Altered Plasma and Brain Disposition and Pharmacodynamics of Methadone in Abstinent Rats

The pharmacokinetics and pharmacodynamics of methadone were investigated in control and abstinent rats. Minipumps filled with saline (control group) or saline-morphine (abstinent group) solutions were used to induce physical dependence. Solutions were delivered continuously by minipumps for 6 days. The physical dependence was evaluated 12 h after minipump removal by measuring specific withdrawal signs. Animals from the abstinent group showed clear withdrawal signs such as hostility on handling and weight loss. Plasma and brain disposition and pharmacodynamics of methadone were evaluated after a 0.35 mg/kg i.v. bolus dose administered 12 h after minipump removal. Plasma clearance, distribution clearance, and volume of distribution at steady-state were significantly decreased (P < 0.05) in the abstinent group. Plasma levels of alpha1-acid glycoprotein and plasma protein binding were significantly increased (P < 0.05) in the abstinent group. The estimates of pharmacokinetic parameters based on unbound plasma concentrations did not differ between groups, with the sole exception of the unbound apparent volume of distribution. The access of methadone to the brain was significantly faster (P < 0.05) in the abstinent group, although the extent of distribution in the brain was diminished in comparison with the control group. Analgesia recorded with tail-flick was used as the pharmacodynamic endpoint. Analgesic response and effect compartment concentrations of methadone were related by the sigmoidal Emax model. Estimates of C50 [steady-state plasma concentrations eliciting half of maximum effect (Emax)]] based on unbound concentrations did not differ between groups. On the other hand, the estimate of Emax had decreased by 65% in the abstinent group

Study of the Molecular Weight Influence on the Formation of the ß-polymorph in Metallocenic Isotactic Polypropylene

Isotactic polypropylene, iPP, is one of the most important thermoplastic polymers due to its low manufacturing cost and rather versatile properties. iPP exhibits a very interesting polymorphic behavior depending on the polymerization procedure, thermal history and use of different nucleating agents. Recently, studies on different aspects of the iPP β-polymorph have been published [1, 2]. This paper completes these previous works by analyzing the formation of the β-polymorph starting from samples of metallocenic iPP of different molecular weight. We also consider the effect of the cooling rate in the appearance of β-polymorph in the iPP samples that were studied

Pharmacokinetic-pharmacodynamic modeling of the antinociceptive effects of main active metabolites of tramadol, (+)-O-desmethyltramadol and (-)-O-desmethyltramadol, in rats.

The pharmacokinetics and pharmacodynamics of the two main metabolites of tramadol, (+)-O-desmethyltramadol and (-)-O-desmethyltramadol, were studied in rats. Pharmacodynamic endpoints evaluated were respiratory depression, measured as the change in arterial blood pCO(2), pO(2), and pH levels; and antinociception, measured by the tail-flick technique. The administration of 10 mg/kg (+)-O-desmethyltramadol in a 10-min i.v. infusion significantly altered pCO(2), pO(2), and pH values in comparison with baseline and lower-dose groups (P <.05). However, 2 mg/kg administered in a 10-min i.v. infusion was enough to achieve 100% antinociception without respiratory depression. Moreover, the beta-funaltrexamine pretreatment completely eliminated the antinociception of the 2-mg/kg dose, suggesting that such an effect is due to mu-opioid receptor activation. To describe and adequately characterize the in vivo antinociceptive effect of the drug, (+)-O-desmethyltramadol was given at different infusion rates of varying lengths (10-300 min). Pharmacokinetics was best described by a two-compartmental model. The time course of response was described using an effect compartment associated with a linear pharmacodynamic model. The estimates of the slope of the effect versus concentration relationship were significantly decreased (P <. 05) as the length of infusion was increased, suggesting the development of tolerance. Doses of up to 8 mg/kg (-)-O-desmethyltramadol given in 10-min i.v. infusion did not elicit either antinociception in the tail-flick test or respiratory effects. These in vivo results are in accordance with the opiate and nonopiate properties reported for these compounds in several in vitro studies

Modeling of the In Vivo Antinociceptive Interaction between an Opioid Agonist, (+)-O-Desmethyltramadol, and a Monoamine Reuptake Inhibitor, (—)-O-Desmethyltramadol, in Rats

The pharmacokinetic-pharmacodynamic (pk-pd) characterization of the in vivo antinociceptive interaction between (+)-O-desmethyltramadol [(+)-M1] and (-)-O-desmethyltramadol [(-)-M1], main metabolites of tramadol, was studied in three groups of rats. (+)-M1 and (-)-M1, both with different pd properties, were studied under steady-state and nonsteady-state conditions, depending on the group. Plasma drug concentration and antinociception were simultaneously measured in each animal by using an enantioselective analytical assay and the tail-flick test, respectively. Respiratory depression also was evaluated in another series of experiments according to the same experimental conditions. The pk behavior was similar for both enantiomers and no significant (P >.05) interaction between two compounds was found at this level. However, a significant (P .05) respiratory effects were seen during or after (+)-M1 and (-)-M1 administration

Acoustic assessment and distribution of the main pelagic fish species in ICES Subdivision 9a South during the ECOCADIZ-RECLUTAS 2021-10 Spanish survey (October 2021).

The present working document summarises the main results obtained from the ECOCADIZ-RECLUTAS 2021-10 Spanish (pelagic ecosystem-) acoustic-trawl survey conducted by IEO between 21st October and 07th November 2021 in the Portuguese and Spanish shelf waters (20-200 m isobaths) off the Gulf of Cadiz (GoC) onboard the R/V Ramón Margalef. The survey suffered a ten-day delay in relation to the usual starting dates. The survey’s main objective is the acoustic assessment of anchovy and sardine juveniles (age 0 fish) in the GoC recruitment areas. The 21 foreseen acoustic transects were sampled. A total of 18 valid fishing hauls were carried out for echo-trace ground-truthing purposes. Chub mackerel, anchovy and sardine were the most frequent captured species in the fishing hauls, followed by horse mackerel, bogue, Atlantic mackerel, Mediterranean horse mackerel and blue jack mackerel. Boarfish, longspine snipefish and pearlside showed an incidental occurrence in the hauls performed in the surveyed area. Sardine and chub mackerel showed the highest yields in these hauls, followed by anchovy and Mediterranean horse mackerel. Total and Spanish estimates of total NASC allocated to the “pelagic fish species assemblage” in this survey showed lower values than those recorded last year, whereas the Portuguese estimates showed an increasing trend. GoC anchovy was widely distributed in the surveyed area, although avoided the easternmost waters. Higher densities were recorded between Alfanzina and west of Cape Santa Maria, in the Algarve, and between Isla Cristina and Bay of Cadiz. Anchovy acoustic estimates in autumn 2021, 17 512 t and 1973 million fish, experienced 38% and 51% decreases in abundance and biomass, respectively, in relation to the last year’s autumn estimates and they were lower than their time-series averages. The population was composed by fishes not older than 2 years. As usual, the bulk of the population, including juveniles, was located in Spanish waters. Age-0 anchovies accounted for 83% (1629 million) and 69% (12 063 t) of the total estimated abundance and biomass, respectively. Age-0 estimates experienced a similar decreasing trend than the one showed by the whole population in relation to the historical peak recorded in 2019, but with values close to the time-series average. GoC sardine was widely distributed all over the surveyed area (also avoiding the easternmost waters) and recorded a relatively high acoustic echo-integration in autumn 2021 as a consequence of the occurrence of dense mid-water schools in the Algarve coastal and inner shelf waters (20-78 m). Abundance (2986 million fish) and biomass (151 320 t) estimates were the second historical records within its respective series, although they represented 83% and 38% decreases in relation to the last year’s estimates. GoC sardine population was mainly concentrated in Portuguese waters. Age-5 group was the oldest age group in the population, although the occurrence of fishes older than 4 years was incidental. The population was mainly composed by fishes belonging to the age-0 to age-2 groups. Juvenile sardines (age-0 group) were not the dominant group, accounting for 21% (638 million) and 9% (12 854 t) of the total abundance and biomass, respectively. The bulk of this juvenile fraction was recorded in Spanish coastal waters. Chub mackerel was also widely distributed in the surveyed area, but showing higher densities in three between Cape San Vicente and Mazagón. Chub mackerel estimates were of 13 115 t and 106 million fish, accounting for 64% and 43% strong decreases in relation to the estimates in the previous year and with the above values being lower than their time-series average. The population was mainly concentrated in Portuguese waters and it was composed by fishes not older than 5 years, with the age-1 group being the dominant one. Age-0 fish was the second most important age group in the estimated population ((24%, 26 million fish, and 13%, 1689 t, of the total abundance and biomass estimates). The bulk of the age-0 and age-1 groups were recorded in the Portuguese waters, whereas older age-groups were more frequent in Spanish waters

Efecto del Peso Molecular en la Formación del Polimorfo Beta en Polipropileno Isotáctico Metalocénico.

Existe un gran número de referencias relativas al efecto que la adición de agentes nucleantes, AN, en el polipropileno, iPP, supone en la generación de los distintos polimorfos, no existiendo estudios previos en el iPP metalocénico, m-iPP. Es objetivo de este trabajo llenar la laguna existente en dicha área, con el fin de mejorar la estabilidad térmica y la transparencia, acortar los ciclos de producción y optimizar las propiedades. Se han estudiado diferentes tipos de nucleantes de última generación que conllevan, en primer lugar, la formación de la celdilla monoclínica α y el aumento de la temperatura de cristalización, lo que acorta los ciclos de transformación. Para la evaluación exhaustiva5 de la forma β, objetivo de este trabajo, se ha utilizado como AN una mezcla de estearato cálcico y ácido pimélico (1:2), denominada a5. La competencia entre las formas α, β y γ en el m-iPP depende de la velocidad de cristalización y de la temperatura de cristalización isoterma5. Además, el contenido de AN β necesario para generar esta forma cristalina en el m-iPP es considerablemente superior en relación con el iPP sintetizado con catalizadores Ziegler-Natta, Z-N, debido a la coexistencia del polimorfo γ en el primero. La competencia entre las tres formas cristalinas en el m-iPP provoca que la generación de la forma β en función de la velocidad de enfriamiento sea, bajo ciertas condiciones, opuesta a la observada previamente en el iPP Z-N convencional. Estos resultados novedosos son de gran interés dado que han establecido las bases científicas sobre las que se cimenta el objetivo de la adición de AN β en los diferentes iPPs seleccionados, objeto de estudio en esta comunicación. Se han mezclado dos m-iPP con índices de fluidez, IF, de 15 y 30 g/min, suministrados por Basell, con un 0.3 % en peso de AN, en un mezclador interno a 190 ºC, 40 rpm y 10 min. Posteriormente, se han preparado filmes mediante moldeo por compresión en muestras sin y con AN. Las muestras se han enfriado desde el fundido a unos 100 ºC/min (entre platos de agua fría y presión), tratamiento Q y a 1.5 ºC/min (velocidad de enfriamiento de la prensa bajo presión), tratamiento S. La caracterización de la estructura y la competición entre las diferentes formas cristalinas se ha seguido mediante difracción de rayos X y DSC, mientras que el estudio de las propiedades mecánicas se ha realizado mediante DMTA y microdureza. En la figura se reproducen los difractogramas de RX para las muestras en estudio sin y con 0.3% de AN y tratamiento térmico S. Las muestras sin aditivar, sn, presentan polimorfismo, es decir, la coexistencia de las difracciones a 18.5 y 21.2º características de las celdillas cristalinas α y γ, respectivamente. Por otro lado, la presencia del AN a5 da lugar a una difracción adicional a 16.1º asociada a la fase trigonal β. La intensidad de dicha difracción es mayor para el polímero de menor peso molecular (mayor IF)

SARS-CoV-2 Vaccination in the Context of Ongoing HIV Cure-Related Research Studies

To the Editors: The SARS-CoV-2 pandemic has affected research efforts worldwide. Previously, we described our strategy to mitigate COVID-19 transmission risk during an ongoing HIV cure-related clinical trial. SARS-CoV-2 vaccines recently have been authorized for emergency use and will become available to people with HIV imminently. As a result, researchers must determine how to adjust study protocols to incorporate the likelihood that participants may be vaccinated

Growth variability and demographic structure of northeast Atlantic chub mackerel (Scomber colias) in southern European Atlantic waters

The Atlantic chub mackerel (Scomber colias) is one of the main fishing resources for the fisheries targeting small pelagics in NW African waters. This species is expanding its geographical distribution through higher latitudes in southern European Atlantic waters, and it has become an important fishing resource in Iberian Atlantic waters during the last decades. The present study addresses the growth variability of S. colias in the Iberian waters, from southern Bay of Biscay up to Gulf of Cadiz. Age estimates based on otoliths and growth parameters were obtained from specimens collected within the study area during one decade (from both commercial landings and scientific-acoustic surveys), and sexual growth variation was analysed. A common pattern of abundant cohorts was observed in various areas. However, differences in the demographic structure of the catches were observed among the different areas, with the southernmost area studied (Portuguese and Spanish waters off Gulf of Cadiz) standing out with younger individuals. These new findings are of interest for the stock assessment of S. colias, which has not been addressed in ICES waters so far

Evaluation of a short RNA within Prostate Cancer Gene 3 in the predictive role for future cancer using non-malignant prostate biopsies.

BACKGROUND: Prostate Cancer 3 (PCA3) is a long non-coding RNA (ncRNA) upregulated in prostate cancer (PCa). We recently identified a short ncRNA expressed from intron 1 of PCA3. Here we test the ability of this ncRNA to predict the presence of cancer in men with a biopsy without PCa. METHODS: We selected men whose initial biopsy did not identify PCa and selected matched cohorts whose subsequent biopsies revealed PCa or benign tissue. We extracted RNA from the initial biopsy and measured PCA3-shRNA2, PCA3 and PSA (qRT-PCR). RESULTS: We identified 116 men with and 94 men without an eventual diagnosis of PCa in 2-5 biopsies (mean 26 months), collected from 2002-2008. The cohorts were similar for age, PSA and surveillance period. We detected PSA and PCA3-shRNA2 RNA in all samples, and PCA3 RNA in 90% of biopsies. The expression of PCA3 and PCA3-shRNA2 were correlated (Pearson's r = 0.37, p<0.01). There was upregulation of PCA3 (2.1-fold, t-test p = 0.02) and PCA3-shRNA2 (1.5-fold) in men with PCa on subsequent biopsy, although this was not significant for the latter RNA (p = 0.2). PCA3 was associated with the future detection of PCa (C-index 0.61, p = 0.01). This was not the case for PCA3-shRNA2 (C-index 0.55, p = 0.2). CONCLUSIONS: PCA3 and PCA3-shRNA2 expression are detectable in historic biopsies and their expression is correlated suggesting co-expression. PCA3 expression was upregulated in men with PCa diagnosed at a future date, the same did not hold for PCA3-shRNA2. Futures studies should explore expression in urine and look at a time course between biopsy and PCa detection

Dynamic Scaling and Two-Dimensional High-Tc Superconductors

There has been ongoing debate over the critical behavior of two-dimensional superconductors; in particular for high Tc superconductors. The conventional view is that a Kosterlitz-Thouless-Berezinskii transition occurs as long as finite size effects do not obscure the transition. However, there have been recent suggestions that a different transition actually occurs which incorporates aspects of both the dynamic scaling theory of Fisher, Fisher, and Huse and the Kosterlitz-Thouless-Berezinskii transition. Of general interest is that this modified transition apparently has a universal dynamic critical exponent. Some have countered that this apparent universal behavior is rooted in a newly proposed finite-size scaling theory; one that also incorporates scaling and conventional two-dimensional theory. To investigate these issues we study DC voltage versus current data of a 12 angstrom thick YBCO film. We find that the newly proposed scaling theories have intrinsic flexibility that is relevant to the analysis of the experiments. In particular, the data scale according to the modified transition for arbitrarily defined critical temperatures between 0 K and 19.5 K, and the temperature range of a successful scaling collapse is related directly to the sensitivity of the measurement. This implies that the apparent universal exponent is due to the intrinsic flexibility rather than some real physical property. To address this intrinsic flexibility, we propose a criterion which would give conclusive evidence for phase transitions in two-dimensional superconductors. We conclude by reviewing results to see if our criterion is satisfied.Comment: 14 page