Michael D. Mosher

Acute Physiologic and Chronic Histologic Changes in Rats and Mice Exposed to the Unique Hallucinogen Salvinorin A

Abstract Salvinorin A is a unique hallucinogen that is seeing increased use in humans. It is not currently a controlled substance and is used as a legal alternative to controlled substances. Usually smoked or buccally absorbed by chewing, doses of approximately 200mcg can produce profound hallucinogenic effects of short duration. The mechanism of action of salvinorin A is at the k-opioid receptor. Little data is available on the medical effects of this substance so animal studies were undertaken to explore the acute toxic effects of this substance in rats and the chronic effects in mice. Rats were anesthetized and administered salvinorin A at 1600mcg/kg or vehicle. Recordings were made of galvanic skin response, EKG, temperature, and pulse pressure for 100 minutes. Mice were chronically exposed to vehicle or 400, 800, 1600, 3200, or 6400 meg/kg of salvinorin A for two weeks. After exposure the animals were sacrificed and brain, heart, kidney, bone marrow, blood and spleen were removed, fixed, sectioned, stained and examined by light microscopy. No effects were seen on cardiac conduction, temperature, or galvanic skin response. A nonsignificant rise was seen in pulse pressure. Histologic studies of spleen, blood, brain, liver, kidney, and bone marrow did not find any significant histologic changes at any of the doses examined. These data suggests that the toxicity of salvinorin A is relatively low, even at doses many times greater than what humans are exposed to. However, further studies should be done on blood pressure effects. The psychological impact of this potent hallucinogen should also be investigated.

Design, synthesis and biological evaluation of a novel class of anticancer agents: Anthracenylisoxazole lexitropsin conjugates

The synthesis and in vitro anti-tumor 60 cell lines screen of a novel series of anthracenyl isoxazole amides (AIMs) (While not a strict acronym, the designation AIM is in honor of the memory of Professor Albert I. Meyers.) (22-33) are described. The molecules consist of an isoxazole that pre-organizes a planar aromatic moiety and a simple amide and/or lexitropsin-oligopeptide. The new conjugate molecules were prepared via doubly activated amidation modification of Weinrebs amide formation technique, using SmCl(3) as an activating agent which produces improved yields for sterically hindered 3-aryl-4-isoxazolecarboxylic esters. The results of the National Cancer Institutes (NCI) 60 cell line screening assay show a distinct structure activity relationship (SAR), wherein a trend of the highest activity for molecules with one N-methylpyrrole peptide. Evidence consistent with a mechanism of action via the interaction of these compounds with G-quadruplex (G4) DNA and a structural based rational for the observed selectivity of the AIMs for G4 over B-DNA is presented.

Double activation preparation of an acridinyl-isoxazolyl-lexitropsin

Abstract The coupling of a sterically hindered acridinyl isoxazole ester directly to the amine group of a lexitropsin is significantly improved by double activation, using trimethylaluminum to activate the amine portion and samarium (III) chloride to enhance the carboxylate reactivity.

Bis-anthracenyl isoxazolyl amides have enhanced anticancer activity

Dimeric analogs of Anthracenyl Isoxazole Amides (AIMs) (the designation AIM is in honor of the memory of Professor Albert I. Meyers) were prepared and dimer 6 exhibited the highest efficacy to date for this class of anti-tumor compounds against the human glioma Central Nervous System cell line SNB-19.

Overview of the Brewing Process

In this chapter, we will explore the basic steps required in modern beer brewing in the USA. Much of what is presented here is discussed again in other chapters in greater detail. This chapter provides a sketch of the overall process and will aid us by providing a blueprint to follow as we explore these subjects. While there are some significant differences in the process steps taken for the homebrewer versus the industrial-scale brewer, the basic steps are the same. In the USA, the most common materials will be the focus of our overview. Other materials such as adjunct grains and fermentables, rice hulls and fillers, hop oils and isomerized extracts, artificial carbonation, and finings are frequently used. Their specific use will be covered as we explore the overall process steps in detail later in this text.

Introduction to Brewing Science

When we think about making beer, what comes to mind? Often we rely on those images with which we are familiar, the TV ads showing brewers sitting around sampling their work or the server pulling a tap to dispense a beautiful yellow liquid into a glass. But there is more to the process than we see on the television. And the science behind that process is quite interesting. We will begin our look into the brewing process from the very beginning of civilization and build our understanding of the methods used today. Along our journey, we will uncover the science behind the scenes and gain a much deeper understanding of this very important beverage.

Quality Assurance and Quality Control

The brewing process is essentially complete when the beer is packaged. But is it really? In this chapter, we will explore the principles of quality control and assurance. These two principles are used by the brewer to ensure that the brewery operates with the highest standards. When coupled with total quality management or other guidelines, the brewery will reproducibly manufacture product that has the best chance of being sold to consumers.

Molecules and Other Matters

In this chapter, we will explore the basics of general and organic chemistry that are needed to understand what happens during beer brewing. Learning how to draw the structure of the compound will allow us to understand the function of those compounds and their likely role in brewing. To fully understand the entirety of general and organic chemistry would require two full years of study. Many texts can aid in that study, but here we will look into the basics from the brewers’ perspective.

The “Food” for the Brew

Brewing beer requires that we convert starches into sugars in order to ferment them. In this chapter, we will uncover the conversion of starches into sugars. This requires the modification of barley (primarily) into malt. The step is very important, because unmodified barley hinders our ability to make sugars later in the process. We will explore the actual processes that make malt and the equipment that is used in the process. In this chapter, we will also take a look at what some brewers consider to be the most important ingredient in making beer; water. We will examine the makeup of water and how its quality impacts the brewing process.

Cooling and Fermenting

After boiling, the wort is prepared for the fermentation stage by cooling it rapidly. This involves the use of a wort chiller. The liquid is then placed into a fermenter and yeasts are added. Fermentable sugars are converted into alcohol and carbon dioxide in this process. Uncovering the principles behind these processes reveals a wealth of theory in thermochemistry and physics. That will be the focus of this chapter.