Increased anxiety-like behavior is associated with the metabolic syndrome in non-stressed rats.

Metabolic syndrome (MS) is a cluster of signs that increases the risk to develop diabetes mellitus type 2 and cardiovascular disease. In the last years, a growing interest to study the relationship between MS and psychiatric disorders, such as depression and anxiety, has emerged obtaining conflicting results. Diet-induced MS rat models have only examined the effects of high-fat or mixed cafeteria diets to a limited extent. We explored whether an anxiety-like behavior was associated with MS in non-stressed rats chronically submitted to a high-sucrose diet (20% sucrose in drinking water) using three different anxiety paradigms: the shock-probe/burying test (SPBT), the elevated plus-maze (EPM) and the open-field test (OFT). Behaviorally, the high-sucrose diet group showed an increase in burying behavior in the SPBT. Also, these animals displayed both avoidance to explore the central part of the arena and a significant increase in freezing behavior in the OFT and lack of effects in the EPM. Also, high-sucrose diet group showed signs of an MS-like condition: significant increases in body weight and body mass index, abdominal obesity, hypertension, hyperglycemia, hyperinsulinemia, and dyslipidemia. Plasma leptin and resistin levels were also increased. No changes in plasma corticosterone levels were found. These results indicate that rats under a 24-weeks high-sucrose diet develop an MS associated with an anxiety-like behavior. Although the mechanisms underlying this behavioral outcome remain to be investigated, the role of leptin is emphasized.

[Common and inductors factors of inflammation in asthma and obesity]. / Factores comunes e inductores de inflamación en asma y obesidad.

The incidence of asthma and obesity is increasing, therefore they have been classified as public health problems; epidemiology suggests a link between these diseases. It has been detected a relationship between the body mass index and lung function, moreover some works show a direct correlation between the aforementioned index and severity of asthma. By a search for articles in indexed journals from medical databases with the key words asthma and obesity: pathogenesis, inflammation, adipokines, hypoxia, nutrition, pregnancy, this paper deeps in the knowledge about basic elements that offer an asthma and obesity link. It was found that the association between body mass index and asthma is more frequent in women. Asthma and obesity might be influenced by genetic elements and fetal programming; at the same time obesity could influence asthma by several mechanisms such as inflammation, hormones and mechanical respiratory dysfunction. The existing coincidence between several inducers and factors which exacerbate these diseases as well as in some molecular routes shows a potential relation between both pathological entities.

La incidencia de asma y obesidad está en aumento, por lo que se han catalogado como problemas de salud pública. Los datos epidemiológicos sugieren una relación entre ellas y se ha detectado una asociación entre el índice de masa corporal y la función pulmonar. Diversos estudios demuestran una correlación directa entre este índice y el asma. Mediante la búsqueda de referencias en bases de datos médicos de artículos publicados en revistas indizadas, con las palabras clave asma y obesidad: patogénesis, inflamación, adipocinas, hipoxia, nutrición, embarazo, este artículo profundiza en el conocimiento de los elementos básicos que interrelacionan el asma con la obesidad. Se encontró que la asociación existente entre el índice de masa corporal y el asma es más evidente en el sexo femenino. El asma y la obesidad pueden estar influidas por elementos genéticos y programación fetal. A su vez, la obesidad puede incidir en el asma por diversos mecanismos, como los mecánicos, hormonales o inflamatorios. La coincidencia existente entre varios inductores y elementos que exacerban a estas enfermedades, así como en algunas vías moleculares, ponen de manifiesto una relación potencial entre ambas afecciones.

[Occupational asthma]. / Asma ocupacional.

The occupational asthma is the most common form of lung disease caused by factors that are attributed to a specific working environment in industrialized countries. It causes variable limitation of airflow and/or hyper-responsiveness of the airway due to contact with specific agents present in an atmosphere of work and not to stimuli found out of this place. It is recognized more and more frequently, and many agents are capable of causing occupational asthma by different pathophysiological mechanisms. More than 400 agents causing occupational asthma are known and every year new triggers are detected. Numerous factors contribute to the pathogenesis of occupational asthma induced chemically, including immunological, non-immunological mechanisms of epithelial damage, airway remodeling, oxidative stress, neurogenic inflammation as well as genetic factors. The most important risk factors for occupational asthma include: atopy, smoking and genetic factors. The diagnosis is based on the clinical history, skin tests, immunological tests and functional studies. The fundamental treatment is removing the worker from exposure as soon as possible. The advance in the knowledge of the pathogenesis of occupational asthma will importantly influence in the prevention and the management of this disease.

El asma ocupacional es la forma más común de enfermedad pulmonar causada por factores que se atribuyen a un ambiente laboral específico en países industrializados. Causa limitación variable del flujo aéreo e hiperrespuesta de las vías aéreas debido al contacto con agentes específicos presentes en un ambiente de trabajo y no a estímulos encontrados fuera de este lugar. Se reconoce cada vez con más frecuencia y muchos agentes son capaces de causar asma ocupacional por diferentes mecanismos fisiopatológicos. Se conocen más de 400 agentes causantes de asma ocupacional y cada año se detectan nuevos desencadenantes. Numerosos factores contribuyen a la patogénesis de asma ocupacional inducida químicamente, incluidos mecanismos inmunológicos, no inmunológicos, de daño epitelial, remodelación de las vías aéreas, estrés oxidativo, inflamación neurogénica y factores genéticos. Entre los factores de riesgo de asma ocupacional están: la atopia, el tabaquismo y factores genéticos. El diagnóstico se basa en la historia clínica del paciente, pruebas cutáneas, inmunológicas y estudios funcionales. El tratamiento principal es la remoción del trabajador del sitio de exposición tan pronto como sea posible. El avance en el conocimiento de la patogénesis del asma ocupacional influirá de manera importante en la prevención y el tratamiento de esta enfermedad.

[Epigenetics, environment and asthma]. / Epigenética, medio ambiente y asma.

Asthma is a chronic inflammatory disease of the respiratory tract with a complex genetic background influenced by the exposition to a series of environmental factors. Genetic studies can only elucidate part of the heritability and susceptibility of asthma and even though several diseases have an evident genetic etiology, only a fraction of the genes involved in their pathogenicity have been identified. The epigenetic regulation of the latter is a fact one should bear in mind in order to explain the major triggers of diseases whose understanding is complicated, such as allergies and asthma. External stimulus such as nourishment, stress, physical activity, atmospheric pollution, tobacco smoking and alcohol drinking can induce either gene silencing or gene expression. In this regard, epigenetics can explain how these environmental factors influence our genetic inheritance. There is growing evidence that backs-up the fact that DNA methylation, histone post-translational modification and microRNA expression are influenced by the environment. This helps explaining how several of the risk factors mentioned contribute to the development and inheritance of asthma. In this review, different environmental factors and their relation with the main epigenetic regulatory mechanisms will be analyzed, as well as their possible role in the development of asthma.

El asma es una enfermedad inflamatoria crónica que afecta las vías respiratorias y tiene un componente genético complejo, que está mediada por la exposición a una variedad de desencadenantes ambientales. Los estudios genéticos no aclaran en su totalidad la herencia y susceptibilidad al asma. Muchas enfermedades son de origen genético; sin embargo, sólo se ha encontrado una fracción de los genes que las explican. La epigenética puede utilizarse para esclarecer las causas principales de padecimientos que son difíciles de entender, como la alergia y el asma. Estímulos externos como la nutrición, el estrés, la actividad física, la contaminación atmosférica y el consumo de tabaco y alcohol pueden silenciar o activar los genes. Al respecto, la epigenética ofrece explicaciones de cómo estos factores modifican sutilmente la herencia. Cada vez hay más evidencias que demuestran que los marcadores epigenéticos reconocidos, como la metilación del ADN, la modificación de histonas y la expresión de microRNAs están influidos por el ambiente. Esto ayuda a entender cómo muchos factores de riesgo similares a los señalados contribuyen a la aparición y herencia del asma. En esta revisión se analizan diferentes factores ambientales y su relación con los principales mecanismos epigenéticos, así como su posible influencia en la aparición del asma.

Monocyte locomotion inhibitory factor produced by E. histolytica improves motor recovery and develops neuroprotection after traumatic injury to the spinal cord.

Monocyte locomotion inhibitory factor (MLIF) is a pentapeptide produced by Entamoeba histolytica that has a potent anti-inflammatory effect. Either MLIF or phosphate buffered saline (PBS) was administered directly onto the spinal cord (SC) immediately after injury. Motor recovery was evaluated. We also analyzed neuroprotection by quantifying the number of surviving ventral horn motor neurons and the persistence of rubrospinal tract neurons. To evaluate the mechanism through which MLIF improved the outcome of SC injury, we quantified the expression of inducible nitric oxide synthase (iNOS), interleukin-10 (IL-10), and transforming growth factor- ß (TGF- ß ) genes at the site of injury. Finally, the levels of nitric oxide and of lipid peroxidation were also determined in peripheral blood. Results showed that MLIF improved the rate of motor recovery and this correlated with an increased survival of ventral horn and rubrospinal neurons. These beneficial effects were in turn associated with a reduction in iNOS gene products and a significant upregulation of IL-10 and TGF- ß expression. In the same way, MLIF reduced the concentration of nitric oxide and the levels of lipid peroxidation in systemic circulation. The present results demonstrate for the first time the neuroprotective effects endowed by MLIF after SC injury.

[Association of obesity in adults with allergic asthma]. / Asociación de obesidad y asma alérgica en adultos.

BACKGROUND: Obesity and asthma are diseases of high prevalence around the world. The increment in their incidence constitutes a challenge to public health. Asthma can be worse in patients with obesity. OBJECTIVE: To know the prevalence of obesity in a group of Mexican allergic asthmatic adults. METHODS: A study about the prevalence of obesity in 158 adult asthmatic allergic patients in the years 2010 and 2011 was performed, according to the body mass index (BMI) obtained from their clinical files. In addition, skin tests with allergens were done and the total serum level of IgE was determined in each one of the individuals. RESULTS: According to the BMI, 112 (70.9%) patients had a weight above normal; 76 (67.9%) were women and 36 (32.1%) were men. The highest number of patients with weight above normal corresponded to the overweight group. Mild persistent asthma presented in two-thirds of the patients with overweight and obesity. Women with overweight and obesity showed a higher severity of asthma than men. Women had more positive skin tests than men. Half of the patients had IgE levels above normal. CONCLUSIONS: We found an increased prevalence of asthmatic adults with associated obesity. Asthmatic women presented more overweight and obesity than men, as well as increased severity of asthma and more positive skin tests with allergens.

The involvement of NF-?B Transcription factor in asthma.

UNLABELLED: PubMed search was performed using the key words: NF-?B, nuclear factors, asthma. Articles were selected based on their relevance to this review. OBJECTIVE: To review the literature regarding the involvement of the nuclear factor kappa-B (NF-?B) transcription factor in asthma. RESULTS: NF-?B is a critical transcription factor for the production of many inflammatory cytokines. NF-?B is associated with several diseases, including asthma, where there is an inflammation of the airways with cell infiltration. It is activated in bronchial asthmatic patient biopsies and active in the epithelium of the airways in mice after stimulation. It also participates in the maintenance of the chronic inflammatory response. NF-?B also acts synergistically with other transcription factors, to induce the maximal expression of genes involved with asthma. Activation of NF- ?B by several stimuli induces the release and degradation of the inhibitory protein I-?B from the dimeric complex followed by translocation of NF-?B to the nucleus. CONCLUSIONS: The NF-?B pathway is central to the pathogenesis of asthma. NF?B is an important therapeutic target for the treatment of asthma, including intermediate products on the signaling pathway and protein related to Rel. Alterations in the NF-?B signaling pathway are associated with the disease.

Anti-inflammatory defense mechanisms of Entamoeba histolytica.

The monocyte locomotion inhibitory factor (MLIF), a heat-stable oligopeptide found in the supernatant fluid of Entamoeba histolytica axenic cultures, may contribute to the delayed inflammation observed in amoebic hepatic abscess. This factor was isolated by ultra-filtration and high powered liquid chromatography, obtaining a primary Met-Gln-Cys-Asn-Ser structure, identified afterwards as the carboxyl-terminal (…Cys-Asn-Ser) active site. The selective anti-inflammatory effects of the pentapeptide have been observed in both in vitro and in vivo models, using a synthetic pentapeptide to maintain the same anti-inflammatory conditions during the experimental assays. Anti-inflammatory effects observed include inhibition of human monocyte locomotion and the respiratory burst in monocytes and neutrophils, increasing expression of anti-inflammatory cytokines and inhibiting expression of the adhesion molecules VLA-4 and VCAM, among others. In this review, we will describe the effects of MLIF detected so far and how it might be used as a therapeutical agent against inflammatory diseases.

Computational study of the electronic structure characterization of a novel anti-inflammatory tripeptide derived from monocyte locomotion inhibitory factor (MLIF)-pentapeptide.

The structure and properties of molecules are determined by their charge-density distribution. Several works have shown that electron delocalization along the peptide backbone and side-chain modulates the physical and chemical features of peptides and protein properties. Research on Entamoeba histolytica-soluble factors led to the identification of the pentapeptide Met-Gln-Cys-Asn-Ser, with anti-inflammatory in vivo and in vitro effects. A synthetic pentapeptide, Met-Pro-Cys-Asn-Ser, maintained the same anti-inflammatory actions in experimental assays. A previous theoretical study allowed proposing the Cys-Asn-Ser tripeptide (CNS tripeptide) as the pharmacophore group of both molecules. This theoretical hypothesis was recently confirmed experimentally. The aim of this study was to characterize the electronic structure and physico-chemical properties of the CNS tripeptide through a theoretical study at the second-order Møller-Plesset perturbation theory (MP2) and density functional theory (DFT) theoretical levels. Our results in deprotonation energies show that the hydrogen atom (H2) of the serine-amide group possesses acidic characteristics. This result was confirmed by means of a study of bond order. Atomic charges, dipole moment, frontier molecular orbitals (Highest occupied molecular orbital [HOMO-1] and Lowest unoccupied molecular orbital [LUMO+1]), and electrostatic potential isosurface and its geometric parameters permitted to characterize its electronic structure and physico-chemical features and to identify some reactive sites that could be associated with this tripeptide's anti-inflammatory activity.

Effect of the monocyte locomotion inhibitory factor (MLIF) produced by E. histolityca on cytokines and chemokine receptors in T CD4+ lymphocytes.

Entamoeba histolytica produces Monocyte Locomotion Inhibitory Factor (MLIF), which may contribute to the delayed inflammation observed in amoebic hepatic abscesses. Leukocytes are affected through the modulation of cytokine expression and/or production. We evaluated the effects of MLIF on the activation and production of intracellular cytokines in human CD4+ T lymphocytes by flow cytometry. Cells were stimulated for 24 h with PMA, MLIF, or PMA+MLIF. Cellular activation was measured using anti-CD69. Th1/Th2 production was studied by the expression of intracellular cytokines and cytokine/chemokine receptors. MLIF increased CD69 and induced the over-expression of the IL-lss, IFN-gamma, IL-2, IL-4, and IL-10 intracellular cytokines; PMA+MLIF inhibited Th1 cytokine (IFN-gamma) and increased Th2 cytokines (IL-4 and IL-10). The co-expression of the cytokine and chemokine receptors IFN-gamma/CCR5 and IL-1ss/CCR5 was inhibited by PMA+MLIF and Th2 co-expression was increased. MLIF effects varied depending on the conditions. MLIF alone activated the Th1 and Th2 cytokines and cytokine/receptor expression; however, PMA+MLIF increased the expression of Th2 but inhibited it in Th1.

Effect of the monocyte locomotion inhibitory factor (MLIF) produced by E. histolityca on cytokines and chemokine receptors in T CD4+ lymphocytes

Entamoeba histolytica produces Monocyte Locomotion Inhibitory Factor (MLIF), which may contribute to the delayed inflammation observed in amoebic hepatic abscesses. Leukocytes are affected through the modulation of cytokine expression and/or production. We evaluated the effects of MLIF on the activation and production of intracellular cytokines in human CD4+ T lymphocytes by flow cytometry. Cells were stimulated for 24 h with PMA, MLIF, or PMA+MLIF. Cellular activation was measured using anti-CD69. Th1/Th2 production was studied by the expression of intracellular cytokines and cytokine/chemokine receptors. MLIF increased CD69 and induced the over-expression of the IL-l©¬, IFN-¥ã, IL-2, IL-4, and IL-10 intracellular cytokines; PMA+MLIF inhibited Th1 cytokine (IFN-¥ã) and increased Th2 cytokines (IL-4 and IL-10). The co-expression of the cytokine and chemokine receptors IFN-¥ã/CCR5 and IL-1©¬/CCR5 was inhibited by PMA+MLIF and Th2 co-expression was increased. MLIF effects varied depending on the conditions. MLIF alone activated the Th1 and Th2 cytokines and cytokine/receptor expression; however, PMA+MLIF increased the expression of Th2 but inhibited it in Th1.

The Cys-Asn-Ser carboxyl-terminal end group is the pharmacophore of the amebic anti-inflammatory monocyte locomotion inhibitory factor (MLIF).

The monocyte locomotion inhibitory factor (MLIF) is an anti-inflammatory oligopeptide produced by Entamoeba histolytica. Among its different effects, it inhibits locomotion of human monocytes, hence its original name. Previous experimental studies have shown that the anti-inflammatory properties of MLIF (Met-Gln-Cys-Asn-Ser) remained when aminoacid glutamine was substituted by a proline in the second position (pMLIF: Met-Pro-Cys-Asn-Ser). By changing the order of MLIF amino acids, the resulting scrambled oligopeptide (sMLIF: Gln-Cys-Met-Ser-Asn) has failed activity. By means of ab initio study at the Hartree-Fock and Density Functional Theory levels, it was found that MLIF and pMLIF peptides maintain a great structural similarity among the last three amino acids (...Cys-Asn-Ser) predicting a pharmacophore. The objective of this work was to experimentally verify in vivo and in vitro the existence of the pharmacophore group in MLIF. We assayed three tripeptides by respiratory burst and delayed hypersensitivity skin reactions. The tripeptide Cys-Asn-Ser carboxyl-terminal end group maintained 100% of its biological properties, as well as the anti-inflammatory activity of MLIF, while the other tripeptides tested did not do that.

[Oral or trandsdermanl hormone replacement therapy reduces interleukine-6 levels]. / La terapia estrogénica de reemplazo, oral o transdérmica, reduce las concentraciones de interleucina-6.

OBJECTIVE: To compare the effect of oral and transdermal estrogen replacement therapy (ET) on circulating interleukin-6 (IL-6) in post-menopausal women. PATIENTS AND METHOD: Prospective open trial study in 55 healthy hysterectomized postmenopausal women with a mean age of 52 years. Twenty-seven women received oral conjugated equine estrogens (0.625 mg daily) and the remaining 28 received transdermal estrogen replacement therapy (50 microg/day) during 6 months. At baseline both groups were similar as to age, body weight, and body mass index as well as serum levels of LH, FSH, 17-beta estradiol (E2) and IL-6. RESULTS: Baseline elevated IL-6 levels decreased significantly (p<0.05) after both oral and transdermal estrogen replacement therapy; this decrement showed no difference between the two groups. After the follow-up there were no differences in body weight and body mass index between groups; however, in the oral group there was a trend to increment this parameters. Serum levels of E2 and IL-6 were negatively correlated in the two groups and IL-6 was positively correlated with body mass index in untreated women and this correlation was the same in women with estrogen replacement therapy. CONCLUSIONS: The decrement of IL-6 after estrogen replacement therapy was similar for both routes of administration; in addition IL-6 had a negative correlation with E2 and a positive correlation with body mass index.