Hiposialia por activación de receptores de cannabinoides en la glándula submaxilar. Revisión

El presente trabajo aporta evidencia de la presencia de receptores de cannabinoides en la glándula submaxilar de la rata, cuya expresión se circunscribe a componentes acinares y ductales. A su vez, los resultados expuestos confirman la participación de los receptores de cannabinoides en el control de la secreción salival, y por ende aportan una explicación empírica a la hiposialia observada luego del consumo de marihuana.Fil: Fernández Solari, Jose Javier. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;Fil: Ossola, Cesar Angel. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina;Fil: Prestifilippo, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina;Fil: Elverdin, Juan Carlos. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina

Incisivo lateral superior con dos raíces y dos conductos. Caso Clínico.

Las anomalías en la morfología del incisivo lateral superior son de muy baja frecuencia. Las anomalías de desarrollo radicular pueden presentarse como alteraciones tanto en el número de conductos, como en el número de raíces, así como en ambas regiones a la vez. En el presente trabajo, se reporta el caso de un paciente que se presenta a la consulta con malestar en el incisivo lateral superior izquierdo. En la radiografía preoperatoria se detectó la presencia de dos conductos y dos raíces, sin anomalía morfológica de su corona clínica, con requerimiento de tratamiento endodóntico. Concluimos que una correcta interpretación de las imágenes radiográficas preoperatorias es esencial, para poder detectar estas variantes y tomar las consideraciones necesarias para el adecuado tratamiento endodóntico.Fil: Martinez, P.. Universidad de Buenos Aires. Facultad de Odontología; Argentina;Fil: Boldo, M.. Universidad de Buenos Aires. Facultad de Odontología; Argentina;Fil: Corominola, P.. Universidad de Buenos Aires. Facultad de Odontología; Argentina;Fil: Sierra, L.. Universidad de Buenos Aires. Facultad de Odontología; Argentina;Fil: Lenarduzzi, A.. Universidad de Buenos Aires. Facultad de Odontología; Argentina;Fil: Fernández Solari, Jose Javier. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina;Fil: Rodriguez, P.. Universidad de Buenos Aires. Facultad de Odontología; Argentina

Endocannabinoids mediate hyposalivation induced by inflammogens in the submandibular glands and hypothalamus

Objective: The aim of this study was to investigate the factors that could participate on salivary glands hypofunction during inflammation and the participation of endocannabinoids in hyposalivation induced by the presence of inflammogens in the submandibular gland (SMG) or in the brain. Design: Salivary secretion was assessed in the presence of inflammogens and/or the cannabinoid receptor antagonist AM251 in the SMG or in the brain of rats. At the end of the experiments, some systemic and glandular inflammatory markers were measured and histopathological analysis was performed. Results: The inhibitory effect observed 1 h after lipopolysaccharide (LPS, 50 μg/50 μl) injection into the SMG (ig) was completely prevented by the injection of AM251 (5 μg/50 μl) by the same route (P < 0.05). The LPS (ig)-induced increase in PGE2 content was not altered by AM251 (ig), while the glandular production of TNFa induced by the endotoxin (P < 0.001) was partially blocked by it. Also, LPS injection produced no significant changes in the wet weight of the SMG neither damage to lipid membranes of its cells, nor significant microscopic changes in them, after hispopathological analysis, compared to controls. Finally, TNFα (100 ng/5 μl) injected intracerebro-ventricularly (icv) inhibited methacholine-induced salivary secretion evaluated 30 min after (P < 0.01), but the previous injection of AM251 (500 ng/5 μl, icv) prevented completely that effect. Conclusion: We conclude that endocannabinoids mediate the hyposialia induced by inflammogens in the SMG and in the brain. The hypofunction would be due to changes on signalling pathway produced by inflammatory compounds since anatomical changes were not observed. © 2013 Elsevier Ltd. All rights reserved.Fil: Prestifilippo, Juan Pablo. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; ArgentinaFil: Medina, Vanina Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaFil: Mohn, Claudia Ester. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Rodriguez, P. A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - La Plata. Unidad de Administración Territorial; Argentina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Elverdin, Juan Carlos. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Fernández Solari, Jose Javier. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Alcohol and endocannabinoids: neuroendocrine interactions in the reproductive axis

Marihuana and alcohol consumption affect adversely reproduction by inhibiting the hypothalamic–pituitary–gonadal axis. The endocannabinoid system, present in the central nervous system and in peripheral tissues, participates in the regulation of hormones involved in the reproductive physiology such as luteinizing hormone, prolactin and oxytocin. This system is activated in response to pathophysiological conditions such as stress and inflammatory/infectious states as well as alcoholism and drug consumption acting as a negative modulator of reproductive function. The secretion of luteinizing hormone from the adenohypophysis is reduced, mainly through hypothalamic inhibitory action of cannabinoids and alcohol on luteinizing hormone releasing hormone release from its nervous terminals in the median eminence. This inhibitory effect is mediated, at least in part, by the activation of cannabinoid type 1 receptors. Cannabinoids also inhibit prolactin release from the lactotropes in the adenohypophysis acting locally and by increasing the release of hypothalamic dopamine mainly from tuberoinfundibular dopaminergic neurons in the external layer of the median eminence. On the contrary, ethanol stimulates prolactin release from the adenohypophysis as well as oxytocin from the neurohypophysis. Besides, endocannabinoids modulate oxytocin synthesis and release from the hypothalamic magnocellular neurons and neurohypophysis. In summary, all the results exposed in the present review suggest that there is interplay between the endocannabinoid system, hormones and neuropeptides in the control of reproduction and that this system mediates, at least in part, ethanol adverse effects on reproductive function.Fil: Besuhli, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: de Laurentiis, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Fernández Solari, Jose Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin

The inhibitory effect of anandamide on oxytocin and vasopressin secretion from neurohypophysis is mediated by nitric oxide

The neurohypophyseal hormones oxytocin (OT) and vasopressin (VP) are involved in behavioral, autonomic and neuroendocrine functions. Both peptides are synthesized in magnocellular neurons of paraventricular and supraoptic nuclei at hypothalamic level whose axons terminate in the neurohypophysis (NH), from where OT and VP are released into the systemic circulation. NH contains abundant nitric oxide (NO) synthase suggesting that NO plays a role in the release of these neuropeptides. The endocannabinoid system is present in magnocellular neurons of the hypothalamic neurohypophyseal system, and we have previously demonstrated that endocannabinoids modulate OT secretion at hypothalamic level. In the present work, we investigated the in vitro effect of the endocannabinoid anandamide (AEA) on OT and VP release from NH of untreated adult male rats and the involvement of NO in this action. Our results showed that AEA decreased OT and VP secretion from NH. AEA action was mediated by NO, since the inhibition of NO synthesis completely blocked this inhibitory effect. We found that cannabinoid receptor type 2 (CB2) and transient receptor potential cation channel subfamily V member 1 (TRPV1) are involved in the inhibitory effect of AEA because AM630 and capsazepine, CB2 and TRPV1 antagonists respectively, but not AM251, a CB1 antagonist, blocked AEA effect at neurohypophyseal level. These findings revealed an interaction between endocannabinoid, nitric oxide and oxytocin/vasopressin systems that could be involved in the modulation of homeostatic, behavioral and reproductive processes.Fil: Luce, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Fernández Solari, Jose Javier. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Besuhli, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: de Laurentiis, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentin

Endocannabinoid system participates in the neuroendocrine control of homeostasis

The hypothalamo-neurohypophyseal system plays a role in homeostasis under a variety of stress conditions, including endotoxemia. Oxytocin (OXT) and vasopressin (VP) are important hormones synthesized by neurons in the hypothalamic paraventricular and supraoptic nuclei and released into different brain regions and from the neurohypophyseal terminals into the blood in response to many patho-physiological stimuli. However, the mechanism that controls OXT and VP secretion has not been fully elucidated. Nitric oxide (NO) is a known mediator that regulates the release of these hormones. The endocannabinoid system is a new intercellular system that modulates several neuroendocrine actions. Endocannabinoids (eCB) are released as retrograde messengers by many neurons, including hypothalamic magnocellular neurons and cannabinoid receptors are localized within these neurons, as well as in the anterior and posterior pituitary lobes, suggesting an eCB role in the production and release of OXT and VP. Lipopolysaccharide (LPS) injection is a model used as immune challenge. LPS causes a neuroendocrine response that is mediated by cytokines, tumor necrosis factor-α being one of them. We focused on NO and endocannabinoid system participation on OXT and VP production and secretion during basal and stress conditions and found that eCB affect basal OXT and VP secretion by acting differently at each level of the hypothalamo-neurohypophyseal system. After LPS, there is an increase in eCB synthesis that enhances OXT secretionFil: de Laurentiis, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Fernández Solari, Jose Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Mohn, Claudia Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Zorrilla Zubilete, María Aurelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Besuhli, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin

Long-term treatment with methanandamide attenuates LPS-induced periodontitis in rats

OBJECTIVE: Evidence exists of the anti-inflammatory and immunological properties of endocannabinoids in various tissues; the aim of the present study was therefore to assess the effect of long-term treatment with the synthetic cannabinoid methanandamide (Meth-AEA) on the progression of periodontitis in rats. MATERIALS AND METHODS: Periodontitis was induced by injecting LPS (1 mg/ml) into the gingiva around the neck of the first upper and lower molars, and into the inter-dental space between the first and second molars. This protocol was repeated for 6 weeks on days 1, 3, and 5 of each week. RESULTS: Long-term treatment with topical Meth-AEA (500 ng/ml), applied daily to gingival tissue of rats induced with periodontitis, significantly diminished the alveolar bone loss, measured as the distance between the cemento-enamel junction and the alveolar crest, in both maxillary and mandibular first molars, compared to rats without treatment (P < 0.05). The treatment also reduced the production of some biological mediators of periodontal disease augmented by LPS, such as tumor necrosis factor alpha (from 119.4 ± 9.9 pg/mg protein to 75.1 ± 10.8, P < 0.05) and nitric oxide produced by inducible nitric oxide synthase (from 507.7 ± 107.1 pmol/min/mg protein to 163.1 ± 53.9, P < 0.01). CONCLUSION: These results demonstrate the beneficial effects of treatment with Meth-AEA on gingival tissue of rats with periodontitis.Fil: Ossola, César Ángel. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Surkin, Pablo Nicolas. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pugnaloni, Antonela. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Mohn, Claudia Ester. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Elverdin, Juan Carlos. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Fernández Solari, Jose Javier. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Reduced methacholine-induced submandibular salivary secretion in rats with experimental periodontitis

OBJECTIVE: Saliva is the first barrier to the entry of bacteria and viruses into the body and is considered a necessary instrument in oral health. Intraperitoneal injection of lipopolysaccharide endotoxins results in submandibular gland (SMG) hyposalivation. The objective of present studies was to assess if periodontitis, a chronic inflammatory disease caused by oral bacteria, alters cholinergic-induced SMG salivary secretion. DESIGN: An experimental periodontitis model (EP) (cotton thread ligature around the neck of the first lower molars) was used. Male Wistar rats (300-380g) were randomly divided into 3 groups: control, 7 days-bilateral EP and 7 days-unilateral EP (to study if there were different effects at the ipsilateral and contralateral side). The following determinations were performed in SMG: (1) dose-response curves to the cholinergic agonist methacholine, (2) prostaglandin E (PGE) content, (3) inducible nitric oxide synthase (iNOS) activity and (4) histology of gland sections. RESULTS: The molars with EP, no matter the group, exhibited significant and similar bone loss (p<0.001). Bilateral EP reduced methacholine-induced salivary secretion (p<0.05, dose 1μg/kg; p<0.001, dose 3-30μg/kg), increased PGE content (p<0.01), stimulated iNOS activity (p<0.05). Ipsilateral glands of unilateral EP animals presented lower methacholine-induced salivary secretion (p<0.05, dose 3μg/kg; p<0.001, dose 10-30μg/kg), and higher PGE content than contralaterals (p<0.001). In turn, at 3 and 10μg/kg of methacholine, contralateral glands showed significantly lower secretion than control animals (p<0.001). Histological studies of glands revealed partial loss of secretor granular material and periductal oedema in the bilateral and unilateral EP groups as compared to controls. CONCLUSIONS: As far as we know, the present results demonstrate for the first time that EP reduces methacholine-induced SMG salivary secretion.Fil: Amer, Mariano. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Elverdin, Juan Carlos. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Fernández Solari, Jose Javier. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chiarenza, Ana P.. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Bioquímica General y Bucal; ArgentinaFil: Vacas, María I.. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Bioquímica General y Bucal; Argentin

Adrenal gland responses to lipopolysaccharide after stress and ethanol administration in male rats

All forms of stress, including restraint stress (RS) and lipopolysaccharide (LPS) administration, activate the hypothalamic–pituitary–adrenal (HPA) axis. LPS binds to a recognition protein (CD14) and toll-like receptor 2/4 in different cells and tissues, including the adrenal gland, to induce the production of cytokines and cause upregulation of cyclooxygenase and nitric oxide synthase (NOS) enzymes. Acute ethanol exposure activates the HPA axis, but in some conditions prolonged administration can dampen this activation as well as decrease the inflammatory responses to LPS. Therefore, this study was designed to evaluate the adrenal response to a challenge dose of LPS (50 mg/kg) injected i.p., after submitting male rats to RS, twice a day (2 h each time) for 5 days and/or ethanol administration (3 g/kg) by gavage also for 5 days, twice daily. At the end of the experiment, plasma corticosterone concentrations and adrenal gland content of prostaglandin E (PGE) and NOS activity were measured as stress mediators. The results showed that repetitive ethanol administration attenuated the adrenal stress response to LPS challenge alone and after RS, by preventing the increase in plasma corticosterone concentrations and by decreasing the PGE content and NOS activity in the adrenal gland. Therefore, we conclude that moderate alcohol consumption could attenuate the effects of psychophysical stress and impair an inflammatory response.Fil: Mohn, Claudia Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Fernández Solari, Jose Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: de Laurentiis, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Bornstein, S. R.. Carl Gustav Carus University Hospital; AlemaniaFil: Ehrhat Bornstein, M.. Carl Gustav Carus University Hospital; AlemaniaFil: Besuhli, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentin