Mononuclear Nitrogen/sulfur-ligated Cobalt(II) Methoxide Complexes: Structural, EPR, Paramagnetic 1H NMR, and Electrochemical Investigations

The first examples of mononuclear nitrogen/sulfur-ligated Co(II) alkoxide complexes, species of relevance to a reactive intermediate observed for Co(II)-substituted liver alcohol dehydrogenase, have been isolated and characterized by multiple methods including X-ray crystallography, EPR, paramagnetic 1H NMR, and cyclic voltammetry

Intranasal peptide-induced tolerance and linked suppression: consequences of complement deficiency.

A role for complement, particularly the classical pathway, in the regulation of immune responses is well documented. Deficiencies in C1q or C4 predispose to autoimmunity, while deficiency in C3 affects the suppression of contact sensitization and generation of oral tolerance. Complement components including C3 have been shown to be required for both B-cell and T-cell priming. The mechanisms whereby complement can mediate these diverse regulatory effects are poorly understood. Our previous work, using the mouse minor histocompatibility (HY) model of skin graft rejection, showed that both C1q and C3 were required for the induction of tolerance following intranasal peptide administration. By comparing tolerance induction in wild-type C57BL/6 and C1q-, C3-, C4- and C5-deficient C57BL/6 female mice, we show here that the classical pathway components including C3 are required for tolerance induction, whereas C5 plays no role. C3-deficient mice failed to generate a functional regulatory T (Treg) -dendritic cell (DC) tolerogenic loop required for tolerance induction. This was related to the inability of C3-deficient DC to up-regulate the arginine-consuming enzyme, inducible nitric oxide synthase (Nos-2), in the presence of antigen-specific Treg cells and peptide, leading to reduced Treg cell generation. Our findings demonstrate that the classical pathway and C3 play a critical role in the peptide-mediated induction of tolerance to HY by modulating DC function

Effect of a web-based chronic disease management system on asthma control and health-related quality of life: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Asthma is a prevalent and costly disease resulting in reduced quality of life for a large proportion of individuals. Effective patient self-management is critical for improving health outcomes. However, key aspects of self-management such as self-monitoring of behaviours and symptoms, coupled with regular feedback from the health care team, are rarely addressed or integrated into ongoing care. Health information technology (HIT) provides unique opportunities to facilitate this by providing a means for two way communication and exchange of information between the patient and care team, and access to their health information, presented in personalized ways that can alert them when there is a need for action. The objective of this study is to evaluate the acceptability and efficacy of using a web-based self-management system, My Asthma Portal (MAP), linked to a case-management system on asthma control, and asthma health-related quality of life.</p> <p>Methods</p> <p>The trial is a parallel multi-centered 2-arm pilot randomized controlled trial. Participants are randomly assigned to one of two conditions: a) MAP and usual care; or b) usual care alone. Individuals will be included if they are between 18 and 70, have a confirmed asthma diagnosis, and their asthma is classified as not well controlled by their physician. Asthma control will be evaluated by calculating the amount of fast acting beta agonists recorded as dispensed in the provincial drug database, and asthma quality of life using the Mini Asthma Related Quality of Life Questionnaire. Power calculations indicated a needed total sample size of 80 subjects. Data are collected at baseline, 3, 6, and 9 months post randomization. Recruitment started in March 2010 and the inclusion of patients in the trial in June 2010.</p> <p>Discussion</p> <p>Self-management support from the care team is critical for improving chronic disease outcomes. Given the high volume of patients and time constraints during clinical visits, primary care physicians have limited time to teach and reinforce use of proven self-management strategies. HIT has the potential to provide clinicians and a large number of patients with tools to support health behaviour change.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN34326236">ISRCTN34326236</a>.</p

Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells.

The CD11b/CD18 integrin (complement receptor 3, CR3) is a surface receptor on monocytes, neutrophils, macrophages and dendritic cells that plays a crucial role in several immunological processes including leukocyte extravasation and phagocytosis. The minor allele of a non-synonymous CR3 polymorphism (rs1143679, conversation of arginine to histidine at position 77: R77H) represents one of the strongest genetic risk factor in human systemic lupus erythematosus, with heterozygosity (77R/H) being the most common disease associated genotype. Homozygosity for the 77H allele has been reported to reduce adhesion and phagocytosis in human monocytes and monocyte-derived macrophages, respectively, without affecting surface expression of CD11b. Herein we comprehensively assessed the influence of R77H on different CR3-mediated activities in monocytes, neutrophils, macrophages and dendritic cells. R77H did not alter surface expression of CD11b including its active form in any of these cell types. Using two different iC3b-coated targets we found that the uptake by heterozygous 77R/H macrophages, monocytes and neutrophils was significantly reduced compared to 77R/R cells. Allele-specific transduced immortalized macrophage cell lines demonstrated that the minor allele, 77H, was responsible for the impaired phagocytosis. R77H did not affect neutrophil adhesion, neutrophil transmigration in vivo or Toll-like receptor 7/8-mediated cytokine release by monocytes or dendritic cells with or without CR3 pre-engagement by iC3b-coated targets. Our findings demonstrate that the reduction in CR3-mediated phagocytosis associated with the 77H CD11b variant is not macrophage-restricted but demonstrable in other CR3-expressing professional phagocytic cells. The association between 77H and susceptibility to systemic lupus erythematosus most likely relates to impaired waste disposal, a key component of lupus pathogenesis

Emission spectroscopy of the A

The high-resolution emission spectrum of the A1 Π–X1Σ+ transition of AlH was observed in the 18 000–25 000 cm-1 spectral region using a conventional spectroscopic technique. The AlH molecules were excited in an Al hollow-cathode lamp filled with a mixture of Ne carried gas and a trace amount of NH3. The emission from the discharge was observed with a plane grating spectrograph and recorded by a photomultiplier tube. In total 163 transition wave numbers belonging to six bands (0-0,1 and 1-0,1,2,3) were precisely measured and rotationally analysed. In the final fit the present data have been combined with available high-resolution measurements of the vibration-rotation bands by White et al. [J. Chem. Phys. 99, 8371 (1993)]. This procedure enabled extracting molecular constants for the A1 Π and X1 Σ+ states of AlH. A very slight local perturbation has been discovered in the v=1 vibration level of the A1 Π state at J=5. This was probably caused by the interaction with the a3Π state

A triglyceride-rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model

Hyperlipidaemia accompanies chronic renal disease either as a consequence of the renal dysfunction or as part of generalized metabolic derangements. Under both situations, the lipid profile is characterized by accumulation of triglyceride‐rich lipoproteins (TGRLs). This lipid profile is recognized as a risk factor for cardiovascular complications. Whether it may pose a risk for renal injury as well remains unclear. A hyper‐TGRL state was generated in C57BL/6 mice using poloxamer‐407 (P‐407) and immune complex‐mediated renal injury was triggered using the accelerated nephrotoxic nephritis (ANTN) model. The hyper‐TGRL animals were hypersensitive to ANTN demonstrated by greater haematuria and glomerular cellularity. These changes were accompanied by increased glomerular accumulation of CD68+ macrophages. The hypersensitive response to ANTN was not seen in low‐density lipoprotein receptor knock‐out mice fed with a high fat diet, where triglyceride levels were lower but cholesterol levels comparable to those obtained using P‐407. These data indicate that a hyper‐TGRL state might be more detrimental to the kidneys than low‐density lipoprotein‐driven hypercholesterolaemia during immune complex‐mediated nephritis. We speculate that the hyper‐TGRL environment primes the kidney to exacerbated renal damage following an inflammatory insult with increased accumulation of macrophages that may play a key role in mediating the injurious effects

Reinvestigation of the B

Conventional, high resolution molecular spectroscopy has been employed to record emission spectra of the first negative bands system in the 12C16O+ molecule. Twenty two bands form the $0-v'',1-v'', 2-v'', 3-v'', 4-v'', 5-v''$ progressions and 6-10 band were photographed in the $34000{-}46000$ cm-1 spectral region. The reduction of the spectrum for the individual bands has been performed via a nonlinear least-squares fit with the effective Hamiltonians of Brown et al. [J. Mol. Spectrosc. 74, 294 (1979)]. The final molecular constants for both the $B^{2}\Sigma^{+}$ ($v=0-6$) and $X^{2}\Sigma^{+}$ ($v=0-10$) states were obtained from global merge calculations of the present data of the $B\rightarrow X$ system and previously obtained in our laboratory data for $A \rightarrow X$ and $B \rightarrow A$ systems in the CO+ molecule. Merged molecular parameters have been used in order to the determine the equilibrium constants for both considered states. The $\gamma_{e}=2.194(14) \times 10 ^{-2}$ cm-1 and $\alpha_{\gamma e}=-1.021(64)\times 10^{-4}$ cm-1 constants for the $B^{2}\Sigma^{+}$ state were obtained for the first time. The RKR potentials have been calculated for both combining states, as well as Franck-Condon factor and r-centroids for the first negative system in the 12C16O+ molecule. Furthermore, we report the value of the electronic isotopic shift $\Delta\nu_{e} = -0.395$ cm -1 of the $B\rightarrow X$ system in 13C16O+, calculated on the basis the presents results and those obtained by us previously for the 13C16O+ molecule.

Reanalysis of the Ångström System (B1Σ+−A1Π)(B^1 Σ^{+} - A^1 \Pi) in the 13C16O\text{}^{13}C^{16}O Isotopic Molecule

The emission spectrum of the Ångström system $(B^1 Σ^{+} - A^1 \Pi)$ of $\text{}^{13}C^{16}O$ was obtained under high resolution with an accuracy estimated to be ± 0.002 $cm^{-1}$ as an emission spectrum using a high accuracy dispersive optical spectroscopy. The light source was a hollow-cathode lamp with two anodes built in our laboratory, with a previously deposited small quantity of $\text{}^{13}C$ carbon on the electrodes. The emission from the discharge was observed with a plane grating spectrograph and recorded by a photomultiplier tube. In total 195 transition wave numbers belonging to the strongest 0-1 and 0-2 bands of the B - A system were precisely measured. The modern rotational reanalysis made it possible to verify the molecular information for the both combining states of the Ångström system. In particular the rovibrational constants for the $B^1 Σ^{+}$ Rydberg state have been significantly improved ($B_0$ = 1.8625054(65) $cm^{-1}$ and $D_0=6.1384(52) \times 10^{-6} cm^{-1}$) and the obtained equilibrium rotational constants of this state are more accurate than known to date. Numerous rotational perturbations observed in the $A^1$ Π state were reanalysed and confronted with the previously known ones