Spectroscopic studies on the interaction of efonidipine with bovine serum albumin

Efonidipine hydrochloride is an antihypertensive and antianginal agent with fewer side effects and is better tolerated in the treatment of hypertension with renal impairment. Its interaction with bovine serum albumin (BSA) is of great use for the understanding of the pharmacokinetic and pharmacodynamic mechanisms of the drug. The binding of efonidipine to BSA was investigated by fluorescence spectroscopy and circular dichroism. BSA fluorescence was quenched by efonidipine, due to the fact that efonidipine quenched the fluorescence of tryptophan residues mainly by the collision mode. The thermodynamic parameters ΔH0 and ΔS0 were 68.04 kJ/mol and 319.42 J·mol-1·K-1, respectively, indicating that the hydrophobic interactions played a major role. The results of circular dichroism and synchronous fluorescence measurements showed that the binding of efonidipine to BSA led to a conformational change of BSA. The fraction of occupied sites (θ) for the 8-anilino-1-naphthalein-sulfonic acid (ANS)-BSA system is 85%, whereas for the NZ-105-BSA system, it is 53%, which suggests that the interaction of ANS with BSA is stronger than that of NZ-105 with BSA. Binding studies in the presence of ANS indicated that efonidipine competed with ANS for hydrophobic sites of BSA. The effects of metal ions on the binding constant of the efonidipine-BSA complex were also investigated. The presence of metal ions Zn2+, Mg2+, Al3+, K+, and Ca2+ increased the binding constant of efonidipine_BSA complex, which may prolong the storage period of NZ-105 in blood plasma and enhance its maximum effects.

Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway

We have shown that the peripheral and spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase-cGMP pathways play an important role in antinociception in the rat experimental formalin model. Our objective was to determine if there is synergism between peripheral (paw) and spinal HO-CO pathways in nociception. Rats were handled and adapted to the experimental environment for a few days before the formalin test, in which 50 µL of a 1% formalin was injected subcutaneously into the dorsal surface of the right hind paw. The animals were then observed for 1 h and the frequency of flinching behavior was taken to represent the nociceptive response. Thirty minutes before the test, rats were pretreated with intrathecal injections of the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is a substrate of the HO pathway. The paw treatments took place 20 min before the test. Low doses of ZnDPBG did not increase nociception, while a low heme-lysinate dose did not change flinching behavior after paw or spinal injections. Combined subactive spinal (50 nmol) and peripheral (40 nmol) low doses of ZnDPBG induced hypernociception (increase of 80% in the first and 25% in the second phase flinching), whereas combined spinal-peripheral heme-lysinate (50 and 30 nmol) led to second phase antinociception (40% reduction in flinching). These findings suggest a synergy between the peripheral and spinal HO-CO pathways. Local activation of the HO system probably regulates the nociception initiation in peripheral tissue and participates in buffering the emerging nociceptive signals at the peripheral and spinal sites of action. In short, an antinociceptive synergy exists between peripheral and spinal HO pathways, which may reduce the doses required and side effects.

Phylogenetic Analysis of Avidins and Expression of Novel Avidins from Lactrodectus hesperus and Hoeflea phototrophica

Avidins (Avds) are homotetrameric or homodimeric glycoproteins with typically less than 130 amino acid residues per monomer. They form a highly stable, non-covalent complex with biotin (vitamin H) with Kd = 10-15 M (for chicken Avd). The best-studied Avds are the chicken Avd from Gallus gallus and streptavidin from Streptomyces avidinii, although other Avd studies have also included Avds from various origins, e.g., from frogs, fishes, mushrooms and from many different bacteria. Several engineered Avds have been reported as well, e.g., dual-chain Avds (dcAvds) and single-chain Avds (scAvds), circular permutants with up to four simultaneously modifiable ligand-binding sites. These engineered Avds along with the many native Avds have potential to be used in various nanobiotechnological applications. In this study, we made a structure-based alignment representing all currently available sequences of Avds and studied the evolutionary relationship of Avds using phylogenetic analysis. First, we created an initial multiple sequence alignment of Avds using 42 closely related sequences, guided by the known Avd crystal structures. Next, we searched for non-redundant Avd sequences from various online databases, including National Centre for Biotechnology Information and the Universal Protein Resource; the identified sequences were added to the initial alignment to expand it to a final alignment of 242 Avd sequences. The MEGA software package was used to create distance matrices and a phylogenetic tree. Bootstrap reproducibility of the tree was poor at multiple nodes and may reflect on several possible issues with the data: the sequence length compared is relatively short and, whereas some positions are highly conserved and functional, others can vary without impinging on the structure or the function, so there are few informative sites; it may be that periods of rapid duplication have led to paralogs and that the differences among them are within the error limit of the data; and there may be other yet unknown reasons. Principle component analysis applied to alternative distance data did segregate the major groups, and success is likely due to the multivariate consideration of all the information. Furthermore, based on our extensive alignment and phylogenetic analysis, we expressed two novel Avds, lacavidin from Lactrodectus Hesperus, a western black widow spider, and hoefavidin from Hoeflea phototrophica, an aerobic marine bacterium, the ultimate aim being to determine their X-ray structures. These Avds were selected because of their unique sequences: lacavidin has an N-terminal Avd-like domain but a long C-terminal overhang, whereas hoefavidin was thought to be a dimeric Avd. Both these Avds could be used as novel scaffolds in biotechnological applications.

Causação circular do crescimento das economias em desenvolvimento: uma ponte entre as abordagens evolucionária e pós keynesiana

Based on the Post Keynesian approach and on the Evolutionary literature, this study seeks to demonstrate the causal relationships between the National Innovation System and the national and international financial systems. This study shows that there is a circular causation in the less developed economies that contributes to the immaturity of its National Innovation System and to its structural external vulnerability. Conclusions highlight that the cycles in the less developed economies mirror the cycles of international liquidity.

Changing roles of nurse educators employed in acute and chronic care settings : the impact of professional and statutory mandates in Ontario at four sites of one hospital corporation /

The role of the hospital-employed nurse educator is evolving. Factors influencing this change include the introduction of standards for nurse educators by the College of Nurses of Ontario (CNO), a change in the way nurses are educated, the emergence of nursing as a profession, and hospital restructuring as a result of budgetary constraints. Two of these influencing factors: the introduction of the updated Standards of Practice for Registered Nurses and Registered Practical Nurses (1996) and hospital restructuring occurred over the last 7 years at several hospitals in southern Ontario. Current literature as well as the Standards of Practice (1996) were utilized to examine the current roles and responsibilities of nurse educators and subsequently develop a questionnaire to study the impact of these influencing factors on the role of the nurse educator. This questionnaire was piloted and revised before its distribution at 4 hospitals in southern Ontario. Twenty-five of the 41 surveys (61%) distributed were returned for analysis. The data reflected that the Standards of Practice had a positive influence on the role of the nurse educator, while hospital restructuring had a negative impact. In addition, many of the roles and responsibilities identified in the literature were indeed part of the current role of nurse educators, as well as several responsibilities not captured in the literature. The predictions for the future of this role in its current state were not positive given the financial status of the health care system as well as the lack of clarity for the role and the current level ofjob satisfaction among practicing nurse educators. However, a list of recommendations were generated which, if implemented, could add clarity to the role and improve job satisfaction. This could enhance the retention of current nurse educators and the possibility of recruiting competent nurse educators to the role in the future.

Anomalous carbonate preservation in the abyssal North Pacific, ODP sites 882 and 1179: planktonic foraminiferal analysis, climate change and palaeogeomagnetism /

Thesis (M.Sc.)--Brock University, 2004.

The micromorphology of Paleoseismic soft sediment deformation structures in glacial deposits from three sample sites in Scotland /

The nature of this research is to investigate paleoseismic deformation of glacial soft sediments from three sampling sites throughout the Scottish Highlands; Arrat's Mills, Meikleour and Glen Roy. The paleoseismic evidence investigated in this research will provide a basis for applying criteria to soft sediment deformation structures, and the trigger mechanisms that create these structures. Micromorphology is the tool used in this to investigate paleoseismic deformation structures in thin section. Thin section analysis, (micromorphology) of glacial sediments from the three sampling sites is used to determine microscale evidence of past earthquakes that can be correlated to modem-day events and possibly lead to a better understanding of the impact of earthquakes throughout a range of sediment types. The significance of the three sampling locations is their proximity to two major active fault zones that cross Scotland. The fault zones are the Highland Boundary Fault and the Great Glen Fault, these two major faults that parallel each other and divide the country in half Sims (1975) used a set of seven criteria that identified soft sediment deformation structures created by a magnitude six earthquake in Cahfomia. Using criteria set forth by Sims (1975), the paleoseismic evidence can be correlated to the magnitude of the deformation structures found in the glacial sediments. This research determined that the microstructures at Arrat's Mill, Meikleour and Glen Roy are consistent with a seismically induced origin. It has also been demonstrated that, even without the presence of macrostructures, the use of micromorphology techniques in detecting such activity within sediments is of immense value.

Vegetational history and geochronology of several sites in South Southwestern Ontario with discussion on mastodon extinction in Southern Ontario /

This study has three purposes: to establish a chronologically controlled vegetational history for a number of sites in south Southwestern Ontario; to utilize the resulting data to support and/or add to the current understanding of Quaternary geology and stratigraphy, and the glacial and postglacial history of the Great Lakes in south Southwestern Ontario; and to attempt to propose a possible explanation for the extinction of the mastodon in Southern Ontario. Palynological and geochronological analyses were conducted on material collected from eleven sites (east to west): Verbeke Mastodon Site, Woloshko Mastodon Site, Walker Pond II, Pond Mills I, Lake Hunger Bog, Bouckaert Site. Mabee Site, Cornell Bog. Colles Lake I, Folden Mastodon Site and Forest Pond. Individual geochronologically controlled (where possible) vegetational histories were reconstructed for each of the sites investigated. The results of the individual studies, when considered in overview. indicated the existance of an established closed boreal forest throughout south Southwestern Ontario by 10,000 years B.P. This evidence for a significant climatic change coincident throughout south Southwestern Ontario supports the proposed age of 10,000 years B.P. for the Pleistocene/Holocene Boundary (Terasmae, 1972). Remnant patches of 'open spruce parkland' persisted in small local 'wet' areas. It was in these areas that the mastodon was restricted during early Holocene time. With continued encroachment by the surrounding boreal forest, possibly speeded up by this browser's destructive feeding habits, the spruce enclaves shrank and the mastodon became extinct in south Southwestern Ontario. The results of this thesis basically support Dreimanis' (1967, 1968) proposed 'Environmental-Climatic' theory for mastodon extinction. It is suggested that increased dryness during the present interglacial compared to the climate of earlier interglacials may be the key to unravelling the problem of mastodon extinction in eastern North America.

Examining and describing professional development and continuing education in the personal training and fitness industry : sites and issues of disconnect

The following phenomenologically oriented study examines and describes the relevance and effectiveness of professional development and continuing education programs for real-world situations of personal trainers. The participants were personal trainers, facility managers, and persons involved in the accreditation process. Data collection took place in 3 phases. The first phase consisted of the participants completing the PUMP Questionnaire, followed by focus groups with personal trainers and interviews with managers. The study's 3 data sets required reduction via a content analysis by question, content analysis by existential categories, and further thematic analysis using the lived relation existential dimension. The discussion contains the salient sites and issues of disconnect between clients, personal trainers, and facility managers and how they might affect the personal training experience. The intergenerational disconnect emphasized between Boomers as clients and Millennials as personal trainers requires further exploration and dialogue and underscores the need for different approaches to content and delivery of professional development and continuing education experiences for personal trainers and managers of fitness facilities.

Bee Communities in Restored Landfill Sites of Niagara Region

This study examined the impact of habitat restoration on bee communities (Hymenoptera: Apidae) of the Niagara Region, Ontario, Canada. Bee abundance and diversity was studied in three restored landfill sites: the Glenridge Quarry Naturalization Site (GQNS) in St. Catharines, Elm Street Naturalization Site in Port Colborne, and Station Road Naturalization Site in Wainfleet during 2011 and 2012. GQNS represented older sites restored from 2001-2003. Elm and Station sites represented newly restored landfills as of 2011. These sites were compared to control sites at Brock University where bee communities are well established and again to other landfills where no stable habitat was available before restoration. The objective of this study is to investigate the impact of restoration level on bee abundance and diversity in restored landfill sites of the Niagara Region. Based on the increased disturbance hypothesis (InDH) and the intermediate disturbance hypothesis (IDH), I hypothesized that bee abundance and diversity will follow two patterns. First pattern according to InDH suggest that as the disturbance decrease the bee abundance and diversity will increased. Second pattern according to the IDH bee abundance and diversity will be the highest at the intermediate level of disturbance. A total of 7 173 bees were collected using pan traps and flower collections, from May to October 2011 and 2012. Bees were classified to five families, 21 genera and sub-genera, containing at least 78 species. In 2011 bee abundance was not significantly different among restoration levels while in 2012 bee abundance was significant difference among restoration level. According to family there were no significant difference in Halictidae and Apidae abundance among restoration level while Colletidae and Megachilidae abundance were varied among restoration levels. The bee species richness was highest in the newly restored sites followed by restored control sites, and then the control site. The current study demonstrates that habitat restoration results in rapid increases in bee abundance and diversity for newly restored sites, and, further, that it takes only 2-3 years for bee assemblages in newly restored sites to arrive at the same levels of abundance and diversity as in nearby control sites where bee communities are well established.