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Potential Approach (potential + approach)
Selected AbstractsSynthesis and calcium channel modulating effects of modified Hantzsch nitrooxyalkyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(pyridinyl or 2-trifluoromethylphenyl)-5-pyridinecarboxylatesDRUG DEVELOPMENT RESEARCH, Issue 4 2000Ramin Miri Abstract A group of racemic nitrooxyalkyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(pyridinyl or 2-trifluoromethylphenyl)-5-pyridinecarboxylates 8a,o were synthesized using modified Hantzsch reactions. In vitro calcium channel antagonist activities, determined using a guinea pig ileum longitudinal smooth muscle (GPILSM) assay, showed that compounds 8a,o exhibited weaker calcium antagonist activity (10,5 to 10,7 M range) than the reference drug nifedipine (IC50 = 1.43 × 10,8 M). Compounds 8 possessing a C-4 R1 = 2-pyridyl substituent were always more potent than the approximately equiactive analogs having an R1 = 3-pyridyl, 4-pyridyl or 2-CF3 -C6H4 -substituent, within each subgroup of nitrooxyalkyl compounds [R2 = , (CH2)nONO2 (n = 2, 3, 4) or ,CH(CH2ONO2)2]. Although the length of the R2 = ,(CH2)nONO2 substituent (n = 2,4) was not a determinant of smooth muscle calcium antagonist activity when the C-4 R1 -substituent was 2-pyridyl, when R1 was a 3-pyridyl, 4-pyridyl, or 2-CF3 -C6H4 -substituent, the relative potency order with respect to the R2 = ,(CH2)nONO2 substituent was n = 3 and 4 > n = 2. Replacement of the isopropyl substituent of the ester moiety of the calcium antagonist (±)-2-pyridyl 3a by a ,(CH2)nONO2 (n = 2,4) moiety increased calcium antagonist activity on GPILSM by 8-fold. In contrast, replacement of the isopropyl substituent of the ester moiety of the calcium agonists (±)-3-pyridyl 3b, (±)-4-pyridyl 3c or the methyl substituent of the ester moiety of Bay K8644 by a R2 nitrooxyalkyl substituent resulted in abolition of their calcium agonist effects on GPILSM that is replaced by a smooth muscle calcium antagonist effect. These calcium antagonist data support the concept that incorporation of a nitrooxyalkyl ester substituent constitutes a valuable drug design strategy to enhance Hantzsch 1,4-dihydropyridine calcium antagonist and/or abolish calcium agonist effects on smooth muscle. Replacement of the isopropyl (8b,c), or the methyl (8d) group by a ,CH2CH2ONO2 moiety resulted in retention of the cardiac positive inotropic effect where the relative potency order with respect to the C-4 substituent was 2-CF3 -C6H6 - (8d) > 3-pyridyl (8b) , 4-pyridyl (8c). Model hybrid (calcium channel modulation, ·NO release) compounds, that exhibit dual cardioselective agonist / smooth muscle selective antagonist activities, represent a novel type of 1,4-dihydropyridine CC modulator that offers a potential approach to drug discovery targeted toward the treatment of congestive heart failure and for use as probes to study the structure,function relationship of calcium channels. Drug Dev. Res. 51:225,232, 2000. © 2001 Wiley-Liss, Inc. [source] Body Mass Index Measurement in Schools,JOURNAL OF SCHOOL HEALTH, Issue 10 2007Allison J. Nihiser MPH ABSTRACT Background:, School-based body mass index (BMI) measurement has attracted much attention across the nation from researchers, school officials, legislators, and the media as a potential approach to address obesity among youth. Methods:, An expert panel, convened by the Centers for Disease Control and Prevention (CDC) in 2005, reviewed and provided expertise on an earlier version of this article. The panel comprised experts in public health, education, school counseling, school medical care, and a parent organization. This article describes the purposes of BMI measurement programs, examines current practices, reviews existing research, summarizes the recommendations of experts, identifies concerns, and provides guidance including a list of safeguards and ideas for future research. Results:, The implementation of school-based BMI measurement for surveillance purposes, that is, to identify the percentage of students in a population who are at risk for weight-related problems, is widely accepted; however, considerable controversy exists over BMI measurement for screening purposes, that is, to assess the weight status of individual students and provide this information to parents with guidance for action. Although some promising results have been reported, more evaluation is needed to determine whether BMI screening programs are a promising practice for addressing obesity. Conclusions:, Based on the available information, BMI screening meets some but not all of the criteria established by the American Academy of Pediatrics for determining whether screening for specific health conditions should be implemented in schools. Schools that initiate BMI measurement programs should evaluate the effects of the program on BMI results and on weight-related knowledge, attitudes, and behaviors of youth and their families; they also should adhere to safeguards to reduce the risk of harming students, have in place a safe and supportive environment for students of all body sizes, and implement science-based strategies to promote physical activity and healthy eating. [source] Thick Nb-Doped Bismuth Titanate Film with Controllable Grain OrientationJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 8 2006Weiwu Chen In the current work, we reported a potential approach to obtain thick ceramic films with controllable grain orientation based on magnetic alignment and polymerization techniques. The slurry containing 40 vol% Bi4Ti2.96Nb0.04O12 (BINT) ceramic powder, monomer, initiator, and catalyst was drop coated on a Pt substrate and then moved into a vertical 10 T magnetic field. In 1,2 min, the ceramic particles were aligned by a strong magnetic force in slurry and then in situ locked by polymerization on the substrate. After sintering at 1000°C, a BINT ceramic film (50,80 ,m in thickness) with a highly a/b plane orientation was obtained. Theoretically, the grain orientation in the films can be easily controlled by adjusting the magnetic field direction. This approach is readily applicable to other materials with a non-cubic structure and is expected to facilitate the fast preparation of grain-oriented thick films. [source] Ex vivo histological characterization of a novel ablative fractional resurfacing device,LASERS IN SURGERY AND MEDICINE, Issue 2 2007Basil M. Hantash MD Abstract Background and Objectives We introduce a novel CO2 laser device that utilizes ablative fractional resurfacing for deep dermal tissue removal and characterize the resultant thermal effects in skin. Study Design/Materials and Methods A prototype 30 W, 10.6 µm CO2 laser was focused to a 1/e2 spot size of 120 µm and pulse duration up to 0.7 milliseconds to achieve a microarray pattern in ex vivo human skin. Lesion depth and width were assessed histologically using either hematoxylin & eosin (H&E) or lactate dehyrdogenase (LDH) stain. Pulse energies were varied to determine their effect on lesion dimensions. Results Microarrays of ablative and thermal injury were created in fresh ex vivo human skin irradiated with the prototype CO2 laser device. Zones of tissue ablation were surrounded by areas of tissue coagulation spanning the epidermis and part of the dermis. A thin condensed lining on the interior wall of the lesion cavity was observed consistent with eschar formation. At 23.3 mJ, the lesion width was approximately 350 µm and depth 1 mm. In this configuration, the cavities were spaced approximately 500 µm apart and interlesional epidermis and dermis demonstrated viable tissue by LDH staining. Conclusion A novel prototype ablative CO2 laser device operating in a fractional mode was developed and its resultant thermal effects in human abdominal tissue were characterized. We discovered that controlled microarray patterns could be deposited in skin with variable depths of dermal tissue ablation depending on the treatment pulse energy. This is the first report to characterize the successful use of ablative fractional resurfacing as a potential approach to dermatological treatment. Lasers Surg. Med. 39:87,95, 2007. © 2007 Wiley-Liss, Inc. [source] Induction of umbilical cord blood,derived ,2m,c-Met+ cells into hepatocyte-like cells by coculture with CFSC/HGF cellsLIVER TRANSPLANTATION, Issue 6 2005Yunfang Wang Several studies have indicated that adult stem cells derived from bone marrow (BM) and cord blood (CB) can differentiate into hepatocyte-like cells. This ability is important for the treatment of hepatic diseases with BM or CB as a potential approach. However, methods are still being developed for the efficient induction of stem cell differentiation and expansion to get enough cells to be useful. In the present study, we enriched a subset of umbilical cord blood ,2m,c-Met+ cells (UCBCCs) and investigated the combination effect of liver nonparenchymal cells (cirrhotic fat-storing cells [CFSCs]) and hepatocyte growth factor (HGF) on the induction of UCBCCs into hepatocyte-like cells. UCBCCs were cocultured with CFSC/HGF feeder layers either directly or separately using insert wells. Flow cytometric analysis showed that most UCBCCs were CD34+/,CD90+/,CD49f+CD29+Alb+AFP+. After cocultured with transgenic feeder layers for 7 days, UCBCCs displayed some morphologic characteristics of hepatocytes. Reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence cell staining proved that the induced UCBCCs expressed several hepatocyte specific genes including AFP, Alb, CYP1B1 and cytokeratins CK18 and CK19. Furthermore, the induced cells displayed liver specific functions of indocyanine green (ICG) uptake, ammonium metabolism and albumin secretion. Hence, our data have demonstrated that UCBCCs might represent a novel subpopulation of CB-derived stem/progenitor cells capable of successful differentiation into hepatocyte-like cells when incubated with CFSC/HGF cells. In conclusion, not only HGF but also CFSCs and/or the secreted extracellular matrix (ECM) have been shown to be able to serve as essential microenvironment for hepatocyte differentiation. (Liver Transpl 2005;11:635,643.) [source] Protective Effect of Sanguinarine on Ultraviolet B-mediated Damages in SKH-1 Hairless Mouse Skin: Implications for Prevention of Skin CancerPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2007Haseeb Ahsan Excessive exposure of solar ultraviolet (UV) radiation, particularly its UVB component (280,320 nm), to human skin is the major cause of skin cancers. UV exposure also leads to the development of precancerous conditions such as actinic keratosis and elicits a variety of other adverse effects such as sunburn, inflammation, hyperplasia, immunosuppression and skin aging. Therefore, there is a need to intensify our efforts towards the development of novel mechanism-based approaches/agents for the protection of UVB-mediated damages. Chemoprevention is being investigated as a potential approach for the management of UV damages including skin cancer. We have earlier shown that sanguinarine, a benzophenanthridine alkaloid, inhibits UVB exposure-mediated damages in HaCaT keratinocytes. In this study, to determine the relevance of our in vitro findings to in vivo situations, we assessed the effects of sanguinarine on UVB-mediated damages in SKH-1 hairless mice. Our data demonstrated that a topical application of sanguinarine (5 ,mol 0.3 mL,1 ethanol per mouse), either as a pretreatment (30 min prior to UVB) or posttreatment (5 min after UVB), resulted in a significant decrease in UVB-mediated increases in skin edema, skin hyperplasia and infiltration of leukocytes. Further, sanguinarine treatments (pre and post) also resulted in a significant decrease in UVB mediated (1) generation of H2O2 and (2) increases in the protein levels of markers of tumor promotion/proliferation viz. ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA) and Kiel antigen-67. Based on this data, we suggest that sanguinarine could be developed as an agent for the management of conditions elicited by UV exposure including skin cancer. However, further detailed studies are needed to support this suggestion. [source] Proliferation- and migration-enhancing effects of ginseng and ginsenoside Rg1 through IGF-I- and FGF-2-signaling pathways on RSC96 Schwann cellsCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2009Ming-Chin Lu Abstract The aim of the present study is to evaluate the proliferation- and migration-enhancing effects of ginseng and its component, ginsenoside (Rg1) on RSC96 Schwann cells. We investigated the molecular signaling pathways, which include: (1) survival signaling, IGFs-IGFIR-Akt-Bcl2 and proliferative signaling, cell cycle factors and mitogen-activated protein kinase (MAPK) pathways, (2) migrating and anti-scar signaling, FGF-2-uPA-MMPs. We treated RSC96 cells with different concentrations (100, 200, 300, 400, 500,µg,ml,1) of ginseng and its constituent, Rg1 (5, 10, 15, 20, 25,µg,ml,1). We observed a proliferative effect in a dose-dependent manner by PCNA western blotting assay, MTT assay, and wound healing test. Furthermore, we also found in the results of western blotting assay, ginseng and Rg1 enhance protein expression of IGF-I pathway regulators, cell cycle controlling proteins, and MAPK signaling pathways to promote the cell proliferation. In addition, ginseng and Rg1 also stimulated the FGF-2-uPA-MMP 9 migrating pathway to enhance the migration of RSC96 Schwann cells. Using MAPK chemical inhibitors, U0126, SB203580, and SP600125, the proliferative effects of ginseng and Rg1 on RSC96 cells were identified to be MAPK signaling-dependent. On the basis of the results, applying appropriate doses of ginseng and Rg1 with biomedical materials would be a potential approach for enhancing neuron regeneration. Copyright © 2009 John Wiley & Sons, Ltd. [source] Erythropoietin administration does not influence the GH,IGF axis or makers of bone turnover in recreational athletesCLINICAL ENDOCRINOLOGY, Issue 3 2005A. E. Nelson Summary Objective, Measurement of biochemical markers of the IGF-system and of collagen turnover is a potential approach to detect GH abuse in sport. These markers are increased in patients on dialysis treated with recombinant human erythropoietin (r-HuEPO), mimicking the effects of GH. The aim was to determine whether r-HuEPO induces similar effects on the IGF-system and collagen turnover in healthy athletes. Subjects and measurements, Young male Caucasian recreational athletes were administered 50 U/kg r-HuEPO (n = 14) or placebo (n = 16) three times a week for 25 days, followed by a 4-week wash-out period. IGF-I, IGFBP-3, the acid labile subunit (ALS), N-terminal propeptide of type I collagen (PINP), C-terminal telopeptide of type I collagen (ICTP) and N-terminal propeptide of type III collagen (PIIINP) were measured in samples collected at baseline (two samples), after 10, 22 and 24 days of r-HuEPO treatment and at the end of the 4-week wash-out period. Results, Treatment with r-HuEPO resulted in approximately threefold elevation of serum EPO and marked elevation of markers of erythropoiesis. There was no significant treatment effect of r-HuEPO compared to baseline on IGF-I, IGFBP-3, ALS, PINP, ICTP or PIIINP. Conclusions, r-HuEPO administration did not change markers of the IGF-system and of collagen turnover in young healthy male athletes. Therefore, use of r-HuEPO in athletes should not affect the validity of a GH doping test using these GH-responsive markers. [source] Developing limits for driving under cannabisADDICTION, Issue 12 2007Franjo Grotenhermen ABSTRACT Objective Development of a rational and enforceable basis for controlling the impact of cannabis use on traffic safety. Methods An international working group of experts on issues related to drug use and traffic safety evaluated evidence from experimental and epidemiological research and discussed potential approaches to developing per se limits for cannabis. Results In analogy to alcohol, finite (non-zero) per se limits for delta-9-tetrahydrocannabinol (THC) in blood appear to be the most effective approach to separating drivers who are impaired by cannabis use from those who are no longer under the influence. Limited epidemiological studies indicate that serum concentrations of THC below 10 ng/ml are not associated with an elevated accident risk. A comparison of meta-analyses of experimental studies on the impairment of driving-relevant skills by alcohol or cannabis suggests that a THC concentration in the serum of 7,10 ng/ml is correlated with an impairment comparable to that caused by a blood alcohol concentration (BAC) of 0.05%. Thus, a suitable numerical limit for THC in serum may fall in that range. Conclusions This analysis offers an empirical basis for a per se limit for THC that allows identification of drivers impaired by cannabis. The limited epidemiological data render this limit preliminary. [source] Sampling and design challenges in studying the mental health consequences of disastersINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue S2 2008Sandro Galea Abstract Disasters are unpredictable and frequently lead to chaotic post-disaster situations, creating numerous methodologic challenges for the study of the mental health consequences of disasters. In this commentary, we expand on some of the issues addressed by Kessler and colleagues, largely focusing on the particular challenges of (a) defining, finding, and sampling populations of interest after disasters and (b) designing studies in ways that maximize the potential for valid inference. We discuss these challenges , drawing on specific examples , and suggest potential approaches to each that may be helpful as a guide for future work. We further suggest research directions that may be most helpful in moving the field forward. Copyright © 2008 John Wiley & Sons, Ltd. [source] Assessment of potential approaches to improve Eucalyptus globulus kraft pulping yieldJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 5 2007A. S. Santiago Abstract The main goal of this work is to study the potential approaches to improve polysaccharides retention during Eucalyptus globulus kraft pulping. The addition of anthraquinone to kraft pulping leads to the highest pulp yield while the addition of urea promotes lower depolymerization of polysaccharides (higher pulp viscosity), but does not have a significant effect on yield. The early interruption of kraft cooking followed by oxygen delignification is a reliable approach to increase pulp yield, particularly when pulping is interrupted at the end of the faster and more selective kinetic regime (bulk phase). Yield loss during oxygen delignification is considerably lower than that incurred in the last phase of kraft pulping. Pulping with OH,/HS, charge profiling, carried out with liquor injection in three different phases leads to a yield increase. However, this increase results from a lower total alkali charge applied when profiling pulping is compared to standard pulping conditions, rather than to alkali profiling. Standard kraft pulping with different active alkali (AA) charges demonstrated that this operational variable is determinant for pulp yield and viscosity. Pulping experiences with lower AA (14%) resulted in a higher and almost constant pulp viscosity and in a higher pulp yield, assigned to improved retention of both cellulose and xylan. During the last stage of pulping, cellulose content decreases, this being mainly responsible for the decrease of pulp yield, while xylan content is almost constant, a feature attributed to the peculiar structure of this E. globulus's hemicellulose. Copyright © 2007 Society of Chemical Industry [source] Reconsidering Regulation and Governance Theory: A Learning ApproachLAW & POLICY, Issue 2 2009JOHN S. F. WRIGHT Theories and frameworks for regulation of particular industries or types of behavior have grown in richness in recent years. This article identifies three perspectives within contemporary regulatory theory: "normative,""descriptive," and "poststructuralist" perspectives. We ask whether contemporary models of regulatory governance arrangements adequately capture and explain the characteristics and operation of existing regulatory spaces. We outline three key models linked to these perspectives (responsive regulation, smart regulation, and nodal governance) and discuss their relevance with specific reference to one complex case study, the gambling industry in a federal polity, Australia, where the regulatory arrangements are quite diverse. We argue that regulatory theory needs to remain flexible if it is to inform an understanding of concrete regulatory challenges, thereby assisting analysts and practitioners to assess current and potential approaches for improved regulatory governance arrangements. Accordingly, we build a case for considering a learning perspective on regulation and governance theory linked to pragmatism. [source] Diversity-affirming ethics and critical epistemology: Institutional decision making in community collegesNEW DIRECTIONS FOR COMMUNITY COLLEGES, Issue 148 2009Antonette Aragon This chapter raises awareness about potential approaches to institutional decision making in community colleges that embody diversity-affirming ethics and a critical epistemological orientation that promotes social justice. [source] Innovations in the Development and Application of Edible Coatings for Fresh and Minimally Processed Fruits and VegetablesCOMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY, Issue 3 2007Daniel Lin ABSTRACT:, One of the major growth segments in the food retail industry is fresh and minimally processed fruits and vegetables. This new market trend has thus increased the demands to the food industry for seeking new strategies to increase storability and shelf life and to enhance microbial safety of fresh produce. The technology of edible coatings has been considered as one of the potential approaches for meeting this demand. Edible coatings from renewable sources, including lipids, polysaccharides, and proteins, can function as barriers to water vapor, gases, and other solutes and also as carriers of many functional ingredients, such as antimicrobial and antioxidant agents, thus enhancing quality and extending shelf life of fresh and minimally processed fruits and vegetables. This review discusses the rationale of using edible coatings on fresh and minimally processed produce, the challenges in developing effective coatings that meet the specific criteria of fruits and vegetables, the recent advances in the development of coating technology, the analytical techniques for measuring some important coating functionalities, and future research needs for supporting a broad range of commercial applications. [source] | |||||||||||||