Novel DFO-functionalized mesoporous silica for iron sensing. Part 2. Experimental detection of free iron concentration (pFe) in urine samples.

Successful in vivo chelation treatment of iron(III) overload pathologies requires that a significant fraction of the administered drug actually chelates the toxic metal. Increased mobilization of the iron(III) in experiments on animals or humans, most often evaluated from urinary output, is usually used as an assessment tool for chelation therapy. Alternatively, the efficiency of a drug is estimated by calculating the complexing ability of a chelating agent towards Fe(III). The latter is calculated by the pFe value, defined as the negative logarithm of the concentration of the free metal ion in a solution containing 10 μM total ligand and 1 μM total metal at a physiological pH of 7.4. In theory, pFe has to be calculated taking into account all the complexation equilibria involving the metal and the possible ligands. Nevertheless, complexation reactions in complex systems such as serum and urine may hardly be accurately modelled by computer software. The experimental determination of the bioavailable fraction of iron(III) in biological fluids would therefore be of the utmost relevance in the clinical practice. The efficiency of the therapy could be more easily estimated as well as the course of overload pathologies. In this context, the aim of the present work was the development of a sensor to assess the free iron directly in biological fluids (urine) of patients under treatment with chelating agents. In the proposed device (DFO-MS), the strong iron chelator deferoxamine (DFO) is immobilized on the MCM-41 mesoporous silica. The characterization of the iron(III) sorption on DFO-MS was undertaken, firstly in 0.1 M KNO3, then directly in urine samples, in order to identify the sorption mechanism. The stoichiometry of the reaction in the solid phase was found to be: with an exchange constant (average value) of log βex = 40(1). The application of DFO-MS to assess pFe in SPU (Simulating Pathology Urine) samples was also considered. The results obtained were very promising for a future validation and subsequent application of the sensor in samples of patients undergoing chelation therapy

Colorimetric detection, quantification and extraction of Fe(III) in water by acrylic polymers with pendant Kojic acid motifs

We synthesized a solid sensory material for the extraction, detection and quantification of iron(III) in aqueous media. The material is a film-shaped colorless polymer membrane that exhibits gel behavior. The Fe(III) extraction and sensing characteristics are imparted by a new monomer derived from a natural product (i.e., Kojic acid), which exhibits chelating properties toward Fe(III). The sorption of Fe(III) on the membrane in water has been thoroughly characterized, including the sorption kinetics, sorption isotherms and profiles as a function of the pH. Fe(III) sorption followed pseudo first-order kinetics and required approximately 30 min to reach equilibrium. The maximum sorption capacity was approximately 0.04 mmol/g, and the sorption isotherms are well modeled by the Langmuir equation. The complexes that were found in the solid phase are in good agreement with those previously identified in the aqueous phase. Moreover, the sorption is highly specific (i.e., a recognition process) and results from the formation of a colored complex (iron(III)-Kojic acid derivative moieties). Therefore, the colorless sensory membrane turns red upon immersion in aqueous solutions containing Fe(III). The color output allows for both the qualitative visual determination of the Fe(III) concentration as well as also titration of Fe(III) using a) a UV/vis technique (limit of detection of 3.6 × 10−5 M; dynamic range of five decades, lower concentration = 1.65 × 10−6 M) and b) a computer vision-based analytical chemistry approach via color definition of the sensory membrane (RGB parameters) obtained from an image recorded with a handy device (e.g., a smartphone) (limit of detection of 2.0 × 10−5 M).Spanish Ministerio de Economía y Competitividad-Feder(MAT2014-54137-R) and by the Consejería de Educación—Junta deCastilla y León (BU232U13)

Seven mutations of the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus

Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation in the Ins2 gene exhibits PNDM associated with pancreatic beta cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset, but rapidly declined over time. When these mutant proinsulins were expressed in HEK293 cells, we observed defects in insulin protein folding and secretion. In these experiments, expression of the mutant proinsulins was also associated with increased Grp78 protein expression and XBP1 mRNA splicing, 2 markers of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

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Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

Simple solid-phase spectrophotometric method for free iron(III) determination

A simple and rapid solid-phase spectrophotometric procedure to determine free Fe(III) in environmental and biological samples is proposed. In particular, a deferoxamine (DFO) self assembled monolayer on mesoporous silica (DFO SAMMS) is developed and here applied as a sensor for iron(III). The solid product became brownish when put in contact with iron(III) solutions; so an immediate application as colorimetric sensor is considered. In order to optimize the DFO SAMMS synthesis and to obtain the best product for iron(III) sensing, a factorial experimental design is performed selecting the maximum absorption at 425 nm as response. The robustness of the spectrophotometric method is also proved. Keywords: Free iron(III), Deferoxamine, Self assembled monolayer, Mesoporous silica, Solid-phase spectrophotometr

Simple solid-phase spectrophotometric method for free iron(III) determination.

AbstractA simple and rapid solid-phase spectrophotometric procedure to determine free Fe(III) in environmental and biological samples is proposed. In particular, a deferoxamine (DFO) self assembled monolayer on mesoporous silica (DFO SAMMS) is developed and here applied as a sensor for iron(III). The solid product became brownish when put in contact with iron(III) solutions; so an immediate application as colorimetric sensor is considered. In order to optimize the DFO SAMMS synthesis and to obtain the best product for iron(III) sensing, a factorial experimental design is performed selecting the maximum absorption at 425nm as response. The robustness of the spectrophotometric method is also proved

Surfactant kinetics in preterm infants on mechanical ventilation who did and did not develop bronchopulmonary dysplasia

Objective: To characterize surfactant kinetics in vivo in two groups of premature infants on different levels of mechanical ventilation and at different risk of developing bronchopulmonary dysplasia. Design: Controlled observational study in two independent groups of infants. Setting: Neonatal intensive care unit. Patients: Thirteen preterm infants (26 \ub1 0.5 wks, birth weight 801 \ub1 64 g) on high ventilatory setting and who finally all developed bronchopulmonary dysplasia (MechVentBPD), and eight (26 \ub1 0.5 wks, birth weight 887 \ub1 103 g) who had minimal or no lung Dis. and of whom none developed bronchopulmonary dysplasia (MechVentNoBPD). Measurements and Main Results: Endotracheal 13C-labeled dipalmitoyl-phosphatidylcholine was administered and subsequent measurements of the 13C enrichment of surfactant-disaturated phosphatidylcholine (DSPC) from serial tracheal aspirates were made by gas chromatography-mass spectrometry. We calculated disaturated phosphatidylcholine pharmacokinetic variables in terms of half-life and apparent pool size from the enrichment decay curves over time. DSPC concentration from tracheal aspirates was expressed as milligrams/milliliter epithelial lining fluid (ELF-DSPC). Data are presented as mean \ub1 SE. In MechVentBPD infants vs. MechVentNoBPD, ELF-DSPC was much reduced, 2.9 \ub1 0.6 vs. 9.4 \ub1 3.0 mg/mL ELF (p = .03), half-life was shorter, 19.4 \ub1 2.8 vs. 42.5 \ub1 6.3 hrs (p = .002), and apparent pool size larger, 136 \ub1 21 vs. 65.8 \ub1 16.0 mg/kg (p = .057). In MechVentBPD, apparent DSPC pool size positively correlated with mean airway pressure x F102 and inversely correlated with ELF-DSPC. ELF-DSPC was inversely correlated with mean airway pressure x F102. No significant correlations were found in the MechVentNoBPD group. Conclusions: MechVentBPD infants showed profound alteration of surfactant kinetics compared with preterm infants with minimal lung disease, and these alterations were correlated with severity of ventilatory support

No sign of proliferative retinopathy in 15 patients with permanent neonatal diabetes with a median diabetes duration of 24 years

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