Simvastatin Prevents Lipopolysaccharide-induced Septic Shock in Rats

Simvastatin is a hypolipidemic drug that inhibits hydroxymethylglutaryl coenzyme A（HMGCoA） reductase to control elevated cholesterol,or hypercholesterolemia.Previous studies have shown that simvastatin may attenuate inflammation in ischemia-reperfusion injury and sepsis.Herein,we hypothesized that simvastatin may prevent rats from lipopolysaccharide（LPS）-induced septic shock.In our study,rats were divided into a saline group,an LPS group and an LPS plus simvastatin group.Male Sprague-Dawley（SD） rats were pretreated with simvastatin（1 mg/kg） for 30 min before the addition of LPS（8 mg/kg）,with variations in left ventricular pressure recorded throughout.Ninety min after LPS injection,whole blood was collected from the inferior vena cava,and neutrophils were separated from the whole blood using separating medium.The neutrophils were then lysed for Western blotting to detect the levels of urokinase-type plasminogen activator（u PA） and plasminogen activator inhibitor-1（PAI-1）.In addition,mesentery microcirculations of inlet diameter,outlet diameter and blood flow rate were measured in all three groups.The results indicated that simvastatin significantly promoted heart systolic function and increased the level of u PA while simultaneously inhibited the expression of PAI-1 as compared with LPS group.Moreover,simvastatin reversed the LPS-induced inhibition of mesentery microcirculation.Taken together,it was suggested that simvastatin can effectively protect the rats from LPS-induced septic shock.

Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1 polarizing adjuvant

Heat shock proteins (HSPs) are reported to act as effective adjuvants to elicit anti-tumor and anti-infection immunity. Here, we report that Hsp70-like protein 1 (Hsp70L1), a novel HSP derived from human dendritic cells (DCs), has potent adjuvant effects that polarize responses toward Th1. With a calculated molecular weight of 54.8 kDa, Hsp70L1 is smaller in size than Hsp70 but resembles it both structurally and functionally. Hsp70L1 shares common receptors on DCs with Hsp70 and can interact with DCs, promoting DC maturation and stimulating secretion of the proinflammatory cytokines interleukin 12p70 (IL-12p70), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and the chemokines IP-10, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and normal T cell expressed and secreted (RANTES). The induction of interferon-gamma-inducible protein 10 (IP-10) secretion by Hsp70L1 is not shared by Hsp70, and other functional differences include more potent stimulation of DC IL-12p70, CC-chemokine, and CCR7 and CXCR4 expression by Hsp70L1. Immunization of mice with the hybrid peptide Hsp70L1-ovalbumin(OVA)(257-264) induces an OVA(257-264)-specific Th1 response and cytotoxic T lymphocyte (CTL) that results in significant inhibition of E.G7-OVA tumor growth. The ability of Hsp70L1 to activate DCs indicates its potential as a novel adjuvant for use with peptide immunizations; the Hsp70L1 antigen peptide hybrid may serve as a more effective vaccine for the control of cancer and infectious diseases.

EFFECTS OF CYPROHEPTADINE ON PLASMA SUPEROXIDE DISMUTASE ACTIVITY AND MALONDIALDEHYDE CONTENT IN RABBITS WITH HEMORRHAGIC SHOCK

Profound hemorrhagic shock was produced in thirty rabbits by exsanguination via the carotid artery until blood pressure (BP) reached 5.3 kPa (40 mmHg) and was sustained for a period of 90 minutes. The rabbits were equally divided into cyproheptadine (Cyp) treated group and control group. Blood samples 30 minutes after liquid and blood infusion and administration of Cyp (10 mg / kg) were collected from the carotid artery, and the plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA) content measured. The results showed that Cyp remarkebly enhanced the plasma SOD activity (2462 338 vs 1955- 596, P<0.01) and reduced MDA content (2.68- 0.24 vs 3.20-0.49, P<0.01). We believe that the in crease of O2 production plays an important role in the develop-ment of shock, the single blood and liquid infusion can not significantly improve the shock conditions. Scavenging oxygen free radicals and alleviating cellular damage and multiple or gan failure are the possible mechanisms of cyproheptadine anti-shock effect.

Triggering star formation by both radiative and mechanical AGN feedback

We perform two dimensional hydrodynamic numerical simulations to study the positive active galactic nucleus （AGN） feedback which triggers, rather than suppresses, star formation. Recently, it was shown by Nayakshin et al. and Ishibashi et al. that star formation occurs when the cold interstellar medium （ISM） is squeezed by the impact of mass outflow or radiation pressure, respectively. Mass outflow is ubiquitous in this astrophysical context, and radiation pressure is also important if the AGN is luminous. For the first time in this subject, we incorporate both mass outflow feedback and radiative feedback into our model. Consequently, the ISM is shocked into shells by the AGN feedback, and these shells soon fragment into clumps and filaments because of Rayleigh-Taylor and thermal instabilities. We have two major findings： （1） the star formation rate can indeed be very large in the clumps and filaments. However, the resultant star formation rate density is too large compared with previous works, which is mainly because we ignore the fact that most of the stars that are formed would be disrupted when they move away from the galactic center. （2） Although radiation pressure feedback has a limited effect, when mass outflow feedback is also included, they reinforce each other. Specifically, in the gas-poor case, mass outflow is always the dominant contributor to feedback.