Distribution measurements of 3,4-methylenedioxymethamphetamine and its metabolites in organs by matrix-assisted laser desorption/ionization imaging mass spectrometry using an automatic matrix spraying system with an air brush and a turntable

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI/IMS) is a useful tool for measuring drug distributions. To obtain reproducible analytical results with MALDI/IMS, it is essential to apply a homogeneous matrix coating onto sample surfaces. A simple and inexpensive automatic matrix spraying system (AMSS) with good reproducibility was developed in this study. In addition, drug distributions in organs were measured by MALDI/IMS using the AMSS for forensic toxicology applications. The AMSS was constructed from simple components, including an air brush, a turntable, and a microscope. Organ slices placed onto conductive sheets were attached to the turntable. The trigger of the air brush was held with a clamp to ensure that it sprayed continuously onto a defined area of the table. Periodic spraying of the matrix solution and evaporation of solvent were performed by rotating the turntable. The droplets and crystals on the sample surfaces were observed under a microscope attached to the turntable. The droplet size, rotation rate of the turntable, and the formulation of the matrix solution were optimized. The homogeneity of the matrix coating was evaluated using the coefficients of variation (CV) obtained by quantifying the color density of the sheet surface. The AMSS enabled more homogeneous matrix coating (intersheet CV?=?5.4?%) than manual spraying (intersheet CV?=?16.7?%) when 10?mL of 0.5?% aqueous trifluoroacetic acid/acetonitrile (1:3, v/v) containing 10?mg/mL α-cyano-4-hydroxycinnamic acid were sprayed as droplets less than 50?μm in diameter onto a turntable rotating at 30?rpm. The distributions of 3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites in the brain, liver, and kidney of a mouse that died from an MDMA overdose (58?mg/kg?i.p.) were visualized by MALDI/IMS using the AMSS. The ion intensities of MDMA obtained from the same regions on three sequential kidney slices showed acceptable variations (CV?=?2.9-8.8?% for five different regions), implying repeatable measurements with MALDI/IMS using the AMSS. It was revealed that MDMA was particularly concentrated around the brain stem and the major calix of the kidney. The AMSS would be suitable for preparing samples for measuring the distributions of drugs in organs at toxic dose levels in forensic toxicological applications.     

A Convenient Synthesis of 1, 2, 5-Trisubstituted 3-Benzoylpyrroles

In the course of our investigation directing toward biologically active compounds, 2, 5-disubstituted 3-acylpyrrole derivatives were found to show a potent inhibiting activity of platelet aggregation.^1,2,3 Thus, various acylation reactions were studied in order to achieve an efficient synthesis of 3-acylated pyrrole system. We wish to report here an effective method for the preparation of 2, 5-disubstituted 3-acylpyrroles dispensing from the formation of by-products such as 3, 4-diacylated pyrroles.     

LOWER ESTIMATE OF THE ATTRACTOR DIMENSION FOR A CHEMOTAXIS GROWTH SYSTEM

This paper estimates from below the attractor dimension of thedynamical system determined from a chemotaxis growth model whichwas presented by Mimura and Tsujikawa. It is already known thatthe dynamical system has exponential attractors and it is alsoknown by numerical computations that the model contains variouspattern solutions. This paper is then devoted to estimatingthe attractor dimension from below and in fact to showing that,as the parameter of chemotaxis increases and tends to infinity,so does the attractor dimension. Such a result is in a goodcorrelation with the numerical results.     

New method to calibrate binding energy using Au nanocolloids in X-ray photoelectron analysis of diamondlike carbon films with different electrical resistivities

A new method to calibrate the binding energy (E_B) using Au nanocolloids as a calibrant in XPS analysis of diamondlike carbon (DLC) is proposed by considering the DLC films with different electrical resistivities. A few microliters of a dilute aqueous solution containing Au nanocolloids were dropped onto a small local surface area of the DLC film, which became a stain before XPS measurements by gradually drying in vacuo. The observed peak E_B of the C 1s spectrum at another native surface (an area without Au nanocolloids) of the DLC film was calibrated by setting that of the Au 4f_7/2 spectrum of the Au nanocolloids to 84.0 (83.98 ± 0.02) eV. The adequacy of this method was investigated by considering the correlation among the full width at half maximums (FWHMs) of the Au 4f_7/2 spectra of the Au nanocolloids on the DLC surfaces and that of a Au plate as a reference. Consequently, the FWHM of the Au 4f_7/2 spectrum of the Au nanocolloids on the DLC surface is a candidate to investigate the differential charging effect of the DLC surface, and the calibration method is reliable if the FWHM agrees with that of the Au plate.     

The inhibitory effect of bis[2-[(E)-2-octenoylamino]ethyl] disulfide on the cyclooxygenase pathway

Bis[2-[(E)-2-octenoylamino]ethyl] disulfide (compd. I-3) inhibited collagen- and arachidonic acid-induced rat platelet aggregation, although not adenosine 5'-diphosphate (ADP)-induced rat platelet aggregation. Based on these results, we then investigated the inhibitory effect of compd. I-3 on thromboxane B2 formation from arachidonic acid in rat platelets, and prostaglandin I2 formation in rat aortae. Compound I-3 inhibited both thromboxane B2 and prostaglandin I2 formation, suggesting that it has an inhibitory effect on cyclooxygenase. The inhibitory effect of compd. I-3 was confirmed in experiments using a crude preparation of sheep seminal vesicle microsomal prostaglandin synthetase. These findings suggested that compd. I-3 has an inhibitory effect on cyclooxygenase activity, like nonsteroidal anti-inflammatory drugs.     

Further studies on the pharmacological effect of the anti-inflammatory compound, bis[2-(E-2-octenoylamino)ethyl] disulfide

Further studies on the pharmacological effect of orally administered bis[2-(E-2-octenoyl-amino)ethyl] disulfide (compd. I-3) was examined by using several experimental models in vivo. Compound I-3 showed analgesic activity, inhibiting both acetic acid- and acetylcholine-induced writhings in mice. This compound also showed antipyretic activity against yeast-induced fever in rats, and significantly inhibited arachidonic acid-induced mortality in mice. However, it had no effect on serotonin-induced paw edema formation or platelet activating factor-acether-induced mortality in mice. The effects of compd. I-3 are suggested to be due to inhibition of prostaglandin biosynthesis.