By O. Silas. Texas Southern University. 2018.

Sakuta M 2.5 mg methotrexate mastercard, Komamine A (1987) In: Vasil I (ed) Cell Culture and Somatic Cell Geneticis of Plants methotrexate 2.5 mg discount. Kintzios S generic methotrexate 2.5 mg on line, Adamopoulou M, Pistola E, Makri O, Delki K, Drossopoulos J (2002) J Herbs Spices Med Plant 9:229 46. Tada H, Murakami Y, Omoto T, Shimomuta K, Ishimaru K (1996) Phytochemistry 42:431 47. Furmanowa M, Glowniak K, Syklowska-Baranek K, Zgorka G, Jozefczyk A (1997) Plant Cell Tiss Org Cult 49:75 57. Bai J, Ito N, Sakai J, Kitabatake M, Fujisawa H, Bai L (2005) J Nat Prod 68:497 63. Bai J, Kitabatake M, Toyoizumi K, Fu L, Zhang S, Dai J, Sakai J, Hirose K, Yamori T, Tomida A, Tsuruo T, Ando M (2004) J Nat Prod 67:58 64. Kintzios S, Barberaki M, Tourgelis P, Aivalakis G, Volioti A (2002) J Herbs Spices Med Plants 9:217 Chapter 5 Guggulsterone: a Potent Natural Hypolipidemic Agent from Commiphora wightii – Problems, Perseverance, and Prospects K. Guggulsterone is a safe and effective natural product for hypercholesterolemia that has been used as such for the past 3000 years in Ayurveda. It is obtained from a very slow growing desert tree endemic to the Thar Desert and has become endangered due to its over exploitation. Oleogum-resin is a complex mixture of several classes of compounds including gum, minerals, essential oils, sterols, fa- vanones, and sterones. Early chemical and pharmacological work was carried out in India, but after approval by the United States Food and Drug Adminis- tration as a food supplement, several reports describe a role for guggulsterone in the excretion of cholesterol, involving the farnesoid X receptor, pregnane X receptor, Cyp-7A1 gene, and the bile salt export pump. Biotechnological ap- proaches have been made to develop micropropagation methods through axil- lary bud break and somatic embryogenesis, as well as guggulsterone produc- tion through cell cultures grown in shake fasks and bioreactors. This review summarizes the research already carried out and that needs to be done to elucidate the biosynthetic pathway, mechanism of action, and biotechnological production of guggulsterone through cell cultures before commercialization of the molecule as a drug. Since it is a very slow growing plant, the returns from the plant are only after several years and thus, not preferred for social forestry. It is generally distributed in arid regions of Africa and the Indian side of Thar Desert. In the Indian subcontinent, Commiphora species occur in Pakistan, Baluchistan, and India. The plant is a shrub that reaches 3 m in height and has crooked, knotty branches ending in sharp spines. The papery bark peels in fakes from the older parts of the stem, whereas younger parts are pubescent and glandular leaves are trifoliate. Hand pollination experiments and embryological studies have confrmed the occurrence of nonpseudogamous apomixis, nucellar polyembryony, and autonomous endosperm formation. It was inferred that apomixis might have a signifcant role in the speciation of tropical trees. Apomixis may be favored by natural selection if the population densities are low and the distance between individual trees is greater than the permissible cross-pollination range. They observed that although pollen grains germinated on stigma, the pistil did not support pollen tube growth, perhaps due to an alteration in the orientation of the cells of the transmitting tissue and the absence of proteins in the intercellular matrix. The seed set is about 16 % in the plant in the Aravalli Ranges [5] and in drier parts of Western Rajasthan it is even lower. The plant is cut mercilessly by villagers for cooking food and is used with other wet woods to facilitate burning [6]. Due to these biological and social problems, the plant has become an endangered species [7]. The development and widening of the gum-resin canal in the young stem occurs schizogenously. The yellow, fra- grant latex oozes out through the incisions and slowly solidifes into vermicular or stalactitic pieces, which are collected manually. Application of ethephon on the incisions enhances guggul production 22-fold over that obtained in the control condition. Guggul production is highest with the onset of summer (a stress-in- duced secondary product formation), as supported by observations with bright- feld and fuorescence microscopy. But in the long-term, excessive production through ethephon application exhausts the plant and as a result, kills it [8]. The ethyl acetate- soluble fraction (45 %), hereafter in this text referred to as gug- gul, contains all active constituents, while the insoluble fraction (55 %) contains gum, minerals, and other toxic ingredients (Fig. Details of the separa- tion of various guggul components are described in an excellent review [10]. Meselhy [11] used a different approach using column chromatography for sepa- ration of guggulsterones and isolated guggulsterone-M. The ketonic part is the most important bioactive fraction (12 % of the ethyl acetate-soluble fraction) and contains about two dozen compounds including sterols and guggulsterone- E and guggulsterone-Z (Fig. Guggulsterone and guggulsterol, and its derivatives, are known to occur in some other plants and lower animals (Ta- ble 5. These compounds help during insect molting [12] and are involved in defense of these insects from predators [13]. The two isomers, guggulsterone-E and guggulsterone-Z, are interconvert- ible, as we recorded in callus and cell cultures of the plant grown under differ- ent conditions in our laboratory. Similarly, fungus (Aspergillus niger, Cepha- losporium aphidicola) culture converted guggulsterone-E into guggulsterone-Z and several other derivatives [14].

The majority of lightening lotions contains a healthy dose of kojic acid in it beside vitamin C (ascorbic acid) order methotrexate 2.5 mg online, bearberry extract buy methotrexate 2.5 mg fast delivery, licorice or mulberry; in some cases cheap methotrexate 2.5mg overnight delivery, kojic acid is the main active ingredient. Most skin lightening lotions that use kojic acid as one of their ingredients also use small amounts of hydroquinone as well as glycolic acid (Fig. In addition, kojic acid is found to prevent photodamage and subsequent wrinkling of the skin in the hairless mouse. It is a good chelator of transition metal ions and a good scavenger of free radicals therefore it is an effective agent for photoprotection (Mitani, 2001). Current evidence suggests that it induces skin depigmentation through suppression of free tyrosinase, mainly due to chelation of its copper at the active site of the enzyme (Chen, 1991; Jun, 2007; Lee, 2006). It has been demonstrated to be responsible for therapy and prevention of pigmentation, both in vitro and in vivo and being used for topical application. In treatment of melasma which continues to be a difficult problem, the addition of kojic acid in a gel containing glycolic acid and hydroquinone improved melasma. Previous antimicrobial activity studies showed that kojic acid was more active against gram negative bacteria than against gram positive ones (Bentley, 2006). However, some of its derivatives have shown adverse effects different from kojic acid’s antibacterial activity results (Aytemir, 2003a, 2003b; Fassihi, 2008; Kotani, 1978; Masoud, 1989; Petrola, 1985; Veverka, 1992). According to its antibacterial and fungicidal properties, kojic acid is used as a food additive (Burdock, 2001). There are several forms of kojic acid containing products including soap, cream, lotion and gel. Kojic acid also has antifungal and antibacterial properties in it, making it a perfect ingredient to be used in soap. Women who choose a kojic acid lotion tend to use it to treat smaller areas of the skin that have been affected by hyperpigmentation, age spots or hormone related skin conditions brought on by pregnancy or birth control pills. Some women favor this lotion because it absorbs directly into the skin much better than creams or soaps. One of the greatest benefits to using kojic acid is reduction of getting wrinkles when you use the lotion before exposure to the sun. Based on such tyrosinase-inhibiting activity of kojic acid, there have been proposed a lot of cosmetic compositions containing kojic acid as an active ingredient. There are a variety of kojic acid creams available for purchase online and in certain specialty stores. Each one has its own unique blend of ingredients which set 8 Medicinal Chemistry and Drug Design them apart from one another. Some creams combine various vitamins like A and E which give them different effects. The reason many people mix these vitamins within the kojic acid creams is to help them alleviate the skin irritation that has been said to occur with kojic acid products. These ingredients are added to this base to help counteract the sensitivity that is associated with prolonged use of kojic acid when it is used by itself. The development of tyrosinase inhibitors is of great concern in the medical, agricultural, and cosmetic fields. Among the many kinds of tyrosinase inhibitors, kojic acid has been intensively studied. It acts as a good chelator of transition metal ions such as Cu2+ and Fe3+ and a scavenger of free radicals. This fungal metabolite is currently applied as a cosmetic skin-lightening agent and food additive to prevent enzymatic browning. Kojic acid shows a competitive inhibitory effect on the monophenolase activity and a mixed inhibitory effect on the diphenolase activity of mushroom tyrosinase. However, its use in cosmetics has been limited, because of the skin irritation caused by its cytotoxicity and its instability during storage. Accordingly, many semi-synthetic kojic acid derivatives have been synthesized to improve its properties by converting the alcoholic hydroxyl group into an ester, hydroxyphenyl ether, glycoside, amino acid derivatives, or tripeptide derivatives (Kang, 2009; Lee, 2006). It was also confirmed that the kojic acid-phenylalanine amides reduced the amount of dopachrome production during the melanin formation. The metal complexes of kojic acid-phenylalanine-amide exhibited potent tyrosinase inhibitory activity both in vitro enzyme test and in cell-based assay system. These results demonstrated that metal complex formation could be applied as a delivery system for hydrophilic molecules which have low cell permeability into cells. In addition, these new Kojic Acid Derivatives 9 materials can be used as an effective whitening agent in the cosmetic industry or applied on irregular hyperpigmentation (Kwak, 2010). Furthermore, kojic acid was shown to inhibit different enzymes relevant to the undesirable melanosis of agricultural products, which is related to its coordination ability to, e. Chemical structure of some synthetic kojic acid derivatives as tyrosinase inhibitors. It was reported that compound, joining to two pyrone rings of kojic acid through an ethylene linkage, exhibited 8 times more potent mushroom tyrosinase inhibitory activity than that of kojic acid and also showed superior melanin synthesis inhibitory activity using B16F10 melanoma cell (Lee, 2006). A series of kojic acid derivatives containing thioether, sulfoxide and sulfone linkages were synthesized. Sulfoxide and sulfone derivatives decreased and kojyl thioether derivatives containing appropriate lipophilic various alkyl chains increased tyrosinase inhibitory activity (Rho, 2010). Kojic acid derivatives, containing ester linkages such as hydrophobic benzoate or cinnamate groups, increased the inhibitory activity of kojic acid. When the enolic hydroxyl group of ester derivatives was protected by a methyl group the activity was lost completely.

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The variables ment Project with signifcant correlation in the Pearson’s correlation analysis *D buy cheap methotrexate 2.5 mg on line. While this abstract contains the pre-intervention and 47 of the projected 100 post – intervention pa- Introduction: In elderly females proven 2.5 mg methotrexate, painful knee osteoarthritis tients discount 2.5mg methotrexate otc, fnal data will be available at the Congress. This infammatory sis on 47 patients was conducted and compared to data collected process of the surrounding synovium has been associated with pre-intervention (n=127). Total number of medications decreased the degree of knee painand the predicted progression of cartilage from 12. Conclusions: Finding support the use of tion program (included hyaluronic acid treatment). Results: All females were accomplished with the outpatient rehabilita- Relationships between Toe Grip Strength, and Dynamic tion. The association between knee synovitisand ing Elderly Japanese Individuals joint effusion was highly signifcant. Conclusion: Synovitis and effusionsare common in of daily walking and twice-a-week strength training. Ultrasound exam is necessary for assessing periarticular was a randomized-controlled crossover with four 6-month phases: and intraarticular abnormalities. Results: The main results concerning physi- destruction by changing the complex infammatory joint process. An increase was also seen in total lean mass, but in the control phase, Pulmonary Function the lean mass decreased back to baseline and the total fat mass *T. Conclusion: The study shows how Introduction/Background: Few adequate community-based health- important it is to pay attention to the health status of older adults. We have developed vention that consists in daily physical activity in form of walking a 10 minute exercise program aimed at: (i) maintenance and and resistance training twice a week. The research outcome shows improvement of pulmonary function for prevention of pneumo- clearly that older adults can obtain multiple benefts by participat- nia; (ii) relief of dependent edema; (iii) prophylaxis against stiff ing in systematic physical training where frequency, duration and shoulder and lumbago; and (iv) maintenance of joint function. One can assume that training of this The purpose of this study was to evaluate the effects of the pro- sort, as organized in the study, can prevent premature impairment gram, particularly on participants’ pulmonary function. Materials of mobility, work against cardio metabolic risk factors and main- and Methods: Pulmonary function, foot swelling, and symptoms tain the quality of life of older adults. Findings were also Analog and Interactive Tests for Training of Selective and compared at initiation of the program, 3 months, and 6 months Sustained Attention in Older Adults in the W/C group (8 subjects). Results: There were no signifcant differences between the groups in sex, age or height. The test is confgured to perform basic troubleshooting, than at initiation of the program (p<0. Community-based search is qualitative for the research on design, where all designed health-enhancing exercise programs to maintain or improve pul- it is a pretext to collect data, by using comprehensive approaches monary function of physically handicapped persons should be fur- on created experiences. Results: Given the conditions of the study cessful Aging population and under the guidance of ethnographic research, the sta- *J. References: 1) Aguerre are of special interest for older individuals, because of their high C. Le vieillissement réussi: Théories, recherches et ap- rate of disability, functional dependence and use of healthcare re- plications cliniques. It is hoped that the experiences of this analysis will 1 2 assist in improving future endeavours of care home research in Chung-Ang University, Chung-Ang University, College of Medi- small communities both locally and abroad. Subject: Pausing Before Ascending a Step During Walking: Ef- 15 elderly and 15 young people who had not have signifcant past fects on Standing Balance after Ascending medical history that might affect the function of mastication or swallowing were enrolled. Methods: On the upright-seated position, subjects were asked to take the test foods that were prepared for this study. While young adults typically climb up the step directly, (5x103 N/m2 hardness), grade2 (2,104 N/m2), grade3 (5x104 N/ older adults can often be observed to deliberately come to a pause m2) and grade4 (5x105 N/m2) and 8 g of each types of food was before ascending. Material and Methods: A total of 23 of oral cavity to swallowing the each bolus of the test foods. An accelerometer with a sampling rate of 148 Hz was placed at the spinous process of the 3rd lumbar vertebrae to estimate cal difference in the young and elderly group. The elderly required higher chewing force ratio than the showed that the acceleration decreased markedly after the frst 0. Conclusion: Pausing before ascending a step could improve Care Home Research: Problems and Limitations the control of the mediolateral balance shortly after step ascent, and *J. Introduction: There is very limited research carried out in care home populations because of the challenges this particular popula- tion presents. Data Collection: Face-to-face interviews with the sevenhealthcare andallied clinical *D. Datta2 professionals, who had conducted research as part of a post-gradu- 1West Bengal State University, 2West Bengal University of Health ate degree, over a fve year period through the University of Malta. Unlike the developed world, this is a relatively recent phe- searchers included appropriate sampling of participants, obtaining nomenon for poorer countries. However, greater longevity has sel- informed consent, involvement of staff and relatives, obtaining dom been associated with good health but with long years of disabil- funding, and issues with publication. The disability prevalence rate for both severe ity issues, staff involvement and interview techniques. Material and Method: To identify bers in the research projects wherever possible; arranging pre- the strongest determinant affecting the wellness of the geriatric disa- interview sessions and ensuring an in-depth knowledge of internal bled, a survey was conducted at Kolkata, an Indian mega polis. The care home politics (both internal and external) prior to commenc- frst stage sample was drawn from the database of 30 physicians (six J Rehabil Med Suppl 54 E-Posters 319 each practicing across fve zones). Every third geriatric patient was 1Kangwon National University Hospital, 2Kangwon National short-listed (n=84, range=20).

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Here buy 2.5mg methotrexate overnight delivery, the connection between primary metabolism and secondary metabolism seems to be caused by pressure in the culture medium discount methotrexate 2.5mg without prescription, 90 S discount methotrexate 2.5 mg online. Although cultures demonstrated a continuous growth during an incubation period of 5 weeks, the cell dehydrogenase activity and the cytochrome c oxidase activity of isolated mitochondria declined. Stem segments, needles, and roots contain taxane diterpenes, among them taxol (paclitaxel; Fig. About 30 % and 43 % of paclitaxel in the cells was located in the cell wall of the cells grown in solid culture in the growth phase and in the stationary phase, respectively. In comparison with the cell suspension culture, protoplasts in a static culture and the protoplasts immobilized in agarose gel in shaking culture resulted in a sixfold increase in the extracellular taxol accumulation. Release of taxol and other taxanes into the culture medium can be facilitated by the digestions of the cell wall of cultured cells, as demonstrated for T. Biosynthesis of the N-ben- zoyl phenylisoserinoyl side chain of the anticancer drug Taxol starts with the conversion of 2S-alpha-phenylalanine to 3R-beta-phenylalanine by phenylala- nine aminomutase [66]. A key enzyme in the taxane biosynthetic pathway is taxadiene synthase, which can be elicited by methyl jasmonate. Reduction of the keto group at the C-3 position of the structure of methyl jasmonate greatly reduced this activity, whereas cis-jasmone, which does not have a carboxyl group at the C-1 position, had almost no activity. A time-course analysis by Tabata [68] revealed two regulatory steps in tax- ane biosynthesis: the taxane-ring formation step and the acylation step at the C-13 position. The production of paclitaxel reached a maximum level of 295 mg·l–1 in a large-scale culture using a two-stage process. Some studies indicate that oxidative stress (in par- ticular the accumulation of intracellular and extracellular H2O2) might be one factor promoting taxol biosynthesis. Furthermore, Han and Yuan [73] investigated the relationship between active oxidative spe- cies and defense responses induced by the shear stress during culture of T. During stage I (biomass growth), B5 medium was gradually supplemented with vanadyl sulfate (0. Since the early experimentation with Taxus cell suspensions, it became rather apparent that taxol would be produced during late or nongrowth stages of the cultures. These early results suggest that a two-stage cul- ture may be benefcial for optimizing taxol accumulation in vitro. Taxol excretion by the cells increased with inoculum age but decreased with inoculum size. They used parental cultures and their subcultures from fve different cell lines to test whether a high-taxol-producing culture grows more slowly or dies more rapidly than a low-producing one. These cell lines were of three types: (1) taxol-produc- ing with and without methyl jasmonate, (2) taxol-producing only upon elicita- tion, and (3) nonproducing. High-producing cultures showed growth inhibition upon subculture, whereas nonproducing cultures and elicited cultures show little growth inhibition. Thus, growth inhibition was due primarily to taxol or taxane accumulation, so that culture components were generated by cells alter culture properties. To assess variability as a function of culture lineage, two groups of replicate cultures were generated either with a mixing of the parental fasks or segregation of parental fasks at each subculture. Although parental culture mixing did not reduce fask-to-fask variation, the production level of taxol in subcultures resulting from mixing inocula was sustained at a higher level relative to segregated subcultures. Taxol was released to the extracellular medium as it was produced, with little intracellular retention (≤10 %). Although the same taxol titers (22 mg·l–1) could be obtained in both reactor types, nutrient uptake rates were faster in the airlift bioreactor than in shake fasks. However, formation of a growth ring in the bioreactor reduced the yield of cell mass. The oxygen supply exhibited signifcant infuence on the production of taxol, which increased when the level of dissolved oxygen was increased to 40–60 %. The taxol content of immobilized cells was fourfold that of suspended cells at day 35. Immobilization shortened the lag period of cell growth and increased H O and O2– contents inside the culture microenvironment. More 2 2 recently [81], the same research group observed distinct spatiotemporal varia- tions of metal ions and taxol production in the immobilized cell culture system. The taxol content in the inner foam layer reached 215 mg·g–1, which was 40- fold higher than that in the outer foam layer and was accompanied by higher intracellular Ca2+ and Mg2+ contents and a lower intracellular K+ content. Indeed, several reports provide technically and economically feasible protocols for a plethora of compounds such as catharanthine [82], podophyllotoxin [83] and mistletoe lectins [84]. One might wonder, however, why in vitro plant systems are currently operating in a very limited number of commercial production systems, such as shikonin, ginsenosides, and berber- ine [8]. It is not diffcult to answer such a question: although both bioreactor and immobilization techniques were developed more than 20 years ago, our knowledge on cellular behavior under conditions of scale-up culture are still extremely limited and are mainly restricted to the level of empirically defning growth–productivity relationships. Unfortunately, basic research in this feld has rather been neglected, at least compared to advances on the side of ap- plications. Therefore, future challenges lie mainly in understanding the principles of scaled up metabolite biosynthesis. Given the current rapid progress in research of cell biology in vitro, it is not unrealistic to expect that plant cell culture systems will provide a signifcant source of pharmaceuticals and other chemicals in the next 5–10 years. Robins R, Parr A, Richards S, Rhodes M (1986) In: Morris P, Scragg A, Stafford A, Fowler M (eds) Secondary Metabolism in Plant Cell Cultures. Shetty K, Ohshima M, Murakami T, Oosawa K, Ohashi Y (1997) Food Biotechnol 11:11 18. Sumaryono W, Prokasch P, Hartmann T, Nimitz M, Wray V (1991) Phytochemistry 30:3267 22. Omoto T, Murakami Y, Shimomura K, Yoshira K, Mori K, Nakashima T (1997) Jpn J Food Chem 4:11 24.

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