Lipidomic signature of stroke recurrence after transient ischemic attack.

While TIA patients have transient symptoms, they should not be underestimated, as they could have an underlying pathology that may lead to a subsequent stroke: stroke recurrence (SR). Previously, it has been described the involvement of lipids in different vascular diseases. The aim of the current study was to perform a lipidomic analysis to identify differences in the lipidomic profile between patients with SR and patients without. Untargeted lipidomic analysis was performed in plasma samples of 460 consecutive TIA patients recruited < 24 h after the onset of symptoms. 37 (8%) patients suffered SR at 90 days. Lipidomic profiling disclosed 7 lipid species differentially expressed between groups: 5 triacylglycerides (TG), 1 diacylglyceride (DG), and 1 alkenyl-PE (plasmalogen) [specifically, TG(56:1), TG(63:0), TG(58:2), TG(50:5), TG(53:7, DG(38:5)) and PE(P-18:0/18:2)]. 6 of these 7 lipid species belonged to the glycerolipid family and a plasmalogen, pointing to bioenergetics pathways, as well as oxidative stress response. In this context, it was proposed the PE(P-18:0/18:2) as potential biomarker of SR condition.The observed changes in lipid patterns suggest pathophysiological mechanisms associated with lipid droplets metabolism and antioxidant protection that is translated to plasma level as consequence of a more intensive or high-risk ischemic condition related to SR.

Fetal exposure to tofacitinib during the first trimester: A healthy newborn case report.

INTRODUCTION: Preclinical studies with tofacitinib demonstrated teratogenic effects. Data about effects on human fetuses are limited and current recommendations are to immediately discontinue the treatment. Our purpose is to report a case of exposure to tofacitinib during the first trimester of pregnancy. CASE SUMMARY: A 40-year-old woman with psoriatic arthritis became pregnant during the first month of treatment with tofacitinib. Tofacitinib was interrupted immediately, and parents were informed about the possible risks of teratogenicity. At the end of pregnancy, our patient gave birth to a healthy newborn. CONCLUSION: All the available evidence of tofacitinib exposure during pregnancy in humans belongs to outcomes of unexpected pregnancies in the context of clinical trials and post-marketing cases. This case may contribute to enriching available data about teratogenic risks of tofacitinib exposure during pregnancy.

Antibodies elicited by the CaniLeish® vaccine: long-term clinical follow-up study of dogs in Spain.

The prevention of canine leishmaniosis in healthy dogs requires a multimodal approach combining repellents with an effective vaccine. A vaccine that modulates the cell-mediated immune response against the protozoan has been available in Europe since 2012 (CaniLeish®, Virbac, France). The aim of the present study was to monitor dogs vaccinated with CaniLeish® to examine the kinetics of the antibody response and the safety and tolerance of CaniLeish®. Dogs vaccinated with CaniLeish® were monitored for 12 months. In follow-up visits at baseline (primovaccination or annual booster) (Visit 1, V1), and 1 (V2), 4 (V3), 8 (V4) and 12 (V5) months later, we examined antibody response kinetics using two serology techniques (IFAT and Speed Leish K™). Tolerance to CaniLeish® and its safety were also monitored. Anti-L. infantum IgG antibodies were determined in 242 dogs (125 dogs after primovaccination (Group P) and 117 dogs after booster vaccination (Group B). In addition, 46, 22 and 19 dogs were followed for 2, 3 and 4 years, respectively. At baseline, 100% of dogs in Group P returned negative IFAT and Speed Leish K™ test results while 9.4% (11/117) in Group B tested IFAT positive though Speed Leish K™ negative. In subsequent visits, seropositivity was detected by IFAT in 31.2% (Group P) and 41% (Group B) of the dogs in V2; 16.8% (Group P) and 10.2% (Group B) in V3; 6.4% (Group P) and 8.5% (Group B) in V4; and 3.2% (Group P) and 5.9% (Group B) in V5. All dogs tested Speed Leish K™ negative except two, in which it was later confirmed by molecular testing that they were not infected. Adverse events that could be associated with the vaccine were detected in 20 out of 314 dogs (6.4%). The good clinical status of all dogs was confirmed in an exhaustive clinical exam and haemato-biochemical profile. The Canileish® vaccine was well-tolerated with exceptions that did not appear to be related to age, sex, race or size of vaccinated dogs. Anti-L. infantum antibodies were detected by IFAT in 31.9-40.3% of the dogs 1 month after vaccination, and these antibodies could still be detected in 3.2% of the dogs 1 year later. This means that veterinarians need to use other tools (eg. PCR) to correctly diagnose seropositive dogs.

Cerebrospinal fluid and blood lactate concentrations as prognostic biomarkers in dogs with meningoencephalitis of unknown origin.

Meningoencephalitis of unknown origin (MUO) is a common inflammatory disease of the central nervous system. Several studies investigated finding prognostic factors, but results are contradictory. The aim of this study was to determine the concentrations of blood lactate (Blood-L) and cerebrospinal fluid lactate (CSF-L) in dogs with MUO for prognostic purposes. A total of 45 dogs with MUO (MUO group) and 11 with idiopathic epilepsy (IE group) were included. In the MUO group, 22 dogs were treated with prednisolone + cytosine arabinoside, 17 with prednisolone ± cyclosporine, and six received no treatment. In the MUO group, there was a strong-moderate positive correlation between Blood-L and CSF-L (ρ = 0.63557; P < 0.0001), a strong-moderate negative correlation between survival and CSF-L (ρ= -0.50210; P < 0.0004), and a weak negative correlation between survival and Blood-L (ρ= -0.35685; P < 0.0220). Dogs with a favourable response to treatment at 1 month had lower initial concentrations of Blood-L and CSF-L (P < 0.0010; P < 0.0037), and those with a worse response had higher values (P < 0.0497; P < 0.0004). Dogs that remained stable with treatment showed lower CSF-L concentrations (P < 0.0013). Dogs with Blood-L>4 mmol/L (P < 0.03) and/or CSF-L> 4 mmol/L (P < 0.009) had lower survival rates with the latter also showing more severe signs, probably indicating severe neuronal damage. These findings suggest that concentrations of CSF-L and Blood-L in dogs with MUO could be used as prognostic indicators.

Visible-light photoelectrodegradation of diuron on WO3 nanostructures.

The degradation of pesticide diuron has been explored by photoelectrocatalysis (PEC) under visible light illumination using two different WO3 nanostructures, obtained by anodization of tungsten. The highest degradation efficiency (73%) was obtained for WO3 nanosheets synthesized in the presence of small amounts of hydrogen peroxide (0.05 M). For that nanostructure, the kinetic coefficient for diuron degradation was 133% higher than that for the other nanostructure (anodized in the presence of fluoride anions). These results have been explained by taking into account the different architecture and dimensions of the two WO3 nanostructures under study.

Comparison of cardiovascular risk factors in young Spanish men between the 1980s and after the year 2000. Data from the AGEMZA study.

INTRODUCTION AND OBJECTIVES: To investigate the cardiovascular risk profile of a sample of young Spanish men taken in the 1980s, the initial AGEMZA study cohort, and to compare the findings with those in another sample with similar characteristics taken after 2000. METHODS: The two AGEMZA study cohorts comprised young men who were resident at the Zaragoza General Military Academy, where they were studying as aspiring cadets. A descriptive study of each cohort was carried out and the participants' anthropometric characteristics, sporting and dietary habits, exposure to toxins, and biochemical and lipid profiles were analyzed. Data on the prevalence of various risk factors were obtained for each cohort and the coronary disease risk was estimated using the Framingham equation. RESULTS: Comparison of data on 248 subjects from the current cohort with data on 260 from the initial cohort showed the following significant changes: weight (+6.03 kg), body mass index (BMI) (+1.57), cholesterol (+12.46 mg/dL), low-density lipoprotein cholesterol (+15.8 mg/dL), high-density lipoprotein cholesterol (-4.11 mg/dL), triglycerides (+3.64 mg/dL), apolipoprotein B (+24.8 mg/dL), estimated coronary disease risk in the next 10 years (+1/1000 individuals) and estimated coronary disease risk up to the age of 65 years (+23/1000 individuals). There were significant correlations between increases in weight and BMI and lipid profile alterations. CONCLUSIONS: The lipid profile and BMI were worse in the current sample. These findings make it essential that preventive measures for young people should be introduced and that an increased effort should be made to develop programs aimed at either stopping the progressive rise in obesity or even preventing it altogether.

Comparación de los factores de riesgo cardiovascular de jóvenes españoles de los años ochenta y tras el 2000. Datos del estudio AGEMZA / Comparison of cardiovascular risk factors in young spanish men between the 1980s and after the year 2000. Data from the AGEMZA study

Introducción y objetivos. Analizar el perfil de riesgo cardiovascular de una muestra de jóvenes varones españoles de los años ochenta, cohorte inicial del estudio AGEMZA, y compararla con otra muestra de similares características, tras el 2000. Métodos. Las dos muestras de AGEMZA están compuestas por varones jóvenes residentes en la Academia General Militar de Zaragoza, donde estudiaban en calidad de cadetes aspirantes. Realizamos un estudio descriptivo de cada cohorte, analizando datos antropométricos, hábitos deportivos, dietéticos y tóxicos y sus perfiles bioquímico y lipídico. Obtuvimos datos de la prevalencia de los diferentes factores de riesgo en cada una de ellas y estimamos el riesgo coronario para las dos cohortes mediante la ecuación de Framingham. Resultados. Comparamos datos de 260 sujetos de la muestra inicial y de 248 de la muestra actual, de lo que se obtuvo las siguientes variaciones significativas: peso (+6,03 kg), IMC (+1,57), colesterol total (+12,46 mg/dl), colesterol de las lipoproteínas de baja densidad (+15,8 mg/dl), colesterol de las lipoproteínas de alta densidad (-4,11 mg/dl), triglicéridos (+3,64 mg/dl) y apolipoproteína B (+24,8 mg/dl), el riesgo coronario estimado en los próximos 10 años (+1/1.000 sujetos) y el proyectado a los 65 años de edad (+23/1.000 sujetos). Los aumentos de peso y del IMC se correlacionan de forma significativa con los cambios encontrados en el perfil lipídico. Conclusiones. La muestra actual tiene peor perfil lipídico e IMC. Estos resultados nos obligan a tomar medidas preventivas en los jóvenes y extremar el desarrollo de campañas destinadas a frenar este aumento progresivo de la obesidad y para prevenir su aparición (AU)

Introduction and objectives. To investigate the cardiovascular risk profile of a sample of young Spanish men taken in the 1980s, the initial AGEMZA study cohort, and to compare the findings with those in another sample with similar characteristics taken after 2000. Methods. The two AGEMZA study cohorts comprised young men who were resident at the Zaragoza General Military Academy, where they were studying as aspiring cadets. A descriptive study of each cohort was carried out and the participants' anthropometric characteristics, sporting and dietary habits, exposure to toxins, and biochemical and lipid profiles were analyzed. Data on the prevalence of various risk factors were obtained for each cohort and the coronary disease risk was estimated using the Framingham equation. Results. Comparison of data on 248 subjects from the current cohort with data on 260 from the initial cohort showed the following significant changes: weight (+6.03 kg), body mass index (BMI) (+1.57), cholesterol (+12.46 mg/dL), low-density lipoprotein cholesterol (+15.8 mg/dL), high-density lipoprotein cholesterol (-4.11 mg/dL), triglycerides (+3.64 mg/dL), apolipoprotein B (+24.8 mg/dL), estimated coronary disease risk in the next 10 years (+1/1000 individuals) and estimated coronary disease risk up to the age of 65 years (+23/1000 individuals). There were significant correlations between increases in weight and BMI and lipid profile alterations. Conclusions. The lipid profile and BMI were worse in the current sample. These findings make it essential that preventive measures for young people should be introduced and that an increased effort should be made to develop programs aimed at either stopping the progressive rise in obesity or even preventing it altogether (AU)

Glial fibrillary acidic protein is a major target of glycoxidative and lipoxidative damage in Pick's disease.

Pick's disease is a subset of fronto-temporal dementia characterised by severe atrophy of the temporal and frontal lobes due to marked neuronal loss accompanied by astrocytic gliosis enriched in glial acidic protein. The remaining neurones have intracytoplasmic inclusions composed of hyperphosphorylated tau, called Pick bodies, in addition to hyperphosphorylated tau in astrocytes and oligodendrocytes. Gel electrophoresis and western blotting using markers of glycoxidation (advanced glycation end products, N-carboxyethyl-lysine and N-carboxymethyl-lysine: AGE, CEL, CML, respectively) and lipoxidation (4-hydroxy-2-nonenal: HNE, and malondialdehyde-lysine: MDAL) were used in the frontal and occipital cortex in three Pick's disease cases and three age-matched controls. In Pick's disease, increased AGE, CML, CEL, HNE and MDAL bands of about 50 kDa were observed in the frontal cortex (but not in the occipital cortex) in association with increased density of glial acidic protein bands. Bi-dimensional gel electrophoresis and western blotting also disclosed increased amounts and numbers of glial acidic protein isoforms in the frontal cortex in Pick's disease. Moreover, redox proteomics showed glycoxidation, as revealed with anti-CEL antibodies and lipoxidation using anti-HNE antibodies, of at least three glial acidic protein isoforms. The present results demonstrate that glial acidic protein is a target of oxidative damage in the frontal cortex in Pick's disease.

Evidence for the Maillard reaction in rat lung collagen and its relationship with solubility and age.

This study investigated age-related changes in collagen solubility and collagen-linked fluorescence, and their relationship with the Maillard reaction. As a result of the collagen purification of rat lung samples, we obtained two pools of collagen with different degrees of solubility. The relative distribution of collagen between these two fractions was time-dependent, and the proportion of the smaller and less soluble fraction increased with time (r = 0.73, P < 0.0001). In this fraction, the intensity of fluorescence at Exc 335 nm/Em 385 nm, and the total amount of pentosidine increased with age (r = 0.66, P < 0.002, and r = 0.69, P < 0.01, respectively). The mean values for fluorescence and pentosidine per milligram of collagen were, respectively, six and ten times greater in the less soluble fraction. In this fraction the pentosidine per milligram of collagen increased with age (r = 0.59, P < 0.03). Our results demonstrated the presence of pentosidine in rat lung collagen. Moreover, its accumulation in the less soluble fraction suggested a relationship between Maillard reaction products, physico-chemical changes in collagen solubility, and the ageing process in rat lungs.

Chromatographic evidence for Amadori product formation in rat liver aminophospholipids.

This work presents data which indicates the presence of Amadori product derived from Maillard reaction in aminophospholipids. The presence of 5-HMF, a stable derivative of acid-treated Amadori product, in the phospholipidic fraction from cell membranes was established by HPLC-UV and subsequent GC/MS analysis. The assay for 5-HMF in rat liver phospholipid revealed the presence of this molecule in membrane phospholipids of euglycemic rats, and showed increased glycation levels in membrane phospholipids from streptozotocin-induced diabetic rats (p < 0.001). This gives a new insight to cell membrane physiology and physiopathology.

Age-related fluorescence in rat lung collagen.

Mechanical lung properties are impaired with age. In other organs an age-related increase in collagen-linked fluorescence, attributable to advanced glycation endproducts (AGE), or other nonenzymatic reactions such as those related to lipid peroxidation derivatives has been described. Moreover, oxidative processes accelerate some of these reactions. In several tissues, these AGE products have been found to be responsible for protein cross-linking and lack of elasticity. We have evaluated the fluorescence levels of lung collagen in rats aged from 1 to 25 months at two distinct wavelengths: the standard AGE fluorescence (Exc 370 nm/Em 440 nm) and the pentosidine fluorescence (Exc 335 nm/Em 395 nm). In pulmonary tissue fluorescence at both 370/440 nm (p < 0.05) and 335/395 nm (p < 0.001) increases with age. However, a relative stabilization of values is seen in the 25 months group that could be related to the kinetics of fluorescent products in vivo. So, as observed in other tissues, AGE products may increase in pulmonary tissues with time. This may explain the age-associated decline in pulmonary compliance.

Mechanisms of glycation in atherogenesis.

Non-enzymatic glycation may affect the arterial wall altering its connective tissue and promoting LDL accumulation. Its recognition by specific receptors and growth factor release, as well as possible alteration of DNA, may stimulate smooth muscle cell proliferation. Free radical generation may favour non-enzymatic PUFA degradation and quench NO, which would alter vascular relaxation. All of these aspects may participate in atherogenesis.