ABSTRACT
BACKGROUND: The macrophage migration inhibiting factor (MIF) is a protein that promotes the activation of immune cells and the production of other proinflammatory cytokines such as TNF-α, IL-1ß, and IFN-γ, which have proposed to play an essential role in the pathogenesis of vitiligo. The study aimed to assess the association between MIF polymorphisms (-794 CATT5-8 and -173 G>C), MIF in situ expression, and MIF serum concentrations with susceptibility and disease activity in patients with non-segmental vitiligo (NSV) from western Mexico. METHODS: The study included 111 patients with NSV and 201 control subjects. Genotyping was performed by conventional PCR (-794 CATT5-8 ) and PCR-RFLP (-173 G>C) methods. MIF mRNA expression was quantified by real-time PCR and MIF serum concentrations were determined by ELISA kit. Histopathological samples were analyzed by automated immunohistochemistry. RESULTS: The MIF polymorphisms were associated with NSV susceptibility. Serum concentrations of MIF were higher in patients with active NSV and correlated negatively with the years of evolution. The depigmented skin from patients with active vitiligo showed a high expression of MIF. CONCLUSION: MIF polymorphisms increase the risk of NSV in the western Mexican population. The serum concentrations of MIF and in situ expression are associated with active NSV.
Subject(s)
Intramolecular Oxidoreductases/genetics , Macrophage Migration-Inhibitory Factors/genetics , Polymorphism, Single Nucleotide , Vitiligo/genetics , Adolescent , Adult , Aged , Female , Humans , Intramolecular Oxidoreductases/blood , Macrophage Migration-Inhibitory Factors/blood , Male , Mexico , Middle Aged , Vitiligo/bloodABSTRACT
Viruses are obligate intracellular pathogens that require the protein synthesis machinery of the host cells to replicate. These microorganisms have evolved mechanisms to avoid detection from the host immune innate and adaptive response, which are known as viral evasion mechanisms. Viruses enter the host through skin and mucosal surfaces that happen to be colonized by communities of thousands of microorganisms collectively known as the commensal microbiota, where bacteria have a role in the modulation of the immune system and maintaining homeostasis. These bacteria are necessary for the development of the immune system and to prevent the adhesion and colonization of bacterial pathogens and parasites. However, the interactions between the commensal microbiota and viruses are not clear. The microbiota could confer protection against viral infection by priming the immune response to avoid infection, with some bacterial species being required to increase the antiviral response. On the other hand, it could also help to promote viral evasion of certain viruses by direct and indirect mechanisms, with the presence of the microbiota increasing infection and viruses using LPS and surface polysaccharides from bacteria to trigger immunosuppressive pathways. In this work, we reviewed the interaction between the microbiota and viruses to prevent their entry into host cells or to help them to evade the host antiviral immunity. This review is focused on the influence of the commensal microbiota in the viruses' success or failure of the host cells infection.
Subject(s)
Immune Evasion , Microbial Interactions/immunology , Microbiota/immunology , Mucous Membrane/microbiology , Symbiosis/immunology , Viruses/pathogenicity , Adaptive Immunity , Animals , Humans , Immunity, Innate , Lipopolysaccharides/biosynthesis , Lipopolysaccharides/immunology , Mucous Membrane/virology , Probiotics/pharmacology , Virus Internalization , Virus Replication , Viruses/growth & developmentABSTRACT
Leprosy is a chronic disease caused by Mycobacterium leprae that affects the skin and peripheral nerves. It may present as one of two distinct poles: the self-limiting tuberculoid leprosy and the highly infectious lepromatous leprosy (LL) characterized by M. leprae-specific absence of cellular immune response. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) enhance the bactericide activities of macrophages after interaction with its receptor, CD74. Importantly, MIF also possesses chemoattractant properties, and it is a key factor in situ for the activation of macrophages and in blood to promote leukocytes migration. MIF-mediated activation of macrophages is a key process for the elimination of pathogens such as Mycobacterium tuberculosis; however, its participation for the clearance of M. leprae is unclear. The aim of this study was to evaluate the serum levels of MIF as well as MIF and CD74 expression in skin lesions of LL and compare it with healthy skin (HSk) taken from subjects attending to dermatological consult. Samples of serum and skin biopsies were taken from 39 LL patients and compared with 36 serum samples of healthy subjects (HS) and 10 biopsies of HSk. Serum samples were analyzed by ELISA and skin biopsies by immunohistochemistry (IHC). IHC smears were observed in 12 100× microscopic fields, in which percentage of stained cells and staining intensity were evaluated. Both variables were used to calculate a semi-quantitative expression score that ranged from 0 to 3+. We found no differences in MIF levels between LL patients and HS in sera. In addition, MIF was observed in over 75% of cells with high intensity in the skin of patients and HSk. Although we found no differences in MIF expression between the groups, a CD74 score statistically higher was found in LL skin than HSk (p < 0.001); this was the result of a higher percentage of cells positive for CD74 (p < 0.001). As a conclusion, we found that CD74-positive cells are intensely recruited to the skin with LL lesions. In this manner, MIF signaling may be enhanced in the skin of LL patients due to increased expression of its receptor, but further studies are required.
Subject(s)
Antigens, Differentiation, B-Lymphocyte/immunology , Histocompatibility Antigens Class II/immunology , Host Microbial Interactions/immunology , Intramolecular Oxidoreductases/blood , Leprosy, Lepromatous/immunology , Macrophage Migration-Inhibitory Factors/blood , Skin/immunology , Adult , Antigens, Differentiation, B-Lymphocyte/metabolism , Biopsy , Case-Control Studies , Female , Healthy Volunteers , Histocompatibility Antigens Class II/metabolism , Humans , Immunity, Cellular , Intramolecular Oxidoreductases/immunology , Intramolecular Oxidoreductases/metabolism , Leprosy, Lepromatous/blood , Leprosy, Lepromatous/pathology , Macrophage Migration-Inhibitory Factors/immunology , Macrophage Migration-Inhibitory Factors/metabolism , Male , Middle Aged , Mycobacterium leprae/immunology , Skin/cytology , Skin/pathologyABSTRACT
Pregnancy is probably the most important challenge in young women with chronic kidney disease (CKD). The challenge is greater in developing countries, in which access to dialysis is uneven, and prenatal care for CKD patients is not uniformly available. This case report summarizes some of the challenges faced by pregnant CKD women in a developing country. A 35-year-old woman, affected by an undiagnosed kidney disease, experienced preeclampsia at 24 years of age, and started dialysis in emergency at age 31 in the context of severe preeclampsia in her second pregnancy. Following slow recovery of kidney function, after 18 months of dialysis she started a moderately restricted, supplemented, low-protein diet, which allowed her to discontinue dialysis. A few months after dialysis discontinuation, she started a new pregnancy in the presence of severely reduced kidney function (serum creatinine 4.6 mg/dl at the last pre-pregnancy control). Interestingly, she discontinued nephrology and nutritional follow-up, mainly because she was worried that she would be discouraged from continuing the pregnancy, but also because she continued to feel well. She self-managed her diet in pregnancy and delivered a healthy baby, with normal intrauterine growth, at term; while the last laboratory data confirmed the presence of severe kidney function impairment, she is still dialysis-free at the time of the present report. Her story, with its happy ending, underlines the importance of dedicated programs for CKD pregnancies in developing countries and confirms the safety of moderately protein-restricted diets in pregnancy.
Subject(s)
Diet, Protein-Restricted , Dietary Supplements , Pregnancy Complications/therapy , Renal Insufficiency, Chronic/therapy , Adult , Female , Humans , Infant, Newborn , Pregnancy , Renal DialysisABSTRACT
PURPOSE: To describe a new technique of femtosecond laser-assisted intracorneal ring segment implantation. METHODS: The study included 6 eyes of 5 patients. Software of the LDV Z6 femtosecond laser was modified to create a 110-degree reverse side cut between the corneal surface and incision instead of the conventional 90 degree angle (which changed the angle between the incision and tunnel from conventional 90-70 degrees) and 2 disjointed tunnels separated by 10 degrees arc length at the proximal and distal ends. RESULTS: One-year postoperatively, there were no cases of segment extrusion or touch/overlap. Anterior segment optical coherence tomography showed appropriate position of the rings in all eyes postoperatively. Improvement was also found in visual, refractive, keratometric, and asphericity parameters. CONCLUSIONS: The results of this pilot study are promising. A comparative prospective study with more eyes and longer follow-up may confirm whether this technique is better than the conventional femtosecond laser-assisted one.
Subject(s)
Corneal Stroma/surgery , Keratoconus/surgery , Laser Therapy/methods , Polymethyl Methacrylate , Prostheses and Implants , Prosthesis Implantation/methods , Adult , Corneal Topography , Female , Follow-Up Studies , Humans , Male , Pilot Projects , Prospective Studies , Tomography, Optical CoherenceABSTRACT
In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine production, and, the most recently described, neutrophil extracellular trap (NET) production. NETs are DNA structures released due to chromatin decondensation and spreading, and they thus occupy three to five times the volume of condensed chromatin. Several proteins adhere to NETs, including histones and over 30 components of primary and secondary granules, among them components with bactericidal activity such as elastase, myeloperoxidase, cathepsin G, lactoferrin, pentraxin 3, gelatinase, proteinase 3, LL37, peptidoglycan-binding proteins, and others with bactericidal activity able to destroy virulence factors. Three models for NETosis are known to date. (a) Suicidal NETosis, with a duration of 2-4 h, is the best described model. (b) In vital NETosis with nuclear DNA release, neutrophils release NETs without exhibiting loss of nuclear or plasma membrane within 5-60 min, and it is independent of reactive oxygen species (ROS) and the Raf/MERK/ERK pathway. (c) The final type is vital NETosis with release of mitochondrial DNA that is dependent on ROS and produced after stimuli with GM-CSF and lipopolysaccharide. Recent research has revealed neutrophils as more sophisticated immune cells that are able to precisely regulate their granular enzymes release by ion fluxes and can release immunomodulatory cytokines and chemokines that interact with various components of the immune system. Therefore, they can play a key role in autoimmunity and in autoinflammatory and metabolic diseases. In this review, we intend to show the two roles played by neutrophils: as a first line of defense against microorganisms and as a contributor to the pathogenesis of various illnesses, such as autoimmune, autoinflammatory, and metabolic diseases.
ABSTRACT
Objetivo: Comparar la incidencia y patrón de taquirritmia supreventricular (fibrilación y flutter) en pacientes sometidos a cirugía de revascularización con y sin el uso de circulación extracorpórea. Materiales y métodos: Se incluyeron consecutivamente un grupo de 45 pacientes sometidos a cirugía de revascularización miocárdiaca con bomba y un segundo grupo de 50 pacientes sometidos a cirugía sin bomba, con total de 95 pacientes. Los pacientes fueron llevados al procedimiento en el tiempo comprendido entre el 1 de enero de 2002 y el 30 de agosto de 2003 y fueron operados por un grupo de dos cirujanos cardiovasculares e intervenidos con esternotomía media. Todos los pacientes recibieron el mismo protocolo de anestesia y de la misma forma, fueron manejados en la unidad de cuidados intensivos en el postoperatorio inmediato. En los pacientes que requirieron circulación extracorpórea, primer grupo, se realizó canulación arterial en la aorta ascendente y venosa en la aurícula derecha. Conclusión: El presente estudio no demuestra una diferencia estadísticamente significativa en la aparición de fibrilación atrial postoperatoria en los pacientes llevados a cirugía de revascularización miocárdica con o sin circulación extracorpórea...