Thursday, December 26, 2019
The Baseline Leadership Survey For The First Cohort Essay
Results Leadership Survey When analyzing the baseline leadership survey for the first cohort, we specifically looked at baseline frequency distributions of the ââ¬Å"I feel like a Leader scenarios, most Littles reported feeling more like a leader at home and with friends. On a scale of one to five, one being Not at all like me and five being A lot like me, many girls indicated that they were less likely to feel like a leader at school. As seen in table 8 below, 14 percent of Littles reported that they did not feel like a leader at school, compared to that of 11.6 percent who did. Conversely, 7 percent of Littles reported that they did not feel like a leader with friends, compared to the 16.3 percent that did. Lastly, when assessing Littles who felt like a leader at home, 11.6 percent reported that they felt less like a leader, compared to the 23.3 percent who did. When analyzing the end of program leadership survey for the first cohort, most Littles reported feeling more like a leader at home and with friends. As seen in table 9, 16.3 percent of Littles reported that they did not feel like a leader at school, compared to that of 7 percent who did. On the other hand, 14 percent of Littles reported that they did not feel like a leader with friends, compared to the 16.3 percent that did. Lastly, when assessing Littles who felt like a leader at home, 16.3 percent reported that they felt less like a leader, compared to the 16.3 percent who did. A paired-samples t-test was runShow MoreRelatedThe New Graduate Nurse Cohort1397 Words à |à 6 Pagesimperative that the new graduate nurse cohort be given a full immersion into the organizational culture, a quality orientation program, and to feel welcomed into their departments to foster embeddedness early in the program (Reitz, 2014). To facilitate this, the program will begin with a welcoming gathering for their inauguration. This gathering will be designed to introduce the new graduates to organizational leaders, former graduates, and new graduates within their cohort in order to begin the buildingRead MoreThe Young Women s Leadership Project Essay1876 Words à |à 8 PagesThe Young Womenââ¬â¢s Leadership Project (YWLP) seeks to increase middle school age girlsââ¬â¢ capacity for leadership, contributing to increased success in high school and post-secondary education. Much like the traditional BBBS model, YWLP provides at-risk middle school age girls in Harrisonburg, VA with high quality one-to-one mentoring services, in combination with out-of-school learning opportunities and a week-long summer camp. Utilizing research as a basis, YWLP integrates individual mentoring withRead MoreQuality and the Balanced Scorecard Approach: Nursing and Health Care1431 Words à |à 6 Pagesa large impact on internal job satisfaction for nurses and medical staff as well. For instance, if the BSA uses an internal survey to gauge satisfaction and asks: Do you think you should have more financial compensation for what you do at work? what employee would not respond yes? Instead, information must be connected to all stakeholders and phrased with careful baseline measurements that are general and reasonable. Thus, the purpose of this type of information collection is the building a relationshipRead MoreThe Value Of Studying And Practicing Transformative Leadership1195 Words à |à 5 PagesThe Value of Studying and Practicing Transformative Leadership ââ¬Å"There is nothing permanent except change.â⬠~ Heraclitus The greatest lesson life has taught me is ââ¬Ëthe only thing that stays the same, is change.ââ¬â¢ Too often individuals respond to change based on fear, becoming exceedingly inflexible and futile, letting an incidence define them instead of seizing the moment. However, change creates opportunity, when versed with empowerment its outcome inaugurates balance, as well as fortifies establishedRead MoreAdvancements Based Practice And Practice2253 Words à |à 10 Pagespractice (Hain and Haras, 2015). It is crucial to be able to establish and enforce new practices as soon as possible for the clientââ¬â¢s benefit. In order to advance current practices into EBP supported practices, the establishment needs transformational leadership, collaboration, and strategic guidance (Hauck, Winsett, Kuric, 2013). When establishing new procedures based on EBP, it is essential to consider improvement of care experienced, enhance the health of populations, and reduce costs of care per individual Read MoreBackground Of The National Longitudinal Transition Study Essay1778 Words à |à 8 Pageswho are less prepared for college and career. Analyses of the data from transcripts and other district data on NLTS youth will inform us on what the special education entails for this generation of high school students. This data will also be the first nationally representative data depicting high school and transition experiences for students qualified for accommodations under Section 504 of the Vocational Rehabilitation Act of 1973. Comparisons made with data from NLTS and NLTS2 will also updateRead MoreWhy Are Patient Outcomes Low When Patients?1921 Words à |à 8 Pagesleads to a whole new list of things that must be assessed. Falls are something that happen much too often in the hospital setting due to lack of nurse staffing. ââ¬Å"Three of four studies on the proportion of RNs reported significant effects. The three cohort studies showed that higher proportions of RNs were significantly related to lower numbers of patient falls. More specifically, small effect sizes were reported for medical/surgical and critical car e units (Patrician et al., 2011) and for step downRead More Civic Engagement through Community Problem Solving Essay6905 Words à |à 28 PagesInstead, they are linked to generational effects, a change in society itself instead of individuals as their lives progress. This is evident when participation rates of young people are compared over time, as shown above. Compared with the same age cohort in years past, levels of voting have declined significantly. Voting may be the most visible, but it is certainly not the only way to participate in a democracy. In his book Bowling Alone, Robert Putnam includes the following in his definitionRead MoreResearch Fundations5609 Words à |à 23 Pageseffectiveness of training given to the new associates. CommunnaTell Wireless will conduct surveys of recent customers to the call center to determine the root cause of the recent complaints. Propose Research CommunnaTell Wireless Company will conduct personal phone interviews with 300 customers recently called into the center. Conducting the survey in the next 30 days will enable ââ¬Å"quick winsâ⬠with the data surveyed. Survey focuses questions on timeliness of service, friendliness of service representativeRead MoreEvaluation Of Routine Immunization Performance Essay8403 Words à |à 34 PagesSindh, Khyber-Pakhtunkhwa and Baluchistan besides the federally administered territories and the capital Islamabad. The population of Pakistan is estimated at 182 million in 2013 with an annual population growth rate of 2%. Pakistan is having a birth cohort of 6.2 million infants, with 5.82 million surviving infants [1]. Routine Immunization and Polio Eradication: In 2013 the UN Inter-agency Group for child mortality estimation, showed that about 50% of under-five deaths occur in only five countries:
Wednesday, December 18, 2019
Ethical Issues Of The Managerial Accounting Profession
Introduction In today s high-rise development markets, there are millions of transactions that have been done every second by millions of employees. These transactions are domestically and globally executed, and due to its complexity in today s business world it may generates sort of excesses that can negatively affect the business environment as well as the social life. Therefore, it becomes necessary to stress on the ethics and morals that should be prevalent in the business community. The term ethics in the business environment expresses the expected attitude of the individuals in organizations that carry out certain activities and services. Clearly, todayââ¬â¢s business environment has obvious ethical issues that not only affect firmsâ⬠¦show more contentâ⬠¦Managerial Accounting nature The management accounting is an effective and important provider for business information that helps the management to make decisions relating to business activities and investment decisions. Managerial accountants play a crucial role in advising managers about the financial implications of projects; and run some analysis such as cost benefit analysis, sensitivity analysis. At the same time managerial accounting streamline the management by explain the financial consequences of business decisions. It plays a crucial role in formulate business strategy to assist the higher management to build the strategic goals and strategic plan. Managerial accountants always monitor spending and financial control as well as conduct internal business audits. The management accounting is a control tool used for various internal business processes of the enterprise, consequently becoming essential in any managerââ¬â¢s daily processes and operations. Business Ethics Ethics was defined by Nelson and Trevino (2005) as ââ¬Ëââ¬Ëa set of moral principles or valuesââ¬â¢Ã¢â¬â¢ a definition that depicts ethics as highly personal and relative. Every individual has his own moral principles and neither of them should try to impose their ethics on the other. But proposed definition of ethics ââ¬Ëââ¬Ëthe principles, norms, and standards of conduct governing an individual or groupââ¬â¢Ã¢â¬â¢ focuses on conduct. Employers are expected to establish guidelines for work-related conduct, including what
Tuesday, December 10, 2019
Cultural Relativism Theory and Virtue ethics free essay sample
Essay 1 Write an essay based on any of the topics covered in class during the period of week 1 and week 6. Paper must be between 2 and 3 pages (excluding cover page, annexes, and reference page). Cultural Relativism Theory Cultural Relativism Theory is morality that differs in every society, and is a convenient term for socially approved habits. It is also the oldest philosophical theory that speaks about the nature of morality. Cultural relativism theory claims that different cultures have different moral codes and nothing is there or an objective standard that can judge a societyââ¬â¢s moral code if itââ¬â¢s better than the other society. Therefore there is no culture or a society that has a better moral code because there is nothing that can judge it, so each culture and societyââ¬â¢s moral codes are the same. In this topic of Cultural Relativism Theory there is no universal truth. The moral code in a society maybe good or bad, nobody knows, so nobody can judge whose better. The moral code of a society determines what is right within that society and it is mere arrogance for us to try judge the conduct of other people In Cultural Relativism Theory each culture has different moral codes and their moral code could be good or bad in that society. For example the Callatians and the Greeks, they have different tradition at which the Callatians donââ¬â¢t agree with the Greeks tradition and the Greeks donââ¬â¢t agree with the Callatians as well. For the Callatians they eat the bodies of their dead fathers whereas the Greeks donââ¬â¢t practice that. Instead they practiced cremation at which they believe that is the proper way of disposing a dead body. Also another example with the Eskimoââ¬â¢s and Belizeans. The Eskimos men have more than one wife at which they share it with a guest as a sign of hospitality in which also other men can have sexual access to a woman at which a woman can leave her husband and find a new partner. They also have less regard for human life and infanticide the female babies and also the old people are left to die at which nobody cares. However for us today as Belizeans everything is different from the Eskimos and nobody would want toà practice what the Eskimos do. For cultural difference argument we might think that it seems reasonable but we found out that it is not. For cultural relativism theory there is a certain form of argument at which its strategy used by cultural relativists is to argue from the facts about the differences between cultural outlooks to a conclusion about the status of morality. As we can go back and look at the example about the Callatians at which the Greeks believed that it was wrong to eat the dead, whereas the Callatians believed it was right. Therefore eating the dead is neither objectively right nor objectively wrong. It is just an opinion that varies from culture to culture. Also there is a general argument in which different cultures have different moral codes and that there is no objective truth in morality and that these are just matter of opinions that varies from culture to culture. The trouble for cultural relativism theory is that the conclusion does not follow the idea that forms the basis of the argument and that is if the idea which forms the argument might be true, the conclusion might still be false. And we donââ¬â¢t know all the truths in the world and as a matter of fact we wouldnââ¬â¢t know the truth about morality. However, we might say that one culture may be wrong while the other is right or both might be wrong, or both might be correct, nobody knows. Furthermore, if you take cultural relativism seriously there are consequences. First, we could no longer say that the customs of other societies are morally inferior to our own. This means that we would stop condemning other societies only because they are different from us. Also we would be stopped criticizing other societies or culture. Second, is that we could decide whether actions are right or wrong just by consulting the standards of our society and this might be simple because anyone can just ask whether their action is in accordance with the code of oneââ¬â¢s society. Also this forbids us to criticize our own culture. ` Moreover, some cultures have common values because their culture does not differ nearly as much as it appears and the difference is in our belief system not in our values. In addition, all cultures value for their children, for honesty and no killing. Also there are some moral rules that all societies will have inà common, because those rules are necessary for a society to exist. In conclusion we learned from cultural relativism that it rest on an invalid argument, universal truth does not exists, there is no better culture, different cultures might have different moral codes but not one is right or wrong because nobody can judge. Essay 2 Write an essay based on any of the topics covered in class during the period of week 7 and week 12. Paper must be between 2 and 3 pages (excluding cover page, annexes, and reference page). The Ethics of Virtue There were three philosophers that approached ethics by asking what is a good man, what makes someone to become virtuous and what traits of character make one a good person? These philosophers are Aristotle, Socrates and Plato. However, the modern philosophers approached ethics in a different way by asking what is the right thing to do? Therefore, this leads them to a different direction and went on to develop their own theories about righteousness, obligation and duty, not of virtue. They talked about ethical egoism in which each person ought to do whatever will best promote his or her own interests. Also utilitarianism that we ought to do whatever will promote the greatest happiness for the greatest number. In addition they spoke about Kantââ¬â¢s theory that our duty is to follow rules that we would be willing to have followed by all people in all circumstances. Lastly they spoke about social contract theory that the right thing to do is to follow the rules that rational, self-interested people can agree to establish for their mutual benefit. These theories were familiar by the modern philosophers from the seventeenth century. However many philosophers disagree with modern philosophers that they are completely lacking in a particular good quality or value and in order to save the subject they returned to Aristotleââ¬â¢s way of thinking. A theory of virtue should have several components. First, there should be an explanation of what a virtue is. Second, a list should be given that specifies which character traits are considered to be virtues. Third, is that they should explain what these virtues consist. Fourth, is that they should explain why these qualities ofà character traits are good ones for a person to have. Lastly, is that the theory should tell us if these are virtues are the same for all people or do they differ from person to person. Aristotle suggested an answer for the definition of what a virtue is and he says that it is a trait of character manifested in habitual action. Pincoff says that virtues are those traits of character that lead us to seek people and vices are those traits of character that leads us to avoid people. However we may define virtue as a trait of character, manifested in habitual action, that it is good for a person to have. Examples of virtue character traits that a person should have are as follows: Courage, honesty, generosity, loyalty etc. Each of the virtue character traits has its own features and its own problems in which Aristotle argued that virtues are means poised between extremes which are the vices that is one of excess and the other of deficiency. For example they looked at Courage in which it is a mean between the extremes of cowardice and foolhardiness in the face of danger. Courage is sometimes said to be a military virtue because it help the soldiers accomplish their task. Also Generosity as an example is the willingness to spend oneââ¬â¢s resources to help others. Also Honesty as an example is needed because without it, relations between people would go wrong in countless ways. However it is sometimes wrong to tell truth and an honest person can sometimes lie when there are compelling reasons. Aristotle says that virtues are important because they are qualities needed for successful human living and virtuous person will fare better in life. Also virtues are not the same for all people because each person possesses different traits of character and these virtues depend on social roles and each society has different social roles and so traits of character to fulfill these roles will differ so this means that virtues will differ in different societies. Aristotle and Rachel say that some virtues are necessary by all people in all times. Virtue ethics have two advantages: moral motivation and doubts about theà ââ¬Å"idealâ⬠of impartiality. Moral motivation is an advantage of virtue ethics because virtue ethics is an appealing and it provides a natural and attractive account of moral motivation. A virtue ethics doubt about the ideal of impartiality is another advantage and impartiality has been the theme for the modern moral philosophy in which the ideas of all persons are morally equal. The total theory of virtue would include an account of all considerations that figure in practical decision making, together with their underlying rationale. References Cite all sources used in your report. Remember it is plagiarism to use otherââ¬â¢s work and give them credit.
Tuesday, December 3, 2019
The Second Brandenburg Concerto free essay sample
Composing for the inauguration of a harpsichord he had acquired in Berlin, Bach prepared the Brandenburg Concertos in 1720. [1] Drawing from a wide range of musical influences and styles, Bach pays tribute to and in many ways surpasses the works of his contemporaries, ultimately and undeniably furthering the concerto form. The concerto is a genre of instrumental works of three movements performed by one or more solo instruments accompanied by an orchestra. In a musical context, the term ââ¬Å"concertoâ⬠(from the Latin concertare; ââ¬Å"to contend, to dispute, to debateâ⬠and ââ¬Å"to work togetherâ⬠)[2] was initially used inconsistently to refer to a variety of forms and functions, including vocal ensembles, mixed vocal/instrumental groups, and the act of accompanying. As the form developed, the term gained its lasting definition. The instrumental concerto emerged in the late 17th century. In Italy, two distinct styles arose, reflecting different approaches to musical structure and scoring. The Roman concerto featured a small ensemble of instrumentalists (called the concertino) playing in unison, contrapuntally or in alternation, accompanied by the larger concerto grosso or ripieno. We will write a custom essay sample on The Second Brandenburg Concerto or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page Northern Italian concertos were written for much smaller orchestras, with sometimes as little as five instrumental voices, and emphasized the role of a single soloist (usually a violinist) backed by relatively light accompaniment. The genre flourished in the early 18th century with the many innovations of Antonio Vivaldi. His earliest concertos made use of the ritornello form, in which tonalities are established and reestablished throughout a movement by orchestral refrains. The form was the first to regularly present a recurring musical motif in several contrasting tonalities. Vivaldi also incorporated techniques largely unused outside of opera, such as the orchestral unison and onomatopoeic effects. His compositions contain slow, lyrical passages that allow for and encourage improvisation and embellishment. Suited to a variety of settings and functions, from secular to recreational, Vivaldiââ¬â¢s concertos were highly accessible and diverse. 2 Bach was among the many influenced by Vivaldiââ¬â¢s style. An unofficial student of the Italian composer, Bach devotedly transcribed Vivaldiââ¬â¢s concertos by hand, often rescoring them. [3] Bachââ¬â¢s attention to detail and expertise in musical structure gave his own works a refreshing individuality. His compositions included new, virtuosic instrumental techniques and applications, particularly for the harpsichord. Bachââ¬â¢s Brandenburg Concertos brim with dense compositional textures, complex instrumentations (combining strings, brass, woodwind and keyboard instruments) and unusual mixtures of conventions usually exclusive to their own specific form of concerto. Featuring an astonishing amount of instruments, the Brandenburg Concertos make for a tonally diverse listening experience. Taking every sound in his palette into consideration, Bach orchestrates passages both instrumentally homogenous (specifically, string ensemble) and unusually varied (combining recorder and trumpet). The instrumental parts are as unique and unusual as they are difficult: violas da gamba back atypically soloing violas, a recorder fights to sing above a trumpet, and a violin piccolo plays a fast melody customarily reserved for other members of its instrumental family. [4] Following the conventions of the concerto grosso form, the second Brandenburg concerto features two ensembles: the concertino, a small group of soloists, and the ripieno, the larger orchestra accompanying them. The concerto is scored for the violin, viola, flute, trumpet, oboe and continuo. The elaborate interplay between the soloists and the ripieno is most apparent in the manipulation of recurring musical themes. [pic] mm. 1-7 The first measures establish the ritornello, played in unison by both the soloist and larger orchestra, with contrapuntal voices in the accompaniment. The theme is grandiose; the repeating 16th-16th-8th note motif excitedly calls for the listenerââ¬â¢s immediate attention, heralding a rising and falling stream of 16th notes that seems to relay some thrilling news. [pic] mm. 8-9, violin A second theme, a brief solo, follows the ritornello, marking the entrance of a solo instrument in its every occurrence. The solo instrument is supported only by the continuo and at most one other instrument in the concertino; the orchestra is at rest. The melody floats sweetly, lingering on a trill as a temporary reprieve from the uproar of the orchestra. The second theme is played by the violin in its first instance and in subsequent occurrences by the oboe, flute and trumpet, respectively. The two themes (the first truncated) alternate in rapid two-measure exchanges. Changes in pitch and direction in the solo passages bring about modulation in the restated ritornellos that follow, shifting the mood of the piece and establishing the soloists and the driving force behind its movement. As the solo guides, the opening of each ritornello serves as a point of arrival. [5] This pattern is characteristic of Vivaldiââ¬â¢s style: his concertos typically began with a full statement of the orchestral ritornello, which would re-emerge between alternating solo passages in a notably altered form. 3 [pic] mm. 9-11 (top), 13-15 (bottom) The first example of this occurs in the transition from the solo passage to the restatement of the ritornello in measures 14 to 15. Reflecting a single change in the solo (a high C replaces the F in the last note), the transposed ritornello moves the piece into the key of C, the dominant to the tonic key of F. To the listener, the key change instills a sense of triumphant accumulation and a desire for eventual resolution. [pic] mm. 31-37, trumpet (top) and oboe (bottom) The next modulation takes the piece to the key of D minor, the relative minor to the tonic key. Against a suddenly (and unexpectedly) downcast orchestra, the high-pitched trumpet introduces a new theme: a simple, prolonged four note sequence that contrasts with the complex and rapid movement of the accompaniment. The oboe answers this sequence between the trumpetââ¬â¢s restatements, gradually guiding it to a lower pitch range. As the trumpetââ¬â¢s sequence tapers off, the full orchestra returns to another restatement of the ritornello.
Wednesday, November 27, 2019
Causas y consecuencias de negación de ingreso a USA
Causas y consecuencias de negacià ³n de ingreso a USA Cada aà ±o millones de personas que llegan a un aeropuerto de EEUU u otro punto legal de entrada como fronteras terrestres o puertos. Ms de 200 mil se encuentran con el problema de que son devueltos al lugar del que vienen. Este es un problema que afecta tanto a los extranjeros que viajan con visa no inmigrante como a los que desean ingresar a Estados Unidos sin visado por pertenecer a un paà s del Programa de Exencià ³n de Visas o, incluso, con una tarjeta de residencia permanente.à Y es que los à ºnicos a los que no se le puede impedir el ingreso en los Estados Unidos es a los ciudadanos estadounidenses, quienes tienen que presentar un documento vlido que acredite esa condicià ³n y permita el paso migratorio. En este artà culo se informa sobre cà ³mo es el control migratorio donde pueden surgir problemas, las razones ms comunes por las que se niega el ingreso a los Estados Unidos, cules son las consecuencias y una referencia a estadà sticas y a sistemas que permiten acelerar el paso migratorio. El control migratorio en los puntos de ingreso a los Estados Unidos Estados Unidos tiene un total de 329 Puntos de Entrada, lo que se conoce por sus siglas en inglà ©s como POE y que son fronteras terrestres, puertos y aeropuertos con controles migratorios internacionales. El control consta de dos partes, primero, uno migratorio y, despuà ©s, otro pero de aduanas. Para el migratorio se forman dos filas, una exclusivamente para ciudadanos a los que pueden acompaà ±ar sus familiares inmediatos extranjeros, y otra para todos los dems. En algunos casos es posible formar parte de programas que aceleran este paso, de lo cual se explica ms al final del artà culo. Como regla general, el control migratorio se demora entre 10 y 30 segundos. Es posible que se envà e a una persona a lo que se conoce como doble inspeccià ³n. No tiene que ser algo malo. Por ejemplo, todas las personas con advance parole pasan por esa situacià ³n.à Sà ³lo despuà ©s de haber obtenido el OK migratorio se pasa a la inspeccià ³n aduanera. Y ya a partir de ahà se ingresa a los Estados Unidos.à à ¿Por quà © son devueltos por inmigracià ³n desde los aeropuertos u otros puestos fronterizos legales? Las razones son varias destacando: En el caso especà fico de los residentes permanentes, puede que se llegue a la conclusià ³n de que no est residiendo en los Estados Unidos y ahà pueden surgir muchos problemas. En todos los dems casos, puede suceder que laà visa se ha cancelado pero su titular no lo sabe. En los casos del Programa de Exencià ³n de visas si la persona ha estado previamente en USA y se ha excedido de los 90 dà as permitidos, ha perdido este privilegio y si viaja sin visa no se le dejar ingresar. Pero el caso ms comà ºn es que el oficial de inmigracià ³n sospecha que la persona tiene la intencià ³n deà quedarse en Estados Unidos o a buscar trabajo ilegalmente o lo ha hecho en el pasado. No importa que se tenga una visa en regla, ese oficial es el que tiene la à ºltima palabra. Recordar que de todas las visas temporales, incluida la de turista, solo las H-1B y las L son de doble intencià ³n, es decir, sà ³lo con ellas se puede tener la intencià ³n de emigrar. El oficial de inmigracià ³n ve en la computadora del sistema TECS que el extranjero es inadmisible para los Estados Unidos o inelegible para la visa que porta por cualquier razà ³n. Un ejemplo de esto à ºltimo es un turista que viene con la intencià ³n de casarse y quedarse en el paà s. El oficial de inmigracià ³n tambià ©n puede ver si la persona tiene pendiente una orden de arresto. Si es asà , eso es lo que va a pasar. Segà ºn los à ºltimos datos conocidos en un sà ³lo aà ±o fiscal se detuvieron a 24,000 personas cuando intentaban ingresar a Estados Unidos. En casos excepcionales, el oficial de inmigracià ³n puede permitir ingresar a USA a un extranjero sin los documentos necesarios. Ello es asà porque le da lo que se conoce como un parole. Por ejemplo, a las personas que de un modo creà ble solicitan asilo en una frontera, puerto o aeropuerto. Quà © puede pasar en un control migratorio En la inmensa mayorà a de los casos, no pasa absolutamente nada y se ingresa sin incidencias. Pero para las personas que tienen problemas hay que destacar dos cosas: Primero, que en el control migratorio no se tiene derecho a abogado, excepto si se ha seà ±alado que una persona es objeto de una investigacià ³n criminal. Adems, las autoridades tienen derecho a registrar sin autorizacià ³n judicial previa el equipaje de cualquier persona y tambià ©n sus aparatos electrà ³nicos, como computadoras, telà ©fonos, tabletas, cmaras digitales, etc. Y segundo, cuando a una persona extranjera no se la deja ingresar hay que saber exactamente quà © pasà ³. Porque pueden darse situaciones tan diversas como: se permite una retira de la peticià ³n de ingresar y se pone en la visa I-275ocurre una expulsià ³n inmediataun residente firma su renuncia a la green card Si ha surgido un problema, lo mejor a partir de ahà es consultar con un abogado migratorio para ver quà © pasos a seguir, segà ºn sea el caso de cada uno. à ¿Quà © tan problemtico es el control migratorio en Estados Unidos? Cada aà ±o, ms de 360 millones de viajeros, entre estadounidenses y extranjeros, cruzan un puerto de entrada al paà s.à De ellos, un poco ms de cien millones ingresan por aeropuertos, siendo el modo ms comà ºn de ingreso el cruce de una frontera terrestre. Aproximadamente, unos 320 mil viajeros no pueden ingresar, lo cual es un nà ºmero grande pero pequeà ±o comparado con el total.à à ¿Es posible evitar las largas filas? En algunos puertos de entrada o en determinadas fechas las demoras para pasar el control migratorio pueden ser muy largas, particularmente en los puentes internacionales.à Existen diferentes tipos de programas que permiten ingresos ms rpidos que aplican a unos viajeros o a otros segà ºn nacionalidades y lugar de ingreso, pero merece la pena familiarizarse con esas posibilidades de ingresos acelerados, como Global Entry, Nexus o Sentri. Consejo Evita problemas en el control de aduanas conociendo quà © se puede ingresar y quà © est sujeto a ser declarado.
Saturday, November 23, 2019
The gastrointestinal tract The WritePass Journal
The gastrointestinal tract The gastrointestinal tract ABSTRACTINTRODUCTION1.1 The gastrointestinal tract1.2à à 5-hydroxytryptamine1.3 à 5-HT4 receptor subtype1.4à à 5-HT4 receptor agonists and antagonists1.3à à Aims of the studyMETHODà 2.1 Krebs solution2.2 Preparation of the tissue2.3 Experimental preparation2.4à à Administration of drugs2.5à à Statistical analysisRESULTSà 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 à cumulative addition of 5-HT on the peristaltic reflex in the mouse proximal colonà 3.3 à The effects of tegaserod on the peristaltic reflex in the mouseà proximal colon3.4à à The effects of the 5-HT4 receptor antagonist, GR113808, on theà à cumulative addition Tegaserod on the peristaltic reflex in the mouseà proximal colon DISCUSSIONà REFERENCESAPPENDIXà à à à à à à à 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 andà à à à à à à à à à 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 meanà ±SEM from number of animals indicated by n. A regular peristalsis was established before the addition of 5-HT (average rate of peristalsis was 77à ±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.à 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).à 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).à 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.à 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 todayââ¬â¢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, Crohnââ¬â¢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.à 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. 1.2à à 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).à 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-HT2à 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 ââ âAC (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 ââ âAC (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 ââ âAC (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 ââ âAC (Gi/o) Cortex, caudate putamen, claustrum, hippocampus, amygdala Unknown BRL 54443 (1129) 5-HT1F ââ âAC (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 ââ â 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 ââ â 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 ââ â PLC Choroid plexus, cortex, limbic system, basal ganglia Hypolocomotion, hypophagia, penile erection, hyperthermia, anxiety, ââ â 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 ââ â 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 ââ â 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 ââ â 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 ââ â 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:à A table summarising the properties of 5-HT receptors and subtypes (tocris.com/pharmacologicalBrowser.php?ItemId=5101) à 1.3 à 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 1.4à à 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.à In the guinea pig ileum, tegaserod was found to stimulate peristalsis by increasing the number of circular muscle contractions (Ji et al, 2004).à 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-HT4à 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,à GR113808à behaved as an antagonist of 5-hydroxytryptamine -induced contraction, with a high affinity for the 5-HT4 receptor (Gale et al, 1994). 1.3à à 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. METHODà 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.à 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.à 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. 2.4à à 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 (0.01à µMââ¬â 10à 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 didnââ¬â¢t recover. Therefore drugs were administered continuously wit hout washout. This process was repeated with the agonist, 5-HT, with concentrations ranging from 0.1à µM-100à µM. To examine the effects of GR113808 and SB204070 (antagonists)à on 5-HT and tegaserod responses, eitherà 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 2.5à à Statistical analysis All results are expressed as meanà ±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 Fisherââ¬â¢s PLSD when more than two groups were compared. à 2.6à à 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. à RESULTSà 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 77à ±7, n=7).à 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 à ± 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 à ± 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 à cumulative addition of 5-HT on the peristaltic reflex in the mouse proximal colonà 3.3 à The effects of tegaserod on the peristaltic reflex in the mouseà proximal colon 3.4à à The effects of the 5-HT4 receptor antagonist, GR113808, on theà à cumulative addition Tegaserod on the peristaltic reflex in the mouseà proximal colon à à à à à à DISCUSSIONà 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 untilà à 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 ),à which was not observed in the current study.à 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). Further studies are required to examine the receptor involved in the inhibitory effect of 5-HT in the mouse colon and to examine whether 5-HT7 receptors are involved.à It is interesting to note that the inhibitory effect of tegaserod could involve a completely different mechanism as peristalsis could not beà recovered by washing in any tissue, in contrast with 5-HT. In conclusion, the current study has shown that 5-HT can both facilitate and inhibit peristalsis. However, the 5-HT receptors mediating these effects are likely to be different from the ones involved in the modulation of peristalsis in the guinea-pig ileum. Further studies are required to establish the receptors involved. REFERENCES ARBAB SIKANDERA, S. V. R., A,à AND KAUSHAL KISHOR PRASADA (2009). Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clinica Chimica Acta, 403, 47-55 BARNES, N. M. SHARP, T. (1999). A review of central 5-HT receptors and their function. 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APPENDIX Table 1: 5-HT alone à S.No à -log C (M) à 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 ââ¬â 10-4 M, to mouse proximal colon. The values are expressed as meanà ±SEM. Table 2: 5-HT in the presence of SB204070 à S.No à -log C (M) à 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 ââ¬â 10-2 in the presence of the 5-HT4 antagonist, SB204070 10-7M, to the mouse proximal colon. The values are expressed as meanà ±SEM. Table 3: Tegaserod alone à à S.No à -logC (M) à 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 ââ¬â 10-5 M, to mouse proximal colon. The values are expressed as meanà ±SEM. Table 4: Tegaserod in the presence of SB204070 à S.No à -logC (M) à 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 à à à à à 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 ââ¬â 10-5 in the presence of the 5-HT4 antagonist, SB204070 10-7M, to the mouse proximal colon. The values are expressed as meanà ±SEM. Table 5: Tegaserod in the presence of GR113808 à à S.No à -logC (M) à 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 à Table 5 shows the rate of peristalsis after adding tegaserod 10-8 ââ¬â 10-5 in the presence of the 5-HT4 antagonist, GR11380810-6M, to the mouse proximal colon. The values are expressed as meanà ±SEM.
Thursday, November 21, 2019
Regulatory, Cultural and Ethical Dimensions to the Introduction of Essay
Regulatory, Cultural and Ethical Dimensions to the Introduction of International Accounting Standards - Essay Example According to the research findings companies are often placed under regulations with respect to international accounting standards to enable the accounting professionals to provide an honest and accurate financial image to companyââ¬â¢s stakeholders. Through compliance with international accounting standards regulations, companies are bound to benefit from their investorsââ¬â¢ confidence with regards to truthful and accurate reporting of the financial situation and performance of the company. More so, compliance to such standards would render financial information more understandable, reliable, comparable, and relevant among the users of financial information in assessing confidence in company management and making economic decisions. Regulatory dimensions of international accounting standards are subject to a two tier endorsement mechanism standards a technical and regulatory level. The regulatory level endorsement mechanism is based on proposals of local accounting commission s that decide on the levels and whether the International Accounting Standards are to be adopted. Local regulatory bodies aim to ensure that full accountability and transparency is achieved in financial reporting through both local regulations and compliance to International Accounting Standards. Countries and regions such as the European Union have enforced compliance regulations among its publicly listed companies to apply International Accounting Standards in preparation of their financial statements. ... The regulatory level endorsement mechanism is based on proposals of local accounting commissions that decide on the levels and whether the International Accounting Standards are to be adopted. Local regulatory bodies aim to ensure that full accountability and transparency is achieved in financial reporting through both local regulations and compliance to International Accounting Standards. Countries and regions such as the European Union have enforced compliance regulations among its publicly listed companies to apply International Accounting Standards in preparation of their financial statements. This is in a bid to improve transparency and foster efficiency in corporate functions in the interest of the public and more particularly, investors (Palea, 2006, p.7). On the other hand, technical level endorsement mechanism uses Accounting Technical Committees and advisory bodies made up of accounting professionals and experts from both public and private sectors. These professional accou ntants committees and advisory bodies seek to provide expertise and support that is needed to assess International Accounting Standards and to advise companies on whether or not it is suitable for them to adopt the standards according to local and country preferences and interests. However, there exist Generally Accepted Accounting Principles that encompass a wide spectrum of local and geographically dispersed accounting interests and preferences all over the world. The GAAP is a common set of accounting standards, principles and procedures that are globally applicable by companies in compiling their financial statements. More so, GAAP include a combination of commonly accepted practices and local board authoritative policies and standards of reporting
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