Plant Medicines in Cancer Treatment

Plant Medicines in Cancer Treatment Review of Literature Plants as therapeutic agents Plant medicines are the most widely used medicines in the world today. The use of herbs and plants as the first medicine is a universal phenomenon. Every culture on earth, through written or oral tradition, has relied on the vast variety of natural chemistry found in healing plants for their therapeutic properties (Serrentino 1991). Plants with therapeutic potential may be defined as any plant that can be put to culinary or medicinal use. Recent researches found that food and their constituents act in a manner similar to modern drugs without the dreaded side effects (Serrentino 1991). Sometimes plant medicine is viewed as complementary medicine, working closely with allopathic drugs. Nearly 5.1 billion people worldwide employ natural plant-based remedies as their primary medicines for both acute and chronic health problems, from treating common cold to controlling blood pressure and cholesterol (Stockwell, 1988). Most of the drugs were substances with a particular therapeutic action extracted from plants. Some medicines, such as the cancer drug Taxol from Taxus brevifolia and the anti-malarial quinine from Cinchona pubescens are manufactured from the plants. Other medicinal agents such as pseudoephedrine originally derived from ephedra species and methylsalicylate, derived from gaultheria procumbens are now synthesized. Plant medicines remain indispensable to modern pharmacology and clinical practice. Much of the current drug discovery and development process are plant-based, and new medicines derived from plants are inevitable. Functional foods A food can be regarded as a functional food if it is demonstrated to affect one or more target functions in the body beyond adequate nutrition and improves health/well-being or reduces the risk of diseases (Tsao and Akhtar, 2005). On this basis, a functional food can be a natural food, a food to which a positive component has been added, or from which a deleterious component has been removed or a food where the nature of one or more components has been modified (Tsao and Akhtar, 2005). While searching for new sources of functional food, attention has been paid to vegetables from the Cruciferae family, which more often used in the human diets. The cruciferous vegetables may thus become a potential source of a nutritious food or food ingredients. Recent research showed that cruciferous vegetables contain an appropriate amount of bioactive compounds such as GLs, ITCs, tocopherols, L-ascorbic acid, vitamin B, reduced glutathione, inositol phosphates and polyphenolic compounds [Nakamura e t al, 2001; Zielinski and Kozlowska, 2003; Zielinski et al, 2005; Takaya et al, 2003]. Cruciferous plants The family Cruciferae (Brassicaceae) is an economically important family with about 350 genera and 3000 species that includes several edible plants. Despite the great diversity among the crucifers, members of only a few genera are eaten. The most commonly eaten cruciferous vegetables belong to the genus Brassica that includes broccoli, cabbage, cauliflower, kale and Brussels sprouts. Other cruciferous vegetables used in the human diet such as radish, water cress, wasabi, horseradish, garden cress, Italian cress, Swiss chard and crambe belong to another genera of the family such as Raphanus, Nasturtium, Wasabia, Armoracia, Lepidium, Eruca, Beta and Crambe respectively. Cruciferous vegetables are important dietary constituents in many parts of the world and appear to account for about 10 15% of total vegetable intake, reaching almost 25% in countries with a high consumption (Bosetti et al, 2002; Chiu et al, 2003). However, regional pattern of crucifer consumption varies substantially in different parts of the world. The highest intake of cruciferous vegetable was reported to that of people in China, who consumed more than 100 g per day, representing about one-fourth of their total vegetable intake (Chiu et al, 2003). Other Asians and some Middle Eastern populations in Japan, Singapore, Thailand and Kuwait also have a relatively high intake of cruciferous vegetables, ranging from 40 80 g per day (Bosetti et al, 2002; Seow et al, 2002; Shannon et al, 2002; Memon et al, 2002). However, the only study carried out in India (Rajkumar et al, 2003) showed a lower daily intake of cruciferous plants, of about 17 g per day. In North America, the daily estima ted consumption was in the range of 16 40 g per day (Lin et al, 1998) and in South America, it was about 3 15 g per day (Atalah et al, 2001). The daily intake of cruciferous vegetables was reported to be about 5 30 g per day in Europe (Bosetti et al, 2002), 50 g per day in Australia (Nagle et al, 2003) and 15 g per day in South Africa (Steyn et al, 2003) respectively. Raphanus sativus R. sativus is believed to have originated in southern Asia and was cultivated in Egypt. The first cultivated R. sativus was black variety and later on white and red R. sativus were developed. It was highly esteemed in ancient Greece, and the Greek physician Androcydes ordered his patients to eat R. sativus as a preservative against intoxication. The Japanese white R. sativus, also named daikon, is the vegetable for which the literature reports the highest per capita consumption, quoted at 55 g per day in Japan (Talalay and Fahey, 2001). In addition to this, Japanese also consumes R. sativus sprouts under the name of Kaiware Daikon. Varieties of R. sativus There are six main varieties of R. sativus such as Daikons, Red Globe, White Globe, Black, White Icicles and California Mammoth White Daikons (R. sativus L) This variety is native to Asia. They are large and carrot-shaped, have a white flesh that is juicy and a bit hotter than a red radish, but milder than black. Red Globe (R. sativus var. red) This variety is the most popular in the United States. It is small, round or oval shaped, referred to as button red radishes and have a solid crisp flesh. White Globe (R. sativus var.white) This variety is small and oval shaped, referred to as hailstone or white button. They have white flesh and milder than the red variety. Black (R. sativus var. niger) This variety is thought to be native to Egypt and Asia. They are turnip-like in size and shape. They are quite pungent and drier than other varieties of radishes. White Icicles (R. sativus L var. thin) This variety is long and tapered. They have a white flesh that is milder than the red variety. California Mammoth White (R. sativus L var. large) A larger variety than the white icicle, these varieties have oblong- shaped roots and their flesh is slightly pungent. Nutritive value of R. sativus R. sativus root and its leafy part are ideal vegetables as they provide an excellent source of vitamin C. Leafy part contains almost six times the vitamin C content of its root and also a good source of calcium and iron. R. sativus is also a good source of potassium and folic acid. It is very low in fats. Approximately, 100 g of raw vegetable provides roughly 20 Kcal, coming largely from carbohydrates (Table 2.1). Thus R. sativus is a dietary food that is relatively filling for its caloric value. Some sources list R. sativus as being rich in dietary fiber, whereas other sources differ in respect of its roughage content (USDA Nutrient Database, 1999; Duke and Ayensu, 1985). Health benefits of R. sativus (Traditional usage of R. sativus) According to Hakeem Hashmi, an eminent Unani physician from India, R. sativus is unparallel in curing any kind of ailments. All the parts of R. sativus including its seed, stem, root and leaves are used in food and medicine. R. sativus is a unique vegetable having a hot and cold effect on the body simultaneously. R. sativus, like other members of the cruciferous family (cabbage, kale, broccoli, Brussels sprouts) contains cancer-protective properties. Liver and gall bladder disorders Throughout the history, R. sativus root and seeds have been effective when used as medicinal food for liver disorders. They contain sulfur-based compounds such as GLs and ITCs that increase the flow of bile and help to maintain healthy gallbladder and liver (Chevallier, 1996). They are useful in treating jaundice and also an excellent remedy for gall bladder stone. Kidney disorders R. sativus root, seeds and leaves are diuretic in nature and increase the urine output. Their diuretic properties help to flush out the toxins accumulated in the kidneys and protect them from infections and inflammatory conditions. It is an old belief that R. sativus can aid in the treatment as well as prevention of kidney stones (Chopra et al, 1986). Respiratory disorders R. sativus is an anti-congestive and relieves congestion of the respiratory system. It has found to be beneficial in problems associated with bronchitis (Bown, 1995) and asthma (Duke and Ayensu, 1985). Skin disorders R. sativus helps to cure skin disorders such as leucoderma, rashes, cracks, etc and also refreshes the skin by maintaining the moisture content of the skin (Duke and Ayensu, 1985). Digestive disorders R. sativus root, seeds and leaves are rich in roughage (indigestible carbohydrates) which facilitates digestion, retain water and relieve constipation (Chopra et al, 1986). They also soothe the digestive system and stimulate appetite (Chevallier, 1996) Nervous and vascular disorders R. sativus decreases nervous tensions and is also useful in enhancing blood circulation. It is a remedy for insomnia, hypochondria and irritative conditions of the central nervous system (Panda, 1999). Other benefits R. sativus is germicidal and suppresses phlegm. It is a good appetizer, mouth fresher, laxative, regulates metabolism, remedy for headache, acidity, piles, nausea, obesity, sore throat, whooping cough, dyspepsia, etc (Nadkarni, 1976; Kapoor, 1990). Chemical constituents of R. sativus GLs are an important and unique class of secondary plant metabolites found in the seeds, roots and leaves of R. sativus (Daxenbichler et al, 1991; Blazevic and Mastelic, 2009). GLSs include several naturally occurring thioglucosides with a common structure (Figure 2.2) characterized by side chains (R) with varying aliphatic, aromatic and heteroaromatic carbon skeletons, all presumably derived from amino acids by a chain-lengthening process and hydroxylation or oxidation (Larsen, 1981). In the intact cell, GLs are separated from thioglucosidase (EC 3.2.3.11), an enzyme generally known as myrosinase. When the plant cell structure is damaged, myrosinase catalyzes the hydrolysis of GLs to yield D-glucose, sulfate and a series of compounds including isothiocyanates, thiocyanates and nitriles, depending on both the substrate and the reaction conditions, especially the pH (Figure 2.2). GLs are also hydrolyzed by thioglucosidase activity of the intestinal microflora (Jeffery and Jarrell, 2001). 4-(methylthio)-3-butenyl glucosinolate (glucoraphasatin), 4-(methylsulfinyl) butyl glucosinolate (glucoraphanin) and 4- (methylsulfinyl)-3-butenyl glucosinolate (glucoraphenin) are the most predominant GLs in the root and seeds of R. sativus (Daxenbichler et al, 1991; Carlson et al, 1985). These GLs on hydrolysis by myrosinase yield MTBITC, sulforaphane and sulforaphene respectively. GLs are not uniformly distributed and are highest in the distal end of the root, decreasing in upper root sections with the lowest level in vegetative tops (Esaki and Onozaki, 1980). Apart from GLs and their breakdown products, R. sativus also contains polyphenolics such as phenolic acid, flavonoids and anthocyanins. Several polyphenolic compounds including sinapic acid esters and kaempferol were isolated from R. sativus sprouts (Takaya et al, 2003). Twelve acylated anthocyanins (pelargonidin) were isolated from R. sativus red variety (Otsuki et al, 2002). Phytochemical screening showed the presence of other phytochemicals such as triterpenes, alkaloids, saponins and coumarins in R. sativus seeds (Mohamed et al, 2008). The myrosinase catalyzed hydrolysis of glucosinolates. (Adapted from Rusk et al, 2000) Novel classes of plant defensins (small basic cysteine rich peptides) such as Raphanus sativus antifungal peptide 1 and 2 (RsAFP1 and RsAFP2) were isolated from the seeds of R. sativus (Terras et al, 1992a). RsAFP1 and RsAFP2 are highly basic oligomeric proteins composed of small (5 KDa) polypeptides that are rich in cysteine. Both RsAFP1 and RsAFP2 have a broad spectrum antifungal activity and show a high degree of specificity to filamentous fungi (Terras et al, 1992b). They are active against both phytopathogenic fungi such as Fusarium culmorum and Botrytis cinerea (Terras et al, 1992b), human pathogenic fungi such as Candida albicans (Aerts et al, 2007) and occasionally possess antibacterial activity. However, they are non-toxic to humans and plant cells. R. sativus 2S storage albumins were identified as second novel class of antifungal protein (Terras et al, 1992a). They also inhibit the growth of different plant pathogenic fungi and certain bacteria (Terras et al, 1992a). At least eight distinguishable isoperoxidases were isolated and purified to apparent homogeneity from Korean R sativus roots. Among them are two cationic isoperoxidases such as C1 and C3 and four anionic isoperoxidases such as A1, A2, A3n and A3 (Lee and Kim, 1994). Plant peroxidases play an important role in several physiological functions such as removal of peroxide, oxidation of indole-3-acetic acid and toxic reductants, wound healing and cell wall biosynthesis (Hammerschmidt et al, 1982). Further, peroxidase represents an important component of an early response in plants to pathogen attack and plays a key role in the biosynthesis of lignin, which limits the extent of pathogen spread (Bruce and West, 1989). The products of this enzyme in the presence of a hydrogen donor and hydrogen peroxide have antimicrobial activity and even antiviral activity (Van Loon and Callow, 1983). Recently, a novel heme peroxidase intrinsically resistant to H2O2 was isolated from R. sativus (Japanese d aikon), which showed relatively stronger oxidative stability than that of reference horse radish peroxidase (HRPA2) (Rodrà ­guez et al, 2008). Biological activities of R. sativus Evidence from numerous investigations reveals that the biological and pharmacological functions of R. sativus are mainly due to its GLs and its breakdown products ITCs (Esaki and Onozaki, 1982; Nakamura et al 2001; Barillari et al, 2006; Papi et al, 2008). These compounds provide to R. sativus its characteristic odor and flavor as well as most of their biological properties. GLs and/or ITCs have long been known for their fungicidal, bacteriocidal, nematocidal and allelopathic properties (Brown et al, 1991) and have attracted intense research interest because of their cancer chemoprotective attributes (Fahey et al, 2001; Verhoeven et al, 1997). Polyphenolics, alkaloids, saponins, isoperoxidases and antifungal peptides are also accountable for significant part of the health benefits of R. sativus. These constituents are reported to exhibit several biological effects, including radical scavenging activity (Takaya et al, 2003), gut stimulatory, uterotonic and spasmogenic effects (Gilani and Ghayur, 2004; Ghayur and Gilani, 2005), anti-hyperlipidemic activity (Wang et al, 2002) and anti-atherogenic effects (Suh et al, 2006) and would perhaps work synergistically with GLSs and ITCs of R. sativus. Antioxidant activity Damage to proteins, lipids and DNA by reactive oxygen species (ROS) and reactive nitrogen species (RNS) can lead to a variety of chronic diseases such as cancer, cardiovascular, inflammatory and age-related neurodegenerative diseases (Borek, 1997; Richardson, 1993). ROS/RNS can damage cell membranes, disrupt enzymes, reduce immunity (Ahsan et al, 2003) and induce mutations (Loft and Poulsen, 1996). ROS/RNS are by-products of normal aerobic metabolism and could occur during mitochondrial/microsomal electron transport chain, phagocytic activity or generated from oxidase enzymes and transition metal ions (Nohl et al, 2003; Aruoma et al, 1989). Other sources of ROS/RNS are environmental factors such as pollution, sun damage, cigarette smoke or even some kinds of the foods (Schroder and Krutmann, 2004). These reactive species and the resulting oxidative damages are usually counteracted by the antioxidant defense mechanisms (Bagchi and Puri, 1998). Recent studies evidence that plant-based diets, particularly those rich in vegetables and fruits, provide a considerable amount of antioxidant phytochemicals such as vitamins C and E, glutathione, polyphenolics, sulfur containing compounds and pigments, which offer protection against cellular damage (Dimitrios, 2006). Vitamins Ascorbic acid is found to be the most effective antioxidant in inhibiting lipid peroxidation initiated by a peroxyl radical initiator among several types of antioxidants including a-tocopherol (Fei et al, 1989). Ascorbic acid is also capable of scavenging hydrogen peroxide, singlet oxygen, superoxide and hydroxyl radicals efficiently (Fei et al, 1989). It is also involved in the regeneration and recycling of tocopherols and ß-carotene (Niki et al, 1995). Numerous studies have shown that ascorbic acid is effective in lowering the risk of developing cancers (Block, 1991) and cardiovascular diseases (Trout, 1991). In spite of the overwhelming evidence on the health benefits, however, there are reports that demonstrated the pro-oxidant activity of ascorbic acid (Podmore, 1998). Tocopherols are essential vitamins with their major role as antioxidants in protecting polyunsaturated fatty acids (PUFAs) and other components of cell membranes and low-density lipoprotein (LDL) from oxidation , thereby preventing the onset of heart diseases (Rimm et al, 1993). Polyphenolics Polyphenolics is an extremely comprehensive phrase that covers many different subgroups of phenols and phenolic acids. These compounds are most commonly present in fruits and vegetables. They are essential to the physiology of plants, being involved in diverse functions such as lignification, pigmentation, pollination, allelopathy, pathogen/predator resistance and growth (Haslam, 1996). Polyphenolics include single-ring structure such as hydroxybenzoic acids and hydroxycinnamic acids and multi-ring structure such as flavonoids, which can be further classified into anthocyanins, flavan-3-ols, flavones, flavanones and flavonols. Some of the flavonoids such as flavan-3-ols can be found in their dimeric, trimeric and polymeric forms. Most of the polyphenolics are often associated or conjugated with sugar moieties that further complicate the polyphenolic profile of vegetables. Polyphenolics are especially important as antioxidants, because they have high redox potentials, which permit the m to act as reducing agents, hydrogen donors, singlet oxygen quenchers and metal chelator (Kahkonen et al, 1999) and alleviate free radical mediated cellular injury (Shahidi and Wanasundara, 1992). The antioxidant ability of individual polyphenolics may differ, but, as a group, they are one of the strongest groups of antioxidants. The antioxidant activity of a polyphenolic compound is chiefly determined by its structure, in particular the electron delocalization over an aromatic nucleus (Tsao and Akhtar, 2005). When these compounds react with a free radical, delocalization of the gained electron over the phenolic antioxidant and the stabilization of the aromatic nucleus by the resonance effect take place that prevent the continuation of the free radical-mediated chain reaction (Tsao and Akhtar, 2005). Sulfur-containing compounds GLs are a group of sulfur-containing compounds found in the cruciferous plants such as R. sativus, broccoli, cabbage, mustard, wasabi etc. These compounds are found to be strong antioxidants, which are indeed through activation of detoxification enzyme mechanisms for the efficient removal of xenobiotics, rather than through direct radical scavenging capability (Zhang and Talalay, 1998). This property of GLs and its hydrolysis products ITCs is considered as one of the major contributors to its anti-cancer activity (Zhang and Talalay, 1998). Antioxidant activity of R. sativus R. sativus is one of the major sources of dietary phenolic acids and flavonoids, which are mostly present as sugar conjugates (Takaya et al, 2003). The major phenolic acids found in R. sativus sprout are sinapic acid and ferulic acid, which are present in conjugated form as 1-sinapoyl-1-ß-D-glucopyranoside, ß-D-(3-sinapoyl) frucofuranosyl -a-D-(6-sinapoyl) glucopyranoside and 1-feruloyl-ß-D-glucopyranoside (Takaya et al, 2003). The major flavonoids present in R. sativus sprouts is kaempferol that occurs in a conjugated form as kaempferol-3,7-O- a-L-dirhamnopyranoside and kaempferol-3-O- a-L-rhamnopyranosyl-(1-4)- ß-D-glucopyranoside (Takaya et al, 2003). Lugasi et al (1998) demonstrated the strong antioxidant property of squeezed juice extracted from a black R. sativus root through its ability to donate electrons, chelate metal ions and scavenge free radicals in a H2O2/ ·OH-luminol system. Since HPLC analysis revealed the presence of a considerable amount of GLs degradation products and polyphenols in the squeezed juice of black R. sativus, antioxidant activity of black R. sativus root could be attributed to these compounds. Takaya et al (2003) tested methanolic extracts from 11 different plants including Daikon R. sativus sprouts for their ability to scavenge free radicals. Daikon R. sativus sprouts proved to be the most potent, almost 1.8 times more effective than Vitamin C. Souri et al (2004) studied the antioxidant activity of 26 commonly used vegetables in Iranian diet and found that methanolic extract of R. sativus leaf significantly inhibited the peroxidation of linoleic acid as compared to standard antioxidant such as a-tocopherol and quercetin. Katsuzaki et al (2004) found that hot water extract of Daikon R. sativus extract showed more significant antioxidant activity than the extract obtained at an ambient temperature. L-tryptophan was isolated and identified as the compound responsible for the antioxidant activity. They also found that L-tryptophan changed to 5-hydroxy tryptophan (5-HTP), a precursor to serotonin in the rat liver microsome model system. A plant-based 5-HTP supplement is popular for its anti-depressant, appetite suppressant and sleep aiding properties. Lugasi et al (2005) further demonstrated that squeezed juice from black R. sativus significantly alleviated the free radical reaction in rats with hyperlipidaemia by decreasing the lipid peroxidation reactions and by improving the antioxidant status. Recent study also showed that R. sativus extract reduced the extent of lipid peroxidation in a dose dependent manner in rat liver homogenate treated with cumene hydroperoxide by increasing the levels of reduced glutathione and thereby protecting the liver from the toxin induced oxidative damages (Chaturvedi, 2008). Salah-Abbes et al (2008a) showed the protective effect of Tunisian R. sativus root extract against toxicity induced by zearalenone in mice by virtue of its ability to alleviate oxidative stress through stimulation and improvement of the antioxidant status. Polyphenolics in R. sativus may act in a synergistic or additive manner with GLs and/or ITCs and exert their antioxidant activity through inhibition of lipid peroxidation, enhancing the cellular antioxidant enzymes and increasing the glutathione in the cells. Apart from these phytochemicals, R. sativus also contain several classes of peroxidases that could play a significant role in the elimination of toxic peroxides and thus reduce the impact of free radical mediated cellular injury (Wang et al, 2002). Antimicrobial activity Infectious diseases are the worlds leading cause of untimely death, killing approximately 50,000 people every year. Bacteria have a remarkable ability to develop resistance to most pharmaceutical antibiotics. An increase in such antibiotic-resistant bacteria are menacing the human population with a recurrence of infectious diseases that were once thought to be under control, at least in developed countries (Pinner et al, 1996). These antibiotic-resistant bacteria have also caused unique problems in treating infections in patients with cancer and AIDS (Dennesen et al, 1998). Since tenacious and virulent bacteria develop immunity to solitary antibiotics at an alarming speed, there is an imperative need for a holistic targeted approach to search for novel antimicrobials from natural sources, especially from plant kingdom. Long before mankind ascertained the existence of microbes, the fact that certain plants had therapeutic potential was very well accepted. Since ancient times, man has used plants as the widespread remedial tool to treat common infectious diseases. Some of these traditional medicines are still included as part of the habitual treatment of various maladies. Bearberry (Arctostaphylos uva-ursi) and cranberry juice (Vaccinium macrocarpon) are employed to treat urinary tract infections, while species such as lemon balm (Melissa officinalis), garlic (Allium sativum) and tee tree (Melaleuca alternifolia) are described as broad-spectrum antimicrobial agents (Heinrich et al, 2004). Plant based antimicrobials represent a vast unexploited source for medicines, which need to be explored further. They have an immense therapeutic potential as they are effectual in the treatment of infectious diseases while concomitantly alleviating many of the side effects that are frequently connected with synthetic antimicrobials (Cowan, 1999). Plant based anti-infective agents generally have manifold effects on the body and often act beyond the symptomatic treatment of the infectious diseases. Plants have a virtually unlimited capacity to produce secondary metabolites, especially for their defense against predation by microorganisms, insects and herbivores. Many of these secondary metabolites give plants their characteristic odors and also responsible for plant pigments. Antimicrobial phytochemicals are divided into several categories based on their structural similarity as follows: Phenolic acids These are the simplest bioactive phytochemicals consisting of a single substituted phenolic ring. Cinnamic acid and caffeic acids are the common representatives of this group. Phenolic acids are reported to be effective against viruses (Wild, 1994), bacteria (Brantner et al, 1996) and fungi (Duke, 1985). The number and site of the hydroxyl group on the phenol structure are considered to be related to their relative toxicity to microorganisms. Phenolic acids which are in the higher oxidized state are often more inhibitory towards microorganisms than the one with the lower oxidation state (Scalbert, 1991). Thus the mechanisms thought to be responsible for the antimicrobial activity of phenolic acid could include enzyme inhibition by the oxidized compound through interaction with SH groups or through nonspecific interaction with the microbial proteins (Mason and Wasserman, 1987). Quinones They are aromatic compounds with two ketone substitutions in the phenolic ring. They are ubiquitous in nature and show general antimicrobial properties (Duke, 1997). They are extremely active as they can switch between hydroquinone and quinone through oxidation/reduction reactions. Quinones bind with proteins irreversibly, leading to inactivation of proteins and loss of function (Stern et al, 1996). They may also make substrates unavailable to the microbes. Flavonoids They are phenolic structures containing hydroxyl groups. They are ubiquitous and are commonly found in fruits, vegetables, nuts, tea, wine, honey, etc. They are known to be effective antimicrobial compounds against a wide variety of microorganisms (Cushnie and Lamb, 2005). Catechins are the most extensively researched flavonoids for their possible antimicrobial activity due to their occurrence in green tea (Toda et al, 1989). Flavonoids have the ability to complex with extracellular proteins as well as with bacterial cell walls, rendering them inactive (Cushnie and Lamb, 2005). More lipophilic flavonoids may also have the ability to disrupt microbial membrane (Tsuchiya et al, 1996). Terpenoids and essential oils Essential oils are secondary metabolites that are highly supplemented in compounds based on an isoprene structure (Cowan, 1999). They are called as terpenes and usually occur as di, tri, tetra, hemi and sesquiterpenes. When the compounds contain extra elements such as oxygen, they are called as terpenoids. Camphor, farnesol, artemisin and capsaicin are the common examples of terpenoids. Terpenes and terpenoids are active against an array of bacteria (Habtemariam et al, 1993) and fungi (Rana et al, 1997). Previous research showed that terpenoids present in the essential oils of plants could be useful in the control of Listeria monocytogenes (Aureli et al, 1992). The mechanism action of terpenes is not yet established precisely, but is speculated to be due to the disruption of bacterial cell membrane by the lipophilic terpenoids (Mendoza et al, 1997). Alkaloids Alkaloids constitute large groups of compounds containing a nitrogen atom in a heterocyclic ring, with a broad range of biological activities. The first medically functional alkaloid was morphine isolated from Papaver somniferum (Fessenden and Fessenden, 1982). Alkaloids are generally found to have potent antimicrobial activity (Ghoshal et al, 1996). Solamargine, a glycoalkaloid from the berries of Solanum khasianum reported to be useful against HIV infection and intestinal infections associated with AIDS (McMahon et al, 1995). Berberine is an important and frequently studied member of the alkaloid group. It is potentially efficient against trypanosomes (Freiburghaus et al, 1996) and plasmodial infections (Wright et al, 1992). The mode of action responsible for the antimicrobial activity of alkaloids may be attributed to their ability to intercalate with DNA and arresting the metabolic activity of the bacterial cells (Phillipson and ONeill, 1987). Sulfur-containing compounds Sulfur-containing compounds encompass a wide array of compounds and usually found in the plants as glucosides (glucosinolates, alliin, etc). These glucosides, during the rupturing of the plant cell wall, are hydrolyzed into volatile sulfur compounds such as ITCs, allicin, allyl sulfide, diallyl disulfate, etc. Biological activity of sulfur-containing compounds is considered to be chiefly due to glucoside degradation products, as intact glucosides usually display much fewer biological activities than their subsequent hydrolysis products (Donkin et al, 1995). The mechanism of action responsible for the antimicrobial activity of sulfur-containing compounds varies. Antimicrobial activity of ITCs, degradation products of GLs, is thought to be related to its NCS group, in which the central carbon atom is highly electrophilic, which could interact irreversibly with

Complicating Conditions of Pregnancy and Childbirth

Maternal stays with complications were about fifty percent more costly $4,100 for non-delivery stays and $3,900 for delivery stays) than delivery stays without complications ($2,600). delivery-related complications accounted for $17. 4 billion, or nearly 5 percent of total hospital costs in the United States. Among non-delivery maternal stays, the following conditions occurred at a rate of 100 or more for every 1,000 hospital stays: early or threatened labor, infections of the genitourinary tract, and hypertension, including eclampsia and pre-eclampsia.Among maternal stays with delivery, rate of 50 99 for every 1 ,OOO eliveries: umbilical cord complications, 1st and 2nd degree perineal lacerations, previous Csection, and abnormal fetal heart rate or rhythm. Patients 35 to 44 years accounted for 15 percent of maternal stays with complicating conditions (with or without delivery), but comprised only 1 percent of delivery stays without complicating conditions. Anne Elixhauser, Ph.D. and Lauren M. Wier, M. P. H. Introduction Complications during pregnancy can pose a serious risk to both maternal and infant health, and are associated with various adverse outcomes, including miscarriage, emorrhage, preterm labor, and low birth weight. An objective of the U. S. Department of Health & Human Services' Healthy People 2020 is to reduce maternal illness and complications related for labor and delivery.This Statistical Brief presents data from the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (N'S) on pregnancy and childbirth hospitalizations with complicating conditions in 2008. All data are reported from the maternal perspective (i. e. , reflecting the experience of the mother, not the newborn). For the purpose of his Brief, †complicating conditions] include all ICD-9-CM diagnosis codes that are in the section entitled †Complications of 3 Pregnancy, Childbirth, and the Puerperium. This Brief presents information on hospital utiliza tion and patient characteristics for the following types of hospital stays for: complicated pregnancy during which no delivery occurred (†non-delivery with complicating conditions]), delivery with complicated pregnancy or delivery (†delivery with complicating conditions]), and delivery without any mention of complicated regnancy or delivery (†delivery without complicating conditions]). In addition, this report provides information on specific types of complicating conditions of pregnancy and delivery.

The Pain of Compare and Contrast Essay Samples for High School

The Pain of Compare and Contrast Essay Samples for High School The cost of an essay rides on the quantity of effort the writer has to exert. Writing a high school essay if you've got the tips about how to do essay effectively. Writing a superb essay requires a lot of time and efforts. Writing a great essay might be a bit of cake if you are feeling inspired. When it has to do with writing an essay, you must deal with an appropriate structure. One other important question is the way to select the ideal essay topics. You are able to use any as the subject of your essay especially whenever you're not assigned any specific theme. Now's the opportunity to compose the core of your essay. It's possible for you to choose books from fiction and non-fiction categories but make sure whatever books you pick, they are from the exact same category. You are able to use books, documentaries, videos, and newspapers to discover relevant information concerning the topics you're discussing. Before you start to compare the 2 subjects, research to secure more knowledge on the topics you're writing about. Keep in mind it cannot be a single subject! Compare and Contrast Essay Samples for High School Ideas The comparison and contrast essay is among the most frequent kinds of academic write-ups you are going to have to write in middle school, higher sc hool or in college. Obviously, writing is among the top learning programs in any significant school institution. When you're in high school, it's definite that you're predicted to do a few write-ups and projects which require pen and paper. There are several more ways, however, in which high school and college are extremely different. Instead, it is going to be up to the student to find out from whom to find the notes he missed when he did not attend class. More when it has to do with high school students they're kept in a well-behaved fashion and asked to adhere to the set rules of dressing as well. Ideas, Formulas and Shortcuts for Compare and Contrast Essay Samples for High School On the flip side, college is a selection. Together with a rise in workload, students are also made to learn appropriate time management skills like how to juggle work, school, all while keeping a social life. Furthermore, the student should receive all the books mainly paying from their own pocket, have some money for their day-to-day requirements and transportation. Only 34% of comparison contrast essay topics are just about to observe the typical graduate, in comparison to the revision stage. Compare and contrast essays are extremely common as they show your comprehension of the topic. Argumentative essays are also called position papers due to their justification of the side of the issue they are written in support of. Have a look at our compare and contrast essay samples to observe how to compose essays of this sort by yourself. If you think differences as opposed to similarities are somewhat more important for your essay, you should wind up getting stressing differences, and vice versa. Or it may be an introduction, then the similarities between the 2 subjects, the differences between both subjects, and a conclusion. To begin with, you'll have to select two distinct topics that you need to compare and contrast. You're able to choose topics that are linked to the differences between the 2 cultures, languages or eras. Any sphere and degree of complexity is going to be taken care of successfully. If you're going to write a comparative essay you have to have a notion of the impacts of distinct elements to the result that you can get at the close of the writing activity. The main reason why it's called block structure is it is discussing the ideas in various blocks. A good example will give a general idea.

Solitary Confinement Is The Violation Of Rights Essay

Solitary confinement surpasses the violation of rights and reaches the level of torture as prolonged exposure to isolation can have irreversible effects. The United Nations, established following the end of World War II, attempted to form universal standards of human rights that would force accountability for each country. This charter was in direct response to the heinous crimes against targeted groups, especially those that were placed in concentration camps. While the U.N. does not specifically mention prisoners, it is clear that everyone is viewed as equal under the law (The United Nations, 1945). In 1948, the United Nations produced the Universal Declaration of Human Rights, in an effort to strive further for equality of rights. Article 5 in this legislation states, â€Å"No one shall be subjected to torture or to cruel, inhuman or degrading treatment or punishment† (The United Nations, 1948). These documents did not have any legal consequences, but were globally viewed a s international law. By 1949, prisoners’ rights became a critical issue in the Geneva Conventions. In particular, the Geneva Convention Relative to the Treatment of Prisoners of War defined how prisoners of war should be treated in the same manner as civil prisoners, while outlining the human rights for all prisoners (The United Nations, 1949). Solitary confinement was viewed as legal, but used sparingly. It would take several decades and numerous studies on the effects of solitary confinement for globalShow MoreRelatedSocial Welfare Policy Reading Essay : Solitary Confinement Essay1663 Words   |  7 PagesSocial Welfare Policy Reading Essay: Solitary Confinement RaeLynn Barott Minnesota State University, Mankato September 26th, 2016 There have been various studies conducted over the past few decades that show the devastating consequences of the use of solitary confinement in prisons. Studies show that the method of solitary confinement has the potential to lead to severe psychological effects on prison inmates. To address the consequences of solitary confinement in the U.S. federal prison system, PresidentRead MoreThe Efforts Of Solitary Confinement Essay1355 Words   |  6 Pagesdedicated to the efforts of stopping solitary confinement completely. Most are dedicated community members coming together in solidarity to make a change. States such as California have begun to organize one day per month for advocates to participate in Statewide Coordinated Actions to End Solitary Confinement. People gather at various locations to expose the Department of Corrections and Rehabilitation’s actions and rally support efforts to secure their rights. They hope that as more people becomeRead MorePrison Officials : A New Form Of Punishment Essay1398 Words   |  6 Pagesa cramped, concrete, windowless cell for between 22 and 24 hours a day. Solitary confinement for many prison officials has been a method to deal with difficult or dangerous prisoners. Recreation for these prisoners is often only three to five hours a week alone in another cage with little to no purposeful activities. There has been numerous class actions challenging prolong solitary confinement. Due process along with rights guaranteed under the eighth and fourteenth amendment has been brought intoRead MoreA Look Into The World Of Solitary Confinement Essay1614 Words   |  7 PagesA Look into the World of Solitary Confinement Looking back to the early nineteenth century, the United States had adopted a new form of punishment. The punishment involves imprisoning a person in a cramped, concrete, sometimes windowless cell for hours ranging from 22 to 24 hours a day. Solitary confinement for many prison officials has been one of the primary methods to deal with difficult and sometimes dangerous inmates. Recreation for the rest of the prison population is usually about an hourRead MoreDrawbacks of Solitary Confinement1716 Words   |  7 PagesNot too many people know what Solitary confinement is or what it can do to a human being. Solitary confinement is a special form of imprisonment. The prisoner is confined in a small windowless unit completely isolated from any human contact. It is a form of punishment for behavior modification beyond incarceration for a prisoner and is used as an additional measure of protection from the inmate. The issue of solitary confinement is extremely controversial and is a complicated subject to decide onRead MoreIncarceration : Cruel And Unregulated Punishment Essay907 Words   |  4 PagesIncarceration: Cruel Unregulated Punishment Inmates held in the United State’s prison system face critical exposure to numerous violations of their basic human rights. Abuses of power present themselves in a myriad of ways, including; the unregulated approach in which prison facilities enforce solitary confinement, the misuse of â€Å"compassionate release† policies and the judicial system’s wrongful imprisonment of individuals suffering from mental illness and, or mental disability. In most casesRead MorePros And Cons Of Solitary Confinement1001 Words   |  5 PagesOver the last couple of decades, prison systems have adopted the use of solitary confinement as a means of punishment and have progressively depended on it to help maintain obedience and discipline inside the prison structure. Solitary confinement is a form of incarceration in which a prisoner is isolated in a cell for multiple hours, days, or weeks with limited to no human contact. According to the American Civil Liberties Union, the Unite d States represents only 5% of the worlds population yetRead MoreThe Incarceration Of Solitary Confinement1722 Words   |  7 Pagesby inmates were because they were in solitary confinement (Breslow, 2014). Although some inmates have failed at their suicide attempts, that does not mean that they have not attempted to end their lives. There is a higher rate of inmates self mutilating while being in solitary confinement than if they were in the general prison population (Breslow, 2014). This means that inmates that are isolated are more of a danger to themselves. Being in solitary confinement also attributes to personality disordersRead MoreThe Effects Of Solitary Confinement On Adolescents1243 Words   |  5 PagesThe Effects of Solitary Confinement in Adolescents Solitary confinement is a method of reform in prisons, which is mainly used when inmates defy the rules and regulations of the prison system. It is also used to protect juveniles from adult inmates and/or dangerous situations within the prison; however, solitary confinement can be viewed as cruel and unusual punishment. Prisoners can be in complete isolation in a cell that is approximately six feet by eight feet with little or no light; there isRead MoreSolitary Confinement Is The United States State Penitentiary2391 Words   |  10 PagesMerriam-Webster dictionary, Solitary Confinement is the confinement of a prisoner in a cell or other place which he or she is completely isolated from any and everyone. Merriam Webster also states that even some prisoners are held from 22.5 to 24 hours a day. Solitary confinement is sometimes referred to as isolation, segregation, separation, and cellular confinements so that it seems different from solitary confinement or too make it sound like a less harsh punishment. Solitary Confinement is a huge controversy