86 resultados para Concomitant Methotrexate


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The variations in the activities of the alkaline and acid phosphatases of the silkworm, Bombyx mori, were studied in all stages of the life cycle. From hatching until the spinning stage a steady increase was recorded in the activity of both the enzymes followed with a conspicuous decrease at each moult. During the pupal stage the alkaline phosphatase was almost absent, whereas the acid phosphatase maintained a high and constant value. Increase or decrease of the activity of the enzymes during larval development was reflected in a decrease or increase in the acid-soluble phosphorus content. Acid phosphatase activity slowly increased from laying of the eggs to hatching of the larvae with a concomitant decrease in the acid-soluble phosphorus. Tissue analysis showed a high concentration of the alkaline enzyme in the intestines, but the haemolymph was almost free of both enzymes. Feeding of inorganic phosphate increased the alkaline enzyme in the intestines, whereas glucose had no effect on either of the enzymes in the intestines.

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1,2-Enedioic systems, being sterically perturbed from planarity do not show the effect of the extended conjugation expected of a (formal) trienic entity. In the absence of a model which approximates to a uniplanar situation, the strategy of replacing an ester group in the enedioates by a cyano (for which less stringent steric demand may be presumed) and noting the correction concomitant to this replacement was adopted to arrive at a notional figure for the position of maximal absorption in the planar enedioates. From this the conclusion, subject to substantiation by molecular mechanical or quantum chemical calculations, was drawn that even the E-isomeric and comparatively less substituted enedioates are highly sterically perturbed. An alternative to an earlier explanation of the bathochromic shift of absorption maxima encountered in the 5-cyclic ene-ester and ene-nitrile, relative to the 6-cyclic analogues (observed also with the enedioates and cyanovinyl ester systems), seen later to have been based on unwarranted premises, has been advanced. A comment on the absorption characteristics of enedioic anhydrides has been appended.

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The utility of rice husk as an adsorbent for metal ions such as iron, zinc and copper from acid mine water was assessed. The adsorption isotherms exhibited Langmuirian behavior and were endothermic in nature. The free energy values for adsorption of the chosen metal ions onto rice husk were found to be highly negative attesting to favorable interaction. Over 99% Fe3+, 98% of Fe2+ and Zn2+ and 95% Cu2+ uptake was achieved from acid mine water, with a concomitant increase in the pH value by two units using rice husk. The remediation studies carried out on acid mine water and simulated acid mine water pretreated with rice husk indicated successful growth of Desulfotomaculum nigrificans (D. nigrificans). The amount of sulphate bioreduction in acid mine water at an initial pH of 5.3 was enhanced by D. nigrificans from 21% to 40% in the presence of rice husk filtrate supplemented with carbon and nitrogen. In simulated acid mine water with fortified husk filtrate, the sulphate reduction was even more extensive, with an enhancement to 73%. Concurrently, almost 90% Fe2+, 89% Zn2+ and 75% Cu2+ bioremoval was attained from simulated acid mine water. Metal adsorption by rice husk was confirmed in desorption experiments in which almost complete removal of metal ions from the rice husk was achieved after two elutions using 1 M HCl. The possible mechanisms of metal ion adsorption onto rice husk and sulphate reduction using D. nigrificans are discussed.

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Temperature-dependent x-ray powder-diffraction study of the tetragonal compositions of PbTiO3-BiFeO3 series has revealed that, unlike for all the known ferroelectric perovskites, the compositions exhibiting giant tetragonality is stabilized from the cubic phase via a complex transition pathway which involve (i) formation of minor monoclinic phase with a large pseudotetragonality along with an intermediate tetragonal phase (major) with a small tetragonality, (ii) gradual vanishing of the intermediate tetragonal phase and concomitant increase in the monoclinic regions, and finally (iii) gradual transformation of the monoclinic phase to the tetragonal phase with giant tetragonality.The system seems to adopt such a complex transition pathway to create amicrostructure with very large number of domains and interfaces for stress relief, which would not have been possible in case of a direct cubic-tetragonal transition.

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Several lines of evidence suggest that cancer progression is associated with up-regulation or reactivation of telomerase and the underlying mechanism remains an active area of research. The heterotrimeric MRN complex, consisting of Mre11, Rad50 and Nbs1, which is required for the repair of double-strand breaks, plays a key role in telomere length maintenance. In this study, we show significant differences in the levels of expression of MRN complex subunits among various cancer cells and somatic cells. Notably, siRNA-mediated depletion of any of the subunits of MRN complex led to complete ablation of other subunits of the complex. Treatment of leukemia and prostate cancer cells with etoposide lead to increased expression of MRN complex subunits, with concomitant decrease in the levels of telomerase activity, compared to breast cancer cells. These studies raise the possibility of developing anti-cancer drugs targeting MRN complex subunits to sensitize a subset of cancer cells to radio- and/or chemotherapy. (C) 2010 Elsevier Inc. All rights reserved.

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Significant destruction (68%) of liver microsomal cytochrome P-450 and homogeneous cytochrome P-450 purified from PB-treated rats is noticed upon incubation with 10 mM pulegone at 37-degrees-C for 30 min. There is also a concomitant loss of heme. The destructive phenomenon does not require metabolic activation of pulegone. The destruction of purified cytochrome P-450 is time-dependent and saturable. Structure-activity studies suggest that an alpha-isopropylidine ketone unit with a methyl positioned para to the isopropylidine group as in pulegone is necessary for the in vitro destruction of cytochrome P-450. SKF-525A at a concentration of 4-mM obliterates the destruction of cytochrome P-450 by pulegone. Experiments with C-14-pulegone suggest that pulegone or its rearranged product binds covalently to the prosthetic heme of cytochrome P-450.

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Ternary cobalt(III) complexes CoL(B)] (1-3) of a trianionic tetradentate phenolate-based ligand (L) and phenanthroline bases (B), viz. 1,10-phenanthroline (phen in 1), dipyridoquinoxaline (dpq in 2) and dipyridophenazine (dppz in 3) are synthesized, characterized from X-ray crystallographic, analytical and spectral techniques, and their utility in photodynamic therapy (PDT) of thyroid diseases caused by TSH receptor dysfunction is probed. The complexes display a visible spectral band within the PDT spectral window at similar to 690 nm. Photodynamic potential was estimated through DNA cleavage activity of the dpq and dppz complexes in UV-A light of 365 nm and red light of 676 nm. The reactions proceed via the hydroxyl radical pathway. The complexes retain their DNA photocleavage activity in red light under anaerobic conditions, a situation normally prevails in hypoxic tumor core. Investigation into the photocytotoxic potential of these complexes showed that the dppz complex 3 is approximately 4-fold more active in the HEK293 cells expressing human thyrotropin receptor (HEK293-hTSHR) than in the parental cell line and has an insignificant effect on an unrelated human cervical carcinoma cell line (HeLa). Photoexcitation of complex 3 in HEK293-hTSHR cells leads to damage hTSHR as evidenced from the decrease in cAMP formation both in absence and presence of hTSH and decrease in the TSHR immunofluorescence with a concomitant cytoplasmic translocation of the membrane protein, cadherin. The involvement of hTSHR is evidenced from the ability of complex 3 to bind to the extracellular domain of hTSHR (hTSHR-ECD) with a K-d value of 81 nM and from the photocleavage of hTSHR-ECD.

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A specific membrane receptor for plasma retinol-binding protein has been demonstrated in testicular cells. Prealbumin-2 did not show any specific binding to the membrane. The affinity of retinol-binding protein for receptor drastically decreases upon delivery of retinol and the retinol-binding protein does not enter the cell. The mechanism of delivery of retinol to the target cell by plasma retinol-binding protein has been investigated. The process involves two steps: direct binding of retinol-binding protein to the receptor and uptake of retinol by the target cell with a concomitant drastic reduction in the affinity of the retinol-binding protein to the receptor. Probably the second step of the process needs a cytosolic factor, possibly the cellular retinol-binding protein or an enzyme.The binding of retinol-binding protein to the receptor is saturable and reverible. The interaction shows a Kd value of 2.1 · 10−10 M. The specific binding of a retinol-binding protein with great affinity has been employed in the development of a method for radioassay of the receptor. The receptor level of the gonadal cell has been found to vary with the stage of differentiation. The receptor concentrations in 11-week-old birds and adult birds are comparable. Testoterone treatment of 11-week-old birds produced a substantial increase in the receptor concentration over control, while the protein content increased marginally, indicating that, probably, synthesis of the receptor is specifically induced by testoterone during spermatogenesis, and the concentration of receptor is relatively higher before the formation of the acrosome.

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The 21st century poses many challenges for global sustainability. Among them, most importantly, the human race will encounter scarcity of raw materials and conventional energy resources. And, India may have to take the brunt of these problems as it is going to be the most populated region of the world with concomitant increase in energy demand and requirement of other resources. India will be the testing ground for introducing newer ways of green technology and innovative principles of resource management and utilization. With the vagaries of potential climate change gathering clouds in the background, Earth sciences will have a special and predominant role in guiding the society in prioritizing our resource discovery, utilization and their consumption and the upkeep of environment. On the fundamental level, Earth sciences are going through a most exciting phase of development as a born-again science. Technological breakthroughs including the satellite-based observations augur well for gaining new insights into Earth processes. A set of exciting fundamental problems that are globally identified will set the stage for an exhilarating period of new discoveries. Improvements in numerical and computer-based techniques will assist in modelling of Earth processes to unprecedented levels. India will have to take special effort in improving the existing experimentation facilities in the Earth science departments of the country, and also the general level of Earth science education to meet the global standards. This article presents an Earth science vision for the 21st century in an Indian context.

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We have examined the monthly variations in sperm output and attempted to correlate the profiles of endocrine hormones secreted with the sperm counts throughout the ,year in the adult male bonnet monkey. As previously reported, there was a distinct spurt in sperm output beginning September through December months. A concomitant increase in serum testosterone and prolactin concentrations were also noted during September through November (mid and post-monsoon season). Although there was a marked increase in gonadotropin releasing hormone stimulated testosterone secretion, the peak testosterone concentrations post gonadotropin releasing hormone injection did not vary significantly (P>0.05) throughout the year. Basal serum follicle stimulating hormone concentrations did not vary significantly (P>0.05) during April to June months compared to September-November months. Serum inhibin concentration remained unaltered throughout the year, except in the month of March. The results of this study provide evidence for annual rhythms in prolactin and testosterone secretion and a distinct seasonality in the sperm output of the adult male bonnet monkey, but the pituitary responsiveness to exogenous gonadotropin releasing hormone remains unaltered throughout the year. Because of the existence of seasonality as noted in the present study, future studies which utilize the adult male bonnet monkey as an experimental model need to take into consideration the seasonal effects on reproductive function in this species.

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Biotransformation of 3 beta-acetoxy-19-hydroxycholest-5-ene (19-HCA, 6 g) by Moraxella sp. was studied. Estrone (712 mg) was the major metabolite formed. Minor metabolites identified were 5 alpha-androst-1-en-19-ol-3,17-dione (33 mg), androst-4-en-19-ol-3,17-dione (58 mg), androst-4-en-9 alpha,19-diol-3,17-dione (12 mg), and androstan-19-ol-3,17-dione (1 mg). Acidic metabolites were not formed. Time course experiments on the fermentation of 19-HCA indicated that androst-4-en-19-ol-3,17-dione was the major metabolite formed during the early stages of incubation. However with continuing fermentation its level dropped, with a concomitant increase in estrone. Fermentation of 19-HCA in the presence of specific inhibitors or performing the fermentation for a shorter period (48 h) did not result in the formation of acidic metabolites. Resting-cell experiments carried out with 19-HCA (200 mg) in the presence of alpha,alpha'-bipyridyl led to the isolation of three additional metabolites, viz., cholestan-19-ol-3-one (2 mg), cholest-4-en-19-ol-3-one (10 mg), and cholest-5-en-3 beta,19-diol (12 mg). Similar results were also obtained when n-propanol was used instead of alpha,alpha'-bipyridyl. Resting cells grown on 19-HCA readily converted both 5 alpha-androst-1-en-19-ol-3,17-dione and androst-4-en-19-ol-3,17-dione into estrone. Partially purified 1,2-dehydrogenase from steroid-induced Moraxella cells transformed androst-4-en-19-ol-3,17-dione into estrone and formaldehyde in the presence of phenazine methosulfate, an artificial electron acceptor. These results suggest that the degradation of the hydrocarbon side chain of 19-HCA does not proceed via C-22 phenolic acid intermediates and complete removal of the C-17 side chain takes place prior to the aromatization of the A ring in estrone. The mode of degradation of the sterol side chain appears to be through the fission of the C-17-C-20 bond. On the basis of these observations, a new pathway for the formation of estrone from 19-HCA in Moraxella sp. has been proposed.

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PROBLEM: It is yet to be determined clearly whether the two hormones FSH and T act synergistically in the same cell type-the Sertoli cells-to control overall spermatogenesis or influence independently the transformation of specific germ cell types during spermatogenesis in the adult mammal. METHOD: Adult male bonnet monkeys specifically deprived of either FSH or LH using immunoneutralization techniques were monitored for changes in testicular germ cell transformation by DNA flow cytometry. RESULTS: FSH deprivation caused a significant reduction (>40%; P < 0.05) in [H-3] thymidine incorporation into DNA of proliferating 2C (spermatogonial) cells, a marked inhibition (>50%) in the transformation of 2C to primary spermatocytes (4C) and a concomitant, belated reduction (50%) in the formation of round spermatids (1C). In contrast, specific LH/T deprivation led to an immediate arrest in the meiotic transformation of 4C to 1C/HC leading to an effective and significant block (<90%; P < 0.01) in sperm production. CONCLUSION: Thus, LH rather than FSH deprivation has a more pronounced and immediate effect as the former primarily blocks meiosis (4C --> 1C/HC) which controls production of spermatids. These data provide evidence for LH/T and FSH regulating spermatogenic process in the adult primate by primarily acting at specific germ cell transformation steps.

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The unfolding of the chicken egg white riboflavin carrier protein by disulfide reduction with dithiothreitol led to aggregation with concomitant loss of ligand binding characteristics and the capacity to interact with six monoclonal antibodies directed against surface-exposed discontinuous epitopes. The reduced protein could, however, bind to a monoclonal antibody recognizing sequential epitope. Under optimal conditions of protein refolding, the vitamin carrier protein regained its folded structure with high efficiency with simultaneous complete restoration of hydrophobic flavin binding site as well as the epitopic conformations exposed at the surface in a manner comparable to its native form.

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Fluorene and its derivatives are well-known organic semiconducting materials in the field of opto-electronic devices because of their charge transport properties. Three new organic semiconducting materials, namely, 2,2'-((9,9-butyl-9H-fluorene-2,7-diyl)bis(4,1 phenylene))bisbenzod]thiazole, C4; 2,2'-((octyl-9H-fluorene-2,7-diyl)bis(4,1 phenylene))bisbenzod]thiazole, C8; and 2,2'-((9,9-dodecayl-9H-fluorene-2,7-diyl)bis(4,1 phenylene))bisbenzod]thiazole, C12 with a benzothiazole-fluorene backbone, were synthesized and characterized for their photophysical properties. A phenomenon of concomitant polymorphism has been investigated in the first two derivatives (C4 and C8) and has been analyzed systematically in terms of the packing characteristics involving pi ... pi interactions. The conformational flexibility of the pi-conjugated 2,2'-(fluorene-2,7-diyl)bis(4,1 phenylene)bisbenzod]thiazole backbone coupled with orientational freedom of the terminal alkyl chains were found to be the key factors responsible for these polymorphic modifications. Attempts to grow suitable crystals for single crystal X-ray diffraction of compound C12 were unsuccessful.

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Much of the Bangalore sewage is treated in three streams namely Bellandur (K&C Valley),Vrishabhavati and Hebbal-Nagavara stream systems. Among these it is estimated that out of a total of about 500MLD of partially treated sewage is let into the Bellandur tank. We estimate that a total of about 77t N non-industrial anthropogenic nitrogen efflux (mainly urine and excreta) in Bangalore city. This is distributed between that handled by the three sewage streams, soak-pits and land deposition. About 17-24.5t N enters the Bellandur tank daily. This has been happening over few decades and our observations suggest that this approximately 380ha tank is functioning as a C and N removal system with reasonable efficiency. The ammoniacal and nitrate nitrogen content of the water at the discharge points were estimated and found that over 80% of the nitrogen influx and over 75% of the C influx is removed by this tank system. We observed that there are three nitrogen sinks namely bacterial, micro-algal and macrophytes. The micro-algal fraction is dominated by Microcystis and Euglenophyceae members and they appear to constitute a significant fraction. Water hyacinth represents the single largest representative of the macrophytes. This tank has been functioning in this manner for over three decades. We attempt to study this phenomenon from a material balance approach and show that it is functioning with a reasonable degree of satisfaction as a natural wetland. As the population served and concomitant influx into this wetland increases, there is a potential for the system to be overloaded and to collapse. Therefore a better understanding of its function and the need for maintenance is discussed in the paper.