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1.
Sci Rep ; 9(1): 11813, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413300

RESUMO

Sickle cell anaemia (SCA) is characterized by reduced red blood cell (RBC) deformability and nitric oxide (NO) bioavailability. The aim of the study was to investigate whether exercise might affect these parameters in SCA. SCA patients and healthy controls (AA) performed an acute submaximal exercise test until subjects reached the first ventilatory threshold (VT 1). Blood was sampled at rest and at VT 1. At rest, free haemoglobin level was higher and RBC count, haemoglobin and haematocrit were lower in SCA compared to AA. RBC deformability was lower in SCA. Exercise had no effect on the tested parameters. RBC NO level was higher in SCA compared to AA at rest and significantly decreased after exercise in SCA. This might be related to a reduction in RBC-NO synthase (RBC-NOS) activation which was only observed in SCA after exercise. Free radical levels were higher in SCA at rest but concentration was not affected by exercise. Marker for lipid peroxidation and antioxidative capacity were similar in SCA and AA and not affected by exercise. In conclusion, a single acute submaximal bout of exercise has no deleterious effects on RBC deformability or oxidative stress markers in SCA, and seems to modulate RBC-NOS signalling pathway.

2.
Ann Biol Clin (Paris) ; 77(4): 436-438, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31418705

RESUMO

Hyperthyroidism may be associated with several haematological disorders, including an increase in haemoglobin A2 level. We report the case of haemoglobin study in a 29-years old man of Mediterranean origin presenting microcytosis. Results showed a slight increase in haemoglobin A2 level, suggestive of a beta-thalassemia trait, which was finally related to the existence of a recently diagnosed Grave's disease.

3.
Pediatr Blood Cancer ; 66(10): e27934, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31322815

RESUMO

BACKGROUND: Our objective was to investigate the combined and differential effects of alpha-thalassemia -3.7 kb deletion and HbF-promoting quantitative trait loci (HbF-QTL) in Senegalese hydroxyurea (HU)-free children and young adults with sickle cell anemia (SCA). PROCEDURE: Steady-state biological parameters and vaso-occlusive crises (VOC) requiring emergency admission were recorded over a 2-year period in 301 children with SCA. The age of the first hospitalized VOC was also recorded. These data were correlated with the alpha-globin and HbF-QTL genotypes. For the latter, three different genetic loci were studied (XmnI, rs7482144; BCL11A, rs1427407; and the HBS1L-MYB region, rs28384513) and a composite score was calculated, ranging from zero (none of these three polymorphisms) to six (all three polymorphisms at the homozygous state). RESULTS: A positive clinical impact of the HbF-QTL score on VOC rate, HbF, leucocytes, and C-reactive protein levels was observed only for patients without alpha-thalassemia deletion. Conversely, combination of homozygous -3.7 kb deletion with three to six HbF-QTL was associated with a higher VOC rate. The age of the first hospitalized VOC was delayed for patients with one or two alpha-thalassemia deletions and at least two HbF-QTL. CONCLUSION: Alpha-thalassemia -3.7 kb deletion and HbF-QTL are modulating factors of SCA clinical severity that interact with each other. They should be studied and interpreted together and not separately, at least in HU-free children.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31306111

RESUMO

BACKGROUND: Erythrocyte deformability is impaired in sickle cell disease (SCD). The regulation of cytoskeletal protein organization plays a key role in erythrocyte deformability. The activation of adenylyl cyclase (AC)/cAMP/Protein kinase A (PKA) signaling pathway was associated with increased deformability in healthy erythrocytes, however the role of this pathway in SCD is unknown. OBJECTIVE: We evaluated mechanical responses of sickle red blood cells under physiological levels of shear stress and the possible link between their deformability and AC/cAMP/PKA signaling pathway. METHODS: The shearing of sickle red blood cells at physiological level (5 Pa) and the measurement of deformability were performed by a laser assisted optical rotational cell analyzer (LORRCA). RESULTS: Red blood cell deformability increased of 2.5-6.5% by blocking the activity of phosphodiesterase with Pentoxifylline (10µM) (p < 0.05). The inhibition of AC with SQ22536 (100µM) produced more significant rise in deformability (+4.8-12%, p < 0.01). No significant change was observed by the inhibition of PKA with H89 (10µM). CONCLUSION: Pentoxifylline and SQ22536 increased the deformability of sickle red blood cells under fluid shear stress. Modulation of the AC/cAMP/PKA pathway could have the potential to be an effective therapeutic approach for SCD through shear-induced improvements of RBC deformability.

5.
Sci Rep ; 9(1): 6771, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043643

RESUMO

Osmotic gradient ektacytometry is the gold standard to assess red blood cell (RBC) deformability. It has been proposed that, when measured in isotonic condition, RBC deformability at low shear stress would depend on membrane elasticity while it would be influenced by internal viscosity when measured at high shear stress, but this hypothesis needs to be further addressed. Healthy RBCs were rigidified by treatment with lysolecithine (LPC), diamide or nystatine associated with hyperosmolar solutions (OSMO), which reduces membrane surface area, decreases membrane elasticity or promotes cell dehydration, respectively. Diamide treatment resulted in a decrease in isotonic RBC deformability at all shear stresses tested (i.e. from 0.3 to 30 Pa). LPC and OSMO treatments caused a decrease in isotonic RBC deformability above 3 Pa only. Isotonic RBC deformability from patients with hereditary spherocytosis or sickle cell disease was mainly decreased above 1.69 Pa. Our findings indicate that decreased isotonic RBC deformability at shear stresses above 3 Pa would be related to a reduction in the surface-area-to-volume ratio and/or to a loss of membrane elasticity and/or to an increase in internal viscosity while a decrease of RBC deformability below 3 Pa would reflect a loss of membrane elasticity.

6.
Hemoglobin ; 43(1): 50-51, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30700173

RESUMO

We report two members of a French family who are carriers of a rare hemoglobin (Hb) variant leading to erythrocytosis: Hb Saint Nazaire [ß103(G5)Phe→Ile; HBB: c.310T>A]. The proband is a 38-year-old woman referred to our institution for a moderate but persistent polycythemia without any clinical consequence. As her mother had a similar blood count, a diagnosis of a Hb variant with high oxygen affinity was proposed. The variant was difficult to detect by capillary electrophoresis (CE) and not distinguishable by high performance liquid chromatography (HPLC) and isoelectric focusing. Finally, a heterozygous mutation on the HBB gene corresponding to Hb Saint Nazaire was identified. This case report illustrates that this rare cause of erythrocytosis can be easily under or misdiagnosed unless several Hb separation techniques are used.

7.
PLoS One ; 14(2): e0212552, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30768636

RESUMO

Fasting glucose (FG) and glycated hemoglobin A1c (HbA1c) perform sub-optimally in people of African origin, especially in individuals with sickle-cell trait (SCT). The purpose of this study was to compare the relationships between HbA1c, FG, and fructosamine in individuals from Senegal with and without SCT. HbA1c, FG, and fructosamine were measured in 203 adults from Senegal (100 control: 45 with type 2 diabetes (T2D); 103 SCT: 51 with T2D). Significant, positive correlations were observed between HbA1c and FG, fructosamine and FG, and fructosamine and HbA1c in both groups. The limits of agreement were inappropriately large in both groups for the Bland-Altman plots of HbA1c and FG (control: -95.97 to 83.97%; SCT: -115.9 to 91.52%), fructosamine and FG (control: -100.6 to 99.89%; SCT: -105.6 to 100.6%), and fructosamine and HbA1c (control: -52.03 to 38.98%; SCT: -88.04 to 71.41%). In both groups, the greatest proportion of subjects were considered above the clinical cut-point for hyperglycemia when fructosamine was used as the criterion (control: 33%; SCT: 44.6%), and the lowest percentage of subjects were classified as over the clinical cut-point when HbA1c was used as the criterion (control: 21%; SCT: 27.7%).Substantial disparities between HbA1c, FG, and fructosamine were observed in both groups, and these differences were exaggerated in the SCT group. Therefore, these three biomarkers should not be considered to be interchangeable measures of glycemic control. These biomarkers should be used thoughtfully, and special care should be taken when using them in individuals with SCT.

8.
Clin Res Hepatol Gastroenterol ; 43(1): 77-81, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30612958

RESUMO

BACKGROUND: Alpha-1-antitrypsin deficiency (A1ATD) is a common genetic condition which predisposes to emphysema and liver disorders. It is estimated that 10-15% of homozygous individuals for the Z allele (PiZZ) may develop liver fibrosis. The optimal modalities to detect liver disease in PiZZ adult patients need to be defined. The aim of this prospective study was to perform a systematic non-invasive evaluation of the liver fibrosis by elastometry using Fibroscan® in a cohort of A1ATD patients with emphysema. METHODS: Patients followed in our respiratory unit were enrolled in this prospective study and underwent on the same day a physical examination, a biochemical profiling, an abdominal ultrasound (US) and a Fibroscan®. RESULTS: Twenty-nine PiZZ adults (19 male) were included. Median age was 50.4 yrs (21.5-67.2). Median serum A1AT level was 0.20 g/L (0.15-0.33). Liver Function Tests (LFT) were not normal in 2 patients and US was abnormal in 6 patients. Two patients had both abdnormal LFT and US. Fibroscan® was technically feasible in 28/29 (97%) patients. Median liver stiffness was 4.5 kPa (2.8-32.8), and was > 7.2 kPa in 5/28 (18%) and > 14 kPa in 2/28 (7%) patients. Liver stiffness was increased in 2/2 (100%) patients with abnormal LFT and US, in 1/4 (25%) with abnormal LFT or US and in 2/22 (10%) patients with normal LFT and US. CONCLUSIONS: Fibroscan® is an easy and repeatable tool which can be used in PiZZ patients to screen for the presence of significant liver fibrosis and to identify patients at higher risk to develop liver complications in the future and who may benefit from a closer surveillance.

10.
Liver Int ; 39(6): 1136-1146, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30589493

RESUMO

BACKGROUND & AIMS: To identify prognostic factors for liver disease in children with alpha-1 antitrypsin deficiency, irrespective of phenotype, using the DEFI-ALPHA cohort. METHODS: Retrospective, then prospective from 2010, multicentre study including children known to have alpha-1 antitrypsin blood concentration below 0.8 g/L, born in France since 1989. Clinical and biological data were collected. Liver disease was classified as "severe" (portal hypertension, liver failure, liver transplantation or death); "moderate" (persistent abnormal liver biology without portal hypertension); and "mild/none" (normal or almost normal liver biology and native liver). Prognostic factors for severe liver disease were evaluated using a Cox semiparametric model. RESULTS: In January 2017, 153 patients from 19 centres had been included; genotypes were PIZZ in 81.9%, PISZ in 8.1%, other in 10.0%. Mean ± SD follow-up was 4.7 ± 2.1 years. Half of patients had moderate liver disease. Twenty-eight children (18.3%) had severe liver disease (mean age 2.5 years, range: 0-11.6): diagnosis of alpha-1 antitrypsin deficiency was made before two months of age in 65.4%, genotypes were PIZZ in 25 (89.3%), PISZ in 2, PIMlike Z in 1, 15 children underwent liver transplantation, 1 child died at 3 years of age. Neonatal cholestasis was significantly associated with severe liver disease (P = 0.007). CONCLUSION: Alpha-1 antitrypsin-deficient patients presenting with neonatal cholestasis were likely to develop severe liver disease. Some patients with non-homozygous ZZ genotype can develop severe liver disease, such as PISZ and M variants, when associated with predisposing factors. Further genetic studies will help to identify other factors involved in the development of liver complications.

11.
Nitric Oxide ; 81: 28-35, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30342855

RESUMO

Hydroxyurea (HU) has been suggested to act as a nitric oxide (NO) donor in sickle cell anemia (SCA). However, little is known about the HU NO-related effects on red blood cell (RBC) physiology and NO signalling pathway. Thirty-four patients with SCA (22 under HU treatment (HU+) and 12 without (HU-)) and 17 healthy subjects (AA) were included. RBC nitrite content, deformability and reactive oxygen species (ROS) levels were measured. RBC NO-synthase (RBC-NOS) signalling pathway was assessed by the measurement of RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation. We also investigated the in vitro effects of Sodium Nitroprusside (SNP), a NO donor, on the same parameters in SCA RBC. RBC nitrite content was higher in HU+ than in HU- and AA. RBC deformability was decreased in SCA patients compared to AA but the decrease was more pronounced in HU-. RBC ROS level was increased in SCA compared to AA but the level was higher in HU- than in HU+. RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation were decreased in HU+ compared to HU- and AA. SCA RBC treated with SNP showed increased deformability, reduced ROS content and a decrease in AKT and RBC-NOS phosphorylation. Our study suggests that HU, through its effects on foetal hemoglobin and possibly on NO delivery, would modulate RBC NO signalling pathway, RBC rheology and oxidative stress.

12.
Diabetes Care ; 41(12): 2595-2602, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30327363

RESUMO

OBJECTIVE: The prevalence of type 2 diabetes (T2D) is rapidly increasing in sub-Saharan Africa, where sickle cell trait (SCT) is also frequent. Although SCT is generally considered a benign condition, evidence suggests that SCT could exaggerate vascular dysfunction in T2D. However, it remains unclear whether SCT could increase the risk of the development of T2D complications. Therefore, this study was conducted to determine whether T2D complications were more prevalent among Senegalese individuals with SCT and T2D than among those with T2D only. RESEARCH DESIGN AND METHODS: Rates of hypertension, retinopathy, peripheral neuropathy, peripheral artery disease, and impaired renal function as well as arterial stiffness, blood rheology, and concentrations of plasma advanced glycation end products (AGEs) and cytokines were compared between groups of Senegalese individuals with combined SCT and T2D (T2D-SCT) (n = 60), T2D (n = 52), SCT (n = 53), and neither T2D nor SCT (control) (n = 56). Human aortic endothelial cell (HAEC) expression of inflammatory and adhesion factors was measured after treatment with tumor necrosis factor-α and subjects' plasma. Effects of AGE inhibition or tiron on HAEC expression of E-selectin were measured. RESULTS: Retinopathy, hypertension, and reduced renal function were more prevalent, and arterial stiffness, blood viscosity at high shear rates, and thixotropic index were higher, in the SCT group compared with the other groups. Multivariable analysis showed that plasma AGE concentration was significantly associated with arterial stiffness. E-selectin expression was elevated in HAECs treated with T2D-SCT plasma compared with the other groups, but AGE inhibition reversed this. CONCLUSIONS: SCT could potentially augment the risk of the development of T2D-related complications, including retinopathy, nephropathy, and hypertension.

13.
Orphanet J Rare Dis ; 13(1): 161, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30223862

RESUMO

Alpha-1 antitrypsin deficiency is an autosomal co-dominant disorder caused by mutations of the highly polymorphic SERPINA1 gene. This genetic disorder still remains largely under-recognized and can be associated with lung and/or liver injury. The laboratory testing for this deficiency typically comprises serum alpha-1 antitrypsin quantification, phenotyping according to the isoelectric focusing pattern and genotyping if necessary. To date, more than 100 SERPINA1 variants have been described and new genetic variants are frequently discovered. Over the past 10 years, 22 new genetic variants of the SERPINA1 gene were identified in the daily practice of the University Medical laboratories of Lille and Lyon (France). Among these 22 variants, seven were Null alleles and one with a M1 migration pattern (M1Cremeaux) was considered as deficient according to the clinical and biological data and to the American College of Medical Genetics and Genomics (ACMG) criteria. Three other variants were classified as likely pathogenic, three as variants of uncertain significance while the remaining ones were assumed to be neutral. Moreover, we also identified in this study two recently described SERPINA1 deficient variants: Trento (p.Glu99Val) and SDonosti (p.Ser38Phe). The current data, together with a recent published meta-analysis, represent the most up-to-date list of SERPINA1 variants available so far.

14.
BMC Res Notes ; 11(1): 215, 2018 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-29609623

RESUMO

OBJECTIVES: Sickle cell anemia is due to a mutations on the betaglobin gene, inducing abnormal hemoglobin. In West Africa the main mutations lead to S or C types of hemoglobin. Patients with homozygote mutations seem protected against severe malaria, but not against mild disease. The prevalence of abnormal hemoglobin among patients attending dispensaries for mild malaria is thus unknown. A retrospective study was conducted to update data on the prevalence of S and C hemoglobin among patients attending dispensaries with mild malaria. Enrolment of patients was conducted during in vivo malaria treatment efficacy survey following the 42 days WHO protocol. A group of non-infected pregnant women and a group of patients with fever different from malaria, were also recruited in the same dispensaries. RESULTS: 794 blood samples were included. S and C genotypes were found in all the regions of Ivory Coast with the highest prevalence in the Northern region (S and C genotypes, 27%). In non-infected patients, prevalence of mutations was higher than in malaria patients. CONCLUSION: A high proportion of patients with mild malaria carried genetic hemoglobin disorder. This population of high risk must be better investigated to control treatment efficacy and to manage complications.


Assuntos
Anemia Falciforme/epidemiologia , Malária/epidemiologia , Complicações Parasitárias na Gravidez/epidemiologia , Adolescente , Adulto , Alelos , Anemia Falciforme/genética , Criança , Pré-Escolar , Comorbidade , Costa do Marfim/epidemiologia , Estudos Transversais , Feminino , Genótipo , Geografia , Hemoglobina C/genética , Hemoglobina Falciforme/genética , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Prevalência , Estudos Retrospectivos , Adulto Jovem
15.
Clin Hemorheol Microcirc ; 69(1-2): 207-214, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29630544

RESUMO

The aim of the present study was to compare blood rheological parameters between children with homozygous sickle cell disease (SS), sickle cell SC disease or S/ß+-thalassemia syndrome, and healthy children (AA) and to test the associations between blood rheology and the clinical severity in S/ß+-thalassemia. Sixty-two SS, 14 SC, 11 S/ß+-thalassemia and 12 healthy children participated in this study. Blood viscosity was measured with a cone-plate viscometer at 225 s-1. Red blood cell (RBC) deformability was measured by ektacytometry and RBC aggregation, by syllectometry. Nitric oxide and nitrotyrosine levels were determined for each child. While most of the hematological parameters were not different between SC and S/ß+-thalassemia children, we demonstrated that SC patients had lower RBC deformability and aggregation than S/ß+ individuals. Nitrotyrosine level, which indicates peroxynitrite production, was similar and lower in both healthy and S/ß+ compared to SS children. However, S/ß+-thalassemia children who experienced vaso-occlusive crises (VOC) in the 2 previous years had lower NOx and higher nitrotyrosine levels than those who never had VOC within the same period. These findings suggest that vascular function could be impaired in the most severe S/ß+-thalassemia children compared to the less severe one.


Assuntos
Óxido Nítrico/metabolismo , Reologia/métodos , Talassemia/sangue , Criança , Feminino , Humanos , Masculino , Síndrome , Talassemia/diagnóstico
16.
Clin Hemorheol Microcirc ; 68(2-3): 165-172, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29614630

RESUMO

This review focuses on the contribution of abnormal blood rheology in the pathophysiology of sickle cell anemia (SCA). SCA is characterized by a reduction of red blood cell (RBC) deformability but this reduction is very heterogeneous among patients. Recent works have shown that patients with the lowest RBC deformability (measured by ektacytometry) have enhanced hemolysis and would be more prone to develop several complications such as priapism, leg ulcers and glomerulopathy. In contrast, patients with the highest deformability, and not under hydroxyurea therapy, seem to develop more frequently vaso-occlusive like events. Although less studied, RBC aggregation properties are very different between SCA and healthy individuals and it was demonstrated that increased RBC aggregates strength could be involved in some complications. Finally, several studies have established that the vascular system of SCA patients could not fully compensate any increase in blood viscosity because of the loss of vascular reactivity, which may result in vaso-occlusive crises.


Assuntos
Anemia Falciforme/sangue , Deformação Eritrocítica/fisiologia , Reologia/métodos , Feminino , Humanos , Masculino
17.
J Pediatr ; 195: 228-235, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29449005

RESUMO

OBJECTIVES: To investigate the associations between several sickle cell disease genetic modifiers (beta-globin haplotypes, alpha-thalassemia, and glucose-6-phosphate dehydrogenase deficiency) and the level of oxidative stress and to evaluate the association between oxidative stress and the rates of vaso-occlusive events. STUDY DESIGN: Steady-state oxidative and nitrosative stress markers, biological variables, genetic modulators, and vaso-occlusive crisis events requiring emergency admissions were measured during a 2-year period in 62 children with sickle cell anemia (58 SS and 4 Sß0). Twelve ethnic-matched children without sickle cell anemia also participated as healthy controls (AA) for oxidative and nitrosative stress level measurement. RESULTS: Oxidative and nitrosative stress were greater in patients with sickle cell anemia compared with control patients, but the rate of vaso-occlusive crisis events in sickle cell anemia was not associated with the level of oxidative stress. The presence of alpha-thalassemia, but not glucose-6-phosphate dehydrogenase deficiency or beta-globin haplotype, modulated the level of oxidative stress in children with sickle cell anemia. CONCLUSION: Mild hemolysis in children with alpha-thalassemia may limit oxidative stress and could explain the protective role of alpha-thalassemia in hemolysis-related sickle cell complications.

18.
Hemoglobin ; 42(4): 217-224, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30604640

RESUMO

The aim of this study was to evaluate the clinical, biological and genetic factors that could be associated with the use and dose of morphine during hospitalization for vaso-occlussive crisis (VOC) in adults with sickle cell disease. Ninety-nine hospitalizations for acute VOC (58 sickle cell disease patients aged 18 to 60 years, one to six hospitalizations each) were recorded; we investigated the associations between qualitative and quantitative opioid requirements and several biological, clinical, epidemiological and genetic parameters. Visual analog pain scale (VAS) was the only independent predictor of the qualitative need for morphine (mean value of 8.5 vs. 6.1 for the 77 hospitalizations that required morphine). A higher total administered morphine dose, which relates mainly to the overall crisis severity, was associated with a lower hemoglobin (Hb) level at entry. The mean daily morphine dose, which is more influenced by the individual sensitivity to morphine, was not influenced by the studied genetic parameters [sickle cell disease type, α-thalassemia (α-thal) status, UGT2B7 and ABCB1 genotypes] but a very slight negative association was found with the total bilirubin (BIL) level at entry. Our study demonstrated that physicians are often reluctant to prescribe morphine in sickle cell disease as a VAS of 6 corresponds to the usual threshold of administration in other instances. Total Hb at entry was also associated for the first time with higher total morphine consumption and could be used in a predictive VOC severity score. These results have to be confirmed and completed on larger cohorts.


Assuntos
Anemia Falciforme/patologia , Morfina/administração & dosagem , Adolescente , Adulto , Anemia Falciforme/tratamento farmacológico , Hemoglobinas/análise , Hospitalização , Humanos , Pessoa de Meia-Idade , Morfina/uso terapêutico , Dor/tratamento farmacológico , Medição da Dor , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença , Adulto Jovem
19.
Scand J Trauma Resusc Emerg Med ; 25(1): 114, 2017 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-29178941

RESUMO

BACKGROUND: Following tissue injury after trauma, the activation of innate immune pathways results in systemic inflammation, organ failure and an increased risk of infections. The objective of this study was to characterize the kinetics of the S100A8/S100A9 complex, a new-recognized alarmin, as well as its soluble receptor sRAGE, over time after trauma as potential early biomarkers of the risk of organ damage. METHODS: We collected comprehensive data from consenting patients admitted to an ICU following severe trauma. The blood samples were taken at Day 0 (admission), Day1, 3 and 5 S100A8/A9 and sRAGE were measured by ELISA. Biomarkers levels were reported as median (IQR). RESULTS: Thirty-eight patients sustaining in majority a blunt trauma (89%) with a median ISS of 39 were included. In this cohort, the S100A8/A9 complex increased significantly over time (p = 0.001), but its levels increment over time (D0 to D5) was significantly smaller in patients developing infection (7.6 vs 40.1 mcg/mL, p = 0.011). The circulating level of sRAGE circulating levels decreased over time (p < 0.0001) and was higher in patients who remained in shock on day 3 (550 vs 918 pg/mL; p = 0.02) or 5 (498 vs 644 pg/mL; p = 0.045). Admission sRAGE levels were significantly higher in non-survivors (1694 vs 745 pg/mL; p = 0.015) and was higher in patients developing renal failure (1143 vs 696 pg/mL, p = 0.011). DISCUSSION: Our findings reveal an interesting association between the biomarker S100A8/9 least increase over time and the presence of infectious complication after trauma. We describe that the sRAGE decline over time is in relation with shock and markers of ischemic injury. We also confirm the association of sRAGE levels measured at admission with mortality and the development of renal failure. CONCLUSIONS: This work illustrates the importance of following the circulating level of biomarker overtime. The utilization of S1008/9 as a tool to stratify infection risk and trigger early interventions need to be validated prospectively.


Assuntos
Calgranulina A/sangue , Calgranulina B/sangue , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Traumatismo Múltiplo/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Adulto , Biomarcadores/sangue , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/complicações , Traumatismo Múltiplo/mortalidade , Risco , Fatores de Tempo , Adulto Jovem
20.
Liver Int ; 37(11): 1608-1611, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28887821

RESUMO

BACKGROUND & AIMS: Fifteen to twenty percent of alpha-1 antitrypsin deficiency patients (A1ATD) have a severe liver outcome (portal hypertension - PHT) during childhood. Since they all share the same ZZSERPINA1 genotype and that environmental factors such as alcohol cannot be advanced, the presence of modifier genes is now well recognized. SNPs located on the SERPINA1 and MAN1B1 genes have already been tested in very few studies with contradictory or not replicated results. METHODS: Our genotype-phenotype correlation study, performed on 92 ZZ children, aimed at determining once and for all if SERPINA1 and MAN1B1 polymorphisms may be implied in the onset of PHT. To do so, we also performed for the first time a complete haplotype reconstruction for data analysis. RESULTS: The two genetic associations with severe liver disease that had been suspected previously (one SNP for SERPINA1 and another for MAN1B1) were not confirmed in our cohort. Moreover, the haplotype analysis identified only one major genetic background for the SERPINA1 Z-allele, allowing us to exclude the presence of a frequent modifier SNP within. For MAN1B1, four major haplotypes were identified but the prevalence of PHT did not significantly differ between them. CONCLUSION: We conclude that genetic polymorphisms in these two genes probably do not influence the onset of severe liver disease in A1ATD.


Assuntos
Hipertensão Portal/genética , Manosidases/genética , Deficiência de alfa 1-Antitripsina/complicações , alfa 1-Antitripsina/genética , Alelos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , França , Estudos de Associação Genética , Haplótipos , Humanos , Lactente , Masculino , Polimorfismo de Nucleotídeo Único
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