Studies on the effects of the antiandrogen cyproterone acetate on social encounters between pairs of male mice

An attempt was made in two experiments to reinvestigate the effects of the antiandrogen cyproterone acetate (CA) on mouse social behavior in a variety of ethologically-assessed paired encounters. The data confirm that CA reduces offense (threat and attack) in animals when both subjects receive the material but that CA has no such action in other pairings. This suggests that CA's major suppressive effect on "hostility" is expressed in mice via a reduction in "attack-promoting" pheromone production. Indeed, there was evidence in the more chronic study that CA, could augment (via a central mechanism?) offense in subjects paired with docile anosmic opponents. Changes in defense were largely responses to variations in the degree of attack to which animals were subjected. The antihormone also had actions on other aspects of behavior including sexual activity, social investigation and immobility in such tests. CA had a potent suppressive action on the weights of sex accessory glands. The data do not suggest that CA can be used as a specific antihostility agent.     

The atheroprotective effect of 17beta-estradiol depends on complex interactions in adaptive immunity

Estradiol prevents fatty streak formation in chow-fed atherosclerosis-prone apolipoprotein E (ApoE)-deficient mice. We previously reported that fatty streak development of immunodeficient ApoE(-/-)/recombination activating gene 2 (RAG-2(-/-)) double-deficient mice was insensitive to estradiol. In the present work, we demonstrate that the reconstitution of ApoE(-/-)/RAG-2(-/-) with bone marrow from immunocompetent ApoE(-/-)/RAG-2(+/+) mice restores the protective effect of estradiol on fatty streak constitution. We extended this demonstration to the model of low-density lipoprotein receptor-deficient mice, establishing the obligatory role of mature lymphocytes in this process. We then investigated whether the protective effect of estradiol was mediated by a specific lymphocyte subpopulation by studying the hormonal effect on fatty streak constitution in recently developed models of ApoE(-/-) mice deficient in selective T-lymphocyte subsets (either TCRalphabeta+, CD4+, CD8+, or TCRgammadelta+ lymphocytes) or B lymphocytes. In all these specifically immunodeficient mice, estradiol administration to ovariectomized mice conferred protection as in immunocompetent ApoE(-/-) mice, clearly demonstrating that no single lymphocyte subpopulation was specifically required for this effect. These results point to additional lymphocyte-dependent mechanisms such as modulating the interactions among lymphocytes and between lymphocytes and endothelial and/or antigen-presenting cells.     

Cardiac effects of contrast media in MR angiography: evaluation in an experimental model of myocardial ischemia

RATIONALE AND OBJECTIVES: The authors evaluated the cardiac tolerability of paramagnetic contrast agents for magnetic resonance (MR) angiography in an in vitro model of ischemic rat heart. MATERIALS AND METHODS: The left anterior descending coronary artery was temporarily occluded in a perfused rat heart model to induce cardiac ischemia and reperfusion. A dose of 0.4 mL of gadobenate dimeglumine, of gadopentetate dimeglumine, or of D-mannitol was injected directly into the aorta both during the ischemia and during the reperfusion period. The left ventricular pressure and heart rate were recorded. RESULTS: Myocardial ischemia resulted in decreased cardiac activity, with a reduction in left ventricular pressure and heart rate. A further decrease in cardiac activity was temporarily induced by injection of contrast medium during both the ischemic and early reperfusion phases. Less marked responses were induced by a hyperosmolal solution of mannitol. CONCLUSION: These results suggest that the transient cardiac effects induced by bolus injection of paramagnetic contrast medium may be regarded as the combined effects of the osmotoxicity of the contrast medium solution and the chemotoxicity of the contrast medium molecule.     

Evidence for an enterovirus as the cause of encephalitis lethargica

Background

The epidemic of encephalitis lethargica (EL), called classical EL, was rampant throughout the world during 1917?C1926, affecting half a million persons. The acute phase was lethal for many victims. Post-encephalitic parkinsonism (PEP) affected patients for decades. Our purpose was to investigate the cause of classical EL by studying the few available brain specimens. Cases of PEP and modern EL were also studied. Transmission electron microscopy (TEM) and immunohistochemistry were employed to examine brain from four classical EL cases, two modern EL cases and one PEP case.

Methods

Standard methods for TEM, immunohistochemistry and RTPCR were applied.

Results

27?nm virus-like particles (VLP) were observed in the cytoplasm and nuclei of midbrain neurons in all classical EL cases studied. Large (50?nm) VLP and 27?nm intranuclear VLP were observed in the modern EL cases and the PEP case. Influenza virus particles were not found. VLP were not observed in the control cases. TEM of cell cultures inoculated with coxsackievirus B4 and poliovirus revealed both small and large intranuclear virus particles and small cytoplasmic particles, similar to the VLP in EL neurons. In the EL brains, nascent VLP were embedded in putative virus factories and on endoplasmic reticulum (ER). The VLP in the cases of classical EL survived, whereas ribosomes underwent autolysis due to the lack of refrigeration and slow formaldehyde fixation of whole brain. The VLP were larger than ribosomes from well preserved brain. Immunohistochemistry of classical EL cases using anti-poliovirus and anti-coxsackievirus B polyclonal antibodies showed significant staining of cytoplasm and nuclei of neurons as well as microglia and neuropil. Purkinje cells were strongly stained. A 97-bp RNA fragment of a unique virus was isolated from brain tissue from acute EL case #91558. Sequence analysis revealed up to 95% identity to multiple human Enteroviruses. Additional cases had Enterovirus positive reactions by real time PCR.

Conclusions

The data presented here support the hypothesis that the VLP observed in EL tissue is an Enterovirus.     

Enhanced antibacterial nanocomposite mats by coaxial electrospinning of polycaprolactone fibers loaded with Zn-based nanoparticles

ZnO and Zn acetate nanoparticles were embedded in polycaprolactone coaxial-fibers and uniaxial-fibers matrices to develop potential antibacterial nanocomposite wound dressings (mats). Morphology, composition, wettability, crystallinity and fiber structure of mats were characterized. Antibacterial properties of mats were tested against E. coli and S. aureus by turbidity and MTT assays. The effect of UVA illumination (prior to bacteria inoculation) on mats’ antibacterial activity was also studied. Results showed that a coaxial-fibers design maintained nanoparticles distributed in the outer-shell of fibers and, in general, enhanced the antibacterial effect of the mats, in comparison to conventional uniaxial-fibers mats. Results indicated that mats simultaneously inhibited planktonic and biofilm bacterial growth by, probably, two main antibacterial mechanisms; 1) release of Zn²⁺ ions (mainly from Zn acetate nanoparticles) and 2) photocatalytic oxidative processes exerted by ZnO nanoparticles. Antibacterial properties of mats were significantly improved by coaxial-fibers design and exposure to UVA-light prior to bacteria inoculation.     

Characteristics of polytrauma patients with posttraumatic stress disorder in a level 1 trauma center

Aims  

The aims of this study were to determine if the severity of injury is related to the prevalence of posttraumatic stress disorder (PTSD) in polytrauma patients and to review the personality traits of patients with PTSD.     

Hyperhomocysteinemia in healthy young men and elderly men with normal serum folate concentration is not associated with poor vascular reactivity or oxidative stress

The mechanism by which homocysteine (Hcy) causes endothelial dysfunction is probably mediated by oxidative stress. The aim of this study was to evaluate the effect of oxidative stress on endothelial function in young and elderly hyperhomocysteinemic (HHcy) men. A total of 35 HHcy (Hcy > 15 micro mol/L), young (n = 15; 20-40 y) and elderly men (n = 20; > 65 y) and 33 normohomocysteinemic (NHcy; controls) young (n = 14) and elderly (n = 19) men (Hcy < 13 micro mol/L), without classic cardiovascular risk factors were recruited. Serum Hcy, folate, and vitamin B-12, whole-blood glutathione, plasma total antioxidants status, TBARS, and 8-F(2alpha) isoprostanes were determined. Noninvasive ultrasound measurements of endothelium-dependent (EDVR) and -independent dilatation (EIVR) were performed. EDVR, EIVR, and markers of oxidative stress did not differ among the groups. Folate concentrations were higher in elderly than in young men (P < 0.001), independent of Hcy concentrations. Vitamin B-12 concentrations were lower in HHcy than in NHcy elderly men (P < 0.045). EDVR was correlated with folate concentrations in young men (r = 0.40, P = 0.04) and negatively with BMI in elderly men (r = -0.52, P = 0.002). In the present study, HHcy with normal serum folate concentrations was not associated with poor EDVR or oxidative stress in healthy young and elderly men.     

Antiangiogenic properties of fibstatin, an extracellular FGF-2-binding polypeptide

By using the two-hybrid system with basic fibroblast growth factor (FGF-2) as bait, we isolated and characterized fibstatin, an endogenous M(r) 29,000 human basement membrane-derived inhibitor of angiogenesis and tumor growth. Fibstatin, a fragment containing the type III domains 12-14 of fibronectin, was produced as a recombinant protein and was shown to inhibit the proliferation, migration, and differentiation of endothelial cells in vitro. Antiangiogenic activity of fibstatin was confirmed in a Matrigel angiogenesis assay in vivo, and electrotransfer of the fibstatin gene into muscle tissue resulted in reduced B16F10 tumor growth. Taken together, these results suggest that fibstatin could act as a powerful molecule for antiangiogenic therapy.