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991.
Ibrić S Jovanović M Djurić Z Parojcić J Petrović SD Solomun L Stupar B 《AAPS PharmSciTech》2003,4(1):62-70
The purpose of the present study was to model the effects of the concentration of Eudragit L 100 and compression pressure
as the most important process and formulation variables on the in vitro release profile of aspirin from matrix tables formulated
with Eudragit L 100 as matrix substance and to optimize the formulation by artificial neural network. As model formulations,
10 kinds of aspirin matrix tablets were prepared. The amount of Eudragit L 100 and the compression pressure were selected
as causal factors. In vitro dissolution time profiles at 4 different sampling times were chosen as responses. A set of release
parameters and causal factors were used as tutorial data for the generalized regression neural, network (GRNN) and analyzed
using a computer. Observed results of drug release studies indicate that drug release rates vary widely between investigated
formulations, with a range of 5 hours to more than 10 hours to complete dissolution. The GRNN model was optimized. The root
mean square value for the trained network was 1.12%, which indicated that the optimal GRNN model was reached. Applying the
generalized distance function method, the optimal tablet formulation predicted by GRNN was with 5% of Eudragit L 100 and tablet
hardness 60N. Calculated difference (f
1 2.465) and similarity (f
2 85.61) factors indicate that there is no difference between predicted and experimentally observed drug release profiles for
the optimal formulation. This work illustrates the potential for an artificial neural network, GRNN, to assist in development
of extended release dosage forms. 相似文献
992.
D Mišić M Dragićević B Siler J Nestorović Živković V Maksimović I Momčilović M Nikolic 《Journal of plant physiology》2012,169(13):1281-1289
A heterotrophic model system was established in our studies in order to differentiate the effect of high salt concentrations in external medium on growth and sugar metabolism in roots from the effect of reduced sugar availability resulting from decreased photosynthesis under salinity. Soluble sugar content and the activity of acid invertase in root cultures of salt-tolerant (ST) and salt-sensitive (SS) Schenkia spicata (L.) Mansion genotypes were investigated during exposure to different NaCl concentrations (0-200mM). Their response to severe salinity was characterized by a metabolic adjustment that led to the accumulation of sucrose (Suc) in root tissues. There was clear evidence that cell wall invertase (CW-Inv) is the major contributor to the Suc/hexose ratio in roots during exposure to elevated salinity. The results of CW-Inv activity and immunodetection assays in our study suggest that the regulation of CW-Inv expression is most likely achieved in a salt stress dependent manner. Also, NaCl modulated soluble acid invertase (SA-Inv) expression differentially in SS and ST genotypes of S. spicata. Regardless of the salt treatment, genotype, or the amount of enzyme, SA-Inv activity was generally low, indicating regulation at the posttranslational level. The results suggest no direct role of SA-Inv in the regulation of the root tissue carbohydrate pool and therefore in the control of the availability of glucose and fructose for the primary metabolism and/or osmotic adjustment in the present heterotrophic model system. 相似文献
993.
Klaus Stark Rainer H Straub Jozef Rovensky Stanislava Bla?i?ková Gabriele Eiselt Martin Schmidt 《Arthritis research & therapy》2015,17(1)
IntroductionRheumatoid arthritis (RA) is characterized by decreased androgen levels, which was the first hormonal abnormality described. Several studies indicated that steroidogenesis is directed towards endogenous glucocorticoids at the expense of androgens. The decisive step governing androgen synthesis is the 17,20-lyase activity of the CYP17A1 gene-encoded enzyme cytochrome P450 17A1. Here, we focused on the role in RA of the critical cofactor for 17,20-lyase activity, cytochrome b5, encoded by the CYB5A gene.MethodsData sets of two genome wide RA association studies (GWAS) were screened for single nucleotide polymorphisms (SNP) in the CYB5A gene. Candidate SNPs in CYB5A were studied in a case–control study population of Slovakia. Expression analyses were done in synovial fibroblasts from RA patients by quantitative real-time polymerase chain reaction, and cytochrome b5–expression was detected by immunohistochemistry. Real-life androgen production after steroid conversion was measured using radiolabeled substrates.ResultsThe study identified the RA-associated intronic SNP rs1790834 in the CYB5A gene in one GWAS and confirmed the same SNP in our study. The minor allele reduced RA risk selectively in women (P = 4.1*10−3; OR = 0.63, 95% CI [0.46-0.86]). The protective effect was confined to rheumatoid factor-positive (OR = 0.53, [0.37-0.75]) and anti-cyclic citrullinated peptide-positive (OR = 0.58, [0.41-0.83]) cases, respectively. The protective allele doubles CYB5A mRNA-expression resulting in 2-3fold activation of steroid 17,20-lyase activity, and protective allele was accompanied by a higher density of cytochrome b5-positive cells in synovial tissue.ConclusionsCYB5A is the first RA susceptibility gene involved in androgen synthesis. Our functional analysis of SNP rs1790834 indicates that it contributes to the sex bias observed in RA. 相似文献
994.
995.
Verbanac D Jain SC Jain N Chand M Cipčić Paljetak H Matijašić M Perić M Stepanić V Saso L 《Bioorganic & medicinal chemistry》2012,20(10):3180-3185
Xanthones and their thio-derivatives are a class of pleiotropic compounds with various reported pharmacological and biological activities. Although these activities are mainly determined in laboratory conditions, the class itself has a great potential to be utilized as promising chemical scaffold for the synthesis of new drug candidates. One of the main obstacles in utilization of these compounds was related to the difficulties in their chemical synthesis. Most of the known methods require two steps, and are limited to specific reagents not applicable to a large number of starting materials. In this paper a new and improved method for chemical synthesis of xanthones is presented. By applying a new procedure, we have successfully obtained these compounds with the desired regioselectivity in a shorter reaction time (50s) and with better yield (>80%). Finally, the preliminary in vitro screenings on different bacterial species and cytotoxicity assessment, as well as in silico activity evaluation were performed. The obtained results confirm potential pharmacological use of this class of molecules. 相似文献
996.
Skaliczki G Weszl M Schandl K Major T Kovács M Skaliczki J Redl H Szendrői M Szigeti K Máté D Dobó-Nagy C Lacza Z 《Acta physiologica Hungarica》2012,99(2):223-232
Purpose: The clinical demand for bone grafting materials necessitated the development of animal models. Critical size defect model has been criticized recently, mainly for its inaccuracy. Our objective was to develop a dependable animal model that would provide compromised bone healing, and would allow the investigation of bone substitutes. Methods: In the first group a critical size defect was created in the femur of adult male Wistar rats, and a non-critical defect in the remaining animals (Groups II, III and IV). The defect was left empty in group II, while in groups III and IV a spacer was interposed into the gap. Osteoblast activity was evaluated by NanoSPECT/CT imaging system. New bone formation and assessment of a union or non-union was observed by μCT and histology. Results: The interposition model proved to be highly reproducible and provided a bone defect with compromised bone healing. Significant bone regeneration processes were observed four weeks after removal of the spacer. Conclusion: Our results have shown that when early bone healing is inhibited by the physical interposition of a spacer, the regeneration process is compromised for a further 4 weeks and results in a bone defect during the time-course of the study. 相似文献
997.
Gregor Belušič Primož Pirih Doekele G. Stavenga 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2010,196(1):23-35
We have simultaneously measured the electroretinogram (ERG) and the metarhodopsin content via fluorescence in white-eyed,
wild-type Drosophila and the arrestin2 hypomorphic mutant (w
−
;arr2
3
) at a range of stimulus wavelengths and intensities. Photoreceptor response amplitude and termination (transition between
full repolarization and prolonged depolarizing afterpotential, PDA) were related to visual pigment conversions and arrestin
concentration. The data were implemented in a kinetic model of the rhodopsin–arrestin cycle, allowing us to estimate the active
metarhodopsin concentration as a function of effective light intensity and arrestin concentration. Arrestin reduction in the
mutant modestly increased the light sensitivity and decreased the photoreceptor dynamic range. Compared to the wild type,
in the mutant the transition between full repolarization and PDA occurred at a lower metarhodopsin fraction and was more abrupt.
We developed a steady-state stochastic model to interpret the dependence of the PDA on effective light intensity and arrestin
content and to help deduce the arrestin to rhodopsin ratio from the sensitivity and PDA data. The feasibility of different
experimental methods for the estimation of arrestin content from ERG and PDA is discussed. 相似文献
998.
The fluid mosaic model of Singer and Nicolson (1972) is a commonly used representation of the cell membrane structure and dynamics. However a number of features, the result of four decades of research, must be incorporated to obtain a valid, contemporary version of the model. Among the novel aspects to be considered are: (i) the high density of proteins in the bilayer, that makes the bilayer a molecularly “crowded” space, with important physiological consequences; (ii) the proteins that bind the membranes on a temporary basis, thus establishing a continuum between the purely soluble proteins, never in contact with membranes, and those who cannot exist unless bilayer-bound; (iii) the progress in our knowledge of lipid phases, the putative presence of non-lamellar intermediates in membranes, and the role of membrane curvature and its relation to lipid geometry, (iv) the existence of lateral heterogeneity (domain formation) in cell membranes, including the transient microdomains known as rafts, and (v) the possibility of transient and localized transbilayer (flip-flop) lipid motion. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. 相似文献
999.
Maćešić-Petrović D Japundža-Milisavljević M Djuric-Zdravkovic A 《Attention deficit and hyperactivity disorders》2009,1(1):25-31
The paper discusses areas of behavioral functioning of children with intellectual disability, such as behavior with or without hyperactivity. The study covered 124 children with intellectual disability attending elementary schools in Belgrade. The Conners Rating Scale was used, and the areas of behavior in the classroom, participation in the group and attitude towards authority were covered. The results of our study suggest the presence of disorders in behavior and social-emotional functioning ranging from 11.2 to 40.4%. We have highlighted the importance of the use of multimodal approach and method of reeducation of psychomotor activity in rehabilitation of the studied children. 相似文献
1000.
D?iuginta Jako?iūn? Frédérique Pasquali Cristiana Soares da Silva Charlotta L?fstr?m Jeffrey Hoorfar Günter Klein Gerardo Manfreda John Elmerdahl Olsen 《Applied and environmental microbiology》2014,80(5):1616-1622
Salmonellae are a major cause of food-borne outbreaks in Europe, with eggs and egg products being identified as major sources. Due to the low levels of salmonellae in eggs and egg products, direct quantification is difficult. In the present study, enrichment quantitative real-time PCR (qPCR) was employed for enumeration of salmonellae in different matrices: table eggs, pasteurized egg products, and egg-containing dishes. Salmonella enterica serovar Enteritidis and S. enterica serovar Tennessee were used to artificially contaminate these matrices. The results showed a linear regression between the numbers of salmonellae and the quantification cycle (Cq) values for all matrices used, with the exception of pasteurized egg white. Standard curves were constructed by using both stationary-phase cells and heat-stressed cells, with similar results. Finally, this method was used to evaluate the fate of salmonellae in two egg-containing dishes, long egg and tiramisu, at abused refrigeration temperatures, and results indicated the growth of bacteria over a 1-week period. In conclusion, enrichment qPCR was shown to be reliable for enumeration of salmonellae in different egg products. 相似文献