Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related
molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine ...MDMA (3,4-
methylenedioxymethamphetamine, XTC, ?Ecstasy?) is the prototypical representative of a separate class of psychotropic
substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of
consciousness, usually described as an ?open mind state?, may have relevant therapeutic applications, both in
psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure.
Nevertheless, a comprehensive and systematic exploration of the structure-activity relationships associated with
entactogenic activity has remained incomplete and controversial, highlighting the possibility that MDMA might represent
a pharmacological rarity in the field of psychotropics. As the latter is still an open question, the pharmacological
characterization of MDMA analogues remains the logical strategy to attempt the elucidation of the structural requirements
needed to elicit typical MDMA-like effects. Intriguingly, almost no experimental evidence supports the existence of actual
MDMA analogues that truly resemble the whole pharmacological profile of MDMA, probably due to its complex (and
partially not fully understood) mechanism of action that includes a disruption of monoaminergic neurotransmission. The
present review presents a brief summary of the pharmacology of MDMA, followed by the evidence accumulated over the
years regarding the characterization of classical structurally related MDMA analogues in different models and how this
state of the art highlights the need to develop new and better MDMA analogues.
•Two week's methylphenidate (MPH) treatment enhanced LTP in the rat PFC in vivo.•15–18 days after the end of MPH treatment LTP remained strongly enhanced.•Five months later LTP was no longer ...augmented.•Could not be induced after high MPH doses.•Doses of MPH that improved maze-learning also enhanced LTP in the same animals.
Methylphenidate (MPH) is widely used as a “nootropic” agent and in the treatment of disorders of attention, and has been shown to modulate synaptic plasticity in vitro. Here we present in vivo evidence that this MPH-induced metaplasticity can last long after the end of treatment. MPH (0, 0.2, 1 and 5mg/kg) was administered daily to male rats from postnatal day 42 for 15 days. The animals were tested daily in a radial maze. Long-term potentiation (LTP), a marker of neural plasticity, was induced in vivo in the prefrontal cortex after 2–3h, 15–18 days or 5 months without treatment. The behavioral performance of the 1mg/kg group improved, while that of animals that had received 5mg/kg deteriorated. In the 1 and 5mg/kg groups LTP induced 2–3h after the last MPH treatment was twice as large as in the controls. Further, 15–18 days after the last MPH administration, in groups receiving 1 and 5mg/kg, LTP was about fourfold higher than in controls. However, 5 months later, LTP in the 1mg/kg group was similar to controls and in the 5mg/kg group LTP could not be induced at all. No significant changes of LTP were seen in the low-dose group of animals (0.2mg/kg). Thus, firstly, doses of MPH that improve learning coincide approximately with those that augment LTP. Secondly, MPH-induced increases in LTP can last for several weeks, but these may disappear over longer periods or deteriorate at high doses.
In Caribbean coral reefs, many crustacean species associate with sea anemones, but only a few are anemone symbionts. We examined several ecological traits of 3 anemone species (Bartholomea ...annulata,Condylactis gigantea,Lebrunia danae) and their crustacean symbionts (6 species) on a coral reef at Puerto Morelos, Mexico. On average,C. giganteawas the largest andB. annulatathe most abundant of the 3 anemone species. Season did not affect the density distribution of any species, whereas reef zone (back reef, fore reef, reef channels) significantly affected density and mean size ofB. annulataandC. gigantea, but only density ofL. danae. The probability of harboring crusta ceans increased with anemone size in all species, but varied with reef zone and season inB. annulataonly. These patterns may be due to different microhabitat requirements, reproductive strategies, or photosynthetic plasticity of dinoflagellate endosymbionts among hosts, and different flow regimes among reef zones.Alpheus armatusandAncylomenes pedersoniwere strongly associated withB. annulata, andPericlimenes rathbunaewithL. danae.Thor amboinensisandMithraculus cinctimanusoccurred more often inC. gigantea, whileP. yucatanicuswas more evenly associated with the 3 hosts. OnlyAncylomenes pedersoniandT. amboinensisoccurred in conspecific groups more often than expected by chance. Commensal complexes of up to 3 symbiont species occurred in all host species, with symbionts that typically used different parts of the host coexisting more frequently. These results provide a baseline to assess the potential influence of local and global anthropogenic stressors on anemone–crustacean symbioses.
Analysis of coenzyme Q10 in lymphocytes by HPLC–MS/MS Arias, A.; García-Villoria, J.; Rojo, A. ...
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences,
11/2012, Letnik:
908
Journal Article
Recenzirano
► The reference range of CoQ10 was narrower when normalized to units of citrate synthase than when normalized to grams of protein. ► Isolated lymphocyte lysates are a reliable matrix for the ...diagnosis and follow-up of patients with CoQ10 deficiency. ► HPLC–MS/MS is a good procedure to measure CQ10.
Coenzyme Q10 (CoQ10) deficiency syndromes are potentially treatable disorders. Skeletal muscle is the most widely accepted tissue for their study, but sampling is an invasive procedure. Cultured skin fibroblasts seem to improve the biochemical diagnosis, but their growth requires a certain period of time. Our aim was to set up a minimally invasive, fast and reliable analytical procedure to measure CoQ10 in lymphocytes, to prevent any delay in diagnosing primary CoQ10 deficiency. HPLC–MS/MS analysis of CoQ10 showed high sensitivity and specificity. The reference range was established in apparently healthy volunteers (n=33); the mean of CoQ10 in lymphocytes was 107nmol/g protein (95% confidence interval: 105–120) and 2.0nmol/UCS (95% confidence interval: 2.06–2.46). Therefore, the range was narrower when normalized to units of citrate synthase (UCS) than when normalized to grams of protein. The method was linear from 0.01 to 1μM with a good precision and sensitivity (limit of quantification 0.01μM). Intra-assay and inter-assay coefficients of variation were lower than 13%. Recovery was higher than 95%. In our hands, lymphocytes seem to be a reliable matrix as they reflect intracellular content of CoQ10. In addition, they can be obtained by a minimally invasive procedure (venipuncture).
Analysis of coenzyme Q(10) in lymphocytes by HPLC-MS/MS Arias, A; García-Villoria, J; Rojo, A ...
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences,
2012-Nov-01, 20121101, Letnik:
908
Journal Article
Recenzirano
Coenzyme Q(10) (CoQ(10)) deficiency syndromes are potentially treatable disorders. Skeletal muscle is the most widely accepted tissue for their study, but sampling is an invasive procedure. Cultured ...skin fibroblasts seem to improve the biochemical diagnosis, but their growth requires a certain period of time. Our aim was to set up a minimally invasive, fast and reliable analytical procedure to measure CoQ(10) in lymphocytes, to prevent any delay in diagnosing primary CoQ(10) deficiency. HPLC-MS/MS analysis of CoQ(10) showed high sensitivity and specificity. The reference range was established in apparently healthy volunteers (n=33); the mean of CoQ(10) in lymphocytes was 107nmol/g protein (95% confidence interval: 105-120) and 2.0nmol/UCS (95% confidence interval: 2.06-2.46). Therefore, the range was narrower when normalized to units of citrate synthase (UCS) than when normalized to grams of protein. The method was linear from 0.01 to 1μM with a good precision and sensitivity (limit of quantification 0.01μM). Intra-assay and inter-assay coefficients of variation were lower than 13%. Recovery was higher than 95%. In our hands, lymphocytes seem to be a reliable matrix as they reflect intracellular content of CoQ(10). In addition, they can be obtained by a minimally invasive procedure (venipuncture).
Debido a la búsqueda de alternativas económicas para la disminución de contaminantes en aguas residuales, se emplea como opción el uso de las cáscaras de naranja y banano como adsorbente para remover ...metales pesados. Los experimentos se efectuaron utilizando biomasas previamente tratadas para obtener los adsorbentes. Durante los ensayos, se variaron las condiciones de operación: pH, tiempo, cantidad de adsorbente; y como constantes: velocidad de agitación, tamaño de partícula y temperatura. Se determinó la disminución de Cr(VI) mediante colorimetría y Cu(II) por Espectrofotometría UV Visible y la caracterización de los adsorbentes por Espectroscopía Infrarroja por Transformada de Fourier (FTIR). Se aplicaron modelos cinéticos de pseudo primer orden, pseudo segundo orden y Elovich. Los resultados mostraron porcentajes de remoción favorables para el Cr(VI) usando la CN (91,11 %) a pH 4, 3 g/L, 2 h y la CB (92,96 %) a pH 3, 4 g/L, 4 h. Mientras que para el Cu(II) empleando la CN (97,10 %) a pH 5,5, 5 g/L, 30 min y la CB (69,57 %) a pH 5,8, 3 g/L, 30 min, asimismo las concentraciones finales de ambos metales cumplen con la normativa TULSMAN. Se concluye que el uso de ambos bioadsorbentes disminuye metales pesados como el Cr(VI) y Cu(II) en aguas residuales domésticas.
Mediastinal staging in patients with non-small cell lung cancer (NSCLC) with endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) requires a high negative predictive value (NPV) (ie, low ...false negative rate). We provide a conservative calculation of NPV that calls for caution in the interpretation of EBUS results.
We retrospectively analyzed our prospectively gathered database (January 2007 to November 2011) to include NSCLC patients who underwent EBUS-FNA for mediastinal staging. We excluded patients with metastatic NSCLC and other malignancies. We assessed FNAs with rapid on-site evaluation (ROSE). The calculation of NPV is NPV = true negatives/true negatives + false negatives. However, this definition ignores nondiagnostic samples. Nondiagnostic samples should be added to the NPV denominator because decisions based on nondiagnostic samples could be flawed. We conservatively calculated NPV for EBUS-FNA as NPV = true negatives/true negatives + false negatives + nondiagnostic. We defined false negatives as negative FNAs but NSCLC-positive surgical biopsy of the same site. Nondiagnostic FNAs were nonrepresentative of lymphoid tissue. We compared diagnostic performance with the inclusion and exclusion of nondiagnostic procedures.
We studied 120 patients with NSCLC who underwent EBUS-FNA; 5 patients had false negative findings and 10 additional patients had nondiagnostic results. The NPV with and without inclusion of nondiagnostic samples was 65.9% and 85.3%, respectively.
The inclusion of nondiagnostic specimens into the conservative, worst-case-scenario calculation of NPV for EBUS-FNA in NSCLC lowers the NPV from 85.3% to 65.9%. The true NPV is likely higher than 65.9% as few nondiagnostic specimens are false negatives. Caution is imperative for the safe application of EBUS-FNA in NSCLC staging.
Den sharing by conspecific spiny lobsters (aggregation) is modulated by chemical attraction but may confer several, not necessarily mutually exclusive, antipredator byproduct benefits: a “guide ...effect”, which only benefits the individual attracted to a sheltered conspecific; a “dilution effect”, which reduces per-capita risk of predation simply through aggregation; or active “group defense”. Each potential benefit has a different set of predictors (relationships between aggregation and conspecific or predator densities), but conflicting results could suggest the simultaneous operation of more than one benefit. These predictions were tested for coexisting
Panulirus guttatus
(a reef-obligate) and
Panulirus argus
(a temporary reef-dweller) using data collected during 11 surveys on fixed sites over a coral reef in Mexico.
P. guttatus
greatly outnumbered
P. argus
, but
P. argus
showed a greater tendency to aggregate. All three benefits of den sharing operated for the more social
P. argus
, with “group defense” being of the most benefit for larger individuals, and the “guide” and “dilution” effects for smaller individuals recently immigrating into the reef habitat and sharing dens with larger conspecifics.
P. guttatus
did not display “group defense” and its aggregations appeared to be modulated by the interplay between attraction and aggressive behaviors. This species relied more on solitary crypticity, especially at larger sizes, but appeared to benefit from a “guide effect” at high conspecific densities. In experimental tanks, each species tended to aggregate when tested separately, but when tested jointly, aggregation among
P. guttatus
was significantly reduced. The experimental results reflect the differential patterns of aggregation between the fore-reef, where
P. guttatus
dominated, and the back-reef, where coexistence of both species was greater.