Wednesday, October 9, 2019

Feature pitch Assignment Example | Topics and Well Written Essays - 500 words

Feature pitch - Assignment Example Only one third of Australians take part in physical fitness activities and sports. Keeping fit and recreation are the main motivations for the Australians that exercise. This has serious implications not only health-wise but also on the level of professional sports in the country. This story; therefore, seeks to critically analyze this tendency with a view to proposing the way forward. There are other factors that motivate Australians to take part in sports and physical fitness programs. They include peer pressure and checking weight. Some people exercise because their contemporaries are doing it. This is especially the case for young adults. As for older citizens, their major concern is weight. They; therefore, exercise in order to reduce weight. However, the frequency at which citizens are exercising is a major point of concern. 34% of the research sample did not participate in any sports or physical fitness activity while another 6% took part only occasionally. Only 29% of the people interviewed exercised more than twice a week. Is Australian a physically unfit nation? Do these findings have any implications? What is the government’s role in ensuring that Australia is physically fit? What measures can be put into place to remedy this situation? Of course, every individual is responsible for their own health. However, they need an enabling environment to help them uphold healthy practices. In essence, the story will recommend the way forward, basing on available resources. 1. I have planned to hold an interview with Peter McKay, the Chairperson of the Standing Committee on Recreation and Sports Research Group, at Sydney Gardens on 20 May 2014 at 4.00pm. He heads the research group that investigated the factors that motivated or de-motivated Australians in relation to physical fitness and sports. 2. Will hold another interview with Marisol Freanken, the Administration Coordinator, at Kiwi Square on 20 May 2014. Mr. Freanken will shed

Tuesday, October 8, 2019

Application of entry essay Example | Topics and Well Written Essays - 500 words

Application of entry - Essay Example Managing financial flows I was also thrilled when working with people and satisfying their needs. That’s why I was involved into recruitment and orientation as well as training and human resource policy. Later on I followed the path of counseling recruits and developing training programs. This work was bringing me a lot of pleasure as it involved research and development of new approaches which contributed to the enhancement of the staff skills as well as mine. My recruitment and counseling experience made me understand people better. Managing people and bringing changes into their perceptions and beliefs requires robust leadership skills. Particularly these are important when you are going to bring in changes through different training initiatives. I successfully managed to implement professional development programs and to make them as effective as possible. The next fascinating aspect in business is the ability to manage financial flows more efficiently as it is all about well-being of people and their families. Working as a payroll specialist I was aware of the importance of my work for hundreds of people. Processing multi-state payrolls for over 800 employees I felt responsibility for the prosperity of every of them. Through my career these two aspects – financial and humanitarian – intertwined into one amazing journey into life of thousands of people. During my studies I am going to incorporate substantial skills acquired when working as a payroll specialist and a recruiter. My personal statement about education is that it is the way to accomplish oneself and bring in a change into the life of other people. During the years of work I became aware of the need to initiate these changes in myself. I have a strong intention to enlarge my knowledge about business and accomplish it with theory. My practical experience will be a good back up for generating new knowledge and developing new vision of management in all

Monday, October 7, 2019

Review Assignment Example | Topics and Well Written Essays - 250 words

Review - Assignment Example decisions in terms of using the environment in a way that it will be protected from degeneration and pollution which if they would occur would leave the ecosystem in a state that would not support future generations. It entails proper use of resources in order to ascertain that there is continued existence of natural resources, whereby people are required to use resources in a way that they ensure their actions have reduced or no negative impact on the environment. The three videos put emphasis on how people should make it their sole aim to protecting the environment to support humanity into the future. The videos explain that to be able to make the environment sustainable for human life into the future, it is the duty of everyone to ascertain that their actions are in line with the goal of environmental sustainability. I think that the videos are viable in that they explain why humans need to protect the environment through responsible practices so as to ensure that natural resources remain in existence and there is minimal pollution. Sustainability will ensure that humans have access to clean water, food and fresh air, which will be achieved if humans do not become a threat to their way of life by polluting the environment (Igloo

Saturday, October 5, 2019

Business law Assignment Example | Topics and Well Written Essays - 2750 words

Business law - Assignment Example The guests should be in fit and able to make payments as per Section 1(3) HPA 1956. As per the British Law the innkeeper will be in the liability for safeguarding the interest of the guests in reason for the award received from the guests. The innkeepers are also bound to supply accommodation to the guests along with their luggage. The hotels have the right to allocate the rooms to their guest. The hotel authority is responsible for the safety of the guests during their stay in the hotel. The hotel authorities are in charge of taking reasonable care for the safety of their guests during their stay in the hotel. As per the British law the innkeeper’s liability for the safety of their guests is strict. The issue of liability of the hotel authority arises only if there is negligence on the part of the innkeeper regarding the belongings of the customer. In case of non delegable duty greater standard of care is required by the person or authority in responsibility but only in respe ct of those things as stated by them and not those which has been prohibited or not stated by the innkeeper (Brotherton, 2000, pp.145). Again based on exemption clause, a contract between two parties might include some limitations or exemption as per requirement. A party might be exempted from some liabilities based on some clauses (Jones,2011, p.168). Based on the rules stated above, Freda could not blame the hotel authority for the misplacement of her belongings. The hotel authority clearly stated â€Å"The Gullies Hotel and its Management would not be held liable for the safety of any valuable left in the guest's room and the Hotel has safe deposit boxes at the reception.† This is an exemption clause which limits the liability of the innkeeper in this case. Freda’s charge would have relevant if she had kept her belongings under the safe deposit box whose responsibility was borne by the hotel authority. 2. Discuss the doctrine of precedent. Give specific case example s where the court has applied this legal principle. Doctrine of Precedent or Stare Decisis is a part of common law. It is a process by which courts use verdicts made in earlier cases to assist the verdict of the case presently in consideration. The precedent is arrived by combining the verdict given in the previous court cases under similar facts. There have been many cases which came into the court room but their decisions could not be given just because there were no fixed laws prescribed. Judges often delivered verdicts in the courts based on an impulse or sentiment. To overcome such shortcomings the doctrine of precedent was framed where the law stated on a case was followed over time as judges abided by the decisions of previous cases. The judges would meet regularly and evaluate the decisions they made earlier. They would choose the most suitable verdict and apply those if any similar condition came up. The Doctrine of Precedent is subject to certain general rules. As per the binding precedent rule, lower courts are bound to follow verdicts made in superior courts. As per persuasive precedent, superior courts have an option to use the help or refer cases of lower courts in decision making. Most courts are by law bound to follow their own decisions made earlier. The verdict given by the judge has two parts. Ratio decidendi states the principle or cause for deciding the case in a particular way. It forms

Friday, October 4, 2019

Distinguish the mnemonic functions of the hippocampus, striatum and Essay

Distinguish the mnemonic functions of the hippocampus, striatum and amygdale - Essay Example Hippocampus can be related to limbic system of the brain and it has a significant role in not only maintaining long term memory but also in spatial navigation. These roles of hippocampus make it a structure of critical importance for a brain. When we talk about hippocampus’s critical role in the brain, we should also mention its importance in the formation of factual and autobiographical memories in the brain of a human or a mammal. Hippocampus can also work as a gateway for the memory (Cohen & Eichenbaum, 1993). It is in a sense that all new memories pass through this gateway before getting into the permanent storage area of the brain. If we talk about the structure of hippocampus, we can call it a paired structure which is formed so that mirror image lies on both sides of the brain (Matthews, 2000). Damage to this critical structure of the brain can lead to a very detrimental disease which is anterograde amnesia. In anterograde amnesia, new memories can not be formed by the brain because it loses the ability of formation of any sort of new memories in the brain (Traub & Miles, 1991). In such case, older memories don’t get affected and they are kept safe in the brain. The affect is only on new memories. When a person gets damage to the hippocampus of the brain, he loses the ability to store new memories but all those memories which have a relation with his past, are kept safe in the brain. But it is not the case with skills and abilities of a person. Skills don’t get affected by the damage to hippocampus. Even new memories which are related to the skills and habits of a person can be formed without a proper functioning hippocampus in the brain (Buzsaki, 2006). There are various researches which are being made these days by the researchers in the medical field in order to determine those memories which don’t get affected due to improper functioning of hippocampus. These researches are

Thursday, October 3, 2019

Why I want to be a Nurse Essay Example for Free

Why I want to be a Nurse Essay I heard the familiar sound of the front door closing gently. My father was returning from work as a barber. Although he begins his day at 5:00 a.m. every morning, he usually returns at around 7:00 p.m. I never really questioned his schedule when I was a child, but as I entered high school I wondered how my dad could work so hard every day of the week and still enjoy what he does. The uncertainties of barbering are so great and so challenging. It never ceases to amaze me when my father wakes up every morning to start work, that he does so with gusto. The life of a barber can be laborious and stressful, yet my father continues to do his work with passionate enthusiasm. His dedication and pride mystified me throughout high school. Only after I entered college in my late 20s, did I start to understand how he could persevere and face the challenges of raising a family and running his business. I entered college like a small child wandering through a park. Never in my life had I been exposed to anything so grandiose and dominating. Born and raised in a rural town, I wasnt ready for the fast-paced life and crowds. I eventually grew into its lifestyle and learned to adapt to my new environment. I found my communication class, in which we discussed major issues in health care, especially interesting. The nurses dilemma particularly intrigued me: Doing everything to provide the best health care possible, but constrained by limited resources when the funds just are not available. These frustrating situations place a huge strain on nurses, and yet they persevere and continue to work long hours in hospitals, and clinics providing the best care they can. While thoroughly aware of the long hours a nurse must work and the challenges he or she faces, I am choosing medicine because of the unique satisfaction it provides the rewards of helping a sick human being. As I think about a nurses life, I also think of the many times I have watched my father sit silently at the dinner table, deep in thought, contemplating his options when his business was not bringing in enough income and the bills continue to arrive. I didnt hear him complain; I only heard him leave early in the morning and come home late in the evening to make sure that we had everything he did not as a child growing  up. I also saw determination and tenacity in my mother and father to never give up but to keep on trying to the achieve a higher goal. They both came from very large and poor families and were determined to not have me grow up without an education. I will harness that determination in my life and my quest to earn my degree in nursing. They showed me what it means to really enjoy a career. I can have that same enjoyment through nursing the same type of enjoyment my Parents had from tending to their jobs, and businesses. Becoming a nurse is a goal aspired to by many. As a barbers son, I have wakened early and returned home late from long days with my father. I have been able to experience uncertainties, challenges, and plain old hard work similar to that faced by nurses. But like the doctors in the hospitals and my parents in their work, I can find happiness and satisfaction in helping people through medicine. Despite all the hardship nurses face, I want to help people every day. Nursing is something worth stress and long hours. I finally understand my father. I now know how he can wake up every morning at 5:00 a.m. and work hard until 7:00 p.m. and now I will do the same for my family. I will heavily stress the importance of a college degree and a good work ethic. I feel that this is the reason more and more Hispanics are earning their college degrees; they dont want the hardships of their past generations to be placed on their children.

Screening And Bioassay Of Thyroid Hormones

Screening And Bioassay Of Thyroid Hormones The purpose this section is double: too described the methods for determination of the hormones, which became seperate by the thyroid gland and to descriptive investigation of the thyroid function in the experimental models. To information over hypothalamisch pituità ¤re thyroidsystem and, you see its investigation the sections on hormones of the preceding Pituitary (N.7) and hypothalamischen hormones (N.9). The thyroid gland separates two kinds of hormones: the thyroid hormones i.e. Lthyroxin (T) and Triiodothyronine (T34) the metabolic functions have and into neural development to be referred and calcitropic the hormone, Calcitonin. The system of functions for the metabolic regulation, which is helpful by the thyroid hormones, is to the complex system for regulation calcium and phosphate balance ful  ¬Ã‚  completely differently, lled is by (thyro) Calcitonin, ready hormones of the Parathyreoid glands and the Calciferolhormone (in former times the vitamin D) produced by the live r and the kidneys and activated in the skin. The biological main effects of T3and T4 are on growth and development (e.g., development of Tadpoles), it calorigenic effect (increase of the fundamental metabolic rate), the cardiovascular function (sensitivity of the heart increases to the Benzkatechinaminen) and metabolic functions (Lipid, coal hydrate and Kollagenmetabolismus). The primary back discussion effect is inhibition of the thyroid-suggesting isolation of the hormone (TSH). These effects can be used, in order thyroid hormone correspondences and stoffwechselprodukte to examine. The thyroid hormones adjust iodine lifting and application in the thyroid, and its activity can be restrained by Antithyroiddrogen. Historical biological drug tests are based on Morphogenese and neural development in the amphibians (Biedl 1916; Pit tri verse and Tata 1959; Copp et al. 1962; Turner and Premachandra 1962). Thyroid hormones cause premature metamorphosis into that amphibiously for Tadpole s. Since  ¬Ã‚  observation rst by Gudernatsch (1913a, 1913b) this phenomenon by the numerous workers with the purpose of the adjustment of this answer for the sample thyroidal of the substances (Bomskov 1937) was studied. Within a short period the treatment with thyroid hormones causes the transformation of the Tadpole into a small frog with growth of the members, the lungs and other terrestrial equipments, and suggests the synthesis of the enzymes Morphogenese and transformation mediating. The Axolotl (Ambystoma mexicanum or tigrinum) was used like a Testgegenstand, in order to study the metamorphosis, which is caused by thyroid hormones. This animal loses the Kiemen and forms the lungs and changes at the same time the form of its end piece (Huxley and Hogben 1922; Zavadovsky and Zavadovsky 1926; Haffner 1927). Another basic rule activity of T3and T4 is metabolic activation and increased energy expenditure. Kreitmair (1928) standardised thyroid preparations using the weight loss of the guinea pigs after 1 week of the festiveness ment as parameter. A guinea pig unit was at least reduced de  ¬Ã‚ , which is as the dose ned, those the body weight of the guinea pigs with an initial weight 250-300g within 7 days by 10%. Another function role by Calcitonin is helpful. Hypocalcemic the hormones Calcitonin by Copp one discovered (Copp et al. 1962; Copp 1964). Calcitonin develops from parafollicular the C-cells of the thyroid. Its function antagonist is Parathyreoid hormone. The biological drug testing of the Calcitoninvorbereitungen is accomplished, by determining its ability to lower the plasma calcium in the rat. Sample of serum (thyro) Calcitonin has one signi  ¬Ã‚  inclination diagnostic role for thyroid cancer ulcer. As with other hormones, research methods of the biological drug tests of the thyroid hormone activity up to direct measure of the thyroid hormones (Thyroxin and Triiodothyronine) and their Stoffwechselprodukte, up to investigations over enzy matic steps in the thyroid hormone synthesis and inactivating, up to identi  ¬Ã‚  the cation of the thyroid hormone receivers than members of the superfamily of the nuclear receivers and up to signaling are get ahead, that by operation difficulty of the thyroid hormones to their receivers are caused.. Thyroid Hormone Receptors Obligatory proteins of the Kerntriiodothyronine were puri  ¬Ã‚  OD and characterized by Torresanai and Anselmet (1978). Ichikawa and DeGroot (1987a, 1987b) described puri  ¬Ã‚  the cation and the marking Ratteleberder nuclear thyroid hormone receiver and thyroid hormone receivers in a human Hepatomazellform. Apriletti et al. (1988) reported spacious puri  ¬Ã‚  cation of the nuclear thyroid hormone receiver rat liver and sequence speci  ¬Ã‚  C of the operation difficulty of the receiver to DNA. Ichikawa et al. (1988) and Ichikawa and Hashizume (1991) published methods of aqueous two-phases (Dextran and PL glycol) study of the nuclear thyroid hormone receivers distributing. Glucocorticoids, other Steroidhormone, thyroid hormones and vitamin-derived hormones (inclusively retinoids) all have their effects by the regulation of the hormone-accomodating goal genes within the cell core. William and Franklyn (1994) repeated the physiology of the Steroidschilddrà ¼se hormone nucle ar receiver Superfamily. A receiver-connected protein of the nuclear hormone, which restrains transactivation by the thyroid hormone and retinoic the sour receivers, became of Burris et al. described (1995). Two different genes code two different thyroid hormone receivers, thyroid hormone receiver ÃŽ ± and thyroid hormone receiver ÃŽ ² and these two thyroid hormone receivers frequently on different levels in the different fabrics are CO-expressed. Chiellini et al. (1998)  ¬Ã‚  high af nity subtype selective Agonist sketched ligand for the thyroid hormone to one receiver ÃŽ ². The expression of thyroid hormone receiver ISO form in the rat growth disk cartilage in vivo became of Ballock et al. described (1999). Yuan et al. (1998) Coaktivator protein of the thyroid hormone (CASE) described a component of a receiver-connected complex, which affects direct the nuclear receivers on a ligand-dependent way. The sequence thyroid hormone answer of the element and the reinforcement retinoid of the x-receivers for thyroid hormone reactivity became of Wu et al. investigated. Thyroidectomy PURPOSE AND RATIONALE Experiments for pharmacological evaluation of thyroid hormones and analogs were performed in thyroidectomized rats. Bomskov (1937) described the method of thyroidectomy in various animal species, such as tadpoles, frogs, birds, goats, dogs, cats, rabbits, guinea pigs, rats and mice, based on the clinical experience with thyroid resection in humans. PROCEDURE The thyroid in rats consists of three lobes (left, median, and right). The rat is anesthetized, e. g., with pentobarbital, and placed on a surgical table. The fur of the neck is removed with electric clippers and the area disinfected. A median skin incision of 2.0 cm length is made. On both sides large salivary glands and maxillary lymph nodes are found. They are pushed aside, making visible the musculus hyoideus covering the trachea. This muscle is split in the midline. The isthmus of the thyroid connecting both lobes is located below the thyroid cartilage. The lobes and the isthmus are separated with blunt forceps from the trachea and the blood vessels ligated. Alternatively, the thyroid can be removed by electrocauterization. In most cases, the parathyroid glands are severed by the operation, and postoperative substitution with calcium lactate 1% in drinking water is advised. In Vivo Tests for Thyroid Hormones Oxygen Consumption PURPOSE AND RATIONALE Basal metabolic rate, oxygen consumption and CO2 production are increased by thyroid hormones. This has been used for diagnostic procedures in humans as well as for evaluation of thyroid hormones and their derivatives in animals (indirect calorimetry). The historical method based on survival time of mice placed individually into tightly closed glass jars (Smith et al. 1947; Basil et al. 1950; Gemmill 1953) was modi ¬Ã‚ ed, measuring time until occurrence of convulsions. The method was based on the increase in oxygen consumption associated with the markedly increased metabolic rate at high doses of thyroid hormones. PROCEDURE This is a description of the now obsolete assay: mice are placed individually into 200-ml wide-necked bottles. The bottom of the bottles is covered with  ¬Ã‚ lter paper to soak up the urine. The bottles are tilted to an angle of 60 ° and rotated  ¬Ã‚ ve times per minute in a special apparatus. The time until asphyctic seizures occur is noted. Immediately after observation of seizures, the mouse is released for recovery. Due to the de ¬Ã‚ ned muscle work, the time to seizures is shortened in controls to 20-30 min. EVALUATION Average time to seizures was calculated and dose- response curves were established. MODIFICATIONS OF THE METHOD Similar studies were reported by: Bomskov 1937; Lilienthal et al. 1949; MacLagan and Sheahan 1950; Reineke and Turner 1950; Anderson 1954; Heming 1964; Turner 1969 Several apparatuses have been designed to measure oxygen consumption in animals, e. g., by Holtkamp et al. (1955). Stock (1975) described an automatic, closed-circuit oxygen consumption apparatus for small animals. A Perspex animal chamber is surrounded by a water jacket except for one end, which has a removable cover plate. This cover, as well as allowing access to the chamber interior, also holds the connections for the oxygen delivery line and the pressure line. For experiments involving injections, infusions, and blood sampling, catheters are passed through, and sealed into rubber bungs which are then forced into holes in the cover plate. A rubber gasket forms an airtight seal between the cover and the chamber. Within the chamber, the animal is supported on a wire grid over a layer of self-indicating soda lime and silica gel. A major determinant of sensitivity in this system is the dead space of the chamber. Chambers with internal dimensions of 20 10 10 cm are suitable for animals such as mice and rats up to about 250 g body weight. Fixed volumes of oxygen are introduced into the chamber by an automatic syringe dispenser (Fisons Scienti ¬Ã‚ c) which draws pure oxygen from a spirometer through a drying tube  ¬Ã‚ lled with silica gel. When chamber pressure exceeds atmospheric by about 3 mmH2O, the microdifferential pressure switch (KDG Instruments) inactivates the dispenser. The dispenser is reactivated when the pressure differential drops below this threshold value. The volume of oxygen dispensed is adjusted to the smallest volume that, with a single action of the syringe, will return chamber pressure to above the threshold value. The particular dispenser used in this system has the advantages of being (1) gas tight and (2) when activated will complete its pump cycle even if the chamber pressure exceeds the threshold value in midcycle. A discrete  ¬Ã‚ xed volume of oxygen is delivered each time it is activated. To obtain the rate of oxygen consumption it is merely necessary to record the pump rate. Inhibition of Iodine Release PURPOSE AND RATIONALE The thyroid gland has a high avidity for iodine, uptake of which may be measured by isotope-labeled iodine ( 131I), in a dose-related and time-dependent manner. The release of131 I from the thyroid in rats is inhibited by treatment with thyroxine (Wolff 1951), and the degree of inhibition is related to the dose administered (Perry 1951). This phenomenon was used to compare activity of thyroid hormone derivatives with the standard thyroxine. For analytical and diagnostic purposes, direct quantitation of thyroid hormones is now achieved by methods such as radioimmunoassay and HPLC chromatography, and by measuring feedback inhibition of thyroid hormones directly via the decrease in serum TSH. PROCEDURE Male Sprague-Dawley rats weighing 180-240g are fed a commercial laboratory chow without or with addition of 0.03% propylthiouracil (reference compound for thyroid peroxidase inhibition). Food is withheld 8 h before the injection of 25  µC131I or 125 I intraperitoneally. Radioactivity over the thyroid region of the neck is determined 40 h later (if necessary under sedation). This reading is taken as time zero and all fur-ther counts made at 24-h intervals may be expressed as a percentage of time-zero counts after correction for physical decay of the 131I isotope. After the reading at time zero, the diet is changed to a feed containing 0.03% propylthiouracil, and several doses of the test preparation or the standard are injected subcutaneously at 24-h intervals up to a total of four doses. The daily loss of 131I is inversely proportional to the dose of thyroid hormone. EVALUATION Percentage of time-zero counts after 96 h of Iremaining in the thyroid after the last of four doses is plotted against logarithm of dose. From these dose-response curves, potency ratios are calculated. The method has been used by several authors: Reineke and Turner 1950; Anderson 1954; Turner and Premachandra 1962 CRITICAL ASSESSMENT OF THE METHOD The assay described here was used for quantitative estimates and has now been replaced by analytical determination of thyroid hormone contents. For human drug formulations, bioequivalence studies are required when generic formulations are assessed This approach of measuring the uptake and release of labeled iodine may be modi ¬Ã‚ ed for short-term uptake of 131I or 125 as a parameter of thyroid peroxidase inhibition by antithyroid drugs, and other drugs affecting thyroid function. Anti-Goitrogenic Activity PURPOSE AND RATIONALE Thyroid weight and size are controlled by the action of thyroid-stimulating hormone (TSH) on thyroid tissue. In rats, increased secretion of TSH induces thyroid enlargement and weight increase within a few days (addressed as goiter formation). In normal animals the secretion of TSH by the pituitary is regulated by feedback of thyroid hormones. The administration of goitrogenic compounds which block thyroid hormone synthesis and/or secretion reduces the concentrations of circulating thyroid hormones (T)and their pituitary effect (negative feedback inhibition of TSH secretion), releasing TSH from its feedback inhibition. The TSH rise induces hyperplasia of the thyroid follicles as indicated by the dose-related increase of thyroid weight. Hyperplasia is prevented by injection of thyroxine, triiodothyronine or thyroid hormone analogs. PROCEDURE Male Sprague-Dawley rats weighing 150-180 g are used in groups of eight to ten animals. During the treatment period, 0.1% propylthiouracil (PTU) is added to the food or to the drinking water, in order to achieve a stable baseline of thyroid weight. Over a period of 2 weeks, the rats are treated (preferably by gavage) with various doses of the test compound or the thyroxine standard (10-40  µg/kg). PTU controls are treated with the suspension medium or saline injections only. At autopsy on day 14, the thyroid glands are dissected out and weighed rapidly to avoid evaporation loss. Thyroids may also be lyophilized  ¬Ã‚ rst to weigh dry matter. The two- to three-fold increase of thyroid weight by PTU is reversed dose-dependently to normal values by thyroid active substances. EVALUATION Dose-response curves are plotted and potency ratios with con ¬Ã‚ dence limits may be calculated. MODIFICATIONS OF THE METHOD Similar studies were reported by: Reineke et al. 1945; Pitt-Rivers and Tata 1959; Turner and Premachandra 1962; Wiberg et al. 1964; Ortiz-Caro et al. 1983; Pisarev et al. 1994 The effect of PTU-induced baseline suppression is monitored and ascertained by measuring serum TSH, T4 and T.The dose-related inhibition of the TSH rise by thyroid substances is used as the parameter to assess goiter prevention. Tensile Strength of Connective Tissue in Rats, Modi ¬Ã‚ ed for Thyroid Hormones These studies are an example of evaluating the biological effect of high doses of thyroid hormones on tissues other than those involved in the increase of metabolic rate. Thyroid hormone secretion affects almost all tissues in the body, and high doses may exert unwanted effects on connective tissue. Antithyroid drugs general views Antithyroiddrogen obstruct synthesis, release and/or the auxiliary activity of the thyroid hormone and lower the basic conversion. They are used in the treatment of the thyroid disturbances (Hyperthyreose). The reconciliation of the isolation T4/T3 reduces thyroidal inhibition of the pituità ¤ren gland, zunehmenTSH isolation and causes then the goitrogene answer. This answer was used to determine over Antithyroiddrogen and for Siebungverfahren at most was used. It is however nonspeci  ¬Ã‚  C and can by some different mechanisms, including enzyme induction of glucuronyltransferases be caused. The goitrogene answer is from the considerable interest in the toxicology, because it can be produced by some means during the early drug evaluation, which the bio-synthesis and/or inactivating of the thyroid hormones change in an unexpected way. Inhibition of the iodine elevation in the rats PURPOSE AND BASIC PRINCIPLE Propylthiouracil (PTU) and a broad spectrum of the drugs can restrain thyroid hormone synthesis. Some these drugs are used, in order to treat thyrotoxicosis. As consequence of the Schilddrà ¼seperoxydasehemmung the iodine lifting is reduced through and contents in the thyroid. This phenomenon is mix dependent and can appear to increase thyroid weight in the rats (McGinty and Bywater 1945) at the untereren doses as those. The historical parameter of iodine contents was replaced, by measuring a lifting and the release of 131I. PROCEDURE 131I. Groups of the male Wistar rats age 26-28 days and weigh 40-45 g, set within metabolism frameworks. They are drawn in normal diet, and potassium iodide is added the drinking water. In modes  ¬Ã‚  a cation of the method (for toxicology studies), can be added the test means or the reference standard (some concentrations) of the diet over a length of time by 10 days, and the quantity of the means taken by each rat then computed expressed by the total food consumption in 10 days and in the milligram daily paper per kilogram body weight. After 10 days of the treatment, the rats are sacri  ¬Ã‚  ced and the thyroids dismembered freely from the adjacent fabric and from the cap. The thyroid is weighed and determined iodine contents. In the daily doses of between 0.1 and 10.0 mg/kg, Thiouracil reduces iodine contents of the thyroid in a mix-dependent way. Higher doses De  ¬Ã‚  nitely are necessary, in order to increase thyroid weight. EVALUATION responding to the dose curves of the test means and reference standard are plotted, and force conditions with fraud  ¬Ã‚  dence delimitations can be computed. CHANGES of the METHOD Walker and Levy (1989) used transplantable tablets of Propylthiouracil, in order to cause thyroid malfunction in the rats. Lift marked iodine in place of of iodine contents one measures. Release of marked iodine knows through protirelin (TRH) injection to determine over thyroid function or become lively as quantitative biological drug testing for the effect of the hypothalamischen hormone TRH. Antithyroidal of effects in the animal samples the Sauerstoffverbrauch in iodine-treated mice was used as biological drug testing, modes  ¬Ã‚  OD for Antithyroidtà ¤tigkeit. PURPOSE AND BASIC PRINCIPLE historical biological drug testing are based on Sauerstoffverbrauch, which is increased acutely potassium iodidetreated the mice, with the result of a decrease of the asphyxiation time (thyroid activation). This effect is the dose-dependent, which are fought through antithyroidal means, and which is to time to the cramps because of the reduced metabolic rate extended. The methods is based on increased Sauerstoffverbrauch after thyroid hormones (section. N.5.1.1) are applied. CHANGES of the METHOD thyroid weight was an early parameter for querying the Antithyroidtà ¤tigkeit. Rabbit treated with goitrogenen means or with Kohl (Chesney et al. 1928 exclusively drawn in; Navy et al. 1929) a tenfold increase of the thyroid weight to shown, histological announce as hyperplasia without kollodiale arrangement. These phenomena were waived by iodine treatment (Bomskov 1937). Kropfanordnung as side effect of non steroidal anti-  ¬Ã¢â‚¬Å¡ in ammatory the drugs became of Mueller et al. studied (1985). Calcitonin general views calcitropic the hormones (thyro) Calcitonin was discovered in the C-cells of the thyroid gland of Copp (Copp et al. 1962; Copp 1964, 1994). This hypocalcemic hypophosphatemic ba sic rule of the thyroid gland (Austin and heath 1981) became thyrocalcitonin of deer et al. (1964), Munson and deer (1966), Raisz et al. (1967) and MacIntyre (1992) characterized. Its calcitropic effects on bone and kidney function are opposite those of the Parathyreoid of hormone. Calcitonin develops from parafollicular the C-cells of the thyroid. Calcitoninabsonderung can be evaluated using the located gedurchstrà ¶mten pig thyroid (Pento 1985) in vitro. Radioimmunoproben for Calcitonin are present (Tashjian and Voelkel 1979), and sort speci  ¬Ã‚  C methods for Calcitoninermittlung must be regarded. Samples for Calcitoninempfà ¤nger were described (Nissenson et al. 1985). Overviews on effects of the exogenous Calcitonin were given by Deftos (1989); Braga (1994); Embankment oh et al. (1999). The biology and the clinical meaning of the Calcitoningenpeptide were repeated (Reginster 1993; Silverman 2003; Zaidi et al. 1990). Decrease of the serum calcium at the rats PURPOSE AND BA SIC PRINCIPLE the biological drug testing of the Calcitoninvorbereitungen using their ability to lower the plasma calcium accomplished in the rat. Also with the pharmacopeias, existing using the international reference preparation for the Calcitonin (pigs) of gefriertrocknetem puri  ¬Ã‚  OD pork Calcitonin was accepted, and during the international reference preparation consisting this procedure for the Calcitonin (salmon) of gefriertrocknetem puri  ¬Ã‚  OD synthetic Lachscalcitonin. These samples for Calcitoninquantitative regulation however were replaced now by a physicochemical method for pharmaceutical quality control. Either intravenous or subkutane administration can be selected. International standards for Lachscalcitonin, Aal Calcitonin and the Asu 1-7 correspondence of Aal Calcitonin are expenditure work CCIT (Zanelli et al. 1990). A second international standard for pig and human Calcitonins was manufactured by an international cooperative working group, those on dru g testing biological in vivo rat hypocalcemia (Zanelli et al. 1993) are based. If the groups of at least female Wistar rats  ¬Ã‚  of the VE, weighing 100-120g, PROCEED are used. Three doses standard preparation (1, 3 and 9 MU per rat) and three doses test preparation are intravenously injected. Then 1 h is taken back after injection, blood under bright anaesthesia. Plasma calcium is determined through  ¬Ã¢â‚¬Å¡ ame Photometrie or by Atomabsorptionsphotometrie. EVALUATION responding to the dose curves of decreases at the plasma calcium manufactured and force conditions with fraud will become  ¬Ã‚  dence delimitations computed. CHANGES of the METHOD similar studies were reported past: Kumar et al. 1965; Munson et al. 1968; Rittel et al. 1976; Schwartz et al. 1981; Michelangeli et al. 1983; Findlay et al. 1985; Dollar and Maxl 1990; Deming et al. 1994 Yates et al. (1990) determined the acute hypocalcemic answers to individual subkutanen injections of the Calcitoninvorbereitungen into intact young Swiss mice man of the ICR, which weighed 12-20 G. Calcitonin of the Stingray and the SH gold  ¬Ã‚  became of Sasayama et al. marked (1992, 1993). Kapurniotu and Taylor (1995) led hypocalcemic in-vitroproben in the mice by analysis of the serum calcium 1 h after subkutaner injection of lactambridged correspondences of the human Calcitonin through. Effect of Calcitonin on Osteoclasts in vitro PURPOSE AND BASIC PRINCIPLE Calcitonin proceeds mainly in accordance with inhibition osteoclastic of the bone admission (Friedman and Raisz 1965; Aliapoulios et al. 1966). Zaidi et al. (1990, 1994) the development reported and on the validation of three microbioassays for the Calcitonin, which was based on calcitonin caused inhibition of the activity of the located osteoclasts. PROCEDURES of thigh legs and Schienbeine are removed from the newborn Wistar rats. The bones are released to fà ¶talem calf rum, benzyle penicillin (100  µU/ml) and Streptomycin by the adhering soft fabrics and means 199 HEPES moderate by the cut over their Epiphyses in supplemental with heat-inactivated (100  µg/ml). Osteoclasts are mechanically divided, by exciting the bones of each rat with a Skalpellblatt into a 1 ml-means curetting and the abolition with a pipette. Larger fragments will let agree for 10 s, before the Supernatant on suitable substrate fall one leaves (bone disks, PlastikPETRISCHALEN or glass cover glasses). Motilità ¤t created system the morphologic appearance of the stained osteoclasts is used like an index, in order to determine the condition cell plasma tables of the activity. Osteoclasts are agreed upon on coverglass in t he micro titer wells and become for minute of 20 at 37 °C. expenditure-bred. The cover glasses are removed into different wells, each contained 100  µl means, put washed with means 199 and. After a further Ausbrà ¼tung for minute of 30 (37 °C), those series dilutions (tenfold) salmon or human Calcitonin or test preparations or suitable dilutions of the plasma samples are added. The cells are  ¬Ã‚ , nally for 2 h, which are expenditure-bred  ¬Ã‚ , which are stained in the 10% Glutaraldehyd xed and with Toluidinblau. The condition of the Motilità ¤t of everyone, which is osteoclast on each cover glass, is counted, by observing the characteristic deformation, which these cells go through, when Motilità ¤t is restrained; a freely mobile cell marked by a smooth outline by increased staining intensity over everything or partially its periphery, while a immotile cell usually an irregular slat-outline without call  ¬Ã¢â‚¬Å¡ Edrà ¤nder shows. The number immotile cells is co unted and expressed on each cover glass, how a percentage of the total number cells counted. Cytoplasmatic spread system Osteoclasts are agreed upon in the fabric cultural plates (35 millimeters) and expenditure-bred at 37 °C, so that minute permits 20 sediment formation and accessories. The cells are washed with means 199 and to 2 ml the same means into everyone well are then put. The plates are put converted into the Ausbrà ¼tungraum of phase contrasting microscope. Pictures osteoclasts are noted on a time mistake video equipment. A pursuit of their will outline by a digitization system brought into a computer, programmed, in order to measure the range within each pursuit. Those outline of osteoclast everyone before or after the additive of Calcitonin or from carrier to the cultures are noted. For each variable outline by six osteoclasts after a 60-Minute-Ausbrà ¼tung in the area and again in the 40 pursued, which is following minimal the additive of the hormone. The central s urface taken off by six osteoclasts, after Ausbrà ¼tung is expressed as percentage of the central surface osteoclasts before the additive of the hormone or the carrier. Bone photograph system of copies of the human kortikalen thigh bone are received from the donors (patients, who died without proof of the bone illness). The adhering soft fabric is removed and the bone crust cut longitudinal in disks (0,1 millimeters strongly). The disks are then cut into pieces (approximately 3 millimeter of 2). It through ultrasonication (minute of 15, in the sterile distilled water), drained cleaned stored by immersion 80% in aqueous ethanol for 2 h, and, in order to dry at room temperature. Osteoclasts located 199 in means will fallen on 12-16 bone disks, which were put well in 18 Millimetermultiweltellers. After Ausbrà ¼tung (37 °C, minute of 15), the disks are removed, and washed easily supplemented in the minimum substantial means with 10% FCS and antibiotics, as described above. They are put to well-being contained  ¬Ã‚  VE into different wells, each to six disks in 900  µl means. After further Ausbrà ¼tung (37 °C, the 10% humidi  ¬Ã‚  OD CO, minute of 10), is contained added  µl 100 of the means the test concentration of the hormone or the Testlà ¶sung. Human PTH (1-34) (0,1 U/ml) one uses, in order to determine function effects of the contamination of osteoblasts. The Calcitoninentsprechungen is examined with different concentrations (tenfold dilutions). Finally bone disks are expenditure-bred over night (37 °C, the 10% humidi  ¬Ã‚  OD CO2 18 h). The cells are  ¬Ã‚ , which is examined by transferred light microscopy in the Glutaraldehyd xed, with Toluidin blue stained and. Osteoclasts and in-full of seeds cells are counted. The disks are bleached then by immersion in the sodium hypochlorite solution for 30 minimum and drain 80% in aqueous ethanol. Finally are they squirt covered with the gold, randomized and in an electronic microscope of sca nning examined. The numbers osteoclastic weakening, each de  ¬Ã‚ , which is by a continuous edge ned, are counted. The range of the bone surface resorbed is computed, by one outline the concavity into a digitization tablet pursued, connected with a microcomputer. Surfaces of the admission can be expressed as per cent age of the means of the tax answer. EVALUATION data of each sample using the classical methods for analysis of the parallel line samples are analyzed. Estimations of the relative forces are computed of the parallel machine log book addressing on the dose lines of the test preparations and the reference preparation. Osteoclasts are divided and absent-minded mechanically by the long bones of the newborn rat at the low densities on disks devitalized of the cattle cartilage bone. The result areas of the bone weakening are quanti  ¬Ã‚  OD with mikrometric precision, by them electron microscopy as well as computer-assisted image analysis scanning. These  ¬Ã‚  ndings are used, in order to develop a formal biological drug testing for Calcitonin. Reacts to receiver operation difficulty and camp accumulation in located cells PURPOSE AND BASIC PRINCIPLE the human cancer of the breast cell form T47D to Calcitonin and his correspondences by receiver operation difficulty and accumulation of the camp. This can as biological sample (Findlay et al. 1980, 1983, 1985 to be used; Grey et al. 1992; Kà ¼ster and Hilton 1992; Curtains et al. 1993). PROCEED the human cancer of the breast cell form T47D originally by polarizing Urals Erguss of in  ¬Ã‚  one manufactured, ductal cancer of the breast (Horwitz et al. 1978) ltrating are. Washed for obligatory experiments cell-monomolecular films with 0.02% EDTA before treatment with 0.125% Trypsin in 0.02% EDTA for minute of 2 at 37 °C, introduction of the complete means before centrifugation with 200 g and Resuspension in the complete means. Iodination of Calcitonin is accomplished with 125 Iusinge the Chlorami n t method. For obligatory experiments T47D, which cells in the isotonischen buffer shifted, the Lachscalcitonin 125I-labeled are added, which is mixed with the different concentrations of the unlabelled Calcitonin, or correspondences and at 20 °C for 1 H. Nonspeci expenditure-bred  ¬Ã‚  C operation difficulty as the operation difficulty of the 125I marked Lachscalcitonin is determined in presence of the surplus (2  µg/ml) unlabelled Lachscalcitonin. Suggestion of Adenylate Cyclase into the intact T47D cells by Calcitoninentsprechungen is determined, by measuring production of the camp [3H] in the cells, prelabeled is also, adenine [3H]. Zellulare Atp laughter become by Ausbrà ¼tung with [3 H] adenine 2,8 (0,5-2  µCi/ml) for 2 h at 37 °C in 12 wohlen cultural plates in RPMI mark 16