2-methyl butyramide, a previously identified urine biomarker for Ascaris lumbricoides, is not present in infected Indonesian individuals

Abstract ᅟ Previous reports suggest that the 2-methyl butyramide and 2-methyl valeramide metabolites of Ascaris lumbricoides in urine of infected individuals could be considered as urinary biomarkers for active infection. We have developed an LC-MS method with a detection limit of 10 ng/mL using synthetic chemicals as reference material. Urine samples (n = 21) of infected individuals were analyzed for the presence of these metabolites, but they were not detected in any of the samples. Furthermore, the recorded 1H-NMR spectrum for reference 2-methyl butyramide did not match with the spectrum that was described for the Ascaris metabolite. Based on these two observations, we concluded that the urinary biomarkers that were detected for A. lumbricoides infection are not 2-methyl butyramide nor 2-methylvaleramide. New discovery efforts will be required to identify the structure of these metabolite biomarkers in urine of infected individuals. Trial registration Urine samples used in this study were collected as part of a clinical trial with trial number ISRCTN75636394 (12 November 2013)

Magnetic Resonance Monitoring of Opaque Temperature-Sensitive Polymeric Scaffolds

The monitoring of location and degradation rates of injectable biomaterials is an area of particular interest in the design and implementation of therapeutic scaffolds and carriers for tissue repair and replacement. We describe here the fabrication and characterization of gadolinium (Gd)-labeled temperature-responsive hydrogels that can be detected noninvasively using T1-weight magnetic resonance. Two acrylamide-functionalized GdIIIDOTA-monoamide complexes with either a short n-butylene spacer (GdIII-C4-AA) or a long hydrophilic spacer (GdIII-PEG-AA) were synthesized and incorporated into the hydrogels. At temperatures above the lower critical solution temperature (LCST), 37 °C, these hydrogels have the capacity to enhance relaxivity (r1) due to the hydrophobic interactions of the polyamide chains around the gadolinium chelates. This effect is further accentuated by the presence of the polyethylene glycol groups of the Gd complex GdIII-PEG-AA

On the photo-oxidation of perylene bisimide dyes in alcoholic solutions

Irradiation with intense blue LED light of Lumogen orange 240 (1) in non-reactive solvents led to bleaching. The products of these photochemical reactions were not possible to determine. Contrarily, irradiation in ethanol or propanol led to red color shifts caused by the formation of the ethoxy or propoxy derivative of Lumogen orange 240, respectively. These new reaction products are only formed when both light and oxygen are present. A possible mechanism for these photo-oxidation reactions, the implication for the stability of perylene type of fluorescent dyes under LED lamp conditions and possible preparative applications are discussed

Triethylenetetramine penta- and hexa-acetamide ligands and their ytterbium complexes as paraCEST contrast agents for MRI

\u3cp\u3eThe ligand triethylenetetramine-N,N,N′,N″,N′″, N′″-hexaacetamide (ttham) was synthesized with the aim of forming lanthanide complexes suitable as contrast agents for magnetic resonance imaging applications utilizing the chemical exchange-dependent saturation transfer (CEST) effect. It was designed to exclude water molecules from the first coordination sphere and provide a high number of CEST active amide protons per lanthanide ion. The ligand was characterized by its protonation behavior and its complexation properties with ytterbium ions in aqueous solution. The basicity of the ttham backbone amine protons decreases in the order N \u3csub\u3ecentral(1)\u3c/sub\u3e > N\u3csub\u3eterminal(1)\u3c/sub\u3e > N\u3csub\u3eterminal(2)\u3c/sub\u3e > N\u3csub\u3ecentral(2)\u3c/sub\u3e, as deduced from NMR titration experiments and from a comparison of its protonation constants with those of two ttham derivatives, in which either a terminal (N-benzyl-triethylenetetramine-N,N′,N″, N′″,N′″-pentaacetamide, 1bttpam) or a central acetamide group (N′-benzyl-triethylenetetramine-N,N,N″,N′″, N′″-pentaacetamide, 4bttpam) is substituted with a benzyl group. This protonation sequence results from the combined influence of inductive effects, the intramolecular hydrogen bonding network, and the Coulomb repulsion between protonated ammonium groups. The ytterbium complex of ttham, [Yb(ttham)]Cl\u3csub\u3e3\u3c/sub\u3e, is coordinatively frustrated. Due to steric constraints, in addition to the four backbone nitrogen atoms, only three of the four symmetry-equivalent terminal acetamide donors can coordinate simultaneously to the ytterbium ion, and the dangling fourth one exchanges quickly with the other three. The ytterbium complexes of a total of five ligands (ttham, 1bttpam, 4bttpam, 2,2′,2″-triaminotriethylaminehexaacetamide (ttaham), and diethylenetriamine-N,N,N′,N″,N″-pentaacetamide (dtpam)) were studied with respect to their CEST properties. In solution, all of these complexes have a low symmetry. The presence of multiple magnetically different amide groups in each complex prevents the realization of very high CEST effects. These results nevertheless form an excellent basis for a further optimization of this class of ligands.\u3c/p\u3

The thulium complex of 1,4,7,10-tetrakis {[N-(1H-imidazol-2-yl)-carbamoyl]methyl]-1,4,7,10-tetraazacyclododecane (dotami) as a paraCEST contrast agent

\u3cp\u3e1,4,7,10-Tetrakis{[N-(1H-imidazol-2-yl)carbamoyl]methyl}-1,4,7, 10-tetraazacyclododecane (dotami), a tetra(1H-imidazol-2-yl) derivative of the well-studied octadentate 1,4,7,10-tetrakis[(carbamoyl)methyl]- 1,4,7,10-tetraazacyclododecane (dotam) ligand, was synthesized by reaction of 1,4,7,10-tetraazacyclododecane with N-(1H-imidazol-2-yl) chloroacetamide in high yield. Its tricationic thulium complex was isolated as a water-soluble chloride salt. The detection of the mildly acidic amide and amine protons by direct proton NMR in aqueous solution was unsuccessful, but such exchangeable protons could be detected via their chemical exchange-dependent saturation transfer (CEST) effect. The observed CEST effect was distinctly different from that found for respective dotam complexes and is, therefore, ascribed to exchangeable protons associated with the imidazole substituent.\u3c/p\u3

On the photo-oxidation of perylene bisimide dyes in alcoholic solutions

\u3cp\u3eIrradiation with intense blue LED light of Lumogen orange 240 (1) in non-reactive solvents led to bleaching. The products of these photochemical reactions were not possible to determine. Contrarily, irradiation in ethanol or propanol led to red color shifts caused by the formation of the ethoxy or propoxy derivative of Lumogen orange 240, respectively. These new reaction products are only formed when both light and oxygen are present. A possible mechanism for these photo-oxidation reactions, the implication for the stability of perylene type of fluorescent dyes under LED lamp conditions and possible preparative applications are discussed.\u3c/p\u3

Preparation of monodisperse polymer particles and capsules by ink-jet printing

\u3cp\u3eMicron-sized particles with a narrow size distribution are prepared by ink-jet printing technology. Droplets of a polymer solution are printed with the nozzle submerged into an aqueous phase. The particles are formed upon removal of the solvent for the polymer. The particle size can be accurately predicted from the initial drop size and the polymer concentration. The method is also suitable for the preparation of monodisperse capsules with a well-defined core and shell using an additional non-solvent for the polymer. Hollow capsules are prepared by removal of the non-solvent from core of the capsules using freeze-drying. This leads to gas-filled capsules with a well-defined polymeric shell and a diameter in the range of 5 μm, which may be applied as an ultrasound contrast agent.\u3c/p\u3

Demineralized bone matrix-induced ectopic bone formation in rats: in vivo study with follow-up by magnetic resonance imaging, magnetic resonance angiography, and dual-energy X-ray absorptiometry.

Contains fulltext : 57929.pdf (publisher's version ) (Open Access)The aim of this study was to further explore the use of magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and dual-energy X-ray absorptiometry (DEXA) to assess bone formation and blood circulation in a pedicled bone graft substitute. In 14 Wistar rats, initially 10 weeks old, heterogeneous demineralized femur bone matrix implants were wrapped in pedicled adductor thigh muscle flaps. One rat died after surgery. Subsequently, bone formation and maintenance of blood vessel functionality were evaluated in six rats 6 weeks postimplantation by means of in vivo MRI/MRA and postmortem histomorphometry. The other seven rats were left for 12 weeks, whereafter bone formation was evaluated by in vivo DEXA and postmortem histomorphometry. The results demonstrated that after 6 weeks bone formation was present in four of six animals, quantified as 42 (+/-35)% and 25 (+/-19)% by means of MRI and histomorphometry, respectively. MRA was able to show patency of the pedicles of these four rats only, which suggests that the lack of blood supply in the other two rats is the cause of the failure to form bone. In the 12-week group, histology showed increased bone formation without signs of osteolysis, which was quantified histomorphometrically to be as high as 48 (+/-15)%. DEXA failed to show bone formation. It is concluded that in vivo MRI proved to be a reliable method for monitoring ectopic bone formation in a rat model, whereas in vivo DEXA was unable to detect the implants. Furthermore, in vivo MRA proved to be a useful technique for studying the circulation of muscle flaps in this animal model

Relaxometric studies of gadolinium-functionalized perfluorocarbon nanoparticles for MR imaging

Fluorine MRI (19F MRI) is receiving an increasing attention as a viable alternative to proton-based MRI (1H MRI) for dedicated application in molecular imaging. The 19F nucleus has a high gyromagnetic ratio, a 100% natural abundance and is furthermore hardly present in human tissues allowing for hot spot MR imaging. The applicability of 19F MRI as a molecular and cellular imaging technique has been exploited, ranging from cell tracking to detection and imaging of tumors in preclinical studies. In addition to applications, developing new contrast materials with improved relaxation properties has also been a core research topic in the field, since the inherently low longitudinal relaxation rates of perfluorocarbon compounds result in relatively low imaging efficiency. Borrowed from 1H MRI, the incorporation of lanthanides, specifically Gd(III) complexes, as signal modulating ingredients in the nanoparticle formulation has emerged as a promising approach to improvement of the fluorine signal. Three different perfluorocarbon emulsions were investigated at five different magnetic field strengths. Perfluoro-15-crown-5-ether was used as the core material and Gd(III)DOTA-DSPE, Gd(III)DOTA-C6-DSPE and Gd(III)DTPA-BSA as the relaxation altering components. While Gd(III)DOTA-DSPE and Gd(III)DOTA-C6-DSPE were favorable constructs for 1H NMR, Gd(III)DTPA-BSA showed the strongest increase in 19FR1. These results show the potential of the use of paramagnetic lipids to increase 19FR1 at clinical field strengths (1.5-3T). At higher field strengths (6.3-14T), gadolinium does not lead to an increase in 19FR1 compared with emulsions without gadolinium, but leads to an significant increase in 19FR2. Our data therefore suggest that the most favorable situation for fluorine measurements is at high magnetic fields without the inclusion of gadolinium constructs. Copyright © 2014 John Wiley & Sons, Ltd