889 resultados para Low concentrations
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Clinical and mycological investigations were made on 225 cases of suspected dermatomycoses. Of these, 102 were microscopically positive. But only 63 were culturally positive, and these are analysed here with regard to clinical patterns and aetiological species, age, sex and occupational incidence and susceptibility to griseofulvin in vitro. As in most other parts of India, Trichophyton rubrum was the dominant species. A high proportion of Epidermophyton floccosum was an unusual feature seen. Of the clinical types, tinea cruris was the most common. The isolates were sensitive to griseofulvin at low concentrations of 1 to 5 μg per ml of agar medium, E. floccosum being the most sensitive.
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1.The reported inhibition of the succinate oxidase system at high concentrations of dinitrophenol, considered to be at the primary dehydrogenase level, is now confirmed by measuring the activity of succinate dehydrogenase (succinate:(acceptor) oxidoreductase, EC 1.3.99.1) in the presence of dinitrophenol, using the dye reduction method. 2. 2. The results indicate that the inhibition of substrate-activated succinate dehydrogenase by dinitrophenol is competitive. 3. 3. Low concentrations of dinitrophenol inhibited the basal activity, while at higher concentrations the kinetics were complicated by an apparent activation. 4. 4. Preincubation of mitochondria with dinitrophenol stimulated the enzyme activity, a phenomenon shown by succinate and competitive inhibitors. This activation was very rapid at 37°, compared to that by succinate; activation by dinitrophenol was observed even at 25°, under conditions where succinate had no effect. 5. 5. Repeated washing of the activated mitochondrial samples with the sucrose homogenizing medium reduced the succinate-stimulated activity to the basal level, but only partially reversed the dinitrophenol activation. 6. 6. The relevance of this activation phenomenon to the physiological modulation of this enzyme system is discussed.
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A partially purified sheep liver enzyme that hydrolyzed dinucleotides at the pyrophosphate bond was obtained by solubilizing the 18,000g sediment with n-butanol and fractionating the solubilized enzyme with acetone. The enzyme activity when measured using FAD as substrate, (FAD → FMN + AMP), was optimal at pH 9.7 and temperatures between 30 °–36 ° and at 60 °. The rate of release of FMN with time occurred with an initial lag of 30 sec, a linear increase for 1 min, and a subsequent irregular rate. In the presence of orthophosphate (Pi; 10 μImage ), FMN was released at an uniformly continuous and enhanced rate. 32Pi was not incorporated into the substrate or products. Sodium arsenate counteracted the effects of Pi. The apparent Km and Vmax were 0.133 mImage and 100 units; and 0.133 mImage and 200 units, in the absence and presence of Pi, respectively. The temperature optimum was 42 ° in the presence of Pi.Negative cooperative interactions observed at low concentrations of FAD were abolished by the addition of Pi. The inhibition by AMP was sigmoid and Pi abolished this sigmoidal response. The enzyme hydrolyzed in addition to FAD, NAD+ and NADP+. Nucleoside triphosphates were potent inhibitors of the enzyme activity. The partial inhibition of the enzyme by o-phenanthroline and by p-hydroxymercuribenzoate could be reversed by Fe2+ ions and by reduced glutathione, respectively.
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The PI3-kinase pathway is the target of inactivation in achieving better cancer chemotherapy. Here, we report that p53-mediated transcription is inhibited by pharmacological inhibitors and a dominant-negative mutant of PI3-kinase, and this inhibition was relieved by a constitutively active mutant of PI3-kinase. Akt/PKB and mTOR, the downstream effectors of PI3-kinase, were also found to be essential. LY294002 (PI3-kinase inhibitor) pre-treatment altered the post-translational modifications and the sub-cellular localization of p53. Although LY294002 increased the chemosensitivity of cells to low concentrations of adriamycin (adriamycin-low), it protected the cells from cytotoxicity induced by high concentrations of adriamycin (adriamycin-high) in a p53-dependent manner. Further, we found that LY294002 completely abolished the activation of p53 target genes (particularly pro-apoptotic) under adriamycin-high conditions, whereas it only marginally repressed the p53 target genes under adriamycin-low conditions; in fact, it further activated the transcription of NOXA, HRK, APAF1 and CASP5 genes. Thus, the differential effect of PI3-kinase on p53 functions seems to be responsible for the differential regulation of DNA damage-induced cytotoxicity and cell death by PI3-kinase. Our finding becomes relevant in the light of ongoing combination chemotherapy trials with the PI3-kinase pathway inhibitors and underscores the importance of p53 status in the careful formulation of combination chemotherapies. Oncogene (2010) 29, 3605-3618; doi: 10.1038/onc.2010.123; published online 26 April 2010
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Background & objectives: The multiple drug resistance (MDR) is a serious health problem and major challenge to the global drug discovery programmes. Most of the genetic determinants that confer resistance to antibiotics are located on R-plasmids in bacteria. The present investigation was undertaken to investigate the ability of organic extract of the fruits of Helicteres isora to cure R-plasmids from certain clinical isolates. mMethods: Active fractions demonstrating antibacterial and antiplasmid activities were isolated from the acetone extracts of shade dried fruits of H. isora by bioassay guided fractionation. Minimal inhibitory concentration (MIC) of antibiotics and organic extracts was determined by agar dilution method. Plasmid curing activity of organic fractions was determined by evaluating the ability of bacterial colonies (pre treated with organic fraction for 18 h) to grow in the presence of antibiotics. The physical loss of plasmid DNA in the cured derivatives was further confirmed by agarose gel electrophoresis. Results: The active fraction did not inhibit the growth of either the clinical isolates or the strains harbouring reference plasmids even at a concentration of 400 mu g/ml. However, the same fraction could cure plasmids from Enterococcus faecalis, Escherichia coli, Bacillus cereus and E. coli (RP4) at curing efficiencies of 14, 26, 22 and 2 per cent respectively. The active fraction mediated plasmid curing resulted in the subsequent loss of antibiotic resistance encoded in the plasmids as revealed by antibiotic resistance profile of cured strains. The physical loss of plasmid was also confirmed by agarose gel electrophoresis. Interpretation & conclusions: The active fraction of acetone extract of H. isora fruits cured R-plasmids from Gram-positive and Gram-negative clinical isolates as well as reference strains. Such plasmid loss reversed the multiple antibiotic resistance in cured derivatives making them sensitive to low concentrations of antibiotics. Acetone fractions of H. isora may be a source to develop antiplasmid agents of natural origin to contain the development and spread of plasmid borne multiple antibiotic resistance.
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Radiometric determination methods, such as alpha spectrometry require long counting times when low activities are to be determined. Mass spectrometric techniques as Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Thermal Ionisation Mass Spectrometry (TIMS) and Accelerator Mass Spectrometry (AMS) have shown several advantages compared to traditional methods when measuring long-lived radionuclides. Mass spectrometric methods for determination of very low concentrations of elemental isotopes, and thereby isotopic ratios, have been developed using a variety of ion sources. Although primarily applied to the determination of the lighter stable element isotopes and radioactive isotopes in geological studies, the techniques can equally well be applied to the measurement of activity concentrations of long-lived low-level radionuclides in various samples using “isotope dilution” methods such as those applied in inductively coupled plasma mass spectrometry (ICP-MS). Due to the low specific activity of long-lived radionuclides, many of these are more conveniently detected using mass spectrometric techniques. Mass spectrometry also enables the individual determination of Pu-239 and Pu-240, which cannot be obtained by alpha spectrometry. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) are rapidly growing techniques for the ultra-trace analytical determination of stable and long-lived isotopes and have a wide potential within environmental science, including ecosystem tracers and radio ecological studies. Such instrumentation, of course needs good radiochemical separation, to give best performance. The objectives of the project is to identify current needs and problems within low-level determination of long-lived radioisotopes by ICP-MS, to perform intercalibration and development and improvement of ICP-MS methods for the measurement of radionuclides and isotope ratios and to develop new methods based on modified separation chemistry applied to new auxiliary equipment.
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Aikaisemman tutkimuksen perusteella tiedettiin tiettyjen 2,1,3-bentsoksadiatsolirakenteisten molekyylien olevan aktiivisia Chlamydia pneumoniae –bakteeria vastaan. Tutkimusta lähdettiin jatkamaan ja 2,1,3-bentsoksadiatsolimolekyylien rakenne-aktiivisuusuhteista haluttiin saada lisätietoa. Tarkoituksena oli kehittää 2,1,3-bentsoksadiatsolimolekyyleille ja sen avulla muodostaa molekyylikirjasto. Syntetisoidut molekyylit haluttiin testata sekä Chlamydia pneumoniae -bakteeria että Leishmania donovani –parasiittia vastaan. Chlamydia pneumoniae –bakteeri aiheuttaa akuutteja ylä- ja alahengitystieinfektiota, kuten keuhkoputkentulehdusta. Akuutissa tulehduksessa oireet vaihtelevat huomattavasti. Chlamydia pneumoniae –bakteerilla on myös taipumus aiheuttaa kroonisia tulehduksia. Nämä ovat useissa tutkimuksissa yhdistetty kansantaloudellisesti merkittäviin sairauksiin, kuten ateroskleroosiin ja astmaan. Leishmanioosi on toiseksi yleisin loissairaus ihmisellä malarian jälkeen. Leishmania donovani –parasiitti voi aiheuttaa tappavaa viskeraalista leishmanioosia. Vuodessa leishmanioosiin kuolee yli 50 000 ihmistä. Viime vuosina leishmanioosin lääkehoidossa on esiintynyt monenlaisia ongelmia. Osat lääkkeistä ovat menettäneet tehonsa ja osalla esiintyy vakavia haittavaikutuksia. 2,1,3-Bentsoksadiatsolirakenteisille yhdisteille saatiin kehitettyä toimiva synteesireitti. Lähtöaineena käytettiin 4-amino-2-nitrobentsoehappoa, josta saatiin hapettavalla renkaansulkeutumisreaktiolla 2,1,3-bentsoksadiatsoli-5-karboksyylihappoa. Karboksyylihaposta syntetisoitiin amidi-välituotteen kautta 2,1,3-bentsoksadiatsoli-5-karbonitriiliä. Hydroksyyliamiini hydrokloridin avulla 2,1,3-bentsoksadiatsoli-5-karbonitriilistä muodostettiin vastaavaa karboksimidamidia, joka oli synteesireitin yhteinen välituote kaikille molekyyleille. Viimeisessä vaiheessa N´-hydroksidi-2,1,3-bentsoksadiatsoli-5-karboksimidamidin annettiin reagoida joko fenyyli-isosyanaatin tai fenyyli-isotiosyanaatin kanssa, jolloin saatiin lopputuotetta. Synteesireitin kehittäminen osoittautui haastavaksi ja loppujen lopuksi saatiin ainoastaan kolme lopputuotetta syntetisoitua. Yksi lopputuotteista testattiin C. pneumoniae –bakteeria vastaan Åbo akademissa Turussa. Testattavaa yhdiste ei sisältänyt 2,1,3-bentsoksadiatsoliarengasta ja bioaktiivisuuskokeen tulos oli odotusten mukainen. Yhdiste ei ollut aktiivinen C. pneumoniae –bakteeria vastaan alhaisilla konsentraatioilla ja tuloksesta voitiin todeta 2,1,3-bentsoksadiatsolirengaan olevan tärkeä aktiivisuuden kannalta. Kaksi lopputuotetta saatiin testaukseen Leishamania donovani –parasiittia vastaan Israeliin. Ainoastaan toinen molekyyleistä sisälsi 2,1,3-bentsoksadiatsolirakenteen. Bioaktiivisuuskokeiden tulokset olivat erittäin rohkaisevia. Yhdisteet olivat aktiivisia parasiittia vastaan jo alhaisilla konsentraatioilla. Kuitenkin 2,1,3-bentsoksadiatsolirakenteinen molekyyli oli aktiivisempi, joten tämäkin aktiivisuuskokeen perusteella huomattiin rengasrakenteen olevan tärkeä aktiivisuuden kannalta.
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The behaviour of the PbO2 electrode in NaNO3, Na2SO4 NaClO4 and NaCl in the pH range 3.0–10.5 has been studied by cyclic voltammetry. When the electrode is cycled between 0.30 and 1.90 V, a large cathodic current peak appears in the negative scan; in the subsequent cycle, two anodic peaks appear. The addition of H2O2 at low concentrations to the electrolyte also results in two anodic peaks at the same potentials. A number of possible explanations for the appearance of the cathodic peak, and a mechanism for the oxidation of PbO to PbO2 through Pb3O4 corresponding to the two anodic peaks, are proposed.
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The zeta potential of high-purity hematite at pH 6 and in a 10−3N NaCl solution has been determined at different concentrations of acetone using the streaming potential technique and the results correlated with the microhardness of the mineral. The zeta potential has been found to decrease as the hardness increases reaching a minimum at 10 cc per litre concentration of acetone when the hardness reaches a maximum. The results have been explained on the basis of competitive adsorption of chloride ions and acetone molecules at low concentrations of acetone and coadsorption of both species above 10 cc per litre concentration. Acetone in distilled water and 10−3N NaCl in distilled water decrease the microhardness of hematite individually between pH 5 to 7 and in combination increase the microhardness reaching a maximum at pH 6.
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Callus cultures of sandalwood (Santalum album L.) were established from shoot segments and shoot tips of trees over 20 years old. Shoots were induced directly from shoot tip callus, while in shoot segments embryoids developed from the callus within 4 weeks after subculturing on to a medium supplemented with gibberellic acid (GA). Embryoids of 4–5 mm were transferred to basal medium or basal medium supplemented with low concentrations of auxin showed plantlet development.
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Coagulase-negative staphylococci (CNS) are the most common bacteria isolated in bovine subclinical mastitis in many countries, and also a frequent cause of clinical mastitis. The most common species isolated are Staphylococcus (S) chromogenes, S. simulans, S. epidermidis, and S. xylosus. One half of the intramammary infections (IMI) caused by CNS persist in the udder. The pathogenesis of IMI caused by CNS is poorly understood. This dissertation focuses on host response in experimental intramammary infection induced by S. chromogenes, S. epidermidis and S. simulans. Model for a mild experimental CNS infection was developed with S. chromogenes (study I). All cows were infected and most developed subclinical mastitis. In study II the innate immune response to S. epidermidis and S. simulans IMI was compared in eight cows using a crossover design. A larger dose of bacteria was used to induce clinical mastitis. All cows became infected and showed mild to moderate clinical signs of mastitis. S. simulans caused a slightly stronger innate immune response than S. epidermidis, with significantly higher concentrations of the interleukins IL-1beta and IL-8 in the milk. The spontaneous elimination rate of the 16 IMIs was 31%, with no difference between species. No significant differences were recorded between infections eliminated spontaneously or remaining persistent, although the response was stronger in IMIs eliminated spontaneously, except the concentration of TNF-α, which remained elevated in persistent infections. Lactoferrin (Lf) is a component of the humoral defence of the host and is present at low concentrations in the milk. The concentration of Lf in milk is high during the dry period, in colostrum, and in mastitic milk. The effect of an inherent, high concentration of Lf in the milk on experimental IMI induced with S. chromogenes was studied in transgenic cows that expressed recombinant human Lf in their milk. Human Lf did not prevent S. chromogenes IMI, but the host response was milder in transgenic cows than in normal cows, and the former eliminated infection faster. Biofilm production has been suggested to promote persistence of IMI. Phenotypic biofilm formation and slime producing ability of CNS isolates from bovine mastitis was investigated in vitro. One-third of mastitis isolates produced biofilm. Slime production was less frequent for isolates of the most common mastitis causing species S. chromogenes and S. simulans compared with S. epidermidis. No association was found between the phenotypic ability to form biofilm and the persistence of IMI or severity of mastitis. Slime production was associated with persistent infections, but only 8% of isolates produced slime.
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Indole and its derivatives form a class of toxic recalcitrant environmental pollutants. The growth of Aspergillus niger was inhibited by very low concentrations (0.005 to 0.02%) of indole, even when 125- to 500-fold excess glucose was present in the medium. When 0.02% indole was added, the fungus showed a lag phase for about 30 h and the uptake of glucose was inhibited. Indole was metabolized by a new pathway via indoxyl (3-hydroxyindole), N-formylanthranilic acid, anthranilic acid,2,3-dihydroxybenzoic acid, and catechol, which was further degraded by ortho cleavage. The enzymes N-formylanthranilate deformylase, anthranilate hydroxylase, 2,3-dihydroxybenzoate decarboxylase, and catechol dioxygenase were induced by indole as early as after 5 h of growth, and their activities were demonstrated in a cell-free system.
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The presently developed two-stage process involves diping the prefired porous disks of n-BaTiO3 in nonaqueous solutions containing Al-buty rate, Ti-isopropoxide, and tetraethyl silicate and subsequent sintering. This leads to uniform distribution of the grain-boundary layer (GBL) modifiers (Al2O3+ TiO2+ SiO2) and better control of the grain size as well as the positive temperature coefficient of resistivity characteristics. The technique is particularly suited for GBL modifiers in low concentrations (< 1%).
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The blood-brain barrier (BBB) is a unique barrier that strictly regulates the entry of endogenous substrates and xenobiotics into the brain. This is due to its tight junctions and the array of transporters and metabolic enzymes that are expressed. The determination of brain concentrations in vivo is difficult, laborious and expensive which means that there is interest in developing predictive tools of brain distribution. Predicting brain concentrations is important even in early drug development to ensure efficacy of central nervous system (CNS) targeted drugs and safety of non-CNS drugs. The literature review covers the most common current in vitro, in vivo and in silico methods of studying transport into the brain, concentrating on transporter effects. The consequences of efflux mediated by p-glycoprotein, the most widely characterized transporter expressed at the BBB, is also discussed. The aim of the experimental study was to build a pharmacokinetic (PK) model to describe p-glycoprotein substrate drug concentrations in the brain using commonly measured in vivo parameters of brain distribution. The possibility of replacing in vivo parameter values with their in vitro counterparts was also studied. All data for the study was taken from the literature. A simple 2-compartment PK model was built using the Stella™ software. Brain concentrations of morphine, loperamide and quinidine were simulated and compared with published studies. Correlation of in vitro measured efflux ratio (ER) from different studies was evaluated in addition to studying correlation between in vitro and in vivo measured ER. A Stella™ model was also constructed to simulate an in vitro transcellular monolayer experiment, to study the sensitivity of measured ER to changes in passive permeability and Michaelis-Menten kinetic parameter values. Interspecies differences in rats and mice were investigated with regards to brain permeability and drug binding in brain tissue. Although the PK brain model was able to capture the concentration-time profiles for all 3 compounds in both brain and plasma and performed fairly well for morphine, for quinidine it underestimated and for loperamide it overestimated brain concentrations. Because the ratio of concentrations in brain and blood is dependent on the ER, it is suggested that the variable values cited for this parameter and its inaccuracy could be one explanation for the failure of predictions. Validation of the model with more compounds is needed to draw further conclusions. In vitro ER showed variable correlation between studies, indicating variability due to experimental factors such as test concentration, but overall differences were small. Good correlation between in vitro and in vivo ER at low concentrations supports the possibility of using of in vitro ER in the PK model. The in vitro simulation illustrated that in the simulation setting, efflux is significant only with low passive permeability, which highlights the fact that the cell model used to measure ER must have low enough paracellular permeability to correctly mimic the in vivo situation.
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We report in this paper the aggregation properties of amphotericin-B (amp-B) in solution using CD and 1H-NMR techniques. Our results indicate that the preferred structure of amp-B in dimethylsulfoxide is a monomer at low concentrations (10−4M and below) and a stable dimer at higher concentrations (range 5 · 103 M to 10−2M). In a DMSO/ethanol mixture (1:1 (v/v)), the antibiotic is monomeric, irrespective of the concentration within the range studied. We propose a head-to-tail model based on NMR data. An understanding of the head-to-tail dimer, is, we believe important, particularly in view of the recent report wherein it is proposed that the drug inserts into bilayers as head-to-tail oligomers.