Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 27
Filter
1.
Environ Toxicol Pharmacol ; 106: 104381, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38311300

ABSTRACT

In recent decades, glyphosate and glyphosate-based herbicides (GBH) have been extensively used in agriculture all over the world. Initially, they were considered safe, but rising evidence suggests that these molecules reach the central nervous system producing metabolic, functional, and permanent alterations that impact cognition and behavior. This theoretical and non-systematic review involved searching, integrating, and analyzing preclinical evidence regarding the effects of acute, sub-chronic, and chronic exposure to glyphosate and GBH on cognition, behavior, neural activity, and development in adult and juvenile rodents following perinatal exposition. In addition, this review gathers the mechanisms underlying the neurotoxicity of glyphosate mediating cognitive and behavioral alterations. Furthermore, clinical evidence of the effects of exposition to GBH on human health and its possible link with several neurological disorders was revised.


Subject(s)
Herbicides , Neurotoxicity Syndromes , Adult , Humans , Female , Pregnancy , Glyphosate , Cognition , Neurotoxicity Syndromes/etiology , Herbicides/toxicity , Agriculture
2.
Diseases ; 11(4)2023 Nov 05.
Article in English | MEDLINE | ID: mdl-37987271

ABSTRACT

Staphylococcus aureus (S. aureus) is a common pathogen involved in community- and hospital-acquired infections. Its biofilm formation ability predisposes it to device-related infections. Methicillin-resistant S. aureus (MRSA) strains are associated with more serious infections and higher mortality rates and are more complex in terms of antibiotic resistance. It is still controversial whether MRSA are indeed more virulent than methicillin-susceptible S. aureus (MSSA) strains. A difference in biofilm formation by both types of bacteria has been suggested, but how only the presence of the SCCmec cassette or mecA influences this phenotype remains unclear. In this review, we have searched for literature studying the difference in biofilm formation by MRSA and MSSA. We highlighted the relevance of the icaADBC operon in the PIA-dependent biofilms generated by MSSA under osmotic stress conditions, and the role of extracellular DNA and surface proteins in the PIA-independent biofilms generated by MRSA. We described the prominent role of surface proteins with the LPXTG motif and hydrolases for the release of extracellular DNA in the MRSA biofilm formation. Finally, we explained the main regulatory systems in S. aureus involved in virulence and biofilm formation, such as the SarA and Agr systems. As most of the studies were in vitro using inert surfaces, it will be necessary in the future to focus on biofilm formation on extracellular matrix components and its relevance in the pathogenesis of infection by both types of strains using in vivo animal models.

3.
Front Rehabil Sci ; 3: 907603, 2022.
Article in English | MEDLINE | ID: mdl-36188947

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of Coronavirus disease 2019 (COVID-19), a pandemic disease declared in 2020. The clinical manifestations of this pathology are heterogeneous including fever, cough, dyspnea, anosmia, headache, fatigue, taste dysfunction, among others. Survivors of COVID-19 have demonstrated several persistent symptoms derived from its multisystemic physiopathology. These symptoms can be fatigue, dyspnea, chest pain, dry and productive cough, respiratory insufficiency, and psychoemotional disturbance. To reduce and recover from the post-COVID-19 sequelae is fundamental an early and multifactorial medical treatment. Integral post-COVID-19 physiotherapy is a tool to reduce dyspnea, improve lung capacity, decrease psychoemotional alterations, as well as increase the muscle strength affected by this disease. Thus, the aim of this study was to establish a novel physiotherapeutic plan for post-COVID-19 patients, evaluating the effect of this treatment in the reduction of the sequelae in terms of lung capacity, cardio-respiratory, and muscular strength improvements. This was a cross-sectional study in which a protocol of 12 sessions in 4 weeks of physiotherapy was implemented in the patients enrolled. We conducted a medical assessment, an interview, a DASS-21 test, a spirometry, a 6-min walk test, and a hand dynamometer test to evaluate the post-COVID condition of patients before and after the sessions. A total of 42 patients participated in the program. Results of this work showed a decrease of around 50% of post-COVID-19 sequelae and an improvement in the psychoemotional status of patients. Also, we observed an increase of 7.16% in the FEV1 value and 7.56% for FVC. In addition, the maximal functional capacity increased by 0.577 METs, the 6-min walk test performance increased by 13%, and the SpO2 improved by 1.40%. Finally, the handgrip strength test showed an improvement in the left hand and right hand of 2.90 and 2.24 Kg, respectively. We developed this study to propose a novel methodology to provide information for a better treatment and management of post-COVID-19 patients.

4.
Rev Iberoam Micol ; 39(2): 36-43, 2022.
Article in English | MEDLINE | ID: mdl-35738989

ABSTRACT

BACKGROUND: Staphylococcus aureus and Candida albicans have been co-isolated from biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections, as well as from medical devices. However, the polymicrobial biofilm of both microorganisms has not been fully characterized. AIMS: To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents. METHODS: Crystal violet assay was used to measure the biofilm formation. Scanning electron microscopy and confocal microscopy were used to analyze the structure and chemical composition of the biofilms, respectively. RESULTS: Supplemented media with fetal bovine serum (FBS) decreased the biofilm formation of S. aureus and the polymicrobial biofilm. For C. albicans, depending on the culture media, the addition of glucose or FBS had a positive effect in biofilm formation. FBS decreased the adhesion to polystyrene wells for both microorganisms. Supplementing the media with glucose and FBS enhanced the growth of C. albicans and S. aureus, respectively. It seems that C. albicans contributes the most to the adhesion process and to the general structure of the biofilms on all the surfaces tested, including a catheter model. Interestingly, S. aureus showed a great adhesion capacity to the surface of C. albicans in the biofilms. Proteins and ß-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. CONCLUSIONS: The polymicrobial biofilm had a complex structure, with C. albicans serving as a scaffold where S. aureus adheres, preferentially to the hyphal form of the fungus. Detection of polymicrobial infections and characterization of biofilms will be necessary in the future to provide a better treatment.


Subject(s)
Anti-Infective Agents , Candida albicans , Biofilms , Glucose/metabolism , Glucose/pharmacology , Staphylococcus aureus
5.
Rev. iberoam. micol ; 39(2): 36-43, abril 2022. graf, tab
Article in English | IBECS | ID: ibc-207100

ABSTRACT

Background:Staphylococcus aureus and Candida albicans have been co-isolated from biofilm-associated diseases such as denture stomatitis, periodontitis, and burn wound infections, as well as from medical devices. However, the polymicrobial biofilm of both microorganisms has not been fully characterized.Aims:To characterize the polymicrobial biofilm of C. albicans and S. aureus in terms of microbial density, synergy, composition, structure, and stability against antimicrobials and chemical agents.Methods:Crystal violet assay was used to measure the biofilm formation. Scanning electron microscopy and confocal microscopy were used to analyze the structure and chemical composition of the biofilms, respectively.Results:Supplemented media with fetal bovine serum (FBS) decreased the biofilm formation of S. aureus and the polymicrobial biofilm. For C. albicans, depending on the culture media, the addition of glucose or FBS had a positive effect in biofilm formation. FBS decreased the adhesion to polystyrene wells for both microorganisms. Supplementing the media with glucose and FBS enhanced the growth of C. albicans and S. aureus, respectively. It seems that C. albicans contributes the most to the adhesion process and to the general structure of the biofilms on all the surfaces tested, including a catheter model. Interestingly, S. aureus showed a great adhesion capacity to the surface of C. albicans in the biofilms. Proteins and β-1,6-linked polysaccharides seem to be the most important molecules in the polymicrobial biofilm. (AU)


Antecedentes:Staphylococcus aureus y Candida albicans son aislados conjuntamente de infecciones asociadas a la formación de biopelículas, tales como periodontitis, estomatitis e infecciones provenientes de quemaduras, así como en dispositivos médicos. Sin embargo, la biopelícula formada por ambos microorganismos no ha sido completamente caracterizada.Objetivos:Caracterizar la biopelícula de C. albicans y S. aureus en cuanto a densidad microbiana, sinergismo, composición, estructura y estabilidad frente a agentes químicos y antimicrobianos.Métodos:El análisis de la formación de biopelícula se realizó mediante el ensayo de cristal violeta. Se analizó la composición química y la estructura de las biopelículas mediante microscopio confocal y microscopio electrónico de barrido, respectivamente.Resultados:La adición al medio de suero bovino fetal (SBF) redujo la biopelícula mono- y polimicrobiana de S. aureus. En C. albicans, con la adición de glucosa o SBF, se incrementó la formación de biopelícula. La adhesión de los microorganismos a las placas de poliestireno se redujo en presencia de SBF. La suplementación del medio con glucosa y SBF favoreció la proliferación de C. albicans y S. aureus, respectivamente. C. albicans mostró una mejor adhesión y contribuyó más a la densidad total de la biopelícula en diferentes superficies probadas, incluyendo un modelo de catéter. De manera interesante, S. aureus mostró una mejor adhesión a la superficie de C. albicans en la biopelícula. Las proteínas y los polisacáridos con enlaces β-1,6 parecen ser las moléculas más abundantes en la biopelícula. (AU)


Subject(s)
Humans , Anti-Infective Agents , Biofilms , Candida albicans , Glucose/metabolism , Glucose/pharmacology
6.
Vet Rec Open ; 8(1): e20, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34631111

ABSTRACT

BACKGROUND: Actinobacillus pleuropneumoniae (AP) is the causative agent of porcine pleuropneumonia. Apx exotoxins are the most important virulence factors associated with the induction of lesions. ApxI is highly cytotoxic on a wide range of cells. Besides the induction of necrosis and apoptosis of ApxI on porcine alveolar macrophages (PAMs), its role in pyroptosis, a caspase-1-dependent form of cell death, has not been reported. The aim of this study was to analyse if NLRP3 inflammasome participates in cell death induced by ApxI. METHODS: PAMs, the porcine alveolar macrophage cell line 3D4/21 and a porcine aortic endothelial cell line were used in this study. We used Z-VAD-FMK and Ac-YVAD-cmk to inhibit caspase-1. Glyburide and MCC950 were used to inhibit the NLRP3 inflammasome. A lactate dehydrogenase release assay was used to measure the percentage of cell death. Caspase-1 expression was analysed by immunofluorescence. End-point RT-PCR was used to analyse the expression of NLRP3 mRNA. RESULTS: Rapid cell death in PAMs, 3D4/21 cells and the endothelial cell line were induced by ApxI. This cell death decreased by using caspase-1 and NLRP3 inflammasome inhibitors and by blocking the K+ efflux. Expression of NLRP3 mRNA was induced by ApxI in alveolar macrophages while it was constitutive in the endothelial cell line. Detection of caspase-1 in alveolar macrophages was higher after ApxI treatment and it was blocked by MCC950 or heat inactivation. CONCLUSIONS: To the best of the authors' knowledge, we have described for the first time in vitro induction of ApxI associated pyroptosis in alveolar macrophages and endothelial cells, a rapid cell death that depends on the activation of caspase-1 via the NLRP3 inflammasome.

7.
Article in Spanish | LILACS | ID: biblio-1281759

ABSTRACT

El objetivo principal de la investigación fue analizar la estructura factorial y la consistencia de una escala de compromiso académico a través del análisis factorial exploratorio, confirmatorio y multigrupo; y también, con el coeficiente Alfa. La muestra estuvo conformada por 1110 estudiantes de diversas universidades de Lima, Perú y el instrumento analizado fue la Escala de Utrecht de Engagement Académico (UWES-S) de 17 ítems. Durante el análisis factorial exploratorio, se evidenció que los ítems se agrupan en tres factores: dedicación, vigor y absorción; y se eliminó el ítem 10 por presentar carga factorial en más de una dimensión. El análisis factorial confirmatorio indicó que el modelo es óptimo; por otra parte, el análisis factorial multigrupo señaló que el instrumento presenta un ajuste adecuado para la muestra de varones y mujeres. Además, la escala final de 16 ítems obtuvo un coeficiente Alfa igual a .83. Con lo anterior, se aporta un instrumento válido para la evaluación del compromiso académico en estudiantes universitarios peruanos.


The main purpose of the research was to analyze the factor structure and consistency of an academic engagement scale through exploratory, confirmatory and multigroup factor analysis; and also, with the Alpha coefficient. The sample consisted of 1,110 students from several universities in Lima, Peru and the instrument analyzed was the Utrecht Academic Engagement Scale (UWES-S) of 17 items. During the exploratory factor analysis, it was evident that the items are grouped into three factors: dedication, vigor and absorption; and item 10 was eliminated for presenting factor loading in more than one dimension. Confirmatory factor analysis indicated that the model is optimal; on the other hand, the multigroup factor analysis indicated that the instrument presents an appropriate adjustment for a sample of men and women. Furthermore, the final scale of 16 items obtained an alpha coefficient equal to .83. With the above, a valid instrument is provided for the evaluation of academic engagement in Peruvian university students.


O principal objetivo da investigação foi analisar a estrutura fatorial e a consistência de uma escala de engajamento acadêmico por meio de análise fatorial exploratória, confirmatória e multigrupo; e também com o coeficiente alpha. A amostra foi composta por 1110 estudantes de várias universidades de Lima, Peru, e o instrumento analisado foi a Escala Utrecht de Engajamento Acadêmico (UWES-S) de 17 itens. Durante a análise fatorial exploratória, demonstrou-se que os itens estão agrupados em três fatores: dedicação, vigor e absorção; e o item 10 foi eliminado por apresentar carga fatorial em mais de uma dimensão. A análise fatorial confirmatória indicou que o modelo é ótimo; Por outro lado, a análise fatorial multigrupo indicou que o instrumento apresenta um ajuste adequado para a amostra de homens e mulheres. Além disso, a escala final de 16 itens obteve um coeficiente alfa igual a .83. Com o exposto, este trabalho fornece um instrumento válido para avaliar o engajamento acadêmico em estudantes universitários peruanos.


Subject(s)
Male , Female , Adolescent , Adult , Research , Factor Analysis, Statistical , Universities , Absorption
8.
Article in English | MEDLINE | ID: mdl-32670893

ABSTRACT

Urinary tract infections (UTIs) affect more than 150 million people, with a cost of over 3.5 billion dollars, each year. Escherichia coli is associated with 70-80% of UTIs. Uropathogenic E. coli (UPEC) has virulence factors including adhesins, siderophores, and toxins that damage host cells. Vacuolating autotransporter toxin (Vat) is a member of serine protease autotransporter proteins of Enterobacteriaceae (SPATEs) present in some uropathogenic E. coli (UPEC) strains. Vat has been identified in 20-36% of UPEC and is present in almost 68% of urosepsis isolates. However, the mechanism of action of Vat on host cells is not well-known. Thus, in this study the effect of Vat in a urothelium model of bladder cells was investigated. Several toxin concentrations were tested for different time periods, resulting in 15-47% of cellular damage as measured by the LDH assay. Vat induced vacuole formation on the urothelium model in a time-dependent manner. Vat treatment showed loss of the intercellular contacts on the bladder cell monolayer, observed by Scanning Electron Microscopy. This was also shown using antibodies against ZO-1 and occludin by immunofluorescence. Additionally, changes in permeability of the epithelial monolayer was demonstrated with a fluorescence-based permeability assay. Cellular damage was also evaluated by the identification of cytoskeletal changes produced by Vat. Thus, after Vat treatment, cells presented F-actin distribution changes and loss of stress fibers in comparison with control cells. Vat also modified tubulin, but it was not found to affect Arp3 distribution. In order to find the nature of the vacuoles generated by Vat, the Lysotracker deep red fluorescent dye for the detection of acidic organelles was used. Cells treated with Vat showed generation of some vacuoles without acidic content. An ex vivo experiment with mouse bladder exposed to Vat demonstrated loss of integrity of the urothelium. In conclusion, Vat induced cellular damage, vacuole formation, and urothelial barrier dysregulation of bladder epithelial cells. Further studies are needed to elucidate the role of these vacuoles induced by Vat and their relationship with the pathogenesis of urinary tract infection.


Subject(s)
Bacterial Toxins , Escherichia coli Infections , Escherichia coli Proteins , Urinary Tract Infections , Uropathogenic Escherichia coli , Animals , Cytoskeleton , Epithelial Cells , Mice , Type V Secretion Systems , Urinary Bladder , Vacuoles
9.
J Obstet Gynaecol Res ; 44(1): 81-86, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29094444

ABSTRACT

AIM: We aimed to assess the use of metformin (MTF) in the prevention of gestational diabetes mellitus (GDM) in patients with pregestational insulin resistance (PIR). METHODS: A double blind, multicenter, randomized trial was carried out in patients with a history of PIR and pregestational MTF treatment. Groups were allocated either to MTF 1700 mg/day or placebo. Patients were recruited between 12+0 and 15+6 gestational weeks, and treatment was extended until week 36. A multiple logistic regression analysis was applied to determine the relation between the use of metformin and the development of GDM. RESULTS: One hundred and forty one patients were randomized (68 patients in the MTF group and 73 in the placebo group). A total of 30 patients withdrew from the study during follow-up. Administration of MTF was not associated with a decrease in the incidence of GDM as compared to placebo (37.5% vs 25.4%, respectively; P = 0.2). Moreover, MTF administration was associated with a significant increase in drug intolerance as compared to placebo (14.3% vs 1.8%, respectively; P = 0.02). CONCLUSION: The use of MTF is not effective in prevention of GDM in populations with PIR. The use of MTF shows a significantly higher frequency of drug intolerance than placebo.


Subject(s)
Diabetes, Gestational/prevention & control , Hypoglycemic Agents/pharmacology , Insulin Resistance , Metformin/pharmacology , Treatment Failure , Adult , Double-Blind Method , Female , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Metformin/administration & dosage , Metformin/adverse effects , Pregnancy
10.
Eur J Immunol ; 44(12): 3696-707, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25251560

ABSTRACT

Listeria monocytogenes induces the formation of inflammasomes and subsequent caspase-1 activation, and the adaptor apoptosis-associated speck-like protein containing a CARD (ASC) is crucial for this response. However, the role of ASC in L. monocytogenes infection in vivo is unclear. In this study, we demonstrate that ASC has a detrimental effect on host defense against L. monocytogenes infection at a lethal dose (10(6) CFU), but not at a sublethal dose (10(3) CFU). During lethal L. monocytogenes infection, serum levels of IL-18 and IL-10 were markedly elevated in WT mice, but not in ASC KO mice. IL-18 KO mice were more resistant to lethal L. monocytogenes infection than WT mice and had lower levels of serum IL-10. Furthermore, blockade of IL-10 receptor resulted in a reduction in bacterial counts, suggesting that ASC and IL-18 might exacerbate L. monocytogenes infection through induction of IL-10. We noticed that maturation of IL-18 during lethal infection was partially independent of caspase-1, but was critically dependent on ASC. ASC was required for the elevation of serum neutrophil serine protease activity, which correlated with caspase-1-independent IL-18 maturation and IL-10 production. Collectively, these results suggest that ASC plays a detrimental role in lethal L. monocytogenes infection through IL-18 production in an inflammasome-dependent and -independent manner.


Subject(s)
Apoptosis Regulatory Proteins/immunology , Inflammasomes/immunology , Interleukin-10/immunology , Interleukin-18/immunology , Listeria monocytogenes/immunology , Listeriosis/immunology , Animals , Apoptosis Regulatory Proteins/genetics , CARD Signaling Adaptor Proteins , Inflammasomes/genetics , Interleukin-10/genetics , Interleukin-18/genetics , Listeriosis/genetics , Listeriosis/pathology , Mice , Mice, Knockout , Neutrophils/immunology , Neutrophils/pathology , Receptors, Interleukin-10/genetics , Receptors, Interleukin-10/immunology , Serine Proteases/genetics , Serine Proteases/immunology
11.
Infect Immun ; 82(6): 2310-7, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24643540

ABSTRACT

Streptococcus pneumoniae, a Gram-positive bacterial pathogen, causes pneumonia, meningitis, and septicemia. Innate immune responses are critical for the control and pathology of pneumococcal infections. It has been demonstrated that S. pneumoniae induces the production of type I interferons (IFNs) by host cells and that type I IFNs regulate resistance and chemokine responses to S. pneumoniae infection in an autocrine/paracrine manner. In this study, we examined the effects of type I IFNs on macrophage proinflammatory cytokine production in response to S. pneumoniae. The production of interleukin-18 (IL-18), but not other cytokines tested, was significantly decreased by the absence or blockade of the IFN-α/ß receptor, suggesting that type I IFN signaling is necessary for IL-18 production. Type I IFN signaling was also required for S. pneumoniae-induced activation of caspase-1, a cysteine protease that plays a central role in maturation and secretion of IL-18. Earlier studies proposed that the AIM2 and NLRP3 inflammasomes mediate caspase-1 activation in response to S. pneumoniae. From our results, the AIM2 inflammasome rather than the NLRP3 inflammasome seemed to require type I IFN signaling for its optimal activation. Consistently, AIM2, but not NLRP3, was upregulated in S. pneumoniae-infected macrophages in a manner dependent on the IFN-α/ß receptor. Furthermore, type I IFN signaling was found to contribute to IL-18 production in pneumococcal pneumonia in vivo. Taken together, these results suggest that type I IFNs regulate S. pneumoniae-induced activation of the AIM2 inflammasome by upregulating AIM2 expression. This study revealed a novel role for type I IFNs in innate responses to S. pneumoniae.


Subject(s)
Inflammasomes/physiology , Interferon Type I/physiology , Nuclear Proteins/metabolism , Pneumococcal Infections/metabolism , Animals , Caspase 1/metabolism , Cytokines/metabolism , DNA-Binding Proteins , Disease Models, Animal , Female , Immunity, Innate/physiology , Interleukin-18/metabolism , Macrophages/immunology , Mice , Mice, Inbred C57BL , Pneumococcal Infections/immunology , Signal Transduction/physiology , Streptococcus pneumoniae
12.
Nat Immunol ; 14(12): 1247-55, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24185614

ABSTRACT

The inflammasome adaptor ASC contributes to innate immunity through the activation of caspase-1. Here we found that signaling pathways dependent on the kinases Syk and Jnk were required for the activation of caspase-1 via the ASC-dependent inflammasomes NLRP3 and AIM2. Inhibition of Syk or Jnk abolished the formation of ASC specks without affecting the interaction of ASC with NLRP3. ASC was phosphorylated during inflammasome activation in a Syk- and Jnk-dependent manner, which suggested that Syk and Jnk are upstream of ASC phosphorylation. Moreover, phosphorylation of Tyr144 in mouse ASC was critical for speck formation and caspase-1 activation. Our results suggest that phosphorylation of ASC controls inflammasome activity through the formation of ASC specks.


Subject(s)
Cytoskeletal Proteins/immunology , Inflammasomes/immunology , Intracellular Signaling Peptides and Proteins/immunology , JNK Mitogen-Activated Protein Kinases/immunology , Protein-Tyrosine Kinases/immunology , Animals , Apoptosis Regulatory Proteins , Bone Marrow Cells/immunology , Bone Marrow Cells/metabolism , CARD Signaling Adaptor Proteins , Carrier Proteins/genetics , Carrier Proteins/immunology , Carrier Proteins/metabolism , Caspase 1/immunology , Caspase 1/metabolism , Cells, Cultured , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , DNA-Binding Proteins , Dendritic Cells/immunology , Dendritic Cells/metabolism , Female , HEK293 Cells , Humans , Immunoblotting , Inflammasomes/genetics , Inflammasomes/metabolism , Interleukin-18/immunology , Interleukin-18/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , JNK Mitogen-Activated Protein Kinases/genetics , JNK Mitogen-Activated Protein Kinases/metabolism , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein , Nigericin/pharmacology , Nuclear Proteins/genetics , Nuclear Proteins/immunology , Nuclear Proteins/metabolism , Phosphorylation/immunology , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , RNA Interference , Syk Kinase , Tyrosine/genetics , Tyrosine/immunology , Tyrosine/metabolism
13.
Cell ; 153(5): 1036-49, 2013 May 23.
Article in English | MEDLINE | ID: mdl-23706741

ABSTRACT

Regnase-1 (also known as Zc3h12a and MCPIP1) is an RNase that destabilizes a set of mRNAs, including Il6 and Il12b, through cleavage of their 3' UTRs. Although Regnase-1 inactivation leads to development of an autoimmune disease characterized by T cell activation and hyperimmunoglobulinemia in mice, the mechanism of Regnase-1-mediated immune regulation has remained unclear. We show that Regnase-1 is essential for preventing aberrant effector CD4(+) T cell generation cell autonomously. Moreover, in T cells, Regnase-1 regulates the mRNAs of a set of genes, including c-Rel, Ox40, and Il2, through cleavage of their 3' UTRs. Interestingly, T cell receptor (TCR) stimulation leads to cleavage of Regnase-1 at R111 by Malt1/paracaspase, freeing T cells from Regnase-1-mediated suppression. Furthermore, Malt1 protease activity is critical for controlling the mRNA stability of T cell effector genes. Collectively, these results indicate that dynamic control of Regnase-1 expression in T cells is critical for controlling T cell activation.


Subject(s)
Caspases/metabolism , Lymphocyte Activation , Neoplasm Proteins/metabolism , Ribonucleases/metabolism , T-Lymphocytes, Helper-Inducer/immunology , Animals , Autoimmune Diseases/immunology , Humans , Interleukin-2/genetics , Jurkat Cells , Membrane Glycoproteins/genetics , Mice , Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein , OX40 Ligand , Proto-Oncogene Proteins c-rel/genetics , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes, Helper-Inducer/metabolism , Tumor Necrosis Factors/genetics
14.
J Immunol ; 189(11): 5113-7, 2012 Dec 01.
Article in English | MEDLINE | ID: mdl-23100513

ABSTRACT

Although the NLRP3 inflammasome plays a pivotal role in host defense, its uncontrolled activation is associated with inflammatory disorders, suggesting that regulation of the inflammasome is important to prevent detrimental effects. Type I IFNs and long-term LPS stimulation were shown to negatively regulate NLRP3 activation. In this study, we found that endogenous NO is involved in the regulation of NLRP3 inflammasome activation by either IFN-ß pretreatment or long-term LPS stimulation. Furthermore, S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, markedly inhibited NLRP3 inflammasome activation, whereas the AIM2 and NLRC4 inflammasomes were only partially inhibited by SNAP. An increase in mitochondrial reactive oxygen species induced by ATP was only modestly affected by SNAP treatment. Interestingly, S-nitrosylation of NLRP3 was detected in macrophages treated with SNAP, and this modification may account for the NO-mediated mechanism controlling inflammasome activation. Taken together, these results revealed a novel role for NO in regulating the NLRP3 inflammasome.


Subject(s)
Carrier Proteins/antagonists & inhibitors , Inflammasomes/drug effects , Macrophages, Peritoneal/drug effects , Nitric Oxide/metabolism , S-Nitroso-N-Acetylpenicillamine/pharmacology , Adenosine Triphosphate/pharmacology , Animals , Apoptosis Regulatory Proteins/antagonists & inhibitors , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/immunology , Calcium-Binding Proteins/antagonists & inhibitors , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/immunology , Carrier Proteins/genetics , Carrier Proteins/immunology , Cells, Cultured , DNA-Binding Proteins , Female , Gene Expression Regulation/drug effects , Inflammasomes/immunology , Interferon-beta/immunology , Interferon-beta/pharmacology , Lipopolysaccharides/pharmacology , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Mice , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondria/immunology , Mitochondria/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Nuclear Proteins/antagonists & inhibitors , Nuclear Proteins/genetics , Nuclear Proteins/immunology , Reactive Oxygen Species/metabolism , S-Nitroso-N-Acetylpenicillamine/metabolism , Signal Transduction/drug effects , Signal Transduction/immunology
15.
J Immunol ; 187(9): 4890-9, 2011 Nov 01.
Article in English | MEDLINE | ID: mdl-21957143

ABSTRACT

Streptococcus pneumoniae is a Gram-positive, extracellular bacterium that is responsible for significant mortality and morbidity worldwide. Pneumolysin (PLY), a cytolysin produced by all clinical isolates of the pneumococcus, is one of the most important virulence factors of this pathogen. We have previously reported that PLY is an essential factor for activation of caspase-1 and consequent secretion of IL-1ß and IL-18 in macrophages infected with S. pneumoniae. However, the host molecular factors involved in caspase-1 activation are still unclear. To further elucidate the mechanism of caspase-1 activation in macrophages infected with S. pneumoniae, we examined the involvement of inflammasomes in inducing this cellular response. Our study revealed that apoptosis-associated specklike protein containing a caspase recruitment domain (ASC), an adaptor protein for inflammasome receptors such as nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2), is essentially required for the induction of caspase-1 activation by S. pneumoniae. Caspase-1 activation was partially impaired in NLRP3(-/-) macrophages, whereas knockdown and knockout of AIM2 resulted in a clear decrease in caspase-1 activation in response to S. pneumoniae. These results suggest that ASC inflammasomes, including AIM2 and NLRP3, are critical for caspase-1 activation induced by S. pneumoniae. Furthermore, ASC(-/-) mice were more susceptible than wild-type mice to S. pneumoniae, with impaired secretion of IL-1ß and IL-18 into the bronchoalveolar lavage after intranasal infection, suggesting that ASC inflammasomes contribute to the protection of host from infection with PLY-producing S. pneumoniae.


Subject(s)
Caspase 1/metabolism , Cytoskeletal Proteins/physiology , Immunity, Innate , Inflammasomes/physiology , Pneumococcal Infections/immunology , Pneumococcal Infections/metabolism , Animals , Apoptosis Regulatory Proteins , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/biosynthesis , CARD Signaling Adaptor Proteins , Carrier Proteins/physiology , Caspase 1/deficiency , Caspase 1/genetics , Cell Line , Cell Line, Transformed , Cells, Cultured , Cytoskeletal Proteins/deficiency , Cytoskeletal Proteins/genetics , DNA-Binding Proteins , Disease Resistance/immunology , Enzyme Activation/immunology , Female , Interleukin-18/metabolism , Interleukin-1beta/metabolism , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein , Nuclear Proteins/physiology , Pneumococcal Infections/enzymology , Streptolysins/antagonists & inhibitors , Streptolysins/biosynthesis
16.
Acta Ortop Mex ; 21(5): 234-8, 2007.
Article in Spanish | MEDLINE | ID: mdl-18159910

ABSTRACT

UNLABELLED: The jumper's knee or patellar tendonitis is a common injury in the athlete with an incidence between 14% and 16% among high-performance athletes. In addition to an overuse injury, there are some intrinsic factors for its development. Conservative treatment is indicated for the initial form, but when it fails, surgical treatment should be performed with an appropriate rehabilitation program. MATERIAL AND METHODS: We retrospectively studied 18 high performance athletes in various disciplines, with an average age of 22 years, operated by arthroscopy and mini-arthrotomy scraping and application of povidone collagen sponge between March 2001 and December 2005. There after patients underwent a rehabilitation program specific for their return to their athletic activity. RESULTS: The patients returned to their sports activity in an average of 15 weeks, with functional knees without pain, with full range of motion. We did not find postoperative fibrosis. DISCUSSION: The results were similar and slightly better in time of return to sports activities to those reported in the world literature, with the difference in follow up. According to the clinical evaluation, treatment performed allows functional improvement with a return to athletic activity in a reasonable time.


Subject(s)
Arthroscopy/methods , Athletic Injuries/surgery , Debridement/methods , Knee Injuries/surgery , Patellar Ligament/surgery , Tendinopathy/surgery , Adolescent , Adult , Athletic Injuries/drug therapy , Athletic Injuries/etiology , Athletic Injuries/rehabilitation , Drug Implants , Female , Fibrosis/prevention & control , Gelatin Sponge, Absorbable , Humans , Knee Injuries/drug therapy , Knee Injuries/etiology , Knee Injuries/rehabilitation , Male , Povidone/administration & dosage , Povidone/therapeutic use , Retrospective Studies , Tendinopathy/drug therapy , Tendinopathy/etiology , Tendinopathy/rehabilitation , Wound Healing/drug effects
17.
Acta Ortop Mex ; 21(5): 267-73, 2007.
Article in Spanish | MEDLINE | ID: mdl-18159916

ABSTRACT

OBJECTIVE: Evaluate the results of Pridie chondroplasty as an efficient treatment to recover the complete activity in soccer players and compare this with others chondral repair techniques. MATERIAL AND METHODS: The patients were professional soccer players, all with a knee cartilage injury treated with the Pridie technique in an arthroscopic surgery between March 1999--December 2004. The age of the patients and the presence of a simple meniscal tear wasn't a fact to exclude a patient. Complex meniscal tear and a ACL rupture were an exclusion criteria. We deferred the support by 6 to 8 weeks. We initiated rehabilitation to the 4-5 post operating day. The follow up average was of 30 months. RESULTS: We included 34 patients, age rank 19-31 years (average 24.6), 11 of them with meniscal injury Degree I associated with chondral damage. In 26 patients (76.47%) the outcomes were good allowing them to take up again their high level sport activity. The rest (23.53%) had regular or bad results with decrement in the game level, 4 of which (11%) they retired of the professional practice in relation to the found injuries. CONCLUSIONS: The follow up time give us a good validation to establish that the used technique is a treatment of low cost, surgically simple with favorable outcomes and low morbidity comparable to the results obtained with other useful techniques of condral repair in the professional soccer player.


Subject(s)
Anterior Cruciate Ligament Injuries , Arthroscopy , Occupational Diseases/surgery , Plastic Surgery Procedures/methods , Soccer/injuries , Tibial Meniscus Injuries , Adult , Anterior Cruciate Ligament/surgery , Arthroscopy/methods , Arthroscopy/statistics & numerical data , Bone Nails , Combined Modality Therapy , Debridement , Humans , Knee Injuries/rehabilitation , Knee Injuries/surgery , Knee Injuries/therapy , Male , Menisci, Tibial/surgery , Motion Therapy, Continuous Passive , Occupational Diseases/rehabilitation , Occupational Diseases/therapy , Osteochondritis Dissecans/complications , Physical Therapy Modalities , Recovery of Function , Retirement/statistics & numerical data , Retrospective Studies , Treatment Outcome
18.
Int J Colorectal Dis ; 18(5): 451-4, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12756590

ABSTRACT

BACKGROUND AND AIMS: Rectovaginal fistulas in patients with Crohn's disease are difficult to resolve, and surgical failure is very frequent. Recent studies have shown that adult stem cells extracted from certain tissues, such as adipose tissue, can develop into different tissues, such as muscle. PATIENT AND METHODS: We report here the case of a young patient with Crohn's disease who had a recurrent rectovaginal fistula that was treated by autologous stem-cell transplantation with a lipoaspirate as the source of stem cells. RESULTS: Although Crohn's disease is the worst condition for a surgical approach in cases of rectovaginal fistula, we observed good closure. Since the surgical procedure 3 month ago the patient has not experienced vaginal flatus or fecal incontinence through her vagina. Thus our treatment seems to be effective. CONCLUSION: Cell transplantation to overcome healing problems is a new surgical tool, and careful evaluation of this new modality may provide an opportunity to define a new era in the treatment of surgical challenges associated with healing disorders. Ethical and safety items do not seem to be critical problems using autologous stem cells.


Subject(s)
Crohn Disease/complications , Lipectomy , Rectovaginal Fistula/therapy , Stem Cell Transplantation/methods , Adult , Female , Humans , Rectovaginal Fistula/etiology , Secondary Prevention , Transplantation, Autologous , Treatment Outcome
19.
Rev. mex. ortop. traumatol ; 15(6): 251-252, nov.-dic. 2001.
Article in Spanish | LILACS | ID: lil-312261

ABSTRACT

Se realizó una evaluación retrospectiva de tres pacientes que presentaron fractura supracondílea femoral periprotésica que se trataron mediante un clavo retrógrado supracondíleo. Los tres tenían previamente una prótesis total de rodilla. Su evolución posquirúrgica fue sin complicaciones, regresando a su actividad en un periodo de dos a tres meses después del acto quirúrgico. No se presentaron retardos de consolidación ni consolidación viciosa. En una paciente se trataba de su segunda prótesis.


Subject(s)
Humans , Female , Aged , Postoperative Complications , Femoral Neck Fractures , Bone Screws , Recurrence , Splints
20.
Rev. mex. ortop. traumatol ; 15(6): 261-268, nov.-dic. 2001. tab, graf
Article in Spanish | LILACS | ID: lil-312263

ABSTRACT

De enero a diciembre de 1997 se trataron 285 pacientes adultos, entre 15 y 95 años de edad con fractura expuesta de la tibia, con localización diafisaria en 211 casos (74 por ciento), cuyo trazo más común fue en ala de mariposa (169 casos). El primer desbridamiento se hizo en menos de ocho horas en el 49.8 por ciento de los casos. La estabilización fue con fijador externo en 38.6 por ciento y con clavo centromedular en el 41.9 por ciento. Se logró la consolidación en 30.6 semanas en promedio. Las complicaciones fueron retardo de consolidación en 13.4 por ciento, consolidación viciosa en 13.4 por ciento y osteítis en el 11 por ciento.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Social Security , Tibial Fractures , Fractures, Open , Metronidazole , External Fixators , Fracture Fixation/methods
SELECTION OF CITATIONS
SEARCH DETAIL
...