Molecular structure and stereoelectronic properties of sarmazenil--a weak inverse agonist at the omega modulatory sites (benzodiazepine receptors): comparison with bretazenil and flumazenil

X-ray diffraction and ab initio MO theoretical calculations were used in order to investigate the structural and electronic properties of sarmazenil, a weak inverse agonist at the omega modulatory sites (benzodiazepine receptors). This compound was compared to bretazenil, a partial agonist, and to the antagonist flumazenil on the basis of structural and electronic data. The conformational and theoretical properties (interatomic pi overlap populations, molecular electrostatic potential (MEP), the topology of frontier orbitals, and proton affinity) of these three imidazobenzodiazepinones were determined in order to analyse the stereoelectronic properties in relation with their distinct intrinsic efficacies at the omega modulatory sites.     

Glyconanoparticle-DNA interactions: an atomic force microscopy study.

Glyconanoparticles which present carbohydrate and amino groups motifs at their surface were produced. These particles were highly stable and soluble in aqueous solutions. The presence of the carbohydrate groups also allowed the inclusion of more strongly binding groups, without affecting solubility. The binding of a model DNA, plasmid by these nanoparticles was studied by atomic force microscopy, transmission electron microscopy, and gel electrophoresis. Significant differences between the nanoparticles based on their affinities for the DNA were found, with implications for their potential use as nonviral gene delivery agents.     

Peritoneal healing after fibrin glue application: a comparative study in a rat model

The influence of fibrin glue on adhesion formation and peritoneal healing is evaluated in a prospective, randomized, controlled study. In all, 20 Wistar rats underwent microsurgical suturing of two silicone sheets, one covered with a fibrin glue barrier, to the anterior peritoneum. Each animal thus served as its own control. After 10 days, adhesions and peritoneal healing were evaluated by a blinded observer through a second-look laparotomy. Adhesions were scored using a modification of the classification of Diamond. Tissue around the silicone sheet was examined histologically and by scanning electron microscopy to evaluate the inflammatory reaction and peritoneal healing (ingrowth of blood vessels and quality of peritoneal cells). Adhesion scores for treated and control sides were (mean +/- SD) 2.89 +/- 4.68 and 6.79 +/- 9.09 (P = 0.181) respectively, and the percentage of the sheet covered by peritoneum was 26.25 +/- 31.50 and 29.21 +/- 40.21 (P = 0.226) respectively. Using the paired Wilcoxon rank test, the P values for the ingrowth of blood vessels and peritoneal healing evaluated by histology and scanning electron microscopy were 0.842, 0.692 and 0.695 respectively. We conclude that although the mean adhesion score was reduced by > 50% by fibrin glue, there is no statistically significant difference concerning adhesion formation or peritoneal healing with the use of fibrin glue.     

Test of the deterministic conjecture for the instantaneous time phase fluctuations of an oscillator

The fluctuations observed by recording the picosecond pulses of a mode-locked laser with a synchroscan streak camera are due to the laser jitter and to the variations of the zero crossing of the synchronization. By means of a simple model, it is shown that the dispersions measured when the synchronization is generated from the mode-locker oscillator reflect the instantaneous time phase fluctuations of this oscillator. From the study of the experimental recordings with methods of time series analysis it results that the phase noise of the electronic oscillator is consistent with an underlying low-dimensional strange attractor.     

Clinical case of the month. Metastatic endocarditis: clinical observation and review of the literature

The authors describe a case of metastatic endocarditis associated with a gastric carcinoma. The diagnosis was made early and the treatment by surgery and chemotherapy allowed a survival of 18 months, which is unusually long. The differential diagnosis is discussed and includes nonbacterial thrombotic endocarditis, infectious endocarditis and primary tumors of the heart.     

Decomposition of solid explosives by laser irradiation: A mass spectrometric study

Experimental investigations have been made in which single crystals of solid explosives such as cyclotrimethylene trinitramine, RDX, pentaerythritol tetranitrate, PETN, AgN₃ and Pb(N₃)₂, were irradiated with a focused laser beam of wavelength 266 nm and duration 5 nsec in an ultra high vacuum system housing a fast and sensitive time-of-flight mass spectrometer. From the mass spectra (both +ve and -ve ions) of the chemical species obtained, possible decomposition schemes of RDX and PETN have been proposed. For silver and lead azides, the laser irradiation did not cause explosions if the power density was sufficiently low, but micrometre size craters were formed. In the mass spectra of AgN₃ products N₃ ^– and silver cluster ions, Ag _n ⁺, have been found for the first time. It has been suggested that such investigations may possibly throw some light on our understanding of the reactions taking place in a deflagration/detonation wave.     

Multicomponent Bioluminescence Imaging with Naphthylamino Luciferins

Bioluminescent tools have been used for decades to image processes in complex tissues and preclinical models. However, few distinct probes are available to probe multicellular interactions. We and others are addressing this limitation by engineering new luciferases that can selectively process synthetic luciferin analogues. In this work, we explored naphthylamino luciferins as orthogonal bioluminescent probes. Three analogues were prepared using an optimized synthetic route. The luciferins were found to be robust emitters with native luciferase in vitro and in cellulo. We further screened the analogues against libraries of luciferase mutants to identify unique enzyme-substrate pairs. The new probes can be used in conjunction with existing bioluminescent tools for multi-component imaging.     

Lipid products formed during desaturation of [1-14C] stearyl CoA by hen liver microsomes

A number of lipid products are formed during the desaturation of stearyl CoA by hen liver microsomes. This article presents an analysis of the products formed when [1-¹⁴C] stearyl CoA is incubated with hen liver microsomes for various time periods. [1-¹⁴C] Oleyl CoA was the first radioactive unsaturated product formed. Synthesis of phospholipids containing [1-¹⁴C] oleic acid occurs only after the desaturase activity has begun to decline. The specific radioactivity of [1-¹⁴C] oleyl CoA was similar to the specific radioactivity of [1-¹⁴C] stearyl CoA at all time periods tested. The specific radioactivities of [1-¹⁴C] oleic acid and phospholipids containing [1-¹⁴C] oleic acid were much lower than that of the [1-¹⁴C] stearyl CoA.     

Differently sized native milk fat globules separated by microfiltration: fatty acid composition of the milk fat globule membrane and triglyceride core

The aim of this study was to characterize the fatty acid composition of the core and membrane of differently sized milk fat globules separated by microfiltration, which can now be used to manufacture dairy products. Native milk fat globules of various mean diameters, ranging from d₄₃ = 2.3 µm to 8.0 µm, were obtained using microfiltration of raw whole milk. After milk fat globule washing, the milk fat globule membrane (MFGM) and the triglyceride core (TC) were separated by manual churning. After total lipid extraction from each fraction, their fatty acid composition was characterized using methyl ester analysis by gas chromatography. Regardless of season, no significant differences were observed in the fatty acid composition of the MFGM phospholipids. Conversely, significant differences were found in the fatty acid composition of TC; particularly, small fat globule TC contained more medium‐chain fatty acids and less stearic acid than large fat globule TC. These results show that the previously observed differences in total fatty acid composition among differently sized milk fat globules are due to their triglyceride composition and MFGM amount rather than to the composition of the MFGM.     

Regulation of phosphatidylinositol turnover,calcium metabolism and enzyme secretion by phorbol dibutyrate in neutrophils

The action of the tumor promoter, phorbol 12,13-dibutyrate (PDBu), on rabbit peritoneal and human neutrophils is associated with stimulation of¹⁴C-arachidonic acid incorporation into phospholipids within 1–2 min. Stimulated¹⁴C-arachidonate incorporation was relatively selective for phosphatidylinositol (PI) in rabbit neutrophils. In contrast, the secretory response of human neutrophils to PDBu coincided with stimulated label incorporation into phosphatidylserine (PS), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA) and PI. Significant increases in label incorporation were observed with PDBu concentrations as low as 2 nM, and the dose response of stimulated label incorporation paralleled that of evoked lysozyme secretion. A parallel, but partial, inhibition of PDBu-stimulated PI labeling and enzyme release was observed after exposing rabbit neutrophils to calcium-deprived medium, whereas calcium deprivation failed to significantly depress either of these stimulant actions of PDBu in human neutrophils. Further, in rabbit neutrophils PDBu elicited an increase in cell associated⁴⁵Ca. However, PDBu was unable to promote the incorporation of³²P orthophosphate into PI or enhance phospholipase A₂ activity in broken cells. These findings suggest that one expression of the interaction between phorbol esters and their receptors on neutrophils involves the turnover of arachidonic acid in phospholipids. This stimulated turnover of arachidonate may be a critical step in the cascade of events associated with neutrophil activation.