Inhibiting Concentration (inhibiting + concentration)

Distribution by Scientific Domains


Selected Abstracts


Combined Use of PCA and QSAR/QSPR to Predict the Drugs Mechanism of Action.

MOLECULAR INFORMATICS, Issue 4 2009
An Application to the NCI ACAM Database
Abstract During the years the National Cancer Institute (NCI) accumulated an enormous amount of information through the application of a complex protocol of drugs screening involving several tumor cell lines, grouped into panels according to the disease class. The Anti-cancer Agent Mechanism (ACAM) database is a set of 122 compounds with anti-cancer activity and a reasonably well known mechanism of action, for which are available drug screening data that measure their ability to inhibit growth of a panel of 60 human tumor lines, explicitly designed as a training set for neural network and multivariate analysis. The aim of this work is to adapt a methodology (previously developed for the analysis of DNA minor groove binders) for the analysis of NCI ACAM database, using Principal Component Analysis (PCA) and QSAR/QSPR for the prediction of the mechanism of action of anti-cancer drugs. The entire database was splitted in a training set of 60 structures and a test set of 48 ones, and each set was expressed in form of a matrix on which further procedures were performed. Three statistical parameters were calculated: First Attempt of Prediction (FAP) expresses the percentage of correct predictions at first attempt, Total Attempt of Prediction (TAP) expresses the total percentage of correct predictions across all the three attempts, Non-Classified (NC) expresses the percentage of compounds whose mechanism of action has failed to be predicted. The predictive ability of this approach is variable, but the results obtained are generally good; using 50% Growth Inhibiting concentration (GI50) values as training data, we were able to assign a correct mechanism of action with a good degree of reliability (more than 79%). [source]


Inhibition of bacterial translation and growth by peptide nucleic acids targeted to domain II of 23S rRNA

JOURNAL OF PEPTIDE SCIENCE, Issue 4 2007
Huang Xue-Wen
Abstract The objective of this work was to study the inhibitory effects of antisense peptide nucleic acids (PNAs) targeted to domain II of 23S rRNA on bacterial translation and growth. In this paper, we report that PNA(G1138) or peptide-PNA(G1138) targeted to domain II of 23S rRNA can inhibit both translation in vitro (in a cell-free translation system) and bacterial growth in vivo. The inhibitory concentration (IC50) and the minimum inhibiting concentration (MIC) are 0.15 and 10 µM, respectively. The inhibition effect of PNA(G1138) in vitro is somewhat lower than that of tetracycline (IC50 = 0.12 µM), but the MIC of peptide-PNA(G1138) against Escherichia coli is significantly higher than that of tetracycline (MIC = 4 µM). Further studies based on similar colony-forming unit (CFU) assays showed that peptide-PNA(G1138) at 10 µM is bactericidal, but the bactericidal effect is less effective than that of tetracycline. Nevertheless, the results demonstrated that the peptide-PNA(G1138) treatment is bactericidal in a dose- and sequence-dependent manner and that the G1138 site of 23S rRNA is a possible sequence target for designing novel PNA-based antibiotics. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source]


Characterization of Phosphodiesterase Type 5 Expression and Functional Activity in the Human Male Lower Urinary Tract

THE JOURNAL OF SEXUAL MEDICINE, Issue 1pt1 2010
Benedetta Fibbi MD
ABSTRACT Introduction., Phosphodiesterase type 5 (PDE5) inhibitors ameliorate low urinary tract (LUT) symptoms in men with ED and symptomatic benign prostatic hyperplasia (BPH). PDE5 is highly expressed in rat and human bladder, where it regulates cyclic guanosine monophosphate (cGMP) degradation, muscle tone, and proliferation. Aim., To investigate PDE5 tissue distribution and activity in human LUT tissues (urethra, prostate, and bladder). Main Outcome Measures., PDE5 expression and activity were analyzed and compared within the same BPH patient in LUT tissues and in smooth muscle cells (SMCs) cultured from urethra, prostate, and bladder. Methods., In LUT tissues, PDE5 was localized by immunohistochemistry and mRNA expression by quantitative real-time polymerase chain reaction. Proliferation assay was used as readout of PDE5 activity, evaluated as ability of vardenafil to increase the antiproliferative effect of different nitric oxide (NO)/cGMP pathway activators [the PDE5-resistant cGMP analog Sp-8-Br-PET-cGMPS, the NO donor sodium nitroprusside (SNP), and the soluble guanylate cyclase (sGC) stimulator BAY 41-8543]. Results., In all the LUT tissues, PDE5 was immunolocalized in blood vessels and in muscular fibres, but not in epithelium. PDE5 mRNA expression was higher in urethra and bladder than in prostate SMC. The antiproliferative effect of Sp-8-Br-PET-cGMPS was similar in all LUT SMC. In prostatic SMC, SNP and BAY 41-8543 show a dose-dependent antiproliferative effect that resulted marginally enhanced by vardenafil. Conversely, in urethra and bladder SMC the antiproliferative effect of SNP and BAY 41-8543 was lower than in prostatic SMC, but it was significantly enhanced by vardenafil. In urethral and bladder cells vardenafil half-maximal response inhibiting concentration was in the subnanomolar range, whereas in prostate cells it resulted significantly higher. Conclusions., The highest expression and biological activity of PDE5 was found in bladder. However, a consistent PDE5 expression and activity was also found in prostatic urethra. In contrast, the prostate gland showed the lowest PDE5 abundance and cultures derived from this tissue were less sensitive to vardenafil. Fibbi B, Morelli A, Vignozzi L, Filippi S, Chavalmane A, De Vita G, Marini M, Gacci M, Vannelli GB, Sandner P, and Maggi M. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med 2010;7:59,69. [source]


Production of PHB from Crude Glycerol

ENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 5 2007
G. Mothes
Abstract Crude glycerol , a by-product of the large scale production of diesel oil from rape , is examined for its possible use as a cheap feedstock for the biotechnological synthesis of poly(3-hydroxybutyrate) (PHB). The glycerol samples of various manufacturers differ in their contamination with salts (NaCl or K2SO4), methanol or fatty acids. At high cell density fermentation these pollutants could possibly accumulate to inhibiting concentrations. The bacteria used were Paracoccus denitrificans and Cupriavidus necator JMP 134, which accumulate PHB from pure glycerol to a content of 70 % of cell dry mass. When using crude glycerol containing 5.5 % NaCl, a reduced PHB content of 48 % was observed at a bacterial dry mass of 50 g/L. Furthermore the PHB yield coefficient was reduced, obviously due to osmoregulation. The effect of glycerol contaminated with K2SO4 was less pronounced. The molecular weight of PHB produced with P. denitrificans or C. necator from crude glycerol varies between 620000 and 750000 g/mol which allows the processing by common techniques of the polymer industry. [source]