Efeitos do Verapamil (Dilacoron), bloqueador dos canais de calcio, na regenaração do figado de ratos apos hepatectomia parcial

Orientador: Thales Rocha de Mattos FilhoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaDoutorad

Ação do verapamil, bloqueador de canais de calcio, sobre o desenvolvimento do germe dentario de ratos e sua correlação com os teores sericos de calcio

Orientador: Jose Ranali, Wilma P. Bastos RamosDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: Tendo em vista que os bloqueadores dos canais de cálcio, são utilizados na terapêutica, geralmente, por longos períodos de tempo, muitas vezes em gestantes, propôs-se estudar neste trabalho, os efeitos do verapamil sobre o germe dentário de filhotes de ratas tratadas com a droga, antes e durante a prenhez. Avaliou-se os efeitos da droga sobre implantações uterinas, reabsorções fetais, desenvolvimento ósseo e níveis plasmáticos de cálcio, fosfatos e proteínas totais em mães e filhotes. Utilizou-se 73 ratos Wistar...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digitalAbstract: Calcium channel blockers are widely used in therapeutics, usually in long term treatments, often in pregnant women. It was intended, this occasion, to study the effects of verapamil on dental germ of new-born from mothers treated with this drug, before and during pregnancy. It was studied the effects of the drug on uterine implantation, fetal reabsorption, bone development and serum levels of calcium, phosphate and total proteins in mothers and new-born. It was used 73 Wistar rats (Ratus norvergicus, varoAlbinus), quality controlled. The female were randomly divided in 3 groups, as fa11ows: the first received verapamil in doses of 24 mg/ratlEtay,named group (01) the second received the drug in doses of 2.4 mg/ratlday, named group (02); the third was a control group. The rats were kept in individual cases and received the drug in the drinking water during 10 weeks: 7 weeks before mating and three weeks during pregnancy. The cesarean surgery was performed at the 21st day. This occasion, heparinized blood samples were taken (to biochemical determinations) as well as isolated the femoral bone (to bone development determination). The new-born heads were isolated to histology of dental germs and taken blood samples to biochemical determinations...Note: The complete abstract is available with the full electronic digital thesis or dissertationsMestradoFarmacologiaMestre em Ciência

CALCIUM CHANNEL BLOCKER VERAPAMIL STIMULATES OVULATION AND INDUCES FETAL REABSORPTION IN RATS

Os bloqueadores dos canais de cálcio são largamente utilizados em distúrbios cardiovasculares, usualmente em tratamentos prolongados, ocasionalmente em mulheres grávidas. Foram estudados os efeitos do verapamil sobre a implantação uterina, a reabsorção fetal e os níveis de cálcio, fosfato e proteínas totais plasmáticos de mães e filhotes. Foram utilizadas 75 ratas fêmeas Wistar, com qualidade controlada. Os animais tratados foram divididos em dois grupos: o primeiro recebeu verapamil na dose 2,4 mg/rato/dia de e o segundo, 24 mg/rato/dia. A droga foi administrado na água de beber durante 10 semanas: 7 semanas antes do acasalamento e 3 semanas durante a gestação, sendo a operação cesariana realizada ao 21º dia. Por ocasião da cesariana, foram tomadas amostras de sangue das mães e filhotes. O verapamil, na dose mais elevada, causou diminuição dos níveis plasmáticos de cálcio e fosfato nas mães a par de diminuir o peso corpóreo dos filhotes. Os níveis séricos de cálcio, fosfato e proteínas foram comparáveis nos filhotes dos grupos controle e tratado. Contudo, foram significativamente mais baixos em todos os filhotes, em comparação com as respectivas mães. Os resultados mostraram que o verapamil estimulou a ovulação, aumentando o número de implantações uterinas, enquanto induziu morte fetal precoce e reabsorção fetal. Abstract Calcium channel blockers are widely used in cardiovascular diseases, usually in long-term treatments, occasionally in pregnant women. The effects of verapamil were studied on uterine implantation, fetal reabsorption and mothers and offsprings plasmatic levels of calcium, phosphate and total protein. Seventy-five quality-controlled female Wistar rats were used. The drug-treated animals were divided in two groups: the first received verapamil in doses of 2.4 mg/rat/day and the second, doses of 24 mg/rat/day. The drug was administered by means of the drinking water for 10 weeks: 7 weeks before mating and 3 weeks during pregnancy; cesarean surgery was performed on the 21st. day. On the occasion of the cesarean, mothers and newborns blood samples were taken. Verapamil, in the higher dose, caused a lowering of plasmatic calcium and phosphate in mothers and reduced body weight in offspring. In the young, plasmatic calcium, phosphate and total proteins were comparable in verapamil treated and control. However, these values were significantly lower in newborn of treated and control groups, as compared to their respective mothers. Results show that verapamil stimulated ovulation, increasing the uterine implantation but induced early fetal death and reabsorption

EFFECTS OF CALCIUM CHANNELBLOCKER VERAPAMIL ON BONE AND DENTAL GERM IN RATS

O verapamil e outros bloqueadores dos canais de cálcio são usados como antihipertensivos e antiarrítmicos tratamentos prolongados ou por toda a vida, podendo ser indicados em gestantes. Foi estudado o efeito do bloqueador dos canais de cálcio sobre o germe dental, tempo de erupção dentária de filhotes nascidos de mães tratadas e mineralização óssea nas mães. As fêmeas tratadas foram divididas em dois grupos: o primeiro recebeu verapamil na dose de 2,4 mg/rato/dia e o segundo, 24 mg/rato/dia. Os animais foram divididas em dois subgrupos: o primeiro recebeu a droga durante 10 semanas: 7 semanas antes do acasalamento e 3 semanas durante a gestação realizando-se a operação cesariana ao 21o dia; o outro foi tratado como o primeiro, porem os filhotes nasceram de parto natural e o tratamento das mães foi continuado por 15 dias. Foram determinados os níveis plasmáticos de cálcio e fosfato de mães e filhotes. As cabeças dos filhotes foram seccionadas para histologia dos germes dentários e determinados os pesos úmido e seco do osso femoral das mães. Os resultados mostraram que a droga, na dose mais elevada, diminuiu os níveis séricos de cálcio e fosfato nas mães, enquanto que nos filhotes, os valores foram significativamente mais baixos em comparação com as mães. O verapamil causou aumento da mineralização óssea nas mães durante a gestação, mas não após o parto. Um aumento da calcificação dos germes dentários dos filhotes não pôde ser demonstrada, porem na dose mais elevada, o verapamil causou retardo significativo na erupção dentária. Abstract Verapamil and other calcium blocker drugs are used as antihypertensive and antiarrhythmic in long term treatments and appropriate to be prescribed for pregnant women. It was studied in rats the effects of verapamil on dental germ calcification, the time of dental eruption in offspring born from treated mothers and on mothers bone mineralization. The rats were divided in two groups: one received verapamil in doses of 2.4 mg/rat/day and the other, 24 mg/rat/day. The animals were divided in two subgroups: one was treated during 10 weeks: 7 before mating and 3 during pregnancy, cesarean surgery performed on the 21st day; the other was treated in the same way but the offspring were born by natural delivery and the mothers treatment continued for 15 days. Plasma calcium and phosphate were assayed in mothers and offspring. The offsprings heads were isolated to histology of dental germs and determined mothers femoral bone fresh and dry weights. Results show that the higher dose verapamil lowered mothers plasmatic calcium and phosphate while a significant lower values were observed in offspring as compared to their mothers. Verapamil increased mothers femoral bone mineralization during mineralization but not after delivery. An increased calcium deposition of dental germ could not be demonstrated but verapamil significantly delayed newborns dental eruption

EFFECTS OF CALCIUM CHANNELBLOCKER VERAPAMIL ON BONE AND DENTAL GERM IN RATS

O verapamil e outros bloqueadores dos canais de cálcio são usados como antihipertensivos e antiarrítmicos tratamentos prolongados ou por toda a vida, podendo ser indicados em gestantes. Foi estudado o efeito do bloqueador dos canais de cálcio sobre o germe dental, tempo de erupção dentária de filhotes nascidos de mães tratadas e mineralização óssea nas mães. As fêmeas tratadas foram divididas em dois grupos: o primeiro recebeu verapamil na dose de 2,4 mg/rato/dia e o segundo, 24 mg/rato/dia. Os animais foram divididas em dois subgrupos: o primeiro recebeu a droga durante 10 semanas: 7 semanas antes do acasalamento e 3 semanas durante a gestação realizando-se a operação cesariana ao 21o dia; o outro foi tratado como o primeiro, porem os filhotes nasceram de parto natural e o tratamento das mães foi continuado por 15 dias. Foram determinados os níveis plasmáticos de cálcio e fosfato de mães e filhotes. As cabeças dos filhotes foram seccionadas para histologia dos germes dentários e determinados os pesos úmido e seco do osso femoral das mães. Os resultados mostraram que a droga, na dose mais elevada, diminuiu os níveis séricos de cálcio e fosfato nas mães, enquanto que nos filhotes, os valores foram significativamente mais baixos em comparação com as mães. O verapamil causou aumento da mineralização óssea nas mães durante a gestação, mas não após o parto. Um aumento da calcificação dos germes dentários dos filhotes não pôde ser demonstrada, porem na dose mais elevada, o verapamil causou retardo significativo na erupção dentária. Abstract Verapamil and other calcium blocker drugs are used as antihypertensive and antiarrhythmic in long term treatments and appropriate to be prescribed for pregnant women. It was studied in rats the effects of verapamil on dental germ calcification, the time of dental eruption in offspring born from treated mothers and on mothers bone mineralization. The rats were divided in two groups: one received verapamil in doses of 2.4 mg/rat/day and the other, 24 mg/rat/day. The animals were divided in two subgroups: one was treated during 10 weeks: 7 before mating and 3 during pregnancy, cesarean surgery performed on the 21st day; the other was treated in the same way but the offspring were born by natural delivery and the mothers treatment continued for 15 days. Plasma calcium and phosphate were assayed in mothers and offspring. The offsprings heads were isolated to histology of dental germs and determined mothers femoral bone fresh and dry weights. Results show that the higher dose verapamil lowered mothers plasmatic calcium and phosphate while a significant lower values were observed in offspring as compared to their mothers. Verapamil increased mothers femoral bone mineralization during mineralization but not after delivery. An increased calcium deposition of dental germ could not be demonstrated but verapamil significantly delayed newborns dental eruption

Homogenous demineralized dentin matrix for application in cranioplasty of rabbits with alloxan-induced diabetes: Histomorphometric analysis

Purpose: The aim of this work was to evaluate the bone-repair process after implantation of homogenous demineralized dentin matrix (HDDM) slices in surgical defects created in the parietal bones of rabbits with alloxan-induced diabetes. Materials and Methods: Forty-eight rabbits were selected and divided into 4 groups of 12 rabbits: the control group, diabetic rabbits (D), diabetic rabbits with a PTFE barrier (D-PTFE), and diabetic rabbits with a PTFE barrier and with slices of homogenous demineralized dentin matrix (D-PTFE+HDDM). The diabetic animals received a single dose of alloxan monohydrate (90 mg/kg) intravenously on the marginal ear vein, and their blood glucose was verified daily. The rabbits were sacrificed after 15, 30, 60, and 90 days. The histologic findings show both better bone structure and significantly greater bone density, as determined by histomorphometric analysis, for the D-PTFE + HDDM group than for the other 3 groups (P < .01). It was also observed that the mean bone density increased gradually from 15 to 90 days (except in the D-PTFE group). Conclusion: It was concluded that the HDDM was biocompatible with the bone repair of diabetic rabbits and that HDDM slices stimulated bone tissue formation. Facilitation of bone repair with HDDM could be useful in diabetic patients

Bone regeneration in cranioplasty and clinical complications in rabbits with alloxan-induced diabetes

This research evaluated the bone repair process in surgical defects created on the parietal bones of diabetic rabbits using the guided bone regeneration technique to observe the effects of alloxan in the induction of diabetes mellitus. Twenty-four adult rabbits were divided into three study groups: control (C), diabetic (D) and diabetic associated to polytetrafluoroethylene (PTFE) membrane (D-PTFE). For diabetes induction the animals received one dose of monohydrated alloxan (90 mg/kg) by intravenous administration in the auricular or femoral vein. In group D-PTFE the membrane covered both the floor and the surface of the bone defect. In groups D and C, the bone defect was filled up with blood clot. The specimens were fixed in 10% formol and prepared for histomorphometric analysis. The results showed that the 90 mg/kg dose of monohydrate alloxan was sufficient to promote diabetes mellitus when administered in the auricular vein. Bone regeneration was slower in the diabetic group when compared with the control and diabetic-PTFE groups, but there was no significant statistical difference between the two experimental groups (D and D-PTFE). The oral and general clinical complications among the diabetics were weight loss, polyuria, polyphagia and severe chronic gingivitis

Optical density of bone repair after implantation of homogenous demineralized dentin matrix in diabetic rabbits

This research evaluated the bone repair process after implantation of homogenous demineralized dentin matrix (HDDM) in surgical defects in the parietal bone of rabbits with alloxan-induced diabetes, using a polytetrafluorethylene (PTFe) barrier for guided bone regeneration. Thirty-six rabbits were used and divided into four groups: control (C, n = 12), diabetic (D, n = 12, left parietal bone), diabetic with PTFe (DPTFe, same 12 rabbits, right parietal bone), and diabetic with PTFe associated to HDDM (D-PTFe+HDDM, n = 12). Bone defects were created in the parietal bone of the rabbits and the experimental treatments were performed, where applicable. The rabbits were sacrificed after 15, 30, 60 and 90 days. The bone defects were examined radiographically and by optical density (ANOVA and Tukey test, p < .05). The radiographic findings showed that the D-PTFe+HDDM group presented greater radiopacity and better trabecular bone arrangement when compared to that of the C, D and D-PTFe groups. The statistical analysis showed significant differences in the optical density of the newly formed bone among the studied groups. It was possible to conclude that HDDM was biocompatible in diabetic rabbits