ABSTRACT
Muitos protocolos experimentais pré-clinicos in vivo empregam a estreptozotocina (STZ) como ferramenta farmacológica para a compreensão das sequelas que acometem os indivíduos expostos à hiperglicemia gestacional. O objetivo deste estudo foi sintetizar os diversos protocolos experimentais utilizados para os estudos de embriões, fetos e filhotes de ratas com diabetes mellitus gestacional (DMG) induzida por estreptozotocina (DMG-STZ). Realizou-se uma revisão integrativa da literatura sobre as abordagens metodológicas aplicadas aos estudos da DMG-STZ em ratos. Três pontos foram destacados nesta revisão: a) Doses e principais vias de administração da STZ, concentração plasmática de glicose para reconhecimento do DMG-STZ; b) Protocolos empregados para a avaliação pré-natal; c) Protocolos empregados para a avaliação do desenvolvimento pós-natal. As doses encontradas nos protocolos variaram entre 30 e 135 mg/Kg para administração por via intraperitoneal; entre 15 e 65 mg/Kg para via intravenosa e na dose de 45 mg/Kg para via subcutânea. Os valores glicêmicos sanguíneos para reconhecimento do DMG ficaram entre 97 e 500 mg/dL. Os estudos pré-natais abordaram a embriopatia diabética associada ao desenvolvimento do sistema nervoso central e à função renal, além das alterações do transporte útero- -placentário-fetal; os estudos pós-natais enfatizaram a correlação entre a macrossomia neonatal e a dislipidemia pós-natal, o desenvolvimento comportamental pós-natal e as alterações cardiovasculares. Embora existam grandes diferenças metodológicas entre os protocolos empregados, podemos concluir que a DMG-STZ ainda é um bom modelo para os estudos dos efeitos da hiperglicemia sobre os conceptos.
Many in vivo preclinical experimental protocols employ streptozotocin (STZ) as a pharmacological tool for understanding sequelae affecting individuals exposed to gestational hyperglycemia. The objective of this study was to synthesize the different experimental protocols that have been used to examine the embryos, fetuses, and pups of rats with Gestational Diabetes Mellitus (GDM) induced by streptozotocin (GDM-STZ). In this work, we have developed an integrative literature review, including quantitative methodological approaches that can be applied to studies of GDM-STZ in rats. Three points were highlighted in this study: a) Doses and central routes of STZ administration, and plasma glucose concentration for recognition of GDM-STZ; B) Protocols used for prenatal evaluation; c) Protocols used for the assessment of postnatal development. The doses ranged from 30 to 135 mg/kg for intraperitoneal administration; Between 20 and 65 mg/kg for the intravenous route and 45 mg/kg for the subcutaneous route. The blood glucose values for recognition of GDM were between 97 and 500 mg/dL. Prenatal studies approached diabetic embryopathy associated with central nervous system development and renal function in addition to changes in utero-placental-fetal transport. On the other hand, postnatal studies emphasized the correlation between neonatal macrossomia and postnatal dyslipidemia, postnatal behavioral development and cardiovascular changes. Although there are large methodological differences between the protocols employed, we can conclude from this review that GDM-STZ is still a good model for the studies of the effects of hyperglycemia on the concepts.
Subject(s)
Female , Animals , Pregnancy , Rats , Diabetes, Gestational/diagnosis , Diabetes, Gestational/chemically induced , Streptozocin/analysis , Guidelines as Topic , Fetal Macrosomia/veterinaryABSTRACT
Muitos protocolos experimentais pré-clinicos in vivo empregam a estreptozotocina (STZ) como ferramenta farmacológica para a compreensão das sequelas que acometem os indivíduos expostos à hiperglicemia gestacional. O objetivo deste estudo foi sintetizar os diversos protocolos experimentais utilizados para os estudos de embriões, fetos e filhotes de ratas com diabetes mellitus gestacional (DMG) induzida por estreptozotocina (DMG-STZ). Realizou-se uma revisão integrativa da literatura sobre as abordagens metodológicas aplicadas aos estudos da DMG-STZ em ratos. Três pontos foram destacados nesta revisão: a) Doses e principais vias de administração da STZ, concentração plasmática de glicose para reconhecimento do DMG-STZ; b) Protocolos empregados para a avaliação pré-natal; c) Protocolos empregados para a avaliação do desenvolvimento pós-natal. As doses encontradas nos protocolos variaram entre 30 e 135 mg/Kg para administração por via intraperitoneal; entre 15 e 65 mg/Kg para via intravenosa e na dose de 45 mg/Kg para via subcutânea. Os valores glicêmicos sanguíneos para reconhecimento do DMG ficaram entre 97 e 500 mg/dL. Os estudos pré-natais abordaram a embriopatia diabética associada ao desenvolvimento do sistema nervoso central e à função renal, além das alterações do transporte útero- -placentário-fetal; os estudos pós-natais enfatizaram a correlação entre a macrossomia neonatal e a dislipidemia pós-natal, o desenvolvimento comportamental pós-natal e as alterações cardiovasculares. Embora existam grandes diferenças metodológicas entre os protocolos empregados, podemos concluir que a DMG-STZ ainda é um bom modelo para os estudos dos efeitos da hiperglicemia sobre os conceptos.(AU)
Many in vivo preclinical experimental protocols employ streptozotocin (STZ) as a pharmacological tool for understanding sequelae affecting individuals exposed to gestational hyperglycemia. The objective of this study was to synthesize the different experimental protocols that have been used to examine the embryos, fetuses, and pups of rats with Gestational Diabetes Mellitus (GDM) induced by streptozotocin (GDM-STZ). In this work, we have developed an integrative literature review, including quantitative methodological approaches that can be applied to studies of GDM-STZ in rats. Three points were highlighted in this study: a) Doses and central routes of STZ administration, and plasma glucose concentration for recognition of GDM-STZ; B) Protocols used for prenatal evaluation; c) Protocols used for the assessment of postnatal development. The doses ranged from 30 to 135 mg/kg for intraperitoneal administration; Between 20 and 65 mg/kg for the intravenous route and 45 mg/kg for the subcutaneous route. The blood glucose values for recognition of GDM were between 97 and 500 mg/dL. Prenatal studies approached diabetic embryopathy associated with central nervous system development and renal function in addition to changes in utero-placental-fetal transport. On the other hand, postnatal studies emphasized the correlation between neonatal macrossomia and postnatal dyslipidemia, postnatal behavioral development and cardiovascular changes. Although there are large methodological differences between the protocols employed, we can conclude from this review that GDM-STZ is still a good model for the studies of the effects of hyperglycemia on the concepts.(AU)
Subject(s)
Animals , Female , Pregnancy , Rats , Diabetes, Gestational/chemically induced , Diabetes, Gestational/diagnosis , Streptozocin/analysis , Guidelines as Topic , Fetal Macrosomia/veterinaryABSTRACT
Background: The advent of animal cloning from embryos reconstructed with nuclei from cells at different stages of differentiation has been responsible for the appearance of several anomalies in calves, with some alterations diagnosed during pregnancy and others after the birth of cloned animals. Despite efforts over the past five years, the rate of mortality after the birth of cloned calves is still high, at about 50%. Below is reported the research experience gained at the University of São Paulo in the period from 2005 to 2010, related to the birth of cloned calves from Nellore. Review: Research showed that cloned calves present cardiopulmonary disorders characterized by tachycardia with episodes of arrhythmia with bradycardia, increase in the 1st heart sound, presence or absence of heart murmurs in the 1st and 2nd heart sound associated with dyspnea, breathing harsh and crackling dry, moist and crackling. During the first days of life of cloned calves that died, ultrasound examination demonstrated the presence of concentric hypertrophy congenital cardiac and turbulent flow at the foramen of botal towards the right heart to left heart, indicating reversal of blood flow to the pattern observed in fetal life. As a result, mixture of arterial and venous blood occurs, compromising the ability of oxygen to the blood of cloned calves. The occurrence of macrosomia was observed in 20.9% of Nellore calves. It is believed that this syndrome is associated with disorders of carbohydrate metabolism in the placenta and/or fetus, leading to fetal gigantism, which mimicks excessive fetal growth seen in pregnant women with diabetes. We observed the occurrence of moderate to severe normocytic and normochromic anemia, with the anemia gradually appearing from 12 h of life onwards, reaching its maximum intensity at the end of the first week, to start a gradual recovery to normal values from the 15th day of life. The anemia observed in cloned calves was ferropriva, as such animals showed a significant decrease in serum iron levels associated with decreased transferrin saturation index (STI). Umbilical anomalies occurred in most clones. There was an increase in the thickness of the umbilical cord, which hindered its spontaneous rupture at birth. The umbilical arteries did not undergo retraction into the abdominal cavity, leaving them exposed in the remnant of the umbilical cord. In the first three days after birth, strong pulse of these arteries was noted in umbilical cord, making it necessary to use clamps on the arteries in order to prevent bleeding. There were also intra-abdominal hematomas involving the arteries and the urachus. Between 15 and 20 days of life, it was observed the occurrence of alopecia in about 75.0% of the calves, whose origin may be related to disturbances in the synthesis and absorption of vitamins, since the supplementation of calves with ADE vitamin complex decreased symptoms. Conclusion: The results confirm the occurrence of serious cardiopulmonary disorders characterized by tachycardia, hyperphonesis, presence of heart murmurs in the 1st and 2nd heart sounds, episodes of arrhythmia and bradycardia associated with dyspnea, rales, and coarse breath. As a result of the non-closure of the foramen of Botal and the Ductus Arteriosus, arterial and venous blood a mix, compromising the oxygen carrying capacity in the blood of cloned calves. There was also the occurrence of macrosomia, hypoglycemia, hypothermia, abnormal umbilical structures, anemia and alopecia