Monday, January 27, 2020
Age Related Nuclear Cataract Treatment
Age Related Nuclear Cataract Treatment P750 LOGBOOK 5 STUDENT ID : 6469969 Age related nuclear cataract is the anterior segment disease and it is the clouding of ocular lens characterized by reduced antioxidant levels in the lens core. Antioxidant cystine is a amino acid having molecular weight 240.3 g/mol and solubility of 50 mg/ml in 1 M Hcl is used to prevent cataract formation. To treat cataract, cystine is applied topically in the form of eye drops. The factors that reduce cystine bioavailability are, Tear film :- Topically applied drugs will first encounter tear film and it is considered as first protective structure. Nasolacrimal drainage system :- After the application cystine eye drops tear fluid turnover doubles it is called as washout effect. Due to pH and foreign body sensation reflex tearing will occur. Cornea :- It is the main mechanical barrier. Due to its sandwich like structure drugs with molecular weight less than 5 K Da and partition coefficient of 10 to 100 can pass through it. Cornea is composed of three layers, the outermost layer is epithelium which is lipophilic in nature, middle layer is stroma which is hydrophilic in nature and innermost layer is endothelium which is lipophilic in nature. FORMULATION PARAMETERS : The formulation parameters to be considered in formulating a topical cystine eye drops are, Physico chemical drug properties :- Partition coefficient log p of the formulation should range from 10 to 100. Molecular weight ââ¬â molecular weight of the formulation should be less than 5 K Da. Charge ââ¬â charge of the drug should be positive. Buffer capacity and pH :- eye drops should be formulated with a pH range of 7.0 to 7.7. If the pH is 7, 99% of the drug remains in unionized form and favors the permeation through lipophilic epithelium. If the pH is more than 7, most of the drug ionizes and easily diffuses through the hydrophilic stroma. Viscosity : viscosity of the eye drop preparation must be around 15 m Pa. Instillation volume :- instillation volume must be less than 30 à µl because cul ââ¬â de ââ¬â sac can hold up to 30 à µl. Osmotic pressure :- osmotic pressure of the eye drop must range between 310 to 350 m osm/kg Antioxidants :- cystine itself acts as a antioxidant, no other preservatives are required. FORMULATION APPROACH : Colloidal ocular delivery systems like micro emulsions are used to deliver the antioxidant cystine in the form of topical eye drops. Micro emulsions : Micro-emulsions acts as vehicles for the delivery of antioxidant cystine in the form of topical eye drops. In micro emulsions phase transition will occur between the bi-continuous micro-emulsion, oil in water emulsion, water in oil emulsion, and lamellar crystals. Components of micro emulsions are, Water. Oils like mineral oil, vegetable oils, di and triglycerides, fatty acid ester. Surfactant ââ¬â non ionic, amphoteric and less commonly anionic and cationic surfactants are used. Co-surfactant ââ¬â short and medium chain alcohols are used as co-surfactants. Advantages of phase transitions of micro-emulsions W/O micro :-emulsion : these micro-emulsions are responsible for protection of water soluble drugs and sustained release of water soluble drugs. O/W micro-emulsions :- these micro-emulsions are responsible for increasing solubility of lipophilic drugs. Bi-continuous micro-emulsions :- these micro-emulsions are having good wetting and spreading properties on the ocular surface hence these are used in ocular drug delivery systems. Micro-emulsions are having low viscosity hence it is easy to instill. These micro-emulsions are thermodynamically stable. These are easy to prepare, no mixing is required. In these micro-emulsions we can detect the phase separation easily, drug precipitation and microbial contamination. Micro-emulsions are used as vehicles due to solubilization of hydrophilic and lipophilic drugs. By using the micro-emulsions as vehicles we can increase the bio-availability of drugs. Glaucoma is anterior segment disease characterized by raised intra ocular pressure, which results in the loss of regional ganglia cells and degeneration of optic nerve. Glaucoma is the main ocular disease responsible for blindness. Antisense oligonucleotides (As ODN) helps in curing glaucoma disease. Antisense oligonucleotides (As ODN) : These are single stranded DNA fragments of 10 to 30 nucleotides, complementary to the target mRNA. Mechanism of action ââ¬â Generally, DNA transcripts mRNA in the nucleus and this mRNA enters into the cytoplasm and ribosomes translate the mRNA. Finally results in the formation of proteins. Antisense oligonucleotides (As ODN) having complementary base sequence to that of mRNA binds with mRNA and prevents the formation of Cx proteins from it. Delivery route : I would like to choose intra-vitreous delivery route because, periocular injections of antisense oligonucleotides is responsible for poor stability and it is difficult for antisense oligonucleotides to penetrate through the cells. Intra-vitreous injection : It is the injection of antisense oligonucleotides into the vitreous with the help of a needle. In the treatment of many of the ocular diseases intra-vitreous administration of drugs is used. Advantages of intra-vitreous injection : This delivery route is responsible for achieving high concentration of drug in the vitreous. There will be no side effects, because it is not a systemic administration. Disadvantages of intra-vitreous injection : From the vitreous, many drugs are rapidly cleared due to blood ââ¬â retinal barrier, therefore repeated dose administration is required. Frequent injections leads to endopthalmitis, lens damage, detachment of retina. FORMULATION PARAMETERS :- Chemical modification : chemical modification of antisense oligonucleotides leads to increased or decreased solubility, stability etc.. Phospho-diester group :- By replacing oxygen from the phospho-diester group with sulphur, stability and solubility increases and RNase H cleavage will occur. By replacing oxygen with methyl group there is increased stability but decrease in solubility, due to lack of charge cellular uptake will not occur, no RNase H activity. Sugar moiety modification :- By adding a alkyl group at the 2nd position of ribose, there is increase in hydrophilicity and binding affinity but mismatches will occur and no RNase H cleavage. Other modification :- Replacement of phospho-diester group with polyamide results in high affinity to mRNA but aqueous solubility decreases, cellular uptake decreases and no RNase H cleavage. FORMULATION APPROACH :- To prevent antisense oligonucleotides (As ODN) from enzymatic degradation and to improve the cellular uptake a variety of formulation approaches have been put forward. They are, liposomes, nanoparticles, peptides, dendrimers, and physical methods. Among these i would like to choose multi functional dendrimer carriers. Dendrimer carriers :- Dendrimers are branched molecules and spherical in nature. Dendrimers are divided into low molecular weight and high molecular weight species. The properties of dendrimers depends on the functional groups at their molecular level. Dendrimers are cationic in nature and possess positive charge on it. Antisense oligonucleotides shows its therapeutic effect at cytoplasmic level and these antisense oligonucleotides are anionic in nature and possess negative charge. During the formulation, dendrimer undergoes complexation and condensation with antisense oligonucleotides. The functional groups present at the molecular level are. Cell penetrating peptide :- TAT peptide is derived from human immunodeficiency virus and it acts as a cell penetrating peptide. TAT helps in cellular uptake of dendrimer antisense oligonucleotide complex. Fusogenic peptide :- Dendrimer- antisense oligonucleotide complex binds to the cell membrane than enters in to the cell through endocytosis. These fusogenic peptide helps in endisomal escape. Influenza virus hemagglutinin subunit-2 is a fusogenic peptide. Lipoamino acid :- This functional group helps in improving permeability and stability. Example, C14 Disadvantage of dendrimer carrier : cytotoxicity increases due to the presence of cell penetrating peptides and fusogenic peptides REFERENCE :- Dr Ilva Rupenthal lecture notes given on 4th April 2014.
Sunday, January 19, 2020
How College Aids You in Life :: Education College University
Have you ever thought how college could help you improve in life? College is important because it helps you get a good career, good education, and rewards you with vacations. To begin with, college helps one get a good career. In particular, people that have a good education have a much easier time finding success in their life. Most of the highest paying jobs in the world require a college education. In the same way, a college education helps one earn much more money. Having a degree makes sure that you will keep that job and will help you earn a bigger salary within the years you work. In addition, having a college education can help your health and keep you happy. People that enjoy their careers are much happier and have a higher level of well being. Unquestionably, a college education gives you a better paying job. In addition, going to college gives you a good education. For example, a good college education gives you wisdom. Most of college educated people have lots of education, and gives you lots of knowledge. Next, a college education gives you lots of intelligence. A college educated person will a lot on many things especially on what they majored in. Also, a college educated person has autonomy. A person with a college education that has autonomy is independent and has freedom. Obviously, having s college education makes you a better person. Next, going to college rewards you with vacations. Specifically, you go on many vacations. When you have a steady job you earn at least two vacations. Correspondingly, when you are on a vacation you learn that culture. If you go to different places you learn how people talk, eat, how they dress, and how they act. In addition, when you take vacations you go wherever place you want. How College Aids You in Life :: Education College University Have you ever thought how college could help you improve in life? College is important because it helps you get a good career, good education, and rewards you with vacations. To begin with, college helps one get a good career. In particular, people that have a good education have a much easier time finding success in their life. Most of the highest paying jobs in the world require a college education. In the same way, a college education helps one earn much more money. Having a degree makes sure that you will keep that job and will help you earn a bigger salary within the years you work. In addition, having a college education can help your health and keep you happy. People that enjoy their careers are much happier and have a higher level of well being. Unquestionably, a college education gives you a better paying job. In addition, going to college gives you a good education. For example, a good college education gives you wisdom. Most of college educated people have lots of education, and gives you lots of knowledge. Next, a college education gives you lots of intelligence. A college educated person will a lot on many things especially on what they majored in. Also, a college educated person has autonomy. A person with a college education that has autonomy is independent and has freedom. Obviously, having s college education makes you a better person. Next, going to college rewards you with vacations. Specifically, you go on many vacations. When you have a steady job you earn at least two vacations. Correspondingly, when you are on a vacation you learn that culture. If you go to different places you learn how people talk, eat, how they dress, and how they act. In addition, when you take vacations you go wherever place you want.
Saturday, January 11, 2020
Unexpected Benefits
In the fourteenth century, the face of Europe was forever changed by a devastating event known as the Black Plague. This plague would rear its ugly head time and again throughout Europe in lesser outbreaks right up through the eighteenth century, when it finally disappeared from the continent for good. However, its initial appearance happened in the fourteenth century, and this debut performance was its most dramatic and destructive.Called the ââ¬Å"great mortalityâ⬠by contemporary writers1, for the great number of people killed in the outbreak, the term ââ¬Å"black plagueâ⬠or ââ¬Å"black deathâ⬠became more commonly used later on as more outbreaks hit the European continent. Carried by fleas on rats, the Black Plague is now commonly thought to be bubonic plague, a disease characterized by sub-dermal hemorrhages that blacken the skin; it is highly contagious and has a high mortality rate. It is thought that Black Plague first entered Europe from Asia, along the si lk roads that merchants used to travel between the continents for the purposes of trade. 4 1Boccaccio, Giovani.The Decameron. Signet Classics: New York. 2002 (reissue). 4Kelly, John. The Great Mortality: An Intimate History of the Black Death, the Most Devastating Plague of All Time. Harper Collins: New York. 2005. When the Black Plague first hit Europe, the conditions in Europe were ripe for a devastating outbreak. Warfare and a widespread famine that lasted nearly a century had weakened the population of Europe to the point that the people were extremely vulnerable to disease. Famine also hurt productivity by weakening workers, thus further reducing the output of food and other necessary goods; it was an ugly, self-perpetuating cycle.In a population already suffering and on the brink of disaster, the Black Plague, which first made its European appearance in 1347, was a final push toward a dramatic re-alignment of society. Over one-third of the population of Europe was killed by th e Black Plague (and over half the population in Britain). It wiped out entire families, and even entire communities. When it was over, the stunned and decimated population had to face a virtual rebuilding of their entire society from scratch.However, as devastating as the Black Plague was on the inhabitants of Europe, and as hard as things were on the survivors, the Black Plague did have some unexpected benefits for the survivors and their descendants, benefits that would improve the overall quality of life for everyone in Europe, peasants included, for generations to come. One of the most immediate benefits to survivors of the Black Plague was an increase in wages. Before the population was decimated by the Black Plague, Europe had been drastically overpopulated for its resources, resulting in widespread poverty, especially among the peasants.After the Black Plague, however, labor came at a premium, due to the reduction in the population. There were not nearly as many people availa ble to do much-needed work, and therefore those who were available to do it were more sought-after. As a result, wages increased, because employers were now competing for the smaller pool of workers, rather than workers competing for a smaller pool of jobs, as had been the case before. With higher wages, survivors were better able to provide for their families, and the standard of living for many families dramatically increased.In fact, some families fortunes increased so dramatically that they began to live as the nobility did, dressing in fine clothes, living in fine houses, and even employing servants of their own. In some European countries, the nobility were so threatened by the new upward mobility of the peasants that laws were enacted that regulated just what the peasant class could wear and where they could live, so as to prevent the peasant class from mingling with the nobility or trying to become part of the nobility2.In fact, increased opportunities for social advancement were another unexpected benefit of the Black Plague for survivors. Before the Black Plague, Europe was fairly 2Cantor, Norman. In the Wake of the Plague: The Black Death and the World it Made. Harper Perennial: New York. 2002. entrenched in the feudal system, whereby peasants worked the land for wealthy nobles, being allowed to take only a small portion of the harvest they worked to bring in for their own use, and being pretty much tied to the land of their patron for life.After the Black Plague, the surviving population realized it now had options. With so few peasants available to work the land, landlords began competing to attract tenants to their estates, a phenomenon that was new in Europe. Previous to the Black Plague, landlords had a self-propagating population of peasants on their land, generation upon generation of families that stayed on the same land, on the same estate, and worked under whatever conditions the landlord set, as there was nowhere else for them to go.Howev er, after the Black Plague, landlords offered incentives for peasants to come work their land, incentives ranging from actual wages to improved living conditions to increased freedoms. In fact, some historians believe that the conditions in Europe just after the end of the initial Black Plague laid the roots of what was to become capitalism centuries later. A reduction in the population also meant that there was an increase in the amount of fertile land available to the population.With entire families wiped out, sometimes noble or land-owning families, their land became available, land that had often been in the same family for centuries. This opening up of new land created opportunities not only for landlords to increase their holdings and attract new peasants to work for them, but also created opportunities for upwardly mobile peasants to become landowners in their own right. With land available for those who could afford to purchase it, many peasants found that their newfound inc rease in wages also bought them the opportunity to become settled on their own land, and, in effect, their own masters.The Black Plague also, in effect, put an end to the century-long famine in Europe. With fewer people to feed, there was more food available for those who were left. The opening up of new, tillable land on which to grow food, the demand for labor that produced more food, and the increase in wages that allowed a family to buy more food, all led to an increase in consumable food available for everyone. As a result of the Black Plague, the survivors became better nourished and healthier, and thus better able to work to produce more food, as well as better able to fight off new outbreaks of disease as they came.Even with an increase in wages and other benefits attracting most of the available workers after the Black Plague, there were still too few people around to work to do everything that needed to be done in the time in which it needed to be done. Therefore, out of n eed, a plethora of labor-saving devices began to be invented following the Black Plague. These devices helped to speed along necessary work, and reduced the number of people necessary to complete certain jobs. The spinning wheel is an excellent example of this.The spinning wheel was a post-Black Plague invention that dramatically reduced the time and effort involved in turning wool into thread. 3 With more thread able to be produced more quickly than by traditional methods, cloth was able to be weaved quicker and in greater quantities, thus creating an abundance of fabric available for sale and for personal use. Springs and gears were invented to control the hands of clocks. Horseshoes and spring carriages were invented that eased the burden of travel and increased its efficiency.Three-crop field rotation was invented, which increased farming efficiency by dropping the old idea of individual farming plots and introducing the idea of open-field communal farming. In addition, heavier plows with wheels and horizontal plowshares were invented, which saved much time and labor in the process of farming. Finally, the ultimate of all medieval inventions, the printing press, was invented post-Black Plague, an invention that saved an enormous amount of time and energy by ending the need of copying books by hand, thus making the written word more widely available to the general public.3 3Herlihy, David. The Black Death and the Transformation of the West. Harvard University Press: Cambridge. 1997. The effects of the Black Plague were felt in every facet of life, not just social and economic. The Black Plague utterly changed the face of life in Europe forever. The plague even affected the art of the times. Whereas before the Black Plague, religious themes were the most common topic of art, after the Black Plague, a more pessimistic feeling pervaded a society that was terrified of the plague returning.As a result, themes of death became dominant in the artwork for more than a century after the plague. The prestige and authority of the Church were also negatively affected by the Black Plague. Because the church was not able to cure victims of the plague, or even explain what was causing the plague, cynicism of the church grew among the populace. As a result, many sought out alternatives to the traditional church, particularly through smaller religious cults such as self-flagellants (who flogged themselves in atonement for the sins that supposedly brought on the plague).Others sought out secular solutions to ending the plague. Further, because so many monks died in the plague (from living in close quarters and from generously tending the sick), the church experienced an influx of new, less dedicated clergy, who were more opportunistic than the old guard, and contributed to an upcoming period of severe corruption within the Catholic church that eventually led to the Protestant Reformation. 2While the Black Plague was a devastating event for all of Europe , killing millions, it left behind conditions that lead to some positive changes in European society. While wiping out entire families and towns, the Black Plague nonetheless created a fertile ground for economic improvement and upward social mobility for the underclass in its wake. The Black Plague led to the downfall of the feudal system and created the conditions that later ushered in the Age of Enlightenment.It ushered in a new age of labor-saving inventions that changed the face of production in the world. Because it was such a powerful force on both society and the psyche, the Black Plague also ushered in an era of change in both art and religion, changes that eventually led to the Protestant Reformation, which in turn led to the founding of America by the Puritans. The Black Plague, though it destroyed, also provided the seeds of sowing something new and good. 2Cantor, Norman. In the Wake of the Plague: The Black Death and the World it Made.Harper Perennial: New York. 2002. B ibliography Boccaccio, Giovani. The Decameron. Signet Classics: New York. 2002 (reissue). Cantor, Norman. In the Wake of the Plague: The Black Death and the World it Made. Harper Perennial: New York. 2002. Herlihy, David. The Black Death and the Transformation of the West. Harvard University Press: Cambridge. 1997. Kelly, John. The Great Mortality: An Intimate History of the Black Death, the Most Devastating Plague of All Time. Harper Collins: New York. 2005.
Friday, January 3, 2020
Racism, Sexism, And Sexism Essay - 976 Words
Everywhere I go, I see people wearing a multitude of different clothing, itââ¬â¢s something all humans do, we all have our own way of dressing. I get judged based on the things I wear, just how people are judged based on their race. What people wear can say a lot about them and make others act or think a certain way. Clothes can show the wearerââ¬â¢s thoughts, social status, enjoyments, jobs, and even more. People can often figure these things out just based on their clothes without even thinking about it. However, assumptions and stereotypes of any kind can be highly inaccurate. Clothism is as real as racism and sexism. Judging people based on the clothes they wear is the same as judging people based on their race. One thing that can be gathered about someone based on their clothes is their opinions. Political shirts saying to vote a certain way reflect the wearerââ¬â¢s political views. If someone wears a shirt that says ââ¬Å"Vote for Pedro,â⬠theyââ¬â¢re probabl y voting for Pedro themselves and want to sway others to vote the same way. A shirt that has a musicianââ¬â¢s name on it shows that the wearer likes their music. A jersey or hat of a sports team shows that they like that sport and team. Iââ¬â¢ve worn political shirts for campaigns before. Iââ¬â¢ve worn different artistsââ¬â¢ shirts. I wear shirts of teams and schools. Wearing these clothing items was to show others my thoughts and opinions of the topics. Similar to how people dress, a personââ¬â¢s race can often times give leway to their opinions.Show MoreRelatedRacism, Sexism, And Sexism889 Words à |à 4 Pagesconstructs that have made little progress such as racism, sexism, and homophobia. In reality vaccines and sexism are manmade, a vaccine is a manmade invention and sexism is a manmade idea. Neither would exist without human beings backing the idea that they are necessary. 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