Saturday, December 28, 2019

Animal Abusers Can Turn Into Real Criminals - 1485 Words

Animal abusers can turn into real criminals in the future Ever thought about why such people abuse animals and how they carry on their lives living with the guilt? According to the research I have read online, many have found that abusing animals will lead to abusing people since this act of violence on animals cooperates with the act of violence on the humans as well. So the real question is, do abusing animals lead to abusing humans? Abusing to animals physically or mentally are very negative actions that people should not do. Every day in the United States animals are beaten, neglected, or forced to struggle for survival. Left in critical conditions with no food or water, these poor animals have little hope as they live out their days to survive in such a harsh world. While some are found and rescued, and given a chance to experience how great life can become; others aren t so lucky. From actual incidents, brutal people sometimes abused animals by monstrous intensive methods such as putting them in the microwave, throwing them of the ba lcony, dragging them with cars and etc. As the rate of animal cruelty is increased all over the world, there were many effects of it on these animal abusers as well. What can happen to these type of people is that even children who inflict cruelty on animals often also inflict cruelty on other people especially to other children, and also from my own personal experiences and actual studies, people who commit animals’ cruelty crimesShow MoreRelatedAnimal Abuse And Neglect1090 Words   |  5 PagesAnimal abuse is defined as either the physical mistreatment of an animal or neglect where the animal is denied basic necessities of care. The mistreatment of animals is a serious issue within society. It often goes unreported because many people believe it is only abuse if it is intentional. This lack of understanding allows minor cases of neglect to progress into major cases that can end in the death of the animals involved. Animal abuse needs a better definition due to the results of neglect, psychologicalRead MoreAnimal Abuse And Its Impact1325 Words   |  6 PagesAnimal Abuse Its Impact This project is an in depth look at animal abuse. What is animal abuse? Animal abuse is defined as either the physical mistreatment of an animal or neglect where the animal is denied basic necessities of care. The mistreatment of animals is a serious issue in society. It often goes unreported because many people believe it is only abuse if it is intentional. This lack of understanding allows minor cases of neglect to progress into major cases that can end in the deathRead MoreEssay on Feminist Criminology3530 Words   |  15 PagesCriminology: How useful is it in its analysis of female crime? MSc Criminology and Forensic Psychology Feminist criminology emerged out of the realisation that criminology has from its inception centred on men and the crimes they commit. Although it can be argued female criminality was researched by Lombroso, as far back as 1800’s, female crime, it’s causes and the impact in which it had on society was largely ignored by the criminological futurity. Those Criminologist who did attempt to researchRead MoreDrug Addiction in Bangladesh4730 Words   |  19 Pagescolleges. Even university’s professors are getting addicted recently. These addicts are turning to various criminal activities, in order to procure drugs. What are Drugs? World Health Organization (WHO) defines Drug; Drug is a chemical substance of synthetic, semi synthetic or natural origin intended for diagnostic, therapeutic or palliative use or for modifying physiological functions of man and animal. Drug impacts directly influence the economic and social aspects of a country and physically to a humanRead MoreEssay on Can Pedophiles Be Cured?2642 Words   |  11 PagesHave you ever asked the question, how we know if a pedophile or sex offender can ever be cured or rehabilitated. Would I be comfortable with them living in my neighborhood? If you have you are just like the rest of the world. Pedophilia is a true illness, and not just in my opinion it also in the DSMIV 302.2. We may never truly be comfortable with the thought that researchers say Pedophiles can not be cured, but they can be rehabilitated in time with and they have test to prove it, Read MoreThe Incarceration Of The United States2529 Words   |  11 Pagesimprisoned within the U.S. will be released and rearrested within three years (Langan Levin, 2002). Unfortunately, research has been mixed shown that the time spent in prison does not successfully rehabilitate most inmates, and the majority of criminals return to a life of crime almost immediately. Most experts believe that many prisoners will learn more and better ways to commit crimes while they are locked up with fellow convicts. There is a combination of programs and environmental conditionsRead MoreCausation of Serial Killers Essay2039 Words   |  9 Pagesargue that the inability to cope with the stresses of trauma and victimization endured during their childhood are the main cause of the formation of serial killers. Both psychopaths and psychotic people can endure problems during their early childhood development, which can trigger their deviant criminal actions, making early childhood development th e main cause of serial killers. One possible cause of becoming a serial killer is psychosis. Psychotic patients, unlike psychopaths, have lost their senseRead MoreThe Pursuit Of Oblivion By Richard Davenport2193 Words   |  9 Pagespoints out that drug use is a part of human nature and â€Å"Intoxication is neither unnatural or deviant.â€Å" I agree that it is a natural desire for humans to want to feel aroused or intoxicated. What brings us pleasure and how often we require this feeling can differ significantly from person to person. Davenport writes, absolute sobriety is not a natural or primary human state. Again, I believe this feeling of intoxication must be able to include behaviors that bring some people to that same alteredRead MoreDrug Addiction in Bangladesh4031 Words   |  17 Pagesdefines it: â€Å"Drug is a chemical substance of synthetic, semi synthetic or natural origin intended for diagnostic, therapeutic or palliative use or for modifying physiological functions of man and animal.† A drug abuser can undergo different stages of tasting apart from normal lifestyle. Drug abuse can decay normal human senses through deep feelings. It creates different types of excitement both in the body and mind. Finally, it makes a person passionate to drugs. In the long run the user has toRead MoreChemical Castration Essay4712 Words   |  19 Pagesdefined as a person who has been convicted of a sex crime and released back into the community either directly after sentencing or after serving time in prison for the commission of the sex crime. It should be noted that both men and women commit criminal sex acts, however, this paper will focus on the male offender. First and foremost, it is of prime importance to clarify the nature of rape and sex crimes. According to Groth and Birnbaums study in Men Who Rape: the Psychology of the

Thursday, December 19, 2019

Should People Less Than Eighteen Years Old...

Should people less than eighteen years old (minors/juveniles/adolescents) ever be tried and sentenced as adults? The legislation of trying and sentencing youth criminals under adult justice system has been a hot topic of debate. Supporters of tough laws on insist the need to enforce harsh penalties to uphold justice. The practice of treating youth criminals as adults since the 1990s is a result of the steep rise in youth crimes. However, youth advocates argue that tough laws should not be applied to youth offenders anymore. The core issue of the controversy is whether, because adolescents are biologically and mentally different from adults, they should be treated differently. For minor offenses such as property crime in which nobody is†¦show more content†¦Similar findings can 1|Page HENG, SIN YI be seen in the article â€Å"Jailing Juveniles† (2008, p.127) revealing the danger of juveniles in adult facilities. Because youths are often isolated from other adult prisoners to prevent sexual and physical abuse, they are more vulnerable to various mental disorders. Moreover, suicide ideation of youth offenders in adult jails is 36 times higher than that of those in juvenile correctional facilities. As a result, youth advocates oppose treating youth offenders as adults. However, violent juvenile criminals should be punished for their misdeeds. Hunter (2010, p.101) insists that age should not be an excuse to oppose incarceration of youth criminals in adult prisons as a punishment for their crimes. In Hunter’s opinion, â€Å"cold-blooded murderers† like Jordan Brown, who killed his father’s fiancà ©e while she was sleeping must be punished to the maximum extent of the law although Brown was only 11 years old when the murder took place. In her opinion, to ugh laws are crucial for upholding justice for victims and victims’ families who suffered because of these juvenile crimes. Indeed, the culprits should not be easily forgiven to make sure that justice is served for the victims and victims’ families. Juvenile criminals have to bear the responsibilities for their actions regardless of their age. The purpose of tough punishment for violent youth offenders is to let them learn and realizeShow MoreRelatedJuvenile Crimes Of Juveniles1055 Words   |  5 Pagescrime? I live near the nation’s capitol and our local news channel carries stories about people meeting this fate every day. The worst part is that the criminal is often under the age of eighteen. In 2016, in Washington, D.C. alone, there were 3,278 juveniles arrested for criminal activity (â€Å"Biannual Reports†). I find myself wondering if that criminal will be tried as an adult or merely spend time in juvenile detention. I wonder if the child unde rstands the gravity of what they did. I am certainRead MoreEssay on Juvenile Death Penalty3656 Words   |  15 PagesA 16 year old boy is at the peak of their adolescent life, learning and discovering about puberty, maturity, right and wrong and future life goals. On the other hand, a man of 25 has matured, lived long enough to have made both good and bad judgments and has already been in the process of achieving those life goals they once thought of as a teenager. In a given situation, is it ethical to hold these two age groups, with mentalities that are worlds apart, to the same standards and punishments in theRead MoreEssay on Juvenile Death Penalty1824 Words   |  8 Pagesthe most controversial issues in the country today is addressed in the question, Should the death penalty be applied to juveniles, and if so how young is too young? The death penalty has been in the United States for many, many years, and the United States still has yet to figure out how to solve all its d ilemmas and whether or not the penalty is right or wrong. Debates about the use of the death penalty for juveniles have grown more intense because of the recent demand for harsher punishment forRead MoreThe Legal Before 18?3888 Words   |  16 PagesSociety always put thin lines on what exactly the requirements are for being grown. Some people might agree that being grown means that you pay your own bills, have a job, and don’t live under your parents roofs. But most people agree that if you are eighteen then you are legally grown and an adult. However we still have a system that gives prosecutors the unchechecked authority to push children into the adult system. In our court system injustices are treated very differently based on a multitude

Wednesday, December 11, 2019

Steve Tesich the only kind of real rebel left, he figures, is a moral person Essay Example For Students

Steve Tesich: the only kind of real rebel left, he figures, is a moral person Essay How do political plays function in an apolitical society? What is the purpose of art in a bankrupt culture? Steve Tesich ruminates on these questions with the weariness of on whose work is inseparable from the social context of its time. Alternately wry and wary as he discusses his most recent play, On the Open Road, the 49-year-old playwright becomes more animated when the topic turns to what he sees as the virtual collapse of the countrys political system. Like others of his generation who came of age in the hurlyburly activism of the 1960s, only to see their ideals remain unrealized, Tesich is intent on revealing the consequences of Americas retreat from its past promise. In flashes of conersation, Tesich might be a character out of Division Street, his 1980 comic drama about disenchanted radicals desperately seeking a connection to something beyond material success, nearly swooning at the scent of mimeo paper and the threat of tear gas, yet caught between comfort and conscience. You want to live in a place, Tesich insists. You dont want to think of yourself at odds with things. Thats not pleasant. Maybe its kind of pleasant when youre very youngbut I dont want to be at odds with the culture, with the country, now. But when so many things occur that are repugnant and so many people are taking part in them, its just a horrible feeling to be in this tiny, dwindling minority. Despite the almost wistful acknowledgment that only the very young can truly claim a legitimate counterculture experience, Tesich has resolved, in his life as well as his work, to make political discourse once again respectable. I dont let things go by anymore, he says. Everyone knows whats wrong, and there is this kind of agreementlets not talk about it, lets not deal with it. The essential problem has been sealed off as an embarrassment. When you bring up moral issues, as I tend to do, people just look at you as if your fly is open. From homicidal to alienated For the Yugoslavian-born playwright (Tesich fled with his family to England after the Nazi invasion, then moved to the United States as a teenager), moral issues have always had an intrinsic, if sometimes off-beat, worth. Tesich came to prominence in the 1970s with a series of plays (The Carpenter, Lake of the Woods, Baba Goya and Passing Game), almost all produced at New Yorks American Place Theatre, about what would now be called deeply dysfunctional families. Populating his plays with characters ranging from homicidal to merely alienated, Tesich created a myth of the family that both satirized and celebrated the American dream, and at the same time skewered traditional domestic drama. Division Street, the pinnacle of this series of plays, premiered at Los Angeless Mark Taper Forum and then opened on Broadway in 1980 with a cast that included Christine Lahti, John Lithgow, Theresa Meritt and Joe Regalbuto. Featuring a black woman with a Polish accent, a female cop who used to be a man (Tesichs farcical nod to the power of the womens movement) and families lost, found and reunited, Division Street offered a slapstick tribute to multicultural America, political idealism and the belief that true love can conquer all. The play, which ended with the cast gathered on stage singing America the Beautiful, was not well-received, closing on Broadway after 21 performances. By that time, however, Tesichs award-winning original screenplay for Breaking Away, an affecting film about four highschool friends in Indiana, had catapulted him to success in Hollywood. Tesich went on to pen the screenplays for such films as Eyewitness, Four Friends, Eleni and The World According to Garp. .u38d265105a17235ab2a77de69dda7d15 , .u38d265105a17235ab2a77de69dda7d15 .postImageUrl , .u38d265105a17235ab2a77de69dda7d15 .centered-text-area { min-height: 80px; position: relative; } .u38d265105a17235ab2a77de69dda7d15 , .u38d265105a17235ab2a77de69dda7d15:hover , .u38d265105a17235ab2a77de69dda7d15:visited , .u38d265105a17235ab2a77de69dda7d15:active { border:0!important; } .u38d265105a17235ab2a77de69dda7d15 .clearfix:after { content: ""; display: table; clear: both; } .u38d265105a17235ab2a77de69dda7d15 { display: block; transition: background-color 250ms; webkit-transition: background-color 250ms; width: 100%; opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #95A5A6; } .u38d265105a17235ab2a77de69dda7d15:active , .u38d265105a17235ab2a77de69dda7d15:hover { opacity: 1; transition: opacity 250ms; webkit-transition: opacity 250ms; background-color: #2C3E50; } .u38d265105a17235ab2a77de69dda7d15 .centered-text-area { width: 100%; position: relative ; } .u38d265105a17235ab2a77de69dda7d15 .ctaText { border-bottom: 0 solid #fff; color: #2980B9; font-size: 16px; font-weight: bold; margin: 0; padding: 0; text-decoration: underline; } .u38d265105a17235ab2a77de69dda7d15 .postTitle { color: #FFFFFF; font-size: 16px; font-weight: 600; margin: 0; padding: 0; width: 100%; } .u38d265105a17235ab2a77de69dda7d15 .ctaButton { background-color: #7F8C8D!important; color: #2980B9; border: none; border-radius: 3px; box-shadow: none; font-size: 14px; font-weight: bold; line-height: 26px; moz-border-radius: 3px; text-align: center; text-decoration: none; text-shadow: none; width: 80px; min-height: 80px; background: url(https://artscolumbia.org/wp-content/plugins/intelly-related-posts/assets/images/simple-arrow.png)no-repeat; position: absolute; right: 0; top: 0; } .u38d265105a17235ab2a77de69dda7d15:hover .ctaButton { background-color: #34495E!important; } .u38d265105a17235ab2a77de69dda7d15 .centered-text { display: table; height: 80px; padding-left : 18px; top: 0; } .u38d265105a17235ab2a77de69dda7d15 .u38d265105a17235ab2a77de69dda7d15-content { display: table-cell; margin: 0; padding: 0; padding-right: 108px; position: relative; vertical-align: middle; width: 100%; } .u38d265105a17235ab2a77de69dda7d15:after { content: ""; display: block; clear: both; } READ: If George Gibbs were gay EssayWhen he returned to playwriting, Tesich says, things had changed. My three most recent plays were written about the same time, one after another Once I started in again, I saw no point in writing for theatre if I was going to continue to write the same way. Indeed, the trio of post-Hollywood plays share a far bleaker world view than the playwrights earlier works. Square One (which debuted at New Yorks Second Stage in January 1990), The Speed of Darkness and On the Open Road (both of which premiered at Chicagos Goodman Theatre, in April 1989 and March of this year, respectively) address such topics as totalitarian regimes, environmental devasta tion, and the deadening of mass culture. I wish there were a conspiracy that creates our culture, he says, almost in despair, because then we would know where to point the finger: 10 colonels in charge and the junta took over. But instead things go along kind of on automatic pilot. The culture that waits for something of meaning to happen, then takes it and spits it out as trivia. Tesichs casually rumpled manner contrasts nicely with the harder edge of his cynicism. Were now in a mad kind of thing where we are appreciating the quality and the elaborateness of the Governments lie, he continues. If either Bush or Clinton felt the way to win the upcoming election was to sell cancer, they would do it. Survival via high culture In On the Open Road, a sort of post-apocalyptic Waiting for Godot with overtones of a philosophical buddy movie, Tesich surveys a range of topics: the role of the individual in a political structure based on tyranny, the purpose and value of art, the nature of love and friendship. Set in a time and place of Civil War, the play follows the shifting fortunes of Al and Angel, two independents who are trying to reach (in the plays baldly stated irony) the Land of the Free. Al and Angel are scavengers, looting crumbling museums to gather the art of high culture they think will ensure their survival. When a new coalition government asks them to do a little job, howeverkill JesusAl and Angel find that their troubles are just beginning. An unwieldy script (the third draft ran as high as 160 pages), On the Open Road seems elliptical at best, moving from theme to theme without completely drawing focus to any. For Tesich, however, the form of the play is an intentional reaction against the killing approach of Americas consumer-oriented appreciation of art. If you can |get it, he explains, you kill it. If you can |get it, youre either wrong, your perception is twisted, or maybe what youre looking at is something less than art itself. Tesich envisions Jesus as a mute, tortured, cello-playing prisoner-of-war, grounding the play in an image that it isnt possible to get. Robert Falls, artistic director of the Goodman and helmsman for both The Speed of Darkness and On the Open Road, attributes the playwrights new emphasis on sounds and images to his time in Hollywood. The movies have expanded Steves imagination; he thinks on a larger scale, visually and lyrically. Hes among the most fluid writers Ive ever seen, Falls says admiringly. He keeps himself constantly evolving and changing. Hes great to work with in rehearsal for that reason, because hes able to see the large picture. For Tesich, the large picture remains not just the stage, but society. There was a time, I think, he says, when a majority of people lived what I would call lives rooted in reality. That reality could become so powerful that they would want an escape from it in whats called entertainment. I now honestly feel that people live in |unreality. The purpose of art now must be just the oppositeto remind people of what theyve abandoned.

Wednesday, December 4, 2019

Thyroid Gland Essay Example

Thyroid Gland Essay The thyroid gland is located immediately below the larynx on each side of and anterior to the trachea. * The colloid contains thyroglobulin which contains the thyroid hormones. * The parafollicular cells contain calcitonin. Iodide Kinetics Average daily intake: 0. 1 mg Absorption: iodine to inorganic iodide in stomach and upper SI Transport amp; Metabolism: iodide (ECF) pool thyroid pool hormone (T3T4 pool) issues (liver,muscle,etc) thyroid-serum iodide ratio: 25 to 1 Clearance: kidneys Synthesis amp; Release – stimulated by TSH * The iodide in the ECF will enter the follicular cells (idodide trapping) through active transport (Sodium-Iodide Symport). * The iodide will then diffuse to the apical cells where it will be oxidized (catalyzed by thyroid peroxidase) to iodine to make it capable of binding directly with thyroglobulin. * Electron acceptor: hydrogen peroxide * Iodine will enter the colloid through the Iodide-Chloride symport. Within the colloid, tyrosine, which is cont ained in the thyroglobulin will be iodinated which will result in the formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT). * MIT and DIT will undergo coupling reaction resulting in the formation of T3 and T4. * When the thyroid cells are stimulated, iodinated thyroglobulin is taken back in to the follicular cells by endocytosis. * Lysosomal enzymes then digest thyroglobulin, releasing T3 and T4 into the circulation. * Leftover MIT and DIT are deiodinated by thyroid deiodinase. The iodine released is reutilized to synthesize more thyroid hormones. The most important regulator of the thyroid gland function and growth is the hypothalamic-pituitary thyroid releasing hormone-thyroid stimulating hormone axis. Thyrotropin releasing hormone (TRH) secreted by the hypothalamus stimulates the anterior pituitary to secrete thyroid stimulating hormone. TSH regulates the secretion of T4 and T3 of the thyroid gland; it has immediate, intermediate, and long-term actions on the thyroid epithelium IMMEDIATE: * Induction of pseudopod extension, endocytosis of colloid, formation of colloid droplets in the cytoplasm. TSH also stimulates entry of glucose into the hexose monophostphate shunt pathway, which generates NADPH that is needed for the peroxidas reaction. * Stimulates proteolysis of thyroglobulin and release of T4 and T3 INTERMEDIATE: * Occur after a delay of hours to days and involve protein synthesis and expression of numerous genes, including those encoding NIS, thyroglobulin, TPO, and megalin. LONG TERM: * Sustained TSH stimulation lea ds to hypertrophy and hyperplasia of follicular cells. *Regulation is under exquisite negative-feedback control: Circulating TH act on the pituitary gland to decrease TSH secretion, primarily by repressing TSH ? subunit gene expression. The pituitary gland expresses the high affinity type 2 deiodinase. Thus, small changes in free T4 in blood result in significant changes in intracellular T3. * Because the diurnal variation of TSH secretion is small, TH secretion and plasma concentrations are relatively constant. Only small nocturnal increases in secretion of TSH and release of T4 occur. * TH also feed back on hypothalamic TRH-secreting neurons. We will write a custom essay sample on Thyroid Gland specifically for you for only $16.38 $13.9/page Order now We will write a custom essay sample on Thyroid Gland specifically for you FOR ONLY $16.38 $13.9/page Hire Writer We will write a custom essay sample on Thyroid Gland specifically for you FOR ONLY $16.38 $13.9/page Hire Writer T3 inhibits the expression of the prepro-TRH gene. * Iodide is also an important regulator. At low levels, rate of TH synthesis is directly related to the availability of the iodide. * Circulating T4 and T3 act on the pituitary gland to decrease TSH secretion; if the levels of T4 and T3 fall, TSH secretion increases. It is free T4 and T3, not the protein-bound portions that regulate pituitary TSH output. The pituitary gland is capable of deiodinating T4 to T3, and the latter acts as the final effector molecule in turning off TSH. Fig. TSH actions on the thyroid cell. Cyclic adenosinemonophosphate (cAMP) along with calcium ions (Ca2+) and phosphoinositol products act as second messengers generated by TSH binding to its receptor. All steps in thyroid hormone production, as well as many aspects of thyroid cell metabolism and growth, are stimulated by TSH. Growth factors are important intermediaries in cell proliferation and in synthesis of some proteins such as thyroglobulin. Thyroid Autoregulation related to iodide availability involves iodide transport amp; organification odide excess transport/organification till maximum sudden decrease (Wolff-Chaikoff effect) ** when iodide intake exceeds 2mg/day. The intraglandular concentration of iodide reaches a level that suppresses NADPH oxidase activity and the NIS and TPO genes and thereby the mechanism of hormone biosynthesis, this phenomenon is calle Wolff-Chaikoff effect. iodide deficiency transport/organification TSH levels normal Stimuli| Inhibitors| Epinephrine (inc rease SNS activity, increase TH)| Iodides (inhibit NIS)| VIP| Thyroglobulin (negative feedback)| Prostaglandin| Acetylcholine| Leptin (low food intake, high energy expenditure thru TH synthesis)| Lithium| Cold exposure (thermogenic effect, maintenance of body temp)| Fasting (prolonged starvation, low TH [BMR])| Transport and Metabolism | T4| T3| Reverse T3| Rate of Secretion| 90%| 10%| gt;1%| t ? | 6-7 days| 24 hours| | Free form| 0. 03%| 0. 3%| | Comment| Serves as a prohormone in peripheral tissue; undergoes monoiodoniationInactive formTetraiodothyronine| 10x more potent than T4Active formTriiodothyronine| | | Behaves like steroid hormone| Peripheral Conversion Type 1 5’ DI rT3 T2 Type 2 5’ DI T4 T3 (more important, 80% of T3 is formed through this process) Type 3 5 DI T4 rT3 (reverse T3, more produced rather than the active T3) High T4 conversion to T3 - conversion to type 1 Low T4 Type 2 Peripheral metabolism of thyroxine (T4) is largely by successive deiodinations. Key regulatory step: T4 T3 rT3 (deiodination) * The liver, kidneys, and skeletal muscles are the major sites of T4 degradation. * T4 increases its own degradative metabolism * Sequential deiodination steps is regularly increased in the plasma in yperthyroidism (T4 excess) and is usually decreased in hypothyroidism (T4 deficiency). 3 Types of deiodinase: * function of these enzymes depends critically on the presence of selenium at the active catalytic sites. (D1) Type 1 5-deiodinase| rT3 is the preferred substrate yielding 3,3-T2| expressed in the thyroid gland, liver, and kidney; regulates the circulating T3 supply by augmenting T3 production and disposing of rT3 generated from excess T4. | (D2) Type 2 5-deiodinase| T4 T3| skeletal muscle, brain, and brown fat; favors local T3 generation| Type 3 5-deiodinase| T4 rT3| brain, skin, and placenta. | 5-monodeiodination * T3-generating activity * supplied by D1 and D2 * D1 5-monodeiodinase activity has a lower affinity but a higher capacity for T4 than does D2. * In humans, the normal distribution of T4 products is approximately 45% T3 and 55% rT3. An increase in T4 concentration leads to a decrease in its conversion to T3. Thus, the biological effects of T4 excess or deficiency are automatically mitigated slightly by accelerated or retarded metabolic inactivation, respectively. Clinical states and factors associated with a reduced conversion of T4 to T3 amp; reciprocally enhanced conversion of T4 to rT3 Gestational period * Fasting * Major medical and surgical stress * Catabolic disease * Hepatic disease * Renal failure * Thiouracil drugs * Beta-adrenergic blockers * inhibition of hepatic D1 activity appears to explain this switch * inhibition of 5-monodeiodinase decreases the production of T3 from T4 (reducing plasma T3), and it simultaneously decreases the degradation of rT3 to 3,3-T2 (increasing plasma rT3). Reduction of 5-monodeiodinase activity may also result from * Decreased glucose metabolism * Increased FFA metabolism Excess secretion of cortisol * When 5-monodeiodinase activity is reduced, sulfation of T4 and T3 increases, and the addition of sulfate greatly diminishes the biological activity of whatever T3 is produced. Transport Carrier Proteins * Secreted T4 and T3 circulate in the bloodstream almost entirely bound to proteins. * About 0. 03% of total plasma T4 and 0. 3% of total plasma T3 exist in the free state * TBG- thyroxine-binding globulin; major binding protein 70% * Maintains lar ge circulating reservoir of T4 Binding of plasma T4 and T3 to large proteins prevents the loss of these relatively small hormone molecules into the urine, and thereby helps conserve iodide * primary change in TBG concentration will also disturb the ratio of free to bound T4 TTR-transthyretin; 10-15% * may provide thyroid hormones to the central nervous system. TBA – albumin; much lower affinities but much higher capacities for binding T4 and T3 Clinical Correlation TBGClinical Condition Free T4 normal hyperthyroidincreased normal euthyroid normal normal hypothyroid low levated pregnancy normal * more sensitive indicator of primary hypothyroidism: increased TSH, not the decrease in circulating T4, * Total circulating T4 represents mainly bound T4 which is not an index of activity. * Measurement of free T4 index would be a sensitive indicator of thyroid status. * The goal in replacement therapy for primary hypothyroidism: raise plasma T4 to the point where TSH returns to normal . Thyroid Receptors TR-1 skeletal/cardiac muscle* TR-2 does not bind T3, inhibits TR TR-1 brain, liver, kidney^ TR-2 pituitary, hypothalamus; Responsible for inhibiting the expression of the prepro-TRH gene in the paraventricular neurons of the hypothalamus and of the ? -subunit TSH gene in pituitary thyrotropes. * Thus negative feedback effects of thyroid hormone on both TRH and TSH secretion * most common mutations occur in this subtype; therefore there is incomplete negative thyroid hormone feedback at the hypothalamic-pituitary level. INTRACELLULAR ACTIONS OF THYROID HORMONE Mechanism of Action hormone binds with nuclear receptors gene transcription- proteins- mitochondrial enzymes other enzymes eg. Na-K-ATPase hormone binds with mitochondrial R oxidative phosphorylation Figure. Overall schema of thyroid hormone effects. The upper portion represents intracellular actions resulting from T3 binding to its nuclear receptor (TR), which is linked to thyroid regulatory elements (TREs) in target DNA molecules. The lower portion catalogs all the various whole body effects of thyroid hormone that sustain increased oxygen consumption and permit disposal of the excess CO2, heat, and metabolic products. Biologic effects of Thyroid Hormone cellular metabolic systemic rowth and development whole body effects -biologically, T3 is much more important than T4. WHY 1. T4 is bound more tightly to plasma protein than T3 (resulting to free T4 in the circulation only about 2fold higher than T3) 2. Once T4 enter the cell, the target cell converts it to T3 3. THR in the nucleus has greater affinity for T3 than T4 (so mas potent ang effect ni T3 on a molar basis) Physiological Effects 1. Stimulate BMR o r calorigenesis O2 consumption (indirect calorimetry) amp; heat production (direct calorimetry) thyroid hormone deficiency leads to decreased BMR Thyroid hormone increases the BMR by stimulating both the catabolic and anabolic reactions in pathways affecting fats, carbohydrates and proteins 2. Respiratory effects RR, VE, ventilatory control 3. Cardiovascular effects CO, HR, SV TPR 4. Metabolic effects protein degradation amp; protein synthesis glycogenolysis amp; gluconeogenesis (E) glycogenesis amp; glucose utilization (I) lipolysis amp; cholesterol metabolism 5. Others NS effects bone growth amp; remodeling interaction with SNS Physiological Effects of Tyroid hormone| Parameter| Hypothyroid| Hyperthyroid| BMR| v| ^| Carbs metab| v gluconeogenesisv glycogenolysis| ^ gluconeogenesis^ glycogenolysis| Protein metab| v synthesisv proteolysis| ^synthesis^proteolysisMuscle wasting| Lipid synthesis| v lipogenesisvlipolysis^serum [cholesterol]| ^ lipogenesis^ lipolysisv serum [cholesterol]| Thermogenesis| v| ^| Autonomic nervous sytem| Normal level of catecholamines| ^ expression of ? -adrenoreceptor| Major Functions of Thyroid Hormones 1. Required for normal maturation of the NS in the fetus and infants Deficiency: mental retardation (cretinism) 2. Required for normal bodily growth (permissive effects to GH) Deficiency: deficient growth in children . Required for normal alertness and reflexes at all ages Deficiency: mentally and physically slow and lethargic Excess: restless, irritable, anxious, wakeful 4. Major determinant of the rate at which body produces heat during the basal metabolic stage Deficiency: low BMR, sensitivity to cold, decreased appetite Excess: High BMR, sensitivity to heat, increased appetite 5. Facilitates SNS activity by stimulating synthesis of receptors for epinephrine and norepinephrine Excess: symptoms similar to activation of SNS (eg. HR) Functional Disorder of Thyroid Gland Hyperthyroidism – result from a number of causes. Most commonly the entire gland undergoes hyperplasia as a result of autoimmune stimulation (Grave’s Disease), in which antibodies formed against the TSH receptor bind to it and mimic TSH action. Symptoms Nervousness Heat insensitivity Sweating Weightloss Tachycardia Palpitations Muscle weakness Moist skin Increased appetite Sleeplessness Tremor Goiter Bruit over thyroid Diarrhea antibodies (TSHR-Ab) bind to the TSH receptors, which are located on the cells that produce thyroid hormone in the thyroid gland (follicular cells), and chronically stimulate them, resulting in an abnormally high production of T3 and T4 types of autoantibodies to the TSH receptor currently recognized: * TSI, Thyroid stimulating immunoglobulins: these antibodies (mainly Immunoglobulin G) act as LATS (Long Acting Thyroid Stimulants), activating the cells in a longer and slower way than the normal thyroid-stimulating hormone (TSH), leading to an elevated production of thyroid hormone. * TGI,Thyroid growth immunoglobulins: these antibodies bind directly to the TSH-receptor and have been implicated in the growth of thyroid follicles. TBII,Thyrotropin Binding-Inhibiting Immunoglobulins: these antibodies inhibit the normal union of TSH with its receptor. Some will actually act as if TSH itself is binding to its receptor, thus inducing thyroid function. Other types may not stimulate the thyroid gland, but will prevent TSI and TSH from binding to and stimulating the receptor. Hypothyroidism – in adults most often results from idiopathic atrophy of the gland, which is thought to be preceded by a chronic autoimmune inflammatory reaction. Symptoms Muscle weakness Sleepy Sluggish Poor appetite Sensitive to cold Dry skin and hair Slow speech Infertility Loss of memory Constipation Weight gain Edema of face Decreased heart rate LAST HOROSCOPE EVER Aries Magpakatotoo ka na. Bading ka noh? Lucky Color: Indigo Blue Angkop na NY resolution: Hindi na ako matutulog sa klase. Taurus Bagay sayo ang suot mo. 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