Platelet Activation by Streptococcus pyogenes Leads to Entrapment in Platelet Aggregates,from Which Bacteria Subsequently Escape

Platelet activation and aggregation have been reported to occur in response to a number of Gram-positive pathogens. Here, we show that platelet aggregates induced by Streptococcus pyogenes were unstable and that viable bacteria escaped from the aggregates over time. This was not due to differential activation in response to the bacteria compared with physiological activators. All the bacterial isolates induced significant platelet activation, including integrin activation and alpha and dense-granule release, at levels equivalent to those induced by potent physiological platelet activators that induced stable aggregates. The ability to escape the aggregates and to resist the antibacterial effects of platelets was dependent on active protein synthesis by the bacteria within the aggregate. We conclude that S. pyogenes bacteria can temporarily cover themselves with activated platelets, and we propose that this may facilitate survival of the bacteria in the presence of platelets.     

Effect of AndoSan(™) on expression of adhesion molecules and production of reactive oxygen species in human monocytes and granulocytes in vivo

Abstract Background. Oral intake (60 ml daily) over 12 days in eight healthy volunteers of an immunostimulatory extract based on the medicinal mushroom Agaricus blazei Murill (AbM (AndoSan(?))), reduced the monocyte and granulocyte release of mainly proinflammatory cytokines in vivo, suggesting an anti-inflammatory effect. In this foremost in vivo study, the aim was to examine the effect of such AndoSan(?) consumption on the expression of adhesion molecules CD11b, CD11c and CD62L and production of reactive oxygen species (ROS) in leukocytes. Methodology/Principal findings. As shown by flow cytometry, there was a significant increase of CD62L expression on monocytes and granulocytes from before (day 0) compared with 12 days after daily AndoSan(?) consumption. However, only minor alterations and no clear trend in the expression of CD11b and CD11c were detected. Intracellular ROS (mainly superoxide ion) were significantly reduced in these cells from days 0 to 12. Conclusions/Significance. These results support that oral intake of AndoSan(?) exhibits an anti-inflammatory effect in humans in vivo.     

The 5‐HT4 receptor levels in hippocampus correlates inversely with memory test performance in humans

The cerebral serotonin (5‐HT) system is involved in cognitive functions such as memory and learning and animal studies have repeatedly shown that stimulation of the 5‐HT type 4 receptor (5‐HT₄R) facilitates memory and learning and further that the 5‐HT₄R modulates cellular memory processes in hippocampus. However, any associations between memory functions and the expression of the 5‐HT₄R in the human hippocampus have not been investigated. Using positron emission tomography with the tracer [¹¹C]SB207145 and Reys Auditory Verbal Learning Test we aimed to examine the individual variation of the 5‐HT4R binding in hippocampus in relation to memory acquisition and consolidation in healthy young volunteers. We found significant, negative associations between the immediate recall scores and left and right hippocampal BP_ND, (p = 0.009 and p = 0.010 respectively) and between the right hippocampal BP_ND and delayed recall (p = 0.014). These findings provide evidence that the 5‐HT₄R is associated with memory functions in the human hippocampus and potentially pharmacological stimulation of the receptor may improve episodic memory. Hum Brain Mapp 34:3066–3074, 2013. © 2012 Wiley Periodicals, Inc.     

Effect of regular exercise on blood pressure in normotensive pregnant women. A randomized controlled trial

Objective: To evaluate the effect of regular exercise on maternal arterial blood pressure (BP) at rest and during uphill walking, in healthy former inactive pregnant women. Methods: A single-blind, single-center, randomized controlled trial including 61 out of 105 healthy, inactive nulliparous pregnant women, initially enrolled in a controlled trial studying the effect of 12 weeks of aerobic exercise (60 min 2/week) on maternal weight gain. Primary outcome was the mean adjusted difference in change in resting systolic and diastolic BP from baseline to after intervention. Secondary outcome was the mean adjusted difference in change in systolic BP during uphill treadmill walking at critical power. Measurements were performed prior to the intervention (gestation week 17.6 ± 4.2) and after the intervention (gestation week 36.5 ± 0.9). Results: At baseline, resting systolic and diastolic BP was 115/66 ± 12/7 and 115/67 ± 10/9 mmHg in the exercise (n = 35) and control group (n = 26), respectively. After the intervention, resting systolic BP was 112 ± 8 mmHg in the exercise group and 119 ± 14 mmHg in the control group, giving a between-group difference of 7.5 mmHg (95% CI 1.5 to 12.6, p = 0.013). Diastolic BP was 71 ± 9 and 76 ± 8 mmHg, with a between-group difference of 3.9 mmHg (95% CI ?0.07 to 7.8, p = 0.054). During uphill treadmill walking at critical power, the between-group difference in systolic and diastolic BP was 5.9 mmHg (95% CI ?4.4 to 16.1, p = 0.254) and 5.5 mmHg (95% CI –0.2 to 11.1, p = 0.059), respectively. Conclusions: Aerobic exercise reduced resting systolic BP in healthy former inactive pregnant women.     

Reduced Anxiety in Forensic Inpatients after a Long-Term Intervention with Atlantic Salmon

The aim of the present study was to investigate the effects of Atlantic salmon consumption on underlying biological mechanisms associated with anxiety such as heart rate variability (HRV) and heart rate (HR) as well as a measure of self-reported anxiety. Moreover, these biological and self-reported outcome measures were investigated in relation to specific nutrients; vitamin D status, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Ninety-five male forensic inpatients were randomly assigned into a Fish (Atlantic salmon three times per week from September to February) or a Control group (alternative meal, e.g., chicken, pork, or beef three times per week during the same period). HRV measured as the root mean square of successive differences (rMSSD), HR, state- and trait-anxiety (STAI), were assessed before (pre-test) and at the end of the 23 weeks dietary intervention period (post-test). The Fish group showed significant improvements in both rMSSD and HR. The Fish group also showed significant decreases in state-anxiety. Finally, there was a positive relationship between rMSSD and vitamin D status. The findings suggest that Atlantic salmon consumption may have an impact on mental health related variables such as underlying mechanisms playing a key role in emotion-regulation and state-anxiety.     

Psychosocial,Behavioral, and Cultural Predictors of Sexual Risk for HIV Infection Among Latino Men Who Have Sex with Men

This study sought to replicate and extend an investigation by Diaz et al. (1999) on determinants of HIV risk among Latino gay and bisexual men living in San Francisco who were predominantly English-speaking. Compared to the Diaz et al. study, the current study sample consisted of predominantly Spanish-speaking MSM, who resided outside of HIV/AIDS epicenters and whose countries of origin were primarily Central & South American. The relationships of unprotected anal sex and multiple sexual partners with demographic, developmental, behavioral, cultural and psychosocial variables were examined. Data were collected in a convenience sample of 250 participants (primarily immigrants from El Salvador) residing in Virginia. Most men in the sample had more than one sexual partner in the last 3 months (62%) and more than a third had unprotected anal sex with a casual partner in the same time period. Communication about HIV, sexual attraction, machismo, and experiences of discrimination based on homosexual behavior were predictive of HIV risk behaviors. The findings support an integrative approach to investigating HIV risk among Latino MSM. Implications for prevention programs are discussed.     

The effect of intra-aortic balloon counterpulsation on left ventricular functional recovery early after acute myocardial infarction: a randomized experimental magnetic resonance imaging study.

AIMS: We sought to determine whether intra-aortic balloon pump (IABP) counterpulsation improves the recovery of left ventricular (LV) systolic function after reperfused acute myocardial infarction (AMI). METHODS AND RESULTS: Fourteen dogs underwent 90-min coronary artery occlusion followed by reperfusion. Seven animals were randomized to IABP counterpulsation immediately after reperfusion. Tagged, cine, and contrast-enhanced magnetic resonance imaging were used for regional and global LV functional assessment and MI characterization, respectively. Image acquisition was performed at 1 h, 6 h, and 24 h after reperfusion, during which the IABP device was paused. Animals randomized to IABP demonstrated an earlier improvement of LV ejection fraction when compared with controls (25+/-3 vs. 25+/-2% at 1 h, P=0.91; 36+/-3 vs. 26+/-2% at 6 h, P=0.015; and 38+/-3 vs. 35+/-1% at 24 h, P=0.34). Regional functional analyses revealed the same behaviour among non-infarcted risk regions, i.e., earlier circumferential systolic strain improvement in the IABP group than in controls (-5.4+/-0.4 vs. -5.3+/-0.5% at 1 h, P=0.86; -12.1+/-1.0 vs. -6.0+/-0.4% at 6 h, P<0.001; and -13.9+/-1.1% vs. -12.8+/-0.6% at 24 h, P=0.40). Importantly, however, the degree of LV functional recovery 24 h after reperfusion was similar whether IABP counterpulsation was used or not. CONCLUSION: IABP counterpulsation accelerates but does not significantly improve the recovery of LV systolic function after reperfused AMI.     

New Hits as Antagonists of GPR103 Identified by HTS

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Functional conservation of suppressors of cytokine signaling proteins between teleosts and mammals: Atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling

Suppressor of cytokine signaling (SOCS) proteins are crucially involved in the control of inflammatory responses through their impact on various signaling pathways including the JAK/STAT pathway. Although all SOCS protein family members are identified in teleost fish, their functional properties in non-mammalian vertebrates have not been extensively studied. To gain further insight into SOCS functions in bony fish, we have identified and characterized the Atlantic salmon (Salmo salar) SOCS1, SOCS2 and CISH genes. These genes exhibited sequence conservation with their mammalian counterparts and they were ubiquitously expressed. SOCS1 in mammalian species has been recognized as a key negative regulator of interferon (IFN) signaling and recent data for the two model fish Tetraodon (Tetraodon nigroviridis) and zebrafish (Danio rerio) suggest that these functions are conserved from teleost to mammals. In agreement with this we here demonstrate a strong negative regulatory activity of salmon SOCS1 on type I and type II IFN signaling, while SOCS2a and b and CISH only moderately affected IFN responses. SOCS1 also inhibited IFNγ-induced nuclear localization of STAT1 and a direct interaction between SOCS1 and STAT1 and between SOCS1 and the Tyk2 kinase was found. Using SOCS1 mutants lacking either the KIR domain or the ESS, SH2 and SOCS box domains showed that all domains affected the ability of SOCS1 to inhibit IFN-mediated signaling. These results are the first to demonstrate that SOCS1 is a potent inhibitor of IFN-mediated JAK-STAT signaling in teleost fish.