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PubMed2003

Spinal cord injury: promising interventions and realistic goals.

Long regarded as impossible, spinal cord repair is approaching the realm of reality as efforts to bridge the gap between bench and bedside point to novel approaches to treatment. It is important to recognize that the research playing field is rapidly changing and that new mechanisms of resource development are required to effectively make the transition from basic science discoveries to effective clinical treatments. This article reviews recent laboratory studies and phase 1 clinical trials in neural and nonneural cell transplantation, stressing that the transition from basic science to clinical applications requires a parallel rather than serial approach, with continuous, two-way feedback to most efficiently translate basic science findings, through evaluation and optimization, to clinical treatments. An example of mobilizing endogenous stem cells for repair is reviewed, with emphasis on the rapid application of basic science to clinical therapy. Successful and efficient transition from basic science to clinical applications requires (1) a parallel rather than a serial approach; (2) development of centers that integrate three spheres of science, translational, transitional, and clinical trials; and (3) development of novel resources to fund the most critically limited step of transitional to clinical trials.

Animals↗

PubMed2003

White-light filaments for atmospheric analysis.

Most long-path remote spectroscopic studies of the atmosphere rely on ambient light or narrow-band lasers. High-power femtosecond laser pulses have been found to propagate in the atmosphere as dynamically self-guided filaments that emit in a continuum from the ultraviolet to the infrared. This white light exhibits a directional behavior with enhanced backward scattering and was detected from an altitude of more than 20 kilometers. This light source opens the way to white-light and nonlinear light detection and ranging applications for atmospheric trace-gas remote sensing or remote identification of aerosols. Air ionization inside the filaments also opens promising perspectives for laser-induced condensation and lightning control. The mobile femtosecond-terawatt laser system, Teramobile, has been constructed to study these applications.

Journal Article↗

PubMed2006

Changes in serum leptin and beta endorphin levels with weight loss by electroacupuncture and diet restriction in obesity treatment.

This study aims to investigate the role of changes in leptin and beta endorphin (BE) levels in weight loss following electroacupuncture (EA) application in obesity treatment. EA was applied to 20 females who were 41.45 +/- 4.71 years old and had a body mass index of 36.00 +/- 2.66; and a diet program was applied to 20 females who were 42.30 +/- 4.35 years old and had a body mass index of 34.90 +/- 3.21. There was a 4.5% weight reduction in the patients with EA application, whereas patients on diet restriction had a 3.1% weight reduction. A decrease of loss of body weight was observed in the EA group (p < 0.000) when compared against the diet restricted group. A decrease of serum leptin levels (p < 0.000) and an increase in the serum BE (p < 0.05) levels were observed in the EA group compared to the diet restricted group. In this study, reduced serum leptin levels paralleling to weight loss were observed in the EA group. Furthermore, it is thought that in the EA applied group, increasing serum BE level probably enhanced the lipolitic activity which may have caused weight loss in obese people by mobilizing energy stores. It may be considered that the EA application with diet restriction in obesity treatment is more effective than the diet restriction alone.

Adult↗

PubMed1989

Supercritical fluid chromatography and microbore liquid chromatography for drug analysis.

Supercritical fluid and microbore liquid chromatography offer potential applications for drug analysis. In supercritical fluid chromatography (SFC), the mobile phase is a gas (e.g., carbon dioxide) maintained at its supercritical state--that is, above its critical temperature and pressure, above which it cannot be liquefied even with further increases in applied pressure. The SFC mobile phase has low viscosity, approximating that of a gas, and high diffusivity, between those of a gas and a liquid. These properties yield favorable column efficiency, between that of capillary gas chromatography (GC) and liquid chromatography (LC). SFC analysis may be performed by either packed or open tubular capillary columns and with GC and LC detectors. SFC, interfaced with mass spectrometry, may become a viable alternative to GC/MS for drug identification in clinical and forensic toxicology. Advantages of microbore liquid chromatography include enhanced mass sensitivity, reduced solvent consumption, and others. Microbore columns (internal diameters 1 to 2 mm) may be packed with 3-, 5-, or 10-micron particles. Potential applications include micro-sample analysis (5-200 microL) for neonatal and pediatric drug monitoring, and drug confirmation analysis for toxicology.

Chromatography↗

PubMed1996

Methods of stem cell mobilization.

The rapid rescue of hematopoiesis following transplantation of peripheral blood stem cells (PBSC) has facilitated expanded application of high-dose chemotherapy regimens for several malignancies. A variety of regimens have been described to enhance the circulation of PBSC, including the use of hematopoietic growth factors, either alone or following myelosuppressive chemotherapy. Such improvements of PBSC mobilization can increase the number of hematopoietic progenitors for transplantation and reduce the number of leukapheresis procedures required. We review several approaches to the collection of PBSC, including our experience with the use of cytokines in addition to chemotherapy. In addition, we discuss the investigation of novel cytokine combinations and in vitro expansion techniques, which may lead to further improvements in both the efficiency of PBSC collection and hematopoietic recovery following transplantation.

Antineoplastic Agents↗

PubMed1996

Screening the environmental fate of organic contaminants in sewage sludges applied to agricultural soils: 1. The potential for downward movement to groundwaters.

The potential for organic contaminants present in sewage sludge to leach and cause groundwater contamination following sludge application to agricultural land has been assessed. Models used to predict compound mobility in soil on the basis of physico-chemical parameters were applied to a range of contaminants prioritised and/or detected in sludge and a provisional list of potential "leachers' compiled. In addition, theoretical soil water concentrations following sludge application were calculated using mean reported sludge contaminant concentrations and soil/water partition coefficients. These estimated aqueous phase concentrations were compared with Dutch groundwater quality standards in the absence of appropriate UK standards to identify those compounds which could be present in groundwater at levels of concern. The two prioritised lists were used to identify compounds in sludge which could pose a possible threat to groundwater. Appropriate experimental data were not available to qualify model results. However, the screening exercise indicated that under routine operation practice with typical sludge application rates, and the usual range of compound concentrations detected in sludge, groundwater quality standards were unlikely to be exceeded. However, data variability, reliability and scarcity limited the usefulness of this screening approach.

Agriculture↗

PubMed2002

Rapid screening of pKa values of pharmaceuticals by pressure-assisted capillary electrophoresis combined with short-end injection.

A method applying pressure-assisted capillary electrophoresis combined with short-end injection has been developed for the rapid screening of the pKa values of pharmaceuticals. The electrophoretic separation is performed on a short capillary length with short-end injection under an applied pressure, and the effective mobility is measured in a series of 10 different buffers with constant ionic strength (I = 0.05). The application of pressure not only reduces migration times, particularly in lower pH buffers, but also improves the repeatability of effective mobility measurements. The influence of pressure on the effective mobility was investigated at various pH values. It was observed for the first time that an increase in pressure resulted in a slight decrease in the effective mobility when the pH was above the pKa for acidic analytes, whereas an increased effective mobility with increasing pressures was observed when the pH was below the pKa. However, the observed effective mobility shift by the applied pressure did not significantly affect the determined pKa values. The determined pKa values were in good agreement with published data. Furthermore, a stacking condition was applied to increase the sensitivity, and a concentration down to 2 microM could readily be detected with UV detection using a 50 microm I.D. capillary. This technique is particularly suitable for measurement of pKa values for compounds with poor aqueous solubility. The method also omits the commonly used preconditioning steps with sodium hydroxide and water. The exclusion of excessive preconditioning steps and the use of pressure reduces the total cycling analysis time, and makes it possible to determine the pKa in less than 40 min per compound without loss of accuracy.

Electrolytes↗

PubMed2002

Application of sequential extraction with supercritical CO(2), subcritical H(2)O, and an H(2)O/CO(2) mixture for estimation of environmentally mobile heavy metal fractions in sediments.

Results from use of a new isolation procedure based on sequential extraction with supercritical CO(2), subcritical H(2)O, and an H(2)O/CO(2) mixture in the same supercritical fluid extractor have been compared with results from the BCR-recommended three-step sequential extraction procedure. The new procedure gives more detailed information about environmentally mobile fractions (water-soluble, bicarbonate-forming), and in less time (5-6 h), than the BCR procedure.

Carbon Dioxide↗

PubMed2001

Hydrophilic interaction chromatography using amino and silica columns for the determination of polar pharmaceuticals and impurities.

Hydrophilic interaction chromatography (HILIC) is described as a useful alternative to reversed-phase chromatography for applications involving polar compounds. In the HILIC mode, an aqueous-organic mobile phase is used with a polar stationary phase to provide normal-phase retention behavior. Silica and amino columns with aqueous-acetonitrile mobile phases offer potential for use in the HILIC mode. An examination of the retention and separation of several pyrimidines, purines, and amides on silica and amino columns from three manufacturers revealed that mobile phases should contain a buffer or acid for pH control to achieve similar and reproducible results among columns from different sources. Amino columns may also be used in an anion-exchange mode, which provides an advantage for some applications. In some cases, silica can provide different selectivity and better separation than an amino column. Example applications include: low-molecular-mass organic acids and amides as impurities in non-polar drug substances, 5-fluorouracil in 5-fluorocytosine, guanine in acyclovir, and different selectivity for polar basic compounds compared to an ion-pairing system.

Acetamides↗

PubMed1997

Using protein charge ladders to estimate the effective charges and molecular weights of proteins in solution.

This paper describes the use of capillary electrophoresis (CE) and protein charge ladders to estimate values of effective charge (Z) and molecular weight of proteins under nondenaturing conditions. A panel of 14 proteins with a range of charges and shapes was modified by acetylation with acetic anhydride to yield protein charge ladders. A protein charge ladder is a family of derivatives of a protein that differ in integral units of charge, but minimally in hydrodynamic drag; this mixture of proteins appears in electrophoresis as a set of peaks with regular spacings. Analysis of the electrophoretic mobilities of the members of these charge ladders yields values of Z and electrophoretic coefficients: for a description of mobility based on the equation mu = CPZ(MW)-alpha, CP = 6.3 cm2 min-1 kV-1 charge-1 kD0.48, alpha = 0.48; for mu = C(r)Z[r(1 + kappa r)]-1, C(r) = 55 cm2 min-1 kV-1 charge-1 A (r is the spherical radius of the protein and kappa is a function of ionic strength). The primary usefulness of charge ladders is in measuring the effective charge, Z, of proteins in solution; this information is difficult to obtain by any other procedure. A secondary value of the method is to estimate values of molecular weight. Although less general and convenient than SDS-PAGE, this method allows estimates of molecular weight of nondenatured proteins and is thus applicable to oligomers, noncovalent aggregates, proteins with multiple, non-cross-linked chains, and other systems to which SDS-PAGE is not applicable. The values of molecular weight calculated using the electrophoretic mobilities of proteins in solution and the above constants agreed with literature values to within 20% (with an ambiguous result for ovalbumin). A combination of this technique and SDS-PAGE will be useful in estimating the number of subunits or stage of aggregation of proteins in solution.

Acetic Anhydrides↗

PubMed1978

Population movement and city-suburb redistribution: an analytic framework.

This paper introduces an analytic framework that can be used to assess the relationships between individual movement differentials and place characteristics, on the one hand, and aggregate mobility levels and city-suburb population change (in size or composition), on the other. Application of this framework using census data for individual metropolitan areas allows the analyst to decompose population changes due to net migration into contributing mobility streams and their component rates which are subject to unique community and individual influences. The paper provides both theoretical and empirical rationale for the framework, illustrates its use with 1970 census data, and discusses its implications for empirical research on city-suburb population redistribution.

Humans↗

PubMed2001

A rapid and stable ITLC procedure for the determination of the radiochemical purity of 99Tcm-tetrofosmin.

99Tcm-tetrofosmin (Myoview, Amersham Healthcare) is widely used as a radiopharmaceutical for myocardial perfusion imaging. Control of its radiochemical purity after reconstitution is usually performed by means of ITLC-SG paper chromatography in a mobile phase of methylene chloride/acetone (65/35), as recommended by the manufacturer. The present study describes the application of tetrahydrofuran in phosphate buffer for the development of 99Tcm-tetrofosmin on ITLC-SG strips. The use of this mobile phase significantly improves the separation between labelled tetrofosmin and unbound pertechnetate. The time for development is about 1 min and the solvent is stable for at least 1 year. In addition, the volume spotted on the strip does not affect the migration of 99Tcm-tetrofosmin. The labelling efficiency of 99Tcm-tetrofosmin can successfully be monitored by means of this method as a daily routine procedure.

Chromatography, Paper↗

PubMed2006

[Effects of different immunodepressants on the sperm parameters of kidney transplant recipients].

OBJECTIVE: To study the effects of different immunodepressants on the sperm parameters of kidney transplant recipients. METHODS: In 15 healthy fertile men and 37 kidney transplant recipients, ejaculates were aseptically obtained by masturbation. Thirty-seven patients were divided into two groups, 20 patients were treated with Prograf (FK506) combination with mycophenolate mofetil (MMF) and prednisone; 17 patients were treated with cyclosporine (CsA) combination with azathioprine with prednisone. The sperm viability, mobility parameters such as prorsad percentage motility, straight line velocity (VSL), curve line velocity (VCL), velocity of average path (VAP) and morph were estimated with a computer-assisted sperm analyzer (CASA) provided with a multiple-exposure photography system. RESULTS: There were no significant difference in sperm viability rate [(81.7 +/- 5.7)%, (79.4 +/- 6.8)% and (83.8 +/- 6.0)%], VCL [(24.1 +/- 8.6)%, (23.9 +/- 4.4)%, (24.8 +/- 4.2)% ] and VAP [(19.7 +/- 6.6)%, (18.6 +/- 2.9)%, (21.0 +/- 4.0)%] among groups of FK506, CsA and control, respectively (P > 0.05). The rate of anomaly [(67.8 +/- 5.7)%], the prorsad percentage motility [(46.4 +/- 8.1)%] and VSL [(15.4 +/- 4.6)%] in the group of FK506 were respectively significantly lower and higher than those in the group of CsA [(80.1 +/- 5.6%, (33.3 +/- 6.4)%, (10.2 +/- 2.4)%] (P < 0.05). CONCLUSION: The application of FK506 combined with MMF could help recover the mobility and morphology of the sperm in kidney transplantation recipients.

Adolescent↗

PubMed1986

An experimental test of new theoretical models for the electrokinetic properties of biological membranes. The effect of UO2++ and tetracaine on the electrophoretic mobility of bilayer membranes and human erythrocytes.

For a large smooth particle with charges at the surface, the electrophoretic mobility is proportional to the zeta potential, which is related to the charge density by the Gouy-Chapman theory of the diffuse double layer. This classical model adequately describes the dependence of the electrophoretic mobility of phospholipid vesicles on charge density and salt concentration, but it is not applicable to most biological cells, for which new theoretical models have been developed. We tested these new models experimentally by measuring the effect of UO2++ on the electrophoretic mobility of model membranes and human erythrocytes in 0.15 M NaCl at pH 5. We used UO2++ for these studies because it should adsorb specifically to the bilayer surface of the erythrocyte and should not change the density of fixed charges in the glycocalyx. Our experiments demonstrate that it forms high-affinity complexes with the phosphate groups of several phospholipids in a bilayer but does not bind significantly to sialic acid residues. As observed previously, UO2++ adsorbs strongly to egg phosphatidylcholine (PC) vesicles: 0.1 mM UO2++ changes the zeta potential of PC vesicles from 0 to +40 mV. It also has a large effect on the electrophoretic mobility of vesicles formed from mixtures of PC and the negative phospholipid phosphatidylserine (PS): 0.1 mM UO2++ changes the zeta potential of PC/PS vesicles (10 mol % PS) from -13 to +37 mV. In contrast, UO2++ has only a small effect on the electrophoretic mobility of either vesicles formed from mixtures of PC and the negative ganglioside GM1 or erythrocytes: 0.1 mM UO2++ changes the apparent zeta potential of PC/GM1 vesicles (17 mol % GM1) from -11 to +5 mV and the apparent zeta potential of erythrocytes from -12 to -4 mV. The new theoretical models suggest why UO2++ has a small effect on PC/GM1 vesicles and erythrocytes. First, large groups (e.g., sugar moieties) protruding from the surface of the PC/GM1 vesicles and erythrocytes exert hydrodynamic drag. Second, charges at the surface of a particle (e.g., adsorbed UO2++) exert a smaller effect on the mobility than charges located some distance from the surface (e.g., sialic acid residues).

Electrophoresis↗

PubMed2004

Endothelium-targeted gene and cell-based therapies for cardiovascular disease.

Most common cardiovascular diseases are accompanied by endothelial dysfunction. Because of its predominant role in the pathogenesis of cardiovascular disease, the vascular endothelium is an attractive therapeutic target. The identification of promoter sequences capable of rendering endothelial-specific transgene expression together with the recent development of vectors with enhanced tropism for endothelium may offer opportunities for the design of new strategies for modulation of endothelial function. Such strategies may be useful in the treatment of chronic diseases such as hypertension, atherosclerosis, and ischemic artery disease, as well as in acute myocardial infarction and during open heart surgery for prevention of ischemia and reperfusion (I/R)-induced injury. The recent identification of putative endothelial progenitor cells in peripheral blood may allow the design of autologous cell-based strategies for neovascularization of ischemic tissues and for the repair of injured blood vessels and bioengineering of vascular prosthesis. "Proof-of-concept" for some of these strategies has been established in animal models of cardiovascular disease. However the successful translation of these novel strategies into clinical application will require further developments in vector and delivery technologies. Further characterization of the processes involved in mobilization, migration, homing, and incorporation of endothelial progenitor cells into the target tissues is necessary, and the optimal conditions for therapeutic application of these cells need to be defined and standardized.

Animals↗

PubMed2001

[Effect of boron fertilization on B uptake and utilization by oilseed rape(Brassica napus L.) under different soil moisture regimes].

Pot experiment was conducted in greenhouse to determine the effect of boron fertilization on B uptake and utilization by oilseed rape at seedling stage as influenced by soil moisture regime. The results showed that B concentration in shoot and root increased with the increase of soil water content and B fertilization level, while its utilization efficiency(BUE) and mobilization index(BMI) increased with the decrease of soil water content and B application level. Differences in BUE and BMI of test oilseed rape cultivars were significant, i.e., V1 showed higher BUE and BMI than V4 under the same conditions. It is concluded that BUE and B mobility in plant were the major factors responsible for the differences in response of different oilseed rape cultivars to B deficiency.

Absorption↗

PubMed2006

Effect of system variables involved in packed column supercritical fluid chromatography of stavudine taken as model analyte using response surface methodology along with study of thermodynamic parameters.

A multifactor optimization technique is successfully applied to study the effect of simultaneously varying the system variables on feasibility of stavudine analysis by packed column supercritical fluid chromatography (PC-SFC). The effect of simultaneously varying the pressure, temperature and modifier concentration was studied to optimize the method in order to obtain excellent chromatographic figures of merit. The method is based on isocratic elution using methanol-modified supercritical carbon dioxide as the mobile phase at the flow rate of 3.0 ml/min through a JASCO Finepak SIL-5, ODS [C(18) (5 microm, 25 cm x 4.6 mm, i.d.)] column support using photodiode array detection. The optimal conditions were determined with the aid of the response surface methodology using 3(3) factorial designs. From the response surface graphs optimum regions were selected to be +1, -1, and +1 for temperature (60 degrees C), pressure (20 MPa) and percent modifier concentration (17.81%, v/v), respectively. Linearity dynamic range was found to be in the range of 2.0-150.0 microg/ml with significantly high value of correlation coefficient. The method was validated for precision, robustness and recovery to assess the viability of the established method. The chromatographic limit of detection and quantitation were 0.80 and 1.50 microg/ml respectively. The method has been successfully used to analyze commercial dosage form to assess the chromatographic performance of SFC system which was found to be 99.91%+/-1.62. The present work briefs the thermodynamic applications of PC-SFC with an emphasis on the results of stavudine. The foremost of such applications is the determination of solute diffusion coefficient in supercritical mobile phase by Taylor-Aris peak broadening technique.

Analysis of Variance↗

PubMed1997

General equation for calculating the dissociation constants of polyprotic acids and bases from measured retention factors in high-performance liquid chromatography.

A general equation relating the observed retention factor to the pH of the mobile phase, the dissociation constants, and the retention factors of the different ionic species has been derived. This equation is applicable to polyprotic weak acid and base dissociation events, that is, the secondary equilibria existing in the HPLC mobile phase. It is written as: [formula: see text] where the kr values are the retention factors of the dissociated species, and Ka(r), the product of the first r-dissociation constants, [formula: see text] is related to the pH of the mobile phase: x = 2.303.pH. The derived equation was used to calculate three dissociation constants of leukotriene E4. Also, a formula is established for calculating the range of pH values where an ionic species is most likely to be predominant in the mobile phase.

Acids↗