The Life of Susan B. Anthony Essay - 578 Words

Susan B. Anthony has gone through many rough times and had to go through many obstacles. She has had many ideas to try and get women equal rights. Susan, I believe, is an amazing person to accomplish what she did. This is the reason she should be in the History Hall of Fame. Susan B. Anthony was born on February 15, 1820 (Bio.com). She studied at a Quaker school near Philadelphia and found work as a teacher (Bio.com). The article â€Å"Susan B. Anthony† states that Susan was paid less than men. Susan and her family became involved in the fight to end slavery (Bio.com). The article â€Å"Susan Brownell Anthony† states that she devoted more of her time to social issues. Sochen states that Susan B. Anthony became close friends with Elizabeth Stanton†¦show more content†¦The article â€Å"Susan B. Anthony† states that she was active in the antislavery movement and became an agent for the American Antislavery Society. Bio.com says that Susan and Elizabeth est ablished the women’s New York State Temperance Society in 1852 and the New York State Women’s Rights committee. They helped established the American Equal Rights Association in 1866 (Bio.com). Sochen states that Susan was one of the first leaders of the campaign for women’s rights. Susan published a weekly journal that demonstrated equal right’s, Sochen says. She became an editor of The Revolution the newspaper of the American Equal Rights Association (National Parks Service). Susan coedited three volumes of a book called History of Women Suffrage. She completed the fourth volume of the book in 1902, Sochen states. Sochen also says, she helped organize the Women’s Suffrage Movement. She was an icon of woman’s suffrage movement (National Parks Service). Bio.com states that she started petitions for women and gave speeches around the country. Sochen says she supported a dress reform by wearing bloomers which became a symbol of the womenâ€℠¢s rights movement. Sochen also says that the US made a one dollar coins with her picture on it, she was the first women to be pictured on a US coin. She helped get women the right to vote Sochen states. Susan was a figure in women’s voting rights movement (Bio.com). Sochen saysShow MoreRelatedThe Heroic Of Women Rights807 Words   |  4 Pagesearly eighteen century in Canajoharie New York, Susan B. Anthony, a teacher discovered that men and women have different hourly wages. This commotion made Susan B. Anthony and other female to join the â€Å"teacher union to fight for equal wages.† (â€Å"SusanBAnthony† par.5) Nevertheless there was one problem, - Susan B Anthony continued to fight for the teacher union actively but she had to end her career as a teacher. Under the circumstances, Susan B Anthony had taken a role to acknowledge that women wereRead MoreSusan B. Anthony : An American Icon1462 Words   |  6 PagesSusan B. Anthony Susan B. Anthony was a born a fighter she never stopped protesting the morally incorrect in her first years to her last she fought for equality. Susan B. Anthony is an American icon known for her work with the Women Suffrage Movement she influenced the American culture and brought all American women a better future. Her legacy sculpted feminism and helped the community pave the way to equality. Susan B. Anthony was born an activist her family being involved in the Anti-SlaveryRead MoreFeminism : The Advocacy Of Women s Rights On The Basis Of Equality1645 Words   |  7 Pagesman. There were women that were just fine living like that although there were women like Susan B Anthony. She became a key player in the women’s suffrage movement. Anthony would go on to protest, participate in different causes, and give speeches. Fast forward to today where there has been drastic changes for women. Women are allowed to do things like vote and run for office. Many women credit Susan B Anthony for standing up for all women during a time where it was needed. Although during her timeRead More`` What Is A Hero Without Love For Mankind `` By Doris Lessing1559 Words   |  7 Pagespursuit of reform, and those who are passionate about their work are the worthy, deserving heroes. In the aspect of encompassing said traits, Susan B. Anthony is the definition of a worthy hero. In 1820, Susan B. Anthony was born in Adams, Massachusetts, to Daniel and Lucy Anthony. Raised as a Liberal Quaker with sharp features and beliefs, Susan B. Anthony was prompted by her parents to be hard-working, confident, and self-sufficient. In 1846, she moved to Canajoharie, New York, where she acceptedRead MoreWomen Activists Essay example1126 Words   |  5 PagesAmerica? One women activist was Susan Brownell Anthony who was born February 15, 1820 in South Adams, Massachusetts (â€Å"Susan B. Anthony†). Susan B. Anthony was a great woman who was determined to change women’s rights. For example, there is a quote that states, â€Å"Susan B. Anthony dedicated her life to the cause, the woman Suffrage Movement† (qtd. in â€Å"Susan Brownell Anthony†). Through Susan’s life she had many major accomplishments toward women’s rights. In 1869 with a life-long friend Elizabeth Cady StantonRead MoreThe Journey Of Susan B. Anthony1088 Words   |  5 PagesDare to Vote: The Journey of Susan B. Anthony Susan B. Anthony entered the juryless courtroom. A judge sat before her. Just shortly after she arrived, Anthony said, â€Å"I have many things to say. My every right, constitutional, civil, political and judicial has been tramped upon. I have not only had no jury of my peers, but I have had no jury at all† (ecssba.rutgers.edu). Anthony stressed that the laws were not fair only because they were created by men. The courtroom tensed as she made more pointsRead MoreSusan B. Anthony, A Leader Of The Women s Rights Movement1589 Words   |  7 Pagesgained their full rights including the right to vote, most would recognize Susan B. Anthony, a leader of the women’s rights movement that never gave up. Born and raised in an outspoken Quaker household, Anthony believed from a young age that all should be treated equally despite their gender. She took after her father, who had radical views on issues such as temperance and slavery. Susan B. Anthony, a leader for most of her li fe, fought endlessly in a battle against those of ignorance and unfair viewsRead MoreHistorical Female Leaders Exhibiting Civil Disobedience1295 Words   |  6 PagesHistorical Female Leaders exhibiting Civil Disobedience Susan B. Anthony lived in a time, 1820-1906, that lacked equality. Thus, She dedicated most of her life’s time to social issues (Susan B. Anthony†). Anthony was known in history as a suffragist and Women’s Rights activist and is recognized for her demonstration of nonviolent resistance also known as civil disobedience. Civil Disobedience is the refusal to obey governmental demands or commands especially as a nonviolent and usually collectiveRead More Susan B. Anthony Essay531 Words   |  3 PagesSusan B. Anthony Susan Brownell Anthony was a magnificent women who devoted most of her life to gain the right for women to vote. She traveled the United States by stage coach, wagon, and train giving many speeches, up to 75 to 100 a year, for 45 years. She went as far as writing a newspaper, the Revolution, and casting a ballot, despite it being illegal. Susan B. Anthony was born on February 15, 1820, in Adams, Massachusetts. She was the second of eight children in her familyRead MoreBiography of Susan B Anthony1496 Words   |  6 PagesSusan B. Anthony (Your name) (college) Susan B. Anthony On February 15, 1820, Susan B. Anthony was born in Adams Massachusetts to Lucy and Daniel Anthony. Susan out of eight children was raised in a strict Quaker family. Her father, Daniel Anthony, was a very rigid man, a Quaker cotton manufacturer and abolitionist. He believed in making sure children were guided right, not targeting them. Her father did not let his kids experience the childish enjoyments of toys, games, and music, because

Depending On Who They Talk To, People Often Treat Others

Depending on who they talk to, people often treat others differently depending on who they are, developing their relationships in either a positive, or negative way. Who you talk to, and live with can also affect how you develop as a person; when children are young, they are often taught many things from the adults, and role models around them. However, as that child gets older, they may begin to act differently, suddenly deciding things for themselves, which can affect the previous relationships between that child, and their caretakers. The same can be said for the main character of Hamlet, in William Shakespeare’s play of the same name. Before the play takes place, most of the characters Hamlet is already familiar with, with much being†¦show more content†¦In a journal entry called, Gender Tragedies: East Texas Cockfighting and Hamlet, the writer, Barney Dews writes about how, much like Hamlet’s father, his father and grandfather gave him examples of how to be a man, however, on the other side, the females of his family were giving him a counter message of sorts. Dew continues by stating, â€Å" When I read the play, I began to identify with Hamlet, to see him as the product of a society similar to my own. We both received irreconcilably mixed messages about gender.† This is very similar to what Hamlet struggles with throughout the play. When Hamlet sees the ghost of his father, his father beckons him to seek revenge for his unrighteous death by his brother’s hand with, â€Å"If thou hast nature in thee, bear it not. Let not the royal bed of Denmark be a couch for luxury and damned incest,† (Shakespeare,81). While he states this though, it comes out as more of a challenge of Hamlet, as if questioning his son if he could do it or not. Hamlet’s relationship with his father after his death is very complicated one, as he looks up to him, but seems to be a bit indecisive with his father’s strengths and teachings, as he hesitates to murder his uncle, when he has several chances to do so, using the excuse of him not being in the middle of a sin. Moore 3 Hamlet’s relationship with his mother drastically changes throughout the play. Originally, Hamlet and his mother were presumably close before hisShow MoreRelatedBipolar Disorder And Major Depression1358 Words   |  6 Pagesdisorders, and the two most common disorders within this category are bipolar disorder and major depression (also known as clinical depression). These disorders often require a patient to take medications to regulate their mood, which is often paired with psychotherapy or â€Å"talk therapy.† While they are common, they are no less serious than any other psychological disorder and should be treated as such. Major depression, also called clinical depression, is mostly identified by its significant symptomsRead MoreSchizophreni Living With Schizophrenia1623 Words   |  7 PagesSchizophrenia In the world today, there are many illnesses and disorders that affect people each and every day. One illness in particular that is very big in the US and all around the world is Schizophrenia. It is also the most researched topic. A person who is diagnosed with Schizophrenia lives a very different lifestyle than someone who is not. Many people would consider a person with schizophrenia to be â€Å"crazy.† Sadly enough, people with this illness do posses symptoms that might come off as crazy or insaneRead MoreA Research Study On Identical Twins1723 Words   |  7 Pageshas been many studies and research. Identical twins have almost exact copies of each other’s genes, but they still turn out to be different from each other. Because of their genes they have a lot in common and studies have shown things like twins separated at birth will pose the same in front of the camera and if one is religious the other one will often also be religious (Cobb). The twins Jim Springer a nd Jim Lewis reunited after 39 years after their separation at birth, they found out that both hadRead MoreFast Food Restaurants Are Being Blamed For Obesity Essay1133 Words   |  5 Pageseffects of fast food in society. Fast food is vastly blamed for the rising obesity epidemic, which as discussed in the article is fictional. Depending on the income of a household, the age group of the consumers, or someone always on the go, fast food is something people rely on every day as their source of food. This article discusses how fast food is often blamed for obesity, but in fact has little, to nothing to deal with obesity rates. I will be using this article in my research as a scholarlyRead MoreSymptoms And Symptoms Of Schizophrenia940 Words   |  4 PagesSchizophrenia is a serious mental illness that interferes with a person’s ability to think clearly, manage emotions, make decisions and relate to others. It is a complex, long-term medical illness, affecting about 1% of Amer icans (NAMI). Schizophrenia has many causes, symptoms, and treatments and affects a wide variety of people. While it may be hard to diagnose the cases that are can receive treatment to help with their worst symptoms. Some symptoms of Schizophrenia include hallucinations, delusionsRead MoreObsessive Compulsive Disorder ( Ocd ) Essay986 Words   |  4 PagesThe time that they should be spending to be better members of our community is therefore spent in dealing with unrealistic means of decreasing false anxiety and impractical fears. Thus, it is very important for people with obsessive-compulsive disorders to seek treatment to help them ease symptoms and become more effective in their daily lives. Treatment for OCD OCD treatment may not always result to cure, however, it can become a big help in decreasing and controlling symptoms so that they willRead MoreThe Publics Interaction With Anxiety, Depression, And Its Treatment1587 Words   |  7 Pagesdepression and anxiety, a lot of people have misconceptions such as â€Å"they just want attention† or â€Å"men don’t get depressed†. The truth is that anxiety and depression disorders are real and pretending it’s not there will only make things worse. The best way to fight misconception, stigmas, and stereotypes is to educate and spread knowledge to the masses. It is important to be knowledgeable for many reasons including understanding the signs. The thought Is that only people who are depressed think aboutRead MoreA Child with Bipolar Disorder Makes Parenting Difficult Essays666 Words   |  3 Pagesto be mistaken with the occasional ups or downs many people go through. The National Institute of Mental Health’s website provides parents valuable information of the disorder’s symptoms and treatments, as well as information on how to live with a child with bipolar disorder. Symptoms of bipolar disorder often appear in the person’s late teens or early adult. However, some signs are developed during childhood. Children with bipolar disorder often experience periods of intense emotional states calledRead MoreMajor Depression Disorder ( Mdd )866 Words   |  4 PagesMajor Depressive Disorder (MDD) and is one of the most common and serious disorders leading to morbidity. Major Depression Disorder varies on the person s age or gender, symptoms, the cause of the disorder, the triggers, and the methods of helping treat the disorder. According to the American Psychiatric Association, â€Å"If Five symptoms have been present during the same 2- week period and represent a change from previous functioning; at least one of the symptoms can be a depressive disorder or lossRead MoreBipolar Disorder And Dissociative Identity Disorder Essay1651 Words   |  7 Pagesand depression. These usually last weeks or even months depending on the person. People who are manic have a high energy level and often irrational beliefs. After a manic mood, the person will often â€Å"crash† into a depressive mood characterized by sadness and lethargy. It is found in both men and women equally and cause significant sleeping problems in both the manic mood and depressive mood. This disorder can pose a great challenge to treat due to the medications that are prescribed causing the patient

Use Your Organisational Behaviour Skills in Your Future Job Free Essays

Organisational behaviour is the study organisational culture; the study of people as a group or as an individual in an organisation. If you want to become a good entrepreneur, it is necessary to learn about your organisational structure more accurately. By leaning organisation behaviour managers can build up a better environment in an organisation and can achieve a successful career. We will write a custom essay sample on Use Your Organisational Behaviour Skills in Your Future Job or any similar topic only for you Order Now Organisational behaviour is an important subject in, which every student has to write number of essays, in order to enhance their writing and learning skills.Writing a good quality essay is one of the most complicated tasks for students who are poor in grammar and punctuation. In this article you will find the importance of organisational behaviour in an organisation. Students of organisational behaviour can easily take help from this article, in order to write a good quality essay in less possible time. Business environment changes rapidly, in order to handle your employees, managers must have some know-how regarding organisational behaviour.They must know three essential aspects in order to handle a new workforce, these important factors are: (a) motivation (b) communication (c) leadership. One of the essential fundamentals to any booming organisation is the people in place of leadership. â€Å"Leadership is the capability to control a group toward the accomplishment of goals and objectives. †Ã‚   Following are some most significant advantages of study organisational behaviour: The study of organisational behaviour plays a major role in all parts of an organisation. It helps you to know the human behaviour within and outside the organisation.The second biggest advantage of studying organisational behaviour is that, organisational behaviour can tell managers how they manage their operations successfully and professionally. The main objective of a company is to maximise their profits and minimise their risks. By studying organisational behaviour managers can pay more attention on how to handle different situations of their employees, so that they can successfully take a company towards success. Above are some advantages of study organisational behaviour. If a manager knows about his or her employees they will eventually lead to a better more stable company. How to cite Use Your Organisational Behaviour Skills in Your Future Job, Papers

Create dramatic tension Essay Example For Students

Create dramatic tension Essay Inspector Calls By J. B. Priestley was written post World War II, but set in the early 1910s. This was a time of great innovation, with the Titanic making its voyage to New York, and trouble in the Balkans that was about to spread throughout Europe. Britain at this time was booming after the effects of the Industrial revolution. With this came social ordering, and a difference between the gentry and working class of society. The top 3 percent of the country belong to the Upper class and they contained a staggering 98 percent of the countrys wealth. The Birling family are members of the Upper part of society, Mrs Birling being born into it, and Mr Birling achieving it through business. They are leading there lives the way they want to lead them, ignorant to the poverty and suffering of the working class, and indulge in their superficial nonsense they find so important. This is why the Inspector calls in on the family, and finally opens their eyes to the reality of the world, and their role within it. These two chosen extracts are taken from the ends of Act 1 and Act 2. They both have vital roles in the revelation in the death of this mysterious character Eva Smith, both creating a dramatic climax to the end of each act.  In Act 1 we see the introduction of all the characters, and an understanding of their personalities. This extract is taken just after the Inspector has made Mr Birling and then Sheila reveal their involvement in the downfall of Evas life. Sheila has just entered the scene after storming off crying. She is upset and wallowing in her own self pity due to her role in having Eva sacked from her job at Millwoods due to her own jealousy and subsequently having a role in Evas suicide. She is trying to convince herself she hasnt done it before, and is quite selfishly thinking about herself, and how this has damaged her life instead of the life supposedly Eva Smith has lost, Ive noticed them giving me a sort of look sometimes at Milwoods, the repetitive use of I, Ive, and Ill all back up this spoilt selfish response. Within these extracts Priestly creates dramatic tension through verbal communication and non verbal communication through the stage direction in the book and the presentation in the stage production. In this extract the way in which the lines are delivered by the character is an important part of telling the story. After Sheilas wallowing, the Inspector cuts in sharply with the harsh reality the characters have got to face. He repeats this throughout the play, continuously trying to place their lives in reality and present the consequences of their actions. He uses harsh phrases such as I was looking at that dead girl, to make it real. He takes charge of the situation, and changes the focus of Sheilas thoughts, and reiterates the style Sheila was talking in, and by him using his personal and possessive pronouns, I said to myself, Im here, Im not going until I know what happened, it redirects the focus to the death of Eva, where it should be. The Inspector retells the story up to its current stage, everything the reader knows up to that point, and then suddenly reveals the next instalment of the mystery by mentioning the name Daisy Renton. Not only does this create interest for the reader, but the sudden instinctive reaction of Gerald and his startled question, what? suddenly introduces the next character to be interrogated by the Inspector. Gerald is actually shocked, and this is presented in his tone of voice, and his body actions. He may suddenly stand with such surprise, a sudden change in body movement draws in the audiences eyes, and his behaviour is from then on closely watched. .u64dbe7527dc022b10aade769301b53fd , .u64dbe7527dc022b10aade769301b53fd .postImageUrl , .u64dbe7527dc022b10aade769301b53fd .centered-text-area { min-height: 80px; position: relative; } .u64dbe7527dc022b10aade769301b53fd , .u64dbe7527dc022b10aade769301b53fd:hover , .u64dbe7527dc022b10aade769301b53fd:visited , .u64dbe7527dc022b10aade769301b53fd:active { border:0!important; } .u64dbe7527dc022b10aade769301b53fd .clearfix:after { content: ""; display: table; clear: both; } .u64dbe7527dc022b10aade769301b53fd { display: block; transition: background-color 250ms; webkit-transition: background-color 250ms; width: 100%; opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #95A5A6; } .u64dbe7527dc022b10aade769301b53fd:active , .u64dbe7527dc022b10aade769301b53fd:hover { opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #2C3E50; } .u64dbe7527dc022b10aade769301b53fd .centered-text-area { width: 100%; position: relative ; } .u64dbe7527dc022b10aade769301b53fd .ctaText { border-bottom: 0 solid #fff; color: #2980B9; font-size: 16px; font-weight: bold; margin: 0; padding: 0; text-decoration: underline; } .u64dbe7527dc022b10aade769301b53fd .postTitle { color: #FFFFFF; font-size: 16px; font-weight: 600; margin: 0; padding: 0; width: 100%; } .u64dbe7527dc022b10aade769301b53fd .ctaButton { background-color: #7F8C8D!important; color: #2980B9; border: none; border-radius: 3px; box-shadow: none; font-size: 14px; font-weight: bold; line-height: 26px; moz-border-radius: 3px; text-align: center; text-decoration: none; text-shadow: none; width: 80px; min-height: 80px; background: url(https://artscolumbia.org/wp-content/plugins/intelly-related-posts/assets/images/simple-arrow.png)no-repeat; position: absolute; right: 0; top: 0; } .u64dbe7527dc022b10aade769301b53fd:hover .ctaButton { background-color: #34495E!important; } .u64dbe7527dc022b10aade769301b53fd .centered-text { display: table; height: 80px; padding-left : 18px; top: 0; } .u64dbe7527dc022b10aade769301b53fd .u64dbe7527dc022b10aade769301b53fd-content { display: table-cell; margin: 0; padding: 0; padding-right: 108px; position: relative; vertical-align: middle; width: 100%; } .u64dbe7527dc022b10aade769301b53fd:after { content: ""; display: block; clear: both; } READ: The speech used is full of double meanings and there are many symbolic features in the play EssayThe Inspector then in contrast is quite calm and collective, and repeats steadily the fact that Eva Smith changed her name to Daisy Renton. This suggests that he is biding time to not only increase the suspense, but that he is acting steadily so he can keep a firm watch over Geralds reaction to the name. Geralds hesitation and lack of immediate honesty immediately suggests he has an involvement with this girl, and the need for a drink suggests a deep involvement and a great unwillingness to reveal it. This suspense builds the tension between the characters on stage, the fact th at the Inspector knows, and Sheila doesnt, creates a barrier between him and his fiancà ¯Ã‚ ¿Ã‚ ½, and the lack of honesty within their relationship. Sheilas watchful eye suggests her lack of trust and awareness of what is to come, SHEILA merely nods, still staring at him.

Antony and Cleopatra analysis of Act one Scene one Essay Example

Antony and Cleopatra analysis of Act one Scene one Paper Antony and Cleopatra by William Shakespeare is a play about a Roman General Antony and an Egyptian Queen Cleopatra. In Act one Scene one it shows how Antony puts Cleopatra in front of his army but Cleopatra just manipulates him successfully. The first part of the play is set in Alexandria. Cleopatra is a powerful woman and she knows she can get everything she wants. She loves the attention being on her, as she thinks so highly of herself. Cleopatra is experienced and manipulating but she is also captivating, Everything becomes her. She uses charisma and charm to persuade people so she always gets her way. Cleopatra has good looks so she can have any man she wants. She knows that Antony is madly in love with her and he will do anything she commands. She is externally fascinating and strong minded. Antony is a General, before meeting Cleopatra he was seen has a respectful and honourable man. Since meeting Cleopatra he has forgotten about how important he is to the rest of his men. Antony has abandoned them for his true love Cleopatra and as suffered the consequences as now they no longer dote him. We will write a custom essay sample on Antony and Cleopatra analysis of Act one Scene one specifically for you for only $16.38 $13.9/page Order now We will write a custom essay sample on Antony and Cleopatra analysis of Act one Scene one specifically for you FOR ONLY $16.38 $13.9/page Hire Writer We will write a custom essay sample on Antony and Cleopatra analysis of Act one Scene one specifically for you FOR ONLY $16.38 $13.9/page Hire Writer He has been put under Cleopatras powerful spell. His heart is now set on a woman rather than war. He used to have a high reputation but now his own men have turned their backs on him. Antony and Cleopatra enter together. The audience can tell that Cleopatra is the more important one, as she has her ladies and a train behind her and with eunuchs fanning her. Antony has nothing compared to Cleopatra. It shows Cleopatras high status and that her entrance is grand. When Philo and Demetrius enter the stage direction says enter Demetrius and Philo but when Antony and Cleopatra enter before it says Flourish. This entrance showing there important significance. When they leave the narrator has said that Antony and Cleopatra exeunt but the train is also mentioned, so we are reminded of Cleopatras importance. Together as a couple they appear to the audience as well-known and mighty. Through Philo we learn about Antony before he enters. Even though he is Antonys friend he tells Demetrius how the men are no longer inspired by him. The audience can see the ups and downs of Antony before he appears. They understand from Philo that he used to be a straight man but now he has been weakened by a woman. Philo is betraying his friend. From Philo the audience learn a lot about Antonys past and future in a short amount of time. When Antony and Cleopatra have entered an left Demetrius and Philo continue to discuss Antony. Demetrius states how Caesar is so unimportant now to Antony, he has been blinded by love. Demetrius questions this though to Philo showing his astonishment to the way Antony behaved. The audience can see that Antony has changed completely, for the worst. Demetrius says how even the common people speak lowly about him, this showing the audience how hated he has become. Adding to this Demetrius says how he is not performing his deeds in Rome. When the messenger tells Antony of the new news, Antony is ignorant and arrogant by saying how he annoyed it had disturbed him. He now thinks he is so important he does not need to acknowledge anything from Rome. The punctuation when Antony is talking is regular, his sentences are short and meaningful. He is very blunt. The audience have by now a strong dislike for Antony. It is clear he speaks in a arrogant manner and gives direct insults. We stand up peerless Antony bluntly puts across to the audience that himself and Cleopatra and the king and queen of lovers and nothing will come between them. Cleopatra is clearly shown patronising and manipulating Antony through her speech. When she first enters she says, if it be love indeed show me how much, from this everyone can see that she likes compliments and attention. Cleopatra emphasises how Caesar is younger that Antony to annoy her lover and possibly make him jealous. Cleopatra is shown how she uses reverse psychology and is successful with it,. For example she tells Antony to go to Rome but she knows by telling him this, he will stay. The audience can now see just how gullible and weak Antony is. Just from the first few pages of the book, the audience can see the true personalities of Antony and Cleopatra. Antony used to be an inspirational general now he is thought of as little by the poorer people. Cleopatra is seen as an extraordinary sensuous woman to the men. I think it is a good idea for Philo to be talking about Antony first, so the audience know background about him and can begin to decide their opinions of him. The start of the play also helps to make a dramatic opening. Just from the entrance the audience can visibly see the importance and status of Cleopatra without dialogue needed. Therefore each of the main characters are introduced in a different way, making the play more appealing.

The gastrointestinal tract The WritePass Journal

The gastrointestinal tract The gastrointestinal tract ABSTRACTINTRODUCTION1.1 The gastrointestinal tract1.2  Ã‚   5-hydroxytryptamine1.3   5-HT4 receptor subtype1.4  Ã‚   5-HT4 receptor agonists and antagonists1.3  Ã‚   Aims of the studyMETHOD  2.1 Krebs solution2.2 Preparation of the tissue2.3 Experimental preparation2.4  Ã‚  Administration of drugs2.5  Ã‚  Statistical analysisRESULTS  3.1 The effects of 5-HT on the peristaltic reflex in the mouse proximal colon3.2 The effects of the 5-HT4 receptor antagonist, SB204070, on the   cumulative addition of 5-HT on the peristaltic reflex in the mouse proximal colon  3.3   The effects of tegaserod on the peristaltic reflex in the mouse  proximal colon3.4  Ã‚   The effects of the 5-HT4 receptor antagonist, GR113808, on the  Ã‚  cumulative addition Tegaserod on the peristaltic reflex in the mouse  proximal colon DISCUSSION  REFERENCESAPPENDIX     Ã‚  Ã‚              Related ABSTRACT The objective of the present study was to examine the effect of 5-HT4 receptor ligands on the peristaltic reflex in the mouse colon. 5-hydroxytryptamine, a neurotransmitter found mainly within the gastrointestinal tract, has been implicated in the contraction and  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   relaxation of smooth muscle within this region. The actions of 5-HT are mediated by at least one or more of seven subtype receptors. The receptor subtype that will be the focus of attention in this study is the 5-HT4 receptor. Segments of the proximal colon obtained from MF1 mice, were cannulated at the anal and aboral ends, and secured horizontally in a water jacketed bath containing oxygenated Krebs solution. The intraluminal distension pressure was controlled by adjusting the elevation of the reservoir, and the volume ejected to the aboral side was recorded and measured via a a pressure transducer and Power Lab system using Chart v4.1.2 software for Windows.. All drugs were administered serosally. Cumulative concentration response curves of 5-HT and tegaserod (agonists) were obtained by adding increasing concentrations of drugs at an interval of 5-15 minutes. The antagonists GR113808 and SB204070 were added to the tissues after regular peristalsis was obtained and allowed to equilibrate for 15 minutes, after which either 5-HT or tegaserod were added cumulatively. All results are expressed as mean ±SEM from number of animals indicated by n. A regular peristalsis was established before the addition of 5-HT (average rate of peristalsis was 77 ±7, n=7. 5-HT facilitated peristalsis at 10-7M and further cumulative addition of 5-HT caused a slow decrease in peristalsis until at 10-4M, rate of peristalsis was inhibited. In all tissues in which peristalsis was inhibited, it recovered once tissue was washed. In the presence of SB204070 and GR113808, there was no significant change in the rate of peristalsis. The addition of tegaserod produced only a slow decrease in peristalsis until peristalsis was abolished in all tissues at 10-4M. The peristalsis abolished by tegaserod could not be re-established in any tissue by washing. In all tissues, it was possible to obtain peristalsis so the effects of drug testing could be established. The addition of the 5-HT4 selective receptor antagonists, SB204070 and GR113808, showed no significant change in the concentration-response curves. The partial 5-HT4 agonist, tegaserod, also did not facilitate peristalsis in the current study. Both these findings suggest that the 5-HT4 receptor is not implicated in the mouse proximal colon INTRODUCTION 1.1 The gastrointestinal tract The digestive system is a vital component of the human body; the overall function being to provide nourishment for over a trillion cells within the body. To be able to do this, the digestive system is specialised to ingest food, propel it through the digestive tract, digest it, and absorb water, electrolytes and other nutrients from the lumen of the gastrointestinal tract (Seeley et al, 2006). The absorbed substances are transported to the cells, via the circulatory system, whilst the undigested substances are eliminated from the anus. The digestive system consists of the main digestive tract, a tube extending from the mouth to the anus, as well as its associated component organs and accessory organs, which are primarily glands located outside the digestive tract that secrete fluids into the digestive tract (Seeley et al, 2006). The component organs include the oral cavity (mouth), pharynx (throat), oesophagus, stomach, small intestine, large intestine and anus. The accessory organs include three pairs of salivary glands, the exocrine pancreas and the exocrine liver. To enable the homoeostatic environment within the body to be maintained, it is vital that the digestive system is functioning efficiently. The large intestine, which consists of the caecum, colon and rectum, has sufficient homeostatic functions, and contributes to the overall stability of the homoeostatic environment within the body. The colon is the central part of the large intestine, and constitutes the last 150cm of the gastrointestinal tract. It i s approximately a 6cm tube, which extends from the ileum to the anus. Its main function is to store faecal material and regulate its release into the external environment (Smith et al, 2006). It also produces a thick mucous secretion, which lubricates the passage of faecal material during defecation. The gastrointestinal tract of a mouse consists of the oesophagus, stomach, small intestine and large intestine. The mouse colon is similar to the human colon, consisting of the ascending, transverse and descending parts but lacking the sigmoid part (Cook, 1965). http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/G/GITract.html The main physiological processes of the digestive system are digestion, absorption, motility, secretion, and excretion. Digestion involves the breakdown of larger molecules to smaller ones (i.e. glucose and amino acids) to allow efficient utilisation and absorption of these molecules. The ingested material and secretions are transported across the epithelial cell membrane, mainly within the small intestine.   Subsequently, the transported molecules enter the circulation; a central physiological process of the digestive system. The gastrointestinal tract is approximately a 15 feet long tube, and food must be moved along it to reach the correct sites for digestion, mixing and absorption (Smith et al, 2001). This process, known as peristalsis, is aided by the smooth muscle lining the tract, which contracts and relaxes mixing the ingested material, whilst at the same time propelling it through the tract. Propulsion of the intestinal contents is a crucial part of digestion that depends on the coordinated activity of circular and longitudinal smooth muscles brought about by the peristaltic reflex (Shiinaa et al, 2005).   The peristaltic reflex is initiated by either stimulation of the gastrointestinal mucosa or by stretching of the intestinal wall, resulting in a circular contraction behind the stimulus and an area of relaxation in front of it (Shiinaa et al, 2005).   This wave of contraction moves in the oral-anal direction, and subsequently propels the contents within the lumen forward. The reflex is co-ordinated by the intramural nerve plexuses within the intestine and so, can be obtained even in the isolated tissues. Many studies investigating the mechanisms which mediate intestinal motility have predominantly focused on peristalsis.   Trendelengburg (1917) carried out the first in vitro study investigating the peristaltic reflex in guinea pig ileum. Within the ileum, the reflex was found to consist of contractions of both the longitudinal and circular muscles that were both regular as well as coordinated. The increase in intraluminal pressure, which causes the ileum to distend, is followed by an increase in longitudinal muscle contraction, and subsequently, by an increase in circular muscle contraction, which propels the contents towards the anal section (Trendelengburg, 1917). Gastrointestinal disorders are a common problem in today’s society, and many lead to long term diseases and even morbidity, as well as having a negative impact on healthcare costs (Crowell et al, 2004) However, due to the complexity and the differing functions of the various organs of the GI tract, the treatment of disorders within the tract is a very complex task and has not, as of yet, been fully understood. Diseases of the colon can lead to a whole host of illnesses, including diarrhoea, constipation, Crohn’s disease, Inflammatory Bowel disease, Irritable Bowel Syndrome (IBS), and many more. Symptoms occurring outside of the GI tract, in particular symptoms associated with ibs, including anxiety, depression and schizophrenia, have been related to the morbidity of such disorders.   It has been suggested by research, that altered levels of the neurotransmitter, 5-hydroxytryptamine (serotonin), may lead to both intestinal and extra intestinal symptoms in IBS, as well as being implicated in other functional bowel diseases It is therefore important that further studies are carried investigating the link between 5-hydroxytryptamine and disorders of the gastrointestinal tract, and to further understand the pathogenesis of these disorders, so that new, more effective treatments can be formulated. 1.2  Ã‚   5-hydroxytryptamine 5-hydroxytryptamine, also more commonly referred to as serotonin, is a monoamine neurotransmitter, and is predominantly synthesised, stored and released in the enterchromaffin cells of the intestinal mucosa (Costedio et al, 2007). According to Gershon et al (1965), 5-HT is synthesised through the action of two tryptophan hydroxylases, TpH1 and TpH2, which are found within the enterochromaffin cells and neurons. Approximately 95% of all mammalian 5-hydroxytryptamine is found within the gastrointestinal tract (Sanger, G.J, 2008) 5-HT initiates the peristaltic and secretory reflex, and transmits information to the central nervous system, by activating both the intrinsic and extrinsic primary afferent neurones (Sikandar et al 2009).   It can also modulate a wide range of biological processes such as mood, cognition, perception, feeding behaviour, smooth muscle contractility, and platelet aggregation (Setola et al, 2003). Within the guinea pig ileum, 5-HT has been found to cause both facilitation and inhibition of peristalsis (Tuladhar et al), and has been found to facilitate peristalsis, when added serosally in the marmoset ileum (Tuladhar et al, 1996). The actions of 5-HT, particularly contraction or relaxation responses, are mediated by at least one or more of seven subtype receptors (Setola et al, 2003), ranging from 5-HT1 to 5-HT7. 5-HT1 and 5-HT2   receptors have been further subdivided, as can be seen in figure 2.With the exception of the 5-HT3 receptor, the other receptors are, at molecular level, G protein couple metabotropic receptors which span the membrane. The 5-HT3 receptor is a ligand-gated ion channel (Barnes et al, 1999). Many 5-HT receptors can now be associated with various physiological responses, ranging from modulation of neuronal activity and transmitter release to behavioural change (Barnes et al, 1999). Receptor Subtype Transduction Mechanism Localization Function Specific Agonists Specific Antagonists 5-HT1A ↓AC (Gi/o) Limbic system (hippocampus, lateral septum, cortical areas), mesencephalic raphe nuclei Hyperpolarization, modulation of neurotransmitter release, anxiolysis, hypothermia, hyperphagia Xaliprofen (2491) S 14506 (1771) Ipsapirone (1869) BP 554 (0556) U 92016A (2739) Tandospirone (2854)* MM 77 (0933) NAN-190 (0553) Spiroxatrine (0631) (S)-WAY 100135 (1253) 5-HT1B ↓AC (Gi/o) Basal ganglia, striatum, amygdala, trigeminal ganglion, vascular smooth muscle Autoreceptor, locomotion, hypophagia, hypothermia, modulation of neurotransmitter release, vasoconstriction CGS 12066B (0638) CP 93129 (1032) CP 94253 (1317) 5-Nonyloxytryptamine (0901) GR 55562 (1054) Isamoltane (0992) SB 224289 (1221) NAS-181 (1413) 5-HT1D ↓AC (Gi/o) Basal ganglia, hippocampus, cortex, spinal cord, vascular smooth muscle Autoreceptor, modulation of neurotransmitter release L-694,247 (0781) GR 46611 (0864) PNU 109291 (2556) PNU 142633 (1985) BRL 15572 (1207) Cyanopindolol (0993) LY 310762 (3078) 5-ht1E ↓AC (Gi/o) Cortex, caudate putamen, claustrum, hippocampus, amygdala Unknown BRL 54443 (1129) 5-HT1F ↓AC (Gi/o) Hippocampus, cortex, dorsal raphe nucleus, uterus Speculative role in visual and cognitive function BRL 5443 (1129) LY 344864 (2451) LY 334370 (3079) 5-HT2A ↑ PLC Forebrain, caudate nucleus, nucleus accumbens, hippocampus, olfactory tubercle, vascular smooth muscle, blood platelets Neuronal depolarization, head twitch, hyperthermia, modulation of neurotransmitter release smooth muscle contraction, platelet activation TBC-2 (2592) R-96544(1742) Spiperone (0995) MDL 11,939 (0870) 4F 4PP (0523) Risperidone (2865) 5-HT2B ↑ PLC Brain, stomach fundus (rat), gut, heart, kidney, lung Contraction of the stomach fundus, anxiety BW 723C86 (1059) SB 204741 (1372) LY 272015 (3077) 5-HT2C ↑ PLC Choroid plexus, cortex, limbic system, basal ganglia Hypolocomotion, hypophagia, penile erection, hyperthermia, anxiety, ↓ noradrenalin and dopamine release MK 212 (0941) Ro 60-0175 (1854) WAY 161503 (1801) CP 809101 (3041) 1-Methylpsilocin (3017) N-Desmethylclozapine (1007) RS 102221 (1050) SB 242084 (2901) 5-HT3 Ion channel (Na+, K+, Ca2+) Dorsal vagal complex, hippocampus, amygdala, caudate, cerebral cortex, heart, intestines Anxiety, cognition, pain , reward/withdrawal, vomiting reflex, vasodilation, intestinal tone and secretion SR 57227 (1205) Quipazine (0629) 1-phenylbiguanide (0969) m-chlorophenylbiguanide (0440) MDL 72222 (0640) Tropisetron (2459) Y-25130 (0380) Ondansetron (2891) Granisetron (2903) 5-HT4 ↑ AC (Gs) Cerebral cortex, limbic areas, hippocampus, colliculus, intestines Learning and memory, visual perception, anxiety, motor coordination, arousal, smooth muscle relaxation, modulation of neurotransmitter release Cisapride (1695) RS 67333 (0989)* RS 67506 (0990)* CJ 033466 (3089)* GR 113808 (1322) GR 125487 (1658) RS 39604 (0991) RS 23597-190 (0728) 5-ht5A ↓ AC (Gi/o) Amygdala, hippocampus, caudate nucleus, cerebellum, hypothalamus, thalamus, substantia nigra, spinal cord Modulation of exploratory behavior and locomotion SB 699551 (3188) 5-HT6 ↑ AC (Gs) Striatum, olfactory tubercles, nucleus accumbens, hippocampus, stomach, adrenal glands Memory and learning, modulation of neurotransmitter release 5-Methyl-5-hydroxytryptamine (0558) EMD 386088 (2382) SB 258585 (1961) Ro 47-1816/001 (2911) SB 399885 (3189) NPS ALX Compound 4a (3285) 5-HT7 ↑ AC (Gs) Thalamus, hypothalamus, hippocampus, cerebral cortex, amygdala, GI and vascular smooth muscle, heart Circadian rhythms, smooth muscle relaxation, nociception, hypotension, modulation of REM sleep, learning and memory, LH release AS 19 (1968) LP 44 (2534) LP 12 (2925) Pimozide (0937) SB 269970 (1612) SB 259719 (2726) Figure 2:   A table summarising the properties of 5-HT receptors and subtypes (tocris.com/pharmacologicalBrowser.php?ItemId=5101)    1.3   5-HT4 receptor subtype The receptor subtype that will be the focus of attention in this study is the 5-HT4 receptor subtype. These receptors are located primarily in the nigrostriatal and mesolimbic systems and smooth muscle in the gastrointestinal tract, and play a role in gastrointestinal motility (Craig Clark, 1989), as well as in anxiety, visual perception, memory and learning. The 5-HT4 receptors on intrinsic primary and afferent neurones, are activated by endogenous serotonin released from enterchromaffin cells, in response to mechanical or chemical stimuli. These neurons release transmitters such as calcitonin gene-related peptide (CGRP), activating interneurons which in turn stimulate excitatory neurons on the orad side of the mucosal stimulus and stimulate inhibitory neurons on the caudad side (Ji et al, 2004). Subsequently, this results in peristaltic reflexes occurring at the site of the originating stimuli. The effect of 5-HT4 receptor modulated peristalsis has been found in guinea pig ileum (Tuladhar, 1994; Tuladhar et al, 1995). Also, stimulation of 5-HT4 receptors have been reported to enhance the peristaltic reflex in the rat distal colon (Kadowaki et al, 2002). 5-HT4 receptor agonists, such as tegaserod and 5-HT, stimulate gastrointestinal motility and secretion through release of acetylcholine from excitatory neurones. It is important to note that 5-HT4 agonists strengthen, rather than directly activate the peristaltic reflexes 1.4  Ã‚   5-HT4 receptor agonists and antagonists The 5-HT4 receptor agonists that will be focus of this study will be tegaserod and 5-hydroxytryptamine (as mentioned above), and antagonists will be GR113808 and SB204070. Tegaserod [3-(5-methoxy-1H-indol-3-ylmethylene)- N-pentyl-carbazimidamide] hydrogen maleate, is a partial 5-HT4 agonist that has been implicated in gastro-intestinal motility.   In the guinea pig ileum, tegaserod was found to stimulate peristalsis by increasing the number of circular muscle contractions (Ji et al, 2004).   It has been used in the treatment of symptoms of irritable bowel syndrome, including abdominal pain, bloating and constipation (Mà ¼ller-Lissner et al, 2001). The responses mediated by 5-HT4 receptors have been greatly facilitated by a number of highly selective antagonists e.g. GR113808, SB204070 SB204070 (1-Butyl-4-piperidinyl)methyl-8-amino-7-chloro-1,4-benzodioxane-5-carboxylate hydrochloride) is a selective 5-HT4  serotonin receptor antagonist. In the guinea pig distal colon, SB204070 was found to antagonize 5-HT4 receptor mediated-contractions Although the nature of the antagonism is quite complex, it has been suggested that SB204070 acts has a pseudo-irreversible antagonist (Wardle et al, 1994). GR113808 (1-methyl-1H-indole-3-carboxylic acid, [1-[2-[(methylsulfonyl)amino]ethyl] -4-piperidinyl]methyl ester) is a potent, selective 5-HT4 receptor antagonist. In the guinea-pig ascending colon,  GR113808  behaved as an antagonist of 5-hydroxytryptamine -induced contraction, with a high affinity for the 5-HT4 receptor (Gale et al, 1994). 1.3  Ã‚   Aims of the study The aims of our investigation were to investigate whether 5-HT4 receptor ligands were able to modulate the peristaltic reflex within the mouse proximal colon. This study also allowed us to investigate the effect of pharmacological manipulations that have been designed to study the role of 5-hydroxytryptamine on the peristaltic reflex within this region of the intestine. This study was undertaken using a range of 5-HT4 receptor agonists and antagonists. METHOD   2.1 Krebs solution The Krebs-Heinslet solution was prepared at the start of the experiment. To prepare one litre of the solution, 2.1g of sodium hydrogen carbonate (NaHCO3) and 2g of glucose were dissolved in 300ml of dissolved water. 40ml of the Krebs-Heinslet concentration was added to the solution, and the preparation was made up to 1 litre using distilled water. It was found that 5 litres was an adequate volume for the experiment, therefore this was prepared by multiplying each quantity by 5. The marriotte bottle containing the Krebs-Heinslet solution was attached to the apparatus, and used to wash out each organ bath three times, and then added to the required level. 2.2 Preparation of the tissue The experiment was carried out using MF1 mice. The animals were killed by cervical dislocation, and the GI tract was removed. Segments of the proximal colon (approx. 2-3cm) were carefully dissected on a polystyrene board, taking care not to puncture the colon and to disturb it as little as possible. This section was then quickly transferred to the water jacketed glass bath, which contained Krebs-Heinslet solution aerated with 95% oxygen and 5% CO2, and maintained at 37OC.   This was to prevent hypoxia of the tissue and abnormal temperature. All tissues were equilibrated for at least 20 minutes prior to the start of the experiment. The oral end of the proximal colon was cannulated to the inflow glass tube, which was connected to the reservoir containing saline solution, and secured with thread. The intraluminal contents of the colon were allowed to expel naturally via peristalsis, brought about by the raising of the height of the reservoir by 4cm. After the contents had been expelled, the reservoir was lowered and the aboral end was then cannulated to the opposing outflow glass tube. The tissue was then left to equilibrate for at least 20 minutes prior to the start of the experiment.   Finally, to induce peristalsis, the intraluminal pressure was raised, by raising the reservoir by 4cm for at least 15 minutes, until peristalsis became regular and the drugs could be administered; the height of the reservoir needed to achieve steady peristalsis was determined in preliminary experiments. 2.3 Experimental preparation The outflow tube was connected, via a plastic tube, to a T glass tube, which was open to the atmosphere. Changes to the volume of fluid driven into this vertical tube during peristalsis were measured as a pressure changes, and recorded using pressure transducers connected to a quad bridge amplifier and Power Lab system using Chart v4.1.2 software for Windows. Before the proximal colon was cannulated, the computer software was calibrated to zero, and set to commence recording. Figure 3: A schematic diagram representing apparatus used to study peristalsis in mouse proximal colon. The peristalsis trace on the power lab software was recorded as a series of peaks and troughs. During peristalsis the peaks were formed when the tissue contracted, and the troughs formed when the tissue relaxed. This cycle was repeated with each peristaltic stroke. 2.4  Ã‚  Administration of drugs After regular peristalsis had been established, the drugs could be administered serosally. A cumulative response curve for the agonist tegaserod was obtained by adding increasing concentrations of tegaserod (0.01 µM– 10 µM). In the preliminary experiments, it was found that tegaserod 10-2M did not allow the tissue to exhibit peristalsis sufficiently, and was too potent, therefore the highest concentration used was 10-3M. Each concentration had a 15 minute contact time with the tissue before the next concentration was administered. The volume ejected and the rate of peristalsis was measured and recorded. Changes to the rate of peristalsis were then compared to the control values obtained 15 minutes prior to administering the first drug. In the preliminary experiments, it was found that washing the tissue between each drug administration had a negative effect on peristalsis, and subsequently the tissue didn’t recover. Therefore drugs were administered continuously wit hout washout. This process was repeated with the agonist, 5-HT, with concentrations ranging from 0.1 µM-100 µM. To examine the effects of GR113808 and SB204070 (antagonists)   on 5-HT and tegaserod responses, either   antagonist was added to the tissues after regular peristalsis was obtained and allowed to equilibrate for 15 minutes, after which either 5-HT or tegaserod were added cumulatively and their effects on peristalsis were measured as described above 2.5  Ã‚  Statistical analysis All results are expressed as mean ±SEM from number of animals indicated by n. The difference between the values was determined by using the unpaired t test when two groups were compared and using the one way ANOVA followed by Fisher’s PLSD when more than two groups were compared.    2.6  Ã‚   Consideration of safety issues The chemicals used within this investigation were obtained from Tocris bioscience. To ensure the safety of all members of the group throughout the duration of the investigation, a chemical risk assessment form (COSHH) was formulated and signed by all members. This form highlighted all the chemicals that were to be used throughout the experiment, and the risks and precautions associated with each of them. It was ensured that the precautions were adhered to at all stages of the experiment, and general laboratory regulations were also put into place i.e. no eating or drinking in labs, wearing a lab coat etc.    RESULTS   The peristaltic reflex was investigated within the mouse proximal colon. Segments of the proximal colon (approximately 3cm in length) were cannulated in vitro, and regular peristalsis was achieved by raising of the intraluminal pressure. Peristalsis was distinguished as circular muscle contractions arising from the oral side and travelling to the anal side. The proximal part of the colon was distinguished from the distal part by striations across the surface, and also by it containing softer faecal pellets 3.1 The effects of 5-HT on the peristaltic reflex in the mouse proximal colon A regular peristalsis was established before the addition of 5-HT (average rate of peristalsis was 77 ±7, n=7).   The fluid was ejected from the oral to anal direction. The addition of 5-HT 10-7M caused a significant increase in the rate of peristalsis. At this concentration the rate of peristalsis was 101  ± 8, n=7, which was a substantial increase from the control value. Further cumulative addition of 5-HT caused a slow decrease in peristalsis until at 10-4M, rate of peristalsis, at 56  ± 19, n=7 , was lower than the control at the beginning. In all tissues in which peristalsis was inhibited, it recovered once tissue was washed. 3.2 The effects of the 5-HT4 receptor antagonist, SB204070, on the   cumulative addition of 5-HT on the peristaltic reflex in the mouse proximal colon   3.3   The effects of tegaserod on the peristaltic reflex in the mouse  proximal colon 3.4  Ã‚   The effects of the 5-HT4 receptor antagonist, GR113808, on the  Ã‚  cumulative addition Tegaserod on the peristaltic reflex in the mouse  proximal colon                   DISCUSSION   Gastrointestinal disorders within humans and animals have become much more common, and as such more effective treatments need to be formulated. Research has implicated 5-hydroxytryptamine within these disorders, and thus the 5-HT receptors, which are involved in gastrointestinal motility, are potential targets for treating such disorders. The present investigation was designed to study the peristaltic reflex within the mouse proximal colon, and further, to investigate the 5-HT4 receptor, which has been found to modulate peristalsis in the guinea pig ileum (Tuladhar et al., 1995). Peristalsis is the principle mechanism controlling the movement of chyme within the intestine, and takes place without the conscious control. The nervous pathway of the peristaltic reflex is entirely intrinsic (Bulbring et al,1958), and therefore we can obtain this reflex even in isolated tissues. The method used to study peristalsis was similar to the one used by Trendelengburg (1917), in which the peristaltic reflex was triggered by raising of the intraluminal pressure, allowing the measurement of different parameters of peristalsis, including the rate of peristaltic stokes and the volume of intraluminal fluid ejected to the anal side with each peristaltic stroke. Within the present study, regular peristalsis was obtained so the effects of the 5-HT4 receptor ligands could be established. Craig and Clarke (1991) suggested that the 5-HT4 receptors had a facilitatory effect on 5-HT in the guinea-pig ileum and this was further confirmed by Tuladhar et al (1993). However, this finding was not reciprocated within the mouse proximal colon. Cumulative addition of 5-HT produced facilitation of peristalsis within the mouse proximal colon, characterised by an increase in the number of peristaltic strokes per hour and thus the rate of peristalsis at 10-7M.. This facilitation was observed at concentrations up until  Ã‚   10 -4M, where inhibition of peristalsis was observed. At this concentration, 5-HT desensitised the tissues so no further peristalsis could be established. However, peristalsis was re-established in 6 out of the 7 tissues after washing of the tissues. This facilitatory and inhibitory effect of 5-HT was also observed in various studies carried out by Tuladhar et al, Bulbring Crema (1958) and others. Therefore, this study has shown that the addition of 5-HT in vitro can modulate peristalsis within the mouse proximal colon. At lower concentrations, 5-HT facilitates peristalsis, whereas at higher concentrations 5-HT can both facilitate and inhibit peristalsis. In the present study both GR113808 and SB204070 failed to affect the facilitatory effect of 5-HT in the mouse proximal colon. GR113808 and SB204070 are both highly potent 5-HT4 receptor antagonists (Gale et al., 1994; Wardle et al., 1994). This suggests that the 5-HT4 receptor is not implicated within the mouse proximal; had it been implicated both SB204070 and GR113808 would have antagonised the 5-HT4 receptor mediated contractions, and there would have been a significant decrease in the rate of peristalsis. This is in contrast to the findings by Costall et al (1993), where the 5-HT4 receptor was implicated in the guinea pig ileum, in which it exhibited a facilitatory effect on 5-HT. In the guinea-pig ileum tegaserod has also been shown to facilitate peristalsis ( Ji et al, 2004 ),   which was not observed in the current study.   This further suggests that the 5-HT4 receptor is not implicated within the mouse proximal colon; as tegaserod is a partial 5-HT4 agonist, had 5-HT4 receptor been implicated, facilitation of peristalsis would have been observed. The inhibitory effect of 5-HT on peristalsis has been reported to involve the 5-HT7 receptor (Tuladhar et al, 2003). 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Clinica chimica acta; international journal of clinical chemistry, 403, 47-55. TULADHAR, B.R., COSTALL, B. NAYLOR, R.J. (1995). Evidence of a 5-Ht3 Receptor-Mediated Facilitation of the Emptying Phase of the Peristaltic Reflex in the Isolated Guinea-Pig Ileum. Br J Pharmacol, 114, P374-P374. TULADHAR, B.R., COSTALL, B. NAYLOR, R.J. (2002). Modulation of 5-HT4 receptor function in the rat isolated ileum by fluoxetine: the involvement of endogenous 5-hydroxytryptamine. Br J Pharmacol, 136, 150-6. TULADHAR B.R   (2003)   5-HT7 receptors mediate the inhibitory effect of 5-HT on peristalsis in the isolated guinea-pig ileum. Br J Pharmacol WARDLE, K. A., ELLIS, E. S., BAXTER, G. S., KENNETT, G. A., GASTER, L. M. SANGER, G. J. (1994). The effects of SB 204070, a highly potent and selective 5-HT4 receptor antagonist, on guinea-pig distal colon. British journal of pharmacology,  Ã‚  Ã‚   112, 789-94. HTTP://WWW.TOCRIS.COM/PHARMACOLOGICALBROWSER.PHP?ITEMID=5115. APPENDIX Table 1: 5-HT alone    S.No    -log C (M)    RATE OF PERISTALSIS 1 2 3 4 5 6 7 AVG SEM N 1 Before 58.7 56.9 71.6 114.9 73.9 77.1 82.2 77 7 7 2 7.00 126.8 77.6 95.1 115.3 119.4 76.8 95.6 101 8 7 3 6.00 120.4 58.1 77.3 102.7 127.7 92.1 70.2 93 10 7 4 5.00 42.9 26.1 61.9 104.5 93.0 67.9 93.7 70 11 7 5 4.00 0.0 0.0 37.9 105.7 113.7 29.8 105.0 56 19 7 Table 1 shows the rate of peristalsis after adding the agonist,5-HT 10-8 – 10-4 M, to mouse proximal colon. The values are expressed as mean ±SEM. Table 2: 5-HT in the presence of SB204070    S.No    -log C (M)    RATE OF PERISTALSIS 1 2 3 4 5 6 7 AVG SEM N 1 SB-204070 7.00 79.4 129.3 44.1 31.2 101.6 79.2 82.8 78.2 12.4 7 2 5-HT 5.00 149.9 124.6 71.3 30.2 102.7 58.8 95.1 90.4 15.3 7 3 5HT 4.00 113.8 132.2 19.7 27.9 96.3 51.2 130.3 81.6 18.1 7 4 5HT 3.00 90.8 114.9 23.0 25.9 99.2 77.2 0.0 61.6 16.8 7 5 5HT 2.00 0.0 122.1 0.0 0.0 0.0 55.8 0.0 25.4 17.9 7 Table 2 shows the rate of peristalsis after adding 5-HT 10-5 – 10-2 in the presence of the 5-HT4 antagonist, SB204070 10-7M, to the mouse proximal colon. The values are expressed as mean ±SEM. Table 3: Tegaserod alone       S.No    -logC (M)    RATE OF PERISTALSIS 1 2 3 4 5 AVG SEM N 1 Before 42.6 45.6 151.3 45.6 116.6 80.3 22.5 5 2 8.00 40.9 40.9 127.3 41.3 123.0 74.7 20.6 5 3 7.00 38.7 35.2 107.4 32.6 0.0 42.8 17.5 5 4 6.00 31.1 38.1 97.9 27.9 123.3 63.7 19.6 5 5 5.00 0.0 0.00 0.00 0.0 45.4 9.0 9.0 5 Table 3 shows the rate of peristalsis after adding the agonist, tegaserod 10-8 – 10-5 M, to mouse proximal colon. The values are expressed as mean ±SEM. Table 4: Tegaserod in the presence of SB204070    S.No    -logC (M)    RATE OF PERISTALSIS 1 2 3 4 5 AVG SEM N 1 BEFORE 99.4 107.5 121.2 124.3 105.4 111.5 4.7 5 2 SB-204070 7.00 64.5 98.1 65.1 59.8 53.6 68.2 7.7 5 3 Tegaserod 8.00 100.1 105.8 91.3 110.8 54.3 92.5 10.0 5 4 Tegaserod 7.00 107.3 122.2 74.5 72.5 59.7 87.3 11.7 5 5 Tegaserod 6.00 111.4 113.4 99.2 90.5 83.7 99.6 5.7 5 6 Tegaserod 5.00   Ã‚  Ã‚  Ã‚  Ã‚   0.0 0.0 104.9 213.4 75.7 78.8 39.5 5 Table 4 shows the rate of peristalsis after adding tegaserod 10-8 – 10-5 in the presence of the 5-HT4 antagonist, SB204070 10-7M, to the mouse proximal colon. The values are expressed as mean ±SEM. Table 5: Tegaserod in the presence of GR113808       S.No    -logC (M)    RATE OF PERISTALSIS 1 2 3 4 5 6 7 AVG SEM N 1 BEFORE 33.0 108.2 129.9 50.7 31.9 34.1 35.0 64.8 17.6 7 2 GR113808 6.00 15.6 82.6 121.6 47.6 25.2 18.4 19.6 52.0 17.2 7 3 Tegaserod 8.00 37.8 267.2 105.9 48.0 22.2 26.12 21.5 75.5 33.8 7 4 Tegaserod 7.00 71.3 339.7 112.2 49.7 17.4 24.00 9.2 89.0 43.9 7 5 Tegaserod 6.00 74.4 277.4 49.0 37.2 19.9 14.53 0.0 67.4 36.2 7 6 Tegaserod 5.00 20.1 0.0 0.0 30.7 -1.5 10.02 0.0 8.4 4.7 7    Table 5 shows the rate of peristalsis after adding tegaserod 10-8 – 10-5 in the presence of the 5-HT4 antagonist, GR11380810-6M, to the mouse proximal colon. The values are expressed as mean ±SEM.

1.Its not just about the fuel - The challenges of sustainability Essay

1.Its not just about the fuel - The challenges of sustainability facing the car industry - Essay Example Governments are offering incentives in order to propagate sustainability goals. However, there has been a shift towards outsourcing manufacturing to developing economies from developed ones. This implies that competition is rife in the automobile industry. Additionally, this model stretches the supply chain across geographies, thus increasing greenhouse gas emissions in production. Sustainability goals may be perceived negatively by auto investors, who may think of them as additional expenditures. Engineering skills are dwindling in the developed world with several innovation decisions being made in outsourcing nations; regrettably, most are not committed to sustainability. Tax regimes and complex human resource systems may be a force to reckon with in the sustainability agenda. Small and medium enterprises are also involved in the supply chain, especially those which provide small automotive parts. Some of them find it difficult to access finance for their work. Incentives for research and development especially with regard to collaboration with other parties may be difficult. Certain governments have led the way in supporting automobile manufacturers and consumers in making sustainable car choices. Consumers are also learning about their role in enhancing intelligent mobility, as environmental concerns do not just end at manufacturing. Several manufacturers are now prioritising environmental issues in production. A number of them want to improve their internal combustion engines. This ensures that waste recovery takes place in production. Additionally, they facilitate the integration of electric machines and combustion engines, thus minimising utility. Environmental issues have also led to innovation in enhancing the energy storage of automobiles and the material production of those items. Lightweight manufacture of products is becoming a key manufacturing goal. However, the