Inhibition of Methylglyoxal-Mediated Protein Modification in Glyoxalase I Overexpressing Mouse Lenses

Objective. Here we tested the role of Glo I in the prevention of advanced glycation end product (AGE) formation in transgenic mouse lenses. Methods. A transgenic animal line that expressed high levels of human Glo I in the lens was developed from the C57B6 mouse strain. The role of Glo I in the inhibition of MGO-AGE formation was tested in organ-cultured lenses. Results. Organ culture of Wt and Glo I lenses with 5 mM D, L-glyceraldehyde (GLD) enhanced MGO by 29-fold and 17-fold in Wt lenses and Glo I lenses, respectively. Argpyrimidine levels were 192 ± 73 pmoles/mg protein, and hydroimidazolone levels were 22 ± 0.7 units/μg protein in GLD-incubated Wt lenses. In Glo I lenses, formation of AGEs was significantly inhibited; the argpyrimidine levels were 82 ± 18 pmoles/mg protein, and the HI levels were 2.6 ± 2.3 units/μg protein. Incubation of Wt lens proteins with 5 mM ribose for 7 days resulted in the formation of pentosidine. However, the levels were substantially higher in Glo I lens proteins incubated with ribose. Conclusion. Our study provides direct evidence that Glo I activity plays an important role in the regulation of AGE synthesis in the lens; while Glo I activity blocks the formation of MGO-AGEs, it might promote the formation of sugar-derived AGEs

Modified Huo-Luo-Xiao-Ling Dan Suppresses Adjuvant Arthritis by Inhibiting Chemokines and Matrix-Degrading Enzymes

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the joints that can lead to deformities and disability. The prolonged use of conventionally used drugs is associated with severe adverse reactions. Therefore, safer and less expensive therapeutic products are continually being sought. Huo-Luo-Xiao-Ling dan (HLXL), a traditional Chinese herbal mixture, and its modified versions possess anti-arthritic activity. In this paper, we examined the influence of modified HLXL on two of the key mediators of arthritic inflammation and tissue damage, namely, chemokines and matrix-metalloproteinases (MMPs) in the rat adjuvant-induced arthritis (AA) model of RA. We treated arthritic Lewis rats with HLXL (2.3 g/kg) by daily gavage beginning at the onset of AA. The control rats received the vehicle. At the peak phase of AA, rats were sacrificed and their draining lymph node cells (LNC) and spleen adherent cells (SAC) were tested. The HLXL-treated rats showed a significant reduction in the levels of chemokines (RANTES, MCP-1, MIP-1α, and GRO/KC), MMPs (MMP 2 and 9), as well as cytokines (IL-6 and IL-17) that induce them, compared to the control vehicle-treated rats. Thus, HLXL controls arthritis in part by suppressing the mediators of immune pathology, and it might offer a promising alternative/adjunct treatment for RA

Suppression of Ongoing Experimental Arthritis by a Chinese Herbal Formula (Huo-Luo-Xiao-Ling Dan) Involves Changes in Antigen-Induced Immunological and Biochemical Mediators of Inflammation

Rheumatoid arthritis (RA) is one of the major autoimmune diseases of global prevalence. The use of the anti-inflammatory drugs for the treatment of RA is associated with severe adverse reactions and toxicity. This limitation has necessitated the search for novel therapeutic products. We report here a traditional Chinese medicine-based herbal formula, Huo luo xiao ling dan (HLXL), which has potent antiarthritic activity as validated in the rat adjuvant-induced arthritis (AA) model. HLXL (2.3 g/Kg) was fed to Lewis (RT.11) rats daily by gavage beginning at the onset of arthritis and then continued through the observation period. HLXL inhibited the severity of ongoing AA. This suppression of arthritis was associated with significant alterations in the T cell proliferative and cytokine responses as well as the antibody response against the disease-related antigen, mycobacterial heat-shock protein 65 (Bhsp65). There was a reduction in the level of the proinflammatory cytokines IL-17 and IL-1β but enhancement of the anti-inflammatory cytokine IL-10 level. In addition, there was inhibition of both the anti-Bhsp65 antibody response and the serum level of nitric oxide. Thus, HLXL is a promising CAM modality for further testing in RA patients

Accumulation of stress in constrained assemblies: novel Satoh test configuration

A common test used to study the response of a transforming material to external constraint is due to Satoh and involves the cooling of a rigidly constrained tensile specimen while monitoring the stress that accumulates. Such tests are currently common in the invention of welding alloys which on phase transformation lead to a reduction in residual stresses in the final assembly. The test suffers from the fact that the whole of the tensile specimen is not maintained at a uniform temperature, making it difficult to interpret the data. To eliminate this problem, the authors report here a novel Satoh test in which the material investigated is a part of a composite sample. It is demonstrated that this helps avoid some of the complications of the conventional tests and gives results which are consistent with independent tests

Anti-Inflammatory Activities of a Chinese Herbal Formula IBS-20 In Vitro and In Vivo

Irritable bowel syndrome (IBS) is a functional bowel disorder and the etiology is not well understood. Currently there is no cure for IBS and no existing medication induces symptom relief in all patients. IBS-20 is a 20-herb Chinese medicinal formula that offers beneficial effects in patients with IBS; however, the underlying mechanisms are largely unknown. This study showed that IBS-20 potently inhibited LPS- or IFNΓ-stimulated expression of pro-inflammatory cytokines, as well as classically activated macrophage marker nitric oxide synthase 2. Similarly, IBS-20 or the component herb Coptis chinensis decreased LPS-stimulated pro-inflammatory cytokine secretion from JAWS II dendritic cells. IBS-20 or the component herbs also blocked or attenuated the IFNΓ-induced drop in transepithelial electric resistance, an index of permeability, in fully differentiated Caco-2 monolayer. Finally, the up-regulation of key inflammatory cytokines in inflamed colon from TNBS-treated mice was suppressed significantly by orally administrated IBS-20, including IFNΓ and IL-12p40. These data indicate that the anti-inflammatory activities of IBS-20 may contribute to the beneficial effects of the herbal extract in patients with IBS, providing a potential mechanism of action for IBS-20. In addition, IBS-20 may be a potential therapeutic agent against other Th1-dominant gut pathologies such as inflammatory bowel disease

Experimental study on shear performance of RC beams strengthened with NSM CFRP prestressed concrete prisms

This paper presents an experimental investigation of the shear performance of RC beams strengthened with near surface mounted (NSM) carbon fibre reinforced polymer (CFRP) prestressed concrete prisms (PCPs). The shear behaviour of strengthened beams can be affected by several design variables. In this research, the effect of the following parameters were considered: the prestress level, inclination and spacing of the CFRP-PCPs, and material type of the prism. The control beam had conventional shear steel reinforcement only while the other seven beams were shear strengthened with CFRP-PCPs by varying design parameters mentioned above. All the beams were tested under monotonic loading until they reached the failure load. The experimental results showed that the NSM CFRP-PCPs strengthening technique improves the shear performance of the beams effectively. The strengthened beams that applied the CFRP-PCPs at an inclination of 45 • were more efficient in improving the shear capacity compared to vertical CFRP-PCPs. The shear capacity and deformation were enhanced with the increase of prestressing levels of CFRP rods and the decrease of CFRP-PCPs spacing. The failure modes of the strengthened beams were influenced mainly by the spacing and the inclination of the CFRP-PCPs. Moreover, the material type of the prism had little influence on the effectiveness of shear strengthening. The analytical model presented was developed to estimate the shear contribution of NSM CFRP-PCPs and the model was found to predict the shear capacity of the tested beams well

Stainless steel weld metal designed to mitigate residual stresses

There have been considerable efforts to create welding consumables which on solid state phase transformation partly compensate for the stresses which develop when a constrained weld cools to ambient temperatures. All of these efforts have focused on structural steels which are ferritic. In the present work, alloy design methods have been used to create a stainless steel welding consumable which solidifies as δ ferrite, transforms almost entirely into austenite which then undergoes martensitic transformation at a low temperature of about 220◦C. At the same time, the carbon concentration has been kept to a minimum to avoid phenomena such as sensitisation. The measured mechanical properties, especially toughness, seem to be significantly better than commercially available martensitic stainless steel welding consumables, and it has been demonstrated that the use of the new alloy reduces distortion in the final joint

Electroacupuncture activates corticotrophin-releasing hormone-containing neurons in the paraventricular nucleus of the hypothalammus to alleviate edema in a rat model of inflammation

<p>Abstract</p> <p>Background</p> <p>Studies show that electroacupuncture (EA) has beneficial effects in patients with inflammatory diseases. This study investigated the mechanisms of EA anti-inflammation, using a rat model of complete Freund's adjuvant (CFA)-induced hind paw inflammation and hyperalgesia.</p> <p>Design</p> <p>Four experiments were conducted on male Sprague-Dawley rats (n = 6–7/per group). Inflammation was induced by injecting CFA into the plantar surface of one hind paw. Experiment 1 examined whether EA increases plasma adrenocorticotropic hormone (ACTH) levels. Experiments 2 and 3 studied the effects of the ACTH and corticotropin-releasing hormone (CRH) receptor antagonists, ACTH_(11–24)and astressin, on the EA anti-edema. Experiment 4 determined whether EA activates CRH neurons in the paraventricular nucleus of the hypothalammus. EA treatment, 10 Hz at 3 mA and 0.1 ms pulse width, was given twice for 20 min each, once immediately post and again 2 hr post-CFA. Plasma ACTH levels, paw thickness, and paw withdrawal latency to a noxious thermal stimulus were measured 2 h and 5 h after the CFA.</p> <p>Results</p> <p>EA significantly increased ACTH levels 5 h (2 folds) after CFA compared to sham EA control, but EA alone in naive rats and CFA alone did not induce significant increases in ACTH. ACTH_(11–24)and astressin blocked EA anti-edema but not EA anti-hyperalgesia. EA induced phosphorylation of NR1, an essential subunit of the N-methyl-D-aspartic acid (NMDA) receptor, in CRH-containing neurons of the paraventricular nucleus.</p> <p>Conclusion</p> <p>The data demonstrate that EA activates CRH neurons to significantly increase plasma ACTH levels and suppress edema through CRH and ACTH receptors in a rat model of inflammation.</p

How Well Do Randomized Trials Inform Decision Making: Systematic Review Using Comparative Effectiveness Research Measures on Acupuncture for Back Pain

Background: For Comparative Effectiveness Research (CER) there is a need to develop scales for appraisal of available clinical research. Aims were to 1) test the feasibility of applying the pragmatic-explanatory continuum indicator summary tool and the six CER defining characteristics of the Institute of Medicine to RCTs of acupuncture for treatment of low back pain, and 2) evaluate the extent to which the evidence from these RCTs is relevant to clinical and health policy decision making. Methods: We searched Medline, the AcuTrials™ Database to February 2011 and reference lists and included full-report randomized trials in English that compared needle acupuncture with a conventional treatment in adults with non-specific acute and/or chronic low back pain and restricted to those with ≥30 patients in the acupuncture group. Papers were evaluated by 5 raters. Principal Findings: From 119 abstracts, 44 full-text publications were screened and 10 trials (4,901 patients) were evaluated. Due to missing information and initial difficulties in operationalizing the scoring items, the first scoring revealed inter-rater and inter-item variance (intraclass correlations 0.02-0.60), which improved after consensus discussions to 0.20-1.00. The 10 trials were found to cover the efficacy-effectiveness continuum; those with more flexible acupuncture and no placebo control scored closer to effectiveness. Conclusion: Both instruments proved useful, but need further development. In addition, CONSORT guidelines for reporting pragmatic trials should be expanded. Most studies in this review already reflect the movement towards CER and similar approaches can be taken to evaluate comparative effectiveness relevance of RCTs for other treatments. © 2012 Witt et al.published_or_final_versio

SQUIDs in biomagnetism : A roadmap towards improved healthcare

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 686865.Peer reviewedPublisher PD