IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP) located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and also the influence of this SNP in the secretion of IFN-γ <it>in vitro</it>.</p> <p>Methods</p> <p>Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). <it>Leishmania</it>-induced IFN-γ production on peripheral blood mononuclear cell (PBMC) culture supernatants was assessed by ELISA.</p> <p>Results</p> <p>There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers.</p> <p>Conclusion</p> <p>Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.</p

IL10 Haplotype Associated with Tuberculin Skin Test Response but Not with Pulmonary TB

Evidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed to Mycobacterium tuberculosis, among them 129 individuals lacking a tuberculin skin test (PPD) response, we genotyped four IL10 promoter variants at positions −2849 , −1082 , −819 , and −592 and reconstructed the haplotypes. The IL10 low-producer haplotype −2849A/−1082A/−819C/−592C, compared to the high-producer haplotype −2849G/−1082G/−819C/−592C, occurred less frequent among PPD-negative controls than among cases (OR 2.15, CI 1.3–3.6) and PPD-positive controls (OR 2.09, CI 1.2–3.5). Lower IL-10 plasma levels in homozygous −2849A/−1082A/−819C/−592C carriers, compared to homozygous −2849G/−1082G/−819C/−592C carriers, were confirmed by a IL-10 ELISA (p = 0.016). Although we did not observe differences between the TB patients and all controls, our results provide evidence that a group of individuals exposed to M. tuberculosis transmission is genetically distinct from healthy PPD positives and TB cases. In these PPD-negative individuals, higher IL-10 production appears to reflect IL-10-dependent suppression of adaptive immune responses and sustained long-term specific anergy

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Experimental study on leukocyte inf"tltration of tonsils during the acute crisis of the pultácea tonsillitis in children: Therapeutic implications about the modulation of the inflammation

La infección de garganta es uno de los problemas más comunes durante la infancia. El Streptococcus pyogenes está presente en la mayoría de los casos de amigdalitis pultácea. El propósito de este estudio ha sido profundizar en el conocimiento de la respuesta inmune durante la crisis aguda y el período intercrisis de la amigdalitis pultácea. Veinte niños se diagnosticaron de amigdalitis aguda recurrente (más de 4 brotes por año durante más de 1 año) con indicación de amigdalectomía con o sin adenoidectomía. Durante la crisis aguda de la amigdalitis pultácea apareció leucocitosis con neutrofilia y cultivos positivos para Streptococcus pyogenes en el 55% de los casos. También se constató un aumento importante de la tasa de anticuerpos antiestreptolisina O y antidesoxirribonucleasa B, durante la evolución del proceso. La infiltración leucocitaria amigdalar durante la crisis aguda fue a expensas de neutrófilos (incrementaron 23 veces), eosinófilos (incrementaron 18 veces) basófilos (incrementaron 10 veces) y monocitos (incrementaron 5 veces) cuando se compararon con los leucocitos amigdalares del período intercrisis, existiendo un incremento mucho más importante de la infiltración de basófilos (incrementaron 40 veces) en amígdalas durante la crisis aguda, cuando se comparó con los leucocitos de sangre periférica de la misma crisis aguda. En la respuesta inmune amigdalar aguda juegan un papel primordial las células inflamatorias: neutrófilos, eosinófilos, basófilos y monocitos. A la vista de los hallazgos presentados, proponemos tratamientos racionales de la amigdalitis pultácea a través de la modulación de la inflamación, aparte de su tratamiento antibiótico, lo que requiere hasta su completa validación más trabajo experimental y clínico

Characterization of concrete from Roman buildings for public spectacles in Emerita Augusta (Mérida, Spain)

The aim of this work is to characterize the original concrete from Roman buildings for public spectacles, theatre and amphitheatre, from Emerita Augusta, Mérida, Spain. An advanced knowledge of the Roman concrete composition is required for a reliable restoration and preservation of these ancient monuments. The concrete was studied through mineralogical (optical polarized microscopy and X-ray diffraction) and petrophysical (bulk and real density, open porosity to water and Hg, mechanical strength and ultrasonic velocity) analyses. With this work, it is possible to fill the gap that exists in this field and the characterization of the materials used in the Roman concrete from these two buildings, never previously studied, despite the significance of this archaeological ensemble, declared a World Heritage Site by UNESCO in 1993. The results allowed us to determine the composition of the Roman concrete and to infer the provenance of the aggregates used in these monuments.Funding for this study was provided by the Autonomous Community of Madrid under the following programmes: CLIMORTEC (National Project BIA2014-53911-R) from the Ministry of Economy and Competitiveness, GEOMATERIALES 2 (S2013/MIT-2914) and the Operational Programme for Cross-Border Cooperation: Spain-Portugal (POCTEP-RITECA) 2007-2013.Peer reviewe

Changes in the Expression of Vascular Endothelial Growth Factor after Fetal Tracheal Occlusion in an Experimental Model of Congenital Diaphragmatic Hernia

Introduction. Vascular endothelial growth factor (VEGF), an angiogenic factor secreted by type II pneumocytes, could play a role in congenital diaphragmatic hernia (CDH) pathogenesis. Animal studies suggest that VEGF accelerates lung growth. Aim. To quantify VEGF on fetal lungs in a nitrofen rat model for CDH and to analyze the effect of tracheal occlusion (TO) in VEGF in fetal lung rats after nitrofen and in control rats not exposed to nitrofen. Methods. Pregnant rats received nitrofen on day 9.5 of gestation. Fetuses were divided into 2 groups: those that underwent TO on day 20 and those that did not. On day 21, fetuses were delivered, and the lungs were dissected for subsequent VEGF quantification. Results. CDH was detected in 43% of the fetuses that received nitrofen. Fetuses with CDH showed significantly reduced lung weight/fetal weight ratio and lower VEGF levels than the remainder. A higher VEGF value was observed after TO. Conclusions. VEGF protein was significantly lower in fetuses with CDH. TO induced a significant increase in VEGF compared to the fetuses that did not undergo TO. Although not statistically significant, we observed higher VEGF levels in fetuses with CDH and TO compared to fetuses with CDH and no further intervention

Interleukin-1 receptor antagonist gene polymorphism and mortality in patients with severe sepsis

This study aims to determine the influence of the polymorphism within the intron 2 of the interleukin-1 receptor antagonist gene (IL-1RN*) on the outcome of severe sepsis, and to assess its functional significance by correlating this polymorphism with the total production of interleukin-1 receptor antagonist (IL-1Ra) protein determined in stimulated peripheral blood mononuclear cells (PBMC). A group of 78 patients with severe sepsis (51 survivors and 27 nonsurvivors) was compared with a healthy control group of 130 blood donors, and 56 patients with uncomplicated pneumonia. We found a significant association between IL-1RN* polymorphism and survival. Thus, after adjusting for age and APACHE II score, multiple logistic regression analysis showed that patients homozygotes for the allele *2 had a 6·47-fold increased risk of death (95% CI 1·01–41·47, P = 0·04). Besides, compared with patients homozygous or heterozygous for the allele *1, IL-1RN*2 homozygotes produced significantly lower levels of IL-1Ra from their PBMC. Our results suggest that insufficient production of this cytokine might contribute, among other factors, to the higher mortality rate found in severe sepsis patients with the IL-1RN*2 homozygous genotype