Silicon nanocluster sensitization of erbium ions under low-energy optical excitation

The sensitizing action of amorphous silicon nanoclusters on erbium ions in thin silica films has been studied under low-energy (long wavelength) optical excitation. Profound differences in fast visible and infrared emission dynamics have been found with respect to the high-energy (shortwavelength) case. These findings point out to a strong dependence of the energy transfer process on the optical excitation energy. Total inhibition of energy transfer to erbium states higher than thefirst excited state (4I13/2) has been demonstrated for excitation energy below 1.82 eV (excitation wavelength longer than 680 nm). Direct excitation of erbium ions to the first excited state (4I13/2)has been confirmed to be the dominant energy transfer mechanism over the whole spectral range of optical excitation used (540 nm¿680 nm).

Heteromeric nicotinic receptors are involved in the sensitization and addictive properties of MDMA in mice

We have investigated the effect of nicotinic receptor ligands in the behavioral sensitization (hyperlocomotion) and rewarding properties (conditioned place preference paradigm, CPP) of 3,4-methylenedioxy-methamphetamine (MDMA) in mice. Each animal received intraperitoneal pretreatment with either saline, dihydro-β-erythroidine (DHβE, 1 mg/kg) or varenicline (VAR, 0.3 mg/kg), 15 min prior to subcutaneous saline or MDMA (5 mg/kg), for 10 consecutive days. On day 1, both DHβE and VAR inhibited the MDMA-induced hyperlocomotion. After 10 days of treatment, MDMA induced a hyperlocomotion that was not reduced (rather enhanced) in antagonist-pretreated animals. This early hyperlocomotion was accompanied by a significant increase in heteromeric nicotinic receptors in cortex that was not blocked by DHβE or VAR. Behavioral sensitization to MDMA was highest 2 weeks after the discontinuation of MDMA treatment. This additional increase in sensitivity was prevented in animals pretreated with DHβE or VAR. At this time, MDMA-treated mice showed a significant increase in heteromeric receptors in cortex that was prevented by DHβE and VAR. An involvement of α7 nicotinic receptors in this effect is ruled out. MDMA (10 mg/kg) induced positive CPP that was abolished by DHβE (2 mg/kg) and VAR (2 mg/kg). Moreover, chronic nicotine pretreatment (2 mg/kg, ip, b.i.d., for 14 days) caused MDMA, administered at a low dose (3 mg/kg), to induce CPP, which would otherwise not occur. Finally, present results point out that heteromeric nicotinic receptors are involved in locomotor sensitization and addictive potential induced by MDMA. Thus, varenicline might be a useful drug to treat both tobacco and MDMA abuse at once.

Heteromeric nicotinic receptors are involved in the sensitization and addictive properties of MDMA in mice

We have investigated the effect of nicotinic receptor ligands in the behavioral sensitization (hyperlocomotion) and rewarding properties (conditioned place preference paradigm, CPP) of 3,4-methylenedioxy-methamphetamine (MDMA) in mice. Each animal received intraperitoneal pretreatment with either saline, dihydro-β-erythroidine (DHβE, 1 mg/kg) or varenicline (VAR, 0.3 mg/kg), 15 min prior to subcutaneous saline or MDMA (5 mg/kg), for 10 consecutive days. On day 1, both DHβE and VAR inhibited the MDMA-induced hyperlocomotion. After 10 days of treatment, MDMA induced a hyperlocomotion that was not reduced (rather enhanced) in antagonist-pretreated animals. This early hyperlocomotion was accompanied by a significant increase in heteromeric nicotinic receptors in cortex that was not blocked by DHβE or VAR. Behavioral sensitization to MDMA was highest 2 weeks after the discontinuation of MDMA treatment. This additional increase in sensitivity was prevented in animals pretreated with DHβE or VAR. At this time, MDMA-treated mice showed a significant increase in heteromeric receptors in cortex that was prevented by DHβE and VAR. An involvement of α7 nicotinic receptors in this effect is ruled out. MDMA (10 mg/kg) induced positive CPP that was abolished by DHβE (2 mg/kg) and VAR (2 mg/kg). Moreover, chronic nicotine pretreatment (2 mg/kg, ip, b.i.d., for 14 days) caused MDMA, administered at a low dose (3 mg/kg), to induce CPP, which would otherwise not occur. Finally, present results point out that heteromeric nicotinic receptors are involved in locomotor sensitization and addictive potential induced by MDMA. Thus, varenicline might be a useful drug to treat both tobacco and MDMA abuse at once.

Counteracting incentive sensitization in severe alcohol dependence using deep brain stimulation of the nucleus accumbens: clinical and basic science aspects

The ventral striatum / nucleus accumbens has been implicated in the craving for drugs and alcohol which is a major reason for relapse of addicted people. Craving might be induced by drug-related cues. This suggests that disruption of craving-related neural activity in the nucleus accumbens may significantly reduce craving in alcohol-dependent patients. Here we report on preliminary clinical and neurophysiological evidence in three male patients who were treated with high frequency deep brain stimulation of the nucleus accumbens bilaterally. All three had been alcohol dependent for many years, unable to abstain from drinking, and had experienced repeated relapses prior to the stimulation. After the operation, craving was greatly reduced and all three patients were able to abstain from drinking for extended periods of time. Immediately after the operation but prior to connection of the stimulation electrodes to the stimulator, local field potentials were obtained from the externalized cables in two patients while they performed cognitive tasks addressing action monitoring and incentive salience of drug related cues. LFPs in the action monitoring task provided further evidence for a role of the nucleus accumbens in goal-directed behaviors. Importantly, alcohol related cue stimuli in the incentive salience task modulated LFPs even though these cues were presented outside of the attentional focus. This implies that cue-related craving involves the nucleus accumbens and is highly automatic.

Itinerari d'educació ambiental: petjades a Comes de Rubió

El Parc Natural de l’Alt Pirineu (PNAP) va ser creat l’any 2003. A causa de la seva recent creació, manca el desenvolupament de moltes de les seves àrees. Actualment, el parc està creant una xarxa d’itineraris d’Educació Ambiental (EA). Per aquesta raó, és interessant dedicar aquest treball al disseny d’un itinerari d’EA a la zona de Comes de Rubió, situada dins l’àmbit territorial del PNAP. L’objectiu principal del present projecte és l’elaboració d’aquest itinerari amb els recursos necessaris per tal que sigui implementable d’una manera immediata. Per tal d’analitzar la viabilitat de l’itinerari s’ha aplicat el protocol de valoració dissenyat pel grup Edukamb. La puntuació que s’ha obtingut ha estat 61 sobre 100, fet que indica que l’itinerari és viable tot i que compta amb algunes mancances. S’ha constatat que les condicions de l’itinerari són idònies per poder ser visitat pel públic en general, entre altres coses per la forma circular de l’itinerari, per tenir 3 km de recorregut i per disposar d’una gran varietat d’aspectes d’interès. En el disseny de l’itinerari s’ha definit el recorregut, s’han determinat els elements d’interès, s’han proposat 5 parades, s’han dissenyat els materials pedagògics, s’ha definit la situació de la senyalització i s’han proposat correccions per a les mancances detectades en el protocol, entre altres, una millora en l’accessibilitat al punt d’inici i la construcció de passeres en els punts potencialment erosionables. Les principals pautes a seguir a l’hora d’elaborar el material pedagògic han estat la integració de l’aspecte social amb el natural i la promoció de la sensibilització envers el medi ambient.

Silicon nanocrystals as an enabling material for silicon Ppotonics

Silicon nanocrystals (Si-nc) is an enabling material for silicon photonics, which is no longer an emerging field of research but an available technology with the first commercial products available on the market. In this paper, properties and applications of Si-nc in silicon photonics are reviewed. After a brief history of silicon photonics, the limitations of silicon as a light emitter are discussed and the strategies to overcome them are briefly treated, with particular attention to the recent achievements. Emphasis is given to the visible optical gain properties of Si-nc and to its sensitization effect on Er ions to achieve infrared light amplification. The state of the art of Si-nc applied in a few photonic components is reviewed and discussed. The possibility to exploit Si-nc for solar cells is also presented. in addition, nonlinear optical effects, which enable fast all-optical switches, are described.

Energy transfer mechanism and Auger effect in Er3+ coupled silicon nanoparticle samples

We report a spectroscopic study about the energy transfer mechanism among silicon nanoparticles (Si-np), both amorphous and crystalline, and Er ions in a silicon dioxide matrix. From infrared spectroscopic analysis, we have determined that the physics of the transfer mechanism does not depend on the Si-np nature, finding a fast (< 200 ns) energy transfer in both cases, while the amorphous nanoclusters reveal a larger transfer efficiency than the nanocrystals. Moreover, the detailed spectroscopic results in the visible range here reported are essential to understand the physics behind the sensitization effect, whose knowledge assumes a crucial role to enhance the transfer rate and possibly employing the material in optical amplifier devices. Joining the experimental data, performed with pulsed and continuous-wave excitation, we develop a model in which the internal intraband recombination within Si-np is competitive with the transfer process via an Auger electron"recycling" effect. Posing a different light on some detrimental mechanism such as Auger processes, our findings clearly recast the role of Si-np in the sensitization scheme, where they are able to excite very efficiently ions in close proximity to their surface. (C) 2010 American Institute of Physics.

Establishment of an in vitro photoassay using THP-1 cells and IL-8 to discriminate photoirritants from photoallergens

At present, there are no in vivo or in vitro methods developed which has been adopted by regulatory authorities to assess photosensitization induced by chemicals. Recently, we have proposed the use of THP-1 cells and IL-8 release to identify the potential of chemicals to induce skin sensitization. Based on the assumption that sensitization and photosensitization share common mechanisms, the aim of this work was to explore the THP-1 model as an in vitro model to identify photoallergenic chemicals. THP-1 cells were exposed to 7 photoallergens and 3 photoirritants and irradiated with UVA light or kept in dark. Non phototoxic allergens or irritants were also included as negative compounds. Following 24 h of incubation, cytotoxicity and IL-8 release were measured. At subtoxic concentrations, photoallergens produced a dose-related increase in IL-8 release after irradiation. Some photoirritants also produced a slight increase in IL-8 release. However, when the overall stimulation indexes of IL-8 were calculated for each chemical, 6 out of 7 photoallergens tested reached a stimulation index above 2, while the entire set of negative compounds had stimulation indexes below 2. Our data suggest that this assay may become a useful cell-based in vitro test for evaluating the photosensitizing potential of chemicals.

Establishment of an in vitro photoassay using THP-1 cells and IL-8 to discriminate photoirritants from photoallergens

At present, there are no in vivo or in vitro methods developed which has been adopted by regulatory authorities to assess photosensitization induced by chemicals. Recently, we have proposed the use of THP-1 cells and IL-8 release to identify the potential of chemicals to induce skin sensitization. Based on the assumption that sensitization and photosensitization share common mechanisms, the aim of this work was to explore the THP-1 model as an in vitro model to identify photoallergenic chemicals. THP-1 cells were exposed to 7 photoallergens and 3 photoirritants and irradiated with UVA light or kept in dark. Non phototoxic allergens or irritants were also included as negative compounds. Following 24 h of incubation, cytotoxicity and IL-8 release were measured. At subtoxic concentrations, photoallergens produced a dose-related increase in IL-8 release after irradiation. Some photoirritants also produced a slight increase in IL-8 release. However, when the overall stimulation indexes of IL-8 were calculated for each chemical, 6 out of 7 photoallergens tested reached a stimulation index above 2, while the entire set of negative compounds had stimulation indexes below 2. Our data suggest that this assay may become a useful cell-based in vitro test for evaluating the photosensitizing potential of chemicals.

Oncobiguanides: Paracelsus" law and nonconventional routes for administering diabetobiguanides for cancer treatment

The dose makes the poison, the common motto of toxicology first expressed by Paracelsus more than 400 years ago, may effectively serve to guide potential applications for metformin and related biguanides in oncology. While Paracelsus' law for the dose-response effect has been commonly exploited for the use of some anti-cancer drugs at lower doses in non-neoplastic diseases (e.g., methotrexate), the opposite scenario also holds true; in other words, higher doses of non-oncology drugs, such as anti-diabetic biguanides, might exert direct anti-neoplastic effects. Here, we propose that, as for any drug, there is a dose range for biguanides that is without any effect, one corresponding to"diabetobiguanides" with a pharmacological effect (e.g., insulin sensitization in type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect inhibition of insulin and growth factor-dependent cancer growth) but with minimal toxicity and another corresponding to 'oncobiguanides' with pharmacological (i.e., direct and strong anticancer activity against cancer cells) as well as toxic effects. Considering that biguanides demonstrate a better safety profile than most oncology drugs in current use, we should contemplate the possibility of administering biguanides through non-conventional routes (e.g., inhaled for carcinomas of the lung, topical for skin cancers, intravenous as an adjunctive therapy, rectal suppositories for rectal cancer) to unambiguously investigate the therapeutic value of high-dose transient biguanide exposure in cancer. Perhaps then, the oncobiguanides, as we call them here, could be viewed as a mechanistically different type of anti-cancer drugs employed at doses notably higher than those used chronically when functioning as diabetobiguanides

A topical microemulsion for the prevention of allergic rhinitis symptoms: results of a randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial (Nares study)

Background: Since barrier protection measures to avoid contact with allergens are being increasingly developed, we assessed the clinical efficacy and tolerability of a topical nasal microemulsion made of glycerol esters in patients with allergic rhinitis. Methods: Randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial in which adult patients with allergic rhinitis or rhinoconjunctivitis due to sensitization to birch, grass or olive tree pollens received treatment with topical microemulsion or placebo during the pollen seasons. Efficacy variables included scores in the mini-RQLQ questionnaire, number and severity of nasal, ocular and lung signs and symptoms, need for symptomatic medications and patients" satisfaction with treatment. Adverse events were also recorded. Results: Demographic characteristics were homogeneous between groups and mini-RQLQ scores did not differ significantly at baseline (visit 1). From symptoms recorded in the diary cards, the ME group showed statistically significant better scores for nasal congestion (0.72 vs. 1.01; p = 0.017) and mean total nasal symptoms (0.7 vs. 0.9; p = 0.045). At visit 2 (pollen season), lower values were observed in the mini-RQLQ in the ME group, although there were no statistically significant differences between groups in both full analysis set (FAS) and patients completing treatment (PPS) populations. The results obtained in the nasal symptoms domain of the mini-RQLQ at visit 2 showed the highest difference (−0.43; 95% CI: -0.88 to 0.02) for the ME group in the FAS population. The topical microemulsion was safe and well tolerated and no major discomforts were observed. Satisfaction rating with the treatment was similar between the groups. Conclusions: The topical application of the microemulsion is a feasible and safe therapy in the prevention of allergic symptoms, particularly nasal congestion.