Utilidad de los biomarcadores de inflamación e infección en los servicios de urgencias

Infectious processes account for 10% of patient seen in the emergency department. To administer antibiotics early, and before any other therapeutic-diagnostic decisions (complementary tests, microbiological samples, intensity of hemodynamic support, need for admission, etc.) have direct repercussions on the survival of patients with severe bacterial infections (bacteremia, severe sepsis or septic shock). In this context, the emergency department represents a critical level where the suspicion of infection and it diagnosis is made and treatment is started, and the progression and prognosis will be determined by the speed of this action. However, the clinical manifestations of infectious diseases are often non-specific and variable which makes early recognition of these patients and situations difficult. Inflammation and infection biomarkers have been around for years as helpful tools for improving emergency medical diagnoses and management of infection in the emergency department. The aim of this review is to summarize the published scientific evidence, in order to clarify the existing controversies, comparing the usefulness of the major biomarkers of inflammation and infection. It will alas suggest recommendations for their use in order to improve diagnosis, prognostic evaluation and management of infected patients in the emergency department.     

Tratamientos reparadores de la proteína CFTR en la fibrosis quística

Cystic fibrosis is a single gene, autosomal recessive disorder, in which more than 1,900 mutations grouped into 6 classes have been described. It is an example a disease that could be well placed to benefit from personalised medicine. There are currently 2 very different approaches that aim to correct the basic defect: gene therapy, aimed at correcting the genetic alteration, and therapy aimed at correcting the defect in the CFTR protein. The latter is beginning to show promising results, with several molecules under development. Ataluren (PTC124) is a molecule designed to make the ribosomes become less sensitive to the premature stop codons responsible for class i mutations. Lumacaftor (VX-809) is a CFTR corrector directed at class ii mutations, among which Phe508del is the most frequent, with encouraging results. Ivacaftor (VX-770) is a potentiator, the only one marketed to date, which has shown good efficacy for the class iii mutation Gly551Asp in children over the age of 6 and adults. These drugs, or a combination of them, are currently undergoing various clinical trials for other less common genetic mutations. In the last 5 years, CFTR has been designated as a therapeutic target. Ivacaftor is the first drug to treat the basic defect in cystic fibrosis, but only provides a response in a small number of patients. New drugs capable of restoring the CFTR protein damaged by the most common mutations are required.     

Colesterol e ictus: papel de los inhibidores de la proproteína convertasa subtilisina/kexina tipo 9

Introduction

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the modulation of plasma levels of low density lipoprotein cholesterol (LDLC). PCSK9 binds to the LDL receptor (LDLR), disrupts its endocytic recycling itinerary and directs it to lysosomal degradation. Activation of PCSK9 can thus decrease the expression of LDLR in the liver and inhibit LDL uptake, which leads to hypercholesterolaemia.

[Online First]Effect on rabbits’ intraocular structure by cross-linked hyaluronic formations as vitreous substitute

AIM: To develop a new material for retina filling and to investigate its effect on intraocular structure and histocompatibility in rabbit eyes. METHODS: The polymer-derived hyaluronic acid (HA) was formed by UV light cross-linked with N-vinyl-pyrrolidone. Vitrectomy was performed in the rabbits, and then cross-linked HA hydrogels at different concentrations were injected. Intraocular pressure measurements, cornea check-up, and B-ultrasound examination were performed during the follow-up period. After six weeks’ follow-up, the rabbits were sacrificed, and both eyes were removed for hematoxylin-eosin (HE) staining, and the polymer materials were observed under electron microscopy. RESULTS: The particle size of the cross-linked HA hydrogels was mainly around at 100 nm. After vitrectomy and injection into vitreous cavity, optical coherence tomography showed that the polymeric material HA had no significant effect on the overall thickness of the retina. The intraocular pressure returned to the normal level gradually at week 4. B-ultrasound results revealed that there is no significant change in the eye tissue given to HA material. The pathological and transmission electron microscopy results showed no obvious pathological change in the primary cells and rod cells under the retina tissue. CONCLUSION: HA-based cross-linked biopolymers has good biocompatibility in rabbit eyes, showing a promising potential as vitreous substitutes.     

Sequence polymorphisms of Plasmodium vivax ookinete surface proteins (Pvs25 and Pvs28) from clinical isolates in Korea

The Ookinete surface proteins of Plasmodium vivax (P. vivax), Pvs25 and Pvs28, were candidates for the transmission blocking vaccine (TBV), which exhibited great antigenic diversities among various isolates. Polymorphisms of these genes in the isolates from Republic of Korea (ROK) were analysed, which provided valuable baseline data for the field trials of TBV‐based vaccines. A total of 98 isolates were collected over 11 years from 1996 to 2007. pvs25 and pvs28 genes from the above isolates were amplified, sequenced and compared against Sal‐1 strain. Sequencing analysis of PCR products from P. vivax pvs25 revealed two allelic types, Q97T130 and E97/T130 alleles with the frequencies of 54.5% and 45.5%, respectively, in comparison with Sal I type sequence (E97/I130). From pvs28 gene, polymorphisms at M52L and T140S in the first and third EGF‐like domains in comparison to Sal‐1 strain were detected, respectively. Six GSGGE tandem repeats followed by GSGGDT or SSGGDT were identified at the end of the fourth EGF‐like domain in all Korean isolates. Interestingly, different tandem repeats of amino acid substitutions were observed from isolates collected after 2006 in comparison with preceding years. The ROK isolates revealed limited sequence polymorphisms in pvs25 and tandem repeats in pvs28 in comparison with reported isolates from other nations. Current observations suggested the rapid progresses of genetic changes among Korean isolates.     

NRBP1 modulates uric acid transporter ABCG2 expression by activating the Wnt/β-catenin pathway in HK-2 cells

BackgroundNuclear receptor binding protein 1 (NRBP1) and ATP-binding cassette subfamily G member 2 (ABCG2) was the gout risk gene and high-capacity urate exporter respectively. However, the relationship between NRBP1 and ABCG2 and the underlying molecular mechanism contributing to these associations are unknown.MethodsFirstly, the efficiency of the overexpression and knockdown of NRBP1 was confirmed by western blot. Next, the effect of NRBP1 overexpression and knockdown on the expression of ABCG2, organic anion transporter 1 (OAT1), glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) was detected by qRT-PCR and western blot. At the same time, the cellular location of ABCG2 and its expression after NRBP1 overexpression and knockdown was tested by immunofluorescence (IF) staining. Then, the mechanism of NRBP1 modulates ABCG2 expression was evaluated by western blot with or without the β-catenin inhibitor (21H7).ResultsThe lentivirus system was used to generate stable NRBP1 overexpression, while the plasmids carrying a NRBP1 siRNA was generated to knockdown NRBP1 expression in HK-2 cells. Meanwhile, the overexpression of NRBP1 significantly decreased the mRNAs and proteins expression of GLUT9 and URAT1, while the knockdown of NRBP1 increased the mRNAs and proteins expression of ABCG2 significantly. In addition, the NRBP1 modulates the expression of ABCG2 was by ctivating the Wnt/β-catenin pathway in HK-2 cells according to the IF and western blot results.ConclusionTaken together, our study demonstrated that NRBP1 inhibition played an essential role in attenuating hyperuricemia and gout by upregulation of ABCG2 via Wnt/β-catenin signaling pathway in HK-2 cells.     

Cetamina como adjuvante de bupivacaína em bloqueio do nervo infraorbitário para analgesia após correção de lábio leporino

Objectives

We conducted this study to investigate the safety and analgesic efficacy of the addition of Ketamine to Bupivacaine in bilateral extra‐oral infra‐orbital nerve block in children undergoing cleft lip surgeries.

Is Endocan a Novel Diagnostic Marker for the Severity of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants?

IntroductionEndocan levels were found to be associated with severity and mortality of the respiratory system diseases.ObjectiveWe aimed to figure out whether endocan was an important marker for the diagnosis, severity and follow-up of bronchopulmonary dysplasia (BPD).Materials and methodsInfants with moderate/severe BPD, and who required hydrocortisone treatment were included in the study group. Infants without BPD were allocated in the control group. Endocan levels were compared between the control group and the study group, and before and after the treatment in the study group.ResultsA total of 148 infants, 74 infants in the control group and 74 infants in the BPD group, were included. The endocan level was higher in the BPD group than in the control group (P = .001). Endocan levels before treatment in the BPD group was found to be higher than endocan level after treatment (P = .021).ConclusionOur study found that endocan levels increased in moderate/severe BPD. Serum endocan levels may be a safe and novel indicator for the follow-up of response to treatment and the prognosis of the severity of the disease.     

Níveis mais Baixos de Fetuína-A Sérica estão Associados a um Maior Risco de Mortalidade em Dez Anos em Pacientes com Infarto do Miocárdio por Supradesnivelamento do Segmento ST

BackgroundFetuin-A is an anti-inflammatory and anti-calcification factor involved in the course of coronary artery disease (CAD). In line with these functions, fetuin-A has been investigated as a cardiovascular risk marker in many studies. However, the association between fetuin-A and the prognosis of CAD patients is still controversial.ObjectivesThe present study was conducted to identify the association between serum fetuin-A level and long-term cardiovascular disease (CVD) and all-cause mortality of ST-elevation acute myocardial infarction (STEMI).MethodsOne hundred eigthy consecutive patients with STEMI were enrolled in the study. The study population was divided into subgroups (lower, ≤288 µg/ml; and higher, >288 µg/ml) according to the median fetuin-A level. Clinical follow-up data was obtained by annual contact with the patients or family members by telephone. The causes of death were also confirmed by the national health database. Two-sided p-values<0.05 were considered statistically significant.ResultsDuring a median follow-up of 10 years, 71 deaths were recorded , 62 of whom died from CVD. Both CVD and all-cause mortality were found to be significantly higher in the lower fetuin-A group than the higher fetuin-A group (44% vs 24%, p= 0.005; 48% vs 31%, p= 0.022, respectively). In Cox regression proportional hazard analyses, fetuin-A was found to be an independent predictor of CVD and all-cause mortality.ConclusionsLow fetuin-A concentration is associated with a poor long-term prognosis after STEMI, regardless of the traditional cardiovascular risk factors. Our findings have strengthened previous studies that consistently demonstrate the determining role of anti-inflammatory mediators in acute coronary syndromes.