Systemic oxidative stress in children with cystic fibrosis with bacterial infection including Pseudomonas Aeruginosa

IntroductionOxidative stress (OS) occurs in cystic fibrosis (CF).ObjectiveThe objective of this work is to evaluate the influence of bacterial infection on biomarkers of OS (catalase [CAT], glutathione peroxidade [GPx], reduced glutathione [GSH]), markers of oxidative damage (protein carbonyls [PC], thiobarbituric acid reactive substances [TBARS]), together with the nutritional status and lung function in children with CF.MethodsCross‐sectional study including CF group (CFG, n = 55) and control group (CG, n = 31), median age: 3.89 and 4.62 years, respectively. CFG was distributed into CFG negative bacteriology (CFGB−, n = 27) or CFG positive bacteriology (CFGB+, n = 28), and CFG negative Pseudomonas aeruginosa (CFGPa−, n = 36) or CFG positive Pseudomonas aeruginosa (CFGPa+, n = 19).ResultsCompared with CG, CFG (P = .034) and CFGB+ (P = .042) had lower body mass index‐for‐age z‐score; forced expiratory volume in the first second was lower in CFGB+ and CFGPa+ (both P < .001). After adjusting for confounders and compared with CG: CFG showed higher TBARS (P ≤ .001) and PC (P = .048), and lower CAT (P = .004) and GPx (P = .003); the increase in PC levels was observed in CFGB+ (P = .011) and CFGPa+ (P = .001) but not in CFGB− (P = .510) and CFGPa− (P = .460).ConclusionsThese results indicate a systemic OS in children with CF. The presence of bacterial infection particularly Pseudomonas aeruginosa seems to be determinant to exacerbate the oxidative damage to proteins, in which PC may be a useful biomarker of OS in CF.     

Metformin Decreases Circulating Androgen and Estrogen Levels in Nondiabetic Women With Breast Cancer

IntroductionDiabetic patients treated with metformin have a lower risk of developing BC or a better BC prognosis. Metformin might reduce cancer growth through direct antiproliferative effects or through indirect mechanisms, particularly the reduction of insulin. In a randomized study on nondiabetic BC patients in natural menopause with high testosterone levels, we observed a significant decrease in insulin and in testosterone levels with metformin 1500 mg/d compared with 1000 mg/d. We present the results of a new analysis of our study on the effect of metformin on the bioavailability of sex hormones.Patients and MethodsOne hundred twenty-four eligible women were initially invited to take metformin 500 mg/d for 3 months. The 108 women who completed the first 3 months continued the study using 1000 mg/d for 1 month. The women were then randomized into 2 groups, and, for the subsequent 5 months, 1 group increased the dose to 1500 mg/d, and the other group continued with 1000 mg/d.ResultsNinety-six women completed the study, 43 receiving metformin 1500 mg/day, and 53 receiving 1000 mg/day. The women receiving 1500 mg/d showed a greater and significant reduction of free testosterone (?29%) and estradiol (?38%), a borderline significant reduction of estrone and insulin-like growth factor-1, and a nonsignificant reduction of androstenedione. They also showed a nonsignificant increase of dehydroepiandrosterone sulfate.ConclusionMetformin does not interfere with the production of dehydroepiandrosterone sulfate. Besides, it decreases estradiol levels, basically through the reduction of testosterone. These hormonal changes might have clinical relevance.     

Effects of age and gender on neural correlates of emotion imagery

Mental imagery is part of people''s own internal processing and plays an important role in everyday life, cognition and pathology. The neural network supporting mental imagery is bottom‐up modulated by the imagery content. Here, we examined the complex associations of gender and age with the neural mechanisms underlying emotion imagery. We assessed the brain circuits involved in emotion mental imagery (vs. action imagery), controlled by a letter detection task on the same stimuli, chosen to ensure attention to the stimuli and to discourage imagery, in 91 men and women aged 14–65 years using fMRI. In women, compared with men, emotion imagery significantly increased activation within the right putamen, which is involved in emotional processing. Increasing age, significantly decreased mental imagery‐related activation in the left insula and cingulate cortex, areas involved in awareness of ones'' internal states, and it significantly decreased emotion verbs‐related activation in the left putamen, which is part of the limbic system. This finding suggests a top‐down mechanism by which gender and age, in interaction with bottom‐up effect of type of stimulus, or directly, can modulate the brain mechanisms underlying mental imagery.     

Clinical and biochemical approach to the neonate with a suspected inborn error of amino acid and organic acid metabolism

Disorders of amino acid and organic acid metabolism collectively represent a group of over 70 inherited diseases that are most frequently encountered in the neonatal period. A neonate with clinical symptoms caused by one of these disorders is a real clinical emergency, a situation complicated by the similarities to the manifestations seen in sepsis or asphyxia. Delay of diagnosis and proper treatment often results in severe morbidity and high mortality. The vast majority of these patients are likely to be transferred to a neonatal intensive care unit, suggesting that amino acid and organic acid biochemical screenings should be performed in these newborns routinely at admission. The analysis of amino acids and acylcarnitines in blood spots by tandem mass spectrometry has the potential to significantly improve the morbidity and mortality rates of metabolic disorders with neonatal presentation. In the case of disorders lacking an effective treatment, an early diagnosis could lead to proper genetic counseling of the parents and to the option of reliable prenatal diagnosis of future pregnancies. This review offers an updated summary of the clinical, biochemical, and therapeutic features of the aminoacidopathies and organic acidurias most likely to be encountered in neonatal clinical practice.     

An UPLC-MS/MS method for the determination of valproic acid in blood of a fatal intoxication case

Valproic acid (VPA) has been used as an anticonvulsant for the treatment of epilepsy. The authors present a fatal case involving a 45-year-old female, found dead lying in bed with empty tablets of Diplexil^® next to her. She was a chronic alcoholic and epileptic who had been under psychiatric treatment, having repeatedly demonstrated intent to commit suicide.A rapid method was developed and validated to determine VPA in blood by ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS) with electrospray ionization source in negative ion mode.The method involved sample treatment with phosphoric acid followed by solid-phase extraction. Chromatographic separation was achieved using an Acquity UPLC^® BEH (2.1 × 50 mm id, 1.7 μm) column and a mobile phase containing ammonium acetate and acetonitrile, at a 0.5 mL/min flow rate. Detection and quantification of VPA was achieved using multiple reaction monitoring (MRM). The MS/MS transitions used for monitoring were m/z 143.1–143.1 for valproic acid and m/z 296.1–205.0 for hydrochlorothiazide used as an internal standard (IS).The limit of quantification (LOQ) was 0.5 μg/mL and the method was linear in the concentration range of 0.5–100 μg/mL. The coefficients of variation obtained for accuracy and precision were less than 10% and the mean recovery was 95% for the three concentrations levels studied (5 μg/mL, 10 μg/mL and 50 μg/mL). Toxicological results showed high concentration of VPA (556 μg/mL) and therapeutic concentrations of tiapride, mirtazapine, oxazepam and nordiazepam. Blood sample analysis also revealed the presence of ethanol at a concentration of 1.34 g/L.A specific, selective and sensitive method for the determination of VPA in blood was developed and can be used in routine forensic investigation. Toxicological results led the pathologist to rule that death was due to an intoxication caused by the simultaneous ingestion of high VPA concentrations and alcohol, with a suicidal legal-medical etiology.     

Preparation of poly(MePEGCA-co-HDCA) nanoparticles with confined impinging jets reactor: experimental and modeling study

In this work, the biodegradable copolymer poly(methoxypolyethyleneglycolcyanoacrylate-co-hexadecylcyanoacrylate) is used to prepare nanoparticles via solvent displacement in a confined impinging jets reactor (CIJR). For comparison, nanoparticles constituted by the homopolymer counterpart are also investigated. The CIJR is a small passive mixer in which very fast turbulent mixing of the solvent (i.e., acetone and tetrahydrofuran) and of the antisolvent (i.e., water) solutions occurs under controlled conditions. The effect of the initial copolymer concentration, solvent type, antisolvent-to-solvent ratio, and mixing rate inside the mixer on the final nanoparticle size distribution, surface properties, and morphology is investigated from the experimental point of view. The effect of some of these parameters is studied by means of a computational fluid dynamics (CFD) model, capable of quantifying the mixing conditions inside the CIJR. Results show that the CIJR can be profitably used for producing nanoparticles with controlled characteristics, that there is a clear correlation between the mixing rate calculated by CFD and the mean nanoparticle size, and therefore that CFD can be used to design, optimize, and scale-up these processes.     

Detection of Apoptosis in Peripheral Blood Cells of 31 Subjects Affected by Down Syndrome Before and After Zinc Therapy

Thirty-one patients affected by Down syndrome (DS) were investigated to study the presence of apoptosis in peripheral blood cells in relation to the plasma levels of zinc. Twelve patients had undergone therapy with ZnSO₄, while the remaining 19 were untreated. The presence of programmed cell death was evaluated by means of electron microscopy, in situ nick translation (NT), and agarose gel electrophoresis of DNA. These approaches evidenced the presence of apoptosis in peripheral blood cells of patients before therapy with ZnSO₄, while after zinc supplementation there was a reduction in the number of apoptotic cells. These results suggest that the process of programmed cell death in peripheral blood cells of patients with Down syndrome is related to the plasma levels of zinc ion.     

Ecological-level associations between highly processed food intakes and plasma phospholipid elaidic acid concentrations: results from a cross-sectional study within the European prospective investigation into cancer and nutrition (EPIC)

Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.     

Chondroma of the mandibular condyle-relapse of a rare benign chondroid tumour after 5 years' follow-up: case report

Chondroma of the mandibular condyle is rare and its signs and symptoms can mimic those of patients with more common disorders of facial asymmetry or dysfunction of the temporomandibular joint (TMJ). We report a case of chondroma of the mandibular condyle that presented as temporomandibular pain with malocclusion, and which relapsed 5 years after the initial treatment. To our knowledge only 7 cases of chondroma of the mandibular condyle have been reported in the last 70 years. This case is the eighth.