Investigation of teratogenic effects of letrozole on fetal bone development / Investigación de los efectos teratogénicos de letrozol en el desarrollo óseo fetal

SUMMARY: Letrozole is mainly used for the treatment of unexplained infertility, breast cancer and polycystic ovarian syndrome, with secondary use in ovarian stimulation. In cases of unexpected or unknown pregnancy during the use of letrozole, letrozole may cause a teratogenic effect on the fetus. In this reason, in this study, we aimed to determine the effect of letrozole on fetal bone development. In this study, 32 pregnant Wistar albino rats were used. The rats were divided into four groups: Control (saline) and high; 0.3 mg/kg, medium; 0.03 mg/kg, low; 0.003 mg/ kg letrozole. Saline and letrozole were administered in 100 mL solutions by intraperitonaly from day 11 to day 15 of pregnancy. The skeletal system development of fetuses was examined with double skeletal staining, immunohistochemical staining methods and mineral density scanning electron microscopy. A total of 100 fetuses from female rats, 25 in each group, were included in the study. As a result of that, ossification rates were observed to decrease depending on the dose of letrozole in the forelimb limb (scapula, humerus, radius, ulna) and hindlimb (femur, tibia, fibula) limb bones. As a result of the statistical analysis, a statistically significant decrease was found in the ossification rates of all bones between the control group and low, medium, high letrozole groups (p<0.001). Exposure to letrozole during pregnancy adversely affected ossification and bone growth. However, the teratogenic effects of letrozole are unclear. Therefore, it needs to be investigated more extensively.

RESUMEN: Letrozol se usa principalmente para el tratamiento de la infertilidad inexplicable, el cáncer de mama y el síndrome de ovario poliquístico, con estimulación ovárica de uso secundario. En casos de embarazo inesperado o desconocido durante el uso de letrozol, puede causar un efecto teratogénico en el feto. Por esta razón, en este estudio, nuestro objetivo fue determinar el efecto de letrozol en el desarrollo óseo fetal. Se utilizaron 32 ratas albinas Wistar preñadas las cuales se distribuyeron en cuatro grupos: Control (solución salina) y alta; 0,3 mg/kg, medio; 0,03 mg/kg, bajo; 0,003 mg/kg de letrozol. Se administró solución salina y letrozol en soluciones de 100 mL por vía intraperitoneal desde el día 11 hasta el día 15 de la preñez. El desarrollo del sistema esquelético de los fetos se examinó con tinción esquelética doble, métodos de tinción inmunohistoquímica y microscopía electrónica de barrido de densidad mineral. Se incluyeron en el estudio un total de 100 fetos de ratas hembra, 25 en cada grupo. Como resultado, se observó que las tasas de osificación disminuían dependiendo de la dosis de letrozol en los huesos de los miembros torácicos (escápula, húmero, radio, ulna) y de las miembros pélvicos (fémur, tibia, fíbula). Se encontró una disminución estadísticamente significativa en las tasas de osificación de todos los huesos entre el grupo control y los grupos de letrozol bajo, medio y alto (p<0,001). La exposición a letrozol durante la preñez afectó negativamente la osificación y el crecimiento óseo. Sin embargo, los efectos teratogénicos del letrozol no están claros por lo que debe ser investigado más extensamente.

Systemic supplement with resveratrol increased bone formation in rats' alveolar socket / Aumento de la formación ósea en el hueso alveolar de rata con suplemento sistémico con resveratrol

Resveratrol in cell culture media increases osteoblastic markers. Also results from previous studies provide evidence for resveratrol positive effects on bone healing and bone production. In this preclinical study we investigated bone healing in rats by resveratrol systemic application. 30 Wistar male rats were divided into two groups (study group and control group). At first, maxillary second molars of rats were extracted. The rats were kept in laboratory for next 28 days. Study group received resveratrol 20 mg/kg by abdominal injection every day. The control group received placebo in the same manner that study group. Rats were sacrificed after 28 days and bone samples were collected from center of maxillary second molar socket. Samples were evaluated histologically for new bone formation, inflammation, necrosis, fibrosis and foreign body reaction. The mean difference of new bone formation in control group (28.30 %) and study group (45 %) were statistically significant (P=0.014). There were no significant differences in inflammation, fibrosis, necrosis and foreign body reaction (P>0.05). Resveratrol has positive effects on bone healing but more evidence needed from more clinical and animal studies.

El resveratrol en los medios de cultivo celular aumenta los marcadores osteoblásticos. Los resultados de estudios anteriores proporcionan evidencia de efectos positivos del resveratrol sobre la curación ósea y la producción ósea. En este estudio preclínico, investigamos la curación ósea en ratas mediante la aplicación sistémica de resveratrol. Se dividieron 30 ratas macho Wistar en dos grupos (estudio y control). Inicialmente se extrajeron los segundos molares maxilares de las ratas y los animales se mantuvieron en el laboratorio durante los siguientes 28 días. El grupo de estudio recibió todos los días resveratrol 20 mg/kg por inyección abdominal . El grupo control recibió placebo de la misma manera que el grupo estudio. Las ratas fueron sacrificadas después de 28 días y se recogieron muestras de hueso del centro del segundo molar maxilar. Las muestras se evaluaron histológicamente para la formación de hueso nuevo, inflamación, necrosis, fibrosis y reacción de cuerpo extraño. La media de formación de hueso nuevo en el grupo control (28,30 %) y en el grupo estudio (45 %) fueron estadísticamente significativas (P=0,014). No hubo diferencias significativas en la inflamación, fibrosis, necrosis y reacción al cuerpo extraño (P>0,05). El resveratrol tiene efectos positivos sobre la curación de los huesos, pero aún es necesario realizar más pruebas de estudios clínicos, como también en animales.

Efecto de la administración de ácido retinoico sobre el desarrollo del esqueleto axial en embriones de ratón Mus musculus / Effect of administration of retinoic acid on the development of the axial skeleton in mouse embryos Mus musculus

El déficit y exceso de vitamina A provoca malformaciones congénitas que afectan distintos órganos y sistemas. El objetivo de este estudio fue determinar el efecto que causa la administración de ácido retinoico a distintas dosis sobre la morfogénesis ósea del esqueleto axial en embriones de ratón Mus musculus. Mediante aleatorización simple se distribuyeron hembras recién preñadas en 4 categorías: A, B, C y D. El día 8 post fecundación (p.f), se administró 40 mg/kg de peso de ácido retinoico al grupo A, 20 mg/kg de peso de esta solución al grupo B, 1 ml/kg de peso de dimetil sulfóxido al grupo C, y el grupo D es grupo control. El día 17 de la gestación las hembras y sus fetos fueron anestesiadas y eutanasiadas con sobredosis de pentotal sódico intraperitoneal. Los fetos de cada camada fueron procesados mediante diafanización y tinción con azul de Alcian para destacar cartílago hialino y alizarina para observar tejido óseo. Los resultados se expresaron en porcentajes de malformaciones en los siguientes tres segmentos: 1) cráneo-columna cervical, 2) segmento torácico y abdominal y 3) cintura pélvica, considerándose un 100% cuando la totalidad de los elementos óseos se encontraban comprometidos. Se utilizó la prueba de Fisher para la comparación de frecuencias de malformaciones y se consideró estadísticamente significativo cuando p<0,05. En el grupo A se evidenciaron malformaciones mayores como ausencia de huesos frontales y parietales, exencefalia, defectos en el número de vértebras, y fusiones de costillas; y en el grupo B se observaron malformaciones menores como alteraciones numéricas y fusiones de costillas, existiendo diferencias significativas entre ambos grupos. En los grupos C y D no se consignaron malformaciones. El ácido retinoico administrado intraperitonealmente el dìa 8 p.f en dosis de 40 y 20 mg/kg de peso se comporta como un teratógeno en los embriones de ratón, existiendo además diferencias significativas entre las malformaciones generadas por ambas dosis de ácido retinoico. La primera concentración afecta los huesos de los tres segmentos estudiados (cráneo-cervical, toracoabdominal, y pélvico) y la segunda concentración sólo afecta a dos segmentos (cráneo-cervical y toracoabdominal). Ambos tratamientos afectan los segmentos en una gradiente céfalo caudal, independiente del origen embrionario de las estructuras. Esto se debería a que los cambios en las gradientes de ácido retinoico alteran el comportamiento de células de la cresta neural craneal y el orden de la expresión de genes Hox.

The deficit and excess of vitamin A causes birth defects affecting different organ systems. The objectives of this study are to determine the effect caused by the administration of different doses of retinoic acid on bone morphogenesis of the axial skeleton in embryonic mouse Mus musculus. By simple randomization newly pregnant females were distributed into 4 categories: A, B, C and D. On day 8 post fertilization, 40 mg/kg was administered by weight of retinoic acid to the group A, 20 mg/kg body weight of the group B solution 1 ml/kg body weight of dimethyl sulfoxide and group C. Group D is the control group. On day 17 of gestation the females and their fetuses were anesthetized and euthanized with an overdose of intraperitoneal sodium pentothal. Fetuses from each litter were processed using diaphanization and Alcian blue staining to hyaline cartilage and alizarin to observe bone tissue. The results are expressed as percentages of malformations in the following three segments: 1) cranio-cervical spine, 2) thoracic and abdominal segment and 3) pelvic segment, considering 100% when all the bony elements were compromised. Fisher's exact test for comparison of frequencies of malformations was used and considered statistically significant when p<0.05. In group A, major malformations and defects were evident in the indemnity of the cranial vault, exencephaly, defects in the number of vertebrae, and fusion of ribs. In group B minor malformations as numerical alterations and rib fusions were observed. Significant differences were found between both groups. In groups C and D no malformations were recorded. Retinoic acid administered intraperitoneally at doses of 40 and 20 mg/kg acts as a teratogen in mouse embryos. There are significant differences between the defects induced by concentrations of 40 mg/k and 20 mg/k of retinoic acid. Both concentrations affect the bones of the three segments studied (cranio cervical, thoraco-abdominal and pelvic) in a cephalo caudal gradient, independent of the embryonic origin of the structures. Changes in retinoic acid concentration alter the behavior of cranial neural crest and changing the order of the HOX gene expression in the axial skeleton.

Use of a New Fibrin Sealant and Laser Irradiation in the Repair of Skull Defects in Rats

This study evaluated the osteogenic capacity of a new fibrin sealant (FS) combined with bone graft and laser irradiation in the bone repair. Defects were created in the skull of 30 rats and filled with autogenous graft and FS derived from snake venom. Immediately after implantation, low-power laser was applied on the surgical site. The animals were divided in: control group with autogenous graft (G1), autogenous graft and laser 5 J/cm2 (G2), autogenous graft and laser 7 J/cm2 (G3), autogenous graft and FS (G4), autogenous graft, FS and laser 5 J/cm2 (G5), autogenous graft, FS and laser 7 J/cm2 (G6). The animals were sacrificed 6 weeks after implant. Results showed absence of inflammatory infiltrate in the bone defect. New bone formation occurred in all groups, but it was most intense in G6. Thus, the FS and laser 7 J/cm2 showed osteoconductive capacity and can be an interesting resource to be applied in surgery of bone reconstruction.

Este estudo avaliou a capacidade osteogênica de um novo selante de fibrina (FS) associado com enxerto ósseo e irradiação laser no reparo ósseo. Defeitos foram criados no crânio de 30 ratos e preenchidos com enxerto autógeno e FS derivado do veneno de cobra. Imediatamente após implantação, foi aplicado laser de baixa potência na área cirúrgica. Os animais foram divididos em grupo controle com autógeno (G1), autógeno e laser 5 J/cm2 (G2), autógeno e laser 7J/cm2 (G3), autógeno e FS (G4), autógeno, FS e laser 5J/cm2 (G5), autógeno, FS e laser 7J/cm2 (G6). Os animais foram sacrificados 6 semanas após implante. Resultados mostraram ausência de infiltrado inflamatório no defeito ósseo. Neoformação óssea ocorreu em todos os grupos, entretanto, foi mais intenso em G6. Desta maneira, o FS e laser 7J/cm2 mostraram capacidade osteocondutiva e podem ser um interessante recurso a ser aplicado nas cirurgias de reconstrução óssea.

Os glicocorticoides e seus efeitos no crescimento e na mineralização óssea / Effects of glucocorticoids on growth and bone mineralization

OBJETIVO: Revisar os mecanismos de ações dos glicocorticoides e sua capacidade de induzir osteoporose e déficits de crescimento. FONTES DOS DADOS: A revisão bibliográfica de artigos científicos foi realizada na base de dados MEDLINE e utilizou as palavras-chave agrupadas nas sintaxes “glicocorticoides”, “mineralização óssea”, “crescimento” e “efeitos colaterais”, nos últimos 10 anos, e das referências destes nos reportamos para as publicações mais antigas, mas com os estudos fundamentais para a compreensão do assunto. SÍNTESE DOS DADOS: Destacam-se ações dos glicocorticoides sobre hormônios e citocinas responsáveis pelo crescimento longitudinal. Os efeitos finais dos glicocorticoides sobre o esqueleto são determinados por ações sistêmicas no metabolismo ósseo e por ações diretas desses esteroides nas células ósseas, levando a mudanças no número e função das mesmas e favorecendo a perda óssea. Discutem-se os mecanismos indutores da recuperação dos canais de crescimento e recuperação da massa óssea após a descontinuação dos glicocorticoides; os métodos diagnósticos do metabolismo e mineralização óssea; assim como medidas terapêuticas e preventivas das alterações óssea induzidas pelos glicocorticoides. CONCLUSÃO: A monitorização de cada paciente é essencial para identificação e potencial reversão dos danos associados ao uso crônico de glicocorticoides.

OBJECTIVE: To review the various mechanisms of glucocorticoid action and the ability of these agents to induce osteoporosis and growth deficits. SOURCES: A review of the scientific literature was conducted on the basis of a MEDLINE search using the keywords and descriptors “glucocorticoids,” “bone mineralization,” “growth,” and “side effects” and limited to articles published in the last decade. The references cited by these articles were used to identify relevant older publications, with an emphasis on landmark studies essential to an understanding of the topic. SUMMARY OF THE FINDINGS: Emphasis was placed on the actions of glucocorticoids on the hormones and cytokines that modulate linear growth. The end effects of glucocorticoids on the skeletal system are the result of systemic effects on bone metabolism and of direct actions on bone cells, which alter bone cell counts and predispose to bone loss. The mechanisms underlying catch-up growth and bone mass recovery after discontinuation of glucocorticoid treatment are discussed, followed by a review of diagnostic methods available for assessment of bone metabolism and mineralization and of measures for prevention and management of glucocorticoid-induced bone changes. CONCLUSION: Patient monitoring on a case-by-case basis plays an essential role in detection and, potentially, reversal of the damage associated with chronic glucocorticoid therapy.

Petroleum ether extract of Cissus quadrangularis (LINN) stimulates the growth of fetal bone during intra uterine developmental period: a morphometric analysis

OBJECTIVE: The aim of the present study was to analyze the effect Cissus quadrangularis plant petroleum ether extract on the development of long bones during the intra-uterine developmental stage in rats. METHODS: Pregnant rats (n=12) were randomly assigned into either a control group (n=6) or a Cissus quadrangularis treatment (n=6) group. Pregnant rats in the Cissus quadrangularis group were treated with Cissus quadrangularis petroleum ether extract at a dose of 500 mg/kg body weight from gestation day 9 until delivery. The animals in the control group received an equal volume of saline. Newborn pups were collected from both groups for alizarin red S - alcian blue staining to differentiate ossified and unossified cartilage. The ossified cartilage (bone) was morphometrically analyzed using Scion image software. RESULTS: Morphometric analysis revealed that the percentage of the total length of ossified cartilage (bone) in pups born to treated dams was significantly higher (P<0.001- -0.0001) than that of the control group. CONCLUSION: The results of the present study suggest that maternal administration of Cissus quadrangularis petroleum ether extract during pregnancy can stimulate the development of fetal bone growth during the intra-uterine developmental period.

Efficacy of combined treatment with growth hormone and gonadotropin releasing hormone analogue in children with poor prognosis of adult height.

OBJECTIVE: This study was conducted to study the role of combination therapy of growth hormone and Gonadotropin-releasing hormone (GnRH) analogues in girls with idiopathic central precocious puberty (CPP) or idiopathic short stature (ISS). METHODS: Five girls with CPP (median age 9.1 y, pubertal stage 2-3) (3 of them previously treated with GnRH analogue (GnRHa) for 16.2 +/- 0.3 months) and 8 girls with ISS (median age 11.4 y, pubertal stage 2-3) (previously treated with GH for 10.95 +/- 1.42 months), were treated with recombinant human GH (0.33 mg/kg/week) and GnRHa (3.75 mg/28 days) for 22 months. RESULTS: Height of girls with CPP improved from - 1.3 to - 0.2 SDS and height for BA from - 2.1 to - 0.6 SDS (P = 0.042). Predicted adult height (PAH) improved from - 3.1 to - 0.6 SDS (P = 0.042). In girls with ISS only PAH improved from - 3.0 to - 1.5 SDS (P = 0.025). CONCLUSION: Combined treatment improves height and PAH in CPP. Height in ISS is also improved however not significantly.

Efectividad de la terapia con leuprolide acetato de depósito cada tres meses en pubertad precoz central / Effectiveness of Leuprolide acetate therapy every three months in central precocious puberty

Background: Precocious puberty may reduce final adult height, and affected children may suffer social and emotional problems. The efficacy of treatment with a long acting agonist analogue of the gonadotropin releasing hormone (aLHRH) has been well demonstrated. Aim: To evaluated the efficacy of a new formulation of aLHRH (leuprolide, Lupron ®) for the suppression of gonadotropin activation and clinical signs of puberty. Material and methods: Eleven children (ten females) with idiopathic central precocious puberty, with a mean chronological age of 7.5±1.8 years and a bone age of 9.7±1.8 years were recruited. Testicular volume in the male was 15 ml. In females, Tanner stage for breast development was between 2-4 and mean ovarian volume was 2.3±0.8 ml. They were treated during 18 months with aLHRH, 11.25 mg administered intramuscularly every three months. Results: Clinical, hormonal and ultrasonographic signs of puberty regressed in all patients. The degree of suppression of LH was 87.7±5.1% at the end of the 18 months. No significant changes in bone mineral content were observed during the treatment period. Conclusions: Leuprolide (aLHRH) 11.25 mg, injected every three months, is effective for the control of central precocious puberty and allows to reduce the number of yearly injections from 12 to 4.

Growth pattern and skeletal maturation following growth hormone therapy in growth hormone deficiency: factors influencing outcome.

OBJECTIVE: To evaluate pattern of growth and skeletal maturation following growth hormone (GH) therapy in children with GH deficiency (GHD) with special emphasis on factors influencing outcome. METHODS: Records of ninety-six children (67 boys, 29 girls) with GHD treated with GH for 2.3 +/-2.1 years were reviewed. RESULTS: Height SDS at the end of treatment was significantly higher than that at initiation (-3.4 +/- 1.7 versus -4.8 +/-1.6, P < 0.001); it was however lower than target height SDS (corrected height SDS (1.8 +/- 1.6, P < 0.001). The greatest increase in height SDS was observed during the first two years of treatment. Kaplan Meier survival analysis showed that 92%; of all subjects achieving end height SDS in the target height range did so within the first two years of treatment. Height SDS for bone age increased by 0.7 +/-0.9 during treatment (from -2.5 +/- 1.0 to -1.8 +/- 1.5, P < 0.001); the increase was however lower compared to that for height SDS for chronological age (P < 0.01) suggesting inadvertent skeletal maturation. End height SDS was influenced by duration of treatment and corrected height SDS on multivariate analysis. CONCLUSION: GH treatment improves growth parameters in GHD; height however still remains compromised. Most of the catch-up growth occurs within two years of treatment emphasizing the need of optimal treatment during this period. Inadvertent skeletal maturation during treatment indicates a need for evaluating the role of agents effective in retarding skeletal maturation.

Differential Effect of Vitamin K and Vitamin D Supplementation on Bone Mass in Young Rats Fed Normal or Low Calcium Diet

The purpose of this study was to clarify the differential effect of vitamin K and vitamin D supplementation on bone mass in young rats fed a normal or low calcium diet. Ninety female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into nine groups with 10 rats in each group: baseline control, and 0.5% (normal) or 0.1% (low) calcium diet, either alone, or with vitamin K (30 mg/100g, food intake), vitamin D (25microgram/100 g, food intake), or vitamin K + vitamin D. After 10 weeks of feeding, bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. Vitamin K supplementation increased the maturation-related cancellous bone gain and retarded the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation-related cortical bone gain in rats fed a normal calcium diet. Vitamin D supplementation reduced the maturation-related cancellous bone gain, prevented the reduction in periosteal bone gain, and enhanced the enlargement of the marrow cavity, with no significant effect on the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation- related cancellous and cortical bone gains with increased periosteal bone gain in rats fed a normal calcium diet. An additive effect of vitamin K and vitamin D on the maturation- related cortical bone gain was found in rats fed a normal calcium diet. This study shows the differential effects of vitamin K and vitamin D supplementation on cancellous and cortical bone mass in young rats fed a normal or low calcium diet, as well as the additive effect on cortical bone under calcium sufficient condition.

Intermittent parathyroid hormone treatment can promote linear growth in the ovariectomized growing rat

To compare the effect of intermittent parathyroid hormone (PTH) treatment with that of estrogen treatment on epiphyseal growth in ovariectomized rats, 46 Sprague-Dawley female rats aged 9-10 weeks (about 200-220 g) were either ovariectomized or sham operated. From 6 weeks after ovariectomy (ovx), rats were daily injected with subcutaneous human recombinant PTH (1-84)-dosed 30 micrograms/kg (the low dose PTH-treated group) or 300 micrograms/kg (the high dose PTH-treated group), 17 beta-estradiol (the 17 beta-estradiol-treated group, 30 micrograms/kg) or vehicle (the ovx-alone group), 5 times a week for 4 weeks. The decalcified sections of the distal femoral epiphyseal plate were analyzed on light microscopy after H&E stain, and the lengths of the zones of proliferation, maturing and hypertrophic chondrocytes were measured. The length of the growth plate, the zone of proliferation and the zone of hypertrophic chondrocyte in the ovx-alone group were significantly shorter than those of the sham-operated group. The treatment of 17 beta-estradiol speeded up the differentiation of cells from proliferating chondrocytes to maturing and hypertrophic chondrocytes even though the length of the growth plate was comparable to that of the sham-operated group. Both low and high dose PTH treatments increased the length of the growth plate, and those lengths were comparable to that of the sham-operated group. The fractions of proliferating, maturing and hypertrophic zone in the low dose PTH-treated group were also comparable to those of the sham-operated group. However, high dose PTH treatment slowed down the differentiation of cells from proliferating chondrocytes to maturing and hypertrophic chondrocytes to a greater extent, and therefore the fraction of proliferating chondrocytes of the high dose PTH-treated group was larger than that of the low dose PTH-treated group (73.8 +/- 1.8 Vs 63.3 +/- 1.3%, p < 0.005). From these results, we showed that intermittent PTH treatment could promote linear growth in the ovariectomized growing rat. We propose that PTH may be an alternative drug candidate for promoting linear growth of long bones without the risk for early closure of the growth plate.

Cisto ósseo simples determinando encurtamento de úmero: apresentaçäo de um caso / Simple bone cyst causing shortening of the humerus: report of a case

Apresenta-se um caso de cisto ósseo juvenil que ocorreu no 1/3 superior do úmero de uma paciente de 8 anos de idade. Foi tratado conservadoramente por 19 meses, sem resultado satisfatório. Injetou-se corticóide (Depo-Medrol), melhorando. O resultado, 5 anos e 8 meses de evoluçäo, foi o encurtamento do úmero em 7,0 cm

Crecimiento compensatorio en un niño con síndrome de Bartter tratado con indometacina / Cath up growth in Bartter's syndrome after treatment with indometacine

Se estudió el crecimiento físico de un niño de 9.5 años con síndrome de Bartter tratado durante 4.9 años con indometacina. Se observó un crecimiento compensatorio completo de peso, estatura y edad ósea, siendo especialmente notable la aceleración en la velocidad de crecimiento, al iniciar el tratamiento. Se documenta igual crecimiento compensatorio en perímetro cefálico, pliegues cutáneos, estatura sentada y relación estatura/estatura sentada. Se observa una modificación en la las proporciones corporales y un desarrollo madurativo normal. Este crecimiento compensatorio se asoció a una mejoría en la predicción de la estatura adulta final

Efeito de antiinflamatórios enzimáticos (bromelina, escina e papaína) no desenvolvimento de coluna vertebral de ratas / Effect of enzimatic anti-inflammatory agents (bromelain, aescin and papain) in development of vertebral column of rats

O presente trabalho foi desenvolvido com a utilizaçäo de antiinflamatórios de origem vegetal: bromelina, escina e papaína, em doses terapêuticas. Os antiinflamatórios foram injetados intraperitonealmente em ratas prenhas, com a finalidade de verificarmos os possíveis efeitos sobre o desenvolvimento óssseo das colunas vertebrais. Os resultados obtidos segundo as condiçöes de nossa pesquisa, foram: 1. As três drogas antiinflamatórias de origem vegetal - bromelina, escina e papaína - causaram reduçäo do crescimento das colunas vertebrais de ratas. 2. O grupo onde só as mäes tomaram papaína durante a prenhez, foi o mais atingido no crescimento da coluna vertebral, e o grupo onde as mäes e os filhotes tomaram papaína, foi o menos atingido. 3. Quanto ao crescimento, o grupo composto por animais que tomaram escina durante a prenhez, apresentou um aumento de peso significativo em relaçäo ao grupo controle. 4. Quanto à malformaçäo da coluna vertebral, todos grupos apresentaram leves deformaçöes em relaçäo ao grupo controle, sendo que o grupo onde as mäes e os filhotes tomaram escina, foi o que apresentou maior deformaçäo na estrutura da coluna vertebral