basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), spermine NONOate, 8-bromo-cGMP, or sildenafil increased tube length relative to controls in an angiogenesis assay. These responses were abrogated in β-catenin(-/-) MPECs, with the exception of that to bFGF which is NO-independent. In C57BL/6 mice, subcutaneous VEGF-supplemented Matrigel plugs containing β-catenin(-/-) MPECs exhibited reduced angiogenesis compared with plugs containing wild-type MPECs. Angiogenesis was not altered in bFGF-supplemented Matrigel. CONCLUSION: These data reveal bidirectional cross-talk and regulation between the NO-cGMP and β-catenin signalling pathways

Demographic and Clinical Features and Prescribing Patterns of Psychotropic Medications in Patients with the Melancholic Subtype of Major Depressive Disorder in China

BACKGROUND: Little has been known about the demographic and clinical features of the melancholic subtype of major depressive disorder (MDD) in Chinese patients. This study examined the frequency of melancholia in Chinese MDD patients and explored its demographic and clinical correlates and prescribing patterns of psychotropic drugs. METHODS: A consecutively collected sample of 1,178 patients with MDD were examined in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The cross-sectional data of patients' demographic and clinical characteristics and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. The diagnosis of the melancholic subtype was established using the Mini International Neuropsychiatric Interview (MINI). Medications ascertained included antidepressants, mood stabilizers, antipsychotics and benzodiazepines. RESULTS: Six hundred and twenty nine (53.4%) of the 1,178 patients fulfilled criteria for melancholia. In multiple logistic regression analyses, compared to non-melancholic counterparts, melancholic MDD patients were more likely to be male and receive benzodiazepines, had more frequent suicide ideations and attempts and seasonal depressive episodes, while they were less likely to be employed and receive antidepressants and had less family history of psychiatric disorders and lifetime depressive episodes. CONCLUSIONS: The demographic and clinical features of melancholic MDD in Chinese patients were not entirely consistent with those found in Western populations. Compared to non-melancholic MDD patients, melancholic patients presented with different demographic and clinical features, which have implications for treatment decisions

Induction of Apoptosis Coupled to Endoplasmic Reticulum Stress in Human Prostate Cancer Cells by n-butylidenephthalide

BACKGROUND: N-butylidenephthalide (BP) exhibits antitumor effect in a variety of cancer cell lines. The objective of this study was to obtain additional insights into the mechanisms involved in BP induced cell death in human prostate cancer cells. METHODS/PRINCIPAL FINDINGS: Two human prostate cancer cell lines, PC-3 and LNCaP, were treated with BP, and subsequently evaluated for their viability and cell cycle profiles. BP caused cell cycle arrest and cell death in both cell lines. The G0/G1 phase arrest was correlated with increase levels of CDK inhibitors (p16, p21 and p27) and decrease of the checkpoint proteins. To determine the mechanisms of BP-induced growth arrest and cell death in prostate cancer cell lines, we performed a microarray study to identify alterations in gene expression induced by BP in the LNCaP cells. Several BP-induced genes, including the GADD153/CHOP, an endoplasmic reticulum stress (ER stress)-regulated gene, were identified. BP-induced ER stress was evidenced by increased expression of the downstream molecules GRP78/BiP, IRE1-α and GADD153/CHOP in both cell lines. Blockage of IRE1-α or GADD153/CHOP expression by siRNA significantly reduced BP-induced cell death in LNCaP cells. Furthermore, blockage of JNK1/2 signaling by JNK siRNA resulted in decreased expression of IRE1-α and GADD153/CHOP genes, implicating that BP-induced ER stress may be elicited via JNK1/2 signaling in prostate cancer cells. BP also suppressed LNCaP xenograft tumor growth in NOD-SCID mice. It caused 68% reduction in tumor volume after 18 days of treatment. CONCLUSIONS: Our results suggest that BP can cause G0/G1 phase arrest in prostate cancer cells and its cytotoxicity is mediated by ER stress induction. Thus, BP may serve as an anticancer agent by inducing ER stress in prostate cancer

Impact of the Herbal Medicine Sophora flavescens on the Oral Pharmacokinetics of Indinavir in Rats: The Involvement of CYP3A and P-Glycoprotein

Sophora flavescens is a Chinese medicinal herb used for the treatment of gastrointestinal hemorrhage, skin diseases, pyretic stranguria and viral hepatitis. In this study the herb-drug interactions between S. flavescens and indinavir, a protease inhibitor for HIV treatment, were evaluated in rats. Concomitant oral administration of Sophora extract (0.158 g/kg or 0.63 g/kg, p.o.) and indinavir (40 mg/kg, p.o.) in rats twice a day for 7 days resulted in a dose-dependent decrease of plasma indinavir concentrations, with 55%–83% decrease in AUC0-∞ and 38%–78% reduction in Cmax. The CL (Clearance)/F (fraction of dose available in the systemic circulation) increased up to 7.4-fold in Sophora-treated rats. Oxymatrine treatment (45 mg/kg, p.o.) also decreased indinavir concentrations, while the ethyl acetate fraction of Sophora extract had no effect. Urinary indinavir (24-h) was reduced, while the fraction of indinavir in faeces was increased after Sophora treatment. Compared to the controls, multiple dosing of Sophora extract elevated both mRNA and protein levels of P-gp in the small intestine and liver. In addition, Sophora treatment increased intestinal and hepatic mRNA expression of CYP3A1, but had less effect on CYP3A2 expression. Although protein levels of CYP3A1 and CYP3A2 were not altered by Sophora treatment, hepatic CYP3A activity increased in the Sophora-treated rats. All available data demonstrated that Sophora flavescens reduced plasma indinavir concentration after multiple concomitant doses, possibly through hepatic CYP3A activity and induction of intestinal and hepatic P-gp. The animal study would be useful for predicting potential interactions between natural products and oral pharmaceutics and understanding the mechanisms prior to human studies. Results in the current study suggest that patients using indinavir might be cautioned in the use of S. flavescens extract or Sophora-derived products