Modelo animal de ectasia corneal en conejo mediante inyección intraestromal de colagenasa tipo ii / Animal model of corneal ectasia in rabbits by intrastromal injection of type II collagenase

Introducción La colagenasa ii ha sido utilizada para inducir queratocono experimental en modelos animales. Sin embargo, no ha sido estudiado su efecto cuando se administra por inyección intraestromal, por lo que el propósito de este estudio fue estudiar los efectos de la inyección intraestromal de colagenasa ii sobre la superficie corneal y la morfología de la córnea. Método Se trabajó con 6 conejos Nueva Zelanda, se administró colagenasa ii por inyección intraestromal (5μL de 2,5mg/mL) en los ojos derechos y solución salina balanceada en los ojos izquierdos. Se realizaron queratometrías para evaluar la alteración de la curvatura, también al séptimo día se obtuvieron las córneas y se realizó tinción hematoxilina-eosina para examinar los cambios morfológicos. Asimismo, se investigaron los cambios en la expresión de colágeno tipo i por tinción rojo sirio y PCR semicuantitativa. Resultados K1, K2 y Km presentaron diferencias en los promedios con cambios estadísticamente significativos. Los cambios morfológicos que se demostraron fueron degradación y disposición irregular del estroma corneal, incremento en la densidad celular de queratocitos y ligera infiltración celular. Finalmente se demostró que hay mayor expresión de fibras de colágeno tipo i en el grupo experimental a diferencia de los controles y el grosor de las fibras también aumentó por acción de la colagenasa ii; sin embargo, en cuestión génica no hubo cambios en la expresión de colágeno tipo i a nivel molecular entre el grupo control y experimental. Conclusiones La colagenasa ii administrada por inyección intraestromal es capaz de inducir cambios en la superficie corneal y el estroma, pudiendo simular un modelo de queratocono (AU)

Introduction Collagenase II has been used to induce experimental keratoconus in animal models. However, its effect when administered by intrastromal injection has not been studied, so the purpose of this study was to study the effects of intrastromal injection of collagenase II on corneal surface and corneal morphology. Method Six New Zealand rabbits were used, collagenase II was administered by intrastromal injection (5μL of 2.5mg/mL) in the right eyes and balanced salt solution in the left eyes. Keratometry was performed to evaluate curvature alteration, also at day 7 corneas were obtained and hematoxylin–eosin staining was performed to examine morphologic changes. Likewise, changes in type I collagen expression were investigated by Sirius Red staining and semi-quantitative PCR. Results K1, K2, and Km presented differences in the means with statistically significant changes. The morphological changes that were demonstrated were degradation and irregular arrangement of the corneal stroma, increase in the cellular density of keratocytes and slight cellular infiltration. Finally, it was demonstrated that there is greater expression of type I collagen fibers in the experimental group as opposed to the controls and the thickness of the fibers also increased due to the action of collagenase II, however, in terms of genetics there were no changes in the expression of type I collagen at molecular level between the control and experimental groups. Conclusions Collagenase II administered by intrastromal injection is able to induce changes in the corneal surface and stroma, being able to simulate a model of keratoconus (AU)

Animal model of corneal ectasia in rabbits by intrastromal injection of type II collagenase.

INTRODUCTION: Collagenase II has been used to induce experimental keratoconus in animal models. However, its effect when administered by intrastromal injection has not been studied, so the purpose of this study was to study the effects of intrastromal injection of collagenase II on corneal surface and corneal morphology. METHODS: Six New Zealand rabbits were used, collagenase II was administered by intrastromal injection (5µL of 2.5mg/mL) in the right eyes and balanced salt solution in the left eyes. Keratometry was performed to evaluate curvature alteration, also at day 7 corneas were obtained and Hematoxylin-Eosin staining was performed to examine morphologic changes. Likewise, changes in type I collagen expression were investigated by Sirius Red staining and semiquantitative PCR. RESULTS: K1, K2 and Km presented differences in the means with statistically significant changes. The morphological changes that were demonstrated were degradation and irregular arrangement of the corneal stroma, increase in the cellular density of keratocytes and slight cellular infiltration. Finally, it was demonstrated that there is greater expression of type I collagen fibers in the experimental group as opposed to the controls and the thickness of the fibers also increased due to the action of collagenase II, however, in terms of genetics there were no changes in the expression of type I collagen at molecular level between the control and experimental groups. CONCLUSIONS: Collagenase II administered by intrastromal injection is able to induce changes in the corneal surface and stroma, being able to simulate a model of keratoconus.

Eficacia y seguridad de la colagenasa de Clostridium histolyticum en la enfermedad de Peyronie según un protocolo de tratamiento modificado / Efficacy and safety of collagenase Clostridium histolyticum in Peyronie's disease following a modified treatment protocol

Introducción: La colagenasa de Clostridium histolyticum (CCH) es el único medicamento con licencia para el tratamiento conservador en la enfermedad de Peyronie (EP) que ha demostrado eficacia y seguridad en ensayos clínicos. Sin embargo, el protocolo de tratamiento estándar consume tiempo y recursos, por lo que presentamos un nuevo protocolo de tratamiento con CCH con un perfil más rentable. Nuestro objetivo es evaluar su eficacia y su seguridad.Materiales y métodosSe incluyeron pacientes con EP en fase estable, con curvaturas de 30-90°. Se excluyeron curvas ventrales y deformidades complejas. El protocolo de tratamiento consiste en una dosis completa de CCH inyectada a lo largo de la placa de EP formando 2 líneas de 4 inyecciones. Se educó a los pacientes en los ejercicios diarios de modelado del pene. La necesidad de un nuevo ciclo de tratamiento fue reevaluada cada 4semanas hasta un máximo de 8 ciclos o hasta la disminución de la curva de 30°. Para evaluar la eficacia se registraron los cambios en la curvatura y el número de ciclos. Para evaluar la seguridad se registraron los eventos adversos graves relacionados con el tratamiento, incluyendo la rotura de cuerpos cavernosos, hematoma peneano, hematuria e infección local.ResultadosUn total de 31 pacientes fueron tratados bajo el protocolo modificado. La curvatura inicial media fue de 49,84 (±15,83) grados. Se registró mejora en la curvatura en 25 pacientes (80,6%), con una disminución media absoluta de 20,65 (±15,42) grados y relativa del 44%. La curvatura media posterior al tratamiento fue de 30,67 (±17,25) grados. La mayoría de los pacientes requirieron una (19,4%) o dos (54,8%) inyecciones. Ningún paciente presentó eventos adversos graves relacionados con el tratamiento.ConclusionesLos resultados sugieren que el protocolo de tratamiento modificado con CCH es eficaz y seguro, pero se deben realizar más estudios que ayuden a optimizar el protocolo estándar actual. (AU)

Introduction: Collagenase Clostridium histolyticum (CCH) is the only approved treatment for conservative management of Peyronie's disease (PD) that has demonstrated efficacy and safety in clinical trials. However, as the standard treatment protocol is time and resource consuming, we are introducing a new CCH treatment protocol with a more cost-effective profile. Our goal is to evaluate its efficacy and safety.Materials and methodsWe included patients with PD in stable phase, with curvatures of 30-90degrees. Ventral curvatures and complex deformities were excluded. The treatment protocol consists of a full dose of CCH injected along the PD plaque, forming two lines of four injections. Patients were educated in daily penile modeling activities. The need for a new treatment cycle, up to a maximum of 8 cycles or until the 30-degree curve was decreased, was reevaluated every 4weeks. Changes in curvature and number of cycles were recorded to evaluate the efficacy. Regarding safety evaluation, treatment-related adverse events (TRAEs) were recorded, including rupture of the corpora cavernosa, penile hematoma, hematuria, and local infection.ResultsThirty-one patients were treated under the modified protocol. The mean initial curvature was of 49.84 (±15.83) degrees. Curvature improvement was recorded in 25 patients (80.6%), with a mean absolute reduction of 20.65 (±15.42) degrees and relative reduction of 44%. The mean curvature after treatment was 30.67 (±17.25) degrees. Most patients required one (19.4%) or two (54.8%) injections. No patient presented TRAEs.ConclusionsThe results suggest that the modified CCH treatment protocol is effective and safe, but more studies should be carried out to optimize the current standard protocol. (AU)

Efficacy and safety of collagenase Clostridium histolyticum in Peyronie's disease following a modified treatment protocol. / Eficacia y seguridad de la colagenasa de Clostridium histolyticum en la enfermedad de Peyronie según un protocolo de tratamiento modificado.

INTRODUCTION: Collagenase Clostridium histolyticum (CCH) is the only approved treatment for conservative management of Peyronie's disease (PD) that has demonstrated efficacy and safety in clinical trials. However, as the standard treatment protocol is time and resource consuming, we are introducing a new CCH treatment protocol with a more cost-effective profile. Our goal is to evaluate its efficacy and safety. MATERIALS AND METHODS: We included patients with PD in stable phase, with curvatures of 30-90degrees. Ventral curvatures and complex deformities were excluded. The treatment protocol consists of a full dose of CCH injected along the PD plaque, forming two lines of four injections. Patients were educated in daily penile modeling activities. The need for a new treatment cycle, up to a maximum of 8 cycles or until the 30-degree curve was decreased, was reevaluated every 4weeks. Changes in curvature and number of cycles were recorded to evaluate the efficacy. Regarding safety evaluation, treatment-related adverse events (TRAEs) were recorded, including rupture of the corpora cavernosa, penile hematoma, hematuria, and local infection. RESULTS: Thirty-one patients were treated under the modified protocol. The mean initial curvature was of 49.84 (±15.83) degrees. Curvature improvement was recorded in 25 patients (80.6%), with a mean absolute reduction of 20.65 (±15.42) degrees and relative reduction of 44%. The mean curvature after treatment was 30.67 (±17.25) degrees. Most patients required one (19.4%) or two (54.8%) injections. No patient presented TRAEs. CONCLUSIONS: The results suggest that the modified CCH treatment protocol is effective and safe, but more studies should be carried out to optimize the current standard protocol.

Uso de enzimas como tratamiento dermatológico regenerador de las líneas de expresión / Use of enzymes as a regenerative dermatological treatment of expression lines / Uso de enzimas como tratamento dermatológico regenerativo de linhas de expressão

INTRODUCCIÓN: el tratamiento con enzimas es una alternativa estética mínimamente invasiva para mejorar la apariencia facial y disminuir las líneas de expresión. OBJETIVO: Determinar el uso de las enzimas hialuronidasa, colagenasa y lipasa como tratamiento enzimático dermatológico para las líneas de expresión facial. MATERIALES Y MÉTODO: estudio de campo, prospectivo, población 457 pacientes que acudieron a la consulta dermatológica entre los años 2013 y 2018 para tratamiento con enzimas. El instrumento de recolección de datos fue la hoja de registro y la fuente documental las historias clínicas. El método estadístico fue descriptivo, la información se presenta en tablas y gráficos. RESULTADOS: la edad promedio de los pacientes fue de 45,2 ± 10,1 años, 40,9% recibió 2 kits de enzimas con los 3 componentes básicos de colagenasa, hialuronidasas y lipasas. Se encontró diferencia significativa en la relación de atención entre hombres y mujeres, de 1:14, es decir las mujeres acudieron más a la consulta solicitando la colocación de este tratamiento. CONCLUSIÓN: el tratamiento con enzimas aporta beneficios al incrementar la permeabilidad dérmica, aumenta el flujo sanguíneo y el drenaje linfático, disminuye los tabiques fibrosos de la celulitis, la flacidez, adiposidades, y rejuvenece el aspecto general. Por lo que se plantea como un tratamiento efectivo para disminuir las líneas de expresión.

INTRODUCTION: enzyme treatment represents a minimally invasive aesthetic alternative to improve facial appearance and decrease expression lines. OBJECTIVE: to determine the use of the enzymes hyaluronidase, collagenase and lipase as a dermatological enzyme treatment as a regenerative treatment for expression lines. METHODS: a prospective field study was conducted of a population made up of 457 patients who attended the UNIMEL dermatological consultation between 2013 and 2018 to be treated with enzymes. The data collection instrument was the record sheet and the documentary source was the medical records. The statistical method was descriptive, the information is presented in tables and graphs. RESULTS: the average age was 45.2 ± 10.1 years of age, to whom a majority of 40.9% were applied 2 kits of enzymes with the 3 basic components of collagenase, hyaluronidases and lipases to act synergistically each other enhancing functions and revitalizing the cells of the face. A significant difference was found in the care ratio between men and women, 1:14, that is, the women attended the consultation more requesting the placement of this treatment. CONCLUSION: the use of enzymes provides great benefits to increase skin permeability, increases lymphatic drainage, reduces fibrous septa of cellulite, sagging and fat, increases blood flow and rejuvenates the general appearance. So, it is proposed as an effective treatment to reduce expression lines

INTRODUÇÃO: o tratamento enzimático é uma alternativa estética minimamente invasiva para melhorar a aparência facial e diminuir as linhas de expressão. OBJETIVO: determinar o uso das enzimas hialuronidase, colagenase e lipase como tratamento enzimático dermatológico para linhas de expressão facial. MATERIAIS E MÉTODOS: estudo de campo em perspectiva, população de 457 pacientes que compareceram à consulta dermatológica entre 2013 e 2018 para tratamento enzimático. O instrumento de coleta de dados foi a folha de registros e a fonte documental foram os registros médicos. O método estatístico foi descritivo, as informações são apresentadas em tabelas e gráficos. RESULTADOS: a idade média dos pacientes foi de 45,2 ± 10,1 anos, 40,9% receberam 2 kits de enzimas com os 3 componentes básicos de colagenase, hialuronidases e lipases. Foi encontrada diferença significativa de 1:14 na relação de atenção entre homens e mulheres, ou seja, as mulheres compareceram mais frequentemente as consultas para a colocação desse tratamento do que aos homes. CONCLUSÃO: o tratamento enzimático oferece benefícios ao aumentar a permeabilidade dérmica, aumenta o fluxo sanguíneo e a drenagem linfática, reduz os septos fibrosos da celulite, flacidez, adiposidade e rejuvenesce a aparência geral. Por isso, é proposto como um tratamento eficaz para diminuir as linhas de expressão.

Colitis microscópica, un diagnóstico en aumento / Microscopic Cholitis, An Increasingly Frequent Diagnosis

Resumen Actualmente, la colitis microscópica agrupa tres subgrupos de patologías, las clásicas son la colitis linfocítica (CL) y la colitis colagenosa (CC), que histológicamente se distinguen por la presencia o ausencia de engrosamiento subepitelial; el tercer subgrupo corresponde a la colitis microscópica incompleta (CMI), que incluye a pacientes que no cumplen los criterios clásicos de colitis microscópica, pero que presentan cambios histológicos similares. Aunque se considera una enfermedad con baja prevalencia e incidencia, los estudios presentados en los últimos años evidencian un incremento leve de esta patología. Se han mencionado como factores causales los inmunológicos e infecciosos y se ha relacionado con el consumo de algunos medicamentos y de cigarrillo. Clínicamente se caracteriza por la presencia de diarrea acuosa crónica, que en algunos pacientes puede cursar con períodos de estreñimiento. Los tres subgrupos presentan manifestaciones clínicas similares, por lo que su diagnóstico generalmente es histológico. La colonoscopia con toma de biopsias es el pilar diagnóstico y se debe complementar con hemograma, examen parasitológico, estudios inmunológicos (anticuerpos antinucleares, IgG) y de función tiroidea. El tratamiento se basa en la suspensión de medicamentos relacionados, cambios en los hábitos alimenticios y en el uso de medicamentos, como los esteroides, subsalicilato de bismuto, 5-ASA y colestiramina. En la gran mayoría de los pacientes, la mejoría se logra con un bajo porcentaje de recidivas.

Abstract Microscopic colitis currently includes three subgroups. The classical ones are lymphocytic colitis and collagenous colitis which are distinguished histologically by the presence or absence of subepithelial thickening. The third subgroup is Incomplete Microscopic Colitis which includes patients who do not meet the classical criteria for Microscopic colitis but who have similar histological changes. Although prevalence and incidence are low, recent studies show that it has become slightly more common. Causative factors mentioned include immunological and infectious issue, and it has been related to some medications and to cigarette smoking. Clinically it is characterized by watery diarrhea which sometimes oscillate with periods of constipation. The three subgroups have similar clinical manifestations, so their diagnoses are usually histological. Colonoscopy with biopsy is the diagnostic pillar, and should be complemented by complete blood count, a parasitological examination, immunological studies (antinuclear antibodies, IgG) and thyroid function. Treatment is based on the suspension of related medications, changes in eating habits, and the use of medications such as steroids, bismuth subsalicylate, 5-ASA and cholestyramine. Improvement is achieved in the vast majority of patients, and recurrences are rare.

One year follow-up after treatment with CCH for Dupuytren's disease: A prospective view. / Evolución al año de tratamiento con CCH para la contractura de Dupuytren: estudio prospectivo.

Aim Clostridium histolyticum collagenase (CCH) is nowadays an alternative treatment for the contracture of Dupuytren. Our objective is to assess its effectiveness at one year in a series of consecutive patients. MATERIAL AND METHOD: Prospective study with minimum follow-up of one year. Evaluation of results and adverse effects. RESULTS: A total of 75 joints treated in 51 patients were included. The average age was 65.18years (SD: 7.288) and 82.7% were males. The initial mean contraction of the MCP was 34.0 degrees (SD: 27.37), PIP 41.5 degrees (SD: 31.33) and combined impairment (MCF+IFP) of 75.5 degrees (SD: 35.2). Efficacy was achieved in 68 patients (90.7%). Adverse effects were mild and self-limiting. The mean correction for the MCP joint was 28.96 degrees (SD: 26.90) and for PIP it was 28.72 degrees (SD: 24.30). The recurrence rate was 18 (24.0%) joints in 14 patients, being more frequent in severe cases. QuickDASH score showed minimal differences measured before the intervention and once a year. DISCUSSION: Our results show a better outcome in mild cases; the outcome was more favourable and with a higher success rate in the MCP joint. QuickDASH score is not a useful tool for the assessment of Dupuytren's contracture. CONCLUSIONS: Treatment with CCH for Dupuytren's contracture is an effective treatment in the medium term. It has a poorer outcome in combined joint disorders, 5th finger, PIP and severe cases.

El valor de la colagenasa en heridas agudas y crónicas / The value of collagenase in acute and chronic wounds

Se presenta en este trabajo una serie de pacientes con heridas agudas y crónicas, tratados con colagenasa como tratamiento tópico único o combinado. Se describe el producto y su papel en el manejo de heridas, junto a una búsqueda bibliográfica detallada sobre las características de esta enzima y su papel en el proceso de cicatrización.

A series of patients with acute and chronic wounds treated with collagenase, as single or combined topical treatment is presented in this work. This material and its role in wound management with a detailed literature search on the characteristics of this enzyme and its role in the healing process are described.

[Treatment of Dupuytren's disease using collagenase from Clostridium histolyticum]. / Tratamiento de la enfermedad de Dupuytren mediante la colagenasa del Clostridium histolyticum.

OBJECTIVE: The collagenase from Clostridium histolyticum is a new therapeutic option, and the first pharmacological one, in the treatment of Dupuytren's disease. MATERIAL AND METHODS: A prospective study was conducted on 35 patients with Dupuytren's disease. The clinical and functional variables, as well as patient satisfaction and drug safety were evaluated. RESULTS: The functional and clinical results after its administration were good, with a rapid recovery, especially at the metacarpophalangeal (MCP) joint. The index finger contracture prior to MCP puncture was 64 degrees and after puncture it was 4 degrees. In the proximal interphalangeal (PIP) prior to puncture it was 83.3 degrees and after puncture it was 15 degrees; In the MCP/PIP prior to puncture it was 140 degrees, and after puncture it 25 degrees. CONCLUSIONS: Collagenase from Clostridium histolyticum an alternative of treatment of Dupuytren's disease, mainly in the elderly. More research is required in order to clarify the rate of recurrence of the disease, the possible adverse reactions, and to compare the efficiency and permanence with other treatment options.

Efectos de Diclofenac, Celecoxib y sulfato de glucosamina sobre marcadores inflamatorios en cultivo de condrocitos de pacientes con osteoartritis / Articular cartilage in osteoarthritic patients: effects of diclofenac, celecoxib and glucosamine sulfate on inflammatory markers

La osteoartritis (OA) es una enfermedad articular crónica, progresiva que se instala como consecuencia de un proceso complejo que involcra alteraciones mecánicas y biológicas del sistema músculo-esquelético, siendo resultante de múltiples interacciones entre factores genéticos e injurias extrínsecas. La patogenia de esta enfermedad se ralaciona con alta y desviada producción de citokinas flogógenas y de enzimas proteolíticas, que degradan y destruyen la matriz extracelular en tejidos articulares y peri-articulares. Se estudiaron 20 casos con OA, de los cuales se obtuvo cartílago durante intervenciones quirúrgicas programadas. El cartílago se cultivó en medio Dulbecco-Eagle, con o sin agregado de AINEs o condromodulares. En los sobrenadantes se determinaron óxido nítrico por reacción de Giess y la medición espectrofotométrica; y colagenasa por ELISA doble sándwich en presencia de anticuerpos monoclonales. En ausencia de AINEs, los cultivos de condrocitos produjeron 1950 ± 665ng/ml de MMP-1, La adición de Diclofenac redujo esa cifra a 1140 ± 155 ng/ml, aunque esta diferencia no fue estadisticamente significativa, (p<0.60). Por el contrario, Celecoxib redujo el nivel de la enzima a 760 ± 75ng/ml (p<0,01) y la Glucosamina también provocó un descenso (950 ± 89 ng/ml) significativo (p<0.05). Los niveles de ON en ausencia de AINEs llegaron a 47,3 ± 4,9 µM. Su producción no varió significativamente con la adición de Diclofenac, Ceecoxib o Glucosamina (p=ns). Los resultados indicarían la incapacidad de Diclofenac para modificar la generación de enzimas proteolíticas, mientras que Celecoxib y Glucosamina disminuyen su producción significativamente. Ninguno de los fármacos utilizados en nuestro trabajo ha logrado alterar la concentración de ON. Muchos integrantes quedan aún sin resolver y todavía se carece de fármacos de eficacia comprobada para alterar el curso natural de la enfermedad.

Osteoarthritis is a chronic and progressive joint disease. It is established by a complex process involving mechanical and biological alterations of the musculoskeletal system, which are generated by a great variety of interactions between genetic factors and extrinsic injuries. The pathogenesis of this disease is related to an increased and divergent production of inflammatory markers and proteolytic enzymes that promote the degradation and destruction of the extracellular matrix of articular and periarticular tissues. Cartilage samples were taken from 20 osteoarthritic patients during programmed surgical interventions. The cartilage samples were cultured in Dulbecco-Eagle medium, with or without the addition of NSAIDs or modulators of chondrocyte metabolism. The content of nitric oxide in the supernatant was quantified using the Griess reaction; the concentration of MMP-1 was quantified via double-sandwich ELISA. Untreated chondrocyte cultures produced 1950 +/- 665 ng/ml MMP-1. With the addition of Diclofenac this value decreased to 1140 +/- 155 ng/ml, although this difference was not statistically significant (p < 0.06). However, in the presence of Celecoxib the level significantly dropped to 760 +/- 75 ng/ml (p < 0.01). Although the addition ofglucosamine did not produce such a noticeable reduction in the level of MMP-1 (950 +/- 89 ng/ml), it was statistically significant (p < 0.05). On the contrary, none of the drugs (Diclofenac, Celecoxib, Glucosamine) modified the level of nitric oxide which had a mean value of 47.3 +/- 4.9 microM in the control samples. This investigation evidenced the inability of Diclofenac to significantly modify the production of proteolytic enzymes in osteoarthritic chondrocyte cultures. However, both Celecoxib and Glucosamine significantly reduced the production of MMP-1. On the contrary, none of the drugs used in this study managed to modify the concentration of nitric oxide. To the present day, no drugs have been found to be...

Agrandamientos gingivales inducidos por drogas / Drug-induced gingival overgrowth

El objetivo de este trabajo es mostrar al lector los diferentes medicamentos y agentes terapéuticas que pueden ocasionar como efecto colateral, cambios en los tejidos periodontales, sobre todo en la encía. Estos agentes pueden clasificarse en medicamentos sistémicos, compuestos que se aplican en forma tópica y metales pesados. Entre los medicamentos sistémicos más comunes tenemos fenitoína, nifedipinas, ciclosporinas, valproato de sodio. Los cambios que producen estas drogas se relacionan especialmente con la encía en forma de agrandamiento gingival. Revisar algunos aspectos de estas drogas como generalidades farmacológicas, acción sobre el periodonto, diversas hipótesis sobre la patogénesis estas drogas, entre ellas la presencia de fibroblastos sensibles a la fenitoína, aspectos clínico histológicos y tratamiento.

Some therapeutic agents and drugs may induce changes in the periodontal tissues, specially he gingivae. They are classified as sistemic drugs, compounds that may be applied topically and heavy metals. Among the most commonly used sistemic drogs we can find Fenitoyn Nifedipins- Ciclosporin, sodium valproate wich gene rally produce gingival enlargement. This artice reviews farmacocinetics, involvement of periodontal tissue, pathogenesis, like sensitised fibroblast, to Fenitoyn, as well as clinical and histologic changes produced by these drugs. Treatment will also be discussed.