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.

Synergistic effect of honey and Nigella sativa on wound healing in rats

Abstract Purpose: To investigate the therapeutic potential of honey, Nigella sativa (N. sativa) and their combination in rat model of excisional wound healing. Methods: A circular excision wound was established in the back region of 50 Wistar rats. Subsequently, they were divided into 5 groups and daily topical administration of lanolin in the control group, honey in the honey group, cold-pressed N. sativa seed oil in the N. sativa groups, mix of 1:1 ratio of honey and N. sativa seed oil in the mix group, and phenytoin cream in the phenytoin group were used. Then, wound surface areas were evaluated using digital camera immediately after the injury and at post excision days 5, 10, 15 and 20. Results: Significant reduction in wound surface area was observed within and between the groups (P < 0.001). In the post excision days 5, 10, 15 and 20 the wound surface areas in the mix group were significantly lower than the other groups followed by the phenytoin, honey, N. sativa, and control groups. Conclusion: The wound healing may be improved and accelerated by using topical solutions of honey, N. sativa seed oil and especially their mixture.

Comparing anticonvulsive effect of melissa officinalis' hydro-alcoholic extract and phenytoin in rat

Epilepsy originates from brain function disorders that might appear in the forms of overt disorders or fainting [losing consciousness], abnormal motional activities, behavioral abnormalities and sensational impairment and/or disorders in autonomic performance; all these symptoms are observable in early sleeping stages. Epilepsy is one of the most common neural disorders in human beings and with regard to the conducted studies, the Melissa officinalis plant has been used to treat epilepsy disease. Therefore, in this empirical work the effect of pretreatment with hydro-alcoholic extract of this plant compared to Phenytoin in the prevention of the epileptic convulsions caused by Pentylenetetrazole was studied. In this research the following groups receive the following drug doses intraperitoneal: four groups received different concentrations of extract [25, 50, 100, 200 mg/kg body weight], the positive control group was tested by Phenytoin [5 mg/ kg] and the negative control group was tested by normal saline. Data were analyzed by kruskal - Wallis test and Tukey test. Injection of 50 and 100mg of the extract per kilogram of the body weight during the30 minutes interval before the systemic injection of Pentylenetetrazole, resulted in delay in the average onset time of the clonic convulsion Seizures with respect to the control group [P = 0.001] and also delay in the average onset time of the tonic - clonic Seizures with respect to the control group [P = 0.02] and besides the rates of mortality in that group of animals which were pretreated with 50 and 100 mg concentrations of the extract per kg of body weight indicated a significant difference with respect to the control group [P = 0.004] . Mortality rate was 100% in the negative control group, 37.5% in the50 mg/kg weight group and 12.5% in the 100 mg/kg weight group and 12.5% in the group treated by Phenytoin. This study indicated that the hydro-alcoholic extract of the Melissa officinalis plant can cause helpful effects on Seizures induced by Pentylenetetrazole in rats. Therefore, further studies are needed to understand the extent and mechanism of these effects

Comportamiento del estatus convulsivo en niños atendidos en la UCI-P del Hospital Fernando Vélez Paiz de enero 2008-diciembre 2009 / Convulsive status behavior in children treated at the ICU-P Fernando Velez Paiz Hospital January 2008-December 2009

El estudio realizado en niños con Estatus Convulsivo ingresados en la UCIP del HFVP de Enero 2008- Diciembre 2009 la muestra fue de 16 pacientes.En relación a la edad y el sexo, el grupo etareo más afectado fue de 1- 5 años con 58%(9), siendo 6(38%) masculino y 19%(3) femeninas, seguido del 6-10 años con el 19%, de estos13%(2) masculino y 6%(1) femenino.Al revisar los antecedentes patológicos personales el 38%(6) tenía antecedentes de convulsión febril, Epilepsia 25%(5) y el 13%(2) asfixia perinatal. La principal etiología del EC fue la Epilepsia en 44%(7), seguida de la supresión del tratamiento anticonvulsivante y la fiebre en un 25% respectivamente. En el tratamiento se utilizó la Difenilhidantoina en 15 pacientes, la dosis de impregnación fue 18-20 mg/kg en el 80%(12), el Fenobarbital se utilizó en 3 pacientes, con dosis de impregnación de 10mg/kg/d en el 60% de los pacientes que se uso. En el tratamiento de mantenimiento el fármaco más utilizado fue la Difenilhidantoina en 12 pacientes, a dosis 5mg/kg/día en el 75%, seguido del Acido Valproico en 7 pacientes a dosis de 15 mg/kg/día y Fenobarbital en 4 pacientes a dosis 5mg/kg/día .La ventilación mecánica se utilizó en 5 pacientes, de estos el 40% estuvo 4-6 días con soporte ventilatorios.Dentro de los estudios complementarios realizados en los pacientescon estatus convulsivo: al 75% se les realizó Ionograma encontrando Hipocalcemia en el 44%(7), e Hiponatremia e hipernatremia en el 13%(2) de los casos respectivamente.Se presentaron complicaciones en 7 pacientes, y la complicación que se presento con mayor frecuencia fue las alteraciones electrolíticas en el 50%(7), seguida del edema cerebral 35%(5), la hemorragia intracraneal y el infarto isquémico en el 7% respectivamente.La condición de egreso el 100% de los pacientes estudiados fue dado de alta y de estos el 88%(14) no presento ninguna secuela, solo el 13%(2) presentó secuelas dentro de ellas hemiparesias e hipotonía.

Studies on the potentiation analgesic effect of phenytoin and ketorolac with pelitazocine using albino mice by eddy's hot plate method

The analgesic activity was tested by Eddy's hot plate method in albino mice using combination of Pentazocine [1 mg/kg] with Phenytoin [10.20 mg/kg] and Pentazocine [1 mg/kg] with Ketorolac [10.20 mg/kg] was given by intra-peritoneal administration, The results showed a significant increase in reaction time [analgesia] in albino mice and hence the present study indicates that combination of Phenytoin and Ketorolac with Pentazocine has significant prolonged analgesic effect as compared with analgesic effect produced by Pentazocine alone

Comparison of the healing effects of topical phenytoin, estrogen and silver sulfadiazine on skin wounds in male rats

Shortening of the duration of wound healing is an attractive subject for investigators in recent years. In this study, the effects of topical phenytoin, silver sulfadiazine, estrogen and their combination on wound healing were evaluated. This experimental study was accomplished on 30 male albino rats, which had an approximate weight from 110 to 150 grams and were kept under standard conditions. A skin wound with a diameter of 20 mm was cut on the back of neck of each rat. Animals were divided into 6 groups and each animal was carried in a special isolated cage. For the first group, no drugs were used on the wounds. Topical 1% silver sulfadiazine cream was used in the second group.Third group recevied topical 1% phenytoin ointment. Wounds in fourth group were treated with 0.06% estrogen cream. Wounds in the fifth group were treated with the combination of 1% silver sulfadiazine and 1% phenytoin creams and wounds in the sixth group were treated with combination of 1% silver sulfadiazine cream and the estrogen cream. Surgery day was considered as the first day and animals were followed up for 28 days. Wound surface area was assessed on each animal and the healing rate was assessed on days: 1, 3, 7, 14, 21.The most effective treatments were topical estrogen cream alone and topical phenytoin-silver sulfadiazine combination. Combination of topical estrogen and other drugs and phenytoin alone showed less acceleration on wound healing. Although application of topical estrogen cream alone or combination of phenytoin and silver sulfadiazine creams showed more healing effect, but there was no significant difference on the wound healing of animals that were treated by these products. Further studies on human wounds with larger sample size is suggested

Pharmacological studies on mechanisms of aminophylline-induced seizures in rats.

In the present study, the possible role of free radicals in aminophylline-induced seizures was evaluated in albino rats. Aminophylline (theophylline in ethylene diamine; 50 - 300 mg/kg) induced convulsions in rats in a dose-dependent manner, and both incidence of seizure and mortality were maximum at 300 mg/kg. Conventional anti-epileptics, diphenylhydantoin and dizocilpine, as well as adenosine agonists were ineffective in antagonizing these seizures. On the other hand, phosphodiesterase inhibitors, pentoxyphylline and rolipram, showed insignificant seizurogenic effects. Pretreatment with antioxidants (ascorbic acid, alpha-tocopherol, and melatonin) showed differential attenuating effects on aminophylline seizures and lethality. Further, prior administration of 1-buthionine sulfoxamine (BSO, glutathione depletor) and triethyltetramine (TETA, superoxide dismutase inhibitor), precipitated seizures and enhanced lethality in response to subthreshold doses of aminophylline. The present results suggested of the possible involvement of oxidative stress during aminophylline-induced seizures.

Conduta clínica no atendimento odontológico ao paciente submetido à terapia com fenotoína / linical management at the dentistry care provided into patients submitted to phenytoin therapy

A fenitoína, droga comumente utilizada como anticonvulsivante, apresenta diversos efeitos colaterais, dentre os quais, a hiperplasia gengival medicamentosa, dificultando a higienização, favorecendo o acúmulo de biofilme e cálculos dentários, incrementando ainda mais a presneça de lesões cariosas e dos processos inflamatórios e infecciosos na própria gengiva. Assim sendo, diversos cuidados inerentes ao atendimento odontoilógico devem ser seguidos. O propósito deste trabalho foi de apresentar e discutir as condutas do atendiemnto odontológico ao paciente submetido à terapia com esta droga

An experimental evaluation of anticonvulsant activity of Vitex-negundo.

Maximal electroshock seizures (MES) in albino rats and pentylenetetarazole (PTZ) induced seizures in albino mice were used to study anticonvulsant activity of Vitex-negundo leaf extract. The ethanolic leaf extract of Vitex-negundo was administered orally in graded doses (250, 500 and 1000 mg/kg p.o) in both the experimental models and the effects were compared with diphenylhydantoin in MES method and valporic acid in PTZ induced seizures method as standard control respectively. The Vitex-negundo in the doses (250, 500 and 1000 mg/kg, p.o) did not show protection against MES to any significant extent but significant post-ictal depression was observed in the dose of 1000 mg/kg body weight in comparison to control. However, sub-protective dose of test drug (100 mg/ kg, p.o) potentiated the anticonvulsant action of diphenylhydantoin. The test drug in the dose (1000 mg/kg, po) showed 50% protection in clonic seizures and 24-hour mortality against PTZ induced seizures. It also decreased number and duration of convulsions significantly. Vitex-negundo potentiated anticonvulsant activity of valporic acid. The anticonvulsant activity of Vitex-negundo has not been found equi-effective with standard drugs. These findings suggest that Vitex-negundo possesses anticonvulsant activity particularly against PTZ induced convulsions. Moreover, the potentiation of diphenylhydantoin and valporic acid by Vitex-negundo indicates that it may be useful as an adjuvant therapy along with standard anticonvulsants and can possibly lower the requirement of diphenylhydantoin and valporic acid.

Phenytoin action in the lingual mucosa of rat fetuses: morphometric study

Desde 1930 la fenitoina (difenilhidantoina) ha sido el anticonvulsivante elegido en el tratamiento de desórdenes súbitos. Numerosos estudios epidemiológicos y clinicos en humanos mostraron un incremento en malformaciones en descendientes de madres que ingirieron fenitoina durante la gestación, tales como: desarrollo craneofacial y crecimiento anormales, hipoplasia falangica distal, y alta o moderada deficiencia mental. Este trabajo tiene como objetivo estudiar la mucosa lingual, analizando los aspectos histopatológico y morfometrico, en fetos de ratas a los cuales se colocó una dosis única de fenitoina (70 mg/kg de peso) via intraperitoneal. El material examinado fue incluido en parafina y cortada a 6 µm y luego te¤ido con HE. Los parametros morfometricos fueron estimados, usando dibujos (50 bosquejos) hechos en papel y medidos usando una escala milimetrica, obtenido con la ayuda de una cámara de luz JENA, con un aumento final de 1000X. El analisis estadistico fue realizado empleando el test no parametrico Mann-Whitney. Los resultados mostraron que el peso promedio de los animales tratados decreció. Ademas, fueron observados cambios histopatológicos y morfometricos en todas las regiones linguales.

Effects of low-dose phenytoin administered to rats fetuses on developing choroid plexus: kariometric study

The aim of the present study was to determine, by kariometric parameters, the influence of phenytoin, as teratogen, on the epithelial layer of choroid plexus in rats fetuses, using single daily dose ( 75 mg Kg-1 bd.wt.), during gestation GD9 to GD11, and lowest total dose used orally (225 mg Kg-1), to the best of our knowledge. In some of experimental studies in animals, the anticonvulsant drug phenytoin were administered in embriotoxic daily doses (100-1500 mg Kg-1 bd.wt.) increasing concentrations up to 20 times the human therapeutic plasma concentration. There is a significant lack of information regarding the embriotoxicity in pregnancy of these drug, phenytoin, in low doses. Phenytoin was administered in a single daily dose (75 mg Kg-1 bd.wt.) to pregnanty rats in GD9 to GD11 days of gestation, during organogenesis. Histological sections were obtained for analysis of nuclear alterations in the cuboidal epithelium of choroid plexuses of lateral ventricles in the rat fetuses. Eleven kariometric parameters were measured in each of the nuclei. Statistical comparison were made with Mann-Whitney's test. The nuclei of the phenytoin group showed significant reduction of the size parameters : longest axis, mean axis, nuclear volume, nuclear area, nuclear perimeter, ratio of the longest axis to the shortest axis, ratio of the nuclear volume to the nucleararea) but not in shortest axis and shape parameters (contour index, shape factor and eccentricity) . A distinctive pattern of nuclear abnormalities in choroid plexus ephitelium of rat fetuses is associated with the use of low dose of phenytoin during pregnancy. Variations in nuclear size might reflect fundamental nuclear alterations of significance during the process of embriogenesis and could represent teratogenic influence of phenytoin in rats. Even at low dosage and short period of use during gestation, phenytoin can induce embriotoxicity.

Efecto de la fenitoína prenatal en fetos de rata: estudio morfológico y morfométrico de la glándula submandibular / Effect of prenatal phenytoin on rat fetuses: and morphometrical study of the submandibular gland

La fenitoína (difenil hidantoína) es una droga anticonvulsiva y antiarrítmica, que posee acción teratógena en animales y humanos, causando importantes alteraciones, aún cuando se administra en dosis no teratógenas. Con el objetivo de estudiar morfológica y morfométricamente los efectos de la droga sobre la glándula submandibular fetal, ratas Wistar fueron inyectadas el 10ª día de preñez, con 70, 100 ó 150 mg/kg de fenitoína. Las dosis más altas provocaron la muerte intrauterina de todos los fetos. El peso de los fetos de las ratas inyectadas con 70 mg/kg de fenitoína fue menor que el de los controles. El examen histopatológico de la glándulas submandibular reveló una glándula inmadura, constituida por acinos y conductos mayores y con luz disminuida. Las células de los acinos y conductos eran mayores, con núcleos más grandes. El tejido conjuntivo era más escaso en los fetos del grupo tratado. Morfométricamente, fue posible confirmar los hallazgos histopatológicos. Los resultados sugieren que la exposición prenatal a la fenitoína, en dosis no teratógenas, actúa en la embriogénesis, causando alteraciones en el desarrollo (menor peso, cordón umbilical más corto y glándula submandibular menos diferenciada), mostrando el feto tratado aspectos de inmaturidad

Análise quantitativa dos tecidos gengivais de ratos tratados com fenitoína e ciclosporina / Quantitative analysis of gingival tissues of rats treated with phenytoin and cyclosporine

Os aumentos gengivais podem ser decorrentes de reaçöes teciduais a estímulos idiopáticos, patológicos e farmacológicos. O objetivo desse trabalho foi avaliar morfometricamente e estereologicamente a açäo da fenitoína (Fen) e ciclosporina (CsA) sobre os tecidos gengivais de ratos. Dez ratos receberam, por via intraperitonial, Fen na dose inicial de 2 mg/kg de peso corporal/dia, aumentando 2 mg a cada duas semanas, durante 60 dias. Em outros 10 ratos, administraram-se, por via subcutânea, 10 mg/kg de peso corporal/dia de CsA, durante o mesmo período do grupo anterior. Os valores morfométricos e estereométricos dos tecidos gengivais dos ratos tratados com CsA foram significativamente maiores quando comparado com os valores dos tecidos gengivais do grupo tratado com Fen. Esses resultados sugerem que a CsA na dose utilizada é mais eficaz no desenvolvimento do aumento gengival em ratos, podendo estar atuando na proliferaçäo de fibroblastos e no desequilíbrio fisiológico da síntese de fibras colágenas

Teratogenic effects of dilantin on thoraco-abdominal organs of developing chick embryos.

Congenital anomalies on some viscera like heart, liver and kidney have been investigated in chick embryos after a single injection of dilantin (3 mg/egg), a known antiepileptic drug, on 4th day of incubation. On 19th day of incubation, chick embryos were collected to observe the gross malformations and histological changes in heart, liver and kidney. On gross examination, visceroptosis (29%), thin anterior abdominal wall (28%), ectopia cordis (10%) and dextrocardia (1%) were observed. Histological examination of the kidney revealed glomerular degeneration in kidney while in liver, dilated central veins with degenerated hepatocytes were present. Longitudinal section of the heart showed thicker musculature specially of ventricles with a narrower lumen in comparison to that of the control. The results indicate teratogenicity of dilantin in developing chick embryos.

Possible analgesic effect of vigabrin in animal experimental chronic neuropathic pain

Since anticonvulsants have been used for treating neuralgias, an interest has arisen to experimentally test vigabatrin for its gabaergic mechanism of action. For this, 41 Wistar rats were used, and in 25 of them a constractive sciatic neuropathy was induced (Bennet & Xie model). For testing pain symptoms, spontaneous (Scratching) and evoked behaviors to noxious (46 degrees Celsius) and non-noxious (40 degrees Celsius) thermal stimuli were quatified. Moreover, a comparative pharmacological study of vigabatrin with other analgesic anticonvulsant drugs was also performed. The results showed a possible dose-dependent analgesic effect of vigabatrin (gamma-vinyl-GABA) on experimental neuropathic pain, as shown vy the significant (p<0.05) decreasing effect of vigabatrin on scratching and by its significant (p>0.05) increasing effect on the latency of the right hindpaw withdrawal of the animals to noxious thermal stimulus. This was corroborated by similar findings with analgesic anticonvulsants (carbamazepine, phenytoin and valproic acid). This possible and not yet described analgesic effect of vigabatrin seems not to be opioid mediated.

Terapêutica em epilepsia / Therapeutics in epilepsy

Esta revisão sumária sobre terapêutica em epilepsia aborda questões tais como quando começar o tratamento, qual a droga antiepilética (DAE) indicada para os diversos tipos de crise, quando retirar a DAE, sua posologia, frequência de tomadas, efeitos colaterais e idução/inibição enzimática da DAE, monitorização do tratamento e epilepsia refratária. Várias dessas questões são dependentes do conhecimento de farmacocinética e farmacodinâmica, fatos que também são considerados.

Effect of diphenylhydantoin administration on the growth of the functional components of rat skull

With the purpose of studying the effect of diphenylhydantoin (DPH) administration on the growth of the functional components of the rat skull, male Wistar rats weighing 61.6 + 0.6g were assigned to 1 out of 4 different groups. One of them received saline and was taken as normal control. The others were injected once daily with 25,50 or 100 mg/Kg of b.w. of DPH i.p. for 20 days. Another group of rats was put under a restricted diet (RD) (20 percent of normal intake) for the same time for evaluation of the cranial dimensions. On day 21, the rats were killed by ether overdose and fifteen cranial dimensions were evaluated as peviously described employing Pucciarelli's method. The body weight gain of DPH injected rats was up to 20.7 percent lower independently of drug dose. The rats of the RD group showed a similar reduction. The amount of food consumed by DPH rats was 16 percent lower than that consumed by controls independently of drug doses. The concentration of alkaline phosphatase and hemoglobin in rats treated with 50 or 100 mg/kg b.w. of DPH was lower than in controls and RD-animals. However, urea and total calcium in plasma were unchanged in DPH-treated rats as compared to controls. Mean appetite quotient, efficiency of protein and energy utilization did not appear to change in response to the treatment with DPH or maintained under a restricted diet. That cranial dimensions of rats, injected with 25mg/kg b.w. of DPH were not statistically different from those of the control and RD-groups. When the dose of DPH injected was 50 mg/kg b.w. the neurocranial width an height and the spachnocranial length were significantly lower than controls and RD-values. Moreover, all the dimensions corresponding to neurocranium and splachnocranium (width, height and length) of the rats injected with 100 mg/kg b.w. of DPH were significantly lower than those of control and RD-groups. The disharmonius growth of the skull do not appear to be dependent on suboptimal energy intake, efficiency of protein, energy utilization renal failure and anemia.