Absence of delta-9-tetrahydrocannabinol dysphoric effects in dynorphin-deficient mice

The involvement of dynorphin on Delta-9-tetrahydrocannabinol (THC) and morphine responses has been investigated by using mice with a targeted inactivation of the prodynorphin (Pdyn) gene. Dynorphin-deficient mice show specific changes in the behavioral effects of THC, including a reduction of spinal THC analgesia and the absence of THC-induced conditioned place aversion. In contrast, acute and chronic opioid effects were normal. The lack of negative motivational effects of THC in the absence of dynorphin demonstrates that this endogenous opioid peptide mediates the dysphoric effects of marijuana.

Role of the cannabinoid system in the effects induced by nicotine on anxiety-like behaviour in mice

Rationale: Acute behavioural effects and motivational responses induced by nicotine can be modulated by the endocannabinoid system supporting the existence of a physiological interaction between these two systems. Objectives: The present study was designed to examine the possible involvement of the cannabinoid system in the anxiolytic- and anxiogenic-like responses induced by nicotine in mice. Methods: Animals were only exposed once to nicotine. The acute administration of low (0.05, sc) or high (0.8 mg/kg, sc) doses of nicotine produced opposite effects in the elevated plus-maze, i.e., anxiolytic- and anxiogenic-like responses, respectively. The effects of the pretreatment with the CB1 cannabinoid receptor antagonist, rimonabant (0.25, 0.5 and 1 mg/kg, ip), and the cannabinoid agonist, 9-tetrahydrocannabinol (0.1 mg/kg, ip), were evaluated on the anxiolytic- and anxiogenic-like responses induced by nicotine. Results: Rimonabant completely abolished nicotine-induced anxiolytic-like effects and increased the anxiogenic-like responses of nicotine, suggesting an involvement of CB1 receptors in these behavioural responses. On the other hand, 9-tetrahydrocannabinol failed to modify nicotine anxiolytic-like responses, but attenuated its anxiogenic-like effects. In addition the association of non-effective doses of 9-tetrahydrocannabinol and nicotine produced clear anxiolytic-like responses. Conclusions: These results demonstrate that the endogenous cannabinoid system is involved in the regulation of nicotine anxiety-like behaviour in mice, and provide new findings to support the use of cannabinoid antagonists in the treatment of tobacco addiction.

Motivational effects of cannabinoids are mediated by μ-opioid and k-opioid receptor

Repeated THC administration produces motivational and somaticadaptive changes leading to dependence in rodents. Toinvestigate the molecular basis for cannabinoid dependenceand its possible relationship with the endogenous opioid system,we explored Δ9-tetrahydrocannabinol (THC) activity in mice lacking μ-, δ- or κ-opioid receptor genes. Acute THCinduced hypothermia, antinociception, and ypolocomotion remained unaffected in these mice, whereas THC tolerance and withdrawal were minimally modified in mutant animals. In contrast, profound phenotypic changes are observed in several place conditioning protocols that reveal both THC rewarding and aversive properties. Absence of μ receptors abolishes THC place preference. Deletion of κ receptors ablates THC place aversion and furthermore unmasks THC place preference. Thus, an opposing activity of μ- and κ-opioid receptors in modulating reward pathways forms the basis for the dual euphoric–dysphoric activity of THC.

MDMA attenuates THC withdrawal syndrome in mice

3, 4-Methylenedioxymethamphetamine (MDMA) and cannabis are widely abused illicit drugs that are frequently consumed in combination. Interactions between these two drugs have been reported in several pharmacological responses observed in animals, such as body temperature, anxiety, cognition and reward. However, the interaction between MDMA and cannabis in addictive processes such as physical dependence has not been elucidated yet. In this study, the effects of acute and chronic MDMA were evaluated on the behavioral manifestations of Δ9-tetrahydrocannabinol (THC) abstinence in mice. THC withdrawal syndrome was precipitated by injecting the cannabinoid antagonist rimonabant (10 mg/kg, i.p.) in mice chronically treated with THC, and receiving MDMA (2.5, 5 and 10 mg/kg i.p.) or saline just before the withdrawal induction or chronically after the THC administration. Both, chronic and acute MDMA decreased in a dose-dependent manner the severity of THC withdrawal. In vivo microdialysis experiments showed that acute MDMA (5 mg/kg, i.p.) administration increased extracellular serotonin levels in the prefrontal cortex, but not dopamine levels in the nucleus accumbens. Our results also indicate that the attenuation of THC abstinence symptoms was not due to a direct interaction between rimonabant and MDMA nor to the result of the locomotor stimulating effects of MDMA. The modulation of the cannabinoid withdrawal syndrome by acute or chronic MDMA suggests a possible mechanism to explain the associated consumption of these two drugs in humans.

Els primers llums del Delta

Treball de recerca realitzat per un alumne d'ensenyament secundari i guardonat amb un Premi CIRIT per fomentar l'esperit científic del Jovent l'any 2009. El treball és un estudi de l’evolució, tan tècnica com estètica dels fars paral•lela als avenços tecnològics i prenent com a protagonistes els singulars fars de ferro que es varen construir durant la segona meitat del segle XIX i varen funcionar durant un llarguíssim període en el delta de l’Ebre. L’estructura de ferro, ancorada directament sobre les sorres del delta va donar un caràcter especial a aquestes construccions que, d’altra banda, constituïen una tipologia única a Catalunya i a Espanya. Aquests fars van rebre el nom del lloc on foren ubicats estratègicament. De sud a nord: far de la Banya, far de Buda i far del Fangar. Els van projectar conjuntament, es van encendre per primera vegada el mateix dia, van ser l’habitatge dels seus faroners, van anar evolucionant tècnicament tots tres però el final de cadascun d’ells va ser molt diferent. La història dels fars de ferro ha anat lligada al paisatge i la vida d’aquestes singulars terres del Delta i després de més d’un segle de servei foren substituïts per altres que estèticament i tècnicament res tenen a veure amb els seus antecessors.

Specific (granulomatous) oral lesions of sarcoidosis: Report of two cases

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology that usually presents with bilateral hiliar adenopathies, pulmonary infiltrations, and ocular and cutaneous lesions. The specific cutaneous lesions, or granulomatous, are produced in from 9% to 37% of patients with systemic sarcoidosis. Nevertheless, few patients have been described having specific lesions from sarcoidosis in the oral mucous membrane. We present 2 patients with systemic sarcoidosis who developed specific sarcoidosis lesions in the oral mucous membrane. The first patient presented a plaque on the tongue of a chronic nature associated with facial lupus pernio. The second patient presented a rapidly growing nodular lesion on the lower lip that was in fact the presentation sign of the disease. Although infrequent, oral lesions may constitute the first sign of systemic sarcoidosis. For this reason the oral mucous membrane needs to be explored when there is suspicion of sarcoidosis, and systemic sarcoidosis must be included in the differential diagnosis of oral granulomatous lesions.

Treatment of oral mucocele - scalpel versus C02 laser

Objective: To compare the results obtained after oral mucocele resection with the scalpel versus the CO2 laser, based on the complications and recurrences after surgery Patients and Methods: Of the 68 patients we studied who have mucocele, 38 were resected with a scalpel and the remaining 30 with the CO2 laser (5-7 W). Patient sex and age were documented, along with location of the lesion as well as size, symptoms, duration, etiological factors, type of treatment, complications and recurrences after surgical removal. Results: The sample comprised 40 males and 28 females, aged between 6-65 years. The histological diagnosis was extravasation mucocele in 95% of the cases. The most frequent location was the lower lip (73.5%). The mean lesion diameter was 9 mm , and in most cases no evident etiological factor was recorded. The mean duration of the lesion was 4 months. Among the cases of conventional surgical removal of mucocele, recurrence was recorded in 8.8% of the cases, and 13.2% of the patients suffered postoperative complications - the most frequent being the presence of fibrous scars. There were no complications or relapses after a minimum follow-up of 12 months in the cases subjected to CO2 laser treatment. Conclusions: Oral mucocele ablation with the CO2 laser offers more predictable results and fewer complications and recurrences than conventional resection with the scalpel

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male SpragueDawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokineticpharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

Micromorphological characterization and lithification of microbial mats from the Ebro Delta (Spain)

The structural organization of microbial mats from the Ebro Delta (Spain) and their accretion and partial lithification processes were explored using scanning electron microscopy in back-scattered electron mode and low-temperature scanning electron microscopy. Two differentiated zones were distinguished in a transverse section of a fragment taken from the mat at a depth of 2.5 mm. The first consisted of an upper layer in which the dominant microorganisms, Microcoleus spp., actively grew in an embedded slack matrix of exopolysaccharides. Microcoleus filaments were oriented parallel to the surface and to each other, with filaments below arranged perpendicularly to one another but without crossing. Most of the minerals present were allochthonous grains of calcium phosphate biocorroded by cyanobacteria. The second zone was below a depth of 1 mm and made up of accretion layers with large deposits of calcium carbonate and smaller amounts of calcium phosphate of biological origin. The predominance of a particular type of mineral precipitation with a characteristic external shape and/or texture within a zone, e.g., sponge-like deposits of calcium phosphate, appears to depend on the taxa of the prevailing microorganisms

Study of the effect of oral health on physical condition of professional soccer players of the Football Club Barcelona

Objectives: The objective of this study was to evaluate the oral health status of professional soccer players of F.C. Barcelona and its relation to the incidence of sport lesions. Methods: Thirty professional soccer players were consecutively evaluated in the seasons 2003/4, 2004/5 and 2005/6. A research protocol to assess their oral health was developed. DMFT, Quigley & Hein plaque index (PI), Löe & Silness gingival index (GI), World Health Organization malocclusion index, Ramfjord teeth probing pocket depth (PPD), TMJ examination and history of dental trauma were recorded. All physical injuries sustained by players during the season were documented from F.C. Barcelona medical services. Results: Mean DMFT score was 5.7 (SD 4.1), Quigley & Hein plaque index score was 2.3 (SD 1.1), Löe & Silness gingival index was 1.1 (SD 0.8), and periodontal pocket depth was 1.9 mm (SD 0.3). Pearson"s analysis showed a significant correlation between PI and GI (p<0.01). Nine players (30%) presented bruxism - the same proportion of those with severe malocclusion. Seven (23.3%) players had suffered uncomplicated crown fractures. The mean incidence of physical injuries was 8 (SD 3.4) per player. PI and PPD showed a statistically significant correlation to muscle injuries (p<0.05). Conclusions: Soccer players, despite intensive medical follow-up, have significant oral health problems such as untreated caries, gingivitis or malocclusion, and suffer dental trauma as a result of sports activities. Their physical condition could also be associated to oral health

Buccodental health and oral mucositis. Clinical study in patients with hematological diseases

Objectives: The objective of the present study is to assess whether a good buccodental status (evaluated by means of dentogingival indices), is associated with a lower incidence and severity of oral mucositis in patients with hematological diseases who receive treatment with chemotherapy or bone marrow transplant. Study design: The study was carried out on 97 patients admitted to the Hematology Service of the Hospital Duran y Reynals in Barcelona during 2002-2003. These patients received treatment with chemotherapy or conditioning prior to bone marrow transplant. A descriptive study was made, analyzing oral hygiene, one dental index, and two gingivales indices, and evaluating their relationship with the appearance of mucositis. Results: The patients with high plaque (PI) and gingival (GI) indices during chemotherapy presented a higher percentage of mucositis (77.4% and 65.7% respectively) against those who had little or no visible plaque. In the case of the PI, the differences were statistically significant (p=0.015). Likewise, patients who brushed their teeth 3 times/day presented mucositis in only 26.7% of cases, against those who did not brush, or brushed only once a day (65.9% and 68.4%), these differences also being statistically significant (p=0.013). The CAO showed similar results in patients with or without mucositis (7.59 and 7.03 respectively). Conclusions: In our study, a good gingival status as well as good oral hygiene during chemoradiotherapy is associated with a lower incidence and severity of mucositis.

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

Clinical features of oral lichen planus. A retrospective study of 65 cases

Objectives: To describe the clinical features of patients diagnosed with oral lichen planus (OLP) and to establish the prevalence of its malignant transformation in our setting. Study design: A retrospective study was made of 65 patients clinically and histologically diagnosed with OLP in the Service of Oral Surgery (Dental Clinic of the University of Barcelona, Spain) in the period 1990-2005. A descriptive and bivariate statistical analysis was made. Results: The mean patient age was 59 years (SD ± 14.9). Most of the patients (61%) were women, and the most frequent location of the lesions was the buccal mucosa (90.8%). White forms of OLP were noted in 66% of the cases, and 46.2% of the patients reported symptoms of some kind. The patients diagnosed with diabetes mellitus (20%) showed a larger proportion of red lesions (p=0.088). No statistically significant association was observed between chronic liver disease and the OLP lesion types or symptoms. Two cases of squamous cell carcinoma were identified in two patients previously or simultaneously diagnosed with OLP. A statistically significant correlation was observed between dysplastic changes / malignization of the lesions and smoking habit (p=0.019). An association to alcohol abuse was also noted, though in this case statistical significance was not reached (p=0.085). Conclusions: The clinical features of our study population were similar to those described in other studies. Diabetic patients with OLP were seen to be more susceptible to the development of atrophic-erosive lesions. Smokers and/or patients with alcohol abuse in turn showed a greater tendency to develop dysplastic changes / malignization in the histopathological study of the lesions

Graft materials in oral surgery: revision

Oral implantology is a common procedure in dentistry, especially for fully or partially edentulous patients. The implants must be placed in the best location from both the aesthetic and functional point of view. Because of this it is increasingly more frequent to resort to regeneration techniques that use substitutes of the bone itself, in order to be able to insert the implants in the most appropriate location. Material and Methodology: A review was performed on the literature from the last ten years based on the following search limitations: "graft materials', 'allograft', 'xenograft', 'autologous graft" and 'dentistry". Results: 241 works were obtained that after reading their respective summaries, they were reduced to 38, and 9 previous works were included in order to summarize the concepts. Discussion: Autologous grafts are the 'gold standard' of the bone regeneration. They have obvious advantages, but they also have drawbacks. This is why allogeneic and xenogeneic tissues are used. The former because of their clear similarity with the recipient's tissue and the latter due to their wide availability. Given that these grafts also have drawbacks, the industry has developed synthetic materials that have properties similar to those of human bone tissue. However, as of today, the ideal material to substitute human bone has not yet been found. In recent years the tendency has been to combine these synthetic materials with the patient's own bone, which is extracted during drilling in implant placement, with bone marrow aspiration, or with bone morphogenetic proteins. Thus the intention is to equip these substances with the osteogenic capacity. Conclusions: There is currently no ideal graft material, with the exception of those materials that come directly from the patient. We hope that in the coming years we will have products that will allow us to perform rehabilitations with better results and provide a better quality of life for our patients, especially those who have more complex situations to resolve, like the patients that are operated on for head and neck cancer