Two thalidomide analogs induce persistent estrous behavior and inhibit uterus contractility in rats: The central role of cAMP.

The effects of 4NO2PDPMe and 4APDPMe, which are thalidomide (Tha) analogs that act as selective phosphodiesterase (PDE-4) inhibitors, on estrous behavior (lordosis and proceptive behaviors) and on uterine contraction were studied in ovariectomized (OVX) estrogen-primed Sprague Dawley (SD) and in intact non-pregnant Wistar rats, respectively. We found that intracerebroventricular (ICV) infusion of either 4NO2PDPMe or 4APDPMe (20 to 80 µg) stimulated intense lordosis and proceptive behavior in response to mounts from a sexually active male, within the first 4 h after infusion, and persisting for up to 24 h. Inhibitors of the progesterone receptor (RU486, administered subcutaneously), the estrogen receptor (tamoxifen, ICV), the adenylate cyclase (AC)/ cyclic AMP (cAMP)/protein kinase A (PKA) pathway (administered ICV), and the mitogen activated protein kinase (MAPK) pathway (administered ICV) significantly decreased lordosis and proceptive behavior induced by Tha analogs. Uterine contractility studies showed that Tha analogs inhibited both the K+- and the Ca2+-induced tonic contractions in rat uterus. Tha analogs were equally effective, but 4APDPMe was more potent than 4NO2PDPMe. These results strongly suggest the central role of cAMP in both processes, sexual behavior, and uterine relaxation, and suggest that Tha analogs may also act as Ca2+-channel blockers.

Efecto de la edad relativa en las disciplinas de lanzamientos de los participantes españoles en el plan nacional de tecnificación de atletismo / The effect of relative age in throwing disciplines of participants in the national sports training plan in Spanish athletics / Efeito da idade relativa nas disciplinas de lançamentos dos participantes espanhóis no plano nacional de tecnificação do atletismo

El concepto efecto relativo de la edad hace referencia a las consecuencias de las diferencias físicas y psicológicas que pueden existir entre los nacidos más temprana y más tardíamente dentro del mismo año natural. El objetivo del presente estudio fue examinar dicho fenómeno en los lanzadores y lanzadoras españoles menores de 18 años (Sub-18) y de 14 años (Sub-14), identificando la influencia de la disciplina deportiva. La muestra comprendía 1960 lanzadores participantes de las concentraciones técnicas de la Real Federación Española de Atletismo (RFEA) entre los años 2005 y 2018. El análisis estadístico se basó en la prueba chi-cuadrado con un cálculo posterior de los odds ratios y el intervalo de confianza del 95%. Los principales resultados revelan que en todas las disciplinas (disco, jabalina, martillo y peso) hay una sobrerrepresentación de los sujetos nacidos en los primeros meses, siendo mayor la diferencia en lanzamiento de peso y observándose una reducción de dicho efecto con la maduración de los lanzadores. Podemos concluir que la estructura del atletismo español fomenta la aparición de este fenómeno, probablemente por el temprano proceso de selección de lanzadores

The concept of relative effect of age refers to the consequences of the physical and psychological differences that may exist between those born earlier or later within the same calendar year. The objective of the present study was to examine this phenomenon in Spanish throwers under 18s (Sub-18) and under 14s (Sub-14), identifying the influences of the athletic discipline. The sample comprised 1,960 throwers participants in the national sports training plan in Spanish athletics of the Royal Spanish Athletics Federation (RFEA) between 2005 and 2018. Statistical analysis was based on a chi-squared test followed by calculation of the odds ratios and 95% confidence intervals. The main results show that at all disciplines (discus throw, javelin throw, hammer throw and shot put) there was an over-representation of individuals born in the first few months of the year. The biggest difference is observed in shot put and in most cases this effect is reduced with the maturation of the throwers. We can conclude that the structure of Spanish athletics encourages the appearance of this phenomenon, probably due to the early selection process of throwers

O efeito relativo do conceito de idade refere-se às consequências das diferenças físicas e psicológicas que possam existir entre os primeiros e mais tardiamente dentro do mesmo ano civil nascido. O objetivo deste estudo foi examinar este fenômeno em jarros e jarros espanhóis com menos de 18 (U-18) e 14 anos (S14), identificando a influência do desporto. A amostra foi composta por 1960 participantes lançando concentrações técnicas da Real Federação Espanhola de Atletismo (RFEA) entre 2005 e 2018. A análise estatística foi baseada no teste do qui-quadrado com posterior cálculo do odds ratio e intervalo 95% de confiança Os principais resultados mostram que, em todas as disciplinas (disco, dardo, martelo e peso) são indivíduos nascidos nos primeiros meses, com diferenças maiores em peso tiro e com uma redução desse efeito com a maturação sobre-representadas jarros. Podemos concluir que a estrutura do atletismo espanhol favorece o surgimento deste fenômeno, provavelmente no início doslançadores processo de seleção

Reconstructing a Carboniferous inferred coral-alcyonarian association using a biomineralogical approach.

The taxonomic assignation and ecological implications of the genus Syringoalcyon Termier & Termier, 1945 have been a palaeontological problem for a long time. Carboniferous material from Morocco and Spain has been studied using a biomineralogical approach by means of petrographic microscopy, SEM, AFM, EMPA and CIP microscopy analysis. Detailed morphological, structural, chemical composition and crystallographic data enable a deeper understanding of the nature of Syringoalcyon. The coral walls and the so-called epithecal scales exhibit conspicuous differences in microstructure (lamellae and holacanthine fibres in the coral vs. single crystal in scales), nanostructure (pill-shaped vs. granule-shaped nanocrystals), composition (LMC vs. HMC) and crystallographic orientation. The results of these analyses imply that Syringoalcyon is an association between the tabulate coral Syringopora and an epibiont. They also suggest that the epibiont was an alcyonarian (a rare occurrence in the fossil record) that was attached to the syringoporoid. This work highlights the utility of the biomineralizational approaches for solving palaeontological problems, such as systematic affinities, and for advancing knowledge of the evolution of biocrystallization processes.

Interaction between Heliopsis longipes extract and diclofenac on the thermal hyperalgesia test.

Heliopsis longipes is an herbaceous plant found in Mexico, used traditionally for its analgesic and anesthetic activities. Plant extracts in combined use with synthetic drugs may represent a therapeutic advantage for the clinical treatment of pain, allowing the use of lower doses, and limiting side-effects. Therefore, the main objective of this study was to determine the possible pharmacological interaction between Heliopsis longipes ethanolic extract (HLEE) and diclofenac in the Hargreaves model of thermal hyperalgesia in the mouse. HLEE, diclofenac or fixed-dose ratio HLEE-diclofenac combinations were administered systemically to mice and the antihyperalgesic effect was evaluated using the thermal hyperalgesia test. All treatments produced a dose-dependent antihyperalgesic effect. ED(30) values were estimated for all the treatments and an isobologram was constructed. The derived theoretical ED(30) value for the HLEE-diclofenac combination was 54.4+/-9.4 mg/kg body wt, significantly higher than the actually observed experimental ED(30) value, 8.6+/-4.0 mg/kg body wt. This result corresponds to synergistic interaction between HLEE and diclofenac in the Hargreaves model of thermal hyperalgesia. Data suggest that low doses of the HLEE-diclofenac combination can interact synergistically at the systemic level and that this association may therefore represent a therapeutic advantage for the clinical treatment of inflammatory pain.

Short-term effects of thalidomide analogs on hepatic glycogen and nitric oxide in endotoxin-challenged rats.

Hepatic glycogen metabolism is altered by nitric oxide (NO) during endotoxic shock. Thalidomide analogs immunomodulate the endotoxin-induced cytokines which regulate the NO release. We analyzed the short-term effects of some thalidomide analogs on the hepatic glycogen store and on the plasma and hepatic NO in an acute model of endotoxic challenge in rat. An endotoxin dose selection was performed. Rats received vehicle, thalidomide or analogs orally and, two hours after last dose, they were injected with endotoxin (5 mg/kg). Animals were sacrificed 2 h after challenge. Liver glycogen was quantified by the anthrone technique. Plasma and hepatic NO was determined by Griess reagent and HPLC. Hepatic interferon-gamma, a NO co-inducer, was measured by ELISA. Endotoxin caused inverse dose-dependent effects on plasma NO and on glycogen.Thalidomide analogs showed short-term regulatory effects on glycogen, some of them increased it. Plasma NO was almost unaffected by analogs but hepatic NO was strikingly modulated. Analogs slightly up-regulated the liver interferon-gamma and two of them increased it significantly. Thalidomide analogs may be used as a pharmacological tool due to their short-term regulatory effects on glycogen and NO during endotoxic shock. Drugs that increase glycogen may improve liver injury in early sepsis.

Static headspace versus head space solid-phase microextraction (HS-SPME) for the determination of volatile organochlorine compounds in landfill leachates by gas chromatography.

The determination of five volatile organochlorine compounds, VOX (chloroform, 1,1,1-trichloroethane, carbon tetrachloride, trichloroethene and tetrachloroethene) in raw landfill leachates and biologically cleansed leachates by GC-MS is investigated. Two extraction and preconcentration procedures were evaluated for recovery of such analies from the samples, including static headspace (HS) and solid phase microextraction by sampling the headspace above the sample (HS-SPME). Optimisation of operating parameters for the best performance of both, sampling and preconcentration techniques was described. Detection limits, time of analysis, precision and linear ranges of both introduction techniques have been established. Application of proposed methods to the determination of the five VOX under study in the above referred samples revealed the absence of such analytes in both leachates. Then both methods were applied to the determination to the five organochlorine compounds under study on spiked leachates samples. While HS-GC-MS offered better analytical precision than HS-SPME-GC-MS, this last technique gave a faster analytical response because no dilution must be done for a reliable VOX determination in landfill leachates. In any case, both sample introduction techniques tested provides excellent recoveries and good analytical precision (ranged from 1 to 3%).