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PubMed2003

Transmitter modulation of slow, activity-dependent alterations in sodium channel availability endows neurons with a novel form of cellular plasticity.

Voltage-gated Na+ channels are major targets of G protein-coupled receptor (GPCR)-initiated signaling cascades. These cascades act principally through protein kinase-mediated phosphorylation of the channel alpha subunit. Phosphorylation reduces Na+ channel availability in most instances without producing major alterations of fast channel gating. The nature of this change in availability is poorly understood. The results described here show that both GPCR- and protein kinase-dependent reductions in Na+ channel availability are mediated by a slow, voltage-dependent process with striking similarity to slow inactivation, an intrinsic gating mechanism of Na+ channels. This process is strictly associated with neuronal activity and develops over seconds, endowing neurons with a novel form of cellular plasticity shaping synaptic integration, dendritic electrogenesis, and repetitive discharge.

Animals↗

PubMed2003

Availability of corn stover as a sustainable feedstock for bioethanol production.

The amount of corn stover that can be sustainably collected is estimated to be 80-100 million dry tonnes/yr (t/yr), a majority of which would be available to ethanol plants in the near term as only a small portion is currently used for other applications. Potential long-term demand for corn stover by non-fermentative applications in the United States is estimated to be about 20 million dry t/yr, assuming that corn stover-based products replace 50% of both hardwood pulp and wood-based particleboard, and that 50% of all furfural production is from corncobs. Hence, 60-80 million dry t/yr of corn stover should be available to fermentative routes. To achieve an ethanol production potential of 11 billion L (3 billion gal) per year (a target level for a non-niche feedstock), about 40% of the harvestable corn stover is needed. This amount should be available as long as the diversion of corn stover to non-ethanol fermentative products remains limited.

Agriculture↗

PubMed2005

Availability and acceptability of medical abortion in Nepal: health care providers' perspectives.

Abortion was legalised in Nepal in September 2002 and manual vacuum aspiration is the main procedure used for safe abortion. Although medical abortion has not yet officially been introduced in Nepal, with the highly porous Indo-Nepal border and the easy availability of mifepristone and misoprostrol in Indian chemists' shops, it is possible the drugs are entering from Indian markets illegally. This study aimed to gauge current awareness of the availability of medical abortion drugs in Nepal and explore what health professionals and paramedics felt about the use of medical abortion to expand access to safe abortion in the country. Data were drawn from interviews with private obstetrician-gynaecologists, general physicians, paramedics, ayurvedic and homeopathic practitioners and chemists in 24 urban municipalities and peri-urban areas in Nepal. Various types of allopathic and indigenous forms of medicine for menstrual regulation in the Nepalese market were widely known whereas knowledge of the availability of mifepristone and misoprostrol was low. Almost all respondents had a positive view of the potential for providing mifepristone and misoprostol in Nepal and most thought that obstetrician-gynaecologists, general physicians and other certified abortion care providers should be able to provide the drugs. Many respondents were interested in doing so themselves. Registration of mifepristone and misoprostrol is the key to introducing medical abortion in Nepal and should happen as soon as possible.

Abortifacient Agents, Nonsteroidal↗

PubMed2001

[(11)]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy.

Cocaine was initially labeled with carbon-11 in order to track the distribution and pharmacokinetics of this powerful stimulant and drug of abuse in the human brain and body. It was soon discovered that [(11)C]cocaine was not only useful for measuring cocaine pharmacokinetics and its relationship to behavior but that it is also a sensitive radiotracer for dopamine transporter (DAT) availability. Measures of DAT availability were facilitated by the development of a graphical analysis method (Logan Plot) for reversible systems which streamlined kinetic analysis. This expanded the applications of [(11)C]cocaine to studies of DAT availability in the human brain and allowed the first comparative measures of the degree of DAT occupancy by cocaine and another stimulant drug methylphenidate. This article will summarize preclinical and clinical research with [(11)C]cocaine.

Brain↗

PubMed2000

Gun availability, psychopathology, and risk of death from suicide attempt by gun.

PURPOSE: Suicide is the third leading cause of death among adolescents and the 8th leading cause of death overall. Guns figure prominently in this problem. Guns are the most lethal means of suicide, and in the United States about 60% of all suicides are committed by guns. We examined hospital admissions for suicide attempts (para-suicide) in the city of Chicago between 1990-1997. Our aim was to 1) quantify the risk of death from para-suicide by gun versus other methods, 2) determine whether individual with psychopathology are more likely than others to attempt suicide by gun, 3) determine proportion of variation in para-suicide by gun explained by community-level gun availability independent of individual-level determinants of para-suicide by gun.METHODS: Hospital admissions from city of Chicago during 1990-1997 were examined for cases of attempted or completed suicide. 11,584 individuals were identified with a diagnosis of para-suicide (E950-E959, classifiable to ICD-9CM). These individuals were then classified into suicide type (e.g., gun, crash, cut, poison) and were also identified as having a mental disorder or not (mental diagnoses classifiable to ICD-9CM).RESULTS: 1) Those attempting suicide by gun are about 70 times more likely to die from their injuries than those attempting suicide by other means. 2) Depressed and psychotic individuals compared with individuals with no-mental disorders are significantly more likely to attempt suicide with a gun (p < 0.001). 3) Inclusion of community-level gun availability in a hierarchical model reduced the variation in the model by 16%.CONCLUSIONS: Guns are the most lethal suicide method. Community-level availability, independent of individual-level factors, is an important determinant of suicide attempt by gun.

Journal Article↗

PubMed1996

Alcohol availability and motor vehicle fatalities.

PURPOSE: To examine the association between the availability of alcohol and male (15-24-years-old) motor vehicle fatalities. METHODS: Assessed association between motor vehicle fatality rates for each of 75 counties for males with measures of alcohol availability (whether the county was wet or dry, number of licensed on-site and off-site alcohol outlets) after controlling for other variables for a 6-year period. Poisson regression models were employed. RESULTS: No significant relationships were found between county-level motor vehicle fatality rates and any of the alcohol availability measures examined. However, rural residence was associated with much higher fatality rates. CONCLUSIONS: Overall, ecologic models, employing a wide range of variables, account for little of the variance in motor vehicle fatality rates for young men. These findings support the position that further legal or regulatory restrictions on alcohol outlet licensing may not have an impact on fatalities. The higher rates associated with rural residence, while consistent with other work, cannot be explained by alcohol beverage outlets.

Accidents, Traffic↗

PubMedDate not supplied

Validation of a fruit, juice, and vegetable availability questionnaire.

OBJECTIVE: To assess the validity of a self-reported fruit, juice, and vegetable home availability measure. DESIGN: Cross-sectional. SETTING: In-home interviews. PARTICIPANTS: Forty-eight parents of fourth to sixth grade children. MAIN OUTCOME MEASURES: Scales assessing self-reported home availability of fruit, 100% fruit juice, and vegetables over the past 7 days compared with an observed home inventory conducted on the interview day. ANALYSES: Cohen's kappa of agreement, specificity and sensitivity, and correlations, with significance level <.05. RESULTS: There was substantial agreement between self-reported and observed home inventories of many fruit, 100% fruit juice, and vegetables among participating families in this study. CONCLUSIONS AND IMPLICATIONS: Self-reported shelf inventories can be an effective tool for use in assessing the availability of fruit, juice, and vegetables in the home.

Adult↗

PubMedDate not supplied

Fourth-grade children's consumption of fruit and vegetable items available as part of school lunches is closely related to preferences.

OBJECTIVE: To use data from observations and interviews to document fourth-graders' preferences for, and consumption of, fruits compared to vegetables available as part of school lunches. DESIGN: Observations and interviews were conducted for studies regarding the impact of time interval between eating and reporting on the accuracy of children's school lunch recalls. SUBJECTS/SETTINGS: Children were recruited from up to 4 schools in one district during 3 school years; 63% agreed to participate. Randomly selected children (n = 237) were each observed eating school lunch once and were interviewed (regarding items eaten and preferences for items eaten) within 11/2 hours or the next morning. MAIN OUTCOME MEASURES: Observed consumption of servings of items available as part of school lunch was recorded as none, taste, little bit, half, most, and all. Response options for preferences for items available as part of school lunch were liked not at all, a little, and a lot. STATISTICAL ANALYSES PERFORMED: Mixed-model analysis of variance. RESULTS: Preferences were higher for fruits than vegetables. As preferences increased, consumption increased (P <.0001). Consumption of fruits compared to vegetables was similar after adjusting for preferences. IMPLICATIONS: Research is needed to understand how to increase children's preferences for vegetables as a means of increasing consumption.

Child↗

PubMed2002

High-performance liquid chromatographic analysis of cyclosporin A in rat blood and liver using a commercially available internal standard.

All the available HPLC assays of cyclosporin A (CyA) use internal standards that are not commercially available. Our purpose was to develop an HPLC assay for measurements of CyA in rat blood and liver using a commercially available internal standard (I.S.). After the addition of tamoxifen (I.S.), blood (0.25 ml) or the liver homogenate (1 ml) samples were extracted into a mixture of ether:methanol (95:5). The residue after evaporation of the organic layer was dissolved in 200 microl of an injection solution and washed with 1 ml of hexane before analysis. The separation was achieved using an LC-1 column (70 degrees C) with a mobile phase of methanol-acetonitrile-0.01 M KH(2)PO(4) (50:25:25, v/v) and a flow-rate of 1 ml/min. Detection was at 205 nm. Cyclosporin A and I.S. eluted at 5 and 7 min, respectively, free from endogenous peaks. Linear relationships (r>0.98) were observed between the CyA:I.S. peak area ratios and the CyA concentrations within the range of 0.2-10 microg/ml for blood and 0.1-4 microg/ml for the liver homogenates. The intra- and inter-run C.V.s and errors for both the blood and liver samples were <15%. The extraction efficiency (n=5) was close to 100% for both CyA and I.S. in both blood and liver homogenates. The lower limit of quantitation of the assay was 0.2 or 0.1 microg/ml based on 250 microl of blood or 1 ml of liver homogenate, respectively. The assay was capable of measuring blood and liver concentrations of CyA in a rat injected intravenously with a single 5-mg/kg dose of the drug.

Animals↗

PubMed2000

Effect of altering substrate availability on metabolism and performance during intense exercise.

The purpose of this study was to determine the effect of altering substrate availability on metabolism and performance during intense cycling. Seven highly trained men ingested a random order of three isoenergetic meals 90 min before cycling at 80% maximal oxygen uptake (VO2max) for 20 min (about 310 W), followed by a 600 kJ time trial lasting about 30 min. Meals consisted of either 1.2 g saturated fat/kg body mass (BM) with 3500 U heparin intravenously (HIFAT) to elevate circulating plasma free fatty acid (FA) concentration, 2.5 g carbohydrate/kg BM (CHO) to elevate plasma glucose and insulin concentrations or 2.5 g carbohydrate +20 mg nicotinic acid/kg BM (NA) to suppress lipolysis and reduce free FA concentration. HIFAT elevated free FA concentration (HIFAT 1.3 (sem 0.2), CHO 0.2 (sem 0.1), NA 0.1 (sem 0.1) mm; P < 0.001) lowered the RER (HIFAT 0.94 (sem 0.01), CHO 0.97 (sem 0.01), NA 0.98 (sem 0.01); P < 0.01) and increased the rate of fat oxidation (HIFAT 24 (sem 3), CHO 12 (sem 2), NA 8 (sem 3) micromol/kg per min; P < 0.01) during the 20 min ride. Marked differences in fat availability and fuel utilisation, however, had little effect on performance in the subsequent time trial (HIFAT 320 (sem 16), CHO 324 (sem 15), NA 315 (sem 13) W). We conclude: (1) increased fat availability during intense cycling increases the rate of fat oxidation; but (2) the reduction in the rate of carbohydrate oxidation in the presence of high circulating plasma free FA is unlikely to enhance intense exercise performance lasting about 1 h; (3) substrate selection during intense (about 80% VO2max) exercise is dominated by carbohydrate oxidation.

Adult↗

PubMed1993

Availability of marriage partners in England and Wales: a comparison of three measures.

Measures of partner availability introduced by Goldman, Westoff & Hammerslough (1984) and by Veevers (1988) are described and a new measure of partner availability, the Iterated Availability Ratio, is introduced. The three measures are applied to 1981 Census data for England and Wales and their abilities to predict regional variations in age-specific marriage rates are compared.

Adult↗

PubMed2001

Dopamine transporter availability in symptomatic depressed patients with seasonal affective disorder and healthy controls.

BACKGROUND: During recent years hypotheses about the pathophysiology of seasonal affective disorder/winter type (SAD) have focused monoaminergic mechanisms. There is substantial evidence that serotonergic systems play an important role. The potential role of catecholaminergic pathways has not been fully explored. METHODS: Eleven drug-free, symptomatic depressed patients with SAD and 11 healthy age- and gender-matched healthy controls were invited to participate in a 123Ibeta-CIT single photon emission computed tomography (SPECT) study to assess striatal density of dopamine transporters (DATs). The cerebellum was used as reference region. Ratios were calculated between mean counts in left and right striatum and cerebellum. These ratios minus I represent specific/non-displaceable binding and are assumed to be directly related to DAT availability at the time of binding equilibrium. RESULTS: Displaceable 153Ibeta-CIT binding in the area corresponding to the left striatum was significantly reduced in SAD patients compared to healthy controls (10.49+/-0.91 v. 1195+/-1.54, respectively; 2-tailed P = 0.017, Mann-Whitney U test). CONCLUSIONS: These data suggest reductions in the availability of striatal DAT binding sites in untreated symptomatic depressed SAD patients. It remains unclear whether these reductions represent a primary defect or an attempt to overcome a state of possible lowered dopamine availability in the synaptic cleft during a depressive episode of SAD. However, these findings provide evidence that brain dopaminergic systems may be involved in the pathophysiology of SAD.

Adult↗

PubMed2000

Clinical trials. A place for randomization in the interval between the end of recruitment and availability of results.

There is a time delay between the final recruitment of patients to a randomized controlled trial and the publication of results. The practical options available to decision makers during this gap can be listed according to whether all treatments are already widely available or whether at least one has been restricted to the trial. When the treatments are already in widespread use, the options are simply either to stop randomizing or to continue. When one trial treatment is restricted, there are further options: a) withdraw the restricted treatment altogether, pending the final analysis; b) continue to offer randomization, with a view to providing further data should these be needed; or c) make the intervention widely available to patients who would have previously been eligible for the trial. In this paper, we discuss the relative advantages and disadvantages of each option and discuss their attendant ethical implications. In particular, we suggest that continuing randomization is an option worthy of serious consideration. Randomizing patients acts as a "hedge" against the need for more data, given that sample size calculation is an inexact science. However, patients must be made aware of the basis on which randomization is offered.

Decision Making↗

PubMed2006

Requests for euthanasia and physician-assisted suicide and the availability and application of palliative options.

OBJECTIVE: This study investigated the palliative options available when a patient requested euthanasia or physician-assisted suicide (EAS), the extent to which the options were applied, and changes in the patient's wishes. METHODS: In an observational study, 3614 general practitioners (GPs) filled in a questionnaire and described their most recent request for EAS (if any) (n = 1,681). RESULTS: Palliative options were still available in 25% of cases. In these cases options were applied in 63%; in 46% of these cases patients withdrew their request. Medication other than antibiotics, which was most frequently mentioned as a palliative option (67%), and applied most frequently (79%), together with radiotherapy, most frequently resulted in patients withdrawing their request. SIGNIFICANCE OF RESULTS: GPs include the availability of palliative options in their decision making when considering EAS. The fact that not all options are applied or, if applied, the patient persists in the request is related to autonomy of the patient, the burden on the patient, and medical futility of the option.

Decision Making↗

PubMed1980

Interconversion between different states of affinity of the human growth hormone receptor on rat hepatocytes: effects of fractional site occupancy on receptor availability.

Isolated rat hepatocytes accumulate a slowly dissociable human growth hormone (hGH) binding fraction with incubation time. Slowly dissociable [125I]hGH is receptor bound, intact and immunocompetent. Fifty-six percent of the bound hormone was slowly dissociable within 3 min of the initiation of hGH-hepatocyte incubation. Subsequently, the proportion of slowly dissociable [125I]hGH increased at the expense of the rapidly dissociable fraction. This suggested that binding induced interconversion between different states of affinity of the hGH receptor. Preincubation with hGH diminished the capacity of hepatocytes to subsequently bind [125I]hGH. Receptor occupancy resulting from accumulation of slowly dissociable hGH accounted for 37 and 62% of the decreased binding after preincubation with 0.79 and 7.9 nM hGH, respectively. Fractional receptor occupancy, among but distinguishable from other processes, may account for the inverse relationship between site number and applied hormone concentration. Addition of hGH to the medium of [125I]-hGH-hepatocyte incubates increased the extent of loss of label from hepatocytes. The progressive retention of intact [125I]-hGH by hepatocytes with site occupancy and invariant receptor affinity subsequent to fractional saturation was inconsistent with negative cooperativity. A mechanism in which hGH diminished reassociation of [125I]hGH with available sites during dissociation was consistent with the available binding data. The interrelationship between peptide hormone in rapid and slow equilibrium with the medium is of fundamental importance in modulating receptor binding and availability.

Animals↗

PubMed2005

Available nitrogen and arginine deaminase activity in groundnut (Arachis hypogaea L.) fields after imidacloprid, diazinon, and lindane treatments.

Plant available nitrogen and arginine deaminase activities were determined in insecticide-treated groundnut (Arachis hypogaea L.) fields between July and November for three consecutive years (1997-1999). Diazinon was applied for both seed and soil treatments. However, imidacloprid and lindane were used only for the seed treatments. An average half-life (t(1/2)) of diazinon in seed- and soil-treated fields was 29.32 and 34.87 days, respectively. Its residues were detected till 60 days in both seed- and soil-treated fields. Diazinon treatments had shown stimulatory effects on available nitrogen in both types of treatments. However, the increase in arginine deaminase activity was only observed in diazinon soil-treated field. Residues of imidacloprid and lindane were detected in seed-treated fields till 90 and 120 days with an average half-life (t(1/2)) of 40.96 and 53.39 days, respectively. Imidacloprid had stimulatory effects, and lindane had adverse effects on both available nitrogen and arginine deaminase activities.

Arachis↗

PubMed2006

Antioxidant activity and polyphenol and procyanidin contents of selected commercially available cocoa-containing and chocolate products in the United States.

In the United States, commercially available foods, including cocoa and chocolate, are being marketed with statements referring to the level of antioxidant activity and polyphenols. For cocoa-containing foods, there has been no comprehensive survey of the content of these and other chemistries. A survey of cocoa and chocolate-containing products marketed in the United States was conducted to determine antioxidant activity and polyphenol and procyanidin contents. Commercially available samples consisted of the top market share products in each of the following six categories: natural cocoa, unsweetened baking chocolate, dark chocolate, semisweet baking chips, milk chocolate, and chocolate syrup. Composite samples were characterized using four different methods: oxygen radical absorbance capacity (ORAC), vitamin C equivalence antioxidant capacity (VCEAC), total polyphenols, and procyanidins. All composite lots were further characterized for percent nonfat cocoa solids (NFCS) and percent fat. Natural cocoas had the highest levels of antioxidant activities, total polyphenols, and procyanidins followed by baking chocolates, dark chocolates and baking chips, and finally milk chocolate and syrups. The results showed a strong linear correlation between NFCS and ORAC (R (2) = 0.9849), total polyphenols (R (2) = 0.9793), and procyanidins (R (2) = 0.946), respectively. On the basis of principal component analysis, 81.4% of the sample set was associated with NFCS, antioxidant activity, total polyphenols, and procyanidins. The results indicated that, regardless of the product category, NFCS were the primary factor contributing to the level of cocoa antioxidants in the products tested. Results further suggested that differences in cocoa bean blends and processing, with the possible exception of Dutching, are minor factors in determining the level of antioxidants in commercially available cocoa-containing products in the United States.

Antioxidants↗

PubMed1999

Effect of heat treatment on bovine beta-lactoglobulin A, B, and C explored using thiol availability and fluorescence.

Dilute solutions of beta-lactoglobulin (beta-Lg) A, B, and C were heated at temperatures between about 40 and 94 degrees C for 10 min, cooled, and analyzed using Trp fluorescence and extrinsic fluorescence spectra of the probe 1,8-anilinonaphthalene sulfonate (ANS). Thiol availabilities using 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) were determined using a separate set of samples. The normalized ANS fluorescence emission intensity and the thiol availability results showed a 1:1 relationship with the loss of nativelike but not SDS-monomeric protein, as determined by PAGE analysis. The normalized Trp emission intensity results did not show a comparable 1:1 relationship with the loss of nativelike protein, indicating that the Trp intensity arose from consequential disulfide bond reorganization and not the initial unfolding reaction. The results were also analyzed in terms of two-state models, and the midpoint temperatures (T(mid)) for the proteins were generally beta-Lg C > beta-Lg A > beta-Lg B, and the slopes at the midpoint temperatures for the A variant were generally less than those for the B and C variants indicating that beta-Lg A may denature by a different mechanism from that of beta-Lg B or beta-Lg C. The T(mid) parameters derived from the ANS fluorescence intensity results were similar to those for thiol availability and both were lower than the T(mid) values for Trp emission intensity showing that creation of an ANS binding site on a beta-Lg molecule was linked to the irreversible exposure of a thiol group and the loss of native beta-Lg but preceded the decrease in Trp(61) fluorescence quenching. These results for the differences between the behavior of the A and B or the C variants involved the creation of a destabilizing cavity by the Val(118)Ala (A --> B) substitution and the changed charge distribution within the CD loop caused by the Asp(64)Gly (A --> B) substitution.

Animals↗