The Combined Propranolol/TSST Paradigm – a New Method for Psychoneuroendocrinology.

The Combined Propranolol/TSST Paradigm – A New Method for Psychoneuroendocrinology.

PLoS One. 2013; 8(2): e57567
Andrews J, Pruessner JC

Upon perception of a stimulus as stressful, the human brain reacts with the activation of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), to mobilize energy resources to better cope with the stressor. Since the perception of the stressor is the initial stimulus, a synchronicity between the subjective perception of stress and the physiological stress reactivity should be expected. However, according to a recent meta-analysis, these associations are weak and inconsistent. The goal of the current study was to investigate the interaction between the SNS, HPA and subjective stress perceptions, by introducing an experimental manipulation of this interaction. For this purpose, we combined the SNS inhibitor propranolol with the Trier Social Stress Test, and measured endocrinological and psychological responses to the stressor. Thirty healthy male participants were recruited and randomly assigned to either a propranolol (PROP; n?=?15) or placebo (PLC; n?=?15) group. All subjects were administered 80 mg of propranolol 60 minutes prior to exposure to psychosocial stress. Salivary cortisol and alpha amylase (sAA), heart rate, blood pressure and subjective stress responses were assessed throughout the study. We observed significantly reduced sAA levels and heart rate increases in the PROP group in response to stress, with no effects of the drug on systolic or diastolic blood pressure changes. In line with previous studies, a significant increase in cortisol was seen in response to the stress exposure. Importantly, the cortisol increase was significantly higher in the PROP group. A typical increase in subjective stress could be seen in both groups, with no significant group differences emerging. Complementing previous work, this study further demonstrates a significant interaction between the HPA and the SNS during acute stress. The HPA activity was found to be elevated in the presence of a suppressed SNS in reactivity to the TSST. HubMed – drug


Prostatic Cell-Specific Regulation of the Synthesis of MUC1-Associated Sialyl Lewis a.

PLoS One. 2013; 8(2): e57416
Chachadi VB, Ali MF, Cheng PW

Sialyl Lewis antigens are selectin ligands involved in leukocyte trafficking and cancer metastasis. Biosynthesis of these selectin ligands occurs by the sequential actions of several glycosyltransferases in the Golgi apparatus following synthesis of the protein backbone in the endoplasmic reticulum. In this study, we examine how the synthesis of sialyl Lewis a (sLe) is regulated in prostatic cells and identify a mucin that carries this glycotope. We treat human prostatic cells including one normal and three cancerous cells with histone deacetylase inhibitors, valproic acid, tricostatin A (TSA), and suberoylanilide hydroxamic acid (SAHA), and then monitor the expression of sLe. We have found that SAHA enhances the production of sLe in normal prostatic RWPE-1 cells but not prostatic cancer cells. Employing siRNA technology and co-immunoprecipitation, we show that the sLe is associated with MUC1, which is confirmed by confocal immunofluorescence microscopy and proximity ligation assay. The SAHA-induced production of sLe in RWPE-1 cells is resulted from upregulation of gene via enhancement of acetylated histone-3 and histone-4. Interestingly, PC3 and LNCaP C-81 cells do not produce detectable amounts of sLe despite expressing high levels of B3GALT1. However, the MUC1-associated sLe is generated in these cells after introduction of MUC1 cDNA. We conclude that the synthesis of sLe is controlled by not only peptide backbone of the glycoprotein but also glycoprotein-specific glycosyltransferases involved in the synthesis of sLe. Further, the SAHA induction of this selectin ligand in normal prostatic cells may pose a potentially serious side effect of this drug recently approved by the US Food and Drug Administration. HubMed – drug


Bombesin analogue-mediated delivery preferentially enhances the cytotoxicity of a mitochondria-disrupting Peptide in tumor cells.

PLoS One. 2013; 8(2): e57358
Yang H, Cai H, Wan L, Liu S, Li S, Cheng J, Lu X

Tumor-homing peptides that recognize specific markers on tumor cells have shown potential as drug carriers for targeted cancer therapy. Bombesin receptors are frequently overexpressed or ectopically expressed in a wide range of human tumors. Bombesin and its analogues have been widely used as drug carriers for tumor imaging and tumor therapy. However, the cargos used in previous studies, including radioactive and chemotherapeutic agents, are usually small molecules. Mitochondrial-disrupting peptides depolarize the mitochondria and trigger apoptosis after entering tumor cells. We are interested in whether the bombesin analogue, Bn(6-14), which contains a bombesin receptor-binding motif, can specifically deliver the mitochondria-disrupting peptide, B28, to tumor cells. To this end, we created a chimeric peptide, B28Bn(6-14), by conjugating B28 to Bn(6-14) at its N-terminus. The cytotoxicity of B28Bn(6-14) in tumor cells was much stronger than unconjugated B28. The IC values of B28Bn(6-14) in tumor cells (1.7-3.5 µM) were approximately 10 times lower than B28. However, conjugation of B28 to Bn(2-7), which lacks the bombesin receptor-binding motif, did not increase its cytotoxicity. In addition, the IC values of B28Bn(6-14) in tumor cells (1.7-3.5 µM) was 3-10 times lower than in normal cells (10.8-16.8 µM). We found that selective binding of B28Bn(6-14) to tumor cells is Bn(6-14)-dependent. Upon entering the tumor cell, B28Bn(6-14) accumulated in the mitochondria and triggered caspase-dependent apoptosis. Intratumoral and intraperitoneal administration of B28Bn(6-14) substantially suppressed the growth of DU145 tumor xenografts in mice. These results demonstrate that Bn(6-14) is able to deliver the mitochondria-disrupting peptide to tumor cells, and B28Bn(6-14) should be further developed as novel anti-cancer agent. HubMed – drug


Prevalence of HIV, Syphilis, HCV and Their High Risk Behaviors among Migrant Workers in Eastern China.

PLoS One. 2013; 8(2): e57258
Pan X, Zhu Y, Wang Q, Zheng H, Chen X, Su J, Peng Z, Yu R, Wang N

The goal of this study was to understand the knowledge about AIDS, identify the correlates and determine the prevalence of HIV infection, syphilis, HCV among migrant workers in Zhejiang, China.A cross-sectional study using face-to-face anonymous questionnaire interviews was conducted and blood samples were collected for HIV, syphilis and Hepatitis C infection screening.17,377 (92.8%) of 18,730 migrant workers approached were interviewed. Among 17,377 participants, the HIV/AIDS knowledge rate was 66.2%. A total of 12,694 (73%) of the participants reported having ever had sexual intercourse, with 30.1% of single participants reporting having had sexual intercourse. Among those respondents with sexual experiences, 7.5% admitted they had two or more sexual partners and 4.9% reported having had sex with casual (unpaid) partners in the previous 12 months, whilst 3.7% had paid for sex. More than half of those who had paid for sex (59.4%) had not used a condom every time in their sexual acts with the sex workers. Multiple logistic regression analysis indicated that high risk sexual behavior (defined as sex with a casual or commercial sex partner without using a condom consistently) was associated with being divorced or widowed (P<0.05 for single); male gender; shorter duration of stay in Zhejiang; working in factory, market or domestic service (P<0.05 for odd job); having a province of origin inside Zhejiang; and drug use. The prevalence of HIV and HCV infections were 0.02% (95% CI: 0.01%-0.06%) and 0.40% (95%CI: 0.31%-0.51%), respectively. The prevalence of syphilis among those who were sexually active was 0.55% (95% CI: 0.43%-0.70%). Risk factors for syphilis included shorter duration of stay in Zhejiang, ethnic minority status, being divorced or widowed and having had multiple sex partners.Much greater efforts are needed to promote safer sex, and programs for the control of syphilis need to be tailored for migrant workers in China. HubMed – drug


Simultaneous detection of oseltamivir- and amantadine-resistant influenza by oligonucleotide microarray visualization.

PLoS One. 2013; 8(2): e57154
Zhang Y, Liu Q, Wang D, Chen S, Wang S

Presently, the resistance of Influenza A virus isolates causes great difficulty for the prevention and treatment of influenza A virus infection. It is important to establish a drug-resistance detection method for epidemiological study and personalized medicine in the clinical setting. Consequently, a cost-effective oligonucleotide microarray visualization method, which was based on quantum dot-catalyzed silver deposition, was developed and evaluated for the simultaneous detection of neuraminidase H275Y and E119V; matrix protein 2 V27A and S31N mutations of influenza A (H3N2), seasonal influenza A (H1N1), and 2009 influenza A (H1N1). Then, 307 clinical throat swab specimens were detected and the drug-resistance results showed that 100% (17/17) of influenza A (H3N2) and 100% (259/259) of 2009 influenza A (H1N1) samples were resistant to amantadine and susceptible to oseltamivir; and 100% (5/5) of seasonal influenza A (H1N1) samples were resistant to both amantadine and oseltamivir. HubMed – drug