Thursday, October 31, 2019

Security Risk Mitigation Policies Coursework Example | Topics and Well Written Essays - 500 words

Security Risk Mitigation Policies - Coursework Example The first option should involve different methods for making it more intricate to intercept and locate the wireless signals. This way, hackers will have a hard time locating the organization’s signal. Additionally, the other principal option will involve utilization of encryption in order to preserve confidentiality even when the wireless signal gets intercepted (Choi et al., 2008). It will also be imperative for the organization to utilize signal-hiding techniques so as to properly intercept wireless transmissions. This is because for any attacker to successfully intrude into a wireless network, they will first need to locate and identify the wireless network. This will be achieved by utilizing numerous steps that will make it extremely difficult to locate the organizations wireless access point. Therefore, the company should include some of the easiest as well as least costly methods which include turning off the service set identifier (SSID) which broadcasts by wireless access points. This will not only make it hard for hackers to have no access, but also, it will make it hard for them to access the company’s servers and download sensitive and personal materials. Moreover, assigning cryptic names to the SSIDs will also make it hard to access the organizations data. Additionally, reducing the organization’s signal will provide requisite coverage.

Tuesday, October 29, 2019

Germans children Essay Example for Free

Germans children Essay The children of the Jewish Holocaust during the Nazi era were placed under very unjust, cruel, and exacting circumstances. Education, a basic right of children in developed nations of that era, was denied to Jews in areas of Europe where Hitler’s rule and influence were adopted. During the time of transition during which the exclusion of Jewish children from schools was being implemented, non-Jewish children were formally taught that their Jewish counterparts were inferior. In order to do this, Jewish youth were used to demonstrate the appearance of inferiority by placing them in front of the class and pointing out their characteristic phenotypes as being undesirable. Occurrences like this placed severe limitations on the ability of Jews to learn in these schools, as they were constantly mistreated, neglected, and abused because of their race. Growing restrictions were also placed upon these children’s accessibility to the resources within the schools, until finally they were prevented altogether from attending schools, which were open now only to Germans children (FCIT). Fred Spiegel describes his first weeks of school (shul) in Dinslaken, Germany, where he had to attend a Jewish shul, as the German schools were no longer open to Jewish children (Spiegel 27, 29). The alternative Jewish schools were understaffed and unsupported by the state. Spiegel himself recalls his school’s having only one teacher (29). Later, Arnold Blum recalls an even more frightening occurrence in which his school was being burned before his very eyes (Blum, 20). He immortalizes this event in his memoir â€Å"Kristallnacht† (20). More than just restricting these Jewish children’s ability to attend state schools, they were being stripped of their right to any education at all in the burning of their Jewish school. The parks were also an area in which Jewish children felt the abuse of Nazism. German children, who were armed with the idea that Jews were inferior, played in the parks and discriminated against the Jews they found there. The Jewish children were called names, spat upon, and otherwise abused by non-Jewish children. Spiegel also describes his time spent in the park behind his house in Dinslaken. The last time he remembers going there, he was cursed and called a â€Å"Dirty Jew† by the other children (Spiegel, 28). His grandfather too was cursed by his friends. Kristallnacht, which occurred on November 9-10, 1938, ushered in the destruction of all that was Jewish. Beyond the burning of schools came the burning and destruction of Jewish homes, businesses and synagogues (Blum, 20). Fred Spiegel recalls the night he was forced to leave his home and the abuses even he as a child faced. He was already emotionally crippled by the sight of his community being gutted by fires. He further recalls being cursed and spit upon by the non-Jews as he and his family were being forced from their homes. Some Jews were evicted to concentration camps and ghettos. Others were turned out of the country altogether. Spiegel writes about the events he witnessed upon entering his home, which had been destroyed, for the last time as a child: â€Å"My mother, sister, and my Aunt Klara were standing on the balcony crying. My grandfather had been arrested and taken away by two policemen. [†¦] Soon the two policemen returned. We were told we could not stay in our apartment and had to go with them. On the way out we passed by the downstairs apartment that was empty because the Abosch-family, a Jewish family who had rented it from my mother, had been expelled to Poland a few weeks earlier. Their apartment too was totally destroyed† (Spiegel, 30). Children were also abused through the mandate that they live in the ghettos. Because the ghettos were sequestered from the rest of the German civilization and restrictions were placed on items that could be brought into the area, children often suffered hunger. Many of them were reduced to smuggling food into the ghettos in order to aid in the support of their families. While these were very risky actions, some Jewish children were left even more vulnerable as their parents were killed or taken away to concentration camps. These orphaned children were left alone in the ghettos to make a living under doubly cruel circumstances.

Saturday, October 26, 2019

Cocaine Pharmacology and Effects on the Brain

Cocaine Pharmacology and Effects on the Brain Cocaine is a highly addictive substance abused worldwide. Its primary mechanism of action involves blockage of dopamine, norepinephrine and serotonin transporters in specific brain regions, mainly the dopamine reuptake system located on mesolimbic neurons. Cocaine increases the dopaminergic neurotransmission and triggers adaptive changes in several neuronal circuits underlying reinforcement, reward, sensitisation and the high addictive potential of cocaine. However, the long-lasting behavioural effects associate with cocaine addiction show there is complex neurotransmitters interaction within the reward circuit. Excitatory amino acid and inhibitory GABA transmitters also play a part in these changes. Glutamatergic systems regulate dopamine function, while GABAergic modulate the release of basal dopamine and glutamate. Understanding of the molecular and cellular mechanisms that lead to cocaine addiction has given new treatment methods in the pharmacological field to develop better med icine. Especially, useful monoamine agonists treatment may be successfully in controlling behaviour and lead to long term moderation of drug taking. However, more studies are needed in order to identify safe and efficacious pharmacotherapy. Introduction Cocaine, an alkaloid derived from the leaves of Erythroxylon coca is a psychostimulant drug linked to human addiction (Dackis et al., 2001). Cocaine acts as a local anaesthetic with sympathomimetic and vasoconstrictor properties (White and Lambe, 2003). In addition, cocaine is a potent uptake blocker for dopamine (DA), norepinephrine and serotonin (Carrera et al., 2004). As shown in figure one, the chemical structure of cocaine molecule contains two rings, the six-carbon phenyl ring shown on the right and the unusual nitrogen (N)-containing ring shown on the left, both necessary for its biological activity (Meyer and Quenzer, 2005). Cocaine acts by blocking the dopamine transporter within the mesocorticolimbic reward system. Blockade of the transporter increases the level of dopamine in this region of the brain. Increased dopamine level is responsible for the euphoric effect of cocaine (Butterner et al., 2003). However, the long lasting effects of behavioural characteristics of cocaine addiction, such as sensitisation and the vulnerability to the reinstatement of drug seeking years after the acute rewarding effects of the drug have disappeared, shows that there must be complex interactions between additional neurotransmitter systems (Kalivas, 2004). In contrast to dopaminergic system, excitatory amino acid and inhibitory GABA transmitters also play a role in these changes. Glutamatergic systems regulate dopamine function, while GABAergic modulate the release of basal dopamine and glutamate (Baler and Volkow, 2006). Additionally, cocaine can also interact with several receptors and ion channels, including nicotin ic acetylcholine, and opioid receptors coupled to voltage-gated Ca2+ and K+ channels (Kobayashi et al., 2007), resulting in prolonged elevation of extracellular dopamine. The potential abuse of cocaine is mainly based on the rapid development of tolerance to the euphoric effects (Butter et al., 2003). Cocaine addiction is an uncontrollable and continually relapsing drug taking disorder (Torregrossa and Kalivas, 2008). The behavioural manifestation of addiction is mediated by adaptations that chronic administration of drug abuse elicits at the level of individual neurons in the CNS. These adaptations alter the functional properties of neurons, which in turn change the properties of the functioning of neural circuits in the brain in which these neurons are involved (Nestler, 1997). The probability that one will become addicted to cocaine depends on the method, the frequency and the duration of ones cocaine intake (Carrea et al., 2004). Historical aspect of cocaine use The use of cocaine for personal satisfaction dated back over thousands of years ago, when Erythroxylon coca, the plant from which cocaine is extracted was used by indigenous people from Andes and South America for religious, mystical, social, and medical purposes (Dackis et al., 2001). The coca leaf was chewed by these communities because of its euphoric effects and its ability to reduce fatigue and hunger and to enable sustained periods of heavy labour (White and Lambe, 2003). This leaf was introduced in Europe in 1492 by the Spaniards, when they conquered South America and discovered that this leaf would be useful for performing hard labour (Julien et al., 2008). Eventually, the Spaniards started using the coca leaf as a method of payment for the native worker in gold and silver mine, who would take the leaf to reduce appetite and increase physical stamina. Cocaine alkaloid was first isolated by a German chemist Friedrich Gaedche in 1855 (Julien, 2008). The ability of cocaine in reducing fatigue and hunger were recognised by Sigmund Freud who used cocaine himself. Freud and others also recognised the ability of cocaine to cure opioid addiction. As a result, Freud prescribed cocaine to his patients who were addicted to morphine (Boghdadi and Henning, 1997). Unfortunately, many of these patients became addicted to cocaine themselves (Grilly, 1998). Morphine, which is similar to cocaine in reducing hunger, was extracted from opium in the early 1800s by Friedrich Wilhelm Adam Sertà ¼rner. But its use spread in 1853 when the hypodermic needle was developed (Grilly, 1998). Morphine was used as a pain reliever and as a cure for opium and alcohol addiction. Its extensive use during the American Civil war resulted with people suffering from the soldiers disease (addiction), (Julien et al, 2008). Forms of cocaine The use of crack cocaine, or crack, was first reported in 1980 in Europe and the US as a new drug with rapid stimulating effects. Crack cocaine is a by-product of cocaine, C17H21NO4 (figure 1). However, crack is formed through different processes. First, the coca leaves are transformed into a product known as basic cocaine paste. The paste is then turned into either crack cocaine through chemical treatment with sodium bicarbonate, or into a less potent water soluble salt, cocaine hydrochloride when it is refined with either acetone or sulphuric and hydrochloric acids. The powdered hydrochloride salt can be snorted, and because it is water soluble, it can be injected intravenously (Boghdadi et al., 1997). However, in the hydrochloride form, cocaine decomposes when it is heated and is destroyed to temperature, making it unsuitable for use by inhalation. In contrast, crack cocaine is converted to a stable vapour by heating it (Julien et al., 2008), making it more potent than the concentrated form. The paste and crack cocaine forms can be smoked either on their own or together with tobacco or cannabis-marijuana and sometime mixed with heroin and sold on the street (Goldstein et al., 2009). Cocaine hydrochloride compared to crack cocaine, is less potent and it is used as a local anaesthetic. Its use as anaesthetic first came about in 1884, after Niemann described its anaesthetic properties such as bitter taste and the resultant unusual numbness when applied to the tongue (Goldstein et al., 2009). By the late 1800s, when morphine was already used as a pain reliever, the use of cocaine for its analgesic properties which includes nerve blocking anaesthesia, epidural, and spinal anaesthesia has began to spread (Goldstein et al., 2009). Both cocaine hydrochloride and morphine are still used medically today as anaesthetic, despite their addictive properties. Cocaine hydrochloride is used as a vasoconstricting anaesthetic agent in surgery for ears, nose, and throat (White et al., 2003), while morphine is used as anaesthetic to relieve severe pain. Morphine acts through mu, kappa, and delta opioid receptor to block pain messages to the central and peripheral nervous system (Jul ien et al., 2008), However, morphine produces euphoria by interacting mainly with the mu opioid receptor (rosin et al., 2000). Aim: The aim of this project is to view the complex interaction between cocaine and cocaine receptors and the mechanisms of action of cocaine. Special emphasis will be placed on cocaine tolerance and addiction. To begin with, an overview will be provided on the pharmacokinetics of cocaine by discussing how it is absorbed, distributed, metabolised and excreted. Then, a discussion on how cocaine-induced changes in the peripheral and central nervous system contribute to the euphoric effect and addiction. Finally, an overview of how cocaine dependency could be treated. Pharmacokinetics of cocaine The effect of cocaine on the body depends heavily on the rate of accumulation and the concentration of cocaine at its site of action (the brain) and the duration of contact at these sites (Grilly, 1998). The pharmacokinetics of cocaine refers to its movement in the body with respect to its absorption, distribution, metabolism and excretion from the body and this is dependent on multiple factor such as, route of administration, genetics, and consumption of cocaine (Goldstein et al., 2009). Route of Administration/ Absorption As illustrated in figure two, cocaine is rapidly absorbed from the mucous membranes, the stomach and the lungs. Therefore, cocaine can be snorted, smoked, taken orally, or injected intravenously (Julien et al., 2008). However, the onset and duration of cocaine depends on the method of intake (Grilly, 2006). Cocaine hydrochloride poorly crosses the mucosal membranes when snorted, due to its vasoconstriction properties, thereby constricting blood vessels and limiting its own absorption. Because of the slow absorption of cocaine, its euphoric effect is prolonged when administered intranasally (Boghdadi et al., 1997). Cocaine can be also smoked in the form of crack. Because of its rapid absorption in the pulmonary vascular bed, crack produces an intense high in seconds, peaks at 5 minutes and persists for about 30 minutes. Intravenous injection of cocaine hydrochloride bypasses all the barriers to absorption, placing the total dose of drug immediately into the bloodstream. It produces euphoria in 30-45 seconds (Julien et al., 2008). Distribution After administration, cocaine rapidly penetrates the brain. Initial brain concentrations far exceed the concentration in plasma (Julien et al, 2008). After it penetrates the brain, cocaine is rapidly redistributed to other tissues such as the spleen, kidney, and lungs. Cocaine also binds to plasma protein, albumin and also to ÃŽÂ ±1-acid glycoprotein (Boghdadi et al., 1997). Metabolism Drugs taken orally initially pass through the liver (Figure 2), where they may be metabolised before entering the blood. Cocaine is metabolised primarily into ecgonine methyl ester and benzoylecgonine (Figure 3), the main urinary metabolite of cocaine and can be detected in urine for about 48 hours and up to 2 weeks in chronic users (Butttner et al., 2003). Cocaine is catalysed to ecgonine methyl ester by serum and liver cholinesterases, while benzoylecgonine is hydrolysed non-enzymaticaly (Carrera et al., 2004). Benzoylecgonine have vasoconstrictive properties, however it does not appear to cross the blood-brain barrier readily (Goldstein et al., 2009.). In addition, cocaine is demethylated to formed norcocaine (Figure 3) (Carrera et al., 2004), the only metabolite of cocaine that crosses the blood-brain barrier (Flowler et al., 2001). In the presence of ethanol, cocaine is metabolized to cocaethylene (Buttner et al, 2003). Cocaethylene is as active as cocaine in blocking the presynaptic dopamine reuptake transporter, thereby potentiating the euphoric effect of cocaine, increasing the risk of dual dependency and the severity of withdrawal with chronic patterns of use. This metabolite is more toxic than cocaine and aggravates cocaines toxicity. The half-life of cocaethylene is about 150 minutes, outlasting cocaine in the body (Julien et al., 2008). Even though cocaines plasma half-life is about 50 minutes, several metabolites can be detected by way of urinalysis for up to 2 to 5 days after cocaine overdose (Grilly, 2006). Mechanism of actions of cocaine Cocaines euphoric and reinforcing properties are the result of the obstruction of dopamine transporter (Butterner et al., 2003), thus, increasing dopamine level within the mesolimbic dopamine pathways. The mesolimbic dopamine pathways, shown in figure4, are composed of ventral tegmental area (VTA), the prefrontal cortex (PFC), Hipocampus, amygdale, and the nucleus accumbens (NAc) (Cornish and Kalivas, 2001) (figure 5). The nucleus accumbens (NAc) which consists of two sub-regions, the core and the shell, is believed to be the site for both the primary reinforcing properties of drugs of abuse and conditioned control over drug seeking (Kalivas, 2004). Normally, Dopamine is released into the synapse from an axon terminal in response to a pleasurable signal (Dackis and OBrien, 2001). Once this neurotransmitter is released, it diffuses across the synaptic cleft to bind to their respective receptors, D1 and D2 receptors (Howell* and Kimmel, 2008), which are linked to the cAMP second messengers system via membrane-bound G-proteins. D1family receptors (D1 and D5) are coupled to a stimulatory G-protein (Gs), which when activated increases the production of adenylate cyclase and cAMP and stimulation of the D2 family receptors (D2, D3, and D4) leads to the inhibition of adenylate cyclase through activation of an inhibitory G-protein (Gi/Go) (Cunningham and Kelley, 1993). Dopamine is taking back into the presynaptic neurons through the dopamine transporter, as a result shutting off the signal between neurons by preventing new dopamine to be formed (Howell* and Kimmel, 2008). Cocaine, on the other hand, blocks the dopamine transporter (figure 5), preventing the reuptake of dopamine into the presynaptic neurons of the VTA. Blockade of the transporter augment dopamine level in the synaptic clefts, producing continuous stimulation of dopamine receptors (Anderson and Pierce, 2005). Increasing dopamine concentration in the nucleus accumbens is responsible for the euphoric and reinforcing effects of cocaine. Behavioural sensitisation Repeated cocaine treatment increases dopamine levels in the synaptic cleft, which could lead to further stimulation of the dopamine receptors, causing more intense but shorter behavioural responses (Anderson and Pierce, 2005). This progressive change in behavioural response following repeated cocaine administration is known as behavioural sensitisation or reverse tolerance. The enduring neuronal adaptation in the reward circuit that occur after repeated cocaine administration is believed to be associated with motive and reward (Morgan and Roberts, 2004). The neuroadaptations that result in behavioural sensitization is characterised by two processes, known as initiation and expression (Anderson and Pierce, 2005). Initiation, which takes place in the VTA, is referred to as temporary cellular and molecular changes, such as alteration in various genes, second messenger cascades and receptors densities, which occur in response to psychostimulant administration, while expression is the lon g-lasting neuronal changes that start from the VTA and progress to the nucleus accumbens and striatum to increase behavioural response (Pierce and Kalivas, 1997). It has been reported that repeated cocaine treatment for two weeks increases the sensitivity of dopamine D1 receptors in the olfactory tubercle, nucleus accumbens, ventral pallidum, and substantia nigra and subsensitivity of D2 receptor (Unterwald et al., 1996). Activation of D1 receptors stimulates adenylyl cyclase activity via activation of Gs; increasing sensitivity of D1 and also increased adenylate cyclase and cyclic AMP-dependent protein Kinase (PKA) activity in the nucleus accumbens due to continual activation of Gs protein (Cunningham and Kelley, 1993). However, continuous cocaine treatment decreased D1-like receptor density and function, thereby initiated behavioural tolerance (Keys, and Ellison, 1994). Increased release of dopamine in the nucleus accumbens is also calcium-dependent and relies upon activation of calcium-dependent proteins, calmodulin and calcium-calmodulin kinase II (CaM-KII (Pierce and Kalivas, 1997). It is generally believed that increased calcium conductant and activation of calcium-dependent protein kinase are involved in the release of neurotransmitters in presynaptic nerve terminals and initiation of gene transcription (Evans and Zamponi, 2006). Therefore, continuous activation of calmodulin and CaM-KII by cocaine in the nucleus accumbens may mediate the release of dopamine or other neurotransmitters such as glutamate and GABA that are associated with expression of behavioural sensitisation (Pierce and Kalivas, 1997). D1 receptors located on GABA and glutamate afferents to the VTA are responsible for the release of these neurotransmitters in the nucleus accumbens when activated. Interaction between these neurotransmitters in the VTA changes the regulation of dopamine cell, which initiate long-term neuroadaptations (Cornish and Kalivas, 2001). Glutamatergic systems Excitatory amino acid such as glutamate acts as the main mediators of excitatory signals in the central nervous system (Baler and Volkow, 2006). Glutamate is known to produce its action through ionotropic (NMDA and non-NMDA) and metabotropic (mGluR) subclasses receptors (Danbolt, 1997). Although cocaine does not have a direct influence on brain glutamate systems, repeated exposure to cocaine results in alterations in glutaminergic transmission in the nucleus accumbens (Schmidt et al., 2005). However, the PFC, which transmits major glutaminergic projections to the nucleus accumbens (figure 4) has been most implicated in the regulation of dopamine released from dopamine cell terminals through NMDA and non-NMDA receptors (Kalivas, 1997). It is believed that stimulation of NMDA receptors through a voltage-dependent calcium channel initiate burst firing model in dopamine cells, as a result increasing accumbal dopamine release which is similar to what occurs in behavioural sensitisation (E vans and Zamponi, 2006). Administration of cocaine increases dopamine release presynaptically, which stimulates dopamine D1 receptors, located on descending glutamatergic afferent terminals from the prefrontal cortex (PFC). The D1 receptor in turn, stimulates the release of glutamate in the prefrontal cortex postsynaptic neuron. The released glutamate activates NMDA receptors on the dopaminergic dendrites in this brain area. This sequence of events is augmented by the fact that repeated cocaine administration desensitises dopamine D2 autoreceptors. Desensitisation of D2 receptor reduces the hyper-polarisation of dopamine cells, thereby allowing a further augmentation of dopamine release, which causes supersensitivity of D1 receptors, hence, increasing NMDA activity (Johnson and North, 1992). Because the neuronal circuits are interconnected (figure 5), a reduction in PFC dopamine transmission will activate the nucleus accumbens dopamine release, leading to expression of behavioural sensitisation. Increased glutamate release from the PFC to nucleus accumbens core is associated with cocaine-induced reinstatement and expression of locomotor sensitisation (Torregrossa and Kalivas, 2008). Both Glutamatergic and GABAergic neurons are also joined in the prefrontal cortex, indicating a possible interaction between glutamate and GABA. Therefore, the PFC GABA transmission may also be involved in the development of behavioural sensitisation (Giorgi et al., 2005). GABA systems It has been reported that cocaine sensitisation is linked with a cocaine-induced increased glutamate and GABA levels in the PFC. This was supported by Jayaram and Steketee (2005), who observed an increase in both glutamate and GABA concentration in the prefrontal cortex of animals withdrawn from repeated daily cocaine after the first week following repeated exposure to cocaine, but increase in these neurotransmitters were not observed after prolonged withdrawal. Furthermore, Jayaram and Steketee reported that the AMPA/KA receptor antagonist, (DNQX) prevent cocaine from increase the concentration of GABA in the prefrontal cortex in cocaine-sensitised animals. Therefore, increasing the response of GABAergic neurons in the PFC is a consequence of enhance glutamate level in prefrontal cortex. Because the AMPA/KA receptor antagonists seem to block cocaine from augmenting GABA levels, it can be concluded that glutamate acts mainly through AMPA/KA receptors to increase GABAergic activity in the prefrontal cortex. However, decrease in GABAÃŽÂ ² receptors function in the PFC is also associated with sensitisation of locomotors. It is believed that a loss in GABAÃŽÂ ² function in the prefrontal cortex would lead to a decrease in inhibitory modulation of excitatory pyramidal output neurons in the PFC (Badran et al., 1997), and therefore, a simultaneous increase in glutamatergic transmission in subcortical regions associated with the expression of behavioural sensitisation (McFarland et al., 2003). Glutamatergic, GABAergic and midbrain dopamine neurons are joined onto dendritic spines of medium spiny neurons that contain GABA, and endogenous opioid peptides. These opioid-containing neurons project directly to the substantia nigra and VTA to synapse on dopamine cells (Yung and Bolam, 2000). Therefore, alteration of endogenous opioid may participate in the development of drug abuse. Opioid systems It has been suggested that dopamine and opioid act together to modulate locomotion, mood and motivated behavioural, therefore, modification of the endogenous opioids participate in the development of drug of abuse. In addition the opioid system could also influence drug craving and relapse by altering stress physiology (Rosin et al. 2000). Apart from dopaminergic system, the endogenous opioid system is also a major player in addiction. Opioid system consists of three G-protein coupled receptors, termed mu (ÃŽÂ ¼), kappa (ÃŽÂ º), and delta (ÃŽÂ ´) opioid receptors. They act through G-protein second messenger systems (Go/Gi) to inhibit adenylate cyclase and cyclic AMP (Contet et al., 2004). Activation of these receptors on presynaptic axon terminals inhibits the Ca2+ influx that underlies release of neurotransmitters (Evans and Zamponi, 2006). At the postsynaptic membrane, their activation hyperpolarises the membranes by enhancing K+ flow out of neurons (Taddese et al., 1995) mu ( µ)-opioid receptor Mu ( µ) opioid receptors mediate positive reinforcement following direct morphine or indirect alcohol, cannabinoids and nicotine activation (Jullien et al, 2008). The positive reinforcing and euphoric effect of morphine involved dopaminergic as well as mu opioid receptors. Morphine activates ÃŽÂ ¼-opioid receptors through inhibitory Go/Gi protein, which decreases the level of adenylate cyclase and the cAMP pathways in the VTA (Contet et al, 2004). Because opioid and GABA containing-neurons also project in the VTA, activation of  µ receptor inhibits the release of GABA on dopamine, leading to high level of dopamine in the nucleus accumbens and other area. The increase in dopamine level in the nucleus accumbens leads to the positive reinforcement of opioid addiction (Bartoletti et al., 1999), which is also related to cocaine reinforcing effect (Julien et al., 2008). Stimulation of  µ opioid receptor in the VP is thought to promote motor activity, in part, by red ucing presynaptic release of GABA (Torregrossa and Kalivas, 2008). Repeated cocaine administration results in reduced extracellular GABA in the VP due to increasing stimulation of presynaptic  µ opioid receptors (Tang, et al. 2005). 2. K-opioid receptors ÃŽÅ ¡-opioid receptor system is essential in regulating presynaptic dopamine release and administration of dynorphin (DYN) within the nucleus accumbens (Shippenberg and Rea, 1997). DYN, endogenous ligand for the ÃŽÂ º-opioid receptor prevents the sensitisation that develops to locomotor stimulatory and conditioned reinforcing effect of cocaine. Anatomical studies have shown interaction between the mesolimbic dopamine neurons and neurons containing the opioid peptide dynorphin (Yung and Bolam, 2000. As mentioned above, dynorphin are found in dentritic spine of medium spiny neurons and project to the VTA and nucleus accumbens in which ÃŽÂ º-opioid receptors are expressed. However, the accumbens shell express high density of ÃŽÂ º-opioid receptors (Jayaram and Steketee,). Microdialysis studies have shown that the systemic administration of selective ÃŽÂ º-opioid receptor agonists such as U50488 and U69593 depress the firing rate of mesolimbic dopamine neurons and decreases dopamine overflow in the nucleus accumbens (Shippenberg and Rea, 1997). Therefore, activation of ÃŽÂ º-opioid receptor will inhibit dopamine release in the nucleus accumbens. However, Kuzmin et al., 1997 showed that acute administration of selective ÃŽÂ º-opioid receptor antagonist, nor-binaltorphimine increases dopamine overflow within the nucleus accumbens. In addition to these findings, it is believed that dopamine D1 or D2 receptor agonist, apomorphine, increases dynophin immunoreactivity and prodynorphin mRNA in the nucleus (Li et al., 1990). Therefore, repeated administration of cocaine increases prodynorphin mRNA in the nucleus accumbens and striatum. Taken in to account all these findings, and the role of ÃŽÂ º-opioid receptors in presynaptic modulation of dopamine release, it can be concluded that an increase in the extracellular level of dopamine within the nucleus accumbens results in a compensatory increase in the activity of dynorphinergic neurons. However, this increase is insufficient to prevent the development of behavioural sensitisation. Because many of the above intracellular adaptation involve changes in protein levels, it can be though that regulation of gene expression may be involved in the long-lasting effects of cocaine. Cocaine regulates gene expression It has been reported that one of the early molecular events following cocaine administration is the activation of nuclear protein (CREB) (Konradi et al., 1994). CREB control the changing that occur in synaptic neurons through modulation of the expression of several cAMP-inducible genes. CREB is regulated via phosphorylation at serine-133 (Konradi et al., 1994) The kinase inducible domain (KID) that contains serine-133 amino acid residue is phosphorylated by cAMP-dependent protein kinase A (PKA), and Ca2+/calmodulin-dependent protein kinases II and IV (CaMK II and IV) (Lonze and Ginty, 2002). Phosphorylation of CREB by PKA and CaMK II and IV results in the expression of immediate early genes (IEGs) including Fos and Jun, which are members of the transcription factor activator protein-1 (AP-1) family (Soderling, 1999). Acute cocaine administration activates DNA-binding activity of the AP-1 and expression c-Fos, FosB and JunB proteins (Hope et al., 1992). Chronic cocaine exposure is believed to reduce the capability of cocaine to express c-Fos, JunB and FosB proteins. This results in prolonged accumulation of à ¢Ã‹â€ Ã¢â‚¬  FosB proteins (a shorter splice-variant of FosB), which produces more persistent AP-1 complex (Hiroi et al., 1997). Prolonged accumulation of à ¢Ã‹â€ Ã¢â‚¬  FosB was reported in a variety of knockout and transgenic mice studies. Hiroi et al (1997) showed that mice lacking Fos-B and its shorter splice- variant à ¢Ã‹â€ Ã¢â‚¬  Fos-B had reduced AP-1 complexes following chronic cocaine exposure and increases cocaine-mediated hyper-locomotion and conditioned place (CPP) preference. They also observed that the long-term over expression of à ¢Ã‹â€ Ã¢â‚¬  Fos-B increases AP-1 complexes and behavioural sensitisation in both the nucleus accumbens and striatum. Increased neuronal expression of Fos in these regions after cocaine treatment is mediated by increasing D1 dopamine receptor activation, due to high level of extracellular dopamine. Desensitisation Chronic cocaine administration repeatedly stimulates dopamine receptors, as a result, decreases the concentration of dopamine within mesolimbic system and the remaining receptors become less sensitive to dopamine. Decrease in dopamine concentration leads to tolerance. This has been reported in several studies. For example, Maisonneuve et al (1995) observed a reduction in the basal dopamine concentration of rats nucleus accumbens when 10 or 15 mg/kg of cocaine was administered three times every day per hour for 13 days. Additionally, Inada et al (1992) showed that repeated cocaine administration in rats, reduced dopamine response to cocaine striatum 24 h after withdrawal. Decrease in dopaminergic level also leads to behavioural tolerance. Tolerance Tolerance refers to a decrease in response to cocaine due to repeated exposure of the drug (Maisonneuve et al., 1995). The major contributory factor to tolerance is the supersensitivity of D2-like autoreceptors as a result of D1 receptors desensitisation after chronic cocaine treatment (King et al., 1994). King et al showed that following chronic administration of 40 mg/kg of cocaine per day, for 7 days, increases sensitivity of D2-1ike receptors in the nucleus accumbens. Increasing D2 receptors leads to a transient decrease in the levels of GiÃŽÂ ± and GoÃŽÂ ± proteins linked to these receptors (King et al., 1994). Continuous cocaine administration produces tolerance to the inhibitory effects of cocaine on dopamine uptake in striatum and nucleus accumbens. Therefore, blockade of dopamine uptake by cocaine produces a compensatory increase of dopamine reuptake transporters (Letchworth et al, 2001). However, repeated cocaine treatment decreases the mRNA expression of dopamine transporter in the VTA neurons that project to the limbic brain regions during withdraw (Hammer et al., 1997). Polymorphism in the genes of dopamine transporter (DAT1) and receptors could be implicated in the genetic susceptibility to the complications of long-term development use in different individual (Wang et al., 2004). There are two main types of DAT1 genes, the SLC6A3 gene and the 3 untranslated VNTR polymorphism. The SLC6A3 is localised to chromosome 5p15.3 and genetic variation in SLC6A3 are thought to change the expression of DAT1 (Fuke et al., 2001). The variable number tandem repeat (VNTR) polymorphism in the 3untranslated region of DAT1 consists of a 40-bp repetitive sequence and can vary from 3 to 12 repeats. However the two most common alleles are the 9-repeat and the 10-repeat, and several studies have linked these polymorphisms to prolonged psychosis following stimulant withdrawal. Fuke et al (2001) reported that the 10-repeat allele (10R) enhances the expression of the DAT1 protein, while Michelhaugh et al (2001) claimed that the 9-repeat allele (9R) enhanced the DAT1 expression. However both studies found that the DAT1 VNTR is associated with drug addictions. The gene for D2 dopamine receptor (DRD2), TaqI A (rs1800497) is a single-nucleotide polymorphism (SNP) with two variant; A1, the less frequent allele, and A2, the commoner allele. Accumulative evidence from post-mortem brain samples using a [3H] binding ligand and in living subjects using positron emission tomography (PET) showed that the presence of the A1 allele leads to a decrease in D2 dopamine receptor density, as a consequence of chronic cocaine treatment (Thompson et al. 1997). Therefore, the DRD2 A1 allele is implicated in addictive behaviours. Several studies on different populations suggested that the involvement of TaqI A and VNT

Friday, October 25, 2019

Bad Medicine :: Essays Papers

Bad Medicine Before the age of television shows, movies, and the Internet people entertained one another with vibrant and exaggerated tales. Geoffrey Chaucer’s, The Canterbury Tales, is a good example of this form of entertainment. The novel details the journey of a band of pilgrims, who engaged in a storytelling competition, as they travel toward the shrine of Thomas à   Becket. These Middle Age storytellers varied as much as the stories, and consisted of a knight, physician, monk, and many more. In â€Å"the Prologue† the Physician is revealed as a con artist who cares more about himself than his patients. The Physician was a medical doctor, who was responsible for taking care of the ill and disease stricken. â€Å"No one alive could talk as well as he did / On points of medicine and surgery†¦Ã¢â‚¬  (Chaucer 30). He was part of the rising middle class society and his garments that were â€Å"lined with taffeta† (Chaucer 31) made this assumption apparent. During the Middle Ages taffeta was a material like silk, which was very expensive, so only the wealthy could afford it. To many he seemed to be a productive member of society, but appearances can be deceiving. People of the medical profession were looked upon with a certain respect; so many patients did not question what was prescribed. The Physician misused his title to take advantage of his patients’ faith. He was revealed as a liar and a cheat. He was a partner with the druggist, to help each other build their wealth. The reader can draw the appearance of his deceit in the following quote, â€Å"He gave the man his medicine then and there. / All his apothecaries in a tribe / Were ready with the drugs he would prescribe / And each made money from the other’s guile; / They had been friendly for a goodish while† (Chaucer 30). Chaucer describes these habits of the physician in order to allow the reader to paint a mental picture of his morals and character. Chaucer also brings the readers attention to the fact that the Physician â€Å"did not read the Bible very much† (31). Chaucer implies that the Physician is a sinner, who did not see an error in his dishonesty. Many analysts believe that Chaucer was trying to portray certain qualities through the vivid descriptions of the characters’, such as in the following quote describing the physician; â€Å"In blood-red garments, slashed with bluish grey / And lined with taffeta †¦Ã¢â‚¬  (Chaucer 31).

Wednesday, October 23, 2019

English Research Paper Social Change

The idea of social change is something that I would say, deep down, scares us all. When looking at two stories in particular you can see an evolution over the years. Saying this I wonder when you do look very closely at â€Å"The Lottery† by Shirley Jackson and â€Å"Shooting an Elephant† by George Orwell how much you will find alike, but also how much you will find different based on the time period in which they were written. Social Change is not something that’s easy for some people.However, it normally takes place over a time frame of years, therefore making it harder to notice when it is actually taking place. In today’s world, researchers and scientist have even been able to come up with ways in which they believe social change is taking place and can be predicted to an extent. â€Å"The Lottery† took place back in 1948, which is when it was written. Needless to say a lot of the social trends and social norms they had back then are not easily compared with the values of today’s society.What we call socially acceptable today is vastly different than what was acceptable in the 40’s. The values of society then were much more conservative. Today if I were to walk in on a social event like the lottery, wearing shorts and a t-shirt, I bet I would be the one selected to get stoned on the spot. Those days’s it was only acceptable for men to wear long pants and maybe a t-shirt. As the back ground of â€Å"The Lottery† is reveled, you are given more information on the social traditions of their fictional society.It makes you wonder if this is actually something that ever took place in history, or if it was something inspired by the culture of the 1940’s. Today we think of a lottery as being something were you have the chance to win money, but this story shows how different lotteries were then. In this story the author portrays â€Å"The Lottery† as an event were the entire village is gathe red in the courtyard to draw a piece of paper out of a hat. If you were lucky enough to choose the piece of paper out of the hat with a large black dot on it, then you were not the winning a prize.The person who draws the black dot gots stoned to death. During the 1940’s World War Two was taking place. It makes me wonder why the author, Shirley Jackson, wrote a story about people coming together to decide who gets stoned to death (â€Å"America’s†). The activities of Adolf Hitler and the Nazi’s in Germany and the persecution of the Jewish community could have influenced the story line. Considering the story is about a community assembling and deciding at random who gets to die, World War II would be a fitting influence for the author. Shooting an Elephant† has a lot of similar social problems that â€Å"The Lottery† had, but in a very different context. The elements of peer pressure and social acceptance come out in the story. Both issues are still important in today’s society.This is based on my interpretation of the story, realizing how social change is an important part of evolution. The end of the story speaks volumes about why the young man shoots the elephant. The animal was no longer being destructive or harmful. He shot the elephant because people wanted him to. I often wonder whether any of the others grasped that I had done is solely to avoid looking a fool† is the last line from the story â€Å"Shooting an Elephant†. This is further evidence that the elephant’s death was a result of social pressures. Since there were two thousand people standing behind him, waiting on him to make a move, he thought he would look like a coward if he didn’t shoot it. The villagers wanted the elephant shot for it’s meat, not just because it was running through their village. It is safe to say that social pressures were major in this time period.The story actually takes place in 1936, when it was published. You can see that â€Å"the Lottery† and â€Å"Shooting an Elephant† take place around the same time period. The setting of the story is different, however, because it takes place in Europe, just outside of a small town called Burma. The social values are similar in each story, despite them taking place so far apart. In â€Å"Shooting an Elephant†, the elephant actually gets lose from its owner and goes on what is called a â€Å"must† (also known as a rampage).It is my understandings from the story that after elephants have been confined or locked up, they have built up energy that they must get rid of. This is why when the elephant gets lose, or brakes free from its chain, it goes through the village stomping people and tearing through the huts, knocking them down. However, the villagers never give a clear answer as to where the animal was eventually tracked down. Once the man asks for a rifle to kill the elephant, the people are follow ing him to see what happens. They do this out of greed, more than curiosity. They each want dibs on the best parts of elephant meat.This is an example of one form of social change, because in today’s world we can go to the market and get whatever it may be that we need. During the twenty first century, I cannot think of a time that humans in the developed world had to fight other humans in order for survival. Due to the fact, that back in the 1940’s you had to find your own food as it became available. Social change is something that is required for us to evolve as a human race. I believe that point is made clear based on the examples given in these two stories that took place back in the 1940’s.A great way to describe social change is by its definition: â€Å"structural transformation of political, social and economic systems and institutions to create a more equitable and just society (â€Å"What†). † If you pay attention to the part of this defi nition that says â€Å"equitable and just society† then you have more insight to â€Å"The Lottery† (â€Å"What†). All of the towns people may have believed that their form of â€Å"equal and just society†, of drawing from a hat to decide as to whom gets to die, is only way to make it fair. By doing this there could potentially be less acts of random violence.Social control can go hand in hand with social change. Various countries and religions have their own forms of social control. For instance, all Muslim women have to keep their faces covered when in public, and most European countries require you to have your government issued identification cards on you at all times. â€Å"Shooting an Elephant† provides some opposite examples to the definition given above. The village were the elephant was running rampant has political implications behind it. In social change you have the â€Å"transformation of politics† (â€Å"What†).This is t he number one force behind social change a lot of time. To be an elephant owner back in that time period you had to be some form of higher social class. The man working for him is the one that tracks down and ends up killing the animal. He states in the story how he does not want to kill the animal, but felt as if he had to in order to survive himself from the pressure of the villagers. With two thousand people behind you, with their knifes ready to start prying the meat from the carcass of the elephant, you are more likely to chose what will pay off for you in the long run.Instead of waiting on the owner of the elephant to decide what to do when he was confined in the field, he decides to shoot him. Coming down to the fact of did he do what was best for the people? Or did he do it to raise his own political standing with them? Leadership is the number one role when it comes to the social model. Looking at the story â€Å"Shooting an Elephant†, and comparing it to the social change model, you can see the motive behind the man’s role as he takes a leadership position (â€Å"What†). Leadership is socially responsible, it impacts change on behalf of others† almost describes the actions taken during the time when the villagers are seeking the animal (â€Å"What†). The main epicenter of social change is just that, change. Directly in the center of the social change model you will see the word change with different leadership roles surrounding it. Secondly, you can see the same similar behavior from the mayor of the town where â€Å"The Lottery† took place. Enforcing the rules of such an event that takes place once a year, but is sought after to be an endless tradition, is not an easy task.Being the official, the mayor takes on the leadership role, also, not to mention the leadership role he is already in by the position he holds as mayor of the town. To keep the integrity of the lottery there are multiple rules in place to i nsure that it is fair for everyone involved. However, the major part of the social change model that does not fit is the change (Ryder). Any time in the story a villager brought up the fact that they thought the lottery should not continue, the mayor was out raged and spoke up to inform them that it must continue because it was a tradition.Social trends take place as a natural evolution over time, but it requires change in order for it to happen. Without the prospect of change nothing will ever evolve, leaving the villagers to repeat the same destiny year after year. Both Stories have their pros and cons, but there are two different form of social change taking place. The first story â€Å"The Lottery† is dealing with the aspect of leadership and how that leadership affects people of that community.Second, â€Å"Shooting an Elephant† deals more with the issue of pressure and influences from your surroundings. Both however come down to one main topic, and that is change . In Conclusion, social change and evolution is not something that is easy to process sometimes. You can clearly see by these two stories that evolution is self evident during the time of the 1940’s, by comparing the said evolution to recent items such as the social change model you can relate to the methods behind actions that were taken by characters in the stories.Social trend are not something that is easy to break away from. However, you can tell during â€Å"The Lottery† that there are people who are will to accept change and speak out for it! Without change we, as a society, do not have an option of social evolution for the better. With the understanding that change is not always for the better, bad change is what also helps us develop and learn from what we may call bad change at the time.

Tuesday, October 22, 2019

Round vs. Around

Round vs. Around Round vs. Around Round vs. Around By Maeve Maddox One of the differences between American and British English is the usage of the words round and around. Americans use around in contexts in which most British speakers prefer round. The word round has five grammatical functions: noun, verb, adjective, adverb, and preposition. The fighter was able to go another round. (noun) We watched as the runner rounded first base. (verb) Do you want a round plate or a square one? (adjective) The bridge was out, so we had to go round. (adverb) The tiger ran round the tree. (preposition) Round came into the language as a noun meaning â€Å"a circular object.† At various times, the â€Å"circular object† was a racecourse, a ring, and a coin. In a text from 1325, round is the word used for a diadem encircling the head of a man in a painting. Chaucer used round in the sense of a globe. In Macbeth, Shakespeare used round as a word for a sovereign’s crown. Around was formed from the noun round by adding the prefix a-, a variation of the prefix on-, creating an adverb that meant â€Å"in a circle.† In some contexts, British speakers use round and around interchangeably; for example, either â€Å"He put his arm round her,† or â€Å"He put his arm around her.† Otherwise, according to a note in the British English section of Oxford Dictionaries, there’s a general preference among British speakers to use round for â€Å"definite, specific movement,† and around in contexts that are less definite. For example, She turned round. A bus came round the corner. She wandered around for ages. The computer cost around  £3,000. According to a rumor circulating around the track, he’s using steroids. American usage sometimes reflects British usage by using round, but around is more common. Although the Oxford note says that in most contexts, â€Å"round is generally regarded as informal or non-standard,† I haven’t found anything in Merriam-Webster or the Chicago Manual of Style to indicate that using round the way the British do is â€Å"non-standard† in American usage. It may be old-fashioned, but it is not unknown in American writing: By the rude bridge that arched the flood, Their flag to April’s breeze unfurled, Here once the embattled farmers stood And fired the shot heard round the world. Ralph Waldo Emerson, â€Å"Concord Hymn,† 1837 I should like if my sisters are well and all the people round the neighborhood. letter from Peter Van Wagener (son of Sojourner Truth), March 22, 1841 The usage is still seen in emails and web comments by American speakers: We live downtown and I take them round the neighborhood, A mother talking about taking children trick or treating in Sacramento, California. One of the latest scams going round is that someone will stop you and ask if you are interested in perfume, email debunked on Snopes.com/. The strange form ‘round crops up in both British and American contexts, but as round is not a shortening of around, and as there’s no law against the American use of round to mean around, the apostrophe makes no sense in either dialect. Want to improve your English in five minutes a day? Get a subscription and start receiving our writing tips and exercises daily! Keep learning! Browse the Misused Words category, check our popular posts, or choose a related post below:75 Contronyms (Words with Contradictory Meanings)Using the Active Voice to Strengthen Your WritingPreposition Mistakes #3: Two Idioms