Pharmacokinetic and pharmacodynamic modelling of intravenous, intramuscular and subcutaneous buprenorphine in conscious cats

Objective To describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats. Study design Randomized, prospective, blinded, three period crossover experiment. Animals Six healthy adult cats weighing 4.1±0.5kg. Methods Buprenorphine (0.02mgkg-1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p<0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics. Results TT increased above baseline from 15 to 480minutes and at 30 and 60minutes after IV and IM administration, respectively (p<0.05). Maximum increase in TT (mean±SD) was 9.3±4.9°C at 60minutes (IV), 4.6±2.8°C at 45minutes (IM) and 1.9±1.9°C at 60minutes (SC). TT was significantly higher at 15, 60, 120 and 180minutes, and at 15, 30, 45, 60 and 120minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t1/2ke0=47.4minutes) and receptor binding (kon=0.011mL ng-1minute-1). Persistence of thermal antinociception was due to slow receptor dissociation (t1/2koff=18.2minutes). Conclusions and clinical relevance IV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Primordial germ cells (spermatogonial stem cells) of bullfrogs express sex hormone-binding globulin and steroid receptors during seasonal spermatogenesis

In vertebrate species, testosterone seems to inhibit spermatogonial differentiation and proliferation. However, this androgen can also be converted, via aromatase, into estrogen which stimulates spermatogonial differentiation and mitotic activity. During seasonal spermatogenesis of adult bullfrogs Lithobates catesbeianus, primordial germ cells (PGCs) show enhanced testosterone cytoplasm immunoexpression in winter; however, in summer, weak or no testosterone immunolabelling was observed. The aim of this study was to confirm if PGCs express stem cell markers-alkaline phosphatase (AP) activity and GFRα1 (glial-cell-line-derived neurotrophic factor)-and verify whether testosterone is maintained in these cells by androgen receptors (ARs) and/or sex hormone-binding globulin (SHBG) in winter. Furthermore, regarding the possibility that testosterone is converted into estrogen by PGCs in summer, the immunoexpression of estrogen receptor (ER)β was investigated. Bullfrog testes were collected in winter and in summer and were embedded in glycol methacrylate for morphological analyses or in paraffin for the histochemical detection of AP activity. GFRα1, AR, SHBG and ERβ expression were detected by Western blot and immunohistochemical analyses. The expression of AP activity and GFRα1 in the PGCs suggest that these cells are spermatogonial stem cells. In winter, the cytoplasmic immunoexpression of ARs and SHBG in the PGCs indicates that testosterone is maintained by these proteins in these cells. The cytoplasmic immunoexpression of ERβ, in summer, also points to an ER-mediated action of estrogen in PGCs. The results indicate a participation of testosterone and estrogen in the control of the primordial spermatogonia during the seasonal spermatogenesis of L. catesbeianus. © 2012 S. Karger AG, Basel.

Intravenous Tramadol Injection has no Antinociceptive Effect in Horses Undergoing Electrical and Thermal Stimuli

Tramadol combines an μ opiate and nonopiate analgesic mechanism and might be a useful opioid in horses. This study evaluated the effect of IV tramadol on spontaneous locomotor activity (SLA), head height, and hoof withdrawal reflex (HWR) after thermal or electrical nociceptive stimuli in horses. Doses of 2 and 3 mg/kg tramadol did not affect HWR after electrical and thermal nociception, respectively. Head height and SLA were not modified by 2, 3, or 5 mg/kg tramadol. All horses treated with 5 mg/kg tramadol developed trembling in pectoral triceps, and gluteal muscles and adopted a base-wide stance. In conclusion, 2 and 3 mg/kg tramadol IV neither induced sedation nor prolonged HWR after thermal or electrical stimuli in conscious horses. The dose of 5 mg/kg tramadol IV produced excitement, and it is apparently unsuitable for clinical use. © 2013 Elsevier Inc. All rights reserved.

Determinação do escore Apgar, dos valores hemogasométricos e do proteinograma sérico em cordeiros (Ovis aries) nascidos de partos normais e de cesarianas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Measurement of the production cross section for Z gamma -> nu(nu)over-bar gamma in pp collisions at root s=7 TeV and limits on ZZ gamma and Z gamma gamma triple gauge boson couplings

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Measurement of the W+W- cross section in pp collisions at and limits on anomalous WW gamma and WWZ couplings

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Rapidity distributions in exclusive Z plus jet and gamma plus jet events in pp collisions at root s=7 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Measurement of the W gamma and Z gamma inclusive cross sections in pp collisions at root s=7 TeV and limits on anomalous triple gauge boson couplings

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cardiorespiratory and antinociceptive effects of two different doses of lidocaine administered to horses during a constant intravenous infusion of xylazine and ketamine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bayesian inference for two-parameter gamma distribution assuming different noninformative priors

In this paper distinct prior distributions are derived in a Bayesian inference of the two-parameters Gamma distribution. Noniformative priors, such as Jeffreys, reference, MDIP, Tibshirani and an innovative prior based on the copula approach are investigated. We show that the maximal data information prior provides in an improper posterior density and that the different choices of the parameter of interest lead to different reference priors in this case. Based on the simulated data sets, the Bayesian estimates and credible intervals for the unknown parameters are computed and the performance of the prior distributions are evaluated. The Bayesian analysis is conducted using the Markov Chain Monte Carlo (MCMC) methods to generate samples from the posterior distributions under the above priors.

Intravenous versus inhalation anaesthesia for one-lung ventilation

BackgroundThis is an update of a Cochrane Review first published in The Cochrane Library, Issue 2, 2008.The technique called one-lung ventilation can confine bleeding or infection to one lung, prevent rupture of a lung cyst or, more commonly, facilitate surgical exposure of the unventilated lung. During one-lung ventilation, anaesthesia is maintained either by delivering an inhalation anaesthetic to the ventilated lung or by infusing an intravenous anaesthetic. It is possible that the method chosen to maintain anaesthesia may affect patient outcomes. Inhalation anaesthetics may impair hypoxic pulmonary vasoconstriction (HPV) and increase intrapulmonary shunt and hypoxaemia.ObjectivesThe objective of this review was to evaluate the effectiveness and safety of intravenous versus inhalation anaesthesia for one-lung ventilation.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL); The Cochrane Library (2012, Issue 11); MEDLINE (1966 to November 2012); EMBASE (1980 to November 2012); Literatura Latino-Americana e do Caribe em Ciencias da Saude (LILACS, 1982 to November 2012) and ISI web of Science (1945 to November 2012), reference lists of identified trials and bibliographies of published reviews. We also contacted researchers in the field. No language restrictions were applied. The date of the most recent search was 19 November 2012. The original search was performed in June 2006.Selection criteriaWe included randomized controlled trials and quasi-randomized controlled trials of intravenous (e. g. propofol) versus inhalation (e. g. isoflurane, sevoflurane, desflurane) anaesthesia for one-lung ventilation in both surgical and intensive care participants. We excluded studies of participants who had only one lung (i.e. pneumonectomy or congenital absence of one lung).Data collection and analysisTwo review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.Main resultsWe included in this updated review 20 studies that enrolled 850 participants, all of which assessed surgical participants no studies investigated one-lung ventilation performed outside the operating theatre. No evidence indicated that the drug used to maintain anaesthesia during one-lung ventilation affected participant outcomes. The methodological quality of the included studies was difficult to assess as it was reported poorly, so the predominant classification of bias was 'unclear'.Authors' conclusionsVery little evidence from randomized controlled trials suggests differences in participant outcomes with anaesthesia maintained by intravenous versus inhalational anaesthesia during one-lung ventilation. If researchers believe that the type of drug used to maintain anaesthesia during one-lung ventilation is important, they should design randomized controlled trials with appropriate participant outcomes, rather than report temporary fluctuations in physiological variables.

Comparison of oxidative stress in ASA physical status I patients scheduled for minimally invasive surgery under balanced or intravenous anesthesia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)