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Fundamental Factors (fundamental + factor)
Selected AbstractsEvaluation of enantioselective binding of antihistamines to human serum albumin by ACEELECTROPHORESIS, Issue 15 2007María Amparo Martínez-Gómez Abstract The drug binding to plasma and tissue proteins is a fundamental factor in determining the overall pharmacological activity of a drug. HSA, together with ,1 -acid glycoprotein, are the most important plasma proteins, which act as drug carriers, with implications on the pharmacokinetic of drugs. Among plasma proteins, HSA possesses the highest enantioselectivity. In this paper, a new methodology for the study of enantiodifferentiation of chiral drugs with HSA is developed and applied to evaluate the possible enantioselective binding of four antihistamines: brompheniramine, chlorpheniramine, hydroxyzine and orphenadrine to HSA. This study includes the determination of affinity constants of drug enantiomers to HSA and the evaluation of the binding sites of antihistamines on the HSA molecule. The developed methodology includes the ultrafiltration of samples containing HSA and racemic antihistaminic drugs and the analysis of the free or bound drug fraction using the affinity EKC-partial filling technique and HSA as chiral selector. The results shown in this paper represent the first evidence of the enantioselective binding of antihistamines to HSA, the major plasmatic protein. [source] Pharmacokinetic aspects of biotechnology productsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2004Lisa Tang Abstract In recent years, biotechnologically derived peptide and protein-based drugs have developed into mainstream therapeutic agents. Peptide and protein drugs now constitute a substantial portion of the compounds under preclinical and clinical development in the global pharmaceutical industry. Pharmacokinetic and exposure/response evaluations for peptide and protein therapeutics are frequently complicated by their similarity to endogenous peptides and proteins as well as protein nutrients. The first challenge frequently comes from a lack of sophistication in various analytical techniques for the quantification of peptide and protein drugs in biological matrices. However, advancements in bioassays and immunoassays,along with a newer generation of mass spectrometry-based techniques,can often provide capabilities for both efficient and reliable detection. Selection of the most appropriate route of administration for biotech drugs requires comprehensive knowledge of their absorption characteristics beyond physicochemical properties, including chemical and metabolic stability at the absorption site, immunoreactivity, passage through biomembranes, and active uptake and exsorption processes. Various distribution properties dictate whether peptide and protein therapeutics can reach optimum target site exposure to exert the intended pharmacological response. This poses a potential problem, especially for large protein drugs, with their typically limited distribution space. Binding phenomena and receptor-mediated cellular uptake may further complicate this issue. Elimination processes,a critical determinant for the drug's systemic exposure,may follow a combination of numerous pathways, including renal and hepatic metabolism routes as well as generalized proteolysis and receptor-mediated endocytosis. Pharmacokinetic/pharmacodynamic (PK/PD) correlations for peptide and protein-based drugs are frequently convoluted by their close interaction with endogenous substances and physiologic regulatory feedback mechanisms. Extensive use of pharmacokinetic and exposure/response concepts in all phases of drug development has in the past been identified as a crucial factor for the success of a scientifically driven, evidence-based, and thus accelerated drug development process. Thus, PK/PD concepts are likely to continue and expand their role as a fundamental factor in the successful development of biotechnologically derived drug products in the future. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2184,2204, 2004 [source] Fine-scale genetic structure and gene dispersal inferences in 10 Neotropical tree speciesMOLECULAR ECOLOGY, Issue 2 2006OLIVIER J. HARDY Abstract The extent of gene dispersal is a fundamental factor of the population and evolutionary dynamics of tropical tree species, but directly monitoring seed and pollen movement is a difficult task. However, indirect estimates of historical gene dispersal can be obtained from the fine-scale spatial genetic structure of populations at drift,dispersal equilibrium. Using an approach that is based on the slope of the regression of pairwise kinship coefficients on spatial distance and estimates of the effective population density, we compare indirect gene dispersal estimates of sympatric populations of 10 tropical tree species. We re-analysed 26 data sets consisting of mapped allozyme, SSR (simple sequence repeat), RAPD (random amplified polymorphic DNA) or AFLP (amplified fragment length polymorphism) genotypes from two rainforest sites in French Guiana. Gene dispersal estimates were obtained for at least one marker in each species, although the estimation procedure failed under insufficient marker polymorphism, limited sample size, or inappropriate sampling area. Estimates generally suffered low precision and were affected by assumptions regarding the effective population density. Averaging estimates over data sets, the extent of gene dispersal ranged from 150 m to 1200 m according to species. Smaller gene dispersal estimates were obtained in species with heavy diaspores, which are presumably not well dispersed, and in populations with high local adult density. We suggest that limited seed dispersal could indirectly limit effective pollen dispersal by creating higher local tree densities, thereby increasing the positive correlation between pollen and seed dispersal distances. We discuss the potential and limitations of our indirect estimation procedure and suggest guidelines for future studies. [source] Federal University of Santa Catarina follow-up management routine for traumatized primary teeth , part 1DENTAL TRAUMATOLOGY, Issue 6 2004Mariane Cardoso Abstract,,, The objective of this study was to verify if the follow-up management routine of traumatized primary teeth set up by Federal University of Santa Catarina, which performs clinical and radiographic assessments (15 and 45 days; 4, 8 and 12 months) after the oral trauma, enabled an early diagnosis of sequelae which would indicate the need for endodontic intervention, as well as the influence a type of trauma and the child's age could have in the severity of the sequelae. In this study 52 sets of records were used of patients being seen in the last 6 months, with a total of 70 teeth that were receiving follow-up treatment. Patients returned for regular visits set up by the management routine, where clinical and radiographic examinations were performed to check for sequelae, which justified endodontic intervention. Mobility (51.2%) and crown discoloration (25.6%) were the most common sequelae found in the patient's first appointment. In the follow-up visits, replacement root resorption (22.5%) was the second most common sequela found, suggesting endodontic intervention. No significant association was found between severe sequelae, types of trauma and a child's age (,2 = 0.3, P = 0,8613). During the intervals of the follow-up visits, it was noticed that between 46 days and 8 months a higher number of sequelae were diagnosed (P < 0.05). The diagnosis of sequelae such inflammatory and replacement root resorption, which can lead to an early loss of a primary tooth, are frequent and that the interval between the follow-up visits has to be changed, suggesting the setting up of management routine 2. The study also concluded that the type of trauma and the child's age are not fundamental factors in the diagnosis of severe sequelae. [source] Molecular Self-Assembled Monolayers and Multilayers for Organic and Unconventional Inorganic Thin-Film Transistor ApplicationsADVANCED MATERIALS, Issue 14-15 2009Sara A. DiBenedetto Abstract Principal goals in organic thin-film transistor (OTFT) gate dielectric research include achieving: (i) low gate leakage currents and good chemical/thermal stability, (ii) minimized interface trap state densities to maximize charge transport efficiency, (iii) compatibility with both p- and n- channel organic semiconductors, (iv) enhanced capacitance to lower OTFT operating voltages, and (v) efficient fabrication via solution-phase processing methods. In this Review, we focus on a prominent class of alternative gate dielectric materials: self-assembled monolayers (SAMs) and multilayers (SAMTs) of organic molecules having good insulating properties and large capacitance values, requisite properties for addressing these challenges. We first describe the formation and properties of SAMs on various surfaces (metals and oxides), followed by a discussion of fundamental factors governing charge transport through SAMs. The last section focuses on the roles that SAMs and SAMTs play in OTFTs, such as surface treatments, gate dielectrics, and finally as the semiconductor layer in ultra-thin OTFTs. [source] Minamata Disease and Environmental GovernanceINTERNATIONAL JOURNAL OF JAPANESE SOCIOLOGY, Issue 1 2006Harutoshi Funabashi Abstract:, This article aims to clarify the conditions necessary for environmental governance through a case study of one of the most tragic examples of environmental destruction, the Minamata disease. The Minamata disease is methyl-mercury poisoning resulting from the ingestion of contaminated fish and shellfish. The first incident of the Minamata disease occurred in the mid-1950s, in Kumamoto Prefecture. In spite of the grave lesson that the pollution in Kumamoto provided, Japanese society went on to experience a second occurrence of Minamata disease in the mid-1960s, in Niigata Prefecture. Conflicts between victims, the companies responsible for contamination, and the central and prefectural governments have continued for the past 50 years. As a whole, the history of the two incidences of Minamata disease shows a lack of environmental governance in Japanese society. Effective environmental governance is the ability to produce adequate solutions to a variety of environmental problems. In order to resolve an environmental problem such as Minamata disease adequately, four tasks must be achieved. These are the discovery of the cause, the prevention of suffering, recovery from suffering and the learning of a lesson. What factors are crucial to the achievement of these tasks? Through an analysis of the history of Minamata disease, I would like to point out three fundamental factors that have a decisive influence on the solution of an environmental problem. They are the existence of an effective and just juridical system, a mature public sphere, and the quality of individual actors who are concerned with an environmental problem. The following conditions are important to the fostering of environmental governance on a more concrete level: sensitivity of the society and the ability to set an agenda, autonomy of the research process and of any research groups, organization of the antipollution movement, an adequately designed system for compensation, and various measures which help to counter socially amplified suffering. [source] Advancing zoo animal nutrition through global synergyINTERNATIONAL ZOO YEARBOOK, Issue 1 2005E. S. Dierenfeld Global communication and dissemination of information are two fundamental factors that are necessary to advance zoo animal nutrition. To achieve global synergy for nutrition, regional needs must be identified, modified for zoo application and linked through the proper Internet portals so that the information is readily available to the international zoo community. For all groups of animals, the continued development of food composition databases, updated as and when more information becomes available, is an important part of this desired synergy. If balanced nutrition for wild animals in captivity at a global level is to be achieved, then a heightened recognition of the value of implementing science-based nutrition into animal-management programmes and enhanced levels of electronic communication are essential. [source] Early intervention in psychosis: a rural perspectiveJOURNAL OF PSYCHIATRIC & MENTAL HEALTH NURSING, Issue 2 2007M. KELLY rmn dip ma Over the past decade, there has been great interest in both the development and delivery of early intervention in psychosis services in the United Kingdom, supported by national policy and a Policy Implementation Guide (PIG). Despite this, the PIG fails to distinguish the delivery of early intervention services to different population groups. The paper aims to augment available literature with the range of complex issues that practitioners may face when working in rural settings and link this to the development of early intervention services in rural communities. This paper will also outline some of the fundamental factors that challenge delivery of early intervention to individuals with a first episode of psychosis and their families in rural communities. Important key areas for consideration will be highlighted for both the planning and delivery of early intervention to rural communities. [source] Protective organic-inorganic hybrid coatings on mild steel derived from Ti(OC4H9)4 -modified precursorsMATERIALS AND CORROSION/WERKSTOFFE UND KORROSION, Issue 9 2004V. Nguyen Abstract Titania-poly(methyl methacrylate-co-butyl methacrylate-co-methacrylic acid) hybrids prepared by a sol-gel method were deposited by dip coating on mild steel. Transparent and defect free coatings with titania content ranging between 0 and 12.7 wt.% have been prepared. Barrier properties and dry adherence have been tested by electrochemical impedance spectroscopy (EIS) and the vertical pull-off test, respectively. The pull-off test results suggest that the titanium alkoxide precursor must intercede on the substrate/coating interphase during film formation to create specific adhesive bondings with the substrate. In this paper, two capacitance models are used to estimate the water uptake, one based on a uniform and one on a heterogeneous distribution of sorbed water. Water uptake determined from these two models is compared to the gravimetry results. It is suggested that a reliable determination of the actual water uptake in coatings from capacitance measurements require an extensive experimental work. The variations in the state of sorbed water with the specimen type or immersion time, the leaching of organics during immersion or the slow diffusion of ions are fundamental factors that must be considered when comparing the water uptake determined from gravimetry and capacitance models. [source] Primate communities: Past, present, and possible futureAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue S39 2004Kaye E. Reed Abstract An understanding of the fundamental causes of the structure of primate communities is important for studies of primate evolutionary history, primate behavioral ecology, and development of conservation strategies. Research into these structuring factors has benefited from new perspectives such as consideration of primate phylogenetic history, metacommunities, and interactions with predators and nonprimate competitors. This review presents the underlying factors of primate community structure within the biogeographic regions of Madagascar, the Neotropics, Africa, and Asia. One of the major differences among these locations likely resulted from the initial primate taxa that colonized each region (a single colonization event in the case of Madagascar and South America, and multiple radiations of higher-level taxa in Africa and Asia). As most primates live in forests, the differences among the forests in these locations, caused by various climatic influences, further influenced speciation and the development of primate communities. Within these habitats, species interactions with different groups of organisms were also instrumental in developing community dynamics. Through an investigation of these fundamental factors, we identify some of the most important effects on primate communities in each region. These findings suggest that low primate richness in Asia may be caused by either the abundance of dipterocarp trees or high levels of monsoon rains. High numbers of frugivores and a lack of folivores in neotropical communities may be associated with competiton with sloths that were already present at the time of initial radiation. Climatic patterns which affect forest structure and productivity in Madagascar may be responsible for high numbers of folivorous lemurs. The identification of these factors are important for the conservation of existing primate communities, and indicate directions for future studies. Yrbk Phys Anthropol 47:2,39, 2004. © 2004 Wiley-Liss, Inc. [source] Sovereign Risk in the Classical Gold Standard Era,THE ECONOMIC RECORD, Issue 271 2009PRASANNA GAI This paper reassesses the determinants of sovereign bond yields during the classical gold standard period (1872,1913) using the pooled mean group methodology. We find that, rather than lowering risk premia directly, membership of the gold standard hastened the convergence of sovereign bond spreads to their long-run equilibrium levels. Our results also suggest that investors looked beyond the gold standard to country-specific fundamental factors when pricing and differentiating sovereign risk. [source] |