The role of ATP and adenosine in the control of hepatic blood flow in the rabbit liver in vivo

BACKGROUND: The role of adenosine and ATP in the regulation of hepatic arterial blood flow in the "buffer response" was studied in vitro and in a new in vivo model in the rabbit. The model achieves portal-systemic diversion by insertion of a silicone rubber prosthesis between the portal vein and inferior vena cava and avoids alterations in systemic haemodynamics. RESULTS: Hepatic arterial (HA) blood flow increased in response to reduced portal venous (PV) blood flow, the "buffer response", from 19.4 (3.3) ml min(-1 )100 g(-1 )to 25.6 (4.3) ml min(-1 )100 g(-1 )(mean (SE), p < 0.05, Student's paired t-test). This represented a buffering capacity of 18.7 (5.2) %. Intra-portal injections of ATP or adenosine (1 micrograms kg(-1)-0.5 mg kg(-1)) elicited immediate increases in HA blood flow to give -log ED(50 )values of 2.0 and 1.7 mg kg(-1 )for ATP and adenosine respectively. Injection of ATP and adenosine had no measurable effect on PV flow. In vitro, using an isolated dual-perfused rabbit liver preparation, the addition of 8-phenyltheophylline (10 MicroMolar) to the HA and PV perfusate significantly inhibited the HA response to intra-arterial adenosine and to mid-range doses of intra-portal or intra-arterial ATP (p < 0.001). CONCLUSIONS: It is suggested that HA vasodilatation elicited by ATP may be partially mediated through activation of P(1)-purinoceptors following catabolism of ATP to adenosine

Randomised, double-blind, placebo-controlled trials of non-individualised homeopathic treatment: systematic review and meta-analysis

Background: A rigorous systematic review and meta-analysis focused on randomised controlled trials (RCTs) of non-individualised homeopathic treatment has not previously been reported. We tested the null hypothesis that the main outcome of treatment using a non-individualised (standardised) homeopathic medicine is indistinguishable from that of placebo. An additional aim was to quantify any condition-specific effects of non-individualised homeopathic treatment. Methods: Literature search strategy, data extraction and statistical analysis all followed the methods described in a pre-published protocol. A trial comprised ‘reliable evidence’ if its risk of bias was low or it was unclear in one specified domain of assessment. ‘Effect size’ was reported as standardised mean difference (SMD), with arithmetic transformation for dichotomous data carried out as required; a negative SMD indicated an effect favouring homeopathy. Results: Forty-eight different clinical conditions were represented in 75 eligible RCTs. Forty-nine trials were classed as ‘high risk of bias’ and 23 as ‘uncertain risk of bias’; the remaining three, clinically heterogeneous, trials displayed sufficiently low risk of bias to be designated reliable evidence. Fifty-four trials had extractable data: pooled SMD was –0.33 (95% confidence interval (CI) –0.44, –0.21), which was attenuated to –0.16 (95% CI –0.31, –0.02) after adjustment for publication bias. The three trials with reliable evidence yielded a non-significant pooled SMD: –0.18 (95% CI –0.46, 0.09). There was no single clinical condition for which meta-analysis included reliable evidence. Conclusions: The quality of the body of evidence is low. A meta-analysis of all extractable data leads to rejection of our null hypothesis, but analysis of a small sub-group of reliable evidence does not support that rejection. Reliable evidence is lacking in condition-specific meta-analyses, precluding relevant conclusions. Better designed and more rigorous RCTs are needed in order to develop an evidence base that can decisively provide reliable effect estimates of non-individualised homeopathic treatment

Towards standard setting for patient-reported outcomes in the NHS homeopathic hospitals

We report findings from a pilot data collection study within a programme of quality assurance, improvement and development across all five homeopathic hospitals in the UK National Health Service (NHS).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Aims&lt;/b&gt; (1) To pilot the collection of clinical data in the homeopathic hospital outpatient setting, recording patient-reported outcome since first appointment; (2) to sample the range of medical complaints that secondary-care doctors treat using homeopathy, and thus identify the nature and complexity of complaints most frequently treated nationally; (3) to present a cross section of outcome scores by appointment number, including that for the most frequently treated medical complaints; (4) to explore approaches to standard setting for homeopathic practice outcome in patients treated at the homeopathic hospitals.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; A total of 51 medical practitioners took part in data collection over a 4-week period. Consecutive patient appointments were recorded under the headings: (1) date of first appointment in the current series; (2) appointment number; (3) age of patient; (4) sex of patient; (5) main medical complaint being treated; (6) whether other main medical complaint(s); (7) patient-reported change in health, using Outcome Related to Impact on Daily Living (ORIDL) and its derivative, the ORIDL Profile Score (ORIDL-PS; range, –4 to +4, where a score &#8804;−2 or &#8805;+2 indicates an effect on the quality of a patient's daily life); (8) receipt of other complementary medicine for their main medical complaint.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; The distribution of patient age was bimodal: main peak, 49 years; secondary peak, 6 years. Male:female ratio was 1:3.5. Data were recorded on a total of 1797 individual patients: 195 first appointments, 1602 follow-ups (FUs). Size of clinical service and proportion of patients who attended more than six visits varied between hospitals. A total of 235 different medical complaints were reported. The 30 most commonly treated complaints were (in decreasing order of frequency): eczema; chronic fatigue syndrome (CFS); menopausal disorder; osteoarthritis; depression; breast cancer; rheumatoid arthritis; asthma; anxiety; irritable bowel syndrome; multiple sclerosis; psoriasis; allergy (unspecified); fibromyalgia; migraine; premenstrual syndrome; chronic rhinitis; headache; vitiligo; seasonal allergic rhinitis; chronic intractable pain; insomnia; ulcerative colitis; acne; psoriatic arthropathy; urticaria; ovarian cancer; attention-deficit hyperactivity disorder (ADHD); epilepsy; sinusitis. The proportion of patients with important co-morbidity was higher in those seen after visit 6 (56.9%) compared with those seen up to and including that point (40.7%; P &lt; 0.001). The proportion of FU patients reporting ORIDL-PS &#8805; +2 (improvement affecting daily living) increased overall with appointment number: 34.5% of patients at visit 2 and 59.3% of patients at visit 6, for example. Amongst the four most frequently treated complaints, the proportion of patients that reported ORIDL-PS &#8805; +2 at visit numbers greater than 6 varied between 59.3% (CFS) and 73.3% (menopausal disorder).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; We have successfully piloted a process of national clinical data collection using patient-reported outcome in homeopathic hospital outpatients, identifying a wide range and complexity of medical complaints treated in that setting. After a series of homeopathy appointments, a high proportion of patients, often representing “effectiveness gaps” for conventional medical treatment, reported improvement in health affecting their daily living. These pilot findings are informing our developing programme of standard setting for homeopathic care in the hospital outpatient context

Adenosine preconditioning attenuates hepatic reperfusion injury in the rat by preventing the down-regulation of endothelial nitric oxide synthase

BACKGROUND: Previous work has suggested that in the liver, adenosine preconditioning is mediated by nitric oxide. Whether the endothelial isoform of nitric oxide synthase plays a part in this mechanism has however not yet been investigated. METHODS: Wistar rats were used (6 in each group) – Groups: (1) sham, (2) ischemia-reperfusion, (3) adenosine + ischemia-reperfusion, (4) endothelial isoform inhibitor + adenosine + ischemia-reperfusion. RESULTS: Using immunohistochemistry, this study has revealed a decrease in the expression of endothelial nitric oxide synthase following hepatic ischemia-reperfusion. This was prevented by adenosine pre-treatment. When an inhibitor of endothelial nitric oxide synthase was administered prior to adenosine pre-treatment, pre-conditioning did not occur despite normal expression of endothelial nitric oxide synthase. CONCLUSIONS: These findings suggest that adenosine attenuates hepatic injury by preventing the downregulation of endothelial nitric oxide synthase that occurs during ischemia-reperfusion

Physical activity characterization:Does one site fit all?

Background: It is evident that a growing number of studies advocate a wrist-worn accelerometer for the assessment of patterns of physical activity a priori, yet the veracity of this site rather than any other body-mounted location for its accuracy in classifying activity is hitherto unexplored. Objective: The objective of this review was to identify the relative accuracy with which physical activities can be classified according to accelerometer site and analytical technique. Methods: A search of electronic databases was conducted using Web of Science, PubMed and Google Scholar. This review included studies written in the English language, published between database inception and December 2017, which characterized physical activities using a single accelerometer and reported the accuracy of the technique. Results: A total of 118 articles were initially retrieved. After duplicates were removed and the remaining articles screened, 32 full-text articles were reviewed, resulting in the inclusion of 19 articles that met the eligibility criteria. Conclusion: There is no 'one site fits all' approach to the selection of accelerometer site location or analytical technique. Research design and focus should always inform the most suitable location of attachment, and should be driven by the type of activity being characterized

Precise Measurement of the Neutrino Mixing Parameter theta(23) from Muon Neutrino Disappearance in an Off-Axis Beam

New data from the T2K neutrino oscillation experiment produce the most precise measurement of the neutrino mixing parameter theta_{23}. Using an off-axis neutrino beam with a peak energy of 0.6 GeV and a data set corresponding to 6.57 x 10^{20} protons on target, T2K has fit the energy-dependent nu_mu oscillation probability to determine oscillation parameters. Marginalizing over the values of other oscillation parameters yields sin^2 (theta_{23}) = 0.514 +0.055/-0.056 (0.511 +- 0.055), assuming normal (inverted) mass hierarchy. The best-fit mass-squared splitting for normal hierarchy is Delta m^2_{32} = (2.51 +- 0.10) x 10^{-3} eV^2/c^4 (inverted hierarchy: Delta m^2_{13} = (2.48 +- 0.10) x 10^{-3} eV^2/c^4). Adding a model of multinucleon interactions that affect neutrino energy reconstruction is found to produce only small biases in neutrino oscillation parameter extraction at current levels of statistical uncertainty

Measurement of the intrinsic electron neutrino component in the T2K neutrino beam with the ND280 detector

The T2K experiment has reported the first observation of the appearance of electron neutrinos in a muon neutrino beam. The main and irreducible background to the appearance signal comes from the presence in the neutrino beam of a small intrinsic component of electron neutrinos originating from muon and kaon decays. In T2K, this component is expected to represent 1.2% of the total neutrino flux. A measurement of this component using the near detector (ND280), located 280 m from the target, is presented. The charged current interactions of electron neutrinos are selected by combining the particle identification capabilities of both the time projection chambers and electromagnetic calorimeters of ND280. The measured ratio between the observed electron neutrino beam component and the prediction is 1.01 +/- 0.10 providing a direct confirmation of the neutrino fluxes and neutrino cross section modeling used for T2K neutrino oscillation analyses. Electron neutrinos coming from muons and kaons decay are also separately measured, resulting in a ratio with respect to the prediction of 0.68 +/- 0.30 and 1.10 +/- 0.14, respectively

Measurement of the neutrino-oxygen neutral-current interaction cross section by observing nuclear deexcitation gamma rays

We report the first measurement of the neutrino-oxygen neutral-current quasielastic (NCQE) cross section gamma It is obtained by observing nuclear deexcitation. rays which follow neutrino-oxygen interactions at the Super-Kamiokande water Cherenkov detector. We use T2K data corresponding to 3.01 x 10(20) protons on target. By selecting only events during the T2K beam window and with well-reconstructed vertices in the fiducial volume, the large background rate from natural radioactivity is dramatically reduced. We observe 43 events in the 4-30 MeV reconstructed energy window, compared with an expectation of 51.0, which includes an estimated 16.2 background events. The background is primarily nonquasielastic neutral-current interactions and has only 1.2 events from natural radioactivity. The flux-averaged NCQE cross section we measure is 1.55 x 10(-38) cm(2) with a 68% confidence interval of (1.22, 2.20) x 10(-38) cm(2) at a median neutrino energy of 630 MeV, compared with the theoretical prediction of 2.01 x 10(-38) cm(2)

Global Patterns and Controls of Nutrient Immobilization On Decomposing Cellulose In Riverine Ecosystems

Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate