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1.
J Oral Pathol Med ; 53(1): 31-41, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38155549

RESUMEN

INTRODUCTION: Oral submucous fibrosis (OSMF) is a well-known precancerous oral lesion, characterized by scarring, tissue fibrosis, and premalignant lesions. The goal of clinical treatment is to reduce inflammation and improve patients' quality of life by enhancing mouth opening among others. Antioxidant treatment has shown promising results in inducing regression of lesions and preventing OSMF in high-risk individuals. This study investigates the effectiveness of various antioxidant agents against OSMF. MATERIALS AND METHODS: The study followed PRISMA guidelines and searched three scientific databases: PubMed, Web of Science, and Scopus, using specific algorithms related to "antioxidant treatment," "burning sensation," and "mouth opening." The quality assessment of controlled clinical studies adhered to Cochrane guidelines. RESULTS: The analysis included 19 clinical trials comparing different treatments, including various antioxidants. Aloe vera, curcumin, and lycopene, among others, showed positive outcomes in treating OSMF by improving burning sensation, mouth opening, tongue protrusion, and cheek flexibility. CONCLUSION: Antioxidant therapies are found to be effective in treating OSMF, even when compared to conventional treatments such as corticosteroids. The study highlights the need for further research and standardization of clinical protocols.


Asunto(s)
Antioxidantes , Fibrosis de la Submucosa Bucal , Humanos , Antioxidantes/uso terapéutico , Fibrosis de la Submucosa Bucal/tratamiento farmacológico , Calidad de Vida , Licopeno/uso terapéutico , Corticoesteroides/uso terapéutico
2.
Med. oral patol. oral cir. bucal (Internet) ; 28(3): e247-e254, may. 2023. ilus, tab
Artículo en Inglés | IBECS | ID: ibc-220062

RESUMEN

Background: Biomedical engineering proposes the use of stem cells as a bone rehabilitation treatment in patients with alveolar bone defects. Many authors suggest that this innovative technique could represent the future of bone regeneration in dentistry. The present study systematically reviewed the efficacy of stem cells in bone regeneration in patients with alveolar bone atrophy. Material and methods: The study was developed following the criteria of the PRISMA guideline (2020). The literature review was conducted in Pubmed, Medline Complete, and Scopus. The search algorithms used the following key words: stem cells, bone regeneration, and alveolar ridge augmentation. To assess the risk of bias, the CASPe methodology was used. Results: Seven clinical trials in humans were included in this systematic review. In all the studies, the proposed objective of bone regeneration by using stem cells was achieved, although in a different way with different results. Although the authors of the analysed clinical trials achieved favourable results, they highlighted the presence of multiple limitations throughout bone regeneration treatments, such as scarce scientific literature on stem cells, a reduced number of follow-up studies, and a lack of a standardized international protocol. Conclusions: Based on the analysed studies, it is concluded that the therapy proposed by tissue engineering through the use of stem cells to rehabilitate patients with bone atrophies can be considered effective. In addition, the need for further studies and standardization of protocols is highlighted. (AU)


Asunto(s)
Humanos , Pérdida de Hueso Alveolar/cirugía , Aumento de la Cresta Alveolar/métodos , Células Madre , Regeneración Ósea
3.
Br J Pharmacol ; 174(13): 2015-2030, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28369791

RESUMEN

BACKGROUND AND PURPOSE: A NO-mediated desensitization of vasoconstrictor responses evoked by stimulation of α1 -adrenoceptors has been reported in different vessels. We investigated the involvement of each α1 -adrenoceptor subtype and constitutive NOS isoforms and the influence of ageing and hypertension on this process. EXPERIMENTAL APPROACH: Wistar and spontaneously hypertensive rats (SHR), 16, 32, 52 and 72 weeks-old, were used to evaluate the desensitization process. Expression of α1 -adrenoceptor subtypes, endothelial NOS (eNOS) and neuronal NOS (nNOS) were determined in rat aorta and left ventricle (LV). Expression levels were also evaluated in LV of a group of heart failure patients with a wide age range. KEY RESULTS: Repeated application of phenylephrine decreased subsequent α1 -adrenoceptor-mediated vasoconstriction by increasing nNOS protein expression in aorta, but not in tail or mesenteric resistance arteries, where mRNA levels of nNOS were undetectable. This desensitization process disappeared in the absence of endothelium or in the presence of L-NAME (100 µM), nNOS inhibitors, SMTC (1 µM) and TRIM (100 µM), and 5-methylurapidil (100 nM, α1A -antagonist), but not BMY7378 (10 nM, α1D -antagonist). The α1A /nNOS-mediated desensitization was absent in aged SHR and Wistar animals, where the expression of α1A -adrenoceptors was reduced in aorta and LV. In human LV, a negative correlation was found between age and α1A -adrenoceptor expression. CONCLUSIONS AND IMPLICATIONS: The α1A -adrenoceptor subtype, through endothelial nNOS-derived NO, may act as a physiological 'brake' against the detrimental effects of excessive α1 -adrenoceptor-mediated vasoconstriction. Reduced α1A -adrenoceptor- and nNOS-mediated desensitization in aged patients could be involved in the age-dependent elevation of adrenergic activity.


Asunto(s)
Envejecimiento , Aorta Torácica/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo I/metabolismo , Fenilefrina/farmacología , Receptores Adrenérgicos alfa 1/metabolismo , Animales , Aorta Torácica/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Relación Estructura-Actividad
4.
J Vasc Res ; 51(3): 209-20, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24942010

RESUMEN

This work compares the expression of adrenoceptors (ARs) and G-protein-coupled receptor kinase (GRK) 2 (RT-PCR and immunoblotting) and functional responses in conductance (aorta) and resistance vessels (mesenteric resistance arteries; MRA) in two different models of rat hypertension: hypertension induced by chronic treatment with L-NAME (N(G)-nitro-L-arginine methyl-ester) (L-NAME-treated rats; LNHR), and genetically induced hypertension (spontaneously hypertensive rats; SHR). Changes found in the aorta, but not in the MRA, were: (1) a loss of contractile capacity, more evidently in α1-AR-mediated contraction, and an impairment of endothelium-dependent vasorelaxation, with both changes occurring independently of the hypertensive model; (2) a diminished sensitivity to α1-AR-induced vasoconstriction along with increased ß2-AR-mediated vasodilation in LNHR, and (3) a lower expression of ARs and GRK2 in LNHR. The two latter changes are the opposite of those previously found in aortas of SHR. In the MRA of LNHR, a diminished sensitivity to isoprenaline, in parallel with a reduced expression of ß1-AR, was observed without changes in GRK2 expression. In the MRA of SHR, the increased GRK2 expression was not accompanied by significant changes in either ß-AR expression or the vasorelaxant potency of isoprenaline. The present results highlight that changes in AR function differ not only between vessels but also between hypertensive models. Moreover, they suggest that changes in GRK2 expression could contribute to regulating ß2-AR function in conductance vessels but not ß1-AR function in resistance vessels.


Asunto(s)
Quinasa 2 del Receptor Acoplado a Proteína-G/metabolismo , Hipertensión/fisiopatología , Receptores Adrenérgicos alfa 1/fisiología , Receptores Adrenérgicos beta 2/fisiología , Animales , Aorta/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Técnicas In Vitro , Masculino , Arterias Mesentéricas/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Ratas Wistar , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacos
5.
Vascul Pharmacol ; 61(2-3): 80-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24768830

RESUMEN

ß-Adrenoceptors (ß-ARs) modulate ERK1/2 and p38 in different cells, but little is known about the contribution of these signaling pathways to the function of ß-ARs in vascular tissue. Immunoblotting analysis of rat aortic rings, primary endothelial (ECs) and smooth muscle cells (SMCs) isolated from aorta showed that ß-AR stimulation with isoprenaline activated p38 in aortic rings and in both cultured cell types, whereas it had a dual effect on ERK1/2 phosphorylation, decreasing it in ECs while increasing it in SMCs. These effects were reversed by propranolol, which by itself increased p-ERK1/2 in ECs. Isoprenaline ß-AR mediated vasodilation of aortic rings was potentiated by the ERK1/2 inhibitor, U0126, in the presence or absence of endothelium or L-NAME, whereas inhibition of p38 had no impact. Isoprenaline moderately decreased sprouting from aorta rings in the Matrigel angiogenesis assay; conversely propranolol not only prevented isoprenaline inhibition, but stimulated angiogenesis. ERK1/2 inhibition decreased angiogenesis, while a dramatic stimulation was observed by p38 blockade. Our results suggest that ERK1/2 activation after ß-ARs stimulation in the smooth muscle hinders the vasodilator effect of isoprenaline, but in the endothelium ß-ARs decreases ERK1/2 and increases p38 activity reducing therefore angiogenesis.


Asunto(s)
Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Receptores Adrenérgicos beta/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Células HEK293 , Humanos , Masculino , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Propranolol/farmacología , Ratas , Ratas Wistar , Receptores Adrenérgicos beta/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología
6.
Pharmacol Res Perspect ; 1(1): e00001, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25505555

RESUMEN

The objective of this study was to determine whether the different time-course characteristics of α1-adrenoceptor-mediated contraction in arteries can be related to the subtypes involved. Contractile responses to noradrenaline (NA) were compared with inositol phosphate accumulation and extracellular signal-regulated kinase (ERK)1/2 phosphorylation after α1-agonist stimuli in the same vessels in the presence or absence of α1-antagonists in rat or in α1-subtype knockout (KO) mice. Aorta, where α1D-AR is the main functional subtype, had higher sensitivity to NA (in respect of inositol phosphate [IP], pERK1/2, and contractile response) than tail artery, where the α1A-adrenoceptor subtype is predominant. Furthermore, the contraction in aorta exhibited a slower decay after agonist removal and this was consistent in all strains harboring α1D-adrenoceptors (from rat, α1B-KO, and wild-type [WT] mice) but was not observed in the absence of the α1D-adrenoceptor signal (α1D-adrenoceptor blocked rat aorta or aorta from α1D-KO). IP formation paralleled α1-adrenoceptor-mediated contraction (agonist present or postagonist) in aorta and tail artery. High sensitivity to agonist and persistence of response after agonist removal is a property of α1D-adrenoceptors. Therefore, the preponderance of this subtype in noninnervated conductance arteries such as aorta allows responsiveness to circulating catecholamines and prevents abrupt changes in vessel caliber when the stimulus fluctuates. Conversely, in innervated distributing arteries, high local concentrations of NA are required to activate α1A-adrenoceptors for a response that is rapid but short lived allowing fine adjustment of the contractile tone by perivascular sympathetic nerves.

7.
Eur J Pharmacol ; 641(1): 41-8, 2010 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-20511116

RESUMEN

Among the three alpha(1)-adrenoceptor subtypes (alpha(1A), alpha(1B) and alpha(1D)) a peculiar intracellular localization and poor coupling to membrane signals of cloned alpha(1D)-adrenoceptor have been reported. In addition, the alpha(1L)-adrenoceptor (low affinity for prazosin), a functional phenotype of alpha(1A), has been described. The purpose of this work was to analyze the expression, cellular localization and coupling to membrane signalling (inositol phosphate accumulation) of alpha(1)-adrenoceptor subtypes in a native tissue, the rat cerebral cortex. mRNA for the three subtypes was quantified by real-time RT-PCR (alpha(1D)>alpha(1B)>>alpha(1A)). alpha(1)-Adrenoceptors were also detected by immunoblotting, revealing alpha(1A)- and alpha(1B)-adrenoceptors to be predominantly expressed in the membrane fraction and the alpha(1D)-adrenoceptor to be localized in the cytosolic fraction. Competitive radioligand binding studies revealed the presence of alpha(1D)-adrenoceptor in tissue homogenates, whereas only alpha(1A)- and alpha(1B)-subtypes were detected in membranes. The proportion of alpha(1A)-adrenoceptor increased after treatment with noradrenaline, suggesting differences in agonist-mediated trafficking. Saturation experiments detected high- and low (alpha(1A/L))-prazosin binding sites, the latter of which disappeared on incubation with GppNHp. The alpha(1A/L)-adrenoceptor was heavily implicated in the inositol phosphate response, while the alpha(1D)-subtype did not play a relevant role. These results suggest that the predominant cytosolic localization of alpha(1D)-adrenoceptor lies behind its poor coupling to membrane signalling such as inositol phosphate pathway. The fact that the alpha(1L)-adrenoceptor detected in radioligand binding studies disappeared in the presence of GppNHp implies that it represents a conformational state of the alpha(1A)-adrenoceptor coupled to G-protein.


Asunto(s)
Corteza Cerebral/metabolismo , Receptores Adrenérgicos alfa 1/genética , Receptores Adrenérgicos alfa 1/metabolismo , Animales , Unión Competitiva , Membrana Celular/metabolismo , Corteza Cerebral/citología , Corteza Cerebral/efectos de los fármacos , Citosol/metabolismo , Femenino , Regulación de la Expresión Génica , Guanosina Trifosfato/química , Guanosina Trifosfato/farmacología , Fosfatos de Inositol/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
8.
J Pharmacol Exp Ther ; 328(3): 982-90, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19060223

RESUMEN

In human and animal hypertension models, increased activity of G-protein-coupled receptor kinase (GRK) 2 determines a generalized decrease of beta-adrenergic vasodilatation. We analyzed the possibility of differential changes in the expression and functionality of alpha(1A), alpha(1B), alpha(1D), beta(1), beta(2), and beta(3)-ARs also being involved in the process. We combined the quantification of mRNA levels with immunoblotting and functional studies in aortas of young and adult spontaneously hypertensive rats (SHRs) and their controls (Wistar Kyoto). We found the expression and function of beta(1)-adrenoceptors in young prehypertensive SHRs to be higher, whereas a generalized increase in the expression of the six adrenoceptors and GRK2 was observed in aortas of adult hypertensive SHRs. alpha(1D)- and beta(3)-adrenoceptors, the subtypes that are more resistant to GRK2-mediated internalization and mostly expressed in rat aorta, exhibited an increased functional role in hypertensive animals, showing two hemodynamic consequences: 1) an increased sensitivity to the vasoconstrictor stimulus accompanied by a decreased sensitivity to the vasodilator stimulus (alpha(1D)-ARs are the most sensitive to agonists, and beta(3)-ARs are the least sensitive to agonists); and 2) a slower recovery of the basal tone after adrenergic stimulus removal because of the kinetic characteristic of the alpha(1D) subtype. These functional changes might be involved in the greater sympathetic vasoconstrictor tone observed in hypertension.


Asunto(s)
Aorta/fisiología , Hipertensión/fisiopatología , Receptores Adrenérgicos alfa 1/genética , Receptores Adrenérgicos beta/fisiología , Animales , Aorta/fisiopatología , Quinasa 2 del Receptor Acoplado a Proteína-G/genética , Quinasa 2 del Receptor Acoplado a Proteína-G/metabolismo , Frecuencia Cardíaca/fisiología , Humanos , Modelos Biológicos , ARN Mensajero/genética , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptores Adrenérgicos alfa 1/fisiología , Sístole/fisiología , Regulación hacia Arriba , Vasodilatación
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