Study of the discovery potential of light custodians in a clean decay channel at the LHC

Models of warped extra dimensions with custodial symmetry usually predict the existence of a light Kaluza-Klein fermion arising as a partner of the right-handed top quark, sometimes called light custodians which we will denote (b) over tilde (R). The production of these particles at the LHC can give rise to multi-W events which could be observed in same-sign dilepton channels, but its mass reconstruction is challenging. In this paper we study the possibility of finding a signal for the pair production of this new particle at the LHC focusing on a rarer, but cleaner decay mode of a light custodian into a Z boson and a b-quark. In this mode it would be possible to reconstruct the light custodian mass. In addition to the dominant standard model QCD production processes, we include the contribution of a Kaluza-Klein gluon first mode. We find that (b) over tilde (R) stands out from the background as a peak in the bZ invariant mass. However, when taking into account only the electronic and muonic decay modes of the Z boson and b-tagging efficiencies, the LHC will have access only to the very light range of masses, m((b) over tilde) = O(500) GeV.

Quantitative parameters of facial motor evoked potential during vestibular schwannoma surgery predict postoperative facial nerve function

Background Facial motor evoked potential (FMEP) amplitude ratio reduction at the end of the surgery has been identified as a good predictor for postoperative facial nerve outcome. We sought to investigate variations in FMEP amplitude and waveform morphology during vestibular schwannoma (VS) resection and to correlate these measures with postoperative facial function immediately after surgery and at the last follow-up. Methods Intraoperative orbicularis oculi and oris muscles FMEP data from 35 patients undergoing surgery for VS resection were collected, then analysed by surgical stage: initial, dural opening, tumour dissection (TuDis), tumour resection (TuRes) and final. Findings Immediately after surgery, postoperative facial function correlated significantly with the FMEP amplitude ratio during TuDis, TuRes and final stages in both the orbicularis oculi (p = 0.003, 0.055 and 0.028, respectively) and oris muscles (p = 0.002, 0.104 and 0.014, respectively). At the last follow-up, however, facial function correlated significantly with the FMEP amplitude ratio only during the TuDis (p = 0.005) and final (p = 0.102) stages for the orbicularis oris muscle. At both time points, postoperative facial paresis correlated significantly with FMEP waveform deterioration in orbicularis oculi during the final stage (immediate, p = 0.023; follow-up, p = 0.116) and in orbicularis oris during the TuDis, TuRes and final stages (immediate, p = 0.071, 0.000 and 0.001, respectively; follow-up, p = 0.015, 0.001 and 0.01, respectively). Conclusions FMEP amplitude ratio and waveform morphology during VS resection seem to represent independent quantitative parameters that can be used to predict postoperative facial function. Event-to-baseline FMEP monitoring is quite useful to dictate when intraoperative changes in surgical strategy are warranted to reduce the chances of facial nerve injury.

Novel potential therapies for septic shock

Sepsis is the systemic inflammatory response syndrome secondary to a local infection. Septic shock, the severe complication of sepsis associated with refractory hypotension, is frequently a near-fatal condition requiring prompt diagnosis and management. Although the recent years have been associated with considerable improvements in the knowledge of the pathophysiology of the disease and remarkable advances have been achieved in sepsis treatment, the morbidity and mortality of this disease are still unacceptably high. In this review, we will briefly discuss the ongoing standard treatment of septic shock and describe novel potential therapies, aiming to improve hemodynamic support and/or control inflammatory response in sepsis. These therapies were associated with benefits in experimental studies and have been tested or are currently under testing in randomized controlled studies with septic patients.

Evaluation of rhBMP-2 and Natural Latex as Potential Osteogenic Proteins in Critical Size Defects by Histomorphometric Methods

This in vivo study evaluated the osteogenic potential of two proteins, recombinant human bone morphogenetic protein-2 (rhBMP-2) and a protein extracted from natural latex (Hevea brasiliensis, P-1), and compared their effects on bone defects when combined with a carrier or a collagen gelatin. Eighty-four (84) Wistar rats were divided into two groups, with and without the use of collagen gelatin, and each of these were divided into six treatment groups of seven animals each. The treatment groups were: (1) 5 mu g of pure rhBMP-2; (2) 5 mu g of rhBMP-2/monoolein gel; (3) pure monoolein gel; (4) 5 mu g of pure P-1; (5) 5 mu g of P-1/monoolein gel; (6) critical bone defect control. The animals were anesthetized and a 6 mm diameter critical bone defect was made in the left posterior region of the parietal bone. Animals were submitted to intracardiac perfusion after 4 weeks and the calvaria tissue was removed for histomorphometric analysis. In this experimental study, it was concluded that rhBMP-2 allowed greater new bone formation than P-1 protein and this process was more effective when the bone defect was covered with collagen gelatin (P < 0.05). Anat Rec, 293:794-801, 2010. (C) 2010 Wiley-Liss, Inc.

Gene expression profile analysis of primary glioblastomas and non-neoplastic brain tissue: identification of potential target genes by oligonucleotide microarray and real-time quantitative PCR

The prognosis of glioblastomas is still extremely poor and the discovery of novel molecular therapeutic targets can be important to optimize treatment strategies. Gene expression analyses comparing normal and neoplastic tissues have been used to identify genes associated with tumorigenesis and potential therapeutic targets. We have used this approach to identify differentially expressed genes between primary glioblastomas and non-neoplastic brain tissues. We selected 20 overexpressed genes related to cell cycle, cellular movement and growth, proliferation and cell-to-cell signaling and analyzed their expression levels by real time quantitative PCR in cDNA obtained from microdissected fresh tumor tissue from 20 patients with primary glioblastomas and from 10 samples of non-neoplastic white matter tissue. The gene expression levels were significantly higher in glioblastomas than in non-neoplastic white matter in 18 out of 20 genes analyzed: P < 0.00001 for CDKN2C, CKS2, EEF1A1, EMP3, PDPN, BNIP2, CA12, CD34, CDC42EP4, PPIE, SNAI2, GDF15 and MMP23b; and NFIA (P: 0.0001), GPS1 (P: 0.0003), LAMA1 (P: 0.002), STIM1 (P: 0.006), and TASP1 (P: 0.01). Five of these genes are located in contiguous loci at 1p31-36 and 2 at 17q24-25 and 8 of them encode surface membrane proteins. PDPN and CD34 protein expression were evaluated by immunohistochemistry and they showed concordance with the PCR results. The present results indicate the presence of 18 overexpressed genes in human primary glioblastomas that may play a significant role in the pathogenesis of these tumors and that deserve further functional investigation as attractive candidates for new therapeutic targets.

MRI findings of prostate stromal tumour of uncertain malignant potential: a case report

Prostatic stromal tumours are rare neoplasias that include benign, malignant and borderline lesions. Stromal tumour of uncertain malignant potential (STUMP) has been recently described and only a few reports exist in the literature. As a rare and distinct neoplasia, to date, there is no description of MRI findings of prostate STUMP. In this article, we describe the clinical and MRI features with histopathological correlation of a patient with prostate STUMP.

Combining two potential causes of metalloproteinase secretion causes abdominal aortic aneurysms in rats: a new experimental model

P>Progress in understanding the pathophysiology of abdominal aortic aneurysms (AAA) is dependent in part on the development and application of effective animal models that recapitulate key aspects of the disease. The objective was to produce an experimental model of AAA in rats by combining two potential causes of metalloproteinase (MMP) secretion: inflammation and turbulent blood flow. Male Wistar rats were randomly divided in four groups: Injury, Stenosis, Aneurysm and Control (40/group). The Injury group received a traumatic injury to the external aortic wall. The Stenosis group received an extrinsic stenosis at a corresponding location. The Aneurysm group received both the injury and stenosis simultaneously, and the Control group received a sham operation. Animals were euthanized at days 1, 3, 7 and 15. Aorta and/or aneurysms were collected and the fragments were fixed for morphologic, immunohistochemistry and morphometric analyses or frozen for MMP assays. AAAs had developed by day 3 in 60-70% of the animals, reaching an aortic dilatation ratio of more than 300%, exhibiting intense wall remodelling initiated at the adventitia and characterized by an obvious inflammatory infiltrate, mesenchymal proliferation, neoangiogenesis, elastin degradation and collagen deposition. Immunohistochemistry and zymography studies displayed significantly increased expressions of MMP-2 and MMP-9 in aneurysm walls compared to other groups. The haemo-dynamic alterations caused by the stenosis may have provided additional contribution to the MMPs liberation. This new model illustrated that AAA can be multifactorial and confirmed the key roles of MMP-2 and MMP-9 in this dynamic remodelling process.

Lectin extracted from Canavalia grandiflora seeds presents potential anti-inflammatory and analgesic effects

Neutrophil migration is responsible for tissue damage observed in inflammatory diseases and is also implicated in inflammatory nociception. The use of lectins has been demonstrated to be effective in different activities including anti-inflammatory, antimicrobial, and in cancer therapy. In this study, we addressed the potential use of a lectin from Canavalia grandiflora seeds (ConGF) to control neutrophil migration and inflammatory hypernociception. Pretreatment of the animals intravenously (15 min before) with ConGF inhibited neutrophil migration to the peritoneal cavity in a dose-dependent fashion confirmed by an inhibition of rolling and adhesion of leukocytes by intravital microscopy. Another set of experiments showed that pretreatment of the animals with ConGF inhibited the mechanical hypernociception in mice induced by the i.pl. injection of carrageenan or formalin. This anti-nociceptive effect correlated with an effective blockade of neutrophil influx, as assessed by the hind paw tissue myeloperoxidase levels. Furthermore, ConGF had important inhibitory effects on the mouse carrageenan-induced paw edema. In addition, animals treated with ConGF showed inhibition of cytokines release. In conclusion, we demonstrated that the lectin ConGF inhibits neutrophil migration and mechanical inflammatory hypernociception.

Modulation of anxiety-like behaviour by Transient Receptor Potential Vanilloid Type 1 (TRPV1) channels located in the dorsolateral periaqueductal gray

The endocannabinoid anandamide is a possible agonist at the Transient Receptor Potential Vanilloid Type 1 (TRPV1) channel, in addition to its agonist activity at cannabinoid type 1 (CB1) receptor. In the midbrain dorsolateral periaqueductal gray (dlPAC) our previous data showed that CB1 activation induces anxiolytic-like effects. However, the rote of TRPV1 has remained unclear. Thus, in the present study we tested the hypothesis that this channel would contribute to the modulation of anxiety-like behaviour in the dlPAG. Mate Wistar rats received local injections of the TRPV1 antagonist capsazepine (10-60 nmol) and were submitted to the elevated plus-maze (EPM) and to the Vogel test. In addition, animals received local injections of capsaicin (0.01-1nmol), a TRPV1 agonist, and were tested in the same models. In accordance with our hypothesis, capsazepine produced anxiolytic-like effects both in the EPM and in the Vogel test. Capsaicin mimicked these results, which might be attributed to its ability to quickly desensitize the channel. Altogether, our data suggest that, while CB1 receptors seem to inhibit aversive responses in the dlPAG, TRPV1 could facilitate them. Thus, CB1 and TRPV1 may have opposite functions in modulating anxiety-like behaviour in this region. (C) 2008 Elsevier B.V. and ECNP. All rights reserved.

A reassessment of the in vitro RBC haemolysis assay with defibrinated sheep blood for the determination of the ocular irritation potential of cosmetic products: Comparison with the in vivo Draize rabbit test

We examined the correlation between results obtained from the in vivo Draize test for ocular irritation and in vitro results obtained from the sheep red blood cell (RBC) haemolytic assay, which assesses haemolysis and protein denaturation in erythrocytes, induced by cosmetic products. We sought to validate the haemolytic assay as a preliminary test for identifying highly-irritative products, and also to evaluate the in vitro test as alternative assay for replacement of the in vivo test. In vitro and in vivo analyses were carried out on 19 cosmetic products, in order to correlate the lesions in the ocular structures with three in vitro parameters: (i) the extent of haemolysis (H50); (ii) the protein denaturation index (131); and (iii) the H50/DI ratio, which reflects the irritation potential (IP). There was significant correlation between maximum average scores (MAS) and the parameters determined in vitro (r = 0.752-0.764). These results indicate that the RBC assay is a useful and rapid test for use as a screening method to assess the IP of cosmetic products, and for predicting the IP value with a high level of concordance (94.7%). The assay showed high sensitivity and specificity rates of 91.6% and 100%, respectively.

Role of complement C5a in mechanical inflammatory hypernociceptio: potential use of C5a receptor antagonists to control inflammatory pain

particularly neutrophil chemoattraction. Herein, the role of C5a in the genesis of inflammatory hypernociception was investigated in rats and mice using the specific C5a receptor antagonist PMX53 (AcF-[OP(D-Cha)WR]). Experimental approach: Mechanical hypernociception was evaluated with a modification of the Randall-Selitto test in rats and electronic pressure meter paw test in mice. Cytokines were measured by ELISA and neutrophil migration was determined by myeloperoxidase activity. Key results: Local pretreatment of rats with PMX53 (60-180 mg per paw) inhibited zymosan-, carrageenan-, lipopolysaccharide (LPS)- and antigen-induced hypernociception. These effects were associated with C5a receptor blockade since PMX53 also inhibited the hypernociception induced by zymosan- activated serum and C5a but not by the direct-acting hypernociceptive mediators, prostaglandin E-2 and dopamine. Underlying the C5a hypernociceptive mechanisms, PMX53 did not alter the cytokine release induced by inflammatory stimuli. However, PMX53 inhibited cytokine-induced hypernociception. PMX53 also inhibited the recruitment of neutrophils induced by zymosan but not by carrageenan or LPS, indicating an involvement of neutrophils in the hypernociceptive effect of C5a. Furthermore, the C5a-induced hypernociception was reduced in neutrophil-depleted rats. Extending these findings in rats, blocking C5a receptors also reduced zymosan- induced joint hypernociception in mice. Conclusions and implications: These results suggest that C5a is an important inflammatory hypernociceptive mediator, acting by a mechanism independent of hypernociceptive cytokine release, but dependent on the presence of neutrophils. Therefore, we suggest that inhibiting the action of C5a has therapeutic potential in the control of inflammatory pain.

Dysregulation of renal transient receptor potential melastatin 6/7 but not paracellin-1 in aldosterone-induced hypertension and kidney damage in a model of hereditary hypomagnesemia

Rationale Hyperaldosteronism, important in hypertension, is associated with electrolyte alterations, including hypomagnesemia, through unknown mechanisms. Objective To test whether aldosterone influences renal Mg(2+) transporters, (transient receptor potential melastatin (TRPM) 6, TRPM7, paracellin-1) leading to hypomagnesemia, hypertension and target organ damage and whether in a background of magnesium deficiency, this is exaggerated. Methods and results Aldosterone effects in mice selectively bred for high-normal (MgH) or low (MgL) intracellular Mg(2+) were studied. Male MgH and MgL mice received aldosterone (350 mu g/kg per day, 3 weeks). SBP was elevated in MgL. Aldosterone increased blood pressure and albuminuria and increased urinary Mg(2+) concentration in MgH and MgL, with greater effects in MgL. Activity of renal TRPM6 and TRPM7 was lower in vehicle-treated MgL than MgH. Aldosterone increased activity of TRPM6 in MgH and inhibited activity in MgL. TRPM7 and paracellin-1 were unaffected by aldosterone. Aldosterone-induced albuminuria in MgL was associated with increased renal fibrosis, increased oxidative stress, activation of mitogen-activated protein kinases and nuclear factor-NF-kappa B and podocyte injury. Mg(2+) supplementation (0.75% Mg(2+)) in aldosterone-treated MgL normalized plasma Mg(2+), increased TRPM6 activity and ameliorated hypertension and renal injury. Hence, in a model of inherited hypomagnesemia, TRPM6 and TRPM7, but not paracellin-1, are downregulated. Aldosterone further decreased TRPM6 activity in hypomagnesemic mice, a phenomenon associated with hypertension and kidney damage. Such effects were prevented by Mg(2+) supplementation. Conclusion Amplified target organ damage in aldosterone-induced hypertension in hypomagnesemic conditions is associated with dysfunctional Mg(2+)-sensitive renal TRPM6 channels. Novel mechanisms for renal effects of aldosterone and insights into putative beneficial actions of Mg(2+), particularly in hyperaldosteronism, are identified. J Hypertens 29: 1400-1410 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.