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Selected AbstractsMoxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metforminDIABETES OBESITY & METABOLISM, Issue 4 2006Irina Chazova Aim:, To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. Methods:, A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients ,40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. Results:, With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1,35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. Conclusions:, Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease. [source] Background potassium channel block and TRPV1 activation contribute to proton depolarization of sensory neurons from humans with neuropathic painEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2004Thomas K. Baumann Abstract Protons cause a sustained depolarization of human dorsal root ganglion (DRG) neurons [Baumann et al. (1996) Pain, 65, 31,38]. In the present study we sought to determine which ion channels are expressed in human DRG neurons that could mediate the sustained responses observed in the patch-clamp recordings. RT-PCR of material from the DRG tissue revealed the presence of mRNAs for a nonselective cation channel that is activated by protons (TRPV1) and background potassium channels that are blocked by protons (TASK-1, TASK-3 and Kir2.3). Highly acidic solution (pH 5.4) applied to cultured DRG neurons evoked prolonged currents that were associated with a net increase in membrane conductance. Consistent with the involvement of TRPV1, these proton-evoked currents were blocked by capsazepine and were only found in neurons that responded to capsaicin with an increase in membrane conductance. Less acidic extracellular solution (pH 6.0) evoked such currents only rarely, but was able to strongly enhance the currents evoked by capsaicin. Capsazepine (1 µm) blocked the currents evoked by capsaicin at pH 7.35, as well as the potentiated responses to capsaicin at pH 6.0. In neurons that were not excited by capsaicin, moderate extracellular acidification (pH 6.0) caused a sustained decrease in resting membrane conductance. The decrease in membrane conductance by protons was associated with inhibition of background potassium channels. This excitatory effect of protons was not blocked by capsazepine. We conclude that in most neurons the sustained depolarization in response to moderately acidic solutions is the result of blocked background potassium channels. In a subset of neurons, TRPV1 also contributes. [source] Dopamine gating of forebrain neural ensemblesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Patricio O'Donnell Abstract Dopamine may exert different actions depending on a number of factors. A common view is that D1 receptors may be responsible for excitatory actions whereas D2 receptors are involved in inhibitory actions. However, this position cannot be reconciled with several findings indicating otherwise. The role of dopamine on forebrain neural ensembles may be better understood in the light of functional states of the system. Pyramidal cortical neurons and striatal medium spiny neurons alternate between two membrane potential states (,up' and ,down') that could shape dopamine actions. It is proposed that D1 receptors can act as state-stabilizers by sustaining up states and thereby facilitating plasticity mechanisms by providing postsynaptic depolarization and increasing NMDA function. In this way, dopamine can sustain activity in depolarized units. This action is accompanied by a decrease in cell firing (perhaps mediated by D2 receptors), which renders the cells responsive only to strong stimuli. The result would be a net increase in signal-to-noise ratio in a selected assembly of neurons. [source] Cationic Polyelectrolyte Amplified Bead Array for DNA Detection with Zeptomole Sensitivity and Single Nucleotide Polymorphism SelectivityADVANCED FUNCTIONAL MATERIALS, Issue 16 2010Chun Wang Abstract A highly sensitive strand specific DNA assay, which consists of a peptide nucleic acid (PNA) probe, a cationic conjugated polymer (PFVP), and self-assembled polystyrene beads in microwell arrays on silicon chip, is reported. PFVP, as an efficient signal amplifier and signal reporter, has been specially designed and synthesized to be compatible with commercial confocal microscopes for sensing on solid substrates. The assay operates on the net increase in negative charge at the PNA surface that occurs upon single-stranded DNA hybridization, which subsequently allows complex formation with the positively charged PFVP to favor energy transfer between the polymer and Cy5-labeled target. With maximized surface contact provided by bead arrays and signal amplification provided by PFVP, this assay allows detection of ,300 copies of Cy5-labeled DNA using a commercial confocal microscope. In addition, the same strategy is also extended for label-free DNA detection with a detection sensitivity of 150 attomole. Excellent discrimination against single nucleotide polymorphism (SNP) is also demonstrated for both Cy5-labeled and label-free target detection. This study indicates that cationic conjugated polymers have great potential to be incorporated into the widely used microarray technology for simplified process with improved detection sensitivity. [source] Net changes in regional woody vegetation cover and carbon storage in Texas Drylands, 1937,1999GLOBAL CHANGE BIOLOGY, Issue 3 2003GREGORY P. ASNER Abstract Although local increases in woody plant cover have been documented in arid and semiarid ecosystems worldwide, there have been few long-term, large-scale analyses of changes in woody plant cover and aboveground carbon (C) stocks. We used historical aerial photography, contemporary Landsat satellite data, field observations, and image analysis techniques to assess spatially specific changes in woody vegetation cover and aboveground C stocks between 1937 and 1999 in a 400-km2 region of northern Texas, USA. Changes in land cover were then related to topo-edaphic setting and historical land-use practices. Mechanical or chemical brush management occurred over much of the region in the 1940,1950s. Rangelands not targeted for brush management experienced woody cover increases of up to 500% in 63 years. Areas managed with herbicides, mechanical treatments or fire exhibited a wide range of woody cover changes relative to 1937 (,75% to + 280%), depending on soil type and time since last management action. At the integrated regional scale, there was a net 30% increase in woody plant cover over the 63-year period. Regional increases were greatest in riparian corridors (33%) and shallow clay uplands (26%) and least on upland clay loams (15%). Allometric relationships between canopy cover and aboveground biomass were used to estimate net aboveground C storage changes in upland (nonriparian) portions of regional landscapes. Carbon stocks increased from 380 g C m,2 in 1937 to 500 g C m,2 in 1999, a 32% net increase across the 400 km2 region over the 63-year period. These plant C storage change estimates are highly conservative in that they did not include the substantial increases in woody plant cover observed within riparian landscape elements. Results are discussed in terms of implications for ,carbon accounting' and the global C cycle. [source] Pressure,temperature,time evolution of the Central East Greenland Caledonides: quantitative constraints on crustal thickening and synorogenic extensionJOURNAL OF METAMORPHIC GEOLOGY, Issue 9 2003A. P. White Abstract Whereas geologists have known for three-quarters of a century that there was significant crustal thickening in the central East Greenland Caledonides, the crucial role of extensional faulting during Caledonian orogenesis has only been recognized during the past decade. In this paper, new petrographic and thermobarometric observations are presented from migmatitic metasedimentary gneisses of the Forsblad Fjord region (c. 72.5°N). Samples of the Krummedal Sequence, collected from the footwall of the upper of two significant splays of the main extensional fault system in the region,the Fjord Region Detachment (FRD),enable us to establish a relative sequence of metamorphism. Our pressure (P),temperature (T) results imply a clockwise loop in P,T space. As recorded by mineral assemblages in the Krummedal gneisses, prograde metamorphism involved a net increase of c. 4 kbar and 250 °C, with peak conditions of c. 10.5 kbar at 785 °C. Early burial and heating was followed by near-isothermal decompression of 4.5 kbar, a process which is attributed to roughly 18 km of tectonostratigraphic throw on the upper splay of the FRD. Combining data reported here with the published data, it is estimated that the approximate tectonostratigraphic throw along the lower splay of the FRD was c. 16 km. In situ U,Th,Pb-monazite electron microprobe dating suggests that the earliest phase of metamorphism recorded in the Krummedal Sequence gneisses of Forsblad Fjord occurred during the Caledonian orogeny. Furthermore, the combination of our new data with existing conventional TIMS U-Pb and 40Ar/39Ar data imply that: (1) movement along the uppermost splay of the FRD (c. 425,423 Ma) occurred at maximum time-averaged slip-rates equivalent to c. 9 mm of vertical displacement per year; and (2) that the final stages of metamorphism occurred prior to c. 411 Ma, although part of this denudation was likely accommodated on overlying extensional structures that may have been active more recently. There is close agreement between our data and results from the Krummedal Sequence north of the field area (72.5°,74°N), and rocks of the Smallefjord Sequence (75°,76°N) that are suggested to correlate with the Krummedal Sequence. This leads us to infer that the events recorded in the Forsblad Fjord region are of orogen-scale significance. [source] Unaltered neuropeptide Y (NPY)-stimulated [35S]GTP,S binding suggests a net increase in NPY signalling after repeated electroconvulsive seizures in miceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2006D.Z. Christensen Abstract Although electroconvulsive seizures (ECS) are widely used as a treatment for severe depression, the working mechanism of ECS remains unclear. Repeated ECS causes anticonvulsant effects that have been proposed to underlie the therapeutic effect of ECS, and neuropeptide Y (NPY) is a potential candidate for mediating this anticonvulsant effect. Repeated ECS results in prominent increases in NPY synthesis. In contrast, NPY-sensitive receptor binding is decreased, so it is unclear whether ECS causes a net increase in NPY signalling. Agonist-stimulated [35S]GTP,S binding is a method for detecting functional activation of G-protein-coupled receptors. The present study in mice examined the effects of daily ECS for 14 days on NPY-stimulated [35S]GTP,S functional binding and compared this with gene expression of NPY and NPY receptors as well as [125I]peptide YY (PYY) binding in hippocampus of the same animals. Significant increases in NPY mRNA and concomitant reductions in NPY-sensitive binding were found in the dentate gyrus, hippocampal CA1, and neocortex of ECS treated mice, which is consistent with previous rat data. These changes remained significant 1 week after repeated ECS. Significant increases in NPY Y1, Y2, and Y5 mRNA were found in the dentate gyrus after ECS. Surprisingly, unaltered levels of functional NPY receptor binding accompanied the decreased NPY-sensitive binding. This suggests that mechanisms coupling NPY receptor stimulation to G-protein activation could be augmented after repeated ECS. Thus increased synthesis of NPY after repeated ECS should result in a net increase in NPY signalling in spite of reduced levels of NPY-sensitive binding. © 2006 Wiley-Liss, Inc. [source] Abstinence From Moderate Alcohol Self-Administration Alters Progenitor Cell Proliferation and Differentiation in Multiple Brain Regions of Male and Female P RatsALCOHOLISM, Issue 1 2009Jun He Background:, Acute and chronic ethanol exposure has been found to decrease hippocampal neurogenesis, reduce dendritic differentiation of new neurons, and increase cell death. Interestingly, abstinence from such treatment increases hippocampal neurogenesis and microglial genesis across several brain regions. The goal of the current investigation was to study cellular alterations on neuro- and cell-genesis during abstinence following alcohol self-administration using alcohol-preferring rats (P rats). Methods:, Male and female P rats were given the choice of drinking 10% alcohol in water or pure water for 7 weeks. Social interaction behavioral assessments were conducted at 5 hours upon removal of alcohol, followed by bromo-deoxyuridine (BrdU, 150 mg/kg × 1/d × 14 d) injections to label proliferating cells. Animals were then killed 4 weeks later to conduct immunohistochemical and confocal analyses using antibodies against BrdU and other phenotypic markers (NeuN for mature neurons; Iba-1 for microglia; GFAP for astrocytes; and NG2 for oligodendrocyte progenitors). Results:, Mild alcohol withdrawal anxiety was detected by reduction in social interactions. The number of hippocampal BrdU+ cells was increased approximately 50% during alcohol abstinence (26 ± 2.8 in controls vs. 39 ± 4 in alcohol group). BrdU+ cells were also increased in the substantia nigra (SN) approximately 65% in the alcohol abstinent group (12 ± 1 in controls vs. 19 ± 1.5 in alcohol group). No gender differences were found. Confocal analyses indicated that approximately 75% of co-localization of BrdU+ cells with NeuN in the hippocampal dentate gyrus (DG) resulting a net increase in neurogenesis in the alcohol abstinent group compared to controls. In cingulum, greater proportion of BrdU+ cells were co-localized with NG2 in the alcohol abstinent group indicating increased differentiation toward oligodendrocyte progenitors in both genders. However, the phenotype of the BrdU+ cells in SN and other brain regions were not identified by NeuN, Iba-1, GFAP, or NG2 suggesting that these BrdU+ cells probably remain in a nondifferentiated stage. Conclusions:, These data indicate that abstinence from moderate alcohol drinking increases hippocampal neurogenesis, cingulate NG2 differentiation, and SN undifferentiated cell proliferation in both males and females. Such cellular alteration during abstinence could contribute to the spontaneous partial restoration of cognitive deficits upon sobriety. [source] Evaluating land use/land cover changes and fragmentation in the Camili forest planning unit of northeastern Turkey from 1972 to 2005LAND DEGRADATION AND DEVELOPMENT, Issue 4 2007F. Sivrikaya Abstract Changes in land use/land cover have important consequences on the management of natural resources including soil and water quality, global climatic systems and biodiversity. This study analysed the spatial and temporal pattern of land use/land cover change in the Camili forest planning unit that includes the Camili Biosphere Reserve Area within the Caucasian hotspot, in the northeast corner of Turkey. To assess the patterns during a 33-year period, the necessary data were obtained from forest stand maps and evaluated with Geographic Information Systems and FRAGSTATS. Results showed that the total forested areas increased from 19,946·5,ha (78·6% of the study area) in 1972 to 20,797·3,ha (81·9 per cent) in 2005 with a slight net increase of 851,ha. Softwood cover types (411·8,ha) completely transitioned to other cover types over 33-year period. In terms of spatial configuration, the total number of forest fragments increased from 172 to 608, and mean size of forest patch (MPS) decreased from 147·7,ha to 41·8,ha during the period. Nearly 84 per cent of the patches in 1972 and 93 per cent of them in 2005 generally seem to concentrate into 0,100,ha patch size class, indicating more fragmented landscape over time that might create a risk for the maintenance of biodiversity of the area. There were apparent trends in the temporal structure of forest landscape, some of which may issue from mismanagement of the area, social conflict, and illegal utilization of forest resources due to ineffective forest protection measurements. The study revealed that it is important to understand both spatial and temporal changes of land use/land cover and their effects on landscape pattern to disclose the implications for land use planning and management. Copyright © 2007 John Wiley & Sons, Ltd. [source] Varying ratios of wavelengths in dual wavelength LED photomodulation alters gene expression profiles in human skin fibroblastsLASERS IN SURGERY AND MEDICINE, Issue 6 2010D.H. McDaniel MD Abstract Background and Objective LED photomodulation has been shown to profoundly influence cellular behavior. A variety of parameters with LED photomodulation can alter cellular response in vitro. The effects of one visible and one infrared wavelength were evaluated to determine the optimal ratio to produce a net increase in dermal collagen by altering the ratio of total energy output of each wavelength. The ratio between the two wavelengths (590 and 870,nm) was shifted in 25% increments. Study Design/Materials and Methods Human skin fibroblasts in culture were exposed to a 590/870,nm LED array with total combined energy density fixed at 4.0,mW/cm.. The ratio of 590/870,nm tested parameters were: 100/0%, 75/25%, 50/50%, 25/75%, and 0/100%. These ratios were delivered using pulsed duty cycle of exposure (250,milliseconds "on" time/100,milliseconds "off" time/100,pulses) for a total energy fluence of 0.1,J/cm.. Gene expression was examined using commercially available extra cellular matrix and adhesion molecule RT PCR Arrays (SA Biosciences, Fredrick, MD) at 24,hours post-exposure. Results Different expression profiles were noticed for each of the ratios studied. Overall, there was an average (in an 80 gene array) of 6% expression difference in up or downregulation between the arrays. The greatest increase in collagen I and decrease in collagenase (MMP-1) was observed with 75/25% ratio of 590/870,nm. The addition of increasing proportions of IR wavelengths causes alteration in gene expression profile. The ratios of the wavelengths caused variation in magnitude of expression. Conclusions Cell metabolism and gene expression can be altered by simultaneous exposure to multiple wavelengths of low energy light. Varying the ratios of specific wavelength intensity in both visible and near infrared light therapy can strongly influence resulting fibroblast gene expression patterns. Lasers Surg. Med. 42:540,545, 2010. © 2010 Wiley,Liss, Inc. [source] What should non-US behavioral health systems learn from the USA?: US behavior health services trends in the 1980s and 1990sPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2006YASUHIRO KISHI md Abstract Several countries, such as the USA, inadvertently created a different behavioral health payment system from the rest of medicine through the introduction of diagnostic-related group exemptions for psychiatric care. This led to isolation in the administration and delivery of care for patients with mental health and substance abuse disorders from other medical services with significant, yet unintended, consequences. To insure an efficient and effective health-care system, it is necessary to recognize the problems introduced by segregating behavioral health from the rest of medical care. In this review, the authors assess trends in behavioral health services during the last two decades in the USA, a period in which independently managed behavioral health care has dominated administrative practices. During this time, behavioral health has been an easy target for aggressive cost cutting measures. There have been no clinically significant improvements in the number of adults receiving minimally adequate treatment or in the percentage of the population with behavior health problems receiving psychiatric care with the possible exception of depression. While decreased spending for behavioral health services has been well documented during this period, these savings are offset by costs shifted to greater medical service use with a net increase in the total cost of health care. Targeting behavioral health for reduction in health-care spending through independent management, starting with diagnostic procedure code or diagnostic-related group exemption may not be the wisest approach in addressing the increasing fiscal burden that medical care is placing on the national economy. [source] Cost utility in the United States of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone for the treatment of elderly patients with diffuse large B-cell lymphoma,CANCER, Issue 8 2005John C. Hornberger M.D., M.S. Abstract BACKGROUND Findings from the Groupe d'Etude des Lymphomes Adultes LNH 98-5 study showed that rituximab added to combined cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) prolonged progression-free survival and overall survival in adults age , 60 years with diffuse large B-cell non-Hodgkin lymphoma (DLBCL). The current study was conducted to investigate the incremental cost utility of the addition of rituximab to CHOP (R-CHOP) compared with CHOP alone. METHODS Clinical prognosis of the time to disease progression and death was estimated using published evidence from the LNH 98-5 study (n = 399 patients) that was linked mathematically to published long-term outcome data on patients with DLBCL. Drug-acquisition costs were based on published data from formulary pricing sources, and the costs of cancer surveillance and end-of-life care were based on published literature sources. The authors assessed cost utility as the difference in costs between R-CHOP and CHOP divided by the increase in expected overall survival adjusted for quality of life. RESULTS Over 5 years, it was projected that R-CHOP would prolong overall survival by 1.04 years. The mean cumulative cost of CHOP was $3358, and the mean cost of R-CHOP was $17,225, resulting in a cumulative net increase of $13,867. The posttreatment cancer surveillance cost for CHOP was $3950, compared with $5202 for R-CHOP. It was estimated that R-CHOP would have a cost-utility ratio of $19,297 per year of life gained compared with CHOP when adjusted for quality of life. R-CHOP remained cost effective over wide ranges of variables in sensitivity analyses. CONCLUSIONS Compared with CHOP alone, it was predicted that R-CHOP would be cost effective in elderly patients with DLBCL. Cancer 2005. © 2005 American Cancer Society. [source] Do Medicaid Wage Pass-through Payments Increase Nursing Home Staffing?HEALTH SERVICES RESEARCH, Issue 3 2010Zhanlian Feng Objective. To assess the impact of state Medicaid wage pass-through policy on direct-care staffing levels in U.S. nursing homes. Data Sources. Online Survey Certification and Reporting (OSCAR) data, and state Medicaid nursing home reimbursement policies over the period 1996,2004. Study Design. A fixed-effects panel model with two-step feasible-generalized least squares estimates is used to examine the effect of pass-through adoption on direct-care staff hours per resident day (HPRD) in nursing homes. Data Collection/Extraction Methods. A panel data file tracking annual OSCAR surveys per facility over the study period is linked with annual information on state Medicaid wage pass-through and related policies. Principal Findings. Among the states introducing wage pass-through over the study period, the policy is associated with between 3.0 and 4.0 percent net increases in certified nurse aide (CNA) HPRD in the years following adoption. No discernable pass-through effect is observed on either registered nurse or licensed practical nurse HPRD. Conclusions. State Medicaid wage pass-through programs offer a potentially effective policy tool to boost direct-care CNA staffing in nursing homes, at least in the short term. [source] Applied environmental stresses to enhance the levels of polyphenolics in leaves of hawthorn plantsPHYSIOLOGIA PLANTARUM, Issue 2 2004Ara Kirakosyan In this investigation, two species of Crataegus (hawthorn) were chosen because their polyphenolic constituents have recently received greater attention for the treatment of patients with severe heart disease. One-year-old plants of hawthorn (Crataegus laevigata and C. monogyna) were subjected to water-deficit (continuous water deprivation), cold (4°C), flooding (immersion of roots of plants in water) or herbivory (leaf removal) stress treatments (each of 10 days duration) in order to assess their effects on levels of polyphenolics, namely (-)-epicatechin, catechin, chlorogenic acid, vitexin, vitexin-2,,- O -rhamnoside, acetylvitexin-2,,- O -rhamnoside, hyperoside, quercetin, and rutin in the leaves. The working hypothesis followed is that one or more of these stress treatment will elicit increases in the levels of these polyphenolics. Cold stress causes increases in levels of vitexin-2,,- O -rhamnoside, acetylvitexin-2,,- O -rhamnoside, hyperoside, and quercetin in both Crataegus species. Water-deficit stress increased the productivity of chlorogenic acid, catechin, and (-)-epicatechin in both hawthorn species. Flooding and herbivory caused no net increases, and in some cases, decreases in levels of polyphenolics. These studies indicate that either water-deficit stress or cold stress treatments, or a combination of the two, can be used to enhance the levels of desired polyphenolics in the leaves of these two hawthorn species in a photobioreactor system. These results may have significance for hawthorn in adapting to water-deficit or cold stress and are important considerations for the use of hawthorn in the treatment of heart disease in humans. [source] | ||||||||||||||||