Comparison of the effect of etomidate and desflurane on brain tissue gases and pH during prolonged middle cerebral artery occlusion

BACKGROUND: The authors compared the effects of etomidate and desflurane on brain tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2), and pH in patients who had middle cerebral artery occlusion for > 15 min. METHODS: After a craniotomy, a probe that measures PO2, PCO2, and pH was inserted into cortical tissue at risk for ischemia during middle cerebral artery occlusion. A burst suppression pattern of the electroencephalogram was induced with etomidate (n = 6) or 9% end-tidal desflurane (n = 6) started before middle cerebral artery occlusion. Mean blood pressure was supported with phenylephrine to 90-95 mmHg. RESULTS: During baseline conditions, tissue PO2, PCO2, and pH were similar between the two groups (PO2 = 15 mmHg, PCO2 = 60 mmHg, pH = 7.1). During administration of etomidate before middle cerebral artery occlusion, tissue PO2 decreased in five of six patients without a change in PCO2 or pH. During administration of 9% desflurane, tissue PO2 and pH increased before middle cerebral artery clipping. Middle cerebral artery occlusion for an average of 33 min with etomidate and 37 min with desflurane produced a decrease in pH with etomidate (7.09 to 6.63, P < 0.05) but not with desflurane (7.12 to 7.15). CONCLUSION: These results suggest that tissue hypoxia and acidosis are often observed during etomidate treatment and middle cerebral artery occlusion. Treatment with desflurane significantly increases tissue PO2 alone and attenuates acidotic changes to prolonged middle cerebral artery occlusion.     

Sex differences in the nervous system of reptiles

1. The study of sex differences in the brain and behavior of reptiles presents an excellent opportunity both to discern general principles of sexual differentiation in the nervous system and to explore the evolutionary history of this process in amniote vertebrates. 2. Findings in several reptiles suggest that some sex differences found in mammals and birds are conserved while others are not. Conserved features include areas in the limbic forebrain involved in the regulation of social and sexual behaviors. As in mammals and birds, it is rare to find differences in the distribution of sex steroid concentrating neurons in reptiles but common to find differences in the distribution of the various steroid hormone receptors and in their regulation. 3. This research has revealed that differences in social and sexual behavior are reflected better by the activity, not by the size, of hormone-sensitive limbic areas. 4. Finally, species differences in plasma levels of sex hormones are paralleled by differences in behavioral sensitivity to these hormones as well as by differences in the regulation of genes coding for steroid hormone receptors.     

Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure–Degradation Relationships

The immunomodulatory drugs (IMiDs) thalidomide, pomalidomide, and lenalidomide have been approved for the treatment of multiple myeloma for many years. Recently, their use as E3 ligase recruiting elements for small‐molecule‐induced protein degradation has led to a resurgence in interest in IMiD synthesis and functionalization. Traditional IMiD synthesis follows a stepwise route with multiple purification steps. Herein we describe a novel one‐pot synthesis without purification that provides rapid access to a multitude of IMiD analogues. Binding studies with the IMiD target protein cereblon (CRBN) reveals a narrow structure–activity relationship with only a few compounds showing sub‐micromolar binding affinity in the range of pomalidomide and lenalidomide. However, anti‐proliferative activity as well as Aiolos degradation could be identified for two IMiD analogues. This study provides useful insight into the structure–degradation relationships for molecules of this type as well as a rapid and robust method for IMiD synthesis.     

The analysis of sterol degradation products to detect vegetable fats in chocolate

A method for the detection of hydrocarbon sterol degradation products (sterenes) has been adapted for the analysis of noncocoa butter vegetable fats in chocolate. The method involves solvent extraction of the fat separation of the sterene fraction, and analysis of individual sterenes with mass spectrometric detection. The sterene composition of refined noncocoa vegetable fats was determined in samples of cocoa butter, and retail chocolates. The presence of known sterenes was confirmed for all of the refined vegetable fats and for a single sample of cocoa butter, the processing history of which was not known. Detection of vegetable fat added to chocolate at the 5% level was demonstrated. Sterenes were detected only in chocolates labeled as containing vegetable fats. This technique has potential use as a screening method for the detection, but not quantification, of refined vegetable fat in chocolate.     

The effects of domestic cooking on the levels of 3-monochloropropanediol in foods

The results are reported of a study to determine the effect of domestic cooking procedures on the level of 3-monochloropropane-1,2-diol (3-MCPD) in selected foods. Samples of 23 foods comprising stock cubes, gravies, a cake mix, batters, breads, cheese and meats were subjected to a range of cooking procedures including grilling, toasting and microwaving. The resulting levels of 3-MCPD were compared with those present in the foods before cooking. Grilling and toasting produced substantial increases in the 3-MCPD content of bread, forming up to 0.3mg/kg, and of most cheeses, resulting in levels of up to about 0.1mg/kg. Microwave cooking produced elevated 3-MCPD levels in some cheeses. Frying laboratoryproduced batters increased 3-MCPD levels to about 0.1mg/kg whereas a retail batter contained no detectable 3-MCPD when fried. The remaining foods showed little or no discernible increase on cooking.     

Significance, chemistry and determination of ergot alkaloids: a review.

The purpose of this paper is to summarize the most relevant and recent information available on ergot alkaloids. This includes information about their occurrence, toxicity, chemistry, statutory limits, and their significance in feed and food. Recently, in 2005, the European Food Safety Authority (EFSA) concluded that validated analytical methods for the quantification of ergot alkaloids in feed materials are needed. For that reason, the major focus of the present paper is to report on the latest developments for the determination of major ergot alkaloids and their epimers in cereals and cereal-derived products. Information about the stability and the availability of calibrants, sampling issues, extraction and clean-up strategies, and a variety of final separation and detection techniques is provided. The recently developed liquid chromatography-tandem mass spectrometric methods (LC-MS/MS) for the simultaneous quantification and identification of ergot alkaloids are given special consideration.     

Pulping Catalysts in Trees

Abstract

Several hardwood and softwood trees were analyzed for anthraqui-none-type components. Wood samples were reduced to a small size and extracted with an organic solvent; the extracts were then concentrated and analyzed by gas chromatography-mass spectroscopy. Low levels of AQ and anthrone components were detected using a sensitive selected-ion monitoring technique. Ten out of seventeen hardwood samples examined contained AQ-type components; however, the levels were typically below ～6 ppm. Such components were not observed for the few softwood samples that were examined. The AQs were more concentrated in the heart-wood of teak than in the sapwood. Extraction of cottonwood with an organic solvent had little effect on the ease of pulping of the wood.     

Degradation of yew, ragwort and rhododendron toxins during composting

Recent concerns have been raised that plants such as ragwort (Senecio jacobaea), yew (Taxus baccata) and rhododendron (Rhododendron ponticum) that are toxic to livestock may be included in compost windrows but may not be fully detoxified by the composting process. This study investigates the decomposition during composting of toxic pyrrolizidine alkaloids present in ragwort, taxines (A and B) present in yew, and grayanotoxins (GTX I, II, and III) present in rhododendron during composting. Plant samples were contained within microporous bags either towards the edge or within the centre of a pilot-scale compost heap. They were destructively harvested at regular intervals over 1200 °C cumulative temperature (about three months). Samples were analysed for levels of toxins by liquid chromatography time of flight mass spectrometry (LC-TOF-MS). Pyrrolizidine alkaloids and taxines were shown to degrade completely during the composting process. While GTX I showed significant reductions, concentrations of GTX III remained unchanged after 1200 °C cumulative temperature. However, estimates of exposure to grazing livestock coming into contact with source-segregated green waste compost containing up to 7% rhododendron suggest that GTX III poses no appreciable risk.     

The microglial response to progressive hydrocephalus in a model of inherited aqueductal stenosis

A number of different procedures have been developed for use with matrix-assisted laser desorption/ionization mass spectrometry (MALDI/MS) for the analysis of non-covalent protein-protein complexes. These include use of specific matrix and laser combinations, accumulation of "first shot" spectra, modification of pH and solvent conditions during sample preparation and use of cross-linking agents to attach the monomers covalently to each other in the complex. The results have shown the techniques to be effective with some but not all complexes, although cross-linking is the most successful. The physical and chemical nature of the complex is critical and therefore a diversity of approaches is recommended for such studies.     

Simple high-performance liquid chromatographic determination of the protease inhibitor indinavir in human plasma

Indinavir is a member of a class of protease inhibitors that actively prevent the acquired immunodeficiency syndrome virion from maturing. A high-performance liquid chromatographic (HPLC) assay was developed and validated for the determination of indinavir in human plasma. Indinavir and the internal standard were isolated from the plasma by ether extraction. The residue after evaporation of ether was reconstituted with buffer and injected onto a C4 reversed-phase column eluted isocratically with a mobile phase consisting of 35:65 (v/v) of acetonitrile and buffer. A wavelength of 210 nm was found to be optimum for detection. The calibration range of this assay was from 10 to 5000 ng/ml and coefficients of variation for the assay ranged from 4.6% to 11.0% for three different drug concentrations and the limit of quantitation was 10 ng/ml. During the validation, short-term stability of the drug in plasma, stability during heat deactivation and on repeated freezing and thawing of plasma was evaluated. The overall recovery of indinavir by the ether extraction method was 91.4%. This HPLC assay was found to be a simple and reproducible method for monitoring indinavir levels in human plasma obtained during clinical trials of the drug.