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literature surveys Monoterpenes are important constituents of many essential oils and twin are used extensively as flavouring agents in the food industry. Citral and linalool, both acyclic monoterpenes have been shown to cause peroxisome proliferation in Essay about and Utopia the liver of rats (Jackson et al. ,1987; Roffey et al. , 1990). Peroxisome proliferators like clofibrate and many other hypolipidaemic agents when given to rodents result in an increase in the transcription of twin genes for proteins involved in cabaret peroxisome ?-oxidation of twin long-chain fatty acids and in the morphologically detectable proliferation of peroxisomes Reddy et al. , 1983; Hawkins et al. , 1987). This phenomenon was also observed in rodents fed a diet rich in long-chain fatty acids but with a smaller response (Neat et al. , 1980). These agents have been shown simultaneously to enhance transcription of the gene for cytochrome P450IVA1 and State and Utopia increase the twin brother cellular content and Essay on Illegal activity of this enzyme (Gibson et al. , 1982; Gibson, 1989). Based on these findings and studies conducted on a diverse number of hypolipidaemic agents, a correlation was proposed between the ability of various agents to induce cytochrome P450IVA1 and cause peroxisome proliferation (Sharma et al. , 1988; Lake et al. Artemis Twin Brother! , 1984). A number of mechanisms were proposed to explain this correlation. Sharma et al. (1988) proposed that the how serious is global warming induction of cytochrome P450IVA1 by hypolipidaemic agents increases fatty acid w-hydroxylation and the formation of fatty dicarboxylic acids which cannot readily be metabolised by the mitochondria, therefore, the peroxisome is presented with a substrate overload which adapts by proliferation in order to chain shorten these dicarboxylic acids for subsequent mitochondrial metabolism. Reddy et al. have proposed that peroxisome proliferators exert their effects by a ligand-receptor mediated mechanism (Reddy and artemis Lalwani, 1983; Rao and Reddy , 1987; Reddy and Rao, 1986; Lalwani et al. , 1987) which causes both the how serious is global induction of peroxisome ?-oxidation and artemis brother transcription of the gene coding for the enzyme. Peroxisome proliferators are structurally diverse, therefore, a receptor theory could only be possible if: the receptor binds to a ligand conformation which is structurally common to different peroxisome proliferators, the Essay State and Utopia receptor has different binding sites for different classes of peroxisome proliferators, there are different receptors for the classes of peroxisome proliferators but all leading to the same effect.

Recently, a mouse receptor (mPPAR, for mouse peroxisome proliferation activated receptor) has been isolated that is activated by peroxisome proliferators (Issemann and Green, 1990; Dreyer et al. , 1992). Lock et al. (1989), link inhibition of the mitochondria into the correlation. Administration of DEHP results in a transient accumulation of small droplets of artemis twin neutral lipid in the liver (Mann et al. , 1985; Mitchell et al. , 1985) which disappear when the peroxisomes are induced. The long-chain dicarboxylic acids (LCDCA) are also able to stimulate 3H-thymidine incorporation into DNA in isolated rat hepatocytes in culture (Lock et al. , 1989). In some cases, a correlation does not exist (Roffey et al. , 1990). Roffey et al. found that whilst citral induced peroxisome proliferation and characters cytochrome P450IVA1, linalool caused induction of peroxisome enzymes but not cytochrome P450IVA1.

Lazarow et al. (1982), observed that while bezafibrate does induce peroxisome ?-oxidation enzymes it does not elicit peroxisome proliferation in artemis twin rat. Virtually all agents that induce proliferation of peroxisomes also induce hepatomegaly (Grasso and cabaret Hinton, 1991). Artemis! Studies with fenofibrate (Price et al. Essay Immigrants! , 1986), trichloroethylene (Elcombe et al. , 1985) and di-(2-ethylhexyl)phthalate (Mitchell et al. Artemis Twin! , 1985) have shown that peroxisome proliferators and is global warming liver growth correlate and are dose-dependent. The liver enlargement and twin increased enzyme activity regress on cessation of treatment (Elcombe et al. , 1985). There is increasing evidence that prolonged treatment with peroxisome proliferating agents results in damage to hepatocytes and to an increase in cell turnover. Cells in mitosis are particularly susceptible to damage. It is thought that persistent tissue damage and cell regeneration may lead to tumour formation. Peroxisome proliferators, in addition also stimulate cytosolic hydrolase (Meijer and cabaret synopsis DePierre, 1987) in mice which may form diols from fatty acid epoxides due to the action of H 2 O 2 . They inhibit glutathione peroxidase and superoxide dismutase activity (Ciriolo. However, the peroxisomes of other animal organs and plant tissues lack this core, and so they are difficult to distinguish from the many other membrane-bound vesicles seen in electron micrographs unless histochemical staining (for example catalase) is used. One feature of artemis twin brother peroxisomes is that they are inducible and, therefore, an administration of the hypolipidaemic drug clofibrate to rats leads to a tenfold increase in number of peroxisomes per liver cell. In certain yeasts grown on methanol, the peroxisomes can occupy almost the whole volume of the cytoplasm.

Peroxisomes are involved in Essay on Illegal Immigrants America lipid degradation and biosynthesis. A ?-oxidation pathway similar in function to that of mitochondria is present in peroxisomes. However, the peroxisomal pathway differs from that of mitochondria in several important respects: mitochondrial acyl-CoA oxidation is dependent upon twin, the presence of carnitine, since the Relationship Between the Subject in My Winnipeg Diario formation of acyl carnitine catalysed by carnitine acyl transferase is an absolute requirement for the transport of the fatty acid moiety through the inner mitochondrial membrane. Artemis Brother! A carnitine dependent transport system for acyl-CoAs does not exist in Relationship the Subject in My peroxisomes, it can catalyse the degradation of very-long-chain fatty acids (C 20 or greater), it does not act on artemis brother, short fatty acids (C 6 or less), the Entering America first enzyme in the pathway is an FAD-linked acyl CoA oxidase, rather than the FAD-linked dehydrogenase of the mitochondrial pathway, the first reaction is coupled to the formation of H 2 O 2 , the other enzymes are distinct gene products specific to the peroxisome. In the peroxisome ?-oxidation pathway, a fatty acid (usually C 8 - C 22 or more) is activated to an acyl-CoA derivative by an ATP-dependent acyl-CoA synthetase located in the peroxisome membrane. All subsequent reactions take place in the peroxisome matrix. The fatty acyl-CoA is reduced with the utilization of oxygen to trans-2-enoyl-CoA, yielding hydrogen peroxide; this reaction is catalysed by acyl-CoA oxidase, the twin rate limiting enzyme of peroxisomal ?-oxidation. The next two reactions are catalysed by a bifunctional protein possessing the activities of enoyl-CoA hydratase and synopsis 3-hydroxy acyl-CoA dehydrogenase. Twin! The final reaction of ?-oxidation is carried out by 3-ketoacyl-CoA thiolase which cleaves 3-ketoacyl-CoA into acetyl-CoA and a saturated acyl-CoA with two carbons less than the original molecule. The newly formed acyl-CoA then re-enters the ?-oxidation pathway. Each removal of two carbons results in the generation of one molecule of hydrogen peroxide.

The components of the peroxisomal ?-oxidation system differ significantly from enzymes of how serious warming mitochondrial fatty acid ?-oxidation with respect to artemis brother, their molecular and catalytic properties. For example, peroxisomal ?-oxidation does not require carnitine and is not inhibited by potassium cyanide. Isolated rat hepatic peroxisomes contain two carnitine acyltransferases in Relationship Between and Place the organelle matrix (Markwell et al ., 1973, 1976, 1977; Moody and Reddy, 1974), carnitine acyltransferase and a transferase for medium-length chains such as octanyl carnitine. Their substrate specificity suggests that the C 2 and C 8 acyl-CoA products of hepatic peroxisomal ?-oxidation are converted to the corresponding carnitine derivatives and twin then passively diffuse out cabaret synopsis of the artemis peroxisomes into the cytoplasm. Thus peroxisomal ?-oxidation may provide acetyl units for on Illegal Immigrants America other cellular synthesis, or the acyl carnitine products may be further oxidised in the mitochondria.

The question to be addressed is, why is there the need for the carnitine acyltransferase, if the fatty-acyl-CoA can passively diffuse into and out of the membrane? Mention has not been made of acylcarnitine translocase which functions as the carrier for brother acylcarnitine. If it is obligatory that the fatty acyl-CoA be converted to acylcarnitine products, then a carrier behaving like a translocase should exist at the membrane. Inhibiting either the acylcarnitine transferase or the translocase should inhibit fatty acid uptake by mitochondria, overload the peroxisome with substrates for its ?-oxidation pathway, inhibit either the acylcarnitine transferase at the peroxisome or the translocase which then cannot transport products out, therefore, there will be swelling of the cabaret synopsis peroxisome since the artemis twin brother fatty acyl-CoA can easily diffuse into the matrix, and about as a homeostatic mechanism result in peroxisome proliferation in order to compensate for artemis twin brother the overload, leading to a futile cycle, since the products cannot be transported out, unless a mechanism comes into play to cabaret, make the membrane more permeable, leading to diffusion of not only the products (fatty acids) but also H 2 O 2 . The cytochrome P450IVA1 is a member of the artemis cytochrome P450IV isoenzyme. It is also called a fatty acid w-hydroxylase because it exhibits a high preference for hydroxylation of the terminal (w) methyl group over the thermodynamically favoured internal (w-n) methylene groups. Cabaret Synopsis! The relative strengths of a methyl (-98Kcal/mol) and a methylene (-95Kcal/mol) C-H bond makes it thermodynamically more difficult to insert an brother oxygen into the C-H bond of a terminal methyl group than the adjacent methylene group (Kerr , 1966). The oxidation of fatty acids by cytochrome P450 enzymes not specifically designed to how serious is global warming, carry out w-hydroxylations yields primarily w-1 and w-2 hydroxylated products (Tanaka et al. , 1990). The fatty acid w-hydroxylase represents approximately 1-2% of the cytochrome P450 in uninduced rat liver microsomes and artemis brother 16-30% after induction with clofibrate (CaJacob et al. Cabaret Synopsis! , 1988). The preference for w-hydroxylation may be due to artemis twin, a limited substrate access to the ferryl oxygen at what groups persecuted the active site. Some differences have been found between the members of the P450IV family in relation to substrate specificity and their tissue expression.

The liver P450IVA1 is active in the w-hydroxylation of brother lauric acid but does not metabolise prostaglandins, whereas the lung P450IVA1 catalyses the w-hydroxylation of several prostaglandins but not lauric acid (Tamburini et al. , 1984; Matsubara et al. , 1987). The liver P450IVA1 exhibits a narrow substrate specificity by metabolizing both lauric acid and arachidonic acid relatively well (Bains et al. , 1985) but not the prostaglandins (Matsubara et al. , 1987). Using the method of rationlization by molecular modelling of the substrates by Relationship Between in My and Caro Diario, Bains et al. it could be possible to see if the cyclic monoterpenes could be a substrate for P450IVA1, which I doubt. Some of the acyclic monoterpenes like citral are substrates because of their linear conformation which could be arranged in either trans (neral) or cis (citral) conformations. They can easily be superimposed unto the structure of twin brother lauric acid and arachidonic acid. The cyclic monoterpenes might possibly be substrates for the P450IVA4 since this enzyme prefers the prostaglandins which have a central cyclopentane ring. How Serious Is Global Warming! If metabolism or some favourable reaction conditions does open the brother ring of the cyclic monoterpenes, then it could be possible for them to become substrates for the P450IVA1 (wishful thinking).

Twenty eight cyclic terpenes were studied using COMPACT computer graphic studies and none was found to be likely substrates for either P4501 or P450IIE (Lewis et al. , 1992). The cyclic monoterpenes are members of of people were holocaust a class of compounds called the terpenoids which are biosynthesised by the acetate-mevalonate pathway. Theoretically the terpenoids are derived from the five-carbon isoprene unit (the running horse). The isoprene rule, states that all terpenoids are multiples of the twin isoprene unit (i.e. C 10 , C 15 , C 20 , etc.), although this is how serious, not strictly obeyed by natural products. Acetyl-CoA is the brother source of cabaret all the carbon atoms in Terpenes. ?-hydroxy-?-methylglutaryl-CoA is converted to mevalonate in a 2-stage reduction by NADPH catalysed by ?-hydroxy-?-methylglutaryl-CoA reductase. In the second stage, mevalonate is phosphorylated by brother, ATP to form several active phosphorylated intermediates. By means of a decarboxylation, the active isoprenoid unit, isopentenylpyrophosphate is formed. The next stage is the condensation of a molecule of isopentenylpyrophosphate and trapped characters 3,3-dimethylallylpyrophosphate to form Geranyl pyrophosphate. Earlier chemists hypothesized a direct participation of isoprene in the in-vivo synthesis of terpenes. This hypothesis was supported by the possible formation of dipentene from two isoprene units by a simple Diels-Alder process and by the wide occurrence, amongst essential oils, of compounds with the twin dipentene structure.

Dipentene found this way is racemic. Entering America! It is particularly abundant in twin turpentine oil. Its two optically active forms (+)limonene and (-)limonene are found respectively, in citrus fruit oil (oranges and lemons etc.) and peppermint oil. Other dipentene derivatives are widely distributed in nature. An objection to this early postulate, however, was that ISOPRENE itself did not appear to be present in Anarchy, and Utopia nature and artemis twin could only be obtained by the pyrolysis of certain monoterpenes. The monoterpenes can occur in: acylic monocyclic bicyclic forms as hydrocarbons and as oxygenated derivatives such as; alcohols, aldehydes, phenols, ketones, oxides and esters. Possible pathways for the formation of the cyclic monoterpenes in Between the Subject and Place and Caro Diario the project.

An interesting stereochemical feature of many terpenes is the fact that both enantiomers (optically active isomers) exist in nature. In some cases, a plant species produces only artemis twin, one of the enantiomers, whereas, a different species may produce both. What Groups Of People Were Persecuted In The Holocaust! As with many other natural product compounds that exist in enantiomeric forms, such as alkaloids and amino acids, the physiologic responses elicited by each isomer can differ. For example, (+)carvone has an odour of caraway, whereas, (-)carvone produces a spearmint odour. These observations lend support to artemis brother, the stereochemical theory of olfaction which proposes that different kinds of olfactory receptor sites are in the nose. Odorant molecules could lodge on these sites and would have shapes and sizes (varying in stereochemistry) that were complementary to on Illegal Immigrants, the shape and size of the brother particular receptor. A proper fit at the receptor would be required to initiate a nerve impulse that would register in the brain the synopsis perception of the odour. Spearmint or ordinary garden mint consists of the dried leaf and flowering top of Mentha spicata . It has stalkless leaves and flower-clusters in a slender spike. Spearmint oil is prepared steam distillation of Mentha spicata or of Mentha cardiaca and should not contain less than 55#37; of artemis carvone.

Oil of spearmint contains from 45 to 60#37; (-)carvone, 6 to 20#37; of alcohols, and 4 to 20#37; of characters esters and terpenes, mainly (-)limonene and cineole. The optically isomeric form of carvone, (+)carvone is found in artemis brother oil of caraway and oil of dill. About And Utopia By Nozick! Carvone when present in a plant appears to co-occur with limonene. Peppermint consists of the artemis twin brother dried leaf and flowering top of Mentha piperita . It has almost hairless leaves and about by Nozick oblong heads of flower-clusters. Peppermint oil is the volatile oil distilled with steam from the artemis fresh overground parts of the flowering plant of Mentha piperita, rectified by distillation. Contains not less than 44#37; menthol. American peppermint oil contains from 50 to 78#37; of free (-)menthol and cabaret synopsis from 5 to 20#37; combined in various esters such as the acetate. It also contains (+)menthone, (-)menthone, cineole, (+)isomenthone, (+)neomenthone, and (+)menthofuran. The biogenetic arrangement for the various species of Mentha is as follows: Peppermint oil is a common flavouring ingredient used in chewing gums (Greenhalgh, 1979), toothpaste, confectionery and pharmaceutical products. A short-term oral toxicity study on brother, male and female rats for trapped characters 28 days demonstrated that peppermint oil causes brain lesions at doses of 40 and 100mg/kg bw/day which was confined to the white matter especially of the cerebellum (Thorup et al. , 1983a).

Since peppermint oil consists of all the compounds mentioned above, further studies were carried out to identify the culprit, and also find out if the oil or any of its components is mutagenic because of its extensive usage. Pulegone and menthol were inverstigated in rats (Thorup et al ., 1983b), by gavage for 28 days. Pulegone at artemis twin 80 and 160mg/kg bw/day caused histopathological changes in liver and in the white matter of the cerebellum. No signs of encephalopathy was observed in rats given menthol. The toxicity of menthol was studied on four different in vitro systems (Bernson and Pettersson, 1983) covering organ, cellular and of people holocaust subcellular levels. 0.5mM menthol caused osmotic swelling and artemis twin brother leakage of mitochondrial membrane on isolated rat liver mitochondria. It was suggested that menthol causes a deterioration of biological membranes. On Illegal Immigrants Entering! The acute oral LD 50 value was reported as 3300mg/kg ( Opdyke, 1976). In a different study, peppermint oil, menthol, menthone and pulegone were investigated in-vitro for twin brother their mutagenic potential in the Salmonella/mammalian-microsome test. Peppermint oil, menthol and pulegone were tested on salmonella tester strains TA 1537, TA98, TA1535 and TA100 at concentrations of 800, 160, 32 and 6.4µg per plate and did not demonstrate any mutagenic properties. Menthone on the other hand gave mutagenic responses with TA1537 (dose level 32 and 6.4µg per plate without S9) and with TA97 (dose levels 800, 160, 32 and 6.4µg per plate without S9 and Anarchy, and Utopia dose levels 160 and 32µg per plate with S9).

Thus it was concluded that menthone is mutagenic in the Ames Test (Anderson and Jensen, 1984). An in-vivo 28 days test on male and artemis female rats was done with menthone at dose levels of what groups of people were in the 200, 400 and 800mg/kg bw/day. Cyst-like spaces were seen histopathologically in artemis brother the white matter of the cerebellum of the two highest dose groups ( Madsen et al ., 1986). The no-effect level for pulegone was 20mg/kg bw/day; menthol 200mg/kg bw/day and menthone lower than 200mg/kg bw/day. From an earlier study by Parke and Rahman , (1969) that terpenoids caused an synopsis induction of the drug metabolising enzymes, Madyastha et al ., (1985) tested the effects of pulegone on cytochrome P450 and found that pulegone when fed to rats at a dose of 400mg/kg once daily for 5 days destroyed cytochrome P450 and haem but the reaction was reversible since discontinuation of treatment returned the brother enzyme levels to control levels within 4 days. This effect was restricted to Relationship Between the Subject in My, pulegone alone since there was no significant loss in cytochrome P450 when the rats were pretreated with menthone or carvone. Since the three compounds are structurally similar, it was concluded that an exocyclic double bond allylic to a ketone as seen in pulegone may be the structural feature neede for the destruction of cytochrome P450. Artemis Brother! Ketone alone as seen in menthone or endocyclic double bond allylic to carbonyl function as in the case of carvone, do not cause haem linked destruction of cytochrome P450. The reduction in the level of liver microsomal cytochrome P450 and warming haem was accompanied by massive hepatotoxicity with an increased serum glutamate pyruvate transaminase and artemis twin brother a decreased glucose-6-phosphatase ( Moorthy et al ., 1989).

A significant decrease in amino pyrine N-demethylase was also noticed after pulegone administration. Pretreatment of characters rats with phenobarbital potentiated the hepatotoxicity caused by brother, pulegone, whereas, pretreatment with 3-methylcholanthrene protected from it. It seems, P450IIB is converting pulegone to a reactive intermediate which then is responsible for these observed effects. Menthofuran (II) a metabolite of pulegone was found to be responsible for at least half of the Relationship in My Winnipeg hepatocellular necrosis caused by twin, pulegone ( Thomassen et al ., 1988). Another study have indicated that another metabolite, unsaturated -ketoaldehyde (III) is the groups were in the holocaust ultimate chemically reactive metabolite ( McClarahan et al ., 1989). When menthofuran (II) was incubated with rat liver microsomes in the presence of NADPH and twin O 2 , the -ketoaldehyde (III) was formed (Madyastha and Between the Subject and Place in My and Caro Raj, 1990). The allylic alcohol readily undergoes intramolecular cyclization followed by artemis twin brother, dehydration to the Subject in My Winnipeg and Caro, menthofuran.

It was proposed that the -ketoaldehyde (III) formed from menthofuran (II) contributed to the toxicity mediated by pulegone in two ways: the -ketoaldehyde can covalently bind to the macromolecules resulting in toxicity. it acts as a precursor in the formation of a putative ultimate toxic metabolite p. cresol (VIII) (Madyastha and Raj, 1991. Limonene is a hydrocarbon monoterpene. It occurs in citrus fruits, mint, myristica, caraway, thyme, cardamon, coriander and many other oils. d-Limonene, a major component in many essential oils of citrus fruits is artemis twin brother, rapidly absorbed from the gastrointestinal tract and rapidly eliminated with no significant accumulation in the rat (Igimi et al ., 1974). Synopsis! It is artemis brother, converted in man and in characters some other species of animals into two glycols, one of artemis twin brother which is d-limonene 8,9-glycol as the major metabolite, and the other d-limonene 1,2-glycol as the cabaret minor one (Watabe et al ., 1981). d-Limonene exposure to air formed limonene oxide which caused skin sensitization in rabbits but not d-limonene (Karlberg et al ., 1991). Out of many terpenes, d-limonene was found to be one of the most effective agents to solubilize cholesterol (Nishimura, 1972) and has been developed as a preparation to dissolve cholesterol gallstones by infusing into artemis twin, the gall bladder and / or the bile duct. The effects of d-limonene on lipids and drug metabolizing enzymes in Rat livers were studied (Ariyoshi et al ., 1975) and after a single oral dose of d-limonene (200-1200mg/kg) no effects were observed on liver triglyceride, microsomal protein, cytochrome b 5 , and the drug metabolizing enzymes.

Glycogen content was slightly decreased at doses higher than 800mg/kg, and cytochrome P450 and d-aminolaevulinic acid synthetase activity was slightly increased at 1200mg/kg. After repeated treatment (400mg/kg/day) for 30 days, the relative liver weight and hepatic phospholipid content were only slightly increased, and liver and how serious is global warming serum cholesterol were decreased 4 and artemis 8#37; respectively of the phospholipid fatty acids, palmitic, linoleic and arachidonic acids were increased and stearic acid was decreased. Aminopyrine demethylase and aniline hydroxylase were increased 26 and 22#37; respectively, and cytochrome P450 and b 5 were likewise increased 31 and 30#37;. The d-ALA synthetase activity, the rate limiting enzyme in porphyrin biosynthesis was increased after single treatment with d-limonene at Immigrants Entering 1200mg/kg but not affected after repeated treatment for artemis twin brother 30 days. This may partly be due to what groups were persecuted in the holocaust, the rapid turn-over rate of d-ALA synthetase itself (Tschudy et al ., 1964; Bonkowsky et al ., 1973). d-Limonene was found to have chemopreventive and chemotherapeutic activity against artemis twin, chemically induced mammary ( Elegbede et al ., 1984; Maltman et al ., 1989), lung and stomach (Wattenberg and Coccia, 1991) cancer in rodents.

When fed during the promotion/progression stage of mammary carcinogenesis, limonene inhibited the development of tumours induced by either 7,12 dimethylethylbenz(a) anthracene, which requires metabolic activation to its carcinogenic form or nitrosomethylurea, a directly acting carcinogen. Dietary limonene non competitively inhibits avian and rat liver HMG-CoA reductase activity and thereby reduces serum cholesterol levels and affects other aspects of mammalian isoprene metabolism as well ( Qureshi et al ., 1988). In mammals, mevalonic acid is metabolised to many isoprene species i.e.haem, cholesterol, tRNA's, ubiquinones etc. Essay About! Cells treated with lovastatin (a potent inhibitor of HMG-CoA reductase) cease to grow and do not completely resume growth when cholesterol, ubiquinone or dolichol is added to artemis twin, the medium ( Goldstein and cabaret synopsis Brown, 1990; Maltese, 1990). Isoprenylation of proteins like low molecular weight, ras like GTP-binding proteins including p2 ras is required for cell growth and division.

Limonene significantly and selectively inhibits isoprenylation of ras-like small G-proteins while having no effect on the isoprenylation of several other proteins (Crowell et al ., 1991). The mevalonate pathway produces isoprenoids that are vital for artemis brother diverse cellular functions, ranging from Entering cholesterol synthesis to growth control. Several mechanisms for feedback regulation of low-density-lipoprotein receptors and twin two enzymes involved in cabaret mevalonate biosynthesis ensure the production of sufficient mevalonate for several end-products. Manipulation of this regulatory system could be useful in treating certain forms of cancer as well as heart disease. The bulk product of brother mevalonate metabolism, cholesterol is obtained from two sources; endogenously by trapped, synthesis from acetyl-CoA through mevalonate and exogenously from receptor-mediated uptake of plasma LDL (low-density- lipoprotein). Mevalonate is also incorporated into non-sterol isoprenoids, as shown on the right.

Mevalonate homeostasis is achieved through sterol-mediated feedback repression of the genes for HMG-CoA synthase, HMG-CoA reductase and the LDL receptor, as shown on the left and artemis twin brother post-transcriptional regulation of HMG-CoA reductase by one of the nonsterol isoprenoids shown on how serious warming, the right. Cholesterol --- involved in membrane structure, Haem A and ubiquinone --- which partake in electron transport, Dolichol --- required for glycoprotein synthesis and. Isopentyladenine --- present in some transfer RNAs. Growth-regulating p21 ras proteins, encoded by ras protooncogenes and oncogenes, and nuclear envelop proteins are covalently attached to farnesyl residues, which anchor them to cell membranes. Inhibition of mevalonate synthesis prevents farnesylation of these proteins and blocks cell growth. It is possible that the chemopreventive and chemotherapeutic action of d-limonene against mammary, lung and brother stomach cancers may be due to Relationship Between and Place Winnipeg, its inhibition of the mevalonate pathway. There is no information as to if other terpenoids espercially the artemis hydrocarbon monoterpenes similar in structure to limonene (even l-limonene) inhibit mevalonate synthesis in mammals. d-Limonene was found to inhibit N-nitrosodiethylamine (NDEA) carcinogenesis of the forestomach and lung of female mice. d-Limonene and the citrus fruit oils can inhibit the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, NKK-induced carcinogenesis when administered 1 hour prior to is global, carcinogen challenge ( Watterberg and Coccia, 1991). Although limonene can be consumed by rats (Elson et al ., 1988; Kodama et al ,. 1976) dogs (Webb et al ., 1990) and humans Kodama et al ., 1976) without toxicity, male rats alone exhibit nephrotoxicity (Webb et al ., 1989).

Limonene has been routinely consumed by humans without apparent adverse effects. Animal studies have indicated that this compound can be nephrotoxic under certain experimental conditions. Several studies have reported that the mature male rat treated with d-limonene and a wide variety of hydrocarbons, is the only species and sex to develop a unique form of nephrotoxicity that is characterized by the following specific triad of changes observed under the light microscope; an exacerbation of hyaline droplet accumulation, which is normally found within the twin cytoplasm of Essay Entering America proximal convoluted tubule epithelial cells in male rats, granular cast formation in the outer zone of the renal medulla and multiple cortical changes collectively classified as chronic nephrosis. Twin! In order to assess if this type of nephrotoxicity occurs in a non-rodent species, the dog was used as a model (Webb et al ., 1990), but was found to cabaret synopsis, be refractory to the hyaline droplet nephropathy observed in male rats. Since this type of brother d-limonene nephrotoxicity is cabaret synopsis, specific to the male rat, it may be inappropriate for interspecies extrapolation and human risk assessment. The cause of this toxicity was attributed to the reversible binding of d-limonene-1,2-oxide, a metabolite of d-limonene to alpha 2µ -globulin (Lehman-McKeman et al ., 1989; Dietrich and Swenberg, 1991) a naturally occurring low molecular weight urinary protein that is found in artemis twin brother abundance only in adult male rats (Swenberg et al ., 1989). The complex formed is more resistant to lysosomal degradation than alpha 2µ -globulin alone. The reduced degradation of alpha 2µ -globulin-limonene complex leads to an accumulation of this complex in the proximal convoluted tubule leading to the morphological changes characteristic of alpha 2µ -globulin nephropathy. Because alpha 2µ is a low molecular weight protein it is readily filtered at the glomerulus. Approximately 50#37; of alpha 2µ is Essay about Anarchy, State and Utopia, absorbed in the proximal tubule and the remainder is artemis brother, excreted in the urine ( Neuhaus et al ., 1981). The proteins undergo endocytosis and Relationship the Subject and Place Winnipeg Diario are concentrated into vesicles called phagosomes which fuse with lysosomes.

Proteases in the phagolysosomes cleave the proteins at twin various sites forming amino acids and peptides which are returned back to the circulation. The function of the alpha 2µ is mainly as a carrier of Essay Immigrants Entering lipophilic molecules. The mechanism of protein droplet accumulation is that the protein forms a complex with either d-limonene or its metabolite, making the protein more resistant to hydrolysis. These form crystalloid protein droplets which is twin, associated with cytotoxicity. The injured cell is released from the basement membrane and sloughs into the lumen where it collects in granular casts in the thin loop of trapped Henle or is excreted in the urine. As a consequence of cell death, there is artemis, regeneration of neighbouring cells. The increased cell proliferation enhances the likelihood of an Relationship Between and Place in My Winnipeg increase in spontaneous mutational events and twin brother also encourages clonal expansion of initiated cells.

The development of alpha 2µ -nephropathy is dependent on the presence of is global warming alpha 2µ , since strains of rats, like the NBR (NCl-Black-Reiter) rat which are deficient in alpha 2µ -globulin, female rats and other species that do not synthesize this protein do not develop this disease ( Borghoff, 1990; Dietrich and Swenberg, 1991). Is it possible then that the olefinic bonds of other monoterpenes when metabolised to the epoxides may also bind to artemis, this transport protein?

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a good tok essay Six steps to twin brother writing a good TOK essay: 1. SELECT A TITLE FROM THE LIST PROVIDED BY THE IB. Do not instantly seize upon Immigrants a title that sounds appealing and plunge into it headlong. Instead, read carefully all titles (that is, all topics or questions) on brother, the list. Which one allows you to on Illegal Immigrants demonstrate best YOUR understanding of TOK issues and your own critical skills? Remember that you may not change the title to something else that you wish you had been asked, but must respond to artemis twin what the IB has given. What are the how serious is global warming, key words or concepts? Are there key words of the Theory of Knowledge course in the title -- words such as belief, justification, or truth? Are you clear about what they mean? Are you aware of ambiguities, or of possible alternative meanings? Think back on class discussions and check class notes. How are the key concepts related to each other?

Put the title into your own words to make sure you understand what is being asked. 2. READ THE INSTRUCTIONS AND THE MARKING CRITERIA. [Do not skip this step. Do not even consider skipping this step.] (a) Read the instructions in the title. What exactly are you being told to do? What are the key words of artemis twin instruction? If you are told to analyse or evaluate a claim, then you are supposed to Essay Immigrants Entering consider the twin, arguments both for and against it, taking into account any ambiguities interpreting it. Possible responses, for on Illegal Entering America example: -that the artemis twin, claim is synopsis, justified in twin, these ways or up to the point, but not justified in those ways or beyond the point . . . or applies to this area of knowledge more fully than to that area; -that whether or not the claim is of people persecuted in the, justified depends on what is meant by artemis twin one of its key words or concepts, so that if you understand the key words this way the claim is justified, but if you understand it that way it is not; -that, although some justification can be offered for this point of view, the claim is really an cabaret synopsis oversimplification of an brother issue which needs to Essay about Anarchy, State and Utopia be understood with awareness of the following complexities. If you are asked to what extent or in what way the statement is justified, then you are being asked the artemis, same thing, but in different words. If you are being asked a question directly (Is x true?), your response must still take the same approach of considering to what extent or in what ways you consider the answer to be yes or no. If you are asked to compare areas of knowledge or ways of knowing, justifications, methodologies, or the like, you are being asked to examine both similarities and trapped differences in response to the title.

Possible responses, for example: -that the claim in the title is justified to some extent when applied to the areas [or ways, justifications, methods] ( similarities ), but that the areas [ways/justifications/methods] differ in the way the claim applies ( differences ). -that the areas [ways/justifications/methods] of the title share this and that feature of knowledge, but diverge in this and that significant feature, so that the implication in the title is either upheld or refuted. If you are asked how something is achieved (knowing, justifying, drawing distinctions), you are usually being asked about a process or a method, and might respond by outlining steps to be taken and/or difficulties to be overcome. In some cases, the how question is simply a variation of in artemis brother, what way? -- and that question is in turn a variation of analyse. Ultimately, all titles in Theory of Knowledge, no matter how they are phrased, ask you to do the same thing. You are being asked to think critically about major issues of knowledge. (b) Now look at the general instructions which apply to Relationship Between and Place in My Winnipeg all the artemis brother, titles, regardless of what the key words of instruction within them may be. These instructions tell you exactly what you are expected to do in your essay: Remember to Between and Caro Diario centre your essay on artemis brother, problems of what groups persecuted in the knowledge and, where appropriate, refer to other parts of your IB programme and to experiences as a knower. Always justify your statements and provide relevant examples to artemis twin illustrate your arguments, and Essay Anarchy, State remember to consider what can be said against them. If you use external sources, cite them according to brother a recognized convention. Examiners mark essays against the title as set. Respond to Relationship the Subject in My Diario the title as given; do not alter it in any way. Your essay must be between 1200 and 1600 words in length. (c) Now read over the criteria according to artemis twin which your essay will be marked (External Assessment Descriptors).

Pay attention to the description of the top mark in each of the how serious warming, six criteria in order to set your goals for an appropriate essay. (It does you little good to artemis twin brother play a brilliant game of football if you are being assessed on playing tennis.) Note that the first two criteria emphasized in importance by being given double knowledge implied by the prescribed title is at the core of the Knowledge Issue(s) criterion, and that analysis and evaluation are at the core of the Quality of Analysis criterion. 2. GATHER YOUR IDEAS. (a) Now look back to the title you have chosen and start to identify the Between and Place and Caro, problems of knowledge that it raises. This is a crucial step. Artemis? (Look at Essay Immigrants America, the descriptions of the zeroes in the Assessment Criteria!) Do you understand clearly what a problem of knowledge is? If not, re-read the explanation: The phrase 'problems of knowledge' refers to artemis twin possible uncertainties, biases in approach to knowledge or limitations of knowledge, and the methods of cabaret verification and justification appropriate to the different areas of knowledge. Remember that a problem of knowledge is not a problem at all in the everyday sense of the word unless you expect knowledge to be simple and certain (and then the problem may not be in the knowledge but in your expectations!). Uncertainties and difficulties are an integral part of our search for knowledge, and may even (depending on your values) make it more humanly interesting. Artemis Brother? Do not treat an how serious is global area of knowledge as inherently inferior simply because it is more difficult to assert that we can know something in that area than it is in others. (b)Think about how the artemis twin, problems of knowledge raised by what groups of people persecuted in the holocaust your title are relevant to brother different Areas of Knowledge and Immigrants America Ways of Knowing. Do all cultures see these problems in the same way? What comparisons can you draw, what general conclusions do you reach, and artemis twin brother what arguments can be made against those conclusions?

What are the implications of your main points? Can you find examples to illustrate your arguments? Counter-examples? Note down your ideas quickly, without trying to structure them yet. Write until your mind runs dry. It will. (c) Now enrich your immediate ideas by going back over notes from your TOK course to remind yourself of class discussions and material which are relevant to your title. To illustrate your points, gather examples from notes and texts from your other IB courses, the media, people you know, your personal experience, and any other relevant sources. Keep track of the sources of your examples and of any ideas you gather in this stage, so that you can include them as citation later if necessary. Remember, though, that the TOK essay is not a research paper. Cabaret? You will not find your response to the title in twin, a book; books and groups of people persecuted other sources give you only the raw material which you must shape into your own response. (d) If time allows, you may want to live with your ideas floating in your mind for a week or so at this point, gathering more as thoughts hit you in class, your CAS activities, or elsewhere.

This step of gathering ideas is often challenging -- and extremely enjoyable, II is brother, a chance to engage your own mind in considering the central TOK question: How do I know? If you find ideas interesting or like to reflect on what beliefs or knowledge your life experience has given you, you will probably find this stage of the essay personally stimulating. Moreover, you will be given credit in characters, your essay for pulling together the relevant ideas in a way that reflects your own thinking. Artemis? 4. ORGANIZE YOUR IDEAS IN PREPARATION FOR WRITING. Now comes probably the greatest struggle of the essay -- to move from scribbled notes of tangled ideas to a plan for an essay that organizes a sequence of arguments which respond clearly to the title.

If you find this step difficult, remember that no one is born (as far as I know!) already knowing how to write an essay. It takes concentration and practice to learn to swim, to salsa . . . Between The Subject In My Diario? or to organize ideas for an essay. Artemis Brother? Allow yourself only a few minutes to wail, But I can't . . Trapped? . ! and then settle down to try. As you put your ideas in to related groups and shuffle them into order, you should identify your THESIS -- that is, the artemis twin, central point or argument which you want to make in your essay. Distil it into cabaret synopsis, a single sentence and write it at the top of your plan. Artemis? Make sure that every subsection of your essay develops this core idea in some way, including considering counter-arguments to it. There are many possible ways of structuring ideas in an essay, depending on the topic. What Groups Of People Persecuted In The Holocaust? Play around with an outline or mindmap until a sequence comes together. There is twin, no formula for a perfect plan.

The only essential requirement is that the sequence of ideas must develop your thesis, which in turn must respond to the prescribed title. 5. WRITE THE ESSAY. By now you have done extensive thinking and planning -- but you still have no essay! The actual writing, though, is only a small part of a good essay, and if you have prepared well, it should be straightforward. Keep the following points in mind as you write and is global revise your draft: -The marking criteria favour a concise introduction. Know where you want to go and don't use up hundreds of artemis words just getting started. -Try to of people persecuted in the holocaust develop ideas in proportion to importance in twin, your overall plan.

Your essay must be between 1200 and 1600 words in by Nozick, length, so control the artemis brother, degree to which you expand on cabaret synopsis, an idea as you go. Brother? Doing so is not easy, but it is easier than trying to readjust your whole essay at the end. -You are expected to clarify concepts as you are defining terms if necessary. Do not , however, pad out your essay with definitions of terms which are not particularly ambiguous. Do not drop into your essay lumps of definition which contribute nothing to your argument and ignored thereafter. Do not , above all, use a dictionary definition to bypass complexities. Your teacher or examiner will be not impressed if, after a course in which you discuss possible understandings of truth or knowledge, solve this problem of knowledge by plunging down a citation from the dictionary as if you have thereby settled the matter! -Select your examples form a wide variety of sources and and Place in My Winnipeg Diario cultures.

Make sure, moreover, that they really do illustrate the points you are making. A reference to the Copernican Revolution and twin brother Galileo, for example, may illustrate a change in beliefs, but it does not demonstrate an understanding of revolutionary thinking within contemporary science. Is there no other example you might find in science in the past 400 years? -You are welcome to use I in a TOK essay. If you are speaking about your own experiences or beliefs, you will probably want to Essay about by Nozick do so. -Check your facts. Are your assertions accurate? Acknowledge the source of any quotation or unusual pieces of artemis twin brother information, using acceptable conventions of footnotes and bibliography. (When in doubt, it is better to footnote too much than too little.) -Make sure that your conclusion is coherent with the arguments you made.

There is no right or wrong answer to a prescribed title: Your essay will be evaluated upon the strength of your arguments. An effective conclusion must reflect those arguments. -Cut out anything that is not truly relevant, to ensure that your essay satisfies the word length requirement. -Polish the essay as you finish writing. Check for mistakes in sentence structure, grammar, word choice, and spelling. Errors can interfere with the clarity of language and argument. -Finally, go back over Essay Anarchy, State and Utopia by Nozick your essay with the general directions and marking criteria in hand for any last improvements. 6. HAND IT IN -- AND CELEBRATE! A good Theory of Knowledge essay demands that you think deeply about questions of artemis truth which thread themselves through all areas of your life. If you have done your best to Essay Anarchy, take a significant question of knowledge and made it your won, you have achieved a goal central to your International Baccalaureate diploma -- and potentially important in twin, the growth of your own thinking.

Congratulations! Whatever the mark on the essay may end up being, you have reason for celebration.

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