Abordaje Terapéutico de Agrandamiento Gingival Influenciado por Ciclosporina y Nifedipino. Reporte de Caso / Therapeutic Approach of Gingival Enlargement Influenced by Cyclosporine and Nifedipine. Case Report

RESUMEN: Este reporte de caso muestra un paciente atendido en el Postítulo de Periodoncia de la Facultad de Odontología de la Universidad de Chile con diagnóstico de Agrandamiento Gingival influenciado por ciclosporina y nifedipino. El abordaje terapéutico consideró la fase sistémica, la fase higiénica con el tratamiento periodontal no quirúrgico para lograr la eliminación de la infección periodontal antes y después de la fase quirúrgica, y la fase de terapia de soporte periodontal. Se logró así la eliminación de los agrandamientos gingivales influenciados por ciclosporina y nifedipino.

ABSTRACT: This case report shows a patient attended in the Postgraduate Periodontics Program at the Faculty of Dentistry of the University of Chile with a diagnosis of Gingival Enlargement influenced by cyclosporine and nifedipine. The therapeutic approach considered the systemic phase, the hygienic phase with the non-surgical periodontal treatment to achieve the elimination of the periodontal infection before and after the surgical phase, and the phase of periodontal support therapy. Thus, the elimination of gingival enlargements influenced by cyclosporine and nifedipine was achieved.

Agrandamiento gingival inducido por fenitoínas / Phenytoin induced gingival enlargement

Se entiende por agrandamiento gingival el incremento en masa y volumen del tejido gingival. Se considera una condición benigna de la cavidad oral, por lo general de manejo rutinario, que logra regularse con medidas simples de control del biofilm microbiano. El agrandamiento gingival puede ser producido por diversas condiciones clínicas, hereditarias, deficiente higiene oral o fármacos. La epilepsia afecta a 1% de la población mundial y requiere el uso de fármacos antiepilépticos o anticonvulsivantes para lograr su control, dentro de éstos la fenitoína actúa como un bloqueador selectivo de los canales de sodio sensibles al voltaje y constituye uno de los fármacos más empleados por su capacidad en el control de crisis focales y generalizadas. La fenitoína se ha relacionado con los agrandamientos gingivales como uno de sus efectos adversos, los cuales se incluyen dentro de las enfermedades por fármaco inducidas en la cavidad oral. El objetivo de este artículo es brindar la información necesaria sobre el manejo correcto de pacientes con agrandamiento gingival producido por fenitoínas y a la vez poder conocer las consecuencias de estos fármacos en la cavidad oral (AU)

Gingival enlargement means the increase in mass and volumen of the gingival tissue. It is considered a benign condition of the oral cavity, usually of routine management, wich can be regulated with simple measures of biofilm control. The gingival enlargement can be produced by diverse clinical conditions, hereditary deficient oral higiene or drugs. Epilepsy affects 1% of the world population and requires the use of antiepileptic or anticonvulsant drugs to achieve its control, within these phenytoin acts as selective blocker or voltage ­ sensitive sodium channels and is one of the most used grugs for its ability to control focal and generalized crises. Phenytoin has been linked to gingival enlargement as one of its adverse effects which is included within the drug diseases induced in the oral cavity. The objective of this article is to provide the necessary information on the correct managment of patients with gingival enlargemen produced by phenytoins and at the same time to know the consequences of these drugs in the oral cavity (AU)

Agrandamiento gingival medicamentoso en paciente con trasplante renal tratado con ciclosporina A / Drug-induced gingival enlargement in a kidney transplant patient treated with cyclosporine A

Resumen El agrandamiento gingival medicamentoso se describe como un aumento de volumen anormal, exagerado y deformante de las encías, provocado por la ingesta de algunos medicamentos. Entre los más comunes se encuentran: fármacos anticonvulsivantes, antihipertensivos, particularmente los antagonistas del calcio e inmunosupresores. Se presentó el caso de un paciente del sexo masculino, de 44 años de edad, con antecedentes de hipertensión arterial e insuficiencia renal crónica, durante 10 y tres años respectivamente. Después de 22 meses de haber recibido un trasplante renal y tratamiento con ciclosporina, acude a consulta por aumento del volumen de las encías en ambos maxilares, clínicamente compatible con agrandamiento gingival medicamentoso generalizado y grave.

ABSTRACT Drug-induced gingival enlargement is described as an abnormal, exaggerated, and deforming growth of the gingiva caused by the ingestion of some medications. Anticonvulsants, antihypertensive calcium channel blockers and immunosuppressants are among the most common drugs. We present a 44-year-old male patient with a history of arterial hypertension and chronic renal failure, for 10 and three years, respectively. Twenty-two months after receiving a kidney transplant and treatment with cyclosporine, he visited the clinic due to an increase in the volume of the gums in both jaws, clinically compatible with a generalized and severe gingival enlargement.

Effects of cyclosporin, nifedipine and phenytoin on gingival myofibroblast transdifferentiation in monkeys

Abstract Objective: Myofibroblasts have been associated with the development of several pathologic fibrotic conditions. This longitudinal study aims to assess the proliferative and antiapoptotic effects of cyclosporin, nifedipine and phenytoin on gingival connective tissue cells of nonhuman primate, as well as to analyze a possible role of myofibroblasts in gingival overgrowth. Materials and Methods: Gingival samples from the right superior canine area were obtained from 12 male monkeys ( Sapajus spp ) to comprise the control group. After one week, the animals were randomly assigned to three groups, which received daily oral doses of cyclosporin, nifedipine or phenytoin for 120 days. Gingival samples were collected from the left superior canine area of two animals of each group at 52 and 120 days. Histological sections were stained with hematoxylin and eosin, and immunoreacted against α-SMA, Ki- 67 and bcl-2. Results: α-SMA immunoreaction was negative in the control and experimental groups. Similarly, no difference between groups concerning immunostaining against Ki-67 and bcl-2 was observed in connective tissue cells. Conclusion: Based on this methodology, it may be concluded that gingival overgrowths induced by cyclosporin, nifedipine and phenytoin are not associated with neither myofibroblast transdifferentiation, proliferation nor apoptosis of gingival connective cells in monkeys.

Agrandamiento gingival medicamentoso en paciente con trasplante renal tratado con ciclosporina A / Drug-induced gingival enlargement in a kidney transplant patient treated with cyclosporine A

El agrandamiento gingival medicamentoso se describe como un aumento de volumen anormal, exagerado y deformante de las encías, provocado por la ingesta de algunos medicamentos. Entre los más comunes se encuentran: fármacos anticonvulsivantes, antihipertensivos, particularmente los antagonistas del calcio e inmunosupresores. Se presentó el caso de un paciente del sexo masculino, de 44 años de edad, con antecedentes de hipertensión arterial e insuficiencia renal crónica, durante 10 y tres años respectivamente. Después de 22 meses de haber recibido un trasplante renal y tratamiento con ciclosporina, acude a consulta por aumento del volumen de las encías en ambos maxilares, clínicamente compatible con agrandamiento gingival medicamentoso generalizado y grave.

Management of Phenytoin-Induced Gingival Enlargement: A Case Report.

Gingival enlargement is frequently observed in patients taking certain drugs such as anticonvulsants, immune suppressants, and calcium channel blockers. The effects of these drugs are not only directed at the primary target tissues, but also on secondary target tissues, such as gingival connective tissue, causing clinical, and histopathological aberrations. These aberrations can adversely affect speech, mastication, tooth eruption, and esthetics. Disfiguring gingival overgrowth triggered by these medications often impairs the nutrition and provides access to oral infection, caries, and periodontal disease. The present case report describes the treatment of a patient with a phenytoin induced gingival enlargement.

Comparison between Laser, Electrocautery and Scalpel in the Treatment of Drug-Induced Gingival Overgrowth: A Case Report.

Drug-induced gingival overgrowth (DIGO) is a well-recognized, unwanted side-effect associated with three major drug groups - anticonvulsants, immunosuppressants and the calcium channel blockers. The prevalence of this unwanted side effect is 25-80% and is also dependent on other factors such as type of drug, dosage, duration of treatment, genetic predisposition, and patient’s oral hygiene maintenance. Three different treatment modalities viz., scalpel, laser, and electrocautery can be used for treating DIGO. Each method carries its own merits and demerits. In the present case report, these three different treatment modalities are used in the same patient in order to compare their handling properties and effect on initial wound healing. Though scalpel remains to be gold standard treatment, use of laser finds some more advantages over the electrocautery for treatment of DIGO.

Phenytoin-Induced Gingival Overgrowth Management with Periodontal Treatment

Phenytoin-induced gingival overgrowth (PIGO) is a common complication of the continuous use of medications. This paper presents a case of PIGO hindering oral function and compromising oral hygiene and aesthetics, which was treated with a combination of nonsurgical and surgical periodontal therapies. A 39-year-old male patient was referred for dental treatment with several complaints, especially upper and lower gingival overgrowth that hindered speech and swallowing. Generalized deep probing pockets and bone loss were detected. Diagnosis of gingival overgrowth associated with phenytoin and chronic periodontitis was established. The treatment plan consisted of conservative therapy with education on oral health, motivation and meticulous oral hygiene instruction in combination with scaling and root planing. During the revaluation period, a marked reduction in the clinical parameters was noted, particularly probing pocket depth reduction. Surgical therapy for removal of gingival overgrowth was also performed to achieve pocket reduction. Supportive periodontal therapy was proposed and the patient is currently under follow-up for 4 years. Management of PIGO may be obtained by the use of periodontal procedures combined with good oral hygiene and periodontal supportive care.

O crescimento gengival induzido pela fenitoína é uma complicação comum do uso contínuo da medicacão. Este artigo apresenta um caso de crescimento gengival excessivo que dificultava a função oral e comprometia a higiene oral e a estética, o qual foi tratado com uma combinação de terapias periodontais não-cirúrgicas e cirúrgicas. Paciente masculino de 39 anos de idade foi encaminhado para tratamento odontológico com várias queixas, especialmente do crescimento gengival superior e inferior que prejudicava a fala e deglutição. Profundidades de sondagens severas generalizadas e perda óssea foram detectadas. Diagnóstico de crescimento gengival induzido pela fenitoína e periodontite crônica foi estabelecido. O plano de tratamento consistiu de terapia conservadora com educação, motivação e meticulosa instrução de higiene oral em associação com raspagem e alisamento corono-radicular. Durante o período de reavaliação, uma acentuada redução nos parâmentros clínicos foi observada, principalmente uma redução das profundidades de sondagem. Terapia cirúrgica para remoção do excesso de tecido gengival também foi realizada para conseguir redução das bolsas. Terapia periodontal de suporte foi proposta e o paciente está atualmente sob acompanhamento por um período de 4 anos. O manejo do crescimento gengival induzido pela fenitoína pode ser obtido pelo uso de procedimentos periodontais combinados com uma boa higiene oral e cuidados periodontais de suporte.

Gingival Enlargement: Revisited: A Case Series.

Gingival enlargement can be hereditary or acquired. More than 20 prescription medications are associated with gingival overgrowth. A detailed review on the risk factors and pathogenesis from various peer reviewed journals has been discussed in this article. The aim was to discuss the role of drugs causing gingival enlargement, the hereditary gingival fibromatosis (HGF) and its possible pathogenesis. The following case series highlights four cases of gingival enlargement, one being a case of HGF and the other three being drug-induced gingival enlargement. Variable etiopathogenesis such as age, genetic predisposition, pharmacokinetic variables, tissue homeostasis, inflammation and growth factors have been associated with this disease. Inflammatory changes that occur within the gingival tissues appear to orchestrate the interaction between the “modified fibroblast” and the drug. Alternatively, these drugs influence directly the inflammatory response in the form of enlargement. This information is valuable for the clinician as it will have implication to treat the patient effectively.

Agrandamientos gingivales inducidos por fármacos / Drug-induced gingival enlargements

El término agrandamiento gingival por fármacos se refiere a un crecimiento anormal de la encía, secundario al uso de una medicación sistémica. Si bien se reporta una larga lista de medicamentos relacionados, se encontró una fuerte asociación sólo con la Fenitoína , la Nifedipina y la Ciclosporina A. La prevalencia del Agrandamiento Gingival varía ampliamente, sin embargo la prevalencia relacionada con el uso de la Fenitoína es aproximadamente del 50 por ciento. La Nifedipina y la ciclosporina producen cambios en el 25 por ciento de los pacientes tratados. Existe controversia entre la dosis y el riesgo o severidad del Agrandamiento.El grado de Agrandamiento gingival parece estar relacionado con la susceptibilidad del paciente y el grado dehigiene bucal de éste. Después de 1 a 3 meses de iniciada la medicación del fármaco los agrandamientos originadosen la papila interdental, se expande afectando otras áreas de la encía llegando a cubrir en casos extremosuna porción importante de los dientes principalmente en los segmentos anteriores por vestibular. El uso discontinuo de la medicación por el médico de cabecera y más aún la sustitución del fármaco por otroresulta en la regresión y el cese del Agrandamiento.

Low prevalence of gingival overgrowth associated to new imunossupressive protocols with cyclosporin

Gingival overgrowth (GO) is a frequent finding in patients treated with cyclosporine (CsA). This study investigated the prevalence and severity of GO in patients who received kidney transplant and CsA therapy, as well as associations with pharmacological and clinical factors. This cross-sectional study included 63 kidney transplant recipients who were treated with CsA in a university hospital. Demographic, pharmacological, and periodontal data were collected. The primary variable was GO. Independent sample t- and chi-square tests were used to compare means in groups with versusl without GO. The response rate was 86.3%. Overall, 40% of patients had some degree of GO. Eleven individuals presented GO scores > 10%, and 5 individuals reached 30%. The mean GO percentage was low (6.79 ± 15.83). Patients that were concurrently under nifedipine treatment showed a non-significant trend toward a greater prevalence of GO. Mean CsA dosage and serum levels were 3.20 ± 0.94 mg/kg/d and 156.12 ± 162.75 ng/mL, respectively. There were no statistically significant differences between patients with versusl without GO nor between the groups receiving nifedipine, no drug, or verapamil. The GO prevalence and severity rates were lower than those reported in previous studies and seemed to be independent of drug interactions.

Side effects of cyclosporine-A treatment in rats: gingival overgrowth and early hyperglycemia

Gingival overgrowth is an adverse side effect of cyclosporine A (CsA) in the treatment of transplanted patients. The purpose of this study was to evaluate the effects of CsA on new-onset diabetes mellitus and gingival overgrowth in rats, by measuring collagen, nitric oxide and microvascular permeability. Blood glucose level, collagen, nitric oxide level and vascular permeability were determined. Blood glucose level increased significantly from 6.5 +/- 0.9 for the control group to 15+/- 1.2, 17 +/- 1.2 and 21.6+/- 1.6 mM/L at 1, 4 or 8 weeks of CsA treatment, respectively. Collagen (ug HO Proline/mg p) increased significantly from 2.5+/- 0.5 for the control group to 4.2+/- 0.8, 5.9+/- 0.6 and 7.3 +/- 0.8 at 1, 4 or 8 weeks of CsA treatment, respectively. Vascular permeability was 10.3+/- 1.2 for the control group and 15+/-1; 17.2 +/- 1.3, and 22.1+/- 2.1 ug EB/g T; at 1, 4 or 8 weeks of CsA treatment, respectively. Nitric oxide level was 3.5 +/- .9 umol/mg P for the control group and 4+/- 0.2, 8.2+/- 0.9 and 11+/-1 for 1, 2 or 8 weeks of CsA treatment, respectively. These findings appear to indicate that the development of significant gingival changes induced by CsA is related to new-onset of diabetes mellitus during the immunosuppressive treatment.

La hiperplasia gingival es un efecto colateral adverso del tratamiento con ciclosporina A (CsA) en pacientes transplantados. El proposito de este estudio fue evaluar el efecto de CsA en el inicio de diabetes mellitus, la concentracion de colageno, y de oxido nitrico y la permeabilidad capilar gingival. El nivel de glucosa en sangre de los animales controles fue: 6.5+/- 0.9, en tanto que los tratados con CsA fue: 15+/-1.2; 17+/- 1.1 y 21.6+/- 1.6 mM/L a las 1, 4 y 8 semanas respectivamente. El colageno (ug OH prolina/mg p) mostro un aumento significativo en los animales tratados con CsA respecto de los controles: 2.5+/- 0.5; 4.2+/- 0.8; 5.9+/- 0.6; 7.3+/- 0.8 respectivamente a las 1,4 y 8 semanas de tratamiento. Los valores de permeabilidad capilar (ug AE/ g T) fueron: en los animales control 10.3+./- 1.2; en los animales tratados con CsA, a las 1, 4 y 8 semanas 15+/- 1.0; 17.2 +/- 1.3 y 22.1+/- 2.1 respectivamente. Los valores de oxido nitrico (umol/mg p) en los animales control: 3.5+/-0.9; y en los animales tratados con CsA 4+/- 0.2; 8.2+/- 0.9 y 11.2 +/- 1.0 respectivamente. Estos resultados parecen indicar que el desarrollo de los significativos cambios gingivales inducidos por la administracion de CsA esta relacionado con la hiperglucemia temprana que se asocia al tratamiento con inmunosupresores.

Cyclosporin A-induced gingival overgrowth is not associated with myofibroblast transdifferentiation

Cyclosporin A (CyA) induces gingival overgrowth via its stimulatory effects on expression of transforming growth factor-beta1 (TGF-â1) and collagen. It is not known whether CyA has a direct effect on gingival fibroblasts or induces its effect indirectly via stimulation of myofibroblast transdifferentiation. The present study was undertaken to examine the in vivo and in vitro effect of CyA on myofibroblast transdifferentiation. Rats were treated for 60 days with a daily subcutaneous injection of CyA, and the gingival overgrowth tissue was analyzed by immunohistochemistry. In vitro, fibroblasts from normal gingiva (NG) were cultured in the presence of different concentrations of CyA, and subjected to semi-quantitative reverse transcriptase-polymerase chain reaction and western blot. Although CyA treatment stimulated TGF-â1 expression by NG fibroblasts, it lacked to induce expression and production of isoform á of smooth muscle actin (á-SMA), the specific myofibroblast marker. The expression levels of connective tissue growth factor (CTGF), which has been considered a key molecule to promote the transdifferentiation of myofibroblasts via TGF-â1 activation, were unaffected by CyA. Our results demonstrate that CyA-induced gingival overgrowth is not associated with activation of myofibroblast transdifferentiation, since CyA is not capable to increase CTGF expression.

Agrandamientos gingivales en niños y adolescentes transplantados renales / Gingival overgrowths in renal transplant children and adolescents

El receptor de transplante renal requiere terapia medicamentosa compleja con agentes inmunosupresores, corticoides, antimicrobianos, hipotensores y estimuladores de la regeneración ósea para prevenir el posible rechazo del órgano transplantado, controlar las infecciones secundarias a la inmunosupresión, las alteraciones de crecimiento y las variaciones de tensión arterial causadas por la insuficiencia renal. El objetivo de este trabajo fue analizar relación entre agrandamiento gingival y medicaciones recibidas. Fueron evaluados 47 niños y adolescentes transplatados renales, con edades entre 4 y 19 años (media 12.10 +- años) sin tratamiento preventivo bucal durante los 2 años previos a la iniciación del estudio, atendidos en el servicio de Nefrología del Hospital Nacional de Pediatría Juan P. Garrahan, de la Ciudad Autónoma de Buenos Aires, Argentina. Se analizó tipo de donante, tiempo de transplante y medicaciones inmunosupresoras (ciclosporina, micofenolato, azatioprina); corticoides (meprednisona), antimicrobianos (sulfametoxazol + trimetropina furantoína), hipotensores (enalapril, nifedipina); y estimuladores de la regeneración ósea (carbonato de calcio, 1 alfa 25-dihidroxicolecalciferol). Los resultados mostraron un agrandamiento gingival en el 69,6 por ciento de los niños y adolescentes, con un 31,9 por ciento de agrandamiento grado 3 y 4. Se observó correlación entre agrandamiento gingival y tiempo de trasplante P<0.05. No se observó asociación y correlación entre agrandamiento gingival y medicaciones.

Influence of diltiazem in combination with a sucrose-rich diet on gingival alterations in rats

The aim of this study was to evaluate the influence of diltiazem in combination with a sucrose-rich diet on gingival alterations in rats. One hundred and twenty male Holtzman rats were randomly assigned to 10 groups (n = 12), being 2 control groups treated with saline and 8 test groups treated with diltiazem in daily doses of 5, 25, 50 and 100 mg/kg during 40 or 60 days. Afterwards, the mandibles were removed for macroscopic, histologic and histometric analyses of the buccal gingiva of the mandibular right first molar. No macroscopic characteristic of gingival overgrowth was observed in any of the groups. The microscopic analysis showed characteristics of normality with inflammatory cells only adjacent to the crevicular epithelium in all groups for both periods. The histometric analysis showed significant differences only for the epithelial tissue area in the 40-day period (Kruskal-Wallis; P = 0.032). Comparing the periods, significant differences regarding the connective and epithelial tissue areas were observed only in the group treated with a 25 mg/kg dose (Mann-Whitney; P = 0.004 and P = 0.007, respectively). Oral administration of diltiazem in combination with a sucrose-rich diet did not induce gingival alterations in rats.

Agrandamientos gingivales asociados al HLA en pacientes transplantados renales medicados con ciclosporina A / HLA-associated gingival enlargements in transplant patients medicated with cyclosporin A

La patogénesis del agrandamiento gingival en pacientes transplantados renales medicados con ciclosporina A ha sido investigada mediante diferentes factores de riesgo. El propósito del trabajo fue analizar la relación de los diferentes fenotipos de antígenos HLA y los indicadores asociados con el agrandamiento. Material y métodos: fueron incluidos 30 pacientes transplantados renales concurrentes al servicio de Nedrología del Hospital Nacional de Pediatría Juan P. Garrahan, 9 mujeres y 21 varones con una media de edad de 11 años, +- 3,9 (SD) que reciben medicación inmunosupresora, antimicrobiana, hipotensora y corticoide. Se registró: tipo de enfermedad de base, tiempo de transplante expresado en meses, tipo de donante (vivo o cadavérico), grado de agrandamiento gingival según McGaw (1987), profundidad de sondaje, índice gingival de Loe y Silness, índice de placa de Silness y Loe, grupo sanguíneo, alelos del HLA. Se calculó la media aritmética y error estándar, la distribución de frecuencia delt ipo de enfermedad y el grado de agrandamiento. Se analizó la asociación y correlación de cada una de las variables con los fenotipos del HLA. Resultados: no se encontró asociación del AG con edad, tipo de enfermedad, tiempo de trasplante, tipo de donante, grupo sanguíneo. Se encontró asociación y correlación significativa entre variables del receptor e indicadores gingivoperiodontales. Conclusiones: asociación y correlación significativa se identificó entre fenotipos HLA y el estado gingivoperiodontal.

Expression of insulin like growth factor binding protein-5 in drug induced human gingival overgrowth.

BACKGROUND & OBJECTIVE: Insulin like growth factor binding proteins (IGFBPs) control the distribution, function and activity of insulin like growth factors (IGFs) in various cells, tissues and body fluids, thereby modulating their metabolic and mitogenic effects. IGFBP-5, the most conserved IGFBP, can function through IGF or directly play a role in fibrosis. Cyclosporine A (CsA) widely used in organ transplant patients, often causes various side effects including gingival fibrotic overgrowth. This study was carried out to assess the mRNA expression of IGFBP-5 in healthy human gingival, chronic periodontitis and CsA induced gingival overgrowth tissues. METHODS: Total RNA was isolated from gingival tissues collected from eight patients with chronic periodontitis, eight patients with CsA induced gingival outgrowth and an equal number of healthy individuals, and subjected to reverse transcription (RT)-PCR for IGFBP-5 gene expression. RESULTS: CsA induced gingival overgrowth tissues expressed increased IGFBP-5 mRNA compared to control and chronic periodontitis. INTERPRETATION & CONCLUSION: Increased mRNA expression of IGFBP-5 in CsA induced gingival outgrowth tissues may be associated with increased collagen synthesis, thereby promoting fibrogenesis.

Efeitos da ciclosporina, fenitoína e nifedipina sobre a síntese e degradação de colágeno da gengiva de macacos-prego (Cebus apella): estudo histoquímico e através de RT-PCR / Effects of cyclosporin, phenytoin and nifedipine on synthesis and degradation of gingival collagen in tufted capuchin monkeys (Cebus apella): histochemical and MMP-1, MMP-2 and collagen type I gene expression analysis

INTRODUÇÃO: As alterações em gengiva induzidas por medicamentos têm sido pouco estudadas quanto à expressão in vivo dos genes das metoloproteinases (MMPs). O objetivo do presente trabalho foi avaliar o padrão histológico de distribuição de fibras colágenas após a administração de ciclosporina, nifedipina ou fenitoína e correlacionar com a expressão dos genes do colágeno do tipo I, MMP-1 e MMP2. MATERIAL E MÉTODO: Amostras da gengiva da área de canino superior direito foram obtidas de doze macacos prego (Cebus apella) machos. A extremidade mesial de cada amostra foi imediatamente congelada em nitrogênio líquido enquanto que a distal foi processada para inclusão em parafina. Após uma semana, os animais foram divididos em três grupos que receberam doses diárias de ciclosporina, fenitoína ou nifedipina, durante 120 dias. Procedeu-se à remoção de amostras da gengiva da área do canino superior esquerdo de dois animais de cada grupo aos 52 e 120 dias. Os cortes histológicos foram corados pelas técnicas da hematoxilina e eosina, vermelho picrosirius, além da marcação imunoistoquímica para colágeno do tipo IV. O RT-PCR semiquantitativo foi realizado para se determinar os níveis de mRNA. RESULTADOS: No grupo controle, houve o predomínio de fibras colágenas maduras, evidenciadas com a cor vermelha em cortes corados pela técnica do vermelho picrosirius analisados com microscópio de luz polarizada. Observou-se nos grupos tratados aos 52 e 120 dias um aumento da porcentagem de áreas ocupadas por fibras imaturas, em todos os grupos, independentemente da idade do animal. No entanto, não foram observadas diferenças morfológicas entre os grupos controle e tratado nos cortes corados pela hematoxilina e eosina. Houve uma tendência a valores médios mais baixos de expressão da MMP-1 em todos os grupos, aos 52 dias. Contudo, as expressões da MMP-2 e colágeno do tipo I parecem estar sujeitas a mudanças fásicas e dependentes do medicamento. CONCLUSÃO: Os resultados permitiram...

Diltiazem did not induce gingival overgrowth in rats: a clinical, histological and histometric analysis / Diltiazem não induziu crescimento gengival em ratos. Análise clínica, histológica e histométrica

A administração de bloqueadores dos canais de cálcio tem sido associada com crescimento gengival; entretanto, existem poucos estudos em humanos e animais que avaliaram o efeito do diltiazem nos tecidos gengivais. O presente trabalho tem como objetivo avaliar o efeito do diltiazem, em diferentes dosagens e tempos de tratamento, no tecido gengival de ratos, por meio de análises clínica, histológica e histométrica. Oitenta ratos jovens machos foram divididos em oito grupos de acordo com a dosagem e o tempo de administração. Os animais foram tratados por 20 ou 40 dias com uma dosagem diária de diltiazem de 5, 20 ou 50 mg/kg de peso corporal, por via subcutânea. Os resultados confirmaram que o diltiazem não induziu crescimento gengival em ratos. Para todos os animais a avaliação não demonstrou alterações gengivais, independentemente da dosagem e do período de tratamento. A análise histométrica evidenciou ausência de alteração significante na área de tecidos epitelial e conjuntivo, embora, após 40 dias de tratamento, tenha sido observada diminuição na área de tecido conjuntivo, não significante estatisticamente. Dentro dos limites deste estudo, sugerimos que o diltiazem não induziu crescimento gengival.