Diethylpropion produces psychostimulant and reward effects

Diethylpropion (DEP) is a stimulant drug widely used for weight control in Brazil and other American countries. However, its effects on behavior and addiction potential are not yet well known. Data suggest that sensitization resulting from pre-exposure to psychostimulants could be a possible risk factor in subsequent drug addiction. The purpose of this investigation was to verify whether pre-exposure to DEP would sensitize rats to the motor activating effect and to the rewarding value of DEP. Two experiments were conducted. In both experiments rats were pre-exposed to DEP (20 mg/kg) or vehicle for 7 consecutive days. The acute effect of DEP (0.0, 1.0, 2.5 or 5.0 mg/kg) on motor activity (Experiment 1) and induction of Conditioned Place Preference-CPP (Experiment 2) were then measured. Results from Experiment 1 showed that 2.5 and 5.0 mg/kg DEP increased motor activity. Sensitization of this motor effect was observed. In Experiment 2, the doses of 2.5 and 5.0 mg/kg DEP induced CPP, indicating their rewarding value. However, no sensitization effect was observed. The results suggest that DEP at low doses has psychostimulant and rewarding properties. It is recommended that more effort should be dedicated to elucidating DEP abuse Potential. (c) 2008 Elsevier Inc. All rights reserved.

Immunohistochemical features of claudin-low intrinsic subtype in metaplastic breast carcinomas

Purpose: The claudin-low molecular subtype of breast cancer includes triple negative invasive carcinomas, with a high frequency of metaplastic and medullary features. The aim of this study was to evaluate the immunohistochemistry expression of claudins in a series of metaplastic breast carcinomas. We also assessed other claudin-low features, such as the cancer stem cell-like and epithelial-to-mesenchymal transition phenotypes. Results: The majority of the cases showed weak or negative staining for membrane claudins expression. We found 76.9% (10/13) low expressing cases for claudin-1, 84.6% (11/13) for claudin-3 and claudin-4, and 92.3% (12/13) for claudin-7. Regarding the cancer stem cell marker ALDH1, 30.8% (4/13) showed positive staining. We also showed that the majority of the cases presented a CD44(+)CD24(-/low) phenotype, positivity for vimentin and lack of E-cadherin expression. Interestingly, these claudin-low molecular features were specific of the mesenchymal component of metaplastic breast carcinomas, since its frequency was very low in other breast cancer molecular subtypes, as luminal, HER2-overexpressing and non-metaplastic triple negative tumors. Conclusions: The negative/low expression of claudins and E-cadherin, high levels of vimentin, and the breast cancer stem cell phenotype suggests that metaplastic breast carcinomas have similar features to the ones included in the claudin-low molecular subtype, specially their mesenchymal components. (C) 2012 Elsevier Ltd. All rights reserved.

Pollination systems in Pogonieae (Orchidaceae: Vanilloideae): A hypothesis of evolution among reward and rewardless flowers

The tribe Pogonieae of Vanilloideae (Orchidaceae) consists of six genera, including Pogoniopsis, a mycoheterotrophic taxon with morphological characteristics distinct from the remaining of the tribe. A hypothesis about the phylogeny of the tribe was inferred, involving all currently recognized genera, based on isolated and combined sequence data of 5.8S, 18S and 26S (nrDNA) regions using parsimony and Bayesian analyses. Phylogenetic analyses show that inclusion of Pogoniopsis turns the tribe Pogonieae paraphyletic. All analyses reveal that Pogoniopsis is closely related to members of Epidendroideae. The pantropical Vanilla is monophyletic if Dictyophyllaria is assumed as synonym of Vanilla. Members of Pogonieae are pollinated by several groups of solitary and social bees, two pollination systems being recognized: reward-producing and deceptive. The molecular phylogeny suggests that ancestrals related to Pogonieae gave rise to two evolutionary lines: a tropical one with reward production of flowers, and a predominantly temperate regions invading line with deceptive flowers. Reward-producing flowers characterize the South and Central American clade (=Cleistes), while deceptive pollination is prominent in the clade that includes North American-Asiatic taxa plus the Amazonian genus Duckeella. (C) 2012 Elsevier GmbH. All rights reserved.

Corrole isomers: intrinsic gas-phase shapes via traveling wave ion mobility mass spectrometry and dissociation chemistries via tandem mass spectrometry

Corrole and four of its isomers with subtle structural changes promoted by exchange of nitrogen and carbon atoms in the corrole ring have been studied by traveling wave ion mobility mass spectrometry and collision induced dissociation experiments. Significant differences in shapes and charge distributions for their protonated molecules were found to lead to contrasting gas phase mobilities, most particularly for corrorin, the most "confused" isomer. Accordingly, corrorin was predicted by B3LYP/6-31g(d,p) and collisional cross section calculations to display the most compact tri-dimensional structure, whereas NCC4 and corrole were found to be the most planar isomers. Better resolution between the corrole isomers was achieved using the more polarizable and massive CO2 as the drift gas. Sequential losses of HF molecules were found to dominate the dissociation chemistry of the protonated molecules of these corrole isomers, but their unique structures caused contrasting labilities towards CID, whereas NCC4 showed a peculiar and structurally diagnostic loss of NH3, allowing its prompt differentiation from the other isomers.

The periaqueductal gray as a critical site to mediate reward seeking during predatory hunting

Previous studies using morphine-treated dams reported a role for the rostral lateral periaqueductal gray (rIPAG) in the behavioral switching between nursing and insect hunting, likely to depend on an enhanced seeking response to the presence of an appetitive rewarding cue (i.e., the roach). To elucidate the neural mechanisms mediating such responses, in the present study, we first observed how the rIPAG influences predatory hunting in male rats. Our behavioral observations indicated that bilateral rIPAG NMDA lesions dramatically interfere with prey hunting, leaving the animal without chasing or attacking the prey, but do not seem to affect the general levels of arousal, locomotor activity and regular feeding. Next, using Phaseolus vulgaris-leucoagglutinin (PHA-L), we have reviewed the rIPAG connection pattern, and pointed out a particularly dense projection to the hypothalamic orexinergic cell group. Double labeled PHA-L and orexin sections showed an extensive overlap between PHA-L labeled fibers and orexin cells, revealing that both the medial/perifornical and lateral hypothalamic orexinergic cell groups receive a substantial innervation from the rIPAG. We have further observed that both the medial/perifornical and lateral hypothalamic orexinergic cell groups up-regulate Fos expression during prey hunting, and that rIPAG lesions blunted this Fos increase only in the lateral hypothalamic, but not in the medial/perifornical, orexinergic group, a finding supposedly associated with the lack of motivational drive to actively pursue the prey. Overall, the present results suggest that the rIPAG should exert a critical influence on reward seeking by activating the lateral hypothalamic orexinergic cell group. (C) 2011 Elsevier B.V. All rights reserved.

Segmental dataset and whole body expression data do not support the hypothesis that non-random movement is an intrinsic property of Drosophila retrogenes

Background: Several studies in Drosophila have shown excessive movement of retrogenes from the X chromosome to autosomes, and that these genes are frequently expressed in the testis. This phenomenon has led to several hypotheses invoking natural selection as the process driving male-biased genes to the autosomes. Metta and Schlotterer (BMC Evol Biol 2010, 10:114) analyzed a set of retrogenes where the parental gene has been subsequently lost. They assumed that this class of retrogenes replaced the ancestral functions of the parental gene, and reported that these retrogenes, although mostly originating from movement out of the X chromosome, showed female-biased or unbiased expression. These observations led the authors to suggest that selective forces (such as meiotic sex chromosome inactivation and sexual antagonism) were not responsible for the observed pattern of retrogene movement out of the X chromosome. Results: We reanalyzed the dataset published by Metta and Schlotterer and found several issues that led us to a different conclusion. In particular, Metta and Schlotterer used a dataset combined with expression data in which significant sex-biased expression is not detectable. First, the authors used a segmental dataset where the genes selected for analysis were less testis-biased in expression than those that were excluded from the study. Second, sex-biased expression was defined by comparing male and female whole-body data and not the expression of these genes in gonadal tissues. This approach significantly reduces the probability of detecting sex-biased expressed genes, which explains why the vast majority of the genes analyzed (parental and retrogenes) were equally expressed in both males and females. Third, the female-biased expression observed by Metta and Schltterer is mostly found for parental genes located on the X chromosome, which is known to be enriched with genes with female-biased expression. Fourth, using additional gonad expression data, we found that autosomal genes analyzed by Metta and Schlotterer are less up regulated in ovaries and have higher chance to be expressed in meiotic cells of spermatogenesis when compared to X-linked genes. Conclusions: The criteria used to select retrogenes and the sex-biased expression data based on whole adult flies generated a segmental dataset of female-biased and unbiased expressed genes that was unable to detect the higher propensity of autosomal retrogenes to be expressed in males. Thus, there is no support for the authors' view that the movement of new retrogenes, which originated from X-linked parental genes, was not driven by selection. Therefore, selection-based genetic models remain the most parsimonious explanations for the observed chromosomal distribution of retrogenes.

Determination of the intrinsic kinetic parameters of sulfide-oxidizing autotrophic denitrification in differential reactors containing immobilized biomass

Nitrogen removal coupled with sulfide oxidation has potential for the treatment of effluents from anaerobic reactors because they contain sulfide, which can be used as an endogenous electron donor for denitrification. This work evaluated the intrinsic kinetics of sulfide-oxidizing autotrophic denitrification via nitrate and nitrite in systems containing attached cells. Differential reactors were fed with nitrified synthetic domestic sewage and different sulfide concentrations. The intrinsic kinetic parameters of nitrogen removal were determined when the mass transfer resistance was negligible. This bioprocess could be described by a half-order kinetic model for biofilms. The half-order kinetic coefficients ranged from 0.425 to 0.658 mg N-1/2 L-1/2 h(-1) for denitrification via nitrite and from 0.190 to 0.609 mg N-1/2 L-1/2 h(-1) for denitrification via nitrate. In this latter, the lower value was due to the use of electrons donated from intermediary sulfur compounds whose formation and subsequent consumption were detected. (C) 2011 Elsevier Ltd. All rights reserved.

Exploring the intrinsic polar [4?+?2+] cycloaddition reactivity of gaseous carbosulfonium and carboxonium ions

Gas-phase reactions of model carbosulfonium ions (CH3-S+?=?CH2; CH3CH2-S+?=?CH2 and Ph-S+?=?CH2) and an O-analogue carboxonium ion (CH3-O+?=?CH2) with acyclic (isoprene, 1,3-butadiene, methyl vinyl ketone) and cyclic (1,3-cyclohexadiene, thiophene, furan) conjugated dienes were systematically investigated by pentaquadrupole mass spectrometry. As corroborated by B3LYP/6-311?G(d,p) calculations, the carbosulfonium ions first react at large extents with the dienes forming adducts via simple addition. The nascent adducts, depending on their stability and internal energy, react further via two competitive channels: (1) in reactions with acyclic dienes via cyclization that yields formally [4?+?2+] cycloadducts, or (2) in reactions with the cyclic dienes via dissociation by HSR loss that yields methylenation (net CH+ transfer) products. In great contrast to its S-analogues, CH3-O+?=?CH2 (as well as C2H5-O+?=?CH2 and Ph-O+?=?CH2 in reactions with isoprene) forms little or no adduct and proton transfer is the dominant reaction channel. Isomerization to more acidic protonated aldehydes in the course of reaction seems to be the most plausible cause of the contrasting reactivity of carboxonium ions. The CH2?=?CH-O+?=?CH2 ion forms an abundant [4?+?2+] cycloadduct with isoprene, but similar to the behavior of such alpha,beta-unsaturated carboxonium ions in solution, seems to occur across the C?=?C bond. Copyright (c) 2012 John Wiley & Sons, Ltd.

Efficiency of extrinsic and intrinsic charge-carrier photogeneration processes obtained from the steady-state photocurrent action spectra of poly(p-phenylene vinylene) derivatives

The efficiency of the charge-carrier photogeneration processes in poly(2,5-bis(3',7'-dimethyl-octyloxy)-1,4-phenylene vinylene) (OC(1)OC10-PPV) has been analyzed by the spectral response of the photocurrent of devices in ITO/polymer/Al structures. The symbatic response of the photocurrent action spectra of the OC1OC10-PPV devices, obtained for light-excitation through the ITO electrode and for forward bias, has been fitted using a phenomenological model which considers that the predominant transport mechanism under external applied electric field is the drift of photogenerated charge-carriers, neglecting charge-carrier diffusion. The proposed model takes into account that charge-carrier photogeneration occurs via intermediate stages of bounded pairs (excitonic states), followed by dissociation processes. Such processes result in two different contributions to the photoconductivity: The first one, associated to direct creation of unbound polaron pairs due to intrinsic photoionization; and the second one is associated to secondary processes like extrinsic photoinjection at the metallic electrodes. The results obtained from the model have shown that the intrinsic component of the photoconductivity at higher excitation energies has a considerably higher efficiency than the extrinsic one, suggesting a dependence on the photon energy for the efficiency of the photogeneration process.

Intrinsic organization of the suprachiasmatic nucleus in the capuchin monkey

The suprachiasmatic nucleus (SCN), which is the main circadian biological clock in mammals, is composed of multiple cells that function individually as independent oscillators to express the self-sustained mRNA and protein rhythms of the so-called clock genes. Knowledge regarding the presence and localization of the proteins and neuroactive substances of the SCN are essential for understanding this nucleus and for its successful manipulation. Although there have been advances in the investigation of the intrinsic organization of the SCN in rodents, little information is available in diurnal species, especially in primates. This study, which explores the pattern of expression and localization of PER2 protein in the SCN of capuchin monkey, evaluates aspects of the circadian system that are common to both primates and rodents. Here, we showed that PER2 protein immunoreactivity is higher during the light phase. Additionally, the complex organization of cells that express vasopressin, vasoactive intestinal polypeptide, neuron-specific nuclear protein, calbindin and calretinin in the SCN, as demonstrated by their immunoreactivity, reveals an intricate network that may be related to the similarities and differences reported between rodents and primates in the literature.