Food Wasted Research Paper Example | Topics and Well Written Essays - 1250 words

Food Wasted - Research Paper Example These figures are extremely significant when one would consider the fact that millions of people all over the world, including some Americans are currently facing starvation or poverty. As per the 2009 statistics from America, 14.3 percent of all persons lived in poverty (Poverty in the United States). â€Å"How can 50 million people face hunger in a country that wastes billions of pounds of food?†(Feeding America). This paper analyses the reasons and consequences of poverty and food wastage in America. According to Usborne, â€Å"28 million people in the US will be using government food stamps to buy essential groceries in the fiscal year 2008, the highest level since the food assistance program was introduced in the 1960s†. United States is supposed to be the wealthiest countries in the world. Yet, it is surprising to know that 28 million people in America are facing some kind of poverty. It is an accepted fact that American food production is more than what they requ ired for the food needs. In fact America is exporting surplus food items to overseas countries. Yet, a substantial portion of the Americans are facing starvations. This happens mainly because of the problems in the management of food chain in America. â€Å"There is enough food to feed every man, woman and child in America. Hunger in America is not about supply, it is about redirecting the excess food that is lost each year to those who need it most† (Feeding America). Tons in millions of food items are wasting in American warehouses because of the problems in the supply chain. In fact the major reason for starvation is not lack of production, but inadequate supply of food. According to Bloom, 49 million food- insecure Americans were there in 2012. This happens mainly because of the food damage that taking place in between farm and fork. Dana Gunders (p.1) pointed out that 10 percent of the total U.S. energy budget, 50 percent of U.S land and 80 percent of all freshwater reso urces were utilized while food production take place in America. In her opinion, 40% of the total food production in America is getting wasted nowadays. Another argument put forward by Dana is that uneaten foods and the foods thrown away as waste are contributing heavily to the environmental problems in the form of solid waste accumulation. Solid wastes have the ability to generate toxic gases such as methane. In her opinion, reduction of food losses by 15 percent would be enough to feed more than 25 million starving Americans every year. It should be noted that the governments all over the world are spending too much to avoid environmental damage. The objective of these spending is to keep the environment fresh always to make life of animals, human and plants safer. It is a fact that plants are the only food producers in the world and no other thing in this world has the ability to produce food. Because of this awareness, governments are trying hard to fortify plant life in this wo rld. However, dumping of wasted food in agricultural lands is causing huge problems to the plants in the form of solid waste. It should be noted that solid wastes have the ability to produce toxic gases such as methane which is harmful to plant life. â€Å"When food is disposed in a landfill it rots and becomes a significant source of methane - a potent greenhouse gas with 21 times the global warming potential of carbon dioxide. Landfills are a major source of human-related methane

Irish Urban Regeneration Essay Example | Topics and Well Written Essays - 1000 words

Irish Urban Regeneration - Essay Example 8). The evolution of the city saw and increase in urban expansion in the 20th Century, and the Irish economic boom led to an upsurge in the construction of private homes. Standardised housing was implemented in the 1960s, and these regulations included specifications for density, public space, services, etc. Ballymun's high rise towers were the result of experimentations at this time. However, "the classic pattern that has occurred again is that a development pattern has evolved of rapid creation of new residential communities without adequate infrastructure or facilities" (Williams and Shiels, 2001, p. 27). Previous plans to regenerate Dublin included the Integrated Area Plans (Kelly, 2005) and the Urban Renewal Act of 1986 (Suzanne, N. 2001) that came about as a result of the unwillingness of the private sector to enter many Dublin inner city neighbourhoods that had degenerated to dereliction. The government offered tax incentives to attract private business. This was successful in combating the decay of the Dublin cities, but those urban renewal schemes were only questionably effective in some cities. Because of the profit motive, architectural and design concerns were of little value to the investors. In addition, the economic benefits of the investment were mostly unavailable to the residents of those towns. This led to the newest Urban Regeneration Projects (2001). According to the Egan Review and other organisations, regeneration involves the search for long term restoration and renovation of neighbourhoods, improvement of transportation systems, and involves an outlook of encouraging social inclusion and economic stability. These objectives are to be realised concomitant with ones of sustainable use of natural resources, such as energy and water. These objectives have necessitated the support of sound local leadership as well as concurrence among local, regional, and national policies (Carley, et al., 2005). Brief History of Ballymun The Ballymun population stands at approximately 20,000 and 44.6% of these persons are unemployed. It has even been suggested by some authorities that the true unemployment figure might lie in or above the 60% mark. One third of the population is below the age of 14, and over a third of the households are run by a single parent, while the national average is 10%. The percentage of children who attain a school-leaving certificate is only 7% (Environmental Appraisal, p. 43). Before the Regeneration project, the city of Ballymun suffered from several structural, social, and economic problems. Many blocks of high-rise buildings were located in the city, and these were poorly constructed, having internal structural flaws as well as the disadvantage of being poor conservers of energy. This led to wide-scale removal by tenants, high levels of vacancies in apartment buildings, unemployment and drug problems. Voting turnout for local government elections has been as low as 15% (de Rossa, 1998). Social exclusion was also a significant problem in Ballymun that resulted from its spatially isolated location, as it was cut off because of poor links in transportation (Muir, 2003). Ballymun Regeneration Ltd. took up the challenge and with the help of other environmental agencies, constructed an energy and environmental strategy

Nursing theory application paper Parses Human Becoming Theory Essay

Nursing theory application paper Parses Human Becoming Theory - Essay Example The parent of bay AB was distraught of the news. The next couple of days were a time to observe the patients reacting from the different procedures to keep her alive. But the baby got worse and even developed subclinical seizures on continuous encephalagram and was decided to be placed under a pentabarb coma. After a week, physicians attending to the baby saw progress because of adjusted medicines and a more positive eeg results. The team of physicians attending to baby AB decided based on the positive results of the eeg and brought the baby out of the coma. During the patients rest towards recovery in the open heart unit, the neuro and airway status was continuously monitored. One realization during the case is that the patient’s family is another set of patients to be looked upon. Baby AB, given her sensitive and delicate case must be given all the necessary attention and care. The family must is taught of the feeding techniques through g-tube and how to monitor the signs of seizure and respiratory distress of baby AB. Fortunately the family has a very strong faith and believed in the approach if giving utmost importance to baby AB’s condition. Philosophical underpinnings of the human becoming theory Palliative care focuses on quality of life and the life of both the patient and his or her family. Given the sensitivity and serious condition of the patient, giving care to the patient does not only rely on the attending physicians and nurses on the case. But rather the medical team must also encourage support and assistance to the family who will be taking care of the patient and giving their 24 hours care for the patient. In relation with the case specified about, the theory under study that analyzes and is connected with this case is Parse's human becoming theory which focus on the humanly experiences of health that constitutes a process of becoming one with the universe and other entities in it. Parse's human becoming theory has its roots used as a nursing theory in the continental human science tradition. As a resolved theory that uses Parse's own experiences as a nurse, influence of Roger's conceptual system of nursing, and other tenets of existential phenomenology, the theory provides a theoretical system that explains how human beings is viewed as the expert and knowledgeable of his or her own health. The human becoming theory is an alternative theory that is presented by both conventional bio-medical approaches with biological, psychoanalytical, social and spiritual aspects. The theory focuses the personal quality of life as a goal in the nursing practice. The assumptions of this theory were synthesized from the works by European philosophers, Heidegger, Sarte and Marleau- Ponty together with American nurse theories influenced by Rogers.(Cody) Concepts and propositions of the theory The human becoming theory has three main themes or concepts. The first one is meaning. Meaning being the first principle of the theory relates that structuring multidimensional meanings is co- creating reality through the expression of value and image.(Parse, 1998) To simplify this concept, there is the principle that people participates in creating what is real for them through choices and self-expression of the values in their life and how they will implement the

Irish Urban Regeneration Essay Example | Topics and Well Written Essays - 1000 words

Irish Urban Regeneration - Essay Example 8). The evolution of the city saw and increase in urban expansion in the 20th Century, and the Irish economic boom led to an upsurge in the construction of private homes. Standardised housing was implemented in the 1960s, and these regulations included specifications for density, public space, services, etc. Ballymun's high rise towers were the result of experimentations at this time. However, "the classic pattern that has occurred again is that a development pattern has evolved of rapid creation of new residential communities without adequate infrastructure or facilities" (Williams and Shiels, 2001, p. 27). Previous plans to regenerate Dublin included the Integrated Area Plans (Kelly, 2005) and the Urban Renewal Act of 1986 (Suzanne, N. 2001) that came about as a result of the unwillingness of the private sector to enter many Dublin inner city neighbourhoods that had degenerated to dereliction. The government offered tax incentives to attract private business. This was successful in combating the decay of the Dublin cities, but those urban renewal schemes were only questionably effective in some cities. Because of the profit motive, architectural and design concerns were of little value to the investors. In addition, the economic benefits of the investment were mostly unavailable to the residents of those towns. This led to the newest Urban Regeneration Projects (2001). According to the Egan Review and other organisations, regeneration involves the search for long term restoration and renovation of neighbourhoods, improvement of transportation systems, and involves an outlook of encouraging social inclusion and economic stability. These objectives are to be realised concomitant with ones of sustainable use of natural resources, such as energy and water. These objectives have necessitated the support of sound local leadership as well as concurrence among local, regional, and national policies (Carley, et al., 2005). Brief History of Ballymun The Ballymun population stands at approximately 20,000 and 44.6% of these persons are unemployed. It has even been suggested by some authorities that the true unemployment figure might lie in or above the 60% mark. One third of the population is below the age of 14, and over a third of the households are run by a single parent, while the national average is 10%. The percentage of children who attain a school-leaving certificate is only 7% (Environmental Appraisal, p. 43). Before the Regeneration project, the city of Ballymun suffered from several structural, social, and economic problems. Many blocks of high-rise buildings were located in the city, and these were poorly constructed, having internal structural flaws as well as the disadvantage of being poor conservers of energy. This led to wide-scale removal by tenants, high levels of vacancies in apartment buildings, unemployment and drug problems. Voting turnout for local government elections has been as low as 15% (de Rossa, 1998). Social exclusion was also a significant problem in Ballymun that resulted from its spatially isolated location, as it was cut off because of poor links in transportation (Muir, 2003). Ballymun Regeneration Ltd. took up the challenge and with the help of other environmental agencies, constructed an energy and environmental strategy

Biomarkers Essay Example | Topics and Well Written Essays - 1000 words

Biomarkers - Essay Example In aquatic environment, biomarkers depend upon the physical environmental conditions such as temperature, pH or salinity, as well as toxic concentrations of chemical pollutants or any combination of these. Biomarkers can be categorized as non-specific and specific according to their responses to a particular element or a group of environmental factors (Mayer et al., 1992). non-specific biomarkers, for example ribonucleic acid/deoxyribonucleic acid, radiolabelled amino acid or nucleotide incorporation, and adenylate energy charge, give direct information on the growth rate or potential of an organism but they can not be used to determine the particular toxicant. Specific biomarkers can be again categorized n to two sub-categories, organ, and toxicant specific according to method of their recognition. Organ specific biomarkers are analyzed by examining changes in concentration specific enzymes in organisms whether as Toxicant-specific biomarkers are analyzed according to the exposure and effects on an organism due to a chemical or group of chemicals. Lactate dehydrogenase (LDH), transaminases, creatine phosphokina... criteria with which to assess results should be available Biomarkers can be categorized as non-specific and specific according to their responses to a particular element or a group of environmental factors (Mayer et al., 1992). non-specific biomarkers, for example ribonucleic acid/deoxyribonucleic acid, radiolabelled amino acid or nucleotide incorporation, and adenylate energy charge, give direct information on the growth rate or potential of an organism but they can not be used to determine the particular toxicant. Specific biomarkers can be again categorized n to two sub-categories, organ, and toxicant specific according to method of their recognition. Organ specific biomarkers are analyzed by examining changes in concentration specific enzymes in organisms whether as Toxicant-specific biomarkers are analyzed according to the exposure and effects on an organism due to a chemical or group of chemicals. Lactate dehydrogenase (LDH), transaminases, creatine phosphokinase, lysosomal enzymes, alkaline phosphatases and mixed function oxidase are the examples of organ specific biomarkers while as inhibition of acetylcholinesterase (AChE) by organophosphates and inhibition of cytochrome P monooxygenase, methallothionein and metal binding proteins by metals are some of the toxicant specific biomarkers (Mayer et al., 1992; Gagn and Blaise, 1993). There are basically two parameters for biomarker assessment: global reference values and comparative values. global reference values can be developed for DNA adducts, ALA-D, AChE, scope for growth, CEA, PAH-metabolites, GST, lysosomal stability, micronucleus formation, vitellogenin, MT biomarkers and comparative values can be used for ethoxyresoroufin-o-deethylase (EROD), antioxidant enzymes, peroxisomal

Helsinki Watch Group Essay Example for Free

Helsinki Watch Group Essay Often times throughout world history, and particularly the history of freedom movements, the cliche that life imitates art, and that art imitates life shows its face strongly. Two of the leaders of the dissent movement in the Soviet Union and its bloc countries/satellites just as easily could be merely characters in a play as well as characters within the world. The ironic thing is that their power derives from the same source: literary hero. Icons are created and understood things whether their figure is symbolic, archetypal or actual. In the cases of Vaclav Havel and Natan Sharansky their work was accomplished through these literary means. Their books, their histories, and their experiences are shared ones, perhaps only overshadowed by their joint successes. Vaclav Havel began his personal movement through a certain default. His history found itself at a crossroads when his educational pursuits were thwarted at the end of compulsory levels. His family’s identification with intellectuals was more than enough for the Soviet machine to attempt to discourage, by force of rule, further attempts at intelligentsia pursuit. Havel thus was placed into the position of many young idealists: when denied something, the object becomes much more desirable. This method of subjugation tends to be the downfall of many systems. It is seen often in Western countries that many talented individuals left to their own devices fail to achieve their full potential. My understanding is that if they were forcibly detained from their talents, they would begin to fight by human nature, and unlock more than they were ever able to, or motivated to, accomplish. With Havel, as with others, his power was unleashed subconsciously from his earliest days. Military service to the country, again a rigid compulsory reality, and allowance into an Economics program did not manage to reign in the young Czech. He discarded these and pursued quickly his passion – one shared by his family. Humanitarian values and improvement seemed to run strongly in the Havel household, and Vaclav was no different and no stranger to this. Following work as a stagehand, he managed to land himself in studies of Drama at Faculty of Theatre of the Academy of Musical Arts, completing his academics there by correspondence. The failure of the Czech government to discover and end Havel’s studies would ultimately undermine their authority over the playwright, and over those who followed his later writing. By 1966, Havel had his first international successes, and brought himself his first attention on the world political stage . It was during this period that one of his most influential works was written and produced: 1963’s The Garden Party. Havel was not hiding his civic tendencies and participated in what he hoped was a revival of the cultures of his home country. He took parts and positions in various movements, chief among them the Club of Independent Writers and the Club of Engaged Non Partisans. This did not cause him overwhelming trouble yet, even when he took a job with the non Marxist monthly paper Tvar in 1965. But the rulers did begin to take notice. In 1968, he, and many others of similar mind would pay for their ‘treason’ in the cultural revolution and its subsequent Prague Spring. Only 7 years later Havel began his transition from cultural icon to political figure by sending a series of open letters to the political bureaus. One of his most important early ones was a missive to then President Husak, a demonstration of his growing awareness of the plight of Czechoslovakian society. This writing directly resulted in the 1977 Charter, which for the first time openly criticized the standards of life in the state. As spokesman, he began the voice of referendum, and it was his previous popularity as author that provided the groundwork for his ability to draw followers. Unfortunately for him, chief among his followers were the censors and police. But his political life was well underway. Anatoly ‘Natan’ Sharansky, born in Ukraine of the Soviet Union followed a different path to his political life. It is amazing and worthwhile, however, to explore the similarities of life in yet a separate Soviet bloc land. For all intents and purposes, the two could have grown up together. This common bond, as it would turn out, would provide a common ‘enemy’ of sorts for them – an enemy of freedom and expression. Also ironic is the apparent ‘lapse’ of judgment on the part of the government that allowed Sharansky’s influence to foment, and then to spread. When dissident Andrei Sakharov was held under state control, it was Sharansky that was allowed to be his English interpreter. Such close work with the alleged revolutionary inspired the already impressionable Anatoly to develop his own ideas regarding the freedom of man behind the iron curtain. This time period saw him help found, and then act as spokesman for the Moscow Helsinki Watch Group. As with Havel in Czechoslovakia, 1977 would be the time of divergence from active young man to active international freedom fighter, in a cultural way. At the same time that the Charter was criticizing life under communism, Sharansky was first arrested for treason to the state of the Soviet Union. This initial interrogation and incarceration was based upon his supposed spying activities for the United States, charges that were later proven false, as was the case for many others. Upon conviction, Sharansky was sent to the gulags of Eastern Russia, where he would remain until 1986. When he was finally released, one of the first political prisoners to be, he finally realized one of his personal dreams: emigration to Israel where he could recover his Jewish heritage. When he arrived and was greeted with a hero’s welcome, he exchanged his Soviet name ‘Anatoly’ for the Hebrew ‘Natan’, by which he has since been known . Havel, too, would have to escape from behind bars, figuratively speaking. After the 1977 charter, he would find himself unable to publish any of his works which were gaining attention and influence. He was now a de facto politician and had to be stopped. The Czech government attempted to do so by imprisoning him three separate times, placing him behind bars for over 5 years. At the time of his incarceration, he had become the co-founder of the Committee for the Defence of the Unjustly Prosecuted, a committee that he could not have foreseen he would need the personal care of. By the second half of the 1980s, as with Sharansky, Havel would finally begin to realize freedoms. Dialogue with the communist governments and the Soviet Union was finally beginning to open up, and Havel took the opportunity to coauthor a petition of â€Å"A Few Sentences†. This would eventually be signed by 10,000 Czechoslovaks. Despite a setback in 1989 in which a freedom movement was crushed, Havel came to his political pinnacle by gaining the presidency of the new Czechoslovakia. Havel and Sharansky have both been immortalized through their writings. We have their collected works and also now their important histories and memoirs and can study their dissent to compare their achievements and experiences. Theirs is the story of many others, and shows the power of literature, composition and political texts to connect oppressed peoples. Havel’s plays, and especially The Garden Party, and Sharansky’s memoir Fear No Evil are powerful representations of this ideal. The Garden Party could not have been better for uniting and informing the masses. As such, it is quite surprising that the play did not simply ‘go away’, so to speak; that it got into the hands of the public was a serious misstep on the part of the communist government. The play is absolutely a stunning satirical work. It uses humor to attack its target in a sideways fashion, which ultimately is a more successful frontal attack than pure rhetoric, anyway. Its characters are simple and believable, if not highly stereotypical, and work their wonders in different ways. If no other character is remembered after reading The Garden Party for the first time, it is Hugo that sticks in the mind. All at once he is quaint, separated from outer consciousness, and independent. Where he begins as an inner focused chess player in the home – so inner focused that he plays both sides – he grows into his own brutal oppressor. This is great work. We wonder at his childlike manner in playing against himself at the game, only to be shocked when he plays against himself through bureaucratic oppression later on. Most amazing of all is the ease with which he takes both sides in both undertakings. It is a comment at once on deception, and also of childlike qualities of leadership as opposed to mature development. Unfortunately, government cannot be run in this manner with its failure to police itself. Beyond its characters, The Garden Party relies upon dramatic tools to get its message across. These tools help connect the play to its audience, which must be remembered were the oppressed citizens of the Eastern Empire. In particular the writing in of a theme – paranoia – underscores the feelings of the time. It becomes obvious that even supporters of the system are discomfited by their work. Even as they work for the bureaucracy, they are always aware that they are being watched for their loyalty. They do not know who their enemies may be at any time. By way of example, Huge becomes his own enemy – a position that he never becomes truly aware of. Life becomes for him the prevention of danger to his position, the ultimate revelation of paranoia. His ongoing chess metaphor becomes the way of expressing this feeling. Rather than allowing himself to be open to abuse, he ‘checkmates’ his way out of trouble, squashing perceived opponents – squashing freedoms and liberties and ideals – before they can get to him. Sharansky in his life developed similar tactics. He, like many other civil liberties prisoners, had to create methods of dealing with harsh realities. Unlike Havel’s characters in many of his plays, of which The Garden Party’s Hugo remains the archetype and easiest to digest, Sharansky understood and faced his danger openly. His methods of using humor to disengage a situation, though, were the same. Both Havel and Sharansky understood and expressed within their lives, their lifeworks, and the awareness that even in their oppressive modes, humans are humans. Even interrogators can be reached through their own humanity. For all of the things we in the West think we know about the KGB, who were in charge of depriving Sharansky his freedom, we see through Fear No Evil that the secret police still were made up of humans. They were humans that could still be swayed, tempered or delayed through a humorous play. We can almost hear ‘checkmate’ come from Sharansky’s mouth at times, bringing Hugo right into his cell with him. The connections become obvious. We see the power of dissidence through language, whether spoken, read, written or performed. In this way, we see now the connections between Sharansky and Havel. BIBLIOGRAPHY Havel, Vaclav. The Garden Party and Other Plays. New York: Grove Press, 1993. Sharansky, Natan. Fear No Evil: The Classic Memoir of One Man’s Triumph Over a Police State. New York: Random House, 1998. .

Antiglycation Studies of Pd(II)-Hydrazide Complexes

Antiglycation Studies of Pd(II)-Hydrazide Complexes Introduction Glycation is a non-enzymatic spontaneous reaction between sugars and coexisting protein followed by a complex cascade of reactions including dehydration, redox reaction and other rearrangements [1, 2] forming advanced glycation end products (AGEs) [3]. Glycation reactions depend on the generation of reactive oxygen species by trace amounts of redox active metal ions [4] and on the degree and duration of hyperglycemia in vivo [5]. Glycation damages the collagen and elastin throughout the body. It is generally accepted that accumulation of tissue AGEs together with enhanced oxidative stress has an important role in the progression of aging and diabetic complications including retinopathy, neuropathy, embryopathy, delayed healing of wounds and others [6-10]. The increase in diabetic complications is the major cause of increased morbidity and mortality rate that has enhanced considerably in the two decades [11]. It has been estimated that the number of cases of DM will reach to 366 milli on by 2030 [12, 13] showing in fact a great challenge to healthcare systems [14]. The failure of existing antidiabetic drugs are forcing researchers to find out new inhibitors of proteins responsible for glycation in order to have a long term and sustainable solution for management of diabetes and age-related diseases. Protein Glycation The protein glycation, also called Millard reaction, involves non-enzymatic coupling of proteins with reducing sugars eventually producing advanced end products. The glycation is a spontaneous reaction, which stimulates the degradation of proteins with modification of their structures and biological activity [1-3]. Various reducing sugars including glucose, lactose, fructose, xylose, deoxyribose and galactose may take part in protein glycation [15]. Chemistry and Mechanism of Protein Glycation The protein glycation process initiates with the reaction of carbonyl (keto or aldehydic) group of reducing sugar with free amino group of protein forming a labile Schiff base 16. This is called early stage of glycation. The Schiff bases are then transformed through Amadori rearrangement into comparatively stable compounds known as Amadori products. At acidic pH or under oxidative conditions, the Amadori products or Schiff bases undergo degradation generating extremely reactive 1, 2-dicarbonyl compounds, such as methylglyoxal (Figure 94) 17-21. The formation of protein dicarbonyls through a protein enediol may generate superoxide radicals in the presence of transition metal ions and molecular oxygen 22. The superoxide radicals can be converted into most reactive hydroxyl radical via Fenton reaction 7. The reactive carbonyl compounds subsequently react with amino groups of neighboring proteins producing protein dicarbonyl compounds, which further contribute in the formation of various types of protein crosslinks and adducts called ‘Advanced Glycation End Products’ (AGEs). The autoxidation of Amadori products to AGEs is described as glycoxidation process. Figure 94. Structures of some reactive dicarbonyl glycation intermediates Advanced Glycation End Products The advanced glycation end products (AGEs) comprise a complex heterogeneous group of compounds produced primarily through the reaction of reactive carbonyls and proteins. AGEs demonstrate to have diverse molecular biological functions and structures 18, 23]. The amino, sulphydryl and guanidinum functional groups occurring in the intracellular and extracellular proteins are the main targets of reactive carbonyl compounds. Various AGEs have been recognized in different tissues that can be categorized into three major groups: fluorescent cross-linked AGEs (e.g. pentosidine and crossline), non-fluorescent cross-linked AGEs (e.g. alkyl formyl glycosyl pyrrole and arginine-lysine imidazole cross-links) and non-cross linked AGEs (e.g. pyrraline and N-(carboxylmethyl) lysine) 18. The structures of some AGEs are presented in Figure 95. Figure 95. Structures of selected advanced glycation end products Factors Affecting the Formation of AGEs In physiological environment, the generation of AGEs is a relatively slow process. Accordingly, the AGEs accumulation is dominant in long-lived structural proteins, for instance, tissue collagens and lens crystallins. The oxidative conditions are known to accelerate the formation of AGEs, which slows down under anaerobic environment [24]. The transition metal ions may induce the auto-oxidation of sugars to produce keto aldehydes and hydrogen peroxide that speed up the formation of AGEs [25]. The amount of AGEs formed is increased as a function of time and concentration of glucose and hence the AGEs formation is enhanced with aging and under diabetic conditions [26]. Site Specificity of Glycation of Proteins Glycation of protein is considered as a specific reaction; however, it is less specific compared to enzymatic glycosylation. Glycation often takes place at specialized site in the protein, such as the substrate binding site (e.g. Arg-39) of RNase, the allosteric site (e.g. ÃŽ ²V1) of hemoglobin, and the drug binding sites (e.g. Arg-410) on albumin [27]. The specificity of glycation may be determined by endogenous ligands and the structure of protein especially an amino acid sequence within the protein. The specificity of protein glycation is usually affected by both basic and acidic neighboring groups [28], either via catalysis of Amadori rearrangement (the rate-limiting step of protein glycation), or via effecting pKa of amino group that contributes in enhancing its nucleophilicity and formation kinetics of Schiff bases. This shows that there is a variation in the respective rate and extent of glycation shown by amino groups in the protein. The anionic ligands also catalyze the pote ntial glycation of proteins at specific sites [27]. Exogenous Sources of AGEs The formation of AGEs via Maillard reaction was originally described for physical and chemical changes occurring during heating of food [29]. Beside the natural formation of AGEs inside the body, there are some exogenous sources of increased AGEs including diet enriched with AGEs and smoking. The extent of absorption of AGEs ingested with food is very small [30]. However, there is a strong relationship of AGEs circulating in the human body with the AGEs ingested [31]. It has been investigated that tobacco smoke increases the formation of AGEs on plasma proteins due to containing some products, which produce protein crosslinks and AGE-like fluorescence and mutagenicity [32]. For example, the diarbonyl compounds, glyoxal and metbylglyoxal, are most likely to be present in cigarette smoke that act as mediators of AGE formation and formed by thermal decomposition of existing saccharides. Accordingly, the serum of diabetic smokers reveals enhanced levels of AGEs relative to diabetic non-smokers [33]. Similarly, the smokers are more susceptible to incidence of cataract, cardiovascular and lungs diseases as compared to non-smokers due to smoke-mediated AGEs formation [34]. Toxicity or Pathological Conditions Associated to Glycation and AGEs Formation The AGEs are more prone to proteolysis and degradation as compared to the original proteins. The accumulation of AGEs has toxic biological effects, causing disruption of many cellular processes leading to various pathologies. The AGEs as well as intermediate glycation products such as reactive carbonyls induce the production of free radicals in vitro and in vivo [35, 36] and hence increased oxidative stress [37]. The glycation-mediated free radicals are the major cause of protein fragmentation as well as oxidation of lipids (lipid peroxidation) and nucleic acids [7]. The reactive dicarbonyls have ability to bind with naturally active proteins of diverse physiology via intra- and inter-molecular cross linking resulting in deactivation of enzymes, transcription factors, membrane transporters and signaling components with eventual protein degradation and cytotoxicity [38-40]. The AGEs also bind to cell membrane receptors inducing signal cascades leading to inappropriate gene expressions and cellular activities [18]. The elevated level of AGEs in tissues has a strong correlation with severity of diabetic complications [41, 42]. This is because of modification of enzymatic activity in multiple ways including binding of ligand, change in protein half life, increased membrane permeability, decreased binding ability of insulin to its receptors, increased atherogenicity of LPL and variation in the immunogenicity [43-45]. The main diabetic complications include impaired wound healing and the serious damage and failure of various vital organs such as kidneys (nephropathy), nerves (neuropathy), eyes (cataract, retinopathy), blood vessels (atherosclerosis) and heart (cardiomyopathy) [11, 34, 46, 47]. The AGEs formation is also associated to aging, Alzheimer’s disease and other chronic disorders [17, 10, 48-50]. Natural Biological Defense Mechanism against Glycation and AGEs The human body presents a certain mechanism to inhibit the glycation of protein and resulting AGEs formation. For example, ÃŽ ±-keto-glutaraldehyde dehydrogenase, a liver enzyme, has a capability to inactive 3-deoxyglucosone (3-DG), Arnadori-derived reactive intermediate and hence prevents the generation of AGEs [41]. The other enzymes such as aldose reductase and glyoxylase system (I and II) can catalyze the deglycation of reactive intermediate methylglyoxal into D-lactase [51]. Amadoriases are the group of enzymes found in Aspergillus, which catalyze the deglycation of Amadori products [52]. Some NADPH-dependant exogenous enzymes such as aldose reductase and oxoaldehyde reductase that metabolize ÃŽ ±-dicarbonyls, have the ability to reduce 3-DG and thus regulate the formation of AGEs [53]. Similarly, different plasma amines may reduce AGEs formation through reaction with carbonyl groups of sugar and Amadori compounds [54]. Antioxidants such as vitamin E and vitamin C, provide prote ction against glycation-mediated free radicals, whereas, ceruloplasmin and other transport proteins bind with transition metal ions such as Cu2+, preventing them to take part in glycoxidation reactions or autoxidative glycation [55]. Inhibition of Protein Glycation and AGEs Several attempts have been made earlier to explore pharmacologically active antiglycating agents to prevent or slow down the production of AGEs [56]. The major side effects associated with antiglycation therapy limit the use and necessitate the discovery of new inhibitors of glycation with reduced toxicity and long half life to be implicated for large time span. Currently, two therapeutic strategies are highly successful having great effectiveness against diabetic complications and normal aging; one is the inhibition of formation of AGEs and other is the breaking of already established AGEs cross-linkages [57]. Promising Inhibitors of Glycation with Their Mechanism of Inhibition The antiglycating agents such as aminoguanidine, rutin, antioxidants, aspirin and other AGEs breakers have been examined extensively and received great interest. The structures of some potential antiglycating agents are depicted in Figure 96. Aminoguanidine Aminoguanidine is a derivative of hydrazine that inhibits the generation of AGEs and glucose-derived collagen cross-links during in vitro studies [58]. Aminoguanidine does not act on already formed AGEs but it reacts with reactive Amadori products such as 3-deoxyglucosone preventing additional rearrangements and intermediates crosslinking [59]. In addition, aminoguanidine is a free radical scavenger that contributes in reducing oxidative stress [60]. The treatment of diabetic animal models with aminoguanidine reduces AGEs accumulation, kidney lesions, albuminuria and long-term diabetic complications including retinopathy, nephropathy and neuropathy [61]. Aminoguanidine also exerts positive effect on the speed of nerve conduction [22]. Aminoguanidine therapy is limited by serious toxic effects attributable to high reactivity, subliminal concentrations and rapid renal clearance. The human trials with aminoguanidine experience vasculitis (inflammation of lymph or blood vessel), liver fu nction abnormalities [62] and less frequent flu-like symptoms, nausea and headache [63]. Figure 96. Structures of some potential antiglycating agents Aspirin Acetylsalicylic acid commonly known as aspirin is an analgesic has well known analgesic drug that also shows the preventive action against formation of cataract under diabetic conditions. Aspirin may limit the sugar-mediated formation of Amadori products by acetylation of free amino residues of proteins. Aspirin also stops the crosslinking of tendon in rat tail in vitro through inhibition of glycoxidation. Furthermore, aspirin is a free radical scavenger [64]. However, the use of aspirin is unlikely in controlling late diabetic complications because of some serious gastrointestinal side effects [41]. Rutin Rutin is a common flavonoid of vegetables and fruits that modulates the AGEs generation in vitro. The flavonoids including rutin that contain vicinal dihydroxyl groups have established their significant role as antiglycating agents. The mechanism of inhibition by rutin is suggested to involve the trapping of amino groups in proteins at early stage of glycation, especially in ketoamine formation, by rutin metabolites like keto-quinone intermediates. Rutin has shown significant inhibitory effect against hemoglobin glycation and it is more efficient compared to aminoguanidine [65]. Antioxidnats Since non-enzymatic glycation of protein is significantly accelerated by excessive generation of free radicals, the antioxidants and other free radical scavengers are expected to inhibit the process of glycation [24]. For example, vitamin E has been reported to appreciably reduce the glycation of hemoglobin [66]. The compounds that exhibit both antioxidant and antiglycation properties e.g. aminosalicylic acid, can protect endothelial cells with better efficacy than aminoguanidine against adverse effects of glycation and high glucose levels in vitro [46]. Similarly, carnosine that is a naural antioxidant and antiglycating agent, inhibits sugar-induced cross-linking of proteins by reaction with methylglyoxal and also sequesters metal ions (e.g. copper and zinc). Carnosine has shown its role in the treatment of cataracts and other diseases [67]. The glycation-derived free radicals generation may be reduced by chelation of transition metal ions, which are responsible for monosaccharide a utoxidation. For instance, the metal chelator, diethylenetriamine penta acetic acid has shown the inhibition of glucose autoxidation [68, 69]. AGE-Breakers AGE-breakers are the compounds, which remove AGEs cross-links through breakdown of ÃŽ ±-dicarbonyl bonds in glucose-derived cross-links of proteins [70]. However, the exact mechanism of inhibition for cross-link breaking is unclear so far. N-phenacylthiazolium bromide (PTB) and its chloride form, alagebrium chloride (ALT-711) are the examples of AGE-breakers. It has been demonstrated that the increased arterial stiffness related to diabetes is successfully reversed through a short treatment with AGE-breaker, ALT-711. The cardiovascular stiffness related to normal aging process can also be reduced by ALT-711. For example, the treatment of normal aged dogs with AGE cross-link breaker has shown noticeable decrease in stiffness of left ventricle chamber [71]. The clinical trial studies on diabetic humans, dogs and other animals indicate the potentially promising use of antiglycation therapy in near future to prevent diabetic complications and other diseases related to protein glycation [56].