Changes in the severity of gastric mucosal inflammation associated with Helicobacter pylori in humans coinfected with intestinal helminths.

BACKGROUND: Though a few studies in animal models suggest that intestinal helminths (IH) favorably affect evolution of gastritis associated with Helicobacter pylori (H. pylori) the studies supporting this concept in humans are only a few and are based on serological data. METHODS: To evaluate the possible influence of IH on the human gastric mucosa, three groups of Venezuelan adults with gastropathy (endoscopically diagnosed) were studied: H. pylori-/IH- (n = 17), H. pylori+/IH- (n = 18), and H. pylori+/IH+ (n = 11). Histological analysis (hematoxylin-eosin) and immunohistochemical staining (peroxidase) for cytokines interleukin-1beta (IL-1ß), tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and interleukin 4 (IL-4) were undertaken in gastric antral biopsies. RESULTS: Expression of the four cytokines was detected in all individuals in varying degrees, but proinflammatory cytokines were expressed in a higher degree in the H. pylori+/IH- group, mainly IL-1ß (Th1-dominant immune response), associated with a higher degree of both histological inflammation and gastric cancer risk index (GCRI), as compared to the H. pylori-/IH- group. In contrast, an increased expression of IL-4 and a reduced expression of proinflammatory cytokines (Th2-dominant response), plus the tendency to a lower degree of mononuclear infiltration, mucosal atrophy in gastric corpus, and GCRI, were evidenced in the coinfected group. CONCLUSIONS: The findings of the present study is perhaps the first histological evidence of a possible modulatory effect of IH on the gastric mucosal inflammatory response due to H. pylori infection in humans.

Gefitinib and pyrrolidine dithiocarbamate decrease viral replication and cytokine production in dengue virus infected human monocyte cultures.

AIMS: The epidermal growth factor receptor (EGFR) and nucleotide-binding and oligomerization-domain containing 2 (NOD2) are important in cancer and in microbial recognition, respectively. These molecules trigger intracellular signaling pathways inducing the expression of inflammatory genes by NF-kB translocation. Gefitinib (GBTC) and pyrrolidine dithiocarbamate (PDTC) are capable of inhibiting EGFR/NOD2 and NF-kB, respectively. In earlier stages of dengue virus (DENV) infection, monocytes are capable of sustaining viral replication and increasing cytokine production, suggesting that monocyte/macrophages play an important role in early DENV replication. GBTC and PDTC have not been used to modify the pathogenesis of DENV in infected cells. This study was aimed to determine the effect of GBTC and PDTC on viral replication and cytokine production in DENV serotype 2 (DENV2)-infected human monocyte cultures. MAIN METHODS: GBTC and PDTC were used to inhibit EGFR/NOD2 and NF-kB, respectively. Cytokine production was measured by ELISA and viral replication by plaque forming unit assay. KEY FINDINGS: Increased DENV2 replication and anti-viral cytokine production (IFN-α/ß, TNF-α, IL-12 and IL-18) in infected cultures were found. These parameters were decreased after EGFR/NOD2 or NF-kB inhibitions. SIGNIFICANCE: The inhibitory effects of GBTC and PDTC on viral replication and cytokine production can be beneficial in the treatment of patients infected by dengue and suggest a possible role of EGFR/NOD2 receptors and NF-kB in dengue pathogenesis.

Molécula 1 de Adhesión Intercelular Soluble en menopáusicas tratadas con estradiol oral o transdérmico / Soluble Intercellular Adhesion Molecule 1 In Postmenopausal Women Treated With Oral Or Transdermal Estradiol

El objetivo de la investigación fue comparar las modificaciones de las concentraciones plasmáticas de la molécula 1 de adhesión intercelular soluble en menopáusicas tratadas con estradiol oral o transdérmico después de 3 meses de uso. Se realizó una investigación con una muestra de 140 pacientes menopáusicas que asistieron a la consulta de Medicina Interna, Endocrinología y Menopausia del Hospital Central Dr. Urquinaona, Maracaibo, Venezuela. Se asignó a 70 pacientes tratamiento con estradiol oral (grupo A) y a 70 pacientes tratamiento con estradiol transdérmico (grupo B). Se evaluaron las concentraciones plasmáticas de molécula 1 de adhesión intercelular soluble antes y después de 3 meses de tratamiento. (p = ns). Las concentraciones plasmáticas de la molécula 1 de adhesión intercelular soluble demostraron una reducción después de 3 meses de tratamiento en ambos grupos (grupo A: 279,1 +/- 76,5 ng/ml al inicio comparado con 241,7 +/- 68,4 ng/ml después del tratamiento y grupo B: 251,9 +/- 73,2 ng/ml después del tratamiento comparado con el valor promedio inicial de 288,7 +/- 62,7 ng/ml; p < 0,05). Se concluye que el uso de estradiol transdérmico puede ser una alternativa eficaz al uso de estradiol oral después de 3 meses de uso, debido a que ambos tratamientos producen disminuciones en las concentraciones plasmáticas de molécula 1 de adhesión intercelular soluble.

The objective of research was: to compare modifications of plasma concentrations of solubleintercellular adhesion molecule 1 in postmenopausal women treated with oral or estradiol after 3 months of use. This study included 140 postmenopausal women attending the Internal Medicine, Endocrinology and Menopause Departments at the Hospital Central "Dr. Urquinaona", Maracaibo, Venezuela. Seventy patients were assigned to be treated with oral estradiol (group A) and 70 patients were treated with transdermal estradiol (group B). Plasma concentrations of soluble intercellular adhesion molecule 1 were measured before and after 3 months of treatment. There were no statically significant differences in general characteristics between the two treatment groups (p = ns). In both groups, soluble intercellular adhesion molecule 1 was reduced after 3 months of treatment (group A: 279.1 +/- 76.5 ng/ml before treatment compared with 241.7 +/- 68.4 ng/ml after treatment and group B: 251.9 +/- 73.2 ng/ml after treatment compared with initial mean value of 288.7 +/- 62.7 ng/ml; p < 0.05). It is concluded that transdermal estradiol could be an effective alternative to oral estradiol after 3 months of use since both treatments decreased plasma concentrations of soluble intercellular adhesion molecule 1. KEYWORDS: Estradiol; Menopause; Transdermal; soluble intercellular adhesión.

Zika, dengue, and chikungunya co-infection in a pregnant woman from Colombia.

The clinical findings of a pregnant woman from Colombia with a triple co-infection caused by dengue, chikungunya, and Zika viruses are described. Weekly obstetric ultrasounds from 14.6 to 29 weeks of gestation were normal. She remains under follow-up and management according to the standard guidelines for the management of Zika virus-infected pregnant women.

Factor de necrosis tumoral alfa plasmático en mujeres obesas y no obesas con síndrome de ovarios poliquísticos / Plasma tumor necrosis factor alpha in obese and non-obese women with polycystic ovary syndrome

Objetivo: Determinar las concentraciones plasmáticas de factor de necrosis tumoral alfa (FNT-alfa) en mujeres obesas y no obesas con diagnóstico de síndrome de ovarios poliquísticos (SOPQ). Diseño: Estudio de casos y controles. Participantes: Mujeres con diagnóstico de SOPQ y controles sanas de edades similares, con menstruaciones regulares y ovarios normales por ecografía. Métodos: Las participantes fueron divididas en cuatro grupos (grupo A: SOPQ obesas; grupo B: SOPQ no obesas; grupo C: controles obesas; y grupo D: controles no obesas), de acuerdo al índice de masa corporal (obesas > 30 kg/m2 y no obesas < 25 kg/ m2). Principales medidas de resultados: Concentraciones de lutoprina, folitropina, androstendiona, testosterona, globulina fijadora de hormonas sexuales, glucosa sérica, insulina y FNT-alfa. Resultados: Las mujeres con SOPQ obesas y no obesas presentaron concentra ciones más elevadas de hormonas sexuales e insulina comparado con el grupo control de obesas y no obesas respectivamente (p < 0,0001). Se observó que las mujeres con SOPQ tuvieron concentraciones significativamente más altas de FNT-alfa (grupo A: 6,6 +/- 1,2 pg/ mL y grupo B: 4,0 +/- 0,7 pg/mL) comparado con los controles (grupo C: 4,4 +/- 1,3 pg/mL) y grupo D (2,1 +/- 0,4 pg/dL; p < 0,0001). Se observó que las concentraciones de FNT-alfa presentaban correlación positiva y significativa con los valores de glicemia e insulina en ayunas en las mujeres con SOPQ (p < 0,0001). Conclusión: Se ha hallado diferencias significativas en las concentraciones plasmáticas del FNT-alfa entre las mujeres con SOPQ obesas y no obesas respecto a los controles normales.

Objective: To determine plasma concentration of tumor necrosis factor alpha (TNF-alpha) in obese and non-obese women with polycystic ovary syndrome (PCOS). Design: Case control study. Participants: Women with diagnosis of PCOS and age-matched healthy controls, the latter with regular periods and normal ovaries according to ultrasound. Interventions: Participants were divided in four groups (group A: PCOS and obese; group B: PCOS and nonobese; group C: obese controls; and group D: non-obese controls) according to body mass index (obese > 30 kg/m2 y and non-obese < 25 kg/m2). Main outcome results: Concentrations of luteinizing hormone, follicle-stimulating hormone, androstenodione, testosterone, sex hormone-binding globulin, serum glucose, insulin and TNF-alpha. Results: Obese and non-obese women with PCOS had higher luteinizing hormone, follicle stimulating hormone, androstenodione. testosterone, and insulin levels compared to women in the obese and non-obese control group, respectively (p < 0.0001). Women with PCOS had a significantly higher TNF-alpha plasma concentration (group A 6.6 +/-1.2 pg/mL and group B: 4.0 +/-0.7 pg/mL) as compared with controls (group C: 4.4 +/- 1.3 pg/mL and group D 2.1 +/- 0.4 pg/dL; p < 0.0001). TNF-alpha concentrations presented a positive and significant correlation with fasting glycaemia and insulin in women with PCOS (p < 0.0001). Conclusion: There were significant differences in plasma TNF-alpha concentrations between obese and non-obese women as compared with polycystic ovary syndrome and normal controls.

Procalcitonina Plasmática en mujeres obesas y no obesas con Síndrome de Ovarios Poliquísticos / Plasma Procalcitonin in obese and non obese women with Polycystic Ovary Syndrome

Objetivo: Determinar las concentraciones plasmáticas de procalcitonina, marcador de inflamación de bajo grado, en mujeres obesas y no obesas con diagnóstico de síndrome de ovarios poliquísticos (SOPQ). Métodos: Se seleccionaron mujeres con diagnóstico de SOPQ y controles sanas, de edades similares, con menstruaciones regulares y ovarios normales por ecografía, que fueron divididas en cuatro grupos (grupo A: SOPQ obesas; grupo B: SOPQ no obesas; grupo C: controles obesas y grupo D controles no obesas) de acuerdo al índice de masa corporal (obesas > 30 Kg/m² y no obesas < 25 kg/m²). Se analizaron las concentraciones de hormona luteinizante (LH), hormona foliculoestimulante (FSH), androstendiona, testosterona, globulina fijadora de hormonas sexuales, glucosa sérica, insulina y procalcitonina. Resultados: Las mujeres con SOPQ obesas y no obesas presentaron concentraciones más elevadas de LH, FSH, testosterona, androstendiona e insulina comparado con las mujeres del grupo control de obesas y no obesas respectivamente (p< 0,0001). Se observó que las mujeres con SOPQ presentaron concentraciones significativamente más altas de procalcitonina (grupo A: 0,026±0,003 ng/mL y grupo B: 0,024±0,002 ng/mL) comparado con los controles (grupo C: 0,015±0,001 ng/mL y grupo D: 0,012±0,001 ng/dL; p< 0,0001). Se observó que las concentraciones de procalcitonina presentaban una correlación positiva y significativa con los valores de insulina en ayunas en las mujeres con SOPQ (p< 0,0001). Conclusión: Las concentraciones plasmáticas de procalcitonina son significativamente mayores en las mujeres con SOPQ obesas y no obesas comparado con las mujeres controles. La procalcitonina podría ser útil como marcador de inflamación de bajo grado en el SOPQ.

Objective: To determine plasma concentrations of procalcitonina, marker of low-grade inflammation, in obese and non-obese women with diagnosis of polycystic ovary syndrome (PCOS). Methods: Women with diagnosis of PCOS and age-matched healthy controls, with regular menstruations and normal ultrasound ovaries were selected and divided in four groups (group A: PCOS and obese; group B: PCOS and non-obese; group C: obese controls and group D: non-obese controls) according to body mass index (obese > 30 Kg/m² and non-obese < 25 kg/m²). Concentrations of luteinizing hormone, follicle-stimulating hormone, androstenodione, testosterone, sex hormone-binding globulin, serum glucose, insulin and procalcitonin were measured. Results: Obese and non-obese women with PCOS had higher luteinizing hormone, follicle stimulating hormone, androstenodione, testosterone, and insulin levels as compared to women in the obese and non-obese control group, respectively (p< 0.0001). Women with PCOS had significantly higher procalcitonin levels (group A 0.026±0.003 ng/mL and group B: 0.024±0.002 ng/mL) as compared with controls (group C: 0.015±0.001 ng/mL and group D: 0.012±0.001 ng/dL; p< 0.0001). We observed that procalcitonin concentrations presented a positive and significant correlation with fasting insulin in PCOS women (p< 0.0001). Conclusion: Plasma procalcitonin concentrations were significantly higher in obese and non-obese women with PCOS compared with normal controls. Procalcitonin could be useful as a marker of low-grade inflammation in PCOS.

Dimetilarginina asimétrica plasmática en mujeres obesas y no obesas con síndrome de ovarios poliquísticos / Asymmetric plasma dimethylarginine in obese women and non-obese with polycystic ovarian syndrome

Objetivo: determinar las concentraciones plasmáticas de factor de dimetilarginina asimétrica (ADMA) en mujeres obesas y no obesas con diagnóstico de síndrome de ovarios poliquísticos (SOPQ). Métodos: se realizó un estudio de casos y controles en mujeres con diagnóstico de SOPQ y controles sanas de edades similares, con menstruaciones regulares y ovarios normales por ecografía y fueron divididas en cuatro grupos (grupo A: SOPQ obesas; grupo B: SOPQ no obesas; grupo C: controles obesas y grupo D controles no obesas) de acuerdo con el índice de masa corporal (obesas > 30 Kg/m2 y no obesas < 25 kg/m2 . Se midieron las concentraciones de hormonas sexuales, globulina fijadora de hormonas sexuales, glucosa sérica, insulina y ADMA. Resultados: las mujeres con SOPQ obesas y no obesas presentaron concentraciones más elevadas de hormonas sexuales e insulina comparadas con el grupo control de obesas y no obesas (p < 0,0001). Se observó que las mujeres con SOPQ presentaron concentraciones significativamente más altas de ADMA (grupo A: 0,56 +/- 0,05 picomol/L y grupo B: 0,51 +/- 0,03 picomol/L) comparado con los controles (grupo C: 0,47 +/- 0,02 picomol/L y grupo D 0,45 +/- 0,04 picomol/L; p < 0,0001). Se observó que las concentraciones de ADMA presentaban correlación positiva y significativa con los valores de glicemia e insulina en ayunas en las mujeres con SOPQ (p < 0,0001). Conclusión: Existen diferencias significativas en las concentraciones plasmáticas del ADMA entre las mujeres con SOPQ obesas y no obesas respecto a los controles normales.(AU)

Objective: To determine plasma concentrations of asymmetric dimethylarginine (ADMA) in obese and non-obese women with polycystic ovary syndrome (PCOS). Methods: A Case control study was done of women with diagnosis of PCOS and age-matched healthy controls, regular menstruations and normal ultrasound ovaries were selected Participants were divided in four groups (group A: PCOS and obese; group B: PCOS and non-obese; group C: obese controls and group D non-obese controls) according to body mass index (obese > 30 Kg/m2 y non-obese < 25 kg/m2 ). Concentrations of sexual hormones, sex hormone-binding globulin, serum glucose, insulin and ADMA. Results: Obese and non-obese women with PCOS had higher luteinizing hormone, follicle stimulating hormone, androstenodione, testosterone, and insulin levels as compared to women in the obese and non-obese control group, respectively (p < 0.0001). Women with PCOS had significantly higher of of ADMA (group A 0,56 +/- 0.05 picomol/L and group B: 0.51 +/- 0.03 picomol/L) as compared with controls (group C: 0.47 +/- 0.02 picomol/L and group D 0.45 +/- 0.04 picomol/L; p < 0.0001). We observed that ADMA concentrations presented a positive and significant correlation with fasting glycaemia and insulin in PCOS women (p < 0.0001). Conclusion: there are significant differences in plasma ADMA.(AU)

Melatonin, minocycline and ascorbic acid reduce oxidative stress and viral titers and increase survival rate in experimental Venezuelan equine encephalitis.

Venezuelan equine encephalitis (VEE) virus causes an acute central nervous system infection in human and animals. Melatonin (MLT), minocycline (MIN) and ascorbic acid (AA) have been shown to have antiviral activities in experimental infections; however, the mechanisms involved are poorly studied. Therefore, the aim of this study was to determine the effects of those compounds on the viral titers, NO production and lipid peroxidation in the brain of mice and neuroblastoma cultures infected by VEE virus. Infected mouse (10 LD50) were treated with MLT (500 µg/kg bw), MIN (50mg/kg bw) or AA (50mg/kg bw). Infected neuroblastoma cultures (MOI: 1); MLT: 0.5, 1, 5mM, MIN: 0.1, 0.2, 2 µM or AA: 25, 50, 75 µM. Brains were obtained at days 1, 3 and 5. In addition, survival rate of infected treated mice was also analyzed. Viral replication was determined by the plaque formation technique. NO and lipid peroxidation were measured by Griess׳ reaction and thiobarbituric acid assay respectively. Increased viral replication, NO production and lipid peroxidation were observed in both, infected brain and neuroblastoma cell cultures compared with uninfected controls. Those effects were diminished by the studied treatments. In addition, increased survival rate (50%) in treated infected animals compared with untreated infected mice (0%) was found. MLT, MIN and AA have an antiviral effect involving their anti-oxidant properties, and suggesting a potential use of these compounds for human VEE virus infection.

In situ increased chemokine expression in human cervical intraepithelial neoplasia.

Chemokines play a role in tumor-inflammation and angiogenesis that could be involved in tumor progression. Monocyte chemoattractant protein-1 (MCP-1), Interleukin-8 (IL-8) and macrophage inflammatory proteins (MIP) have been identified in tumor tissues of patients with different neoplasms. Therefore, the aim of the current study was to investigate the expressions of MCP-1, IL-8 and MIP-1α, mononuclear leukocyte infiltration and leukocyte/chemokine expressions in cervical tissues from patients with cervical intraepithelial neoplasia (CIN) and controls. MCP-1, IL-8 and MIP-1α expressions and leukocyte infiltration were determined by indirect immunofluorescence in cervix biopsies from CIN patients (n=65) and 7 normal controls. Increased expressions of MCP-1 and IL-8 in CIN were observed. Increment of lymphocyte infiltration and coexpression of CD3/MCP-1 and CD3/IL-8 were found in CIN. CD3/MCP-1 cell percentage was found decreased and CD3/IL-8 percentage increased according to the CIN evolution. MIP-1α remained similar to control values. The increased expression of MCP-1 and IL-8 in cervical neoplasia may lead to tumor progression.

Macrophage migration inhibitory factor in obese and non obese women with polycystic ovary syndrome.

OBJECTIVE: To measure macrophage migration inhibitory factor (MIF) concentrations in obese and non-obese women diagnosed with polycystic ovary syndrome (PCOS). METHODS: Women diagnosed with PCOS and age-matched healthy controls with regular menses and normal ovaries on ultrasound examination were selected and divided into 4 groups (group A, PCOS and obese; group B, PCOS and non-obese; group C, obese controls; and group D, non-obese controls) based on body mass index (obese >30 kg/m2 and non-obese <25 kg/m2). Luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, sex hormone-binding globulin, serum glucose, insulin and MIF levels were measured. RESULTS: Obese and non-obese women with PCOS had higher luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, and insulin levels as compared to the obese and non-obese control groups, respectively (P < .0001). Women with PCOS had significantly higher MIF levels (group A, 48.6 ± 9.9 mg/ml; group B, 35.2 ± 6.0 ng/ml) as compared to controls (group C, 13.5 ± 6.0 ng/ml; group D, 12.0 ± 4.3 ng/dl; P < .0001). A weak, positive and significant correlation was seen between fasting blood glucose and insulin levels in women with PCOS (P < .05). CONCLUSION: Significant differences exist in plasma MIF levels between obese and non-obese women with and without PCOS.

Melatonin decreases brain apoptosis, oxidative stress, and CD200 expression and increased survival rate in mice infected by Venezuelan equine encephalitis virus.

BACKGROUND: Pro-inflammatory and oxidative events during brain Venezuelan equine encephalitis virus infection could lead to apoptosis and induce anti-inflammatory responses (increased expression of CD200). The aim of this study was to determine the effect of melatonin on brain apoptosis, oxidative stress, and CD200 molecule in mice and neuroblastoma cultures infected by Venezuelan equine encephalitis virus. METHODS: Mice were infected with 10 median lethal doses (LD50) of Venezuelan equine encephalitis virus, treated with melatonin (500 µg/kg bw; three days before infection and during all experimental time) and sacrificed on days 1, 3, and 5 postinfection. Brain samples were obtained at those periods of time. In addition, infected neuroblastoma cell cultures (multiplicity of infection [MOI]: 1) were treated with 0, 0.1, 0.5, and 1 mM of melatonin and analyzed at 2, 4, and 6 h. CD200 and apoptosis expressions were analyzed by immunohistochemistry and TUNEL assay, respectively. Nitrites and malondialdehyde were determined by appropriate biochemical methods. RESULTS: Increased brain expression of apoptosis, nitrite, and malondialdehyde productions and CD200 of infected mice were found. Melatonin diminished those expressions. Similarly, high apoptosis expression and nitrite and malondialdehyde productions on infected neuroblastoma cultures were diminished by melatonin. Melatonin increased the survival rate (25%) in Venezuelan equine encephalitis virus-infected animals compared with untreated infected mice (0%). CONCLUSIONS: Neurological damage during brain Venezuelan equine encephalitis virus infection could be mediated by apoptosis and oxidative stress and CD200 molecule could be an important anti-inflammatory response. Melatonin could be beneficial reducing apoptosis and oxidative stress.

Differential induction of cytokines by human neonatal, adult, and elderly monocyte/macrophages infected with dengue virus.

Immunosuppressive status against infections in monocytes from neonates and elderly subjects has been reported. The interaction between dengue virus and monocytes/macrophages plays an important role during dengue disease. The aim of this study was to determine the cytokine response of monocytes from individuals with different ages after infection with dengue virus. Monocyte/macrophage cultures from neonatal, adult, and elderly subjects (n=10 each group) were incubated with all four dengue virus types (DENV-1 to -4). After 1 and 3 days of culture, cytokine concentrations (TNF-α, IL-6, and IL-1ß) were determined in culture supernatants by enzyme-linked immunosorbant assay. Increased production of all studied cytokines was induced by the different viral types in monocyte/macrophage cultures regardless of their source. However, lower cytokine concentrations were found in neonatal and elderly monocytes. The relative monocyte/macrophage immunosuppressive status observed in neonates and the elderly could be relevant during dengue infection in those age groups and important in innate and adaptive immunity responses against this virus.

[Role of toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) in viral infections]. / Papel de los receptores tipo toll (TLRs) y receptores para dominios de oligomerización para la unión a nucleótidos (NLRs) en las infecciones virales.

The immune system (IS) cells are capable of recognizing a wide variety of microorganisms, through receptors that are expressed and distributed throughout the cell architecture. The interaction between the pathogen-associated molecular patterns or damage-associated molecular patterns (PAMPs or DAMPs) and pattern recognition receptors (PRR), present in host cells, is a critical event that involves intracellular signaling processes that end up in the expression of both, proinflammatory and antiviral mediators. Accordingly, the proper functioning of the different mechanisms of signal transduction from the cell membrane to the cytoplasm will depend on the integrity of these receptors (PRR); and therefore, the IS response triggered against pathogens including viral agents. Hence, in this review we discuss the role of toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) in viral infections, using as evidence the studies in humans and mice known to date.

Papel de los receptores tipo toll (TLRs) y receptores para dominios de oligomerización para la unión a nucleótidos (NLRs) en las infecciones virales / Role of toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) in viral infections

Las células del sistema inmunitario (SI) son capaces de reconocer una gran variedad de microorganismos, a través de los receptores que se encuentran expresados y distribuidos a lo largo de su arquitectura celular. La interacción entre los patrones moleculares asociados a microorganismos o a daño (PMAM o PMAD) y los receptores reconocedores de patrones (RRP) presentes en las células del hospedero es un evento crítico que implica procesos intracelulares de señalización que finalizan en la expresión de mediadores tanto proinflamatorios como antivirales. Por consiguiente, de la integridad de estos receptores dependerá el buen funcionamiento de los distintos mecanismos de transducción de señal desde las membranas celulares al citoplasma y por ende, de la respuesta que el SI desencadene contra los patógenos entre ellos los agentes virales. De allí que, en esta revisión se discutirá el papel de los receptores tipo toll (TLRs) y receptores para dominios de oligomerización para la unión a nucleótidos (NLRs) en las infecciones virales, tomando como evidencia los estudios en humanos y ratones que a la fecha se conocen.

The immune system (IS) cells are capable of recognizing a wide variety of microorganisms, through receptors that are expressed and distributed throughout the cell architecture. The interaction between the pathogen-associated molecular patterns or damage-associated molecular patterns (PAMPs or DAMPs) and pattern recognition receptors (PRR), present in host cells, is a critical event that involves intracellular signaling processes that end up in the expression of both, proinflammatory and antiviral mediators. Accordingly, the proper functioning of the different mechanisms of signal transduction from the cell membrane to the cytoplasm will depend on the integrity of these receptors (PRR); and therefore, the IS response triggered against pathogens including viral agents. Hence, in this review we discuss the role of toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) in viral infections, using as evidence the studies in humans and mice known to date.

Employment in a cohort of cancer patients in Spain. A predictive model of working outcomes.

INTRODUCTION: Cancer patients can have problems remaining in employment but the importance of this issue has until now received little attention in Spain. PATIENTS AND METHODS: The study included 347 consecutive cancer patients who were employed at diagnosis. Diagnosis had been confirmed at least 6 months before the interview. Participants completed a questionnaire concerning cancer-related symptoms and work-related factors and clinical details were obtained from their medical records. The study was approved by the Ethical Committee of La Paz Hospital. All patients gave consent to participate. RESULTS: Eighty-five percent of patients were unable to work after diagnosis, but 59% returned to work at the end of treatment. Gender, age, type of worker and type of treatment were independently associated with the ability to work after diagnosis. At the end of treatment these factors were age, education, tumour stage, overall response to the therapy, associated co-morbidity and sequelae of the disease or its treatment. Twenty-one percent noticed changes in their relationship with co-workers and managers, usually in the sense that they tried to be helpful. In a multivariate logistic regression analysis, the strongest predictors for remaining in employment were age, overall response and sequelae of the disease or its treatment. CONCLUSIONS: Cancer survivors in this study encountered some problems in returning to work, mainly linked to the sequelae of their disease and its treatment, rather than to discrimination by employers or colleagues. Prediction of working outcomes is possible to recommend interventions.

O sistema imunológico (II): importância dos imunomoduladores na recuperação do desportista / Immunological system (II): importance of immunomodulatory in the sportsman recovery

De uma forma geral, a atividade física produz processos de adaptação no organismo que são determinados pelo tipo, pela instenidade pela duração das cargas. Quando os processos de adaptação orgânica e muscular são insuficientes, ocorre a síndrome da fadiga. Esta não deve ser considerada somente como um fator negativo, já que a fadiga deve ser compreendida também como um sistema de alerta e um potente fator de mobilização dos recursos funcionais, o que a torna um poderoso elemento de adaptação. O surgimento da fadiga produz uma série de sinais e sintomas caracterizados por uma redução da força com hiperecitabilidade muscular, alterações metabólicas e eletrolíticas e alterações neuroendócrinas, todos esses fatores levando a uma redução do desempenho físico. Nessas condições é originado um grau importante de "estresse" físico e psíquico, com um grande comprometimento muscular (inflamação e lesão), que são mais evidentes à medida em que o estado de fadiga se prolonga. Essa situação de "estress" origina uma supressão de diversos índices da função imunológica. Por trás do período de recuperação, o surgimento tardio de hidroxiporlina excretada e a liberação tardia das enzimas CPK e LDH musculares sugerem uma lesão no tecido muscular. Por outro lado, o processo inflamatório inclui a participação de diversos fatores fisiopatolócigos: sanguíneos, imunológicos, tissulares, metabólicos e vasculares. A instauração de tratamentos com imunomoduladores pode prevenir e auxiliar na recuperação da inflamação e do dano tissular causado pelo extresse ao exercício intenso e mantido