Inflamació i macròfags

Els macròfags tenen un paper clau en la inflamació. Durant l'inici del procés inflamatori aquestes cèl·lules s'activen i mostren una potent funció fagocítica i microbicida que pot tenir efectes destructius en els teixits on actua. L'activació dels macròfags implica la inducció de més de quatre-cents gens, i dóna com a resultat més capacitat per eliminar els bacteris i per regular moltes altres cèl·lules a través de l'alliberament de citocines i quimiocines. L'activació excessiva d'aquestes cèl·lules té efectes perjudicials, com ara el xoc sèptic, que pot conduir a la síndrome de disfunció orgànica múltiple i a la mort. En altres situacions la persistència dels resultats de l'activitat proinflamatòria pot contribuir al desenvolupament de processos d'inflamació crònica, com l'artritis reumatoide, la psoriasi i la malaltia inflamatòria de l'intestí. Per evitar aquests efectes indesitjables els macròfags han desenvolupat diversos mecanismes per regular l'excés d'activació, de manera que es condueix a la desactivació dels macròfags i a la resolució de la inflamació.Macrophages play key roles in inflammation. During the onset of the inflammatory process, these phagocytic cells become activated and have destructive effects. Macrophage activation, which involves the induction of more than 400 genes, results in an increased capacity to eliminate bacteria and to regulate many other cells through the release of cytokines and chemokines. However, excessive activation has damaging effects, such as septic shock, which can lead to multiple organ dysfunction syndrome and death. In other situations, persistence of pro-inflammatory activity results in the development of chronic inflammation, such as rheumatoid arthritis, psoriasis and inflammatory bowel disease. To prevent undesirable effects, several mechanisms have evolved to control excess activation, thereby leading to macrophage deactivation and the resolution of inflammation. In this review we will discuss the molecular mechanisms of proliferation, activation and survival of macrophages

Erectile Dysfunction Associated with Cardiovascular Risk Factors

Objectives: (1) Determine erectile dysfunction (ED) prevalence in patients with cardiovascular risk factors (CVRF). (2) Assess ED incidence in relation to the extent of controlling CVRF. Methodology: Patients: Enrolled participants came to the health centres in the study area. In accordance with the incidence of diseases with cardiovascular risks (CVR) in the Basic Health Regions of the study area, sample size was calculated with a 95% confidence interval and an alpha error of 0.005, resulting in a sample of 210 people, of which 30 could not complete the study for various reasons (change of address, death, refused to complete questionnaire, etc.). A full awareness and diffusion campaign was organized with talks and leaflets. Letters: A standard letter was given to patients which explained the importance of sexual health, offering them an appointment with a DUE (Diploma in Nursing) survey taker. The questionnaire was devised by the research group and was given by a fully trained DUE survey taker. Previously, contact was made with all the health centres, physicians and nursing staff to give them information on ED and CVRF and to inform them about the work to be done in their health region. Those patients who did not come to the appointment were telephoned to insist on the importance of attending and completing the questionnaire. Variables analysis: We analysed age, level of education, civil status, height, weight and body mass index (BMI), SBP, DBP, smoking habit, number cigarettes/day, year smoking began, ex‐smoker, year smoking stopped, alcohol consumption, grams alcohol/week, as well as consumption of other drugs, frequency and type. Blood test: glucose, haemoglobin glycated haemoglobin, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, artherogenic index, creatinine, urea, GOT, GPT, gamma‐GT and PSA. Urine test: micro‐albuminuria, proteinuria and creatinine clearance. ECG: Diabetes diagnosed at least 1 year ago and prescribed drugs to treat it. High blood pressure diagnosed at least 1 year ago and prescribed drugs to treat it. Dyslipidaemia (hypercholesterolaemia) diagnosed at least 1 year ago and prescribed drugs to treat it. Concomitant diseases of at least 1 year and drugs (up to 3) SHIM questionnaire and ED according to SHIM. Statistical analysis: an observational, descriptive, analytical, cross‐sectional study. Qualitative variables are presented as exact values and a percentage; quantitative variables as the mean and standard deviation (SD). A means comparison was done with the Student’s t‐test for independent groups, or the Mann‐Whitney U test if normality conditions (using the Kolmogorov‐Smirnoff or Shapiro‐Wilks test) were not fulfilled. The chi‐squared test was used for qualitative variables. Results: Of the 210 selected people, 179 completed the questionnaire (85.2%). The mean age was 64.5 ± 11.6 years. When analysing all the study variables in relation to the main variable, presence or absence of ED, age played an important role in ED appearing as ED incidence rises with age. Blood pressure had no significant relationship with the studied variable, and the same hold for BMI and its subdivision into normal weight and obesity. As regards toxic habits, neither cigarette smoking nor alcohol consumption influenced the presence of ED. The same hold for the sociological‐type variables (civil states, level of education). Regarding the biochemical variables from blood tests, a significant relationship with the atherogenic index and its recoded variable at high and low atherogenic risk (p < 0.04) was noted. In the glycaemic profile, a glycaemia mean of 126 mg/dl was obtained in the ED presence group, which is the cut‐off point proposed by ADA117 (American Diabetes Association) to consider a subject diabetic. Likewise, glycated haemoglobin presented figures in the two groups can be considered an alternation of a practically diabetic glucose metabolism. In our study, the presence of diabetic disease, high blood pressure (HBP) and dyslipidaemia showed no significant relationship with ED presence for each disease. However, in the combination of these diseases, a statistically significant relationship was seen when CVR increases, according to the Framinghan tables. Neither did each disease’s duration show a significant relationship with ED presence nor significant differences for the drugs used to treat the three pathologies were found. The coronary risk calculated according to the Framinghan tables indicated a statistically significant result, as did excessive risk (the difference between the coronary risk and the average assigned per age) for ED presence. The LISAT 8 test suggested that ED affected health‐associated quality of life and was statistically significant in two items of sex life and economic situation and was borderline statistically significant in the general life and working life items. Conclusions: There is a high ED prevalence in patients with high CVR. When ED improves, the better CVRFs are controlled. These patients’ pluripathology implies aggressive polymedication which doctors must consider as it increases the risk of ED

Inflamació i macròfags

Els macròfags tenen un paper clau en la inflamació. Durant l'inici del procés inflamatori aquestes cèl·lules s'activen i mostren una potent funció fagocítica i microbicida que pot tenir efectes destructius en els teixits on actua. L'activació dels macròfags implica la inducció de més de quatre-cents gens, i dóna com a resultat més capacitat per eliminar els bacteris i per regular moltes altres cèl·lules a través de l'alliberament de citocines i quimiocines. L'activació excessiva d'aquestes cèl·lules té efectes perjudicials, com ara el xoc sèptic, que pot conduir a la síndrome de disfunció orgànica múltiple i a la mort. En altres situacions la persistència dels resultats de l'activitat proinflamatòria pot contribuir al desenvolupament de processos d'inflamació crònica, com l'artritis reumatoide, la psoriasi i la malaltia inflamatòria de l'intestí. Per evitar aquests efectes indesitjables els macròfags han desenvolupat diversos mecanismes per regular l'excés d'activació, de manera que es condueix a la desactivació dels macròfags i a la resolució de la inflamació

Deacetylase activity is required for STAT5-Dependent GM-CSF functional activity in macrophages and differentiation to dendritic cells.

After interaction with its receptor, GM-CSF induces phosphorylation of the -chain in two distinct domains in macrophages. One induces activation of mitogen-activated protein kinases and the PI3K/Akt pathway, and the other induces JAK2-STAT5. In this study we describe how trichostatin A (TSA), which inhibits deacetylase activity, blocks JAK2-STAT5-dependent gene expression but not the expression of genes that depend on the signal transduction induced by the other domain of the receptor. TSA treatment inhibited the GM-CSF-dependent proliferation of macrophages by interfering with c-myc and cyclin D1 expression. However, M-CSF-dependent proliferation, which requires ERK1/2, was unaffected. Protection from apoptosis, which involves Akt phosphorylation and p21waf-1 expression, was not modified by TSA. GM-CSF-dependent expression of MHC class II molecules was inhibited because CIITA was not induced. The generation of dendritic cells was also impaired by TSA treatment because of the inhibition of IRF4, IRF2, and RelB expression. TSA mediates its effects by preventing the recruitment of RNA polymerase II to the promoter of STAT5 target genes and by inhibiting their expression. However, this drug did not affect STAT5A or STAT5B phosphorylation or DNA binding. These results in GM-CSF-treated macrophages reveal a relationship between histone deacetylase complexes and STAT5 in the regulation of gene expression

Ser-estar entre-línguas-culturas: entrevista com Maria José Coracini

A entrevista com a Profa. Dra. Maria José Coracini (Unicamp, IEL/DLA), pesquisadora 1A do CNPq, foi realizada virtualmente em 2020 e oferece uma série de considerações e desenvolvimentos teóricos sobre temas afins ao dossiê “Literatura e práticas translíngues”. A partir da psicanálise, a pesquisadora revisita o conceito de “língua materna” e enfatiza – contra certa dicotomização entre o materno e o estrangeiro – os processos de maternização da língua estrangeira e de estrangeirização da língua materna. Desse modo, a reflexão se deixa acompanhar pela observação e análise de diversos exemplos de deslocamentos territoriais e linguístico-discursivos, notoriamente aqueles ligados à migração e para cujo estudo Coracini propõe e apresenta o conceito de língua-cultura. Por último, as considerações sobre identidade e língua são retomadas para o exame crítico das experiências de escritores e intelectuais que, como Samuel Beckett, Tzvetan Todorov e Paul Celan, exerceram sua escrita fora da ilusão de plenitude em alguma língua específica

Mitogen-activated protein kinases and mitogen kinase phosphatase 1: a critical interplay in macrophage biology

Macrophages are necessary in multiple processes during the immune response or inflammation. This review emphasizes the critical role of the mitogen-activated protein kinases (MAPKs) and mitogen kinase phosphatase-1 (MKP-1) in the functional activities of macrophages. While the phosphorylation of MAPKs is required for macrophage activation or proliferation, MKP-1 dephosphorylates these kinases, thus playing a balancing role in the control of macrophage behavior. MKP-1 is a nuclear-localized dual-specificity phosphatase whose expression is regulated at multiple levels, including at the transcriptional and post-transcriptional level. The regulatory role of MKP-1 in the interplay between MAPK phosphorylation/dephosphorylation makes this molecule a critical regulator of macrophage biology and inflammation