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Rosetti F.,Instituto Nacional Of Ciencias Medicas | Mayadas T.N.,Harvard University
Immunological Reviews | Year: 2016

Mac-1 (CD11b/CD18) is a β2 integrin classically regarded as a pro-inflammatory molecule because of its ability to promote phagocyte cytotoxic functions and enhance the function of several effector molecules such as FcγR, uPAR, and CD14. Nevertheless, recent reports have revealed that Mac-1 also plays significant immunoregulatory roles, and genetic variants in ITGAM, the gene that encodes CD11b, confer risk for the autoimmune disease systemic lupus erythematosus (SLE). This has renewed interest in the physiological roles of this integrin and raised new questions on how its seemingly opposing biological functions may be regulated. Here, we provide an overview of the CD18 integrins and how their activation may be regulated as this may shed light on how the opposing roles of Mac-1 may be elicited. We then discuss studies that exemplify Mac-1's pro-inflammatory versus regulatory roles particularly in the context of IgG immune complex-mediated inflammation. This includes a detailed examination of molecular mechanisms that could explain the risk-conferring effect of rs1143679, a single nucleotide non-synonymous Mac-1 polymorphism associated with SLE. © 2016 John Wiley & Sons A/S. Source

Jimenez-Corona A.,Instituto Nacional Of Salud Publica | Aguilar-Salinas C.A.,Instituto Nacional Of Ciencias Medicas | Rojas-Martinez R.,Instituto Nacional Of Salud Publica | Hernandez-Avila M.,Instituto Nacional Of Salud Publica
Salud Publica de Mexico | Year: 2013

Objective. To determine the frequency of application of prevention and control measures for type 2 diabetes in Mexican population. Materials and methods. ENSANUT 2012 is a nationally and by-state representative survey. Sample design was probabilistic, multistage, stratified and clustered. The information of 46 277 adults=20 was used for this analysis. A weighted analysis was performed using Stata 12. Results. Prevalence of diabetes by previous diagnosis was 9.2% (6.4 millions) in ENSANUT 2012, 7.3% (3.7 millions) in 2006 and 4.6% (2.1 millions) in 2000. In 2012, the mean of medical examinations in the previous year related to diabetes control was 7.3. However, the percentage of cases in which preventive actions for chronic complications were performed (such as foot care [14.6%], ophthalmology [8.6%] and determination of HbA1c [9.6%]) was low. Conclusions. Patients with diabetes have frequent access to medical services. However, preventive actions are applied insufficiently both in quality and quantity. Source

Garcia-Munoz R.,Hospital San Pedro | Llorente L.,Instituto Nacional Of Ciencias Medicas
Immunology | Year: 2014

Immunological tolerance theory in chronic lymphocytic leukaemia (CLL): we suggest that B cells that express B-cell receptors (BCR) that recognize their own BCR epitopes are viewed by immune system as 'dangerous cells'. BCR autonomous signalling may induce constant receptor editing and mistakes in allelic exclusion. The fact that whole BCR recognizes a self-antigen or foreing antigen may be irrelevant in early B cell development. In early B cells, autonomous signalling induced by recognition of the BCR's own epitopes simulates an antigen-antibody engagement. In the bone marrow this interaction is viewed as recognition of self-molecules and induces receptor editing. In mature B cells autonomous signalling by the BCR may promote 'reversible anergy' and also may correct self-reactivity induced by the somatic hypermutation mechanisms in mutated CLL B cells. However, in unmutated CLL B cells, BCR autonomous signalling in addition to self-antigen recognition augments B cell activation, proliferation and genomic instability. We suggest that CLL originates from a coordinated normal immunologic tolerance mechanism to destroy self-reactive B cells. Additional genetic damage induced by tolerance mechanisms may immortalize self-reactive B cells and transform them into a leukemia. © 2014 John Wiley & Sons Ltd. Source

Garcia M.P.M.,Instituto Nacional Of Ciencias Medicas
Annals of Hepatology | Year: 2011

The prevalence of under nutrition in cirrhotic patients is 61% and it usually progresses as the disease becomes more advanced. The deterioration in the nutritional status and its associated metabolic derangements has raised doubts about the benefits of severe and prolonged protein restriction as a treatment for hepatic encephalopathy. However, the practice of dietary protein restriction for patients with liver cirrhosis is deeply embedded among medical practitioners and dietitians. To date, no solid conclusions may be drawn about the benefit of protein restriction. However, the negative effects of protein restriction are clear, that is, increased protein catabolism, the release of amino acids from the muscle, and possible worsening of hepatic encephalopathy. In conclusion, chronic protein restriction causes progressive and harmful protein depletion and must be avoided. Source

Mink S.N.,University of Manitoba | Jacobs H.,University of Manitoba | Gotes J.,Instituto Nacional Of Ciencias Medicas | Kasian K.,University of Manitoba | Cheng Z.-Q.,University of Manitoba
Journal of Applied Physiology | Year: 2011

Although hydrogen peroxide (H2O2) is a well-described reactive oxygen species that is known for its cytotoxic effects and associated tissue injury, H2O2 has recently been established as an important signaling molecule. We previously demonstrated that lysozyme (Lzm-S), a mediator of sepsis that is released from leukocytes, could produce vasodilation in a phenylephrine-constricted carotid artery preparation by H 2O2 signaling. We found that Lzm-S could intrinsically generate H2O2 and that this generation activated H 2O2-dependent pathways. In the present study, we used this carotid artery preparation as a bioassay to define those antioxidants that could inhibit Lzm-S's vasodilatory effect. We then determined whether this antioxidant could reverse the hypotension that developed in an Escherichia coli bacteremic model. Of the many antioxidants tested, we found that ethyl gallate (EG), a nonflavonoid phenolic compound, was favorable in inhibiting Lzm-S-induced vasodilation. In our E. coli model, we found that EG reversed the hypotension that developed in this model and attenuated end-organ dysfunction. By fluorometric H2O2 assay and electrochemical probe techniques, we showed that EG could scavenge H2O2 and that it could reduce H2O2 production in model systems. These results show that EG, an antioxidant that was found to scavenge H 2O2 in vitro, was able to attenuate cardiovascular dysfunction in a canine in vivo preparation. Antioxidants such as EG may be useful in the treatment of hemodynamic deterioration in septic shock. © 2011 the American Physiological Society. Source

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