Fatigue related impairments in oculomotor control are prevented by caffeine

Strenuous exercise can result in an inability of the central nervous system to drive skeletal muscle e ectively, a phenomenon known as central fatigue. The impact of central fatigue on the oculomotor system is currently unexplored. Fatigue that originates in the central nervous system may be related to perturbations in the synthesis and metabolism of several neurotransmitters. In this study we examine central fatigue in the oculomotor system after prolonged exercise. The involvement of central neurotransmission was explored by administering ca eine during exercise. Within a double- blind, randomized, repeated measures, crossover design, 11 cyclists consumed a placebo or ca eine solution during 180 min of stationary cycling. Saccadic eye movements were measured using infra-red oculography. Exercise decreased saccade velocity by 8% (placebo trial). This e ect was reversed by ca eine, whereby velocity was increased by 11% after exercise. A non oculomotor perceptual task (global motion processing) was una ected by exercise. The human oculomotor system is impaired by strenuous exercise of the locomotor system. Ca eine exerts a protective e ect on oculomotor control, which could be related to up-regulated central neurotransmission. In addition, cortical processes supporting global motion perception appear to be robust to fatigue

Non-Enzymatic Decomposition of Collagen Fibers by a Biglycan Antibody and a Plausible Mechanism for Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory and destructive joint disorder that affects tens of millions of people worldwide. Normal healthy joints maintain a balance between the synthesis of extracellular matrix (ECM) molecules and the proteolytic degradation of damaged ones. In the case of RA, this balance is shifted toward matrix destruction due to increased production of cleavage enzymes and the presence of (autoimmune) immunoglobulins resulting from an inflammation induced immune response. Herein we demonstrate that a polyclonal antibody against the proteoglycan biglycan (BG) causes tissue destruction that may be analogous to that of RA affected tissues. The effect of the antibody is more potent than harsh chemical and/or enzymatic treatments designed to mimic arthritis-like fibril de-polymerization. In RA cases, the immune response to inflammation causes synovial fibroblasts, monocytes and macrophages to produce cytokines and secrete matrix remodeling enzymes, whereas B cells are stimulated to produce immunoglobulins. The specific antigen that causes the RA immune response has not yet been identified, although possible candidates have been proposed, including collagen types I and II, and proteoglycans (PG's) such as biglycan. We speculate that the initiation of RA associated tissue destruction in vivo may involve a similar non-enzymatic decomposition of collagen fibrils via the immunoglobulins themselves that we observe here ex vivo

Clinicopathological and prognostic significance of HER-2/neu and VEGF expression in colon carcinomas

<p>Abstract</p> <p>Background</p> <p>HER-2/neu and VEGF expression is correlated with disease behaviors in various cancers. However, evidence for their expression in colon cancer is rather contradictory both for the protein expression status and prognostic value. HER-2/neu is found to participate in VEGF regulation, and has known correlation with VEGF expression in some tumors. In this study, we investigated HER-2/neu and VEGF expression in Chinese colon patients and explored whether there was any correlation between their expression patterns.</p> <p>Methods</p> <p>HER-2/neu and VEGF were investigated immunohistochemically using tumor samples obtained from 317 colon cancer patients with all tumor stages. Correlation of the degree of staining with clinicopathological parameters and survival was investigated.</p> <p>Results</p> <p>Positive expression rates of HER-2/neu and VEGF in colon cancer were 15.5% and 55.5% respectively. HER-2/neu expression was significantly correlated with tumor size and distant metastases (<it>P </it>< 0.05), but was not an independent prognostic marker of survival <it>(P > 0.05)</it>. Expression of VEGF was significantly correlated with tumor size, tumor stage, lymph node metastases, and distant metastases (<it>P </it>< 0.05). The 5-year survival rate in patients with negative and positive VEGF expression was 70.2% and 61.9% respectively; the difference was not statistically significant <it>(P = 0.146)</it>. No correlation between HER-2/neu and VEGF expression was detected (<it>P = </it>0.151).</p> <p>Conclusions</p> <p>HER-2/neu and VEGF are not important prognostic markers of colon cancer. The present results do not support any association between HER2/neu and VEGF expression in this setting.</p

In vitro and in vivo anticancer properties of a Calcarea carbonica derivative complex (M8) treatment in a murine melanoma model

<p>Abstract</p> <p>Background</p> <p>Melanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have had only marginal success. Previous studies in mice demonstrated that a high diluted complex derived from <it>Calcarea carbonica </it>(M8) stimulated the tumoricidal response of activated lymphocytes against B16F10 melanoma cells <it>in vitro</it>.</p> <p>Methods</p> <p>Here we describe the <it>in vitro </it>inhibition of invasion and the <it>in vivo </it>anti-metastatic potential after M8 treatment by inhalation in the B16F10 lung metastasis model.</p> <p>Results</p> <p>We found that M8 has at least two functions, acting as both an inhibitor of cancer cell adhesion and invasion and as a perlecan expression antagonist, which are strongly correlated with several metastatic, angiogenic and invasive factors in melanoma tumors.</p> <p>Conclusion</p> <p>The findings suggest that this medication is a promising non-toxic therapy candidate by improving the immune response against tumor cells or even induce direct dormancy in malignancies.</p

Modeling of negative Poisson’s ratio (auxetic) crystalline cellulose Iβ

Energy minimizations for unstretched and stretched cellulose models using an all-atom empirical force field (Molecular Mechanics) have been performed to investigate the mechanism for auxetic (negative Poisson’s ratio) response in crystalline cellulose Iβ from kraft cooked Norway spruce. An initial investigation to identify an appropriate force field led to a study of the structure and elastic constants from models employing the CVFF force field. Negative values of on-axis Poisson’s ratios nu31 and nu13 in the x1-x3 plane containing the chain direction (x3) were realized in energy minimizations employing a stress perpendicular to the hydrogen-bonded cellobiose sheets to simulate swelling in this direction due to the kraft cooking process. Energy minimizations of structural evolution due to stretching along the x3 chain direction of the ‘swollen’ (kraft cooked) model identified chain rotation about the chain axis combined with inextensible secondary bonds as the most likely mechanism for auxetic response

Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements

A considerable number of genes that code for AU-rich mRNAs including cytokines, growth factors, transcriptional factors, and certain receptors are involved in both chronic inflammation and cancer. Overexpression of these genes is affected by aberrations or by prolonged activation of several signaling pathways. AU-rich elements (ARE) are important cis-acting short sequences in the 3′UTR that mediate recognition of an array of RNA-binding proteins and affect mRNA stability and translation. This review addresses the cellular and molecular mechanisms that are common between inflammation and cancer and that also govern ARE-mediated post-transcriptional control. The first part examines the role of the ARE-genes in inflammation and cancer and sequence characteristics of AU-rich elements. The second part addresses the common signaling pathways in inflammation and cancer that regulate the ARE-mediated pathways and how their deregulations affect ARE-gene regulation and disease outcome

Evidence that involucrin, a marker for differentiation, is oxygen regulated in human squamous cell carcinomas

Hypoxia is associated with poor prognosis in squamous cell carcinomas affecting both local control and distant spread (Hockel et al., 1996a, 1996b, 1999; Nordsmark et al, 1996; Fyles et al, 2002; Kaanders et al, 2002). Local control is believed to depend on local radiation response while distant spread is thought to depend, at least in part, on the induction of oxygen-regulated proteins. In order to test this, pimonidazole, an extrinsic marker for tissue hypoxia (Arteel et al, 1995; Kennedy et al, 1997; Varia et al, 1998; Raleigh et al, 1999), with prognostic value (Kaanders et al, 2002) was used to examine whether ORPs such as VEGF (Raleigh et al, 1998a), metallothionein (Raleigh et al, 2000), HIF-1α (Janssen et al, 2002), Glut-1 (Airley et al, 2003) and CAIX (Olive et al, 2001) were, in fact, associated with cellular hypoxia in human tumours. Unexpectedly, VEGF and metallothionein (MT) were not expressed in the majority of hypoxic cells in squamous cell carcinomas (Raleigh et al, 1998a, 2000) even though these ORPs were induced by hypoxia in experimental systems (Shweiki et al, 1992; Raleigh et al, 1998b; Murphy et al, 1999)

Interpretation of the small-angle X-ray diffraction of collagen in view of the primary structure of the alpha1 chain.

The small-angle X-ray diffraction pattern of collagen has been calculated using the sequence of the alpha 1 chain and a Hodge-Petruska scheme for the packing of the collagen molecules. The molecular stagger giving the best fit of calculated-to observed structure factors has been found to be 236 or 237 amino acid residues for three tendon collagens. But this result depends on the appoximation that the molecular conformation is uniform throughout the molecule. A comparison of the observed and calculated electron density profiles in axial projection leads to a corrected model, in which the COOH-terminal telopeptide is contracted in a way suggesting a saddle-shaped electron density distribution near the collagenase site