Classification According To Maturity Biology Essay

Classification According To Maturity Biology Essay INTRODUCTION The human eye is very nearly spherical, with a diameter of approximately 24 mm (nearly one inch). It consists of three concentric layers, each with its own characteristic appearance, structure and functions. From outermost to innermost, the three layers are the sclera, which protects the eyeball; the choroid, which nourishes the eyeball; and the retina, which detects light and initiates neural messages bound for the brain. The eye is partitioned into two chambers, a small anterior chamber and a larger vitreous chamber. Thus the basic layout consists of three concentric layers, two chambers, iris, pupil and the lens (Ross and wilson, 2001). Fig.1 Anatomy of the eye C:UsersDHINESHDesktopUntitled1.png The Lens One of very important optical element of the eye, the crystalline lens, lies right behind the iris. The lens takes its name from its resemblance to a lentil, or bean. In adults, the lens is shaped about 9 mm in diameter and 4 mm in thickness. The lens consists of three distinct parts: an elastic covering, or capsule; an epithelial layer just inside the capsule; and the lens itself. The thin, elastic capsule around the lens has two jobs. First, it moderates the flow of aqueous humor into the lens, helping the lens retain its transparency to light. Second, the elastic capsule moulds the shape of the lens varying its flatness and, thereby, the lens optical power. This variant in optical power is called accommodation. Lens grows throughout the life span; the outer, epithelial layer of lens continues to produce protein fibres that are added to the surface of the lens. Consequently, those protein fibres nearest the centre of the lens are the oldest (some were present at birth), whereas the fibres on the outside are the youngest. Between birth and 90 years of age, the lens quadruples in thickness and attains a weight of 250 mg. In the centre of the lens, the old fibres become more densely packed, producing sclerosis, or hardening, of the lens (Paterson, 1979). For good vision, the lens must be transparent and light must be able to pass through it easily, without loss or deviation. Like the cornea, this transparency depends on the material out of which the lens is made. Of all the bodys parts, the lens has the highest percentage of protein, and its protein fibres are lined up parallel to one another, maximizing the lens transparency to light. Anything that disturbs this alignment such as excess fluid inside the lens reduces its transparency. An opacity (or reduced transparency) of the lens is called a cataract. While some cataracts are minor, barely reducing the transmission of light, others undermine vision to the extent of blindness (Kyselova, 2004). Cataract Cataract is the opacification and crystalline formation of eye lens, associated with the breakdown of the eye lens micro-architecture, which interferes with the transmission of light onto the retina. Several biochemical processes for example, calcium deposition, oxidative stress, phase transition, altered epithelial metabolism, crystalline precipitation, calpain-induced proteolysis and cytoskeletal loss takes place during the development of cataract (Moghaddam, 2005). Fig.2 Normal, clear lens Fig.3 Lens clouded by cataract C:UsersDHINESHDesktopUntitled.png Fig.4 Etiology of cataract (Jacob, 1999) C:UsersDHINESHDesktopUntitled.png TYPES OF CATARACT A. Acquired cataract 1. Age related cataract a) Morphological classification i) Subcapsular cataract Anterior subcapsular cataract mainly associated with fibrous metaplasia of the epithelium present below the lens capsule. Posterior subcapsular cataract lies just in front of the posterior capsule and a clear vacuolated, granular or plaque-like appearance. Near vision is also most often impaired more than distant vision. ii) Nuclear cataract usually begins as an amplification of the changes most often seen with normal aging lens nucleus. It is often related with increased spherical aberration and also with an increased refractive index leading to myopia. Some elderly patients may consequently be capable to read yet again without spectacles. iii) Cortical cataract may be associated with the anterior, posterior or equatorial cortex. The opacities begin as clefts and vacuoles between lens fibres because of hydration of the cortex. Both cortical and subcapsular cataracts are white on oblique illumination and show black colouration, silhouetted against the red reflex, on retroillumination. b) Classification according to maturity i) An immature cataract means partially opaque lens. ii) A mature cataract means completely opaque lens. iii) A hypermature cataract means the leakage of water from the lens it leads to wrinkled and shrunken anterior capsule. iv) A morgagnian cataract means the total liquefication of lens cortex like hypermature cataract and it allows the lens nucleus to shrink inferiorly (Hejtmancik, 2004). 2. Presenile cataract Cataract may develop early in the following conditions, a) Diabetes mellitus Typically diabetic cataract is rare. In hyperglycemic conditions, the aqueous humor secretes high level of glucose and this excess of glucose diffuses into the lens. Aldosereductase metabolises glucose to sorbitol, which then accumulates in the lens, resulting in secondary osmotic over hydration of the lens substance. Nuclear opacities are common and tend to grow rapidly. Premature dystrophy may be seen due to decreased pliability of the lens. b) Myotonic dystrophy About 90% of patients, in third decade have fine cortical iridescent opacities, which evolve into visually disabling stellate posterior subcapsular cataract by the fifth decade. c) Atopic dertmatitis About 10% of patients with severe atopic dermatitis develop cataracts in the second to fourth decades. The opacities are often bilateral and may mature quickly. Shield like anterior subcapsular plaque which wrinkles the anterior capsule is characteristic. Posterior subcapsular opacities resembling a complicated cataract may also occur. 3. Traumatic cataract Trauma is the major risk factor for unilateral cataract in individuals. The following risk factors are involved in traumatic cataract, a) Direct penetrating injury to the lens. b) Concussion may cause an imprinting of iris colour on the anterior lens capsule (Vossius ring) as flower shaped cortical opacities (rosette cataract). c) Electric shock and lightening are rare causes. d) Ionizing radiation. e) Infrared radiation- In glassblowers, the IR rays causes exfoliation of the lens capsule which results in thickening of the superficial portion of the capsule and it further splits the deeper layer and protrudes into the anterior chamber. B. Drug induced cataract a) Steroidal drugs may induce cataract. Initially the lens opacities formed in posterior subcapsular region spreads into the anterior region. The relation between dose, duration of administration and the cataract development is unclear. It is understood that children may be more at risk to the cataractogenic effects of systemic steroids and genetic susceptibility may also be of significance. Patients who develop lens physiological changes should have their dose decreased to a minimum, reliable with control of the underlying disease, and if feasible be considered for alternate drug therapy. Premature opacities may regress if therapy is discontinued, alternatively progression may occur despite withdrawn and warrant surgical intervention. b) Chlorpromazine may cause the deposit of innocuous fine, stellate, yellowish brown granules on the anterior lens capsule within the papillary area. The deposition of granular material may accumulate on the corneal endothelium and deep stroma. Both lenticular and corneal deposits are dose -related and irreversible. In very high doses (>2400 mg daily), this drug may cause retinotoxicity. c) Lens opacities may occur due to the irregular use of Busulphan (Myleran) for the treatment of chronic myeloid leukaemia. d) Amiodarone, used in the treatment of cardiac arrhythmias, causes visually inconsequential anterior subcapsular lens deposits in about 50% of patients on moderate to high doses. e) Gold used in the treatment of rheumatoid arthritis, causes harmless anterior capsular deposits in about 50% of patients on treatment for more than 3 years. f) Allopurinol, used in the treatment of hyperuricaemia and chronic gout, increases the risk of cataract formation in elderly patients, if the cumulative does exceeds 400 g or duration of administration exceeds 3 years. C. Secondary cataract A secondary (complicated) cataract grows as a result of some other primary ocular diseases. i. Chronic anterior uveitis is the main cause of secondary cataract. The earliest finding is a polychromatic lustre at the posterior pole of the lens which may not progress if the uveitis is arrested. If the inflammation persists, posterior and anterior opacities developed may progress to maturity. ii. Acute congestive angle closure glaucoma may cause small grey white anterior, subcapsular or capsular opacities within the papillary area. a. Myopia (Pathological) is linked with posterior subcapsular lens opacities and early-onset nuclear sclerosis, which may ironically increase the myopic refractive error. Simple myopia, however, is not associated with such cataract formation. b. Hereditary dystrophies such as retinitis pigmentosa, gyrate atrophy, leper congenital amaurosis and stickler syndrome may be associated with posterior subcapsular lens opacities. Cataract surgery may occasionally improve visual acuity even in the presence of severe retinal changes (Kanski et al., 2003). Free radicals involved in cataractogenesis Free radicals may be formed either by the reduction of molecules by electron transfer or by the haemolytic cleavage of covalent bond. Both these reactions may be enzymatic or non-enzymatic. Due to the presence of an odd unpaired electron in its outermost orbital, these free radicals are unstable and readily react with neighbourhood molecules and extract electrons from them, converting the attacked molecule into a few radical, which in turn attacks another molecule generating more free radicals and so on. This enables free radicals to induce chain reactions that may be thousands of events long. A free radical reaction is terminated by reaction between two free radicals or neutralization by antioxidants (Uday et al., 1999). Fig.5 Pathways of ROS formation C:UsersDHINESHDesktopUntitled 3.png Generation of free radicals Biological free radicals include reactive oxygen species, reactive nitrogen species, reactive sulphur species, free radicals obtained form xenobiotics. a) Superoxide anion radical (O2.-) It is generated from NADPH oxidase and from mitochondria. i) NADPH oxidase is present in the lysosomal cell membranes. It steals electron from O2 resulting in the formation superoxide anion radical (O ·2-). It is converted to hydrogen peroxide and is a spontaneous reaction which is known as respiratory burst. This hydrogen peroxide may react with the chlorine in the presence of myeloperoxidase to form hypochlorous acid or it may produce hydroxyl radicals, by the Fenton reaction which uses the metal ion Fe3+. ii) From Mitochondria: Ubiquionone, which is a terminal acceptor of electron, is converted to semiquinone (free radical). By reacting with O2, it forms (O ·2-) super oxide radical with H2O2, it produce hydroxyl radical ion. b) Hydrogen Peroxide H2O2 SOD It is formed by the dismutation of superoxide by the enzyme superoxide dismutase. O · 2 + O ·2 Hydrogen peroxide is generated from i) Aminoacid oxidases: Flavin is a co-enzyme required for the oxidative deamination of amino acid. The reduced flavin attacks molecular oxygen to form hydrogen peroxide. ii) Xanthine oxidase: Xanthine oxidase catalyses the conversion of hypoxanthine to xanthine and hydrogen peroxide is released from molecular oxygen. iii) Peroxisomes: Peroxisomes is the site of  Ã‚ ¢-oxidation of fatty acids.  Ã‚ ¢- Oxidation of the fatty acids is catalysed by acetyl co-enzyme-A dehydrogenase. During this process, a co-enzyme called FAD which donates two electrons gets reduced to FADH2. Again it is converted to FAD. During that process it gives out O2 and H2O (Kovaceva et al., 2007). c) Hydroperoxyl radical They are highly lipophillic and capable of initiating lipid peroxidation. Lipid peroxidation Lipid peroxidation is a self- perpetuating common process and involves the conversion of lipid components from cell organelles into lipid peroxides resulting in the formation of a pigment known as lipofuscin. Lysosomic reactive oxygen species are formed as a result of complex oxidative chain reactions in mitochondria during energy production. H2O2 formed in smaller amounts by mitochondria pass through walls of lysosome and react with Fe (II) in a reaction known as Fenton reaction to form potent hydroxyl radicals which cause lipid peroxidation (Halliwell, 2001). Malondialdehyde is the major reactive aldehyde resulting from the peroxidation of biological membrane polyunsaturated fatty acids (PUFA). MDA, a secondary product of LPO, is used as an indicator of tissue damage by a series of chain reactions. MDA is a by-product of prostaglandin biosynthesis. It reacts with thiobarbituric acid and produces a red-coloured product. MDA is a mutagenic and genotoxic agent that may contribute to d evelopment of human cancer. Ca2+ ATPase The Ca2+ ATPase is a transport protein in the cells that serves to eliminate calcium (Ca2+) from the cell. It is essential for maintaining the amount of Ca2+ within the cells. Based upon the electrochemical gradient calcium ion enter into the cells through the trans membrane. This process is important for the cell signalling by which it lowers calcium level. Thus it is necessary for the cell to utilize ion pumps to remove the Ca2+. The Ca2+ ATPase is expressed in a variety of tissues, together with the brain (Hightower et al., 1982). IN VIVO MODELS IN CATARACT (Gupta, 2004) 1. Sugar cataract i) Galactose induced cataract The changes associated with galactose cataractogenesis include the initial reduction of galactose into dulcitol through intervention of aldose reductase with NADPH as a co-factor. Accumulation of dulcitol in the lens, (since it is not metabolized) creates cellular hypertonicity associated with and/or followed by a cascade of events, which includes an influx of water, swelling of the lens fibres, epithelial cell edema, damage of plasma membrane, compromise of cellular permeability, a drop in myinositol level, a reduction in Na+ K+ ATPase activity an influx of Na+ and Cl- and an efflux of K+ and the loss of glutathione and aminoacids. These are the morphological, biochemical, enzymatic and molecular alterations in the lens associated with galactose cataracts. ii) Alloxan induced cataract Alloxan is a cyclic urea analog which is highly reactive molecule that is readily reduced to dialuric acid, which is then auto oxidized back to alloxan resulting in the formation of hydroxyl radical, O2.-, including H2O2 (hydrogen peroxide). However, the other mechanism reveals the ability of alloxan to react with protein sulfhydryl groups on hexokinase, a signal recognition enzyme in the pancreatic ÃŽ ²-cells that couples changes in the blood glucose concentration to the rate of insulin secretion. By this mechanism, inhibition of glucokinase and other SH containing membrane proteins on the ÃŽ ²-cells would eventually result in cell necrosis within minutes. iii) Streptozocin induced cataract Diabetes related cataractogenic changes are seen in the animals injected with streptozocin. This streptozocin initiates cytotoxic action in pancreatic ÃŽ ² cells because sreptozocin contain glucose molecule and highly reactive nitrosourea side chain. It binds to the membrane receptor to generate structural damage. At the intracellular level three major phenomena are responsible for ÃŽ ² cell death, i) Methylation ii) Free radical production iii) Formation of Nitric oxide (NO). The damage caused to ÃŽ ² cells alters the sugar metabolism leading to diabetes. 2. Selenite induced cataract Selenite cataract resembles human cataract in many ways such as insoluble protein, vesicle formation, increased calcium, reduced glutathione (GSH) and decreased water-soluble proteins. However, selenite cataract shows no high molecular weight protein aggregation or increased disulfide formation and is dominated by rapid calpain-induced proteolytic precipitation, while senile cataracts may be produced by prolonged oxidative stress. 3. Naphthalene induced cataract Naphthalene is oxidized in the liver initially to an epoxide and then it converted into naphthalene dihydrodiol. This stable component is converted enzymatically into dihydroxynaphthalene to reaching the eye. Being unstable at physiological pH, 1, 2- dihydroxynaphthalene and spontaneously autooxidises to 1, 2- naphthoquinone and H2O2 . It alkylates proteins, glutathione and aminoacids and generates free radicals. 4. Glucocorticoid induced cataract Glucocorticoid cataract results in the formation of steroid- adduct protein, induction of transglutaminase and reduction of ATPase activity may lead to cataract. Steroid cataracts are produced by the activities of glucocorthicoids and progressed by way of production of oxidative stress similar to other types of cataract. 5. L- Buthionine S, R- Sulfoximine (BSO) induced cataract Glutathione is present in mammalian lens in high concentrations and is involved in the protection of lens against oxidation. In most of the cataracts the decrease in its level is observed. 6. Smoke induced cataract Cigarette smoke contains trace and heavy metals. The increased metal contents in lens cause lens damage by the mechanism of oxidative stress-forming oxygen radicals, via metal catalyzed Fenton Reaction. In other words cigarette smoke is associated with the accumulation of iron and calcium. 7. UV radiation induced cataract Epidemiological studies have exposed a link between exposure to UV radiation in sunlight and development of cataract. Experimental studies confirm that ultraviolet (UV) radiation induces cataract. There is, however, a lack of data on the age dependence in experimental UV radiation-induced cataract. 8. Microwave induced cataract Microwave radiation has been reported to produce posterior subcapsular and cortical cataracts in rabbits and dogs within a short span of time. 9. Transforming Growth Factor ÃŽ ² (TNFB) induced cataract TGFB is induced by injecting approximately 60 ng TGFB into the vitreous. TGFB induce lens epithelial cells to undergo molecular modify and abnormal morphologic that mimic the changes observed in human posterior subcapsular and cortical cataract (Gupta, 2004). IN VITRO MODELS IN CATARACT (Gupta, 2004) Induction of cataract in isolated animal lenses maintained in organ culture has become a convenient, quick and appropriate method for testing the anticataract efficacy of an agent. Opacification of lens is induced by generating oxidative stress/ hyperglycemic/ hypergalactosemic conditions around the lens by supplementing the culture medium with a variety of exogenous substances. 1. Oxidative stress induced cataract Oxidative mechanisms play an important role in many biological phenomena including cataract formation. Formation of the superoxide radical in the aqueous humor, lens and its derivatization to other potent oxidants may be responsible for initiating various toxic biochemical reactions leading to the progress of cataract. In vitro such cataracts are induced by agents like selenium, H2O2, photosensitizers and enzyme xanthine oxidase. 2. Selenite induced cataract In vitro cataract is produced by supplementing the tissue culture medium with 25 to 100 mM sodium selenite in which freshly enucleated transparent rat lenses are incubated at 370C. This causes membrane damage and faint cortical opacities within 24 h. 3. Photochemically induced cataract Riboflavin, a photosensitizer, is supplemented in the culture medium to induce cataract in cultured lenses. Micro quantities (4-200  Ã‚ ­M) of riboflavin lead to severe physiological damage and opacification within 24 h after exposure to light. The initial membrane damage is evidenced by a disturbed cation ratio between lens water and the medium of incubation. Riboflavin on getting photosensitized generates free radicals in a sequence of reactions. Lenses are maintained in organ culture for 24 to 72 h. The lenses are divided into four groups and incubated in the dark and light both in presence and absence of riboflavin. The lenses are exposed to light with two 15-w daylight fluorescent lamp placed at 8 inches above the cluster plate. The culture medium is replaced every 24 h. Riboflavin shows no effect on the lens in the absence of light, and light without riboflavin has no significant effect. opacification starts in the equatorial zone and gradually extends towards the centre of the lens. 4. Enzymatically induced cataract Supplementation of culture medium with 1 mM xanthine and 0.1 unit xanthine oxidase, which act as substrate and enzyme respectively, leads to generation of superoxide radical. The lenses suffer severe oxidative damage and turn opaque within 24 h when incubated in culture medium at 370C. 5. Hydrogen peroxide induced cataract Incubation of lenses in medium containing 50-500  Ã‚ ­M H2O2 and it produce cataract. Opacification starts in the equatorial region within 24 h. The entire superficial cortex becomes opaque by 96 h. Due to the high instability of H2O2, the medium is changed every 2 h during the first eight hours. 6. Sugar induced cataract Transparent and undamaged lenses are incubated in a basis culture medium with fetal calf serum for 24 to 48 h. In the control group the medium is supplemented with glucose (30 mM), lenses develop opacity in the subcapsular region on day 1 and in the central region on day 2. Biochemical analyses reveal raised polyol, malondialdehyde levels and water content, and decreased glutathione levels in these lenses. 7. Steroid induced cataract Steroid-induced experimental cataract is produced in vitro by incubating the transparent lenses in the medium containing methyl prednisolone (1.5 mg/ml). The test agent and methyl prednisolone added alone and together to the medium form drug control, control and treated groups respectively. Early cataract around the equator is produced within 24 h of incubation. Incubation period may be extended to 48 h for dense opacity. Morphological changes and modulation in biochemical parameters between the groups may show the potential of the anticataract agent. 8. Naphthalene induced cataract TC-199 medium is used for the preincubation of lens. Stock solution of napthalene dihydrodiol is prepared in 20% ethanol at 2.5-10-3 M concentration. The stock solution is diluted 1:100 to obtain the final concentration of 25.5 -10-5 M. The final osmolarity of the solution is 295-300 m Osmol. Rat lenses are incubated in TC-199 medium containing napthalene metabolite solution. Medium is renewed daily till 72 h. Lenses remain clear during the initial 24 h but from shell-like opacity around the nucleus by 48 h. Opacification becomes more peripheral and widespread after 72 h. At 48 h, under such conditions of incubation, development of opacity mimics the in vivo napthalene cataract. Naphthalene is oxidized in the liver first to an epoxide and then is altered into naphthalene dihydrodiol. This stable component on reaching the eye gets converted enzymatically to dihydroxynaphthalene. Being unstable at physiological pH, 1,2 dihydroxynapthalene sponaneously auto oxidises to 1,2 naphthoquinon e and H2O2. It alkylates proteins glutathione and amino acids and generates free radicals. There is a loss of protein thiol in this reaction and the products are less easily digestible by pancreatin than normal lens protein (Rees and Pirie, 1967). 9. Ca2+ induced cataract In this model, the control group contains the lenses incubated in the medium enriched with 20 mM Ca2+ or 1x 10-2 mM A23187 calcium ionopore. The treatment group lenses are cultured in the calcium and the test drug-containing medium. Incubation period can range from 24-72 h (Gupta, 2004). Fig.6 Mechanism of action of glucose-induced cataract C:UsersDHINESHDesktopUntitled 7.png Under physiological conditions, glucose is metabolized through the glycolytic pathway. An excess amount of glucose is converted to sorbitol by enzyme aldose reductase via polyol pathway. The glucose conversion into sorbitol by utilizing NADPH results in the reduction of NADPH/NADP+. Moreover, sorbitol undergoes oxidation to fructose by using sorbitol dehydrogenase (SD). Sorbitol does not easily cross cell membrane. Intra lenticular accumulation of sorbitol, leads to lens damage (Kyselova, 2004). Fig.7 Biomorphological changes during cataract formation C:UsersDHINESHDesktopUntitled 66.png As, the lens starts to swell in response to the hyper osmotic effects of polyol accumulation, membrane permeability changes resulting in an increase in lenticular sodium and decrease in the levels of lenticular potassium, reduced glutathione, ATP and free amino acids. The overall antioxidant status of the lens decreases because of depletion of GSH (Kyselova, 2004). Mechanism of action of calcium-induced cataract Fig.8 Calcium transport pathway Increased levels of lenticular calcium activate calcium dependent proteases. The activated proteases hydrolyze cytoskeletal proteins and lens crystalline. Crystalline cleavage would result from lower molecular weight peptides that could, in turn, aggregate to form higher molecular weight proteins (Wang et al., 1996). Various methods for the prevention of cataract The development of newer drugs for treatment of cataract mainly aims, interacting at the level of changed lens metabolism and lens pathophysiology. The in vitro, in vivo studies are used to identify the anti cataract agents. This epidemiological studies may be widely classified in the following categories (Gupta et al., 1997). Aldose reductase inhibitors Agents acting on glutathione Nonsteroidal anti -inflammatory drugs Vitamins, minerals and antioxidants Miscellaneous agents. 1) Aldose Reductase Inhibitors These drugs are aimed to prevent the metabolic dysfunctions of diabeties by polyol pathways. Aldose reductase inhibitors prevents the accumulation of sorbital within the lens would have an osmotic effect bringing in water and causing swelling and opacification. Sorbinil a spirohydantoin became the most powerful sorbitol lowering agent. Sorbinil prevents increased fluorescence and protein aggregation and it also acts as an antioxidant. 2) Non Steroidal Anti inflammatory Drugs The NSAIDS broadly studied are paracetamol, aspirin, Ibuprofen, sulindac, naproxen, and bendazec. The NSAIDS provide adequate productive effect to lens protein through various steps like acylation, carbamylation and inhibition of glycocylation. Some of them are also reported to inhibit lens AR to varying extent. NSAIDS contains antioxidant properties also. Most of the studies on the evaluation of anticataract potential of drugs have been conducted by feeding the drugs by oral route. 3) Agents which act on glutathione Glutathione is a tripeptide thiol known to control calcium inflex and protect lens protein from various agents like glucose and galactose. With advancing of age there is a considerable decrease in the concentration of glutathione and the decrease more prominent in lens with cataract. 4) Vitamins, minerals and antioxidants If oxidation in lens leads to cataract formation, then is feasible to prevent it by the use of antioxidants such as vitamins C and E and perhaps ÃŽ ²-carotene. The potential role of vitamins and antioxidants in preventing various diseases is well documented there are reports suggesting beneficial effect of vitamins like C and E in preventing cataract. Beta -carotene has also been demonstrated to protect lens damage by hematoporphysin. Ascorbate protects rubidium uptake against free radical damage and prevents light induced protein cross linking. Protective effect of vitamin C has been also reported in various in vitro studies. Vitamin E has been found to delay cataractogenesis in diabetic rats and in Emory mouse. Vitamins C and E,  Ã‚ ¢- Carotene and other anticataract agents probably act via a common mechanism of their scavenging properties of free radicals (Gupta et al., 1997b). Antioxidant enzymes 1) Superoxide Dismutase (SOD) SODs are a family of metalloenzymes that transfer superoxide in to hydrogen peroxide (H2O2) and represents the first line of defence against oxygen toxicity. 2O2- + 2H → H2O2 + O2 Three isoforms of SOD have been found. The first is mainly found in the cytoplasm of cells and it containing Cu and Zn at its active site (Cu/Zn SOD-1), the second containing Mn at its active site is located in mitochondria (Mn SOD-2) and the third (Cu/Zn SOD-3) is present in the extracellular fluid like plasma. SOD is a stress protein which is synthesized mostly in response to oxidative stress. It is found that little amount of Cu, Zn and Mn metals are crucial for maintaining the antioxidant activity of SOD (Halliwell, 1994; Ray and Husain, 2002). 2) Glutathione Peroxidase (GPx) GPx is one of the most important enzymes responsible for the degradation of organic peroxides and hydrogen peroxide in the brain. GPx catalyse the oxidation of GSH to GSSG at the expense of H2O2. There are two isoforms have been identified, selenium-dependent which is highly active towards H2O2 and organic hydroperoxides and selenium independent GPx. GPx activity has been reduced in selenium deficiency (Muller et al., 1984; Son et al., 2007). 3) Catalase (CAT) It is a heme-containing protein present in most cells. 2H2O2+ 2H2O → O2 Catalase is 104 times faster than GPx. It is having four protein subunits, each containing a heme Fe (III)-protoporphyrin group bound to its active site. GPx and CAT were found to be important in the inactivation of many environmental mutagens (Ray and Husain, 2002). 4) Glutathione (GSH) GSH has major intracellular antioxidant molecule and it is a tripeptide synthesised by enzymatic reaction involving two molecules of ATP from aminoacids like glutamate, glycine and cysteine. It plays a very crucial role in detoxification of peroxides and electrophilic toxins, mainly by acting as a substrate for GSH transferase and GSH peroxidase. It was shown that weakening of GSH enhances cerebral ischemic injury in rats (Mizui et al., 1992; Son et al., 2007).

Robbert Harris :: essays research papers

We have all read interesting, touching stories in our lifetime. I have read a few, myself. The one that really sticks out in my mind is, The Unquiet Death of Robert Harris by Michael Kroll. This story left me filled with emotions, opinions, and questions.   Ã‚  Ã‚  Ã‚  Ã‚  The story was told by a man named Michael Kroll that had a very dear friend on death row named Robert Harrison. They had been friends for ten years and now that friendship was to come to an end. Nothing that night seemed to go as planned or on schedule. Michael and a few others including Roberts’s brother, waited several hours in a small room only to be filled into another small room, where they continued to wait. When Robert finally came into sight Michael was a little relieved. Nothing happened for a long time then they took Robert out of the room. Michael was confused and wasn’t sure what was going on. Finally they brought Robert back, and of course they executed him.   Ã‚  Ã‚  Ã‚  Ã‚  At the end of this story my first reaction was sadness. I felt awful for Michael, Robert, and everyone that was involved. I thought this story was the worst thing I ever heard, and I wanted to cry. My next reaction was anger. I was horrified that one human being could do something as horrible as this to another.   Ã‚  Ã‚  Ã‚  Ã‚  Next my brain started rattling with opinions. First I though the death penalty was a horrible thing, and should be outlawed completely. Then I started to think, what if it was my family, and someone had killed one of my family members. I would want that person dead! I wouldn’t care how they did it, when, or even where they did it, as long as I knew that they paid for what they did. In order to insure that they would never hurt anyone in my family, or even anybody at all ever again, they would have to be dead in my opinion.   Ã‚  Ã‚  Ã‚  Ã‚  Then came the questions. One major question I had was how did the death penalty ever come into the picture? Did some creep invent it, or was it discovered by accident? When did they start using the death penalty, and what state was first to use it? Is it legal in all states in the United States of America? After a person is executed, does the family get to perform a proper funeral as they please?

Cyber Bullying

ABC News reported on a survey prepared by I-SAFE. ORG. This of 1,500 students between grades 4-8 reported: 42% OR 630 of kids have been bullied while online. One in four have had it happen more than once. 35% OR 525 of kids have been threatened online. Nearly one in five had had it happen more than once. 1% OR 315 of kids have received mean or threatening e-mails or other messages. 58% OR 870 of kids admit someone has said mean or hurtful things to them online. More than four out of ten say it has happened more than once. 58% OR 870 have not told their parents or an adult about something mean or hurtful that happened to them online. THAT WAS SOME INFORMATION ON CYBER-BULLYING WITH CHILDREN, LETS REVIEW HOW CYBER-BULLYING AFFECTS ADULTS AND THE WORKPLACE. ALTHOUGH IT IS MORE COMMON, CYBER BULLYING IS NOT LIMITED TO CHILDREN.ADULT TO ADULT CYBER-BULLYING, IS IDENTIFIED BY THE SAME BEHAVIORS AS CHILDREN BUT IS REFERRED TO AS CYBER-HARASSMENT, OR CYBER STALKING BECAUSE OR THE AGE DIFFERE NCE. WITH ADULTS THE INTENT IS TO THREATEN THE VICTIMS EARNING, EMPLOYMENT, REPUTATION, OR SAFETY, AND USUALLY TAKES PLACE IN THE WORKPLACE ACCORDING TO THE DIGNITY AND WORK PARTNERSHIP GROUP. A survey of 1,072 workers by the Dignity and Work Partnership found that one in five had been bullied at work by e-mail AND believes cyber-bullying is a problem in their workplace.Cyberstalkers use posts, forums, journals and other online means to present a victim in a false and unflattering light. Various companies provide cases of cyber-stalking (involving adults) follow the pattern of repeated actions against a target. While motives vary, whether romantic, a business conflict of interest, or personal dislike, the target is commonly someone whose life the stalker sees or senses elements lacking in his or her own life. NOW LET ME TELL YOU SOME OF THE HARMFUL EFFECTS OF CYBER BULLYING. Research had demonstrated a number of serious consequences of cyber-bullying victimization. 4][6][7][8] For e xample, victims have lower self-esteem, increased suicidal ideation, and a variety of emotional responses, cyber-bullying back, being scared, frustrated, angry, and depressed. [6]One of the most damaging effects is that a victim begins to avoid friends and activities, often the very intention of the cyber-bully. Cyber-bullying campaigns are sometimes so damaging that victims have committed suicide. There are at least four examples in the United States where cyber-bullying has been linked to the suicide of a teenager. 6] The suicide of Megan Meier is a recent example that led to the conviction of the adult perpetrator of the attacks. Intimidation, emotional damage, suicide The reluctance youth have in telling an authority figure about instances of cyber-bullying has led to fatal outcomes. At least three children between the ages of 12 and 13 have committed suicide due to depression brought on by cyber-bullying, according to reports by USA Today and the Baltimore Examiner. Never be bu llied into silence. Never allow yourself to be made a victim. Accept no one's definition of your life, but define yourself. † Cyber Bullying Is Cyber-bullying really a problem? Bullying has been around forever but cyber bullying is different because it lets a bully remain anonymous. It is easier to bully in cyberspace than it is to bully face to face. With cyber bullying a bully can pick on people with much less risk of being caught. Bullies are natural instigators and in cyberspace bullies can enlist the participation of other students who may be unwilling to bully in the real world. Cyber bullying is any harassment that occurs in the Internet.Vicious forum posts, name calling in chat rooms, posting fake profiles on web sites, and mean or cruel email messages are all ways of cyber bullying. â€Å"Around 10 percent of all adolescents in grades 7-9 are victims of internet bullying. ‘This type of bullying can be more serious than conventional bullying. At least with conventional bullying the victim is left alone on evenings and weekends. † Many people may think that cyber-bullying isn’t a problem in life , well think again it can change a victim’s life forever by just one offensive comment about them.I will make the victim want to commit suicide, drop out of school, and suffer from self-esteem issues like depression and anxiety. We must fight for what is right, sooner the better. What cyber-bullies would do in order for them to trace their victims or look for victims is most likely where they would have easy access and that would be through the internet and through cell phones. For cell phones they are able to contact with others by texting or calling but for the internet it would have websites where most kids would join now a days such as, facebook, myspace, twitter, blogspots, and e-mail.I would say that the internet is one of the best places for cyber-bullying than through cell phones because when communicating through the internet they are able to not only associate with only their victims but with other people in the world so not only that one person that they’re bullying are seeing it many people around the world are able to see it also, which in that case would make the victims situations even worse. Above all, no matter what techniques that bullies use it is a way for them to harm others. Online bullying, called cyberbullying, happens when teens use the Internet, cell phones, or other devices to send or post text or images intended to hurt or embarrass another person. † The internet is appealing to many bullies because it makes it easier for them to be cruel and vicious to their victims when there isn’t any personal contact with them and its difficult to trace the activities that they’re doing. â€Å"Victims of internet bullying — or cyberbullying — have no refuge.Victims may be harassed continuously via SMS and websites, and the information spreads very quickly and may be difficult to remove. In addition, it is often difficult to identify the perpetrator. † Hurting others is a way to call it their comfort zone because makes them feel better about themselves and when they do encounter with problems of their own the only way to makes them feel more respected or get them back on their feet is by causing trouble through the technologies because not many of their victims are able to stand up for themselves so bullies feel more superior.For them to harm others is mostly to gain friends that they always wanted to hangout with, since peer pressure has been an issue for many students bullying others is way for them to gain more respect from others especially from their victims. What cyber-bullies didn’t realize is that it can cause a whole lot of problems for their victim that it created a great nightmare not to only to the victim but even to the victims loved ones because it makes a great destruction to ones life. Cyber bullying In these days, internet has become a vital part of our life – both in working or killing time. We may even regard this invisible site as an epitome of our society in reality. Therefore, every phenomenon that takes place in the internet somehow is a projection from out real life. While, bullying, is transformed to a phenomenon in the internet that called cyber-bullying. Why is this happened? The reason's simple – people's being more and more catty. It's because, cyber bullying hurts more deeply, and these evil wounds may keep bleeding for ever†¦ Bullying in the reality mainly hurt victims physically, while it could also hurt one's self-esteem -For example, verbal insulting†¦etc. But still, victims could have chance to escape from those beliers, and it would be more easier for adults to trace for evidence hence preventing this happen again. But cyber bullying is a touchy issue to deal with. First, cyber bully are usually sly – they could delete the evidence once the victim strike by just pressing a button on the keyboard. Then, the bully would not need to be punished because the evidence disappeared suddenly. Then the victim will certainly be kept on insulted by the bully. Where you may say you could avoid having contact with the internet, but can you? As I said, nowadays, the internet had become a vital part in our daily life, can you avoid accessing to it? And once you get to the internet, could you control your curiosity? Even you can, how about your MSN, inbox, Facebook or Myspace ? Those nasty messages can't be edited by you and, they will just be right there forever if you don't take any action. It would be read by any one including yourself. And this will turnout to become a kind of bullying in the reality. People will laught at you because of the message about you in the internet. It's only a vicious cycle. Everything will turn sour and blue if you just keep on being a silent victim. And eventually, you will terminate your life to relief your suffrage, pressure, pain, anger†¦etc. While the bully may just laughing at your death, while, who love you will burst into tears for your death. Death is absolutely not a solution for a problem! The best way to deal with bullying or cyber bullying is to stand out and face the problem positively. You may keep the evidence but not just ignoring them. Talk this issue with your parents and teachers, they will give you wise advices. If the situation's really worst, you may also seek help from the police force too. Our society won't accept the existence of any kind of bullying. Everyone would try their best to help you – you are not alone! But remember, never revenage. If you did this, you will just become another bully. Remember, anger is a poison – it eats you inside. Without your support, bullying still exist as we may have a devil mind. Let's to create a harmony society in the future together. Cyber Bullying Cyber bullying has become a result of teens committing suicide. Last fall Audrie Pott was allegedly ganged raped by three boys after she had fallen asleep do to the consumption of alcohol the three boys later, tormenting her with pictures of her engaging in a sexual form with one of these boys. Pictures were shared around school as well as texting the images and posting them online. After being tormented for two years she started developing suicidal thoughts which later led to her death. In ohio two star football players were convicted of raping a drunk 16 year old girl. They gained media through lurid text messages, cell phone pictures and videos, and social media post surrounding the sexual abuse of the girl. One of the convicted felons was found guilty disseminating a nude photo of a minor. Once something has been posted on the internet it can never be erased. Imagine these young girls that don’t remember anything that happened the night before then waking up discovering they have been sexually abused. Yea, this can be a traumatizing event leaving scars and wounds that can never be healed. Some can leave these events in the past while others would just take their lives away like Audrie Pott. How can cyber bullying be prevented? Simply having more talks with young kids regarding bullying as well as bringing guest speakers to inspire kids not to bully. Also enforcing the law on young teenagers just because they’re young that doesn’t mean they cannot take care of the mess they have created. Allard the attorney for the pott family, said his clients are pushing the â€Å"Audrie’s Law,† which would stiffen penalties for cyber bullying and strengthen laws on sexual assaults by trying adolescents as adults. Cyber Bullying vCyber bullying has become a huge problem in today’s society. There was once a day where cell phones or social networking did not exist and any problem you had with anyone was handled face to face and not behind a computer screen. If you told this to kids today they would probably be surprised. We’ve all been a victim of minor cyber bullying or bullying in general and although I haven’t experienced cyber bullying to its full potential, I’ve sat on the sidelines and watched how cruel my peers can be. About two weeks ago a fight broke out on Instagram between and friend of mine and her ex-boyfriends best friend.The breakup was bitter and his friends were trying to protect him and fight his battles. The ex-boyfriends friend commented on my friends Instagram picture and called the boys in it â€Å"doofy† not too harsh, but they came back at him ten times worse. I’ve witnessed a lot of people get bullied throughout high school and I myself have ha d some pretty cruel things said to me and I’ve said some things to people that I shouldn’t have said, but what these kids were saying to this boy was worse than any type of bullying I’ve ever witnessed.They told him that the world would be a better place without him and that he should just go hang himself. They told him to go hang out with Amanda Todd, a young teen who recently within the past few months made the news for committing suicide. They told him to that he should go kill himself to rid one more retard of the world and make the world better. Lastly, they told him to go drink bleach. I don’t even know the boys name that they bullied, yet I felt so sorry for him and felt that I had to stick up for him.Fortunately the boy did not take the advice of the cruel teenagers and he fought back until the Instagram feud was over. The problem doesn’t only exist in situations that I explained about but in many more ways where maybe the person that was b eing bullied did nothing wrong to deserve the treatment that they got. Not everyone is cyberbullied because of something they did wrong or because of a fight that they instigated. Some cases of cyber bullying had the cause of just plain jealousy. Approximately seventy-five percent of teenagers today have and are using cell phones.And the ones with cell phones send around three thousand text messages a month. With these cell phones do their parents really know what they are doing? Are they suffering from immense amounts of bullying? Or are they on the other side? The problem is that no one really knows and by the time a teenager takes their own life or starts to self harm, it’s too late because the parents had no clue. Thirty percent of children who are online whether it be Facebook or Twitter has admitted to being harassed.In the past few years, cyber bullying has gotten much more serious because not only are kids calling each other names, they’re starting to blackmail . If a young girl sends a nude picture through text message to a boy, and that picture gets in the hands of one of his friends or even another girl, the girl that sent the picture has the risk of having her picture sent around the school or even uploaded to social networking sites. Some might wonder how does a parent stop their children from sending or receiving these harsh texts.It is recommended that the parent sets a time period where the child can and cannot send or receive text messages. There is also an app that can stop sexts, and cyber bullying texts from send to a cell phone. Add your child on Facebook, follow them on Twitter. They may not like it at first but if you can prevent them from being bullied or from facing charges from cyber bullying, they will thank you in the long run. â€Å"Keep kids safe from cyberbullies – CNN. †Ã‚  Featured Articles from CNN. N. p. , n. d. Web. 6  Feb. 2013. â€Å"Keep kids safe from cyberbullies – Page 2 – CN N. †Ã‚  Featured Articles from CNN. N. p. , n. d. Web. 6  Feb. 2013. Cyber Bullying Cyber bullying has become a result of teens committing suicide. Last fall Audrie Pott was allegedly ganged raped by three boys after she had fallen asleep do to the consumption of alcohol the three boys later, tormenting her with pictures of her engaging in a sexual form with one of these boys. Pictures were shared around school as well as texting the images and posting them online. After being tormented for two years she started developing suicidal thoughts which later led to her death. In ohio two star football players were convicted of raping a drunk 16 year old girl. They gained media through lurid text messages, cell phone pictures and videos, and social media post surrounding the sexual abuse of the girl. One of the convicted felons was found guilty disseminating a nude photo of a minor. Once something has been posted on the internet it can never be erased. Imagine these young girls that don’t remember anything that happened the night before then waking up discovering they have been sexually abused. Yea, this can be a traumatizing event leaving scars and wounds that can never be healed. Some can leave these events in the past while others would just take their lives away like Audrie Pott. How can cyber bullying be prevented? Simply having more talks with young kids regarding bullying as well as bringing guest speakers to inspire kids not to bully. Also enforcing the law on young teenagers just because they’re young that doesn’t mean they cannot take care of the mess they have created. Allard the attorney for the pott family, said his clients are pushing the â€Å"Audrie’s Law,† which would stiffen penalties for cyber bullying and strengthen laws on sexual assaults by trying adolescents as adults. Cyber bullying In these days, internet has become a vital part of our life – both in working or killing time. We may even regard this invisible site as an epitome of our society in reality. Therefore, every phenomenon that takes place in the internet somehow is a projection from out real life. While, bullying, is transformed to a phenomenon in the internet that called cyber-bullying. Why is this happened? The reason's simple – people's being more and more catty. It's because, cyber bullying hurts more deeply, and these evil wounds may keep bleeding for ever†¦ Bullying in the reality mainly hurt victims physically, while it could also hurt one's self-esteem -For example, verbal insulting†¦etc. But still, victims could have chance to escape from those beliers, and it would be more easier for adults to trace for evidence hence preventing this happen again. But cyber bullying is a touchy issue to deal with. First, cyber bully are usually sly – they could delete the evidence once the victim strike by just pressing a button on the keyboard. Then, the bully would not need to be punished because the evidence disappeared suddenly. Then the victim will certainly be kept on insulted by the bully. Where you may say you could avoid having contact with the internet, but can you? As I said, nowadays, the internet had become a vital part in our daily life, can you avoid accessing to it? And once you get to the internet, could you control your curiosity? Even you can, how about your MSN, inbox, Facebook or Myspace ? Those nasty messages can't be edited by you and, they will just be right there forever if you don't take any action. It would be read by any one including yourself. And this will turnout to become a kind of bullying in the reality. People will laught at you because of the message about you in the internet. It's only a vicious cycle. Everything will turn sour and blue if you just keep on being a silent victim. And eventually, you will terminate your life to relief your suffrage, pressure, pain, anger†¦etc. While the bully may just laughing at your death, while, who love you will burst into tears for your death. Death is absolutely not a solution for a problem! The best way to deal with bullying or cyber bullying is to stand out and face the problem positively. You may keep the evidence but not just ignoring them. Talk this issue with your parents and teachers, they will give you wise advices. If the situation's really worst, you may also seek help from the police force too. Our society won't accept the existence of any kind of bullying. Everyone would try their best to help you – you are not alone! But remember, never revenage. If you did this, you will just become another bully. Remember, anger is a poison – it eats you inside. Without your support, bullying still exist as we may have a devil mind. Let's to create a harmony society in the future together. Cyber Bullying vCyber bullying has become a huge problem in today’s society. There was once a day where cell phones or social networking did not exist and any problem you had with anyone was handled face to face and not behind a computer screen. If you told this to kids today they would probably be surprised. We’ve all been a victim of minor cyber bullying or bullying in general and although I haven’t experienced cyber bullying to its full potential, I’ve sat on the sidelines and watched how cruel my peers can be. About two weeks ago a fight broke out on Instagram between and friend of mine and her ex-boyfriends best friend.The breakup was bitter and his friends were trying to protect him and fight his battles. The ex-boyfriends friend commented on my friends Instagram picture and called the boys in it â€Å"doofy† not too harsh, but they came back at him ten times worse. I’ve witnessed a lot of people get bullied throughout high school and I myself have ha d some pretty cruel things said to me and I’ve said some things to people that I shouldn’t have said, but what these kids were saying to this boy was worse than any type of bullying I’ve ever witnessed.They told him that the world would be a better place without him and that he should just go hang himself. They told him to go hang out with Amanda Todd, a young teen who recently within the past few months made the news for committing suicide. They told him to that he should go kill himself to rid one more retard of the world and make the world better. Lastly, they told him to go drink bleach. I don’t even know the boys name that they bullied, yet I felt so sorry for him and felt that I had to stick up for him.Fortunately the boy did not take the advice of the cruel teenagers and he fought back until the Instagram feud was over. The problem doesn’t only exist in situations that I explained about but in many more ways where maybe the person that was b eing bullied did nothing wrong to deserve the treatment that they got. Not everyone is cyberbullied because of something they did wrong or because of a fight that they instigated. Some cases of cyber bullying had the cause of just plain jealousy. Approximately seventy-five percent of teenagers today have and are using cell phones.And the ones with cell phones send around three thousand text messages a month. With these cell phones do their parents really know what they are doing? Are they suffering from immense amounts of bullying? Or are they on the other side? The problem is that no one really knows and by the time a teenager takes their own life or starts to self harm, it’s too late because the parents had no clue. Thirty percent of children who are online whether it be Facebook or Twitter has admitted to being harassed.In the past few years, cyber bullying has gotten much more serious because not only are kids calling each other names, they’re starting to blackmail . If a young girl sends a nude picture through text message to a boy, and that picture gets in the hands of one of his friends or even another girl, the girl that sent the picture has the risk of having her picture sent around the school or even uploaded to social networking sites. Some might wonder how does a parent stop their children from sending or receiving these harsh texts.It is recommended that the parent sets a time period where the child can and cannot send or receive text messages. There is also an app that can stop sexts, and cyber bullying texts from send to a cell phone. Add your child on Facebook, follow them on Twitter. They may not like it at first but if you can prevent them from being bullied or from facing charges from cyber bullying, they will thank you in the long run. â€Å"Keep kids safe from cyberbullies – CNN. †Ã‚  Featured Articles from CNN. N. p. , n. d. Web. 6  Feb. 2013. â€Å"Keep kids safe from cyberbullies – Page 2 – CN N. †Ã‚  Featured Articles from CNN. N. p. , n. d. Web. 6  Feb. 2013.

Essay about Sarah, the Evil Mistress - 1977 Words

Sarah, the Evil Mistress Although Hagar flaunts her pregnancy with Abraham in the face of Sarah who is barren, Sarah is ultimately responsible for generating trouble in Abraham’s household. Through Sarah’s decision to give Hagar to Abraham, Sarah’s jealousy and anger towards Hagar’s reaction to conception, and also Sarah’s harsh treatment of Hagar, we are able to understand why Sarah is truly the one accountable for the negative circumstances throughout her relationship with Hagar. Initially, in Genesis 11:30 we feel remorse for Sarai in her barrenness. Repeatedly it is expressed that Sarai is barren. Sharon Jeansonne explains, â€Å"Indeed, Sarai’s childlessness is predominant in most of the scenes that concern her† (15). Sarai’s†¦show more content†¦Now, let us look at Hagar’s position in the situation. Looking at her status we see that she has no authority and no control over her future. She is wholly under the demands of her mistress Sarai (Jeansonne 43). Hagar is not even introduced as a person, but merely as a maidservant. She is only referred to by titles such as, â€Å"Sarai’s maidservant† or â€Å"her† or â€Å"your slave-woman.† Sarai and Abram do not even give her the status of a person who deserves a name. Due to her lack of power and control, Hagar was given no choice in having a son for Sarai and Abram. The verse reads in Genesis 16:4, â€Å"He cohabited with Hagar and she conceive d†¦Ã¢â‚¬  This is all we are given; none of Hagar’s opinions or feelings are shared with the readers, the narrator remains silent about Hagar in the situation (Jeansonne 44). Barrenness was always blamed on the woman in ancient near eastern times, although it was not always the case. Since Hagar becomes pregnant, it is obvious that Sarai is in fact, the sterile one. After conception, Hagar realizes her status has changed and Frymer-Kensky puts it clearly saying, â€Å"Hagar knows that she has something Sarai doesn’t have, a child in her womb, and this knowledge makes her cease to consider Sarai’s status above her own† (228). In fact, there were three ancient Near Eastern marriage contracts that stated after a certain number of years, the wife must give her slave to her husband (227). Almost inevitably then, this change in attitudeShow MoreRelatedProperty Essay example951 Words   |  4 PagesNovel Property is an immersing and captivating story of Manon Gaudet, the wife of a slave owner and a slave, who is the mistress of the slave owner. The story takes place in the early 19th century deep within slavery, on a sugar plantatio n in Louisiana. While reading, the author, Valerie Martin steers you through the lives of both, Manon Guadet and her slave and servant Sarah. 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