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1.
J Dent Res ; 99(3): 329-338, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31913775

RESUMEN

Macrophages are immune cells with high plasticity that perform many functions related to tissue injury and repair. They are generally categorized as 2 functional phenotypes: M1 (proinflammatory) and M2 (anti-inflammatory and prohealing). To investigate the role of macrophages in human dental pulp, we examined the localization and distributional alterations of macrophages in healthy dental pulp as well as during the reparative process of pulp capping with mineral trioxide aggregate (MTA) and in cariously inflamed pulp of adult human teeth. We also quantified the populations of M1/M2 macrophages in healthy dental pulp by flow cytometric analysis. CD68+CD86+ cells (M1 phenotype) and CD68+CD163+ cells (M2 phenotype) were 2.11% ± 0.50% and 44.99% ± 2.22%, respectively, of 2.96% ± 0.41% CD68+ cells (pan-macrophages) in whole healthy dental pulp. Interestingly, M2 phenotype macrophages were associated with Schwann cells in healthy pulp, during mineralized bridge formation, and in pulp with carious infections in vivo. Furthermore, the M2 macrophages associated with Schwann cells expressed brain-derived neurotrophic factor (BDNF) under all in vivo conditions. Moreover, we found that plasma cells expressed BDNF. Coculture of Schwann cells isolated from human dental pulp and human monocytic cell line THP-1 showed that Schwann cells induced M2 phenotypic polarization of THP-1 cell-derived macrophages. The THP-1 macrophages that maintained contact with Schwann cells were stimulated, leading to elongation of their cell shape and expression of M2 phenotype marker CD163 in cocultures. In summary, we revealed the spatiotemporal localization of macrophages and potent induction of the M2 phenotype by Schwann cells in human dental pulp. M2 macrophages protect neural elements, whereas M1 cells promote neuronal destruction. Therefore, suppressing the neurodestructive M1 phenotype and maintaining the neuroprotective M2 phenotype of macrophages by Schwann cells may be critical for development of effective treatment strategies to maintain the viability of highly innervated dental pulp.


Asunto(s)
Pulpa Dental , Macrófagos , Células de Schwann , Recubrimiento de la Pulpa Dental , Humanos , Fenotipo
2.
Int Endod J ; 51(11): 1187-1195, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29679496

RESUMEN

AIM: To explore the expression profile of CD45+/pro-collagen I+ fibrocytes in intact dental pulps as well as during wound healing in adult dental pulp tissue. METHODOLOGY: A total of 16 healthy permanent teeth were obtained from young patients (18 to 25 years) undergoing orthodontic treatment. Routine pulp capping with mineral trioxide aggregate (MTA) was performed under local anaesthesia to induce a mineralized barrier at the exposed surface. Teeth were extracted from patients after 7, 14 and 35 days. Sections of the extracted teeth were prepared and stained for various markers using indirect immunofluorescence. Fibrocytes were counted, and the data were statistically evaluated using the Dunnett test. RESULTS: In uninflammed pulp tissue, a pro-collagen I-positive reaction was detected in odontoblasts, as well as in perivascular cells. Most of the CD45-positive cells were negative for pro-collagen I in normal pulp tissue, whereas CD45+/pro-collagen I+ fibrocytes were detected 7 days after injury. At day 14, fibrocytes were recognized under the fibrous matrix in contact with MTA and had infiltrated into regions of new capillary formation, where the fibrocytes were positively stained for vascular endothelial growth factor. By 35 days, fibrocytes were few, coincident with the formation of dentine bridges. The number of fibrocytes peaked 7 days post-injury and decreased at 14 days. CONCLUSIONS: The presence of fibrocytes in human pulp wound healing was observed. The spatiotemporal distribution of fibrocytes suggests that fibrocytes are involved in the early stages of pulp wound healing, specifically by contributing to new blood vessel formation.


Asunto(s)
Médula Ósea/patología , Células del Tejido Conectivo/patología , Pulpa Dental/patología , Adolescente , Adulto , Compuestos de Aluminio/farmacología , Compuestos de Aluminio/uso terapéutico , Calcificación Fisiológica , Compuestos de Calcio/farmacología , Compuestos de Calcio/uso terapéutico , Pulpa Dental/efectos de los fármacos , Pulpa Dental/lesiones , Recubrimiento de la Pulpa Dental/métodos , Exposición de la Pulpa Dental/terapia , Combinación de Medicamentos , Humanos , Odontoblastos/efectos de los fármacos , Odontoblastos/patología , Óxidos/farmacología , Óxidos/uso terapéutico , Materiales de Recubrimiento Pulpar y Pulpectomía/farmacología , Materiales de Recubrimiento Pulpar y Pulpectomía/uso terapéutico , Silicatos/farmacología , Silicatos/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Cicatrización de Heridas/fisiología , Adulto Joven
3.
Biol Pharm Bull ; 24(5): 491-5, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11379767

RESUMEN

Ex vivo muscarinic receptor binding of oxybutynin and propiverine, the most commonly used anticholinergic agents for the treatment in patients with urinary incontinence, was investigated in rat tissues. The oral administration of oxybutynin (50.8 and 127 micromol/kg) caused a significant increase in the apparent dissociation constant (Kd) for specific (-)-[3H]QNB binding in the rat bladder, prostate, submaxillary gland, heart and cerebral cortex, compared with each of the control values. Also, in the submaxillary gland of these rats, there was a reduction in the maximal number of binding sites (Bmax) for (-)-[3H]QNB binding. Similarly, oral administration of propiverine at doses of 74.3-297 micromol/kg brought about a significant increase in the Kd values for (-)-[3H]QNB binding in rat tissues including the bladder, and greater increase in Kd values was seen in the rat prostate, heart and submaxillary gland. On the other hand, oral administration of propiverine, unlike oxybutynin, resulted in very little reduction in the Bmax valules for (-)-[3H]QNB binding in the submaxillary gland. In conclusion, the present study has shown that oxybutynin and propiverine, after oral administration, bind significantly to muscarinic receptors in tissues such as the bladder, which is the target organ for the treatment of urinary incontinence, and that oxybutynin appears to exhibit long-term binding to muscarinic receptors in the salivary gland.


Asunto(s)
Bencilatos/farmacología , Ácidos Mandélicos/farmacología , Parasimpatolíticos/farmacología , Receptores Muscarínicos/efectos de los fármacos , Administración Oral , Animales , Masculino , Quinuclidinil Bencilato/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Muscarínicos/metabolismo
4.
Biol Pharm Bull ; 22(7): 687-90, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10443463

RESUMEN

In vitro, ex vivo and in vivo alpha1-adrenoceptor binding of JTH-601 (3-[N-[2-(4-hydroxy-2-isopropyl-5-methylphenoxy)ethyl]-N-methylaminometh yl]-4-methoxy-2,5,6-trimethyl-phenol hemifumarate), a novel alpha1L-adrenoceptor antagonist, in rat tissues was investigated. JTH-601 competed in a concentration-dependent manner with [3H]prazosin for binding sites in the prostate, submaxillary gland and spleen of rats in vitro, and the inhibitory effect was not largely different among these tissues, as shown by the Ki values of 2-3 nM. At 0.25, 0.5 and 3 h after oral administration of JTH-601 (6.5 micromol/kg) in rats, there was a significant (57, 64 and 28%, respectively) increase in the apparent dissociation constant (Kd) for prostatic [3H]prazosin binding, compared to the control value. The administration of a higher dose (21.8 micromol/kg) of this agent produced greater (67-99%) increases in Kd values for prostatic [3H]prazosin binding at 0.5-12 h later. Similar significant increases in Kd values, as with the prostate, were seen in the submaxillary gland and heart 0.25-12 h after the oral administration of JTH-601 (6.5 and 21.8 micromol/kg), but significant increases in the spleen and cerebral cortex were seen only at 0.25-3 h and 0.5 h, respectively. At 10 min of i.v. injection of [3H]JTH-601 in rats, in vivo specific binding was observed in the prostate, cerebral cortex, submaxillary gland, spleen and heart but not in the aorta. The binding in the prostate, submaxillary gland and heart, but not in the cerebral cortex and spleen, lasted until 120 min. It is concluded that JTH-601 may exert a considerably sustained blockade of alpha1-adrenoceptors in the prostate of rats. This finding may be important in characterizing the therapeutic effect of JTH-601 for bladder outlet obstruction in patients with benign prostatic hyperplasia.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1 , Antagonistas Adrenérgicos alfa/farmacología , Cresoles/farmacología , Próstata/efectos de los fármacos , Antagonistas Adrenérgicos alfa/farmacocinética , Animales , Unión Competitiva , Cresoles/farmacocinética , Masculino , Próstata/metabolismo , Radiofármacos/farmacología , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos alfa 1/metabolismo , Distribución Tisular , Tritio
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