The influence of phytoestrogens or estrogens on the proliferation of the rat endocervical mucosa

SUMMARY INTRODUCTION Although estrogen therapy is widely used against post-menopausal symptoms, it can present adverse effects, including endometrial cancer. Soy isoflavones are considered a possible alternative to estrogen therapy. However, there are still concerns whether isoflavones exert trophic effects on the uterine cervix. OBJECTIVES To evaluate the histomorphometric and immunohistochemical alterations in the uterine cervix of ovariectomized rats treated with soy isoflavones (Iso). METHODS Fifteen adult Wistar rats were ovariectomized (Ovx) and divided into three groups: Group I (Ovx), administered with vehicle solution; Group II (OVX-Iso), administered with concentrated extract of Iso (150 mg/kg) by gavage; and Group III (OVX-E2), treated with 17β-estradiol (10 µg/kg), subcutaneously. After 30 days of treatments, the uterine cervix was fixed in 10% formaldehyde and processed for paraffin-embedding. Sections were stained with Hematoxylin and eosin for morphological and morphometric studies or subjected to immunohistochemistry for detections of Ki-67 and vascular endothelial growth factor-A (Vegf-A). The data obtained were subjected to statistical analysis (p ≤ 0.05). RESULTS We noted an atrophic uterine cervix in GI, whereas it was more voluminous in GII and even more voluminous in GIII. The thickness of the cervical mucosa was significantly higher in GIII, as compared to GI and GII. The cell proliferation (Ki-67) was significantly elevated in the estradiol and isoflavones treated groups, whereas Vegf-A immunoexpression was significantly higher in GIII, as compared to groups GII and GI. CONCLUSIONS Soy isoflavones cause less trophic and proliferative effects in the uterine cervix of rats as compared to estrogen.

RESUMO INTRODUÇÃO Embora a terapia estrogênica seja amplamente utilizada contra sintomas pós-menopausais, ela pode apresentar efeitos adversos, incluindo câncer de mama e endometrial. Assim, as isoflavonas da soja são consideradas uma alternativa possível à terapia estrogênica. No entanto, ainda há controvérsias se estes compostos exercem efeitos tróficos significativos no colo do útero. OBJETIVOS Avaliar as alterações histomorfométricas e imuno-histoquímicas no colo do útero de ratas ovariectomizadas tratadas com isoflavonas da soja (iso). MÉTODOS Quinze ratas Wistar adultas foram ovariectomizadas bilateralmente (Ovx) e separadas em três grupos: Grupo I (Ovx) - veículo (propilenoglicol); Grupo II (Ovx-Iso) - receberam extrato concentrado de Iso (150 mg/kg) e Grupo III (Ovx-E2) - tratado com 17β-estradiol (10 µg/kg); as soluções foram administradas via gavagem por 30 dias consecutivos. Posteriormente, os colos uterinos foram retirados, fixados em formaldeído a 10% tamponado e processados para inclusão em parafina. Cortes (4 µm) foram coradas com hematoxilina e eosina para estudo morfológico e morfométricos, enquanto outros foram submetidos à imuno-histoquímica para detecção de Ki-67 e do fator de crescimento endotelial vascular-A (Vegf-A). Os dados obtidos foram submetidos à análise estatística (p≤0,05). RESULTADOS Observamos a presença de colo uterino atrófico no GI (Ovx), sendo este mais volumoso no GII (Ovx+Iso) e ainda mais volumoso no GIII (Ovx+E2). A espessura da mucosa cervical foi significativamente maior no GIII (Ovx-E2), em comparação ao GI (Ovx) e ao GII (Ovx-Iso). A proliferação celular (Ki-67) foi significativamente mais elevada nos grupos tratados com estradiol e isoflavonas, enquanto a imunoexpressão de Vegf-A foi significativamente maior no GIII (Ovx-E2), em comparação ao GII (Ovx-Iso) e ao GI (Ovx-E2). CONCLUSÕES As isoflavonas da soja causam menos efeitos tróficos e proliferativos no colo do útero de ratas em comparação ao estrogênio.

Anastrozole promotes implantation by altering the expression of paxillin and fak in rat luminal uterine epithelium / El anastrozol promueve la implantación alterando la expresión de paxilina y fak en el epitelio uterino luminal de rata

An alternative hyper-ovulator inducer to replace clomiphene citrate (CC) is needed as it is unsuitable for women with polycystic ovarian syndrome and is associated with low pregnancy rates. Anastrozole is an effective hyper-ovulator inducer, but has not been well researched. In order to determine the effectiveness of anastrozole as a hyper-ovulator inducer and to an extent compare it with CC in similar situations, this study ascertained the effects of these drugs on the expression of the focal adhesion proteins, paxillin and FAK, which are uterine receptivity markers in the surface luminal uterine epithelial cells of day 1 and day 6 pregnant Wistar rats. The results show that paxillin is localized in focal adhesions at the base of the uterine epithelial cells at day 1 of pregnancy whereas at day 6, paxillin disassembles from the basal focal adhesions and localizes and increases its expression apically. FAK is faintly expressed at the basal aspect of the uterine epithelial cells while moderately expressed at the cell-to-cell contact at day 1 in all groups from where it disassembles and relocates apically and becomes more intensely expressed at day 6 of pregnancy in untreated and anastrozole treated rats. Although paxillin is localized apically at day 6, its expression is significantly down-regulated with CC treatment suggesting its interference with the implantation process. These findings seem to suggest that anastrozole could favor implantation.

Para reemplazar el citrato de clomifeno (CC) es necesario un inductor de hiperovulación alternativo, ya que no es adecuado para mujeres con síndrome de ovario poliquístico y está asociado con tasas bajas de embarazo. El anastrozol es un inductor eficaz del hiper-ovulador, pero no se ha investigado adecuadamente. Con el fin de determinar la efectividad del anastrozol como inductor del hiper-ovulador y, en cierta medida, compararlo con CC en situaciones similares, este estudio determinó los efectos de estos fármacos en la expresión de las proteínas de adhesión focal, paxillin y FAK, uterinas marcadores de receptividad en la superficie luminal de células uterinas epiteliales, del día 1 y día 6 en ratas Wistar preñadas. Los resultados muestran que la paxilina se localiza en adherencias focales en la base de las células epiteliales uterinas en el día 1 del embarazo, mientras que en el día 6, la paxilina se desmonta de las adherencias focales basales y localiza y aumenta su expresión apicalmente. FAK se expresa débilmente en el aspecto basal de las células epiteliales uterinas, mientras que se expresa moderadamente en el contacto de célula a célula en el día 1 en todos los grupos, donde se separa y se reubica apicalmente y se expresa con mayor intensidad el día 6 de la preñez, en pacientes no tratados y tratados. ratas tratadas con anastrozol. Aunque la paxillina se localiza apicalmente en el día 6, su expresión está significativamente disminuida con el tratamiento con CC, lo que sugiere su interferencia con el proceso de implantación. Estos hallazgos sugieren que el anastrozol podría favorecer el proceso de implantación.

Effects of anastrozole on Ki-67 antigen expression in the vaginal epithelium of female rats in persistent estrus

OBJECTIVES: Aromatase inhibitors are the first-choice drugs for the treatment of hormone sensitive breast cancer. However, in addition to the scarcity of studies, there are controversies about their effects on vaginal epithelial cell proliferation in rats, especially those in persistent estrus. METHODS: To investigate vaginal epithelial cell proliferation by Ki-67 antigen expression, persistent estrus was induced in 42 randomly selected rats. These rats were randomly divided into 2 groups: group I (control, n=21), which received 0.1 mL of propylene glycol (vehicle) daily, and group II (experimental, n=21), which received 0.5 mg/kg or 0.125 mg/day of anastrozole diluted with 0.1 mL of propylene glycol. RESULTS: Light microscopy showed a higher concentration of cells with brown Ki-67 stained nuclei in the control compared to the experimental group. The mean percentage of Ki-67 stained nuclei per 500 cells in the vaginal epithelium was 68.64±2.64 and 30.46±2.00 [mean±standard error of the mean (SEM)] in the control and experimental groups, respectively (p<0.003). CONCLUSION: This study showed that anastrozole, at the dose and treatment duration selected, significantly decreased cell proliferation in the vaginal mucosa of the rats in persistent estrus.

Effect of a gel containing pilocarpine on vaginal atrophy in castrated rats

OBJECTIVES: To evaluate the effect of Carbopol gel formulations containing pilocarpine on the morphology and morphometry of the vaginal epithelium of castrated rats. METHODS: Thirty-one female Wistar-Hannover rats were randomly divided into four groups: the control Groups I (n=7, rats in persistent estrus; positive controls) and II (n=7, castrated rats, negative controls) and the experimental Groups, III (n=8) and IV (n=9). Persistent estrus (Group I) was achieved with a subcutaneous injection of testosterone propionate on the second postnatal day. At 90 days postnatal, rats in Groups II, III and IV were castrated and treated vaginally for 14 days with Carbopol gel (vehicle alone) or Carbopol gel containing 5% and 15% pilocarpine, respectively. Next, all of the animals were euthanized and their vaginas were removed for histological evaluation. A non-parametric test with a weighted linear regression model was used for data analysis (p<0.05). RESULTS: The morphological evaluation showed maturation of the vaginal epithelium with keratinization in Group I, whereas signs of vaginal atrophy were present in the rats of the other groups. Morphometric examinations showed mean thickness values of the vaginal epithelium of 195.10±12.23 μm, 30.90±1.14 μm, 28.16±2.98 μm and 29.84±2.30 μm in Groups I, II, III and IV, respectively, with statistically significant differences between Group I and the other three groups (p<0.0001) and no differences between Groups II, III and IV (p=0.0809). CONCLUSION: Topical gel formulations containing pilocarpine had no effect on atrophy of the vaginal epithelium in the castrated female rats.

Analysis of the Ki-67 index in the vaginal epithelium of castrated rats treated with tamoxifen

OBJECTIVES: Vaginal atrophy and breast cancer are common conditions in postmenopausal women and tamoxifen is the standard endocrine treatment for hormone-sensitive tumors. The present study aimed to assess the effect of tamoxifen on Ki-67 protein expression in the vaginal epithelium of castrated rats. MATERIAL AND METHODS: Forty Wistar-Hannover adult, virgin, castrated rats were randomly divided into two groups, group I (control, n=20) and group II (tamoxifen, n=20), receiving 0.5 ml of propylene glycol and 250 µg of tamoxifen diluted in 0.5 ml of propylene glycol, respectively, daily by gavage for 30 days. On the 31st day, the rats were euthanized and their vaginas were removed and fixed in 10% buffered formalin for the immunohistochemical study of Ki-67 protein expression. Data were analyzed by the Levene and Student’s t tests (p<0.05). RESULTS: The mean index of Ki-67 expression in the rat vagina of groups I and II was 4.04±0.96 and 26.86±2.19, respectively (p<0.001). CONCLUSIONS: According to the results of the present study, tamoxifen, at the dose and treatment length used, induced a significant increase in the cell proliferation of the vaginal mucosa in castrated rats, as evaluated by Ki-67 protein expression.

Postnatal exposure to a progestin does not prevent uterine adenogenesis in domestic dogs

To assess the effects of a single supraphysiological postnatal administration of a progestogen on uterine glands in dogs, 10 females were randomly assigned to a medroxyprogesterone acetate 35 mg (MPA; n = 6) or placebo (n = 4) group within the first 24 h of birth. The safety of the treatment was also evaluated. A transient mild clitoris enlargement appeared in MPA-treated females. Microscopic postpubertal uterine assessment revealed the presence of uterine glands in all cases without significant differences in the area occupied by the glands per µm2 of endometrium nor in the height of the uterine epithelium.

El Campus Virtual de Salud Pública: seis años de formar recursos humanos en México / Virtual Campus of Public Health: six years of human resources education in Mexico

Este trabajo muestra, desde el punto de vista de la normatividad de la Organización Panamericana de la Salud (OPS), el proceso de gestación, la metodología de implementación y los resultados obtenidos de la iniciativa de formación de recursos humanos en salud vía e-learning a través del Campus Virtual de Salud Pública de la Universidad de Guadalajara, México, a seis años de su inicio. Se trata de un informe especial del trabajo realizado por el comité institucional del campus virtual en la región occidental de México para generar un portal de Internet que se ajustara a los lineamientos del Modelo Estratégico establecido por el Nodo México y la OPS para la Región de las Américas. Este Campus Virtual inició sus actividades en el año 2007. Su filosofía es el uso de software libre y la colaboración entre instituciones. El nodo fue implementado en un año y ha logrado capacitar a más de 500 profesionales de la salud a través de cursos virtuales, su plataforma educativa y un repositorio de recursos virtuales de aprendizaje con interoperabilidad con los repositorios de México y de la Región de las Américas. El comité del Campus Virtual de la Universidad de Guadalajara ha intentado respetar lo más posible al modelo propuesto, lo que ha permitido cumplir la mayoría de los objetivos fijados en el plan de trabajo inicial, aunque ha enfrentado una serie de dificultades administrativas y de motivación de sus integrantes.

This paper discusses the gestation process, implementation methodology, and results obtained from the initiative to use e-learning to train human resources for health, six years after the launch of the Virtual Campus of Public Health of the University of Guadalajara (Mexico); the discussion is framed by Pan American Health Organization (PAHO) standards and practices. This is a special report on the work done by the institutional committee of the Virtual Campus in western Mexico to create an Internet portal that follows the guidelines of the strategic model established by Nodo México and PAHO for the Region of the Americas. This Virtual Campus began its activities in 2007, on the basis of the use of free software and institutional collaboration. Since the initial year of implementation of the node, over 500 health professionals have been trained using virtual courses, the node's educational platform, and a repository of virtual learning resources that are interoperable with other repositories in Mexico and the Region of the Americas. The University of Guadalajara Virtual Campus committee has followed the proposed model as much as possible, thereby achieving most of the goals set in the initial work plan, despite a number of administrative challenges and the difficulty of motivating committee members.

Proliferation of the superficial epithelium of ovaries in senile female rats following oral administration of conjugated equine estrogens

OBJECTIVE: To evaluate the effect of different concentrations of estrogen on the ovarian superficial epithelium in senile female rats. Design: Fifty female rats at 15 months of age and with irregular estrous cycles were selected and randomly divided into five experimental groups containing equal numbers of animals in each: GPROP, control group receiving vehicle only; GE0.05mg, group receiving conjugated equine estrogens (CEE) at a dose of 50 µg/kg; GE0.5mg, group receiving CEE at 500 µg/kg; GE1mg, group receiving CEE at 1 mg/kg; and GE2mg, receiving CEE at 2 mg/kg. The length of treatment was 21 days. After this period, the animals were anesthetized and the ovaries were fixed in 10 percent formaldehyde and processed for routine histology. Histomorphology was analyzed by light microscopy, and histomorphometrics were evaluated using the Imagelab program. RESULTS: In the GPROP and GE0.05mg groups, the superficial epithelium of the ovary had a simple cuboidal shape, and as the estrogen dose increased, the epithelium thickened, with pseudo-stratified or stratified epithelium appearing in the GE2mg group. The animals in the group given the highest estrogen dose (GE2mg) showed the thickest ovarian epithelium and the largest perimeter and surface area of the surface ovarian epithelium (P < 0.01). However, the difference in epithelium thickness between the GE0.5mg and GE1mg groups was only slight. CONCLUSION: Our data suggest that CEE at a dose of 2 mg/kg may induce marked proliferation of rat ovarian epithelium.

Histopathologic evaluation of the peritoneum exposed to heat shock: experimental study in rats

PURPOSE: To evaluate histopathologic alterations of the peritoneum exposed to heat shock. METHODS: Sixty rats were randomly distributed into 6 groups: Heat Shock (HS), High Temperature (HT), Body Temperature (BT), Temperature 0oC (TZ), Sham (SH) and Control (CG) with 10 animals each. The peritoneal cavity of animals from groups HS, HT, BT and TZ was irrigated with NaCl solution 0.9 percent at temperatures 50°C, 0°C, 50°C, 37°C and 0°C, respectively. For animals from group SH, the procedures were simulated and those from group CG, laparotomy and biopsies were conducted. Twenty-four hours later, biopsies of the peritoneum for exams under light and electronic microscopy were performed. RESULTS: Edema was found in groups HS 80 percent, HT 60 percent, BT 30 percent TZ 70 percent, SH 40 percent and CG 30 percent. Vascular congestion was found in groups HS 20 percent, HT 30 percent, BT 10 percent and TZ 20 percent. Erythrocyte extravasation was found in groups HT 60 percent and SH 10 percent. Mesothelium destruction was found in 100 percent of specimens from groups HS, HT, BT, TZ, SH and CG 90 percent. Necrosis was found in groups HS 30 percent, HT 20 percent and BT 10 percent. The mean peritoneal thickness ranged from 42.26 μm (TZ) to 26.42 μm (CG). CONCLUSION: The heat shock caused no deaths, but promoted significant peritoneal edema without affecting the other histopathologic indicatives.

OBJETIVO: Avaliar alterações histopatológicas do peritônio exposto a choque térmico. MÉTODOS: Sessenta ratos foram distribuídos aleatoriamente em seis grupos: Choque Térmico (CT), Temperatura Elevada (TE), Temperatura 0°C (TZ) Sham (SH) e Controle (GC) com 10 animais. A cavidade peritoneal dos animais dos grupos CT, TE, TC e TZ foi irrigada com solução de NaCl 0,9 por cento nas temperaturas, 50°C e 0°C, 50°C, 37°C e 0°C, respectivamente. Nos animais do grupo SH foram simulados os procedimentos e nos do GC laparotomia e biópsias. Depois de 24 horas foram realizadas biópsias do peritônio para exames sob microscopia de luz e eletrônica. RESULTADOS: Edema foi encontrado nos grupos CT 80 por cento, TE 60 por cento, TC 30 por cento, TZ 70 por cento, SH 40 por cento e GC 30 por cento. Congestão vascular foi encontrada nos grupos CT 20 por cento, TE 30 por cento, TC 10 por cento e TZ 20 por cento. Extravasamento de hemácias foi encontrado nos grupos TE 60 por cento e SH 10 por cento. Destruição de mesotélio foi encontrada em 100 por cento dos espécimes dos grupos CT, TE, TC, TZ, SH e no grupo GC 90 por cento. Necrose foi encontrada nos grupos CT 30 por cento, TE 20 por cento e TC 10 por cento. A espessura média do peritônio variou de 42,26 μm (TZ) a 26,42 μm (GC). CONCLUSÃO: O choque térmico não causou óbitos, mas promoveu edema peritoneal significante sem alterar os demais indicadores histopatológicos.

Avaliação ultra-estrutural dos efeitos tóxicos da mitomicina C no epitélio ciliar de olhos de coelhos normais com e sem tratamento hipotensor ocular prévio / Ultrastructural evaluation of mitomycin C toxic effects on the ciliary epithelium of normal rabbits eyes with and without aqueous humor suppressant treatment

OBJETIVO: Avaliar o epitélio ciliar interno (ECI) do corpo ciliar após aplicação de mitomicina C (MMC) sob retalho escleral, em animais tratados com dois tipos de inibidores da produção do humor aquoso. MÉTODOS: Foram estudados ambos os olhos de 16 coelhos divididos em 4 grupos experimentais. Foi realizado retalho escleral em todos os olhos dos animais, mas apenas os olhos direitos (OD) receberam MMC. No grupo 1 (G1) não houve tratamento prévio. Nos grupos G2 e G4 foi administrada acetazolamida e nos grupos G3 e G4 maleato de timolol. O ECI foi examinado à microscopia eletrônica de transmissão (MET). Os olhos esquerdos formaram os grupos controle. RESULTADOS: Em todos os grupos exceto no G1 OE, foram observadas: retração das células e/ou alargamento entre invaginações, mitocôndrias com rarefação, vesículas claras e corpos densos. A membrana limitante interna estava espessada, descontínua ou descolada em todos grupos exceto G1 OE e G2 OE. Foi observada liberação de material citoplasmático apenas nos grupos tratados com inibidores da produção de humor aquoso. CONCLUSÕES: 1- MMC, acetazolamida e maleato de timolol causaram alterações morfológicas no epitélio ciliar mesmo usados isoladamente. 2- A associação MMC e acetazolamida causou mais alterações do que a acetazolamida isoladamente, mas não mais do que a MMC isoladamente. 3- Nas demais associações as alterações foram semelhantes.

PURPOSE: To evaluate the effects of mitomycin C (MMC) on the internal ciliary epithelium (ICE) of the ciliary body of animals treated with two differents aqueous humor supressants. METHODS: The eyes of sixteen Norfolk albino rabbits divided into four experimental groups were studied. The right eyes (RE) of the four groups received 0.1 ml of MMC (0.5 mg/ml) under the scleral flap. The left eyes (LE) was the control group. Group 1 (G1) did not have any other treatment. To Group 2 (G2) and Group 4 (G4) acetazolamide was administered. To Group (G3) and Group 4 (G4) timolol maleate was administered. ICE was examined by transmission electron microscopy (TEM). RESULTS: The following aspects were observed in all groups, except in G1 LE: cell shrinkage and/or enlargement of intercellular spaces, rarefied mitochondria, clear vesicular structures and electron-dense bodies. The internal limitant membrane showed to be thickened, discontinued and separeted in all groups, except in G1 LE and G2 LE. Discharge of cytoplasmatic material was observed only in the groups treated with aqueous humor supressants. CONCLUSIONS: 1) MMC, acetazolamide and timolol maleate caused morphological alterations in the ciliary epithelium even when used alone. 2) The combination of MMC and acetazolamide caused more alterations than did isolated acetazolamide, but not more than MMC alone. 3) For the other combinations the alterations were similar.

Lead acetate induced contraction in rat tracheal smooth muscle is independent of epithelium.

Airways are the primary target of lead exposure from atmospheric pollution, its effect on airway smooth muscle and their responsiveness to bronchoactive agents is not clearly understood. In the present investigation the effect of lead on the isolated airway smooth muscle activity was studied in organ bath set-up. Further the involvement of airway epithelium was examined and the responsiveness of airway smooth muscle to adenosine, acetylcholine (bronchoconstrictors) and isoproterenol (bronchodilator) was also investigated. Lead in concentration of 10(-12) M to 10(-4) M produced concentration-dependant contractile response in rat tracheal rings. Acetylcholine and adenosine induced concentration-dependent contractile response was slightly inhibited after lead exposure. The relaxant response to isoproterenol was also inhibited in lead exposed tissues. Epithelium removal did not significantly change the contractile response to lead suggesting that the lead induced contraction of airway smooth muscle is epithelium independent.

Short Term Effects of Topical Cyclosporine and Viscoelastic on the Ocular Surfaces in Patients with Dry Eye

PURPOSE: To compare the short term effects of topical 0.05% cyclosporine (CsA) and a mixture of 0.08% chondroitin sulfate and 0.06% sodium hyaluronate (CS-HA) on dry eye ocular surfaces. METHODS: 36 patients with moderate to severe dry eye (5 mm/5 min or less with Schirmer's test or tear break up time (BUT) less than 6 seconds), were treated with topical application of CS-HA on one eye and CsA on the other 4 times a day for 6-8 weeks. BUT, Schirmer's test without anesthesia, and conjunctival impression cytology (CIC; goblet cell density, nucleus to cytoplasmic ratio, and epithelial cell morphology) were evaluated and compared between eyes before and after treatment (repeated measurement of ANOVA). RESULTS: After treatment, BUT and tear wettings were significantly prolonged in each group. Topical CsA treated eyes had greater increase in BUT (p=0.026); there was no significant difference in tear wetting (p=0.132). While the 3 parameters of CIC improved in both groups, goblet cell density was significantly higher in eyes treated with CsA (p=0.033). CONCLUSIONS: While both CS-HA and 0.05% CsA eyedrops improve ocular surfaces, topical CsA may have a better effect on enhancing tear film stability and goblet cell density.

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.

Assessment of methyl methacrylate vapor toxicity on the rat tracheal epithelium / Análise da toxicidade dos vapores de metil metacrilato sobre o epitélio traqueal de ratos

O metil metacrilato (MMA) é um monômero que se polimeriza em resina pela ação da luz e do calor, transformando-se em plástico claro, resistente e durável, relativamente inerte. Por apresentar tais características, o MMA tem sido muito usado na Medicina, como cimento ósseo, e na Odontologia, em aparelhos e próteses dentais, o que tem suscitado interesse na avaliação de sua toxicidade. Estudos experimentais e clínicos têm mostrado que os monômeros podem causar uma gama de efeitos adversos. A principal via de exposição ocupacional ao MMA é a inalatória. Este trabalho visa a avaliar a ação tóxica do MMA sobre o epitélio traqueal em relação ao tempo de exposição. Para isso, dois grupos experimentais de ratos foram expostos ao MMA por inalação, com restrição de ventilação: um grupo (n = 36) foi exposto continuamente, e outro (n = 36) foi exposto durante oito horas diárias, sem água e comida durante o período de exposição. Um grupo controle (n = 8) recebeu ar normal. Doze animais de cada grupo de estudo foram sacrificados com 5, 8 e 10 dias de exposição, junto com dois ou quatro animais do grupo controle. Vinte e nove (80,5%) dos ratos expostos continuamente ao MMA apresentaram inflamação do epitélio traqueal, assim como 58,33% (n = 21) daqueles expostos 8 horas/dia e 87,5% (n = 7) dos controles. Não se observou associação entre o processo inflamatório e a exposição ao MMA, nem alterações significativas na medida da espessura do epitélio traqueal. Novos estudos, com tempo mais prolongado de exposição e análise de outros parâmetros, devem ser realizados para que seja excluída, totalmente, a possibilidade de dano traqueal por vapores de MMA.

Efeitos da Luffa operculata sobre o epitélio do palato de rã: aspectos histológicos / Luffa operculata effects on the epithelium of frog palate: histological features

Luffa operculata é o nome botânico da buchinha-do-norte ou cabacinha, uma planta medicinal usada popularmente no tratamento das rinites e rinossinusites. Na Europa e nos EUA, está em medicamentos homeopáticos. No Brasil, a infusão (chá) do fruto seco de Luffa operculata é utilizada para inalacão ou instilacão nasal, resultando em liberacão profusa de muco que alivia os sintomas nasossinusais, mas há relatos freqüentes de irritacão nasal, epistaxe e anosmia. FORMA DE ESTUDO: Experimental. MATERIAL E MÉTODO: Avaliamos os efeitos da infusão de Luffa operculata em diferentes concentracões, no modelo experimental do palato isolado de rã, examinando 46 palatos após imersão. Quatro grupos (n=10) foram testados com infusão feita em Ringer-rã (solucão isotônica): controle; 60mg/l; 600mg/l e 1200mg/l. Um grupo foi testado em água (600mg/l H2O, n=6). Coletamos amostras do epitélio para estudo histológico à microscopia-de-luz e microscopia eletrônica de transmissão. RESULTADOS: Nos palatos tratados, os achados à microscopia-de-luz mostram lesões epiteliais de padrão tóxico, dose-dependentes. Na microscopia eletrônica, aumento dos espacos intercelulares e ruptura de tight junctions apontam para anormalidade no transporte iônico e de fluidos. CONCLUSÕES: A infusão de Luffa operculata, nas concentracões utilizadas popularmente, promove alteracões significantes na estrutura e ultraestrutura epitelial deste modelo ex vivo de mucosa respiratória.

In vivo effect of whole grain flour of finger millet (Eleusine coracana) and kodo millet (Paspalum scrobiculatum) on rat dermal wound healing.

Influence of finger millet and kodo millet on rat dermal wound healing was assessed by making a 4 cm2 (2 x 2 cm) excision wound on the shaven back of rats under ether anesthesia. Finger millet or kodo millet flour (300 mg) as aqueous paste was applied topically once daily for 16 days. The granulation tissue formed on day 4, 8 and 12 was used to estimate some biochemical parameters like protein, DNA, collagen and lipid peroxides. There was significant increase in protein and collagen contents and decrease in lipid peroxides. Biophysical parameters like rate of contraction and number of days for epithelialization were also studied. Rate of contraction was 88-90% in kodo millet and finger millet treated rats in comparison to 75% in untreated rats. The number of days for complete closure of wounds was lower for finger millet (13 days) and kodo millet (14 days) treated rats in comparison to untreated (16 days) rats. The results implicate a possible therapeutical role for finger millet and kodo millet in accelerating the process of wound healing.

Scanning electron microscopic evaluation of effect of cortisol on chloride cells of tilapia, Oreochromis mossambicus.

The effect of exogenous administration of cortisol (0.2 microg/g body weight) for 24, 48 and 72 hr on the gill epithelium of Tilapia has been studied. The results clearly revealed that out of the three sub-types of chloride cells viz., shallow basin, wavy convex and deep hole, the shallow basin ones are the most abundant in number. In vivo administration of cortisol conspicuously increased the number of the shallow basin chloride cells and caused noticeable changes in the microridges of pavement cells right from 24 hr treatment onwards. The present study confirms heterogeneity of chloride cells in teleosts.

Further on the causation of oral submucous fibrosis.

Oral submucous fibrosis is perhaps a disease of multifactorial aetiology, of which areca nut usage is definitely a causative factor. We disagree with the previous reports in that the action of areca quid on the oral mucosa is not that simplistic and is not dictated solely by the duration of exposure to it or by simple process of passive diffusion. We noted that the role of copper cannot be segregated from that of zinc, the biochemical relatedness of these two elements is well elucidated. The transport of copper in to the oral epithelium may be dictated more by the composition of the quid rather than the time of exposure. Zinc is implicated in the modulation of mucosal metallothionein, thereby interfering with copper absorption. The bioavailability of zinc in its turn depends on elements like calcium and iron present in oral fluid. The usage of slaked lime(calcium hydroxide) as as ingredient of betel quid, thereby causing an interference with zinc bioavailability is a matter of concern. Of practical importance is the processing of raw areca nut and the various proprietary forms (sachets) available in the market, the toxic effects of which varies depending on its contents. Studies on the role of geochemical factors in modulating the chemical composition of the various nut forms, thereby altering its toxic effects will be an interesting pursuit.

Effects of formaldehyde on the frog's mucociliary epithelium as a surrogate to evaluate air pollution effects on the respiratory epithelium

The increasing use of alcohol as an alternative fuel to gasoline or diesel can increase emission of formaldehyde, an organic gas that is irritant to the mucous membranes. The respiratory system is the major target of air pollutants and its major defense mechanism depends on the continuous activity of the cilia and the resulting constant transportation of mucous secretion. The present study was designed to evaluate the effects of formaldehyde on the ciliated epithelium through a relative large dose range around the threshold limit value adopted by the Brazilian legislation, namely 1.6 ppm (1.25 to 5 ppm). For this purpose, the isolated frog palate preparation was used as the target of toxic injury. Four groups of frog palates were exposed to diluted Ringer solution (control, N = 8) and formaldehyde diluted in Ringer solution at three different concentrations (1.25, 2.5 and 5.0 ppm, N = 10 for each group). Mucociliary clearance and ciliary beat frequency decreased significantly in contact with formaldehyde at the concentrations of 2.5 and 5.0 ppm after 60 min of exposure (P<0.05). We conclude that relatively low concentrations of formaldehyde, which is even below the Brazilian threshold limit value, are sufficient to cause short-term mucociliary impairment

Enhanced mucosal re-epithelialization induced by short chain fatty acids in experimental colitis

The short chain fatty acids (SCFA) are the best nutrients for the colonocytes. Glucose is poorly used as a fuel but may be transformed into SCFA by colonic bacteria. The aim of this study was to investigate the effect of SCFA or glucose on experimental colitis. Colitis was induced in 30 Wistar rats by colonic instillation of 4 percent acetic acid. Five days later they were randomized to receive twice a day colonic lavage containing saline (controls, N = 10), 10 percent hypertonic glucose (N = 10) or SCFA (N = 10) until day 8 when they were killed. At autopsy, the colon was removed and weighed and the mucosa was evaluated macro- and microscopically and stripped out for DNA assay. Data are reported as mean + or -SD or median [range] as appropriate. All animals lost weight but there was no difference between groups. Colon weight was significantly lower in the SCFA group (3.8 + or - 0.5 g) than in the control (5.3 + or - 2.1 g) and glucose (5.2 + or - 1.3 g) groups (PP<0.05). Macroscopically, the severity of inflammation was less in SCFA (grade 2 [1-5]) than in control (grade 9 [4-10]) and glucose-treated (grade 9 [2-10]) animals (P<0.01). Microscopically, ulceration of the mucosa was more severe in the glucose and control groups than in the SCFA group. The DNA content of the mucosa of SCFA-treated animals (8.2 [5.0-20.2] mg/g of tissue) was higher than in glucose-treated (5.1 [4.2-8.5] mg/g of tissue; P<0.01) and control (6.2 [4.5-8.9] mg/g of tissue; P<0.05) animals. We conclude that SCFA may enhance mucosal re-epithelialization in experimental colitis, whereas hypertonic glucose is of no benefit