Potent quinoxaline-spaced phosphono alpha-amino acids of the AP-6 type as competitive NMDA antagonists: synthesis and biological evaluation

A series of alpha-amino-3-(phosphonoalkyl)-2-quinoxalinepropanoic acids was synthesized and evaluated for NMDA receptor affinity using a [3H] CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [3H]TCP binding assay and in vivo by employing an NMDA-induced seizure model. Some analogues also were evaluated in the [3H]-glycine binding assay. Several compounds of the AP-6 type show potent and selective NMDA antagonistic activity both in vitro and in vivo. In particular alpha-amino-7-chloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (1) displayed an ED50 of 1.1 mg/kg ip in the NMDA lethality model. Noteworthy is alpha-amino-6,7-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic++ + acid (3) with a unique dual activity, displaying in the NMDA receptor binding assay an IC50 of 3.4 nM and in the glycine binding assay an IC50 of 0.61 microM.     

Constant-pressure coronary artery perfusion during aortic valve operations

The aim of this study was to investigate the action of isoproterenol (ISP) on the myocardium by means of light microscopy, histochemistry, autoradiography with tritiated ISP and electron microscopy. One hundred and sixty four Wistar rats were divided into 8 groups. Group A, B, C and D were given 10 mg/kg i.p. ISP (plus 5 uC of tritiated ISP). The animals were sacrificed at different intervals. Group E served as control to proceeding groups. Group F was given 10 mg/kg i.p. ISP and subjected to "holding" stress; Group G was its corresponding control. Group H received 9 mg/kg. prenylamine, as inhibiting drug, 1 hour before and hour after ISP injection. Histopathology of "infarct like" lesions presenting localized necrosis, myocytolysis, homogenization and positive tests for ischemia are correlated to the localization of tritiated ISP on sarcolemma and to changes in succine dehydrogenase enzymes in the groups A, B, C and D. Hypercontraction and widening of Z bands of sarcomers are found in electron microscopy. These ischemic changes are inhibited by prenylamine, a drug acting as moderator of catecholamine effects by slowing down Ca transport. It is concluded that myocardial necrosis induced by ISP is probably due to an increased activation of the "calcium pump". The ISP provoked lesions appear to be a promising model to study experimental myocardial necrosis.     

MgO(111) Nanocatalyst for Biomass Conversion: A Study of Carbon Coating Effects on Catalyst Faceting and Performance

Solid base metal oxide catalysts such as MgO offer utility in a wide variety of syntheses from pharmaceuticals to fuels. The (111) facet of MgO shows enhanced, unique properties relative to the other facets. Carbon coatings have emerged as a promising modification to impart metal oxide catalyst stability. Here, we report the synthesis, characterization, and catalytic properties of commercial MgO, MgO(111), and carbon coated derivatives thereof for 2-pentanone condensation. The dimer and trimer products of this reaction can be used as precursors for biofuels upon oxygen removal and thus have relevance in environmental sustainability. MgO(111) maintained impressive selectivity towards the dimer product after carbon coating, whereas the other catalysts experienced a decrease in conversion and selectivity as a consequence of the carbon coating. Our findings highlight the catalytic efficacy of MgO(111), provide insight into carbon coating for catalyst stability, and pave the way for continued mechanistic investigations.

Graphical Abstract

     

Use of the ADM1 to investigate the effects of acetoclastic methanogen population dynamics on mesophilic digester stability.

The ADM1 was employed to assess the effect of variations in solids hydrolysis and acetoclastic methanogen process characterizations on municipal digester stability relating to excess acetate utilization capacity. First-order single- and dual-pathway hydrolysis rate functions and single and competitive acetoclastic methanogen rate functions were implemented in the ADM1. The acetate capacity number (ACN), defined as the ratio between the maximum acetate utilization rate and the average acetate production rate, was used to index digester instability. Simulations of a single CSTR at steady state indicate a similar ACN can be obtained with a 12-day SRT digester dominated by Methanosarcina sp and a 24-day SRT digester dominated by Methanosaeta sp. An increase in ACN with a decrease in SRT representing Methanosarcina sp. selection was observed for particulate feed loadings from 40 g COD/L to 90 g COD/L. Feeding frequency and dual-pathway hydrolysis were found to have less effect on the ACN than the competitive acetoclastic model structure.     

Economic and energy impacts from participation in the regional greenhouse gas initiative: A case study of the State of Maryland

Tradable emissions allowance systems to reduce carbon emissions are increasingly promoted as means to mitigate climate change. This paper briefly reviews the application of such systems at the global, regional, and corporate scales. Given the recent expansion of cap-and-trade systems at the regional level, the paper concentrates on energy and economic implications at that level, using the decision of the State of Maryland, USA, to join the Regional Greenhouse Gas Initiative as an illustration. The paper presents the results of an analysis of the implications for technology choice, generation capacity, energy reliability, and cost to ratepayers of that decision, combining a national electricity market model with a regional model that includes market power and an economic impact model. The results suggest several issues that will be key to the acceptability and effectiveness of cap-and-trade systems for regional climate change mitigation policy, including rules for distribution of allowances and subsidies for energy efficiency programs.     

Understanding soluble arsenate removal kinetics by zerovalent iron media

Zerovalent iron filings have been proposed as a filter medium for removing arsenic compounds from potable water supplies. This research investigated the kinetics of arsenate removal from aqueous solutions by zerovalent iron media. Batch experiments were performed to determine the effect of the iron corrosion rate on the rate of As(V) removal. Tafel analyses were used to determine the effect of the As(V) concentration on the rate of iron corrosion in anaerobic solutions. As(V) removal in column reactors packed with iron filings was measured over a 1-year period of continuous operation. Comparison of As(V) removal by freely corroding and cathodically protected iron showed that rates of arsenate removal were dependent on the continuous generation of iron oxide adsorption sites. In addition to adsorption site availability, rates of arsenate removal were also limited by mass transfer associated with As(V) diffusion through iron corrosion products. Steady-state removal rates in the column reactor were up to 10 times faster between the inlet-end and the first sampling port than between the first sampling port and the effluent-end of the column. Faster removal near the influent-end of the column was due to a faster rate of iron oxidation in that region. The presence of 100 microg/L As(V) decreased the iron corrosion rate by up to a factor of 5 compared to a blank electrolyte solution. However, increasing the As(V) concentration from 100 to 20,000 microg/L resulted in no further decrease in the iron corrosion rate. The kinetics of arsenate removal ranged between zeroth- and first-order with respect to the aqueous As(V) concentration. The apparent reaction order was dependent on the availability of adsorption sites and on the aqueous As(V) concentration. X-ray absorption spectroscopy analyses showed the presence of iron metal, magnetite (Fe3O4), an Fe(III) oxide phase, and possibly an Fe(II,III) hydroxide phase in the reacted iron filings. These mixed valent oxide phases are not passivating and permit sustained iron corrosion and continuous generation of new sites for As(V) adsorption.     

Systemic mycoses in marine mammals

Thirty-four cases of systemic mycosis in marine mammals were represented by 9 genera of fungi. All cases were characterized by pulmonary involvement, with miliary spread to abdominal organs. Cases were geographically distributed among Hawaii, northern United States, Europe, New Zealand, and southern Asia.     

Instructions about nicotine dose influence acute responses to nasal spray.

Effects of substance use are typically assumed to be related to pharmacological actions. However, beliefs about the drug content of a substance may strongly influence subjective and reinforcing responses to that substance (i.e., "placebo" effects). We examined the subjective and reinforcing effects of a nasal spray containing no nicotine as a function of instructions about the nicotine content of the spray (Told Nicotine vs. Told No Nicotine). Smokers (n=49) not interested in quitting smoking abstained overnight prior to a single session in which they were randomly assigned to one of three groups, involving one of the two instructional sets or a group that got no spray. Following dose instructions, subjects in the two spray groups were administered one set of four sprays from the spray bottle and then rated them intermittently on items related to "reward" (e.g., "liking", amount they would pay for more) and other effects. At the same time points, they also rated mood, craving, and withdrawal, and had heart rate and blood pressure measured. Reinforcement was then determined by the number of ad libitum sprays they self-administered during a 20-min period. The no-spray group simply rested quietly during the session, while measures were assessed at the same time points as subjects in the other two groups. Those in the Told Nicotine group reported greater spray ratings of "how much nicotine," "liking," "satisfying," "buzz/head rush," and "similar to smoking" compared with the Told No Nicotine group. Craving decreased more for those Told Nicotine versus those Told No Nicotine, but also decreased more for those Told No Nicotine compared with the no spray group. There were no significant differences in amount they would pay for more sprays, withdrawal, mood, cardiovascular responses, or in spray self-administration. These results show that instructions about the nicotine content of a novel delivery device (nasal spray) can influence self-reported spray ratings and reduce craving but are limited with respect to effects on other measures of drug response.