Effect of Medicinal Plant Extracts on Alzheimers Disease

Effect of Medicinal Plant Extracts on Alzheimers Disease Alzheimer’s disease (AD) is a neurodegenerative disease which causes a lethal twist in the structural integrity, and a roadblock in the function of brain, this eventually channel the situation to degeneration and shrinkage of brain, and override the control of brain over other parts of the body, and comes to the final closing remark of the disease- death. Studies done on the topic have corroborated that the disease is not reversible, and the only patch of hope is slowing down its progress. But as the disease advances through mid stage and evolves into severe AD, the condition of patient becomes pathetic and care giving becomes more painful. Studies have reported that notable symptoms of AD are seen only after 60 years of age, even though the disease has started before that. Initial symptoms are loss of short term memory- being forgetful about the recent events, and gradually over a period of time patient seems more absent –minded about the environment, things which are chemically etched in the long term memory begins to be erased, and the final stage starts pushing the patient into severe AD which is tremendously pathetic. Studies have proved that loss of function of neurons is the cause of AD. A closer look into the aspect revealed a complex set of events that precede the neuronal degeneration- oxidative stress and imbalance in homeostasis, formation of roadblocks in communication, falling apart of integrity and death of neurons. This enabled to go beyond the findings of superficial studies done and hypothesis developed, and helped to delve much deeper into the inner workings and mechanism of the disease. Hypotheses developed to explain mechanism of AD are: amyloid cascade hypothesis, cholinergic hypothesis and tau hypothesis. Amyloid cascade hypothesis says, APP- Amyloid Precursor Protein, a transmembrane protein involved in main roles of growth, survival and repair of nerve cells- is snipped at wrong places by an enzyme called secretase, leading to the formation of amyloid ÃŽ ² peptides which accumulates to form plaques- amyloid plaques- and bind to synapses blocking the communication channel, event ually causes memory loss. According to cholinergic hypothesis, downward drift in the levels of acetylcholine in brain is the cause for Alzheimer’s disease. Loss of function of cholinergic neurons was found in Alzheimer’s disease patients. Shift in the level of acetylcholine happens due to the lack of two enzymes involved in synthesis and breaking down of acetylcholine. This will lead to loss of function of neurons; brain’s functionality falls apart, and eventually leads to symptoms of Alzheimer’s disease. Tau hypothesis approaches the problem in another perspective, tau protein- a protein associated with microtubules in nerve cells- gets hyperphosphorylated, this enables cross linking among tau protein units, and they back off from being attached to the microtubules. This causes loss of structural integrity of nerve cells, and they collapse and clump to form tangles- neurofibrillary tangles. Studies conducted focusing on the inner workings of these hypoth esis have found that oxidative stress is the reason that enhances plaque and tangle formation, repair mechanisms in cells are unable to solve the situation as the oligomer formation and cross linking are predominantly made by non peptide bonds. In another study, amyloid ÃŽ ² peptides have shown close relation with some causes of mad cow disease. Studies related to genetics of AD have found the link between APOE gene on chromosome 21 and the disease. APOE gene codes for apolipoprotein, and one among its functions is breaking down of APP. APOE has variants, APOEÃŽ µ4 is the one which codes for less active protein whose capacity to break down APP is sluggish. People with this variant gene are more tend to develop AD in later stages of life, and any abnormality related to chromosome 21 also results in AD over a period of time. To know more about the mechanism of disease and its attachment to oxidative stress, further studies have done from different angles, and all the studies have come to a common point, the findings from all the studies stitched together gave a complex and elaborate picture about the mechanism of the disease. Free radical damage leads to oxidation of products in cell. Oxidation leads to new end products of glycation, nitration, lipid peroxidation, and oxidation of nucleic acids. These new end products chemically modify other proteins and compartments inside the cell. Oxidized derivatives impede with the channel of trace elements, and imbalances their homeostasis, and enables proteins like tau to form non peptide cross linking. In response to changes cell up the levels of heme oxygenase-1 (HO-1)- an antioxidant enzyme to mitigate the bad effects from free radical damage- but rapid heaping up of neurotoxic substances goes beyond control leading to severe imbalances, blockage of communicati on channels, and eventually death of neuron. Since mitochondria is the main source of free radicals and oxidative precursors. Certain deletions in mtDNA resulted in change in normal levels and rates of metabolism and production of free radicals. Free radicals formed in mitochondria are short lived and they do not have the ability to cross membrane and reach cytoplasm to cause damage, this led studies in a new direction and found free radicals- OH from cytoplasm- can attack guanidine in RNAs in cytoplasm and this both can cross the membrane and reach into mitochondria, and cause imbalance and production of more stable H2O2 radicals which can come to cytoplasm and react with the channel of trace elements, and starts the primary events for the major causes for AD to come into being. AD starts at neocortex area of brain, and as the neurons die and rupture, the neurotoxic substances- plaques, free radicals, tangles, etc. pervade the nearby nerve cells, and the cycle goes on and graduall y covers the brain and makes it slip out of its normal being. Oxidative stress in brain leads to degeneration of neurons, which eventually leads to dementia, and Alzheimer’s disease (AD). This oxidative stress in brain can be slowed down or reversed- to a small extent- using drugs to treat AD or using antioxidant capacity of some medicinal plants. In this study rats were arranged into seven groups, and different groups were treated with different plant extracts and rivastigmine. AD was induced using aluminum chloride- rats were given aluminum chloride for one month, and the dosage was 17mg/kg of body weight. One group was kept as control- healthy control and another group as AD-induced. Rivastigmine was given to group 3. Group 4 and 5 were treated with extracts of a medicinal plant- Salvia triloba; and group 6 and 7 were treated with extract made from Piper nigrum. The rats were given drug and extracts for three months. At the end of three months duration biochemical assays and histopathology was done to examine the changes happened to t he brains. The following things were checked for in serum: malondialdehyde, total antioxidant capacity and nitric oxide, and level of superoxide dismutase were checked in erythrocytes. Acetylcholine and acetylcholine esterase levels were checked in brain samples and another group of brain samples were given for histopathology. From the results, the rats which were treated with Piper nigrum extract and rivastigmine showed increase in brain Ach, and serum TAC and SOD; and a significant decrease in brain AchE, and serum MDA and NO. The rats which were treated with extract of Salvia triloba showed even better result in subduing the oxidative stress to a certain limit. Antioxidant capacity of plants was used to bring down the effects of oxidative stress in brain. Here, the effect of the extract made from Boswellia serrata is compared with rivastigmine on rats with AD- induced by oral administration of aluminum chloride. Ninety male rats were used in the study. They were made into nine groups. Group 1 was kept as healthy control, group 2 was given with aluminum chloride for four weeks, and group 3 was treated with rivastigmine, group 4 and 5 were treated with two different concentrations of plant extract made from Boswellia serrata. Groups 3 to 5 were treated with a combination of aluminum chloride and other things to check the ability of extract and drugs to protect the brain from the stress. Group 6 was given with water after inducing AD. Group 7 was given with rivastigmine, and group 8 and 9 were given with two different concentrations of plant extract- this was done for twelve weeks. Cognitive tests were done at the beginning of each new stage o f the study. At the end of the duration of the study, the brain samples were subjected to biochemical assays and histopathology. From the results, B.serrata has significant ability to reduce the oxidative stress in brain, and higher dose if the extract showed better effect- bringing down the severity of oxidative stress damage. Bacopa monnieri is another plant used to trim the effects of AD. This plant is used since ancient times for improving intelligence, and in this study its ability to protect against AD is checked. Alcoholic extracts of the plant was made for the study. AD was induced using ethylcholine aziridinium ion (AF64A)- administered intracerebroventricular way bilaterally. Plant extract was given to the rats two weeks before and one week after the administration of AF64A. rats were subjected to cognitive tests. Rats treated with the plant extract cleared the tests in less time. Histopathology results showed, low dose of the plant extract brought down the degree of damage in brain- reduction of neurons density. Low dose showed better result compared to the medium and high dose. The study has not revealed the mechanism of action of the plant extract, but it showed the scope for a further study on the same. Targeted drug delivery to brain in case of Alzheimer’s disease is more complex process due to many factors like blood brain barrier and actions of plasma proteins. But nanoparticles are used for targeted drug delivery, and this is again affected by physiochemical properties of Nanoparticles in different surfactants, stability of nanoparticles and organic coating or capping agent on nanoparticles. Blood brain barrier is a homeostatic defense mechanism used by brain to screen out pathogens and unwanted materials from entering brain. The barrier screens the solutes biochemically, physicochemically and structurally at the periphery. There are times when blood brain barrier breaks down due to certain infections or due to any physical reason, and this makes it skew from its usual nature- highly selectively permeable. Studies have been conducted to find how nanoparticles are treated at blood brain barrier. In a study, nanoparticles were made by warm microemulsion precursors, and the nanoparticles were radiolabelled by entrapment. Then an in situ study was conducted to check how nanoparticles cross the blood brain barrier. From the study it was concluded that endocytosis or transcytosis as possible mechanism for the transport across the barrier- more studies are yet to be conducted. Studies have shown that clioquinol- a quinoline derivative- can solubilize amyloid ÃŽ ² plaques in vitro and this could prevent accumulation of amyloid ÃŽ ² plaques in Alzheimer’s disease transgenic mice- an in vivo study. Clioquinol has shown its ability to dissolve plaques which are induced by Zn and Cu ions- NMR studies have shown that clioquinol can remove bound Cu ions from amyloid ÃŽ ² plaques. The study conducted has overlooked the toxicity part of clioquinol- though clioquinol has many side effects attached to it at high doses. It has shown in the later part of the study that clioquinol coupled with nanoparticles could easily cross the blood brain barrier- higher degre e of uptake by brain. So, clioquinol-nanoparticle delivery system is suggested to be considered as one among the models for treating Alzheimer’s disease by targeted drug delivery. Even though using nanoparticles are considered for drug delivery, there are studies showing the side effects, and doses. In a study- toxicity of silver nanoparticles- it was found that exposure to more than 125mg/kg of silver nanoparticles will lead to liver damage due to toxicity. In a study curcumin nanoparticle formulation was used to test its effect on Alzheimer’s disease in mice. Nanocurcumin was synthesized and orally given to the mice for twelve days. Memory tests were done before starting every new stage of the experiment. Results have shown that mice treated with nanocurcumin could clear the cognitive tests- significant improvements were observed.

How to Address Conflicts or Dilemmas Essay

1.1Describe potential conflicts or dilemmas that may arise between the duty of care and an individual`s rights. In our care work we mostly work with children and young people who may not have the ability to judge what is good for them and what is not. In those cases it is our responsibility and job as individuals and as a team to provide them what we judge is best for them. In some other cases they have the skills to get involved in the decisions and this can lead to conflicts and dilemmas. Potential conflicts between the service user and the care worker in our job role can arise from disagreeing in certain questions e.g. what is healthy to eat, what is not, what is more important when having a meal: quality or quantity, what activities or forms of entertainment (films, songs, etc.) are age-appropriate and/or mentally and emotionally adequate and so on. 1.2Describe how to manage risks associated with conflicts or dilemmas between an individual`s rights and the duty of care. If a conflict arises, I can never force a learner to do or not to do things unless the law or the School Policy allows me to (for example if they want to watch an age-inappropriate film, but in these cases I always have to refer to my line manager). What I can do if a conflict in these questions arises between me and the learner is to provide all the information about the risk carried by their decisions in a supportive, encouraging way, and then let them make their own choices. Every time when a conflict arises I should record what actions were taken to provide every source for the learner to make their own decision and what choice they made. I always should seek for advice at my line manager.

The Case of the Floundering Expatriate - A Case Analysis...

INTRODUCTION In an Economic Times article on the 15th of September there is a report that says that more and more expatriates and foreign corporate managers are queuing to take up Indian assignments. This is because the idea of an Indian experience from a growth and role perspective offers them a huge value addition. As an HR head says India is a market of constant learning and provides expatriates with a foundation for a global tomorrow. This article if taken in context with the case in question gives us the clear correlation between foreign assignments and future corporate success. A foreign assignment with all its hardship and adjustment fears is a perfect platform for future CEO s to showcase their abilities. Success in a foreign†¦show more content†¦His wife is bored without work; their eldest daughter is facing problems with grades in the British school. The problem is not just a temporary adjustment problem. Donaldson is at his wit s end as he has tried everything possible to appease and motivate his staff but they refuse to listen. The problem is so serious that Bert has personally admitted to his inability to handle the juniors. Frank has to take a decision with regard to Donaldson. Some of the options include sticking with him for another year, firing him or sending him back to America. ANALYSIS OF THE TWO MAIN CHARACTERS Donaldson His stint in Europe is marked by numerous cultural faux pas due to his lack of cultural savvy. He does not interact with his juniors, learn Swiss German, and is unpunctual too. His schedules run overtime, he does not know how to show adequate respect to his subordinates. The incident with Hassler epitomizes what is wrong with Bert. Even when he tries to be at his best behaviour he is unable to communicate with the vice president. Frank Waterhouse Frank s desire to rise to the top at any cost becomes detrimental to his company as he refuses to see the problem as his own. Frank failed to usher in Donaldson. This can be seen by the fact that he did not even attend the first workshop. As CEO he also does not have any proper communication channels as the news of dissatisfaction with Bert reaches him very late. He is also excessively fearful of adverse reactions fromShow MoreRelatedUnited Arab of Emirates Country Notebook18844 Words   |  76 PagesEmirates Country Notebook Presented to Dr. Shahira El Alfy Prepared by: Mohamed Ibrahim Osama Mosher Ismail Ahmed El-Mohamady Hesham Mostafa Eslsca 36 – Global Management I. Cultural Analysis: Identification of the Emirates History: The United Arab Emirates (UAE) consists of the seven emirates, which are: Abu Dhabi, Dubai, Sharjah, Ras Al-Khaimah, Ajman, Umm Al-Qaiwain, and Fujairah. They were united as a federal state on 2Read MoreUnited Arab of Emirates Country Notebook18844 Words   |  76 PagesEmirates Country Notebook Presented to Dr. Shahira El Alfy Prepared by: Mohamed Ibrahim Osama Mosher Ismail Ahmed El-Mohamady Hesham Mostafa Eslsca 36 – Global Management I. Cultural Analysis: Identification of the Emirates History: The United Arab Emirates (UAE) consists of the seven emirates, which are: Abu Dhabi, Dubai, Sharjah, Ras Al-Khaimah, Ajman, Umm Al-Qaiwain, and Fujairah. They were united as a federal state on 2Read MoreStephen P. Robbins Timothy A. Judge (2011) Organizational Behaviour 15th Edition New Jersey: Prentice Hall393164 Words   |  1573 Pagesaware of a trademark claim, the designations have been printed in initial caps or all caps. Library of Congress Cataloging-in-Publication Data Robbins, Stephen P. Organizational behavior / Stephen P. Robbins, Timothy A. Judge. — 15th ed. p. cm. Includes indexes. ISBN-13: 978-0-13-283487-2 ISBN-10: 0-13-283487-1 1. Organizational behavior. I. Judge, Tim. II. Title. HD58.7.R62 2012 658.3—dc23 2011038674 10 9 8 7 6 5 4 3 2 1 ISBN 10: 0-13-283487-1 ISBN 13: 978-0-13-283487-2 Brief Contents Preface

Can I Own a Gun in America

While gun owners and dealers often cite the Second Amendment to the U.S. Constitution when arguing against restricting any American citizen from owning a gun, the fact is that all gun owners and dealers must follow federal and state laws in order to legally own or sell guns. Since as early as 1837, federal gun control laws have evolved to regulate the sale, ownership, and manufacture of firearms, various firearm accessories, and ammunition. Highly Restricted Types of Firearms First, there are some types of guns most civilian Americans simply cannot legally own. The National Firearms Act of 1934 (NFA) greatly restricts the ownership or sale of machine guns (fully automatic rifles or pistols), short-barreled (sawed-off) shotguns, and silencers. Owners of these types of devices must undergo deep FBI background checks and register the weapon with the Bureau of Alcohol, Tobacco, Firearms, and Explosives NFA registry. In addition, some states, like California and New York, have enacted laws completely banning private citizens from possessing these NFA-regulated firearms or devices. Persons Restricted From Owning Guns The Gun Control Act of 1968, as amended by the 1994 Brady Handgun Violence Prevention Act, prohibits certain people from possessing a firearm. The possession of any firearm by one of these prohibited persons is a felony offense. It is also a felony for any person, including a registered Federal Firearms Licensee to sell or otherwise transfer any firearm to a person knowing or having reasonable cause to believe that the person receiving the firearm is prohibited from firearm possession. There are nine  categories of people prohibited from possessing firearms under the Gun Control Act: Persons under indictment for, or convicted of, any felony crime punishable by imprisonment for a term exceeding one yearFugitives from justicePersons who are unlawful users of, or addicted to, any controlled substancePersons who have been declared by a court as mental defectives or have been committed to a mental institutionIllegal aliens or aliens who were admitted to the United States under a nonimmigrant visaPersons who have been dishonorably discharged from the Armed ForcesPersons who have renounced their United States citizenshipPersons subject to certain types of restraining ordersPersons who have been convicted of a misdemeanor crime of domestic violence In addition, most persons under 18  years of age are prohibited from possessing handguns. These federal laws impose a life-long ban on gun possession by anyone convicted of a felony, as well as those merely under indictment for a felony. In addition, the federal courts have held that under the Gun Control Act, persons convicted of felonies are banned from owning guns even if they never serve jail time for the crime. Domestic Violence In cases involving an application of the Gun Control Act of 1968, the U.S. Supreme Court has rather broadly interpreted the term â€Å"domestic violence.† In a 2009 case, the Supreme Court ruled that the Gun Control Act applies to anyone convicted of any crime involving â€Å"physical force or the threatened use of a deadly weapon† against any person with whom the accused had a domestic relation, even if the crime would be prosecuted as simple â€Å"assault and battery† in the absence of a deadly weapon. State and Local ‘Right to Carry’ While the federal laws regarding the basic ownership of guns apply nationwide, many states have adopted their own laws regulating how legally-owned guns may be carried in public.   As in the case of fully automatic firearms and silencers, some states have enacted gun control laws that are either more or less restrictive than federal laws. Many of these state laws involve an individual’s â€Å"right to carry† handguns openly in public. In general, these so-called â€Å"open carry† laws, in the states that have them, fall into one of four categories: Permissive Open Carry States: People are allowed to carry their legally-owned guns openly and in public.Licensed Open Carry States: People are allowed to carry their legally-owned guns openly and in public only with a permit or license to do so.Anomalous Open Carry States: While openly carrying a gun may generally be legal under state law, local governments are allowed to enact more restrictive open-carry laws.Non-Permissive Open Carry States: State law allows persons to openly carry legally-owned guns only in limited circumstances, like while hunting, during target practice, or when legally carried for self-defense. According to the Law Center to Prevent Gun Violence,  31 states currently allow the open carrying of handguns without the necessity of a license or permit. However, some of those states require that guns carried in public must be unloaded. In 15 states, some form or license or permit is required to openly carry a handgun.   It is important to note that open carry gun laws have many exceptions. Even among those states that allow open carrying, most still prohibit open carrying in some specific locations such as schools, state-owned businesses, places where alcohol is served, and on public transportation, among many other locations. In addition, individual property owners and businesses are allowed to ban openly carried guns on their premises. Finally, some—but not all—states grant visitors to their states â€Å"reciprocity,† allowing them to follow the â€Å"right to carry† in effect in their home states.