Abstract Introduction Hemophagocytic syndromes (hemophagocytic lymphohistiocytosis, HLH) are characterized by a wide range of etiologies, symptoms, and outcomes, but have a common etiopathogenic ...pathway leading to organ damage: an excessive inflammatory response. Biological therapies have been proposed as a therapeutic option for refractory HLH, but have also been related to the development of HLH in severe immunosuppressed patients. Objectives and methods The purpose of this study was to analyze the clinical characteristics and outcomes of adult patients who developed HLH after receiving biological therapies. Results We identified 30 patients (29 from the PubMed search and one unpublished case), including 19 women and 11 men, with a mean age of 46.5 years. Underlying diseases consisted of rheumatologic/autoimmune diseases in 24 patients and hematological neoplasia in the remaining 6. Biological agents received before the development of HLH were mainly anti-TNF agents ( n = 19). Search for microorganisms confirmed systemic infection in 20 (67%) patients, including Mycobacterium tuberculosis ( n = 5), cytomegalovirus (CMV) ( n = 4), Epstein–Barr virus (EBV) ( n = 3), Histoplasma capsulatum ( n = 3), Escherichia coli ( n = 2), Staphylococcus aureus , Leishmania amastigotes and Brucella melitensis ( n = 1, respectively); viral infections were mainly reported in inflammatory bowel disease (IBD) patients. Patients with infections had more frequently received previous immunosuppressive therapies ( p = 0.036) and had lower leukocyte counts ( p = 0.020) in comparison with patients without associated infections. The outcome was described in 29 patients. After a mean follow-up of 6.3 months, 8 patients died (28%) and 6 had received anti-TNF agents. There was a high mortality rate in patients aged >65 years and those with tuberculosis (62% and 60%, respectively). Conclusions In patients receiving biological therapies who develop HLH, searching for a concomitant infectious process is mandatory, and specific surveillance for EBV/CMV infections (in patients with IBD) and for bacteria, including mycobacteria (in elderly patients receiving anti-TNF therapy), is recommended.
Summary
Three
HPLC
methods were optimised for the determination of citric acid, succinic acid and ascorbic acid using a photodiode array detector and fructose, glucose and sucrose using a refractive ...index in twenty eight citrus juices. The analysis was completed in <16 min. Two different harvests were taken into account for this study. For the season 2011, ascorbic acid content was comprised between 19.4 and 59 mg vitamin C/100 mL; meanwhile for the season 2012, the content was slightly higher for most of the samples ranging from 33.5 to 85.3 mg vitamin C/100 mL. Moreover, the citric acid content in orange juices ranged between 9.7 and 15.1 g L
−1
, while for clementines the content was clearly lower (i.e. from 3.5 to 8.4 g L
−1
). However, clementines showed the highest sucrose content with values near to 6 g/100 mL. Finally, a cluster analysis was applied to establish a classification of the citrus species.
A new calibration method for high-performance liquid chromatography was validated. The method was called single-injection calibration approach (SICA) because it allowed to obtain a complete ...calibration curve by means of a single injection of a standard solution containing several non-volatile and semi-volatile organic compounds at different concentration levels. The compounds studied included carboxylic acids, polyalcohols, carbohydrates and water-soluble vitamins. This method allowed a 1–7-fold reduction in the analysis time with regard to conventional calibration methods. The method was applied to three different chromatographic detection methods: refractive index (RI) detection, diode array detection (DAD) and inductively coupled plasma atomic emission detection (ICP-AED). Good linearity was achieved (
r
2
>
0.999) for the three detection methods but signal correction was required for RI detection and DAD. This fact demonstrated that ICP-AES was the most universal because the signal obtained for non-volatile and semi-volatile organic compounds was not a function of the chemical nature of the compound and only depended on the mass content of carbon. The method was validated by analyzing a reference non-fat milk powder sample as well as several real food samples (three fruit juices, four wines, three candies and a multivitamin complex).
Clinical depression (MDD) has been associated with poor prognosis in patients with coronary heart disease (CHD). Possible pathophysiologic pathways linking depression and CHD that have received ...attention recently include immune-inflammatory abnormalities, lifestyle attitudes, and autonomic nervous system dysfunction. MDD is characterized by circadian abnormalities and CHD onset displays a diurnal rhythm, but to our knowledge the influence of depression on the circadian rhythm of cardiac autonomic activity has not been studied among acute CHD patients in a prospective manner.
Modern civilization depends on only a few plant species for its nourishment. These crops were derived via several thousands of years of human selection that transformed wild ancestors into ...high-yielding domesticated descendants. Among cultivated plants, common bean (Phaseolus vulgaris L.) is the most important grain legume. Yet, our understanding of the origins and concurrent shaping of the genome of this crop plant is limited.
We sequenced the genomes of 29 accessions representing 12 Phaseolus species. Single nucleotide polymorphism-based phylogenomic analyses, using both the nuclear and chloroplast genomes, allowed us to detect a speciation event, a finding further supported by metabolite profiling. In addition, we identified ~1200 protein coding genes (PCGs) and ~100 long non-coding RNAs with domestication-associated haplotypes. Finally, we describe asymmetric introgression events occurring among common bean subpopulations in Mesoamerica and across hemispheres.
We uncover an unpredicted speciation event in the tropical Andes that gave rise to a sibling species, formerly considered the "wild ancestor" of P. vulgaris, which diverged before the split of the Mesoamerican and Andean P. vulgaris gene pools. Further, we identify haplotypes strongly associated with genes underlying the emergence of domestication traits. Our findings also reveal the capacity of a predominantly autogamous plant to outcross and fix loci from different populations, even from distant species, which led to the acquisition by domesticated beans of adaptive traits from wild relatives. The occurrence of such adaptive introgressions should be exploited to accelerate breeding programs in the near future.
The oligoelements Guardia, M De La; Garrigues, Salvador; de la Guardia, Miguel
Handbook of Mineral Elements in Food,
2015, 2015-02-20
Book Chapter
The role of trace elements in human nutrition is well recognized by public health agencies, nutritionists and researchers from various areas of knowledge. Humans require several inorganic elements as ...components of the diet. Some of the inorganic elements are required in extremely small quantities, only micrograms per day, while other elements may be needed in higher amounts. A lack, or an insufficient amount, of a nutrient can result in a deficiency disease which can be life‐threatening in extreme cases. The essential nutrients are widely distributed in foods and most people can obtain sufficient amounts by consuming a varied diet. This chapter draws attention to some of the important and unique aspects of the oligoelements, addressed within the context of trace element intake, from deficiency to toxicity. A notable feature is the large number (17) of nutrients discussed: arsenic, boron, chromium, cobalt, copper, fluoride, iodine, iron, magnesium, manganese, nickel, molybdenum, selenium, sulfur, tin, vanadium and zinc. Also, considerable attention is given to the interaction between some of these nutrients, their physiological role (functions) and the enzymes containing these elements. Trace elements recently found to be essential are discussed, along with new ways of conceptualizing the application of nutrient requirements.
Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods to quantify total lurbinectedin, its plasma protein binding to derive the unbound fraction and its main ...metabolites 1',3'-dihydroxy-lurbinectedin (M4) and N-desmethyl-lurbinectedin (M6) in human plasma, were developed and validated.
For lurbinectedin, sample extraction was performed using supported liquid extraction. For metabolites, liquid-liquid extraction with stable isotope-labeled analogue internal standards was used. Plasma protein binding was evaluated using rapid equilibrium dialysis. In vitro investigations at different plasma protein concentrations were carried out to estimate dissociation rate constants to albumin and alpha-1-acid glycoprotein (AAG).
Calibration curves displayed good linearity over 0.1 to 50 ng/mL for lurbinectedin and 0.5 to 20 ng/mL for the metabolites. Methods were validated in accordance with established guidance. The inter-day precision and accuracy ranged from 5.1% to 10.7%, and from -5% to 6% (lurbinectedin in plasma); from 3.1% to 6.6%, and from 4% to 6% (lurbinectedin in plasma:PBS); from 4.5% to 12.9%, and from 4% to 9% (M4); and from 7.5% to 10.5%, and from 6% to 12% (M6). All methods displayed good linearity (r2 >0.99). Recovery was evaluated for lurbinectedin in plasma:PBS (66.4% to 86.6%), M4 (7.82% to 13.4%) and M6 (22.2% to 34.3%). The method for lurbinectedin in plasma has been applied in most clinical studies, while the plasma:PBS and metabolites methods were used to evaluate the impact of special conditions on lurbinectedin PK. Lurbinectedin plasma protein binding was 99.6% and highly affected by AAG concentration.
These UPLC-MS/MS methods enable the rapid and sensitive quantification of lurbinectedin and its main metabolites in clinical samples.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Patients with major depression or borderline personality disorder display similar peripheral autonomic stress response.•Central processing abnormalities are different in major depression and ...borderline personality disorders.•The present findings might help discern diverse pathophysiological mechanisms in two syndromes with a significant clinical overlap.
Major depressive disorder (MDD) and borderline personality disorder (BPD) are highly prevalent and often comorbid psychiatric conditions, with abnormal processing of negative affect resulting from psychological stress. Characteristics of central processing of autonomic response to stress in each disorder are not clearly settled.
We obtained whole brain 3T fMRI with concurrent skin conductance, respiration rate, and heart rate variability measures in a cohort of MDD (N=19), BPD (N=19) patients, and healthy (N=20) individuals. Experiments were conducted in resting conditions, during a control mental arithmetic task, during highly stressful mental arithmetic, and in the period immediately following psychological stress.
Widespread activation of central autonomic network (CAN) structures was observed during stress compared to a control task in the group of healthy participants, whereas CAN activation during stress was less intense in both BPD and MDD. Both patient groups displayed increased sympathetic and decreased parasympathetic activation compared to healthy subjects, as previously reported. The relationship between peripheral sympathetic or parasympathetic activity and simultaneous regional brain BOLD activity was similar in BPD patients and healthy subjects, and markedly different from that seen in MDD patients.
The sample size, the fact it belonged to a single study site, and low grade affective symptomatology in both patient groups limit the generalizability of the present findings.
The diverging neurobiological signature in the homeostatic response to stress in MDD and BPD possibly represents a heuristically valuable candidate biomarker to help discern MDD and BPD patients.
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A comparative study of hydrophobicity in diazepam (5) chlordizepoxide (6), buspirone (7) and four related pyrrolothieno-1,4-dizepine systems (1-4) has been carried out, using HPLC (RPC) technique. ...The capacity factors (K') of compounds studied have been measured in five different elution conditions (mobile phase in which the percentage of methanol varies). The capacity factors (K'
0
) corresponding to the absence of organic solvent in the mobile phase have been calculated. Correlations among hydrophobic parameters of series 1, 2, 3, and 4 have been established and K'
0
of compounds not yet synthesized have been calculated.
•Childhood adversity affects engagement of central autonomic components during effortful emotion regulation in patients with MDD.•Central-peripheral autonomic integration during cognitive reappraisal ...is abnormal in individuals with BPD.•Disruption of the central control of the autonomic response may underlie childhood-adversity related emotion dysregulation in MDD.
Adverse childhood experiences (ACEs) have lifelong effects on emotional behavior and are frequent in Borderline Personality Disorder (BPD) and Major Depressive Disorder (MDD). The Central Autonomic Network (CAN), which modulates heart rate variability (HRV), comprises brain regions that mediate emotion regulation processes. However, it remains unclear the effect of ACEs on CAN dynamics and its relationship with HRV in these disorders. We studied the effects of ACEs on the brain and HRV simultaneously, during regulation of psychological stress in 19 BPD, 20 MDD and 20 healthy controls (HC). Participants underwent a cognitive reappraisal task during fMRI with simultaneous ECG acquisition. ACEs exposure was associated with increased activity of CAN and salience network components in patients with MDD compared to BPD during cognitive reappraisal. A brain-autonomic coupling was found in BPD relative to HC during emotion regulation, whereby greater activity of left anterior cingulate and medial superior frontal gyrus areas was coupled with increased HRV. Results suggest that ACEs exposure is associated with a distinct activation of the CAN and salience network regions governing responses to psychological stress in MDD compared to BPD. These alterations may constitute a distinctive neurobiological mechanism for abnormal emotion processing and regulation related to ACEs in MDD.
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