The concept of "compartment allergy": prilocaine injected into different skin layers

We herein present a patient with delayed-type allergic hypersensitivity against prilocaine leading to spreading eczematous dermatitis after subcutaneous injections for local anesthesia with prilocaine. Prilocaine allergy was proven by positive skin testing and subcutaneous provocation, whereas the evaluation of other local anesthetics - among them lidocaine, articaine and mepivacaine - did not exhibit any evidence for cross-reactivity

Molecularly imprinted polypyrrole sensors for the detection of pyrene in aqueous solutions

Recently, electrochemical sensors have emerged as tools for polyaromatic hydrocarbons (PAH) detection that are cost-effective, easy to produce and use, highly selective and sensitive, and with good reproducibility. Polypyrrole may be easily produced from polymerization of pyrrole, by chemical as well as electrochemical methods, to produce dimensionally stable semi-conductive polymer materials, under mild synthesis conditions. In this study, polypyrrole was used as the stable molecular framework within which to create an imprint of the desired polyaromatic hydrocarbon, in situ, at glassy carbon electrodes. The molecularly imprinted polymer (MIP) sensors were washed to remove the imprint and subsequently characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), and cyclic voltammetry (CV). The MIP sensors were then applied to the detection of pyrene and non-imprinted polymers (NIP) sensors were also evaluated for comparison with the MIP sensors. Calibration curves obtained for the detection of the pyrene at the MIP sensors in aqueous media reported limits of detection (LOD) of 2.28 × 10−7 M for pyrene and limit of quantification (LOQ) of 6.92 × 10−7 M (n = 3). The sensitivity of the MIP sensors (32.53 A/M) determined from the slopes of the calibration curves reported twice the value measured for NIP sensors (14.48 A/M)

Metabolite profiling of obese individuals before and after a one year weight loss program

Objective:We and others have previously characterized changes in circulating metabolite levels following diet-induced weight loss. Our aim was to investigate whether baseline metabolite levels and weight-loss-induced changes in these are predictive of or associated with changes in body mass index (BMI) and metabolic risk traits.Methods:Serum metabolites were analyzed with gas and liquid chromatography/mass spectrometry in 91 obese individuals at baseline and after participating in a 1 year non-surgical weight loss program.ResultsA total of 137 metabolites were identified and semi-quantified at baseline (BMI 42.7±5.8, mean±s.d.) and at follow-up (BMI 36.3±6.6). Weight-loss-induced modification was observed for levels of 57 metabolites in individuals with

Nanoparticles as pseudostationary phase in capillary electrochrornatography/ESI-MS

A novel technique that uses polymer nanoparticles as pseudostationary phase in capillary electrochromatography with electrospray ionization mass spectrometry detection is described. A continuous full filling technique in which the nanoparticles were suspended in the entire electrolyte volume as well as a conventional partial filling technique is presented. No nanoparticles entered the mass spectrometer, which was fitted with an orthogonal electrospray interface, despite the continuous flow of nanoparticles into the interface. Nanoparticles (average diameter 160 nm) were prepared from methacrylic acid, methyl methacrylate, and trimethylolpropane trimethacrylate by utilizing a precipitation polymerization technique. Salbutamol, nortriptyline, and diphenhydramine were used as analytes. The interaction between analytes and nanoparticles was found to be predominantly ionic

Reversed phase continuous full filling CEC-ESI-MS

Nanoparticles were used as a pseudostationary phase in capillary electrochromatography (CEC) electrospray ionisation-mass spectrometry (ESI-MS) for separation of both neutral analytes by a reversed phase mechanism, as well as for cationic analytes by a cation exchange mechanism. Nanoparticles suspended in electrolyte, were injected as a plug prior to the sample using a partial filling technique (PF), or used as electrolyte in a continuous full filling (CFF) technique. An orthogonal ESI probe was used to hinder the nanoparticles from entering the mass spectrometer and to allow detection of analytes co-eluting with concentrated nanoparticle slurries. Two types of nanoparticles were synthesised and used, both of them having a hydrophobic core and a hydrophilic surface. The hydrophobic core gave the nanoparticles reversed phase properties and the hydrophilic surface promoted the formation of stable slurries of nanoparticles in electrolytes with a low concentration of organic modifier. The surface of one of the nanoparticle types was covered with sulphate groups that, besides from enhancing slurry stability and thus enabling reversed phase CEC, also enabled ion exchange CEC. Both nanoparticle types showed reproducible and interpretable retention properties

Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (CIMT) trial

Aim: Metformin is the first-line treatment for Type 2 diabetes. However, not all people benefit from this drug. Our aim was to investigate the effects of metformin on the plasma metabolome and whether the pretreatment metabolite profile can predict HbA1c outcome. Methods: Post hoc analysis of the Copenhagen Insulin and Metformin Therapy (CIMT) trial, a multicentre study from May 2008 to December 2012, was carried out. We used a non-target method to analyse 87 plasma metabolites in participants with Type 2 diabetes (n = 370) who were randomized in a 1: 1 ratio to 18 months of metformin or placebo treatment. Metabolites were measured by liquid chromatography-mass spectrometry at baseline and at 18-month follow-up and the data were analysed using a linear mixed-effect model. Results: At baseline, participants who were on metformin before the trial (n = 312) had higher levels of leucine/isoleucine and five lysophosphatidylethanolamines (LPEs), and lower levels of carnitine and valine compared with metformin-naïve participants (n = 58). At follow-up, participants randomized to metformin (n = 188) had elevated levels of leucine/isoleucine and reduced carnitine, tyrosine and valine compared with placebo (n = 182). At baseline, participants on metformin treatment with the highest levels of carnitine C10:1 and leucine/isoleucine had the lowest HbA1c (P-interaction = 0.02 and 0.03, respectively). This association was not significant with HbA1c at follow-up. Conclusions: Metformin treatment is associated with decreased levels of valine, tyrosine and carnitine, and increased levels of leucine/isoleucine. None of the identified metabolites can predict the HbA1c-lowering effect of metformin. Further studies of the association between metformin, carnitine and leucine/isoleucine are warranted

Dysregulation of glucagon secretion by hyperglycemia-induced sodium-dependent reduction of ATP production

Diabetes is a bihormonal disorder resulting from combined insulin and glucagon secretion defects. Mice lacking fumarase (Fh1) in their β cells (Fh1βKO mice) develop progressive hyperglycemia and dysregulated glucagon secretion similar to that seen in diabetic patients (too much at high glucose and too little at low glucose). The glucagon secretion defects are corrected by low concentrations of tolbutamide and prevented by the sodium-glucose transport (SGLT) inhibitor phlorizin. These data link hyperglycemia, intracellular Na+ accumulation, and acidification to impaired mitochondrial metabolism, reduced ATP production, and dysregulated glucagon secretion. Protein succination, reflecting reduced activity of fumarase, is observed in α cells from hyperglycemic Fh1βKO and β-V59M gain-of-function KATP channel mice, diabetic Goto-Kakizaki rats, and patients with type 2 diabetes. Succination is also observed in renal tubular cells and cardiomyocytes from hyperglycemic Fh1βKO mice, suggesting that the model can be extended to other SGLT-expressing cells and may explain part of the spectrum of diabetic complications