«When Albert Hofmann created LSD 25 during experimentation in his laboratory, he had no idea what was to become of it, or what kind of an impact it would have. "Dr. Humphry Osmond invented the term 'psychodelic', which was later amended to...» Document abstract
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SummaryWhen Albert Hofmann created LSD 25 during experimentation in his laboratory, he had no idea what was to become of it, or what kind of an impact it would have. "Dr. Humphry Osmond invented the term 'psychodelic', which was later amended to 'psychedelic to get rid of the nuthouse connotation of 'psycho'." (Wolfe 39). This term encompasses a whole generation, a cultural revolution that took place during the 60's. Since its creation, LSD, among other psychedelics, has had a great impact on the American culture.
Table of Contents- Albert Hofmann was the chemist who created LSD 25 (lysergic acid diethylamide) in his laboratory in Sandoz Pharmaceutical Laboratories in Basil, Switzerland in 1938.
- Dr. Werner Stoll, the son of Sandoz president Arthur Stoll and a colleague of Albert Hofmann's, was the first person to investigate the psychological properties of LSD
- The government, especially the CIA, became deeply involve in research and testing of psychedelic drugs
- The CIA tested acid on unwitting American citizens, volunteers, and themselves. Results were inconsistent.
- Leary was given a 10 year jail sentence in 1970 for possession of less than a half ounce of marijuana (Brown "Mavericks...").
- Kesey's place in La Honda became a center for the emerging counterculture. People dropped in whenever they felt like it.
- LSD has been found by many to cause profound changes in the mental state.
- He compared the brain to a reducing valve something that closes the Doors of Perception and lets in only the information that is need.
- We must not forget visual art, for that was also very affected by the discovery of LSD.
- The whole psychedelic scene calmed down after the sixties, but never quite stopped.
«Genetic mutations are not uncommon. They can happen for a variety of reasons and have a variety of effects. Those with negative effects are weeded out by natural selection, and those with positive effects prevail and are accumulated due to natural...» Document abstract
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SummaryGenetic mutations are not uncommon. They can happen for a variety of reasons and have a variety of effects. Those with negative effects are weeded out by natural selection, and those with positive effects prevail and are accumulated due to natural selection. These mutations can be caused by a variety of reasons such as copying errors during cell division, exposure to ultraviolet rays and viruses, or can happen deliberately (Wikipedia). Most mutations have no effect on a species or its individuals because DNA repair is quite successful in fixing most mistakes before they become permanent. But there are very few mutations which have beneficial consequences. One such mutation that results in benefits for a species/individuals that make it up, is the CCR5-Delta32 mutation. During this mutation the Delta32 base pair is deleted in human CCR5 which results in immunity to HIV Type 1 (if homozygous) or increased resistance to AIDS (if heterozygous) (Wikipedia). The very controversial current argument on this subject asks several questions: if the absence of the CCR5-Delta32 is ultimately beneficial to humans, or if its negative side effects outweigh the benefits; as well as, where the origins of this mutation are.
Table of Contents- The CCR5-Delta32 mutation is quite a recent discovery which is highly debated and still very circumstantial.
- There is also another possibility that this mutation is much older and has resulted due to smallpox outbreaks in Europe, which is the less popular theory.
- Along with protecting against HIV, the allele also protects against smallpox and the plague.
- Many aspects of CCR5-Delta32 are highly controversial. Its origins alone have split the scientific community.
- The basic question asks which is more beneficial: the absence of the CCR5 receptor or its existence?
«The two venomous lizards of the world are impressive creatures about which much misinformation has been spread for centuries. They have been thought to possess supernatural features such as poisonous breath, a stinging tail and the ability to spit...» Document abstract
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SummaryThe two venomous lizards of the world are impressive creatures about which much misinformation has been spread for centuries. They have been thought to possess supernatural features such as poisonous breath, a stinging tail and the ability to spit their venom. The Gila monster (Heloderma suspectum) reaches a maximum length of approximately 50 cm, whereas the beaded lizard (Heloderma horridum) is larger, reaching almost a meter. They are both heavily built and possess massive muscles of mastication with powerful biting capacity. The venom delivery apparatus consists of a pair of anterior, multilobed, interior labial glands that open through a series of ducts into the labial mucosa. Their teeth are lancet shaped, grooved, and loosely attached to the jaws. When the reptile becomes agitated, it salivates heavily, producing a flow of venom into the labial mucosa. It bites with a powerful, chewing motion, instilling venom into the wounds by capillary action along the grooves of the teeth. Teeth may be left in the wounds, especially if the lizard must be forcefully removed from the victim. The tenacious creature may still be attached when help arrives. Effective envenomation occurs in only about 70% of bites.
Table of Contents- Anatomy
- Venom
- Clinical Presentation
- Management
- Prehospital Care.
- Hospital Care.
- Morbidity and Mortality
«The term pit viper comes from the presence of paired, highly sensitive, thermoreceptor organs (pits) present on the forward portion of these snakes' heads. These structures, also known as foveal organs, serve the snake in locating prey, aiming...» Document abstract
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SummaryThe term pit viper comes from the presence of paired, highly sensitive, thermoreceptor organs (pits) present on the forward portion of these snakes' heads. These structures, also known as foveal organs, serve the snake in locating prey, aiming strikes, and adjusting venom dose. The foveal organs can detect temperature changes of as little as 0.003° C (0.0054° F). A neurologic feedback loop between the foveal organs and the venom delivery apparatus may allow the snake to adjust the volume of venom it injects into a potential meal or a perceived threat.
Table of Contents- Anatomy
- Pit Vipers.
- Coral Snakes.
- Venoms
- Pit viper venom has both offensive (i.e., food gathering) and defensive functions.
- A popular belief is that juvenile rattlesnakes are more dangerous than adult snakes because their venom is more toxic and they are unable to control the volume they release.
- Neurotoxicity has been clinically associated with severe myotoxicity in many cases.
- Mojave toxin is thought to inhibit acetylcholine release at the presynaptic terminal of the neuromuscular junction.
An Assessment of Historical and Contemporary Land Use at Hedgehog Mountain, Freeport, Maine, via Field Observation
«The purpose of this investigation was to collect information that allowed the formulation of a hypothesis as to the land-use history of the Hedgehog Mountain preserve, and to correlate empirical observations with a limited literature review in an...» Document abstract
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SummaryThe purpose of this investigation was to collect information that allowed the formulation of a hypothesis as to the land-use history of the Hedgehog Mountain preserve, and to correlate empirical observations with a limited literature review in an attempt to validate the hypothesis presented.
The author hypothesizes that this land was used primarily for grazing livestock and timber extraction until the homestead was abandoned, after which timber harvesting may have continued for a number of decades. Except for motorized recreational vehicle use the land is presumed to have been free of major human disturbance for the past fifty years or more.
The author hypothesizes that this land was used primarily for grazing livestock and timber extraction until the homestead was abandoned, after which timber harvesting may have continued for a number of decades. Except for motorized recreational vehicle use the land is presumed to have been free of major human disturbance for the past fifty years or more.
Table of Contents- INTRODUCTION:
- METHODS:
- RESULTS:
- Hydrology:
- Disturbance History:
- DISCUSSION:
«Prior to delineating the organization of specific intraneuronal signaling pathways, it is important to consider, in general terms, their role in helping neurons interpret and respond to the barrage of afferent stimulation impinging on them...» Document abstract
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SummaryPrior to delineating the organization of specific intraneuronal signaling pathways, it is important to consider, in general terms, their role in helping neurons interpret and respond to the barrage of afferent stimulation impinging on them continuously. From an evolutionary perspective, second messenger systems predate neurotransmitters and neurotrophins, examples of first messengers detected by cell surface receptors. Before the advent of neurotransmitters, prokaryotic organisms relied on cyclic adenosine monophosphate (cAMP) and other intracellular signaling pathways to coordinate diverse responses located in disparate parts of these unicellular organisms to changes in ambient nutrients or conditions. Neurotransmitters and neurotrophins have evolved subsequently to take advantage of these internal signaling pathways that have undergone a parallel growth process.
Table of Contents- Intraneuronal signaling pathways do more than merely enlarge the sphere of influence of afferent stimuli beyond the local environment of the cell surface receptor.
- Although the overwhelming majority of psychiatric drugs target extracellular receptors or uptake sites, the explosion of information on intraneuronal signaling pathways suggests that these may represent suitable drug targets.
- Psychiatrists have long been taught that a true understanding of normal and abnormal behavior requires an appreciation of the interplay of forces lurking beneath the surface.
- Neurotransmitter receptors may couple to adenylate cyclase via different classes of G proteins, referred to as Gs or Gi, depending on whether they stimulate or inhibit cyclic AMP formation.
- Cyclic GMP Besides cyclic AMP, another cyclic nucleotide, cyclic guanosine monophosphate (GMP) has been identified as a second messenger regulated by neurotransmitter receptor stimulation.
- Because the effects of cAMP are mediated to a large extent via activation of a kinase, it was generally assumed that each of these second messengers acted in a similar fashion.
- However, this view has been challenged recently in light of animal studies demonstrating that inositol levels in brain are unaffected by lithium concentrations within its therapeutic range.
- These alternate arrangements emphasize the notion that intracellular signaling cascades have evolved in ways that heighten their versatility, with each of the components having multiple signaling capacities.
- Another family of tyrosine kinases has been identified that differs from the receptor tyrosine kinases in that it contains only the cytoplasmic domain.
- Cross-Talk Among Signaling Pathways The organization of intraneuronal signaling pathways allows for a high degree of interaction or cross-talk among pathways
«Structure and Function of Voltage-Gated Ion Channels Voltage-gated ion channels allow the flow of ions in response to changes in membrane voltage and are key elements in neuronal excitation and inhibition. Although ion channels can usually pass more...» Document abstract
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SummaryStructure and Function of Voltage-Gated Ion Channels Voltage-gated ion channels allow the flow of ions in response to changes in membrane voltage and are key elements in neuronal excitation and inhibition. Although ion channels can usually pass more than a single type of ion, voltage-gated channels are named according to the predominant ion that flows when the channel is open. Ion channels that are selective for Na+, K+, Ca2+, or Cl– have been described in neuronal membranes. Certain ion channels that are gated directly by chemical neurotransmitters such as glutamate and acetylcholine are selective for Na+, K+, and Ca2+ but exclude Cl– and are called nonselective cationic channels.
Table of Contents- Sodium (Na+) Channels Na+ channels are primarily responsible for the fast upstroke of action potentials, although in some neurons Na+ channels also contribute to lower-level depolarizations and pacemaker firing.
- Relations between primary protein structure and ion channel function in Na+ channels have been examined using mutations of specific amino acid residues.
- The net effect is similar to the scorpion toxins. Finally, certain local anesthetic drugs, including lidocaine and procaine, block Na+ channels by binding reversibly to sites within the hydrophobic regions of the ion channel.
- Delayed-rectifier channels open slowly and show little inactivation during prolonged depolarizations.
- M channels represent a class of K+ channels that are activated in a time- and voltage-dependent fashion but are blocked by the neurotransmitter, acetylcholine, acting at muscarinic receptors.
- KATP channels exist in the CNS and appear to be involved in regulating the release of certain neurotransmitters and perhaps in determining the response of some neurons to changes in intracellular energy levels.
- Calcium (Ca2+) Channels Because Ca2+ is involved in numerous cellular events including enzyme activation, gene expression, and neurotransmitter release, the regulation of intracellular Ca2+ levels is of major importance to neurons.
- Most structural information about Ca2+ channels comes from skeletal muscle HVA Ca2+ channels.
«Classes of Neurotransmitters Much of the information transfer between neurons in the CNS occurs via chemical synapses. These synapses use a variety of messengers (neurotransmitters) that are released in a Ca2+-dependent fashion from presynaptic...» Document abstract
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SummaryClasses of Neurotransmitters Much of the information transfer between neurons in the CNS occurs via chemical synapses. These synapses use a variety of messengers (neurotransmitters) that are released in a Ca2+-dependent fashion from presynaptic terminals and act on specific protein receptors to produce biochemical and excitability changes in the receiving cell. There are two primary groups of neurotransmitters—low–molecular-weight amines and neuroactive peptides. These agents act on two classes of receptors, ligand-gated ion channels, at which the binding of the transmitter directly opens ion channels in the membrane, and G protein coupled receptors. The activated G protein then acts on ion channels or alters biochemical second-messenger systems. Physiologists classify synaptic transmission according to the speed of transmission (fast or slow) and according to the nature of the response (excitatory or inhibitory).
Table of Contents- Currently, there are nine low–molecular-weight amines that serve as neurotransmitters.
- Conductance Mechanisms Underlying Neurotransmitter Actions
- Structure of Neurotransmitter Receptors Considerable information now exists about the primary structure of neurotransmitter receptors.
- The ligand-gated ion channels gated by extracellular ATP (called P2X receptors) are exceptions to the scheme described above and have structures more typical of the inwardly rectifying K+ channels.
- G-protein coupled receptors have a distinctly different structure from the ligand-gated ion channels.
«In its simplest form, the postsynaptic response to neurotransmitter release can be mediated by a single protein complex. For example, nicotinic acetylcholine receptors are self-contained stimulus-response modules that both detect a stimulus,...» Document abstract
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SummaryIn its simplest form, the postsynaptic response to neurotransmitter release can be mediated by a single protein complex. For example, nicotinic acetylcholine receptors are self-contained stimulus-response modules that both detect a stimulus, acetylcholine, and generate a response, passage of ion currents. In a similar vein, other members of this superfamily of ionotropic receptors, including g-aminobutyric acid (GABA) and glutamate receptors, have the ability to function in a manner that is independent of the intracellular signaling pathways discussed. Thus, in contrast to growth factor or G-protein–coupled receptors, which often recruit elaborate cascades to elicit a response, the simplicity of self-sufficient ionotropic receptor complexes represents an optimal design for achieving reliability, precision, and speed. However, this view of ionotropic receptors as insulated from their social environment has had to be abandoned in the face of overwhelming evidence that this class of receptors is dynamically regulated by intraneuronal signaling pathways. Although these receptors do not rely on intraneuronal signaling pathways to operate ion channels, because these channels are an intrinsic feature of the receptor complex the linkage between ligand binding and ion channel gating is nevertheless subject to regulation by the network of intraneuronal signaling pathways just described. For example, phosphorylation of the GABA or glutamate receptors modulates their response to ligand exposure.
Table of Contents- Long-Term Depression The principle that ion channels are regulated by second messenger pathways is of central importance in considering how neuronal responses are altered by experience.
- Long-Term Potentiation The notion that coactivation of multiple second messenger pathways can have a qualitatively different impact than any one individually is also borne out in another well-known model of synaptic plasticity, long-term potentiation.
- This unusual property of NMDA receptors provides a molecular mechanism for conferring associative properties on long-term potentiation.
- Role of Phosphorylation The associative property of this model of synaptic plasticity has focused attention on deciphering the intraneuronal signaling pathways that mediate the long-term change in synaptic transmission triggered by NMDA receptor stimulation.
- Actions of Psychotropic Drugs In addition to providing insight into the molecular mechanism underlying synaptic plasticity, studies of intraneuronal signaling pathways are also directly relevant to deciphering the mode of action of psychotropic drugs.
- Evidence supporting this theory has been provided by recent studies demonstrating that opiate withdrawal is attenuated in transgenic animals that are deficient in CREB.
«Resting Membrane Potential In nerve cells, potassium ions (K+) are at higher concentration inside the membrane than outside whereas the opposite is true for sodium (Na+), calcium (Ca2+), and chloride (Cl–) ions (Fig. 1.9-1). The bulk solutions on...» Document abstract
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SummaryResting Membrane Potential In nerve cells, potassium ions (K+) are at higher concentration inside the membrane than outside whereas the opposite is true for sodium (Na+), calcium (Ca2+), and chloride (Cl–) ions (Fig. 1.9-1). The bulk solutions on either side of the membrane are electrically neutral, with most of the intracellular negative charge being contributed by large organic anions (acids and proteins). The differential distribution of ions across neuronal membranes results in part from the action of membrane pumps that use energy from adenosine triphosphate (ATP) to drive ions against a concentration gradient into or out of the cell. The best characterized pump is the Na+-K+ adenosine triphosphatase (ATPase) that transports 3 Na+ out of and 2 K+ into the cell during each cycle. Because an unequal amount of charge is moved during each cycle, the pump is electrogenic and produces an electrochemical potential across the membrane that makes the inside of the membrane negative with respect to the outside. Na+-K+ ATPase activity is a major contributor to brain energy utilization, with as much as 40 percent of brain oxygen consumption resulting from pump activity required to reestablish ionic homeostasis following action potential firing and synaptic transmission. The cardiac glycosides digoxin (Lanoxin) and ouabain are effective inhibitors of Na+-K+ ATPase in the heart and improve myocardial contractility by depolarizing cardiac myocytes and increasing intracellular Ca2+.
Table of Contents- At rest, neuronal membranes are permeable to K+ and Cl– and to a lesser extent to Na+, partly because of the flow of ions through nongated leakage channels.
- For each ion in solution there is a specific membrane potential at which the opposing forces of the electrical gradient and concentration gradient are balanced.
- Because ions do not directly penetrate the lipid membrane but rather flow through ion channels, the ion channels can be thought of as variable resistors.
- Active Membrane Properties: Action Potentials Changes in membrane potential have important effects on excitability because certain ion channels are activated (gated) by voltage changes.
- Many axons are encased in myelin sheaths that allow them to send action potentials over longer distances.
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