Circulating renin-angiotensin system and catecholamines in childhood: is there a role for birthweight?

There have been only a few reports on the sympathoadrenal and renin-angiotensin systems in children of small gestational age. The purpose of the present study was to investigate plasma levels of ACE (angiotensin-converting enzyme) activity, angiotensin and catecholamines in 8- to 13-year-old children and to determine whether there are correlations between the components of these systems with both birthweight and BP (blood pressure) levels. This clinical study included 66 children (35 boys and 31 girls) in two groups: those born at term with an appropriate birthweight [AGA (appropriate-for-gestational age) group, n = 31] and those born at term but with a small birthweight for gestational age [SGA (small-for-gestational age) group, n = 35]. Concentrations of angiotensin, catecholamines and ACE activity were determined in plasma. Circulating noradrenaline levels were significantly elevated in SGA girls compared with AGA girls (P = 0.036). In addition, angiotensin 11 and ACE activity were higher in SGA boys (P = 0.024 and P = 0.050 respectively). There was a significant association of the circulating levels of both angiotensin 11 and ACE activity with BP levels in our study population. Although the underlying mechanisms that link restricted fetal growth with later cardiovascular events are not fully understood, the findings in the present study support the link between low birthweight and overactivity of both sympathoadrenal and renin-angiotensin systems into later childhood.

Metastatic melanoma positively influences pregnancy outcome in a mouse model: could a deadly tumor support embryo life?

The incidence of melanoma is increasing worldwide. It is one of the leading cancers in pregnancy and the most common malignancy to metastasize to placenta and fetus. There are no publications about experimental models of melanoma and pregnancy. We propose a new experimental murine model to study the effects of melanoma on pregnancy and its metastatic process. We tested several doses of melanoma cells until we arrived at the optimal dose, which produced tumor growth and allowed animal survival to the end of pregnancy. Two control groups were used: control (C) and stress control (SC) and three different routes of inoculation: intravenous (IV), intraperitoneal (IP) and subcutaneous (SC). All the fetuses and placentas were examined macroscopically and microscopically. The results suggest that melanoma is a risk factor for intrauterine growth restriction but does not affect placental weight. When inoculated by the SC route, the tumor grew only in the site of implantation. The IP route produced peritoneal tumoral growth and also ovarian and uterine metastases in 60% of the cases. The IV route produced pulmonary tumors. No placental or fetal metastases were obtained, regardless of the inoculation route. The injection of melanoma cells by any route did not increase the rate of fetal resorptions. Surprisingly, animals in the IV groups had no resorptions and a significantly higher number of fetuses. This finding may indicate that tumoral factors released in the host organism to favor tumor survival may also have a pro-gestational action and consequently improve the reproductive performance of these animals.

Hipertensão Arterial Experimental e Prenhez em Ratas: Repercussões sobre o Peso, Comprimento e Órgãos dos Recém-nascidos

Objetivo: estudar as repercussões da hipertensão arterial sobre o peso e comprimento corpóreo e sobre o peso do fígado e do cérebro de recém-nascidos (RN). Métodos: foram utilizadas 82 ratas virgens da raça Wistar em idade de reprodução. Após a indução da hipertensão arterial experimental (modelo Goldblatt I: 1 rim - 1 clipe) as ratas foram sorteadas para compor os quatro grandes grupos experimentais (controle (C), manipulação (M), nefrectomia (N) e hipertensão (H). A seguir, as ratas foram distribuídas por sorteio em 8 subgrupos, sendo quatro grupos prenhes e quatro grupos não-prenhes. Após acasalamento dos quatro grupos prenhes, obtivemos com o nascimento dos recém-nascidos os seguintes grupos: RN-C, RN-M, RN-N e RN-H, respectivamente controle, manipulação, nefrectomia e hipertensão. Resultados: quanto ao peso e comprimento corpóreo dos recém-nascidos observamos que os grupos RN-N e RN-H apresentaram os menores pesos e comprimentos em relação ao seus controles. Quanto ao peso do fígado os RN-H apresentaram os menores pesos em relação aos seus controles. Conclusão: a hipertensão arterial determinou redução no peso corpóreo, no comprimento, no peso do fígado e no peso do encéfalo dos recém-nascidos.

Evaluation of Cell Proliferation and Apoptosis in Placentas of Rats with Severe Diabetes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Repercussions of mild diabetes on pregnancy in Wistar rats and on the fetal development

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of neonatally-induced mild diabetes in rats: Maternal and fetal repercussions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Metodologia para estudo do volume e densidade absoluta da placenta humana de termo

OBJETIVO: comparar duas metodologias para o cálculo do volume placentário em gestações normais de termo: a do princípio de Arquimedes e a do volume do cilindro, para estimar a densidade absoluta da placenta. Definir a metodologia mais adequada para o cálculo do volume e densidade placentários, que se relacione com o peso e classificação do recém-nascido. MÉTODOS: foram estudadas 50 placentas provenientes de gestações de termo sem complicações e calculados o volume e a densidade absoluta placentários: a) pelo princípio de Arquimedes e b) na suposição de que a placenta seria uma secção de cilindro com duas alturas diferentes do bolo placentário: com a altura média e com a altura da média aritmética do centro e extremidades. As densidades absolutas placentárias foram calculadas pelo quociente entre o peso ao ar da placenta e os diferentes volumes. RESULTADOS: a maioria das gestantes eram multíparas, idade média de 25,4 anos, volume placentário médio entre 547,8 e 610 cm³ e densidade média entre 0,94 e 1,14 g/cm³, dependendo da metodologia empregada. CONCLUSÕES: a metodologia mais adequada para estimar o volume placentário no termo foi a do princípio de Arquimedes, pela melhor correlação com o peso dos recém-nascidos, o índice placentário e a classificação do peso dos recém-nascidos em relação à idade gestacional.

Partial HELLP Syndrome: maternal and perinatal outcome

CONTEXTO: A síndrome HELLP é uma grave complicação da gestação caracterizada por hemólise, elevação das enzimas hepáticas e plaquetopenia. Algumas gestantes desenvolvem somente uma ou duas dessas características da síndrome HELLP. Esse quadro é denominado de síndrome HELLP parcial (SHP). OBJETIVO: O objetivo deste estudo foi avaliar as repercussões maternas e perinatais das mulheres que desenvolveram SHP e comparar os resultados com mulheres que tiveram hipertensão gestacional ou pré-eclâmpsia sem alterações dos exames laboratoriais para síndrome HELLP. TIPO DE ESTUDO: Observacional, retrospectivo e analítico. LOCAL: Maternidade do Hospital das Clínicas da Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, São Paulo, Brasil. AMOSTRA: Foram selecionadas gestantes ou puérperas que tiveram elevação dos níveis pressóricos detectada pela primeira vez após a primeira metade da gestação com ou sem proteinúria entre janeiro/1990 a dezembro/1995. As mulheres foram divididas em dois grupos: Grupo SHP quando as mulheres com hipertensão arterial tinham pelo menos uma, mas não todas as alterações de exames que demonstravam hemólise, elevação das enzimas hepáticas ou plaquetopenia e Grupo Hipertensas pacientes com hipertensão sem alterações nos exames laboratoriais para síndrome HELLP. PRINCIPAIS VARIÁVEIS: Analisamos idade materna, raça, paridade, classificação da hipertensão, idade gestacional no diagnóstico da SHP, alterações nos exames laboratoriais para síndrome HELLP, tempo de permanência no hospital, complicações maternas, via de parto, incidência de prematuridade, restrição de crescimento intra-uterino, natimortos e neomortos. RESULTADOS: 318 mulheres foram selecionadas, das quais 41 (12,9%) tiveram SHP e 277 (87,1%) não desenvolveram alterações dos exames laboratoriais que compõem o diagnóstico da síndrome HELLP. A pré-eclâmpsia foi um tipo de hipertensão mais freqüente no grupo SHP que no grupo hipertensas. Não houve pacientes com hipertensão crônica isolada que desenvolveram SHP. A taxa de cesárea, eclâmpsia e de partos prematuros foi significativamente mais freqüente no grupo SHP que no grupo hipertensas. CONCLUSÃO: Observamos uma conduta agressiva nas pacientes com SHP, que resultou na interrupção imediata da gestação, com elevada taxa de cesárea e de recém-nascido pré-termo. Esta conduta deve ser revista para a redução desses índices.

Alterações do fluxo sanguíneo em artéria umbilical na síndrome hipertensiva gestacional e suas implicações nos resultados neonatais

OBJETIVO: Avaliar as características antropométricas, a morbidade e mortalidade de recém-nascidos (RN) prematuros nascidos vivos de mães hipertensas em função da presença ou não de diástole zero (DZ) ou reversa (DR) na doplervelocimetria arterial umbilical. MÉTODOS: Estudo prospectivo, envolvendo RN prematuros nascidos vivos de gestantes hipertensas, com idade gestacional entre 25 e 33 semanas, submetidas à doplervelocimetria da artéria umbilical nos 5 dias que antecederam o parto, realizado no Hospital do Distrito Federal, entre 1º de novembro de 2009 e 31 de outubro de 2010. Os RN foram estratificados em dois grupos, conforme o resultado da doplervelocimetria da artéria umbilical: Gdz/dr=presença de diástole zero (DZ) ou diástole reversa (DR) e Gn=doplervelocimetria normal. Medidas antropométricas ao nascimento, morbidades e mortalidade neonatal foram comparadas entre os dois grupos. RESULTADOS: Foram incluídos 92 RN, assim distribuídos: Gdz/dr=52 RN e Gn=40 RN. No Gdz/dr a incidência de RN pequenos para idade gestacional foi significativamente maior, com risco relativo de 2,5 (IC95% 1,7‒3,7). No grupo Gdz/dr os RN permaneceram mais tempo em ventilação mecânica mediana 2 (0‒28) e no Gn mediana 0,5 (0‒25), p=0,03. A necessidade de oxigênio aos 28 dias de vida foi maior no Gdz/dr do que no Gn (33 versus10%; p=0,01). A mortalidade neonatal foi maior em Gdz/dr do que em Gn (36 versus 10%; p=0,03; com risco relativo de 1,6; IC95% 1,2 - 2,2). Nessa amostra a regressão logística mostrou que a cada 100 gramas a menos de peso ao nascer no Gdz/dr a chance de óbito aumentou 6,7 vezes (IC95% 2,0 - 11,3; p<0,01). CONCLUSÃO: em RN prematuros de mães hipertensas com alteração na doplervelocimetria da artéria umbilical a restrição do crescimento intrauterino é frequente e o prognóstico neonatal pior, sendo elevado o risco de óbito relacionado ao peso ao nascimento.

A comparative-analysis of glycosaminoglycans from human umbilical arteries in normal subjects and in pathological conditions affecting pregnancy

BACKGROUND: Vascular cells express different phenotypes in adult and fetal vessels, and the extracellular matrix they synthesize should reflect these differences. Alterations of vascular proteoglycan/glycosaminoglycan is verified in disorders such as hypertension and diabetes, and when occurring during pregnancy, they bring about structural changes to fetal vessels that often lead to impaired fetus growth. Yet there is little data about the extracellular matrix of an important human fetal vessel, the umbilical artery.EXPERIMENTAL DESIGN: This study involved the biochemical characterization of the extracellular matrix of normal umbilical arteries, umbilical arteries from complicated pregnancies (maternal hypertension and diabetes and intrauterine growth retardation syndrome), and, for purpose of comparison, normal adult arteries (aorta and iliac and pulmonary arteries). Although the collagen types I:III ratio was determined in some cases, emphasis was placed on analysis of glycosaminoglycans.RESULTS: Normal umbilical arteries differ from normal adult arteries in that they contain greater concentrations of hyaluronic acid and lesser concentrations of heparan sulfate and chondroitin 4-and 6-sulfate. The umbilical artery also differs from adult arteries in the disaccharide composition of its chondroitin and heparan sulfates and in the molecular weight of this latter glycosaminoglycan. The glycosaminoglycan distribution in umbilical arteries derived from complicated pregnancies is roughly similar to that of controls. However, total glycosaminoglycan and collagen were significantly reduced, and the collagen I:III ratio was increased in the umbilical arteries from hypertension-complicated pregnancies.CONCLUSIONS: the glycosaminoglycan composition of the normal umbilical artery, a fully differentiated tissue, differs in many aspects from that of normal adult arteries. of the cases of complicated pregnancies studied, the extracellular matrix of umbilical arteries was altered only in maternal hypertension. The changes, notably a mild fibrosis, were not very pronounced and should not impair hemodynamic properties of the vessel.

Influência do período de gestação e do tamanho da ninhada no crescimento ponderal intra-uterino de coelhos

Intrauterine growth of Norfolk rabbits was studied from the 20th day of gestation until the parturition (31st day). A theoretical equation was adjusted for fetuses body weight. The exponential model was tested by stepwise regression technique after linearization. Both stage of gestation (t) and number of fetuses (n) had significant effects on the growth rate. The following equation was proposed to describe the weight of the pups: W = exp. (-12,9772).n.exp. {(0,991263-0,014007.5-0,00039.n)t} (with R2 = 0,9932). The biological coherence and the interpretation of the coefficients permitted us to conclude that similar models could be used for other multiparous species. This model can also be used with or without the presence of different factors related to fetal growth.

Relação do peso de recém-nascidos e placentas. Estudo em recém-nascidos de termo, pré-termo e pós-termo, de pesos adequado, baixo e grande para a idade gestacional

Birth weight and placental weight of 566 newborns were determined. The newborns were classified by birth weight and gestational age in seven groups: term, preterm and postterm newborns with weight appropriate for gestational age; term and postterm newborns small for gestational age; term and preterm newborns large for gestational age. The differences in the mean placental weight in the preterm, term and postterm newborns with weight appropriate for gestational age were not significant. After 34 weeks of gestation there was little increase in placental weight. The mean placental weight of newborns large for gestational age was significantly different from that of term newborns appropriate for gestational age. In the term and postterm newborns small for gestational age the mean placental weight was significantly different from term and postterm newborns appropriate for gestational age. These findings suggest that newborns with an appropriate intrauterine growth have little increase in placental weight in the gestational period. Gestational age is not an important factor in determining placental weight in this period. Nutrition is important for placental growth-retarded infants have small placentas and large-for-date infants have large placental weight.

Alterações anatomopatológicas placentárias. Relação com o peso e idade gestacional de recém-nascido

The authors studied gross and histological abnormalities of placentae from 566 newborns, grouped according to birth and gestational age. The relation of hemorragic abnormalities, infections of membranes and placental tissue, chronic infections, calcifications, hydropic degeneration of villi, chorangioma, cysts, vascular lesions (endarteritis) with newborn weight, length of gestation and intrauterine growth retardation were determined. We concluded that lesions due to disturbances of placental blood flow were significantly more frequent in placentae from term newborns small for gestational age; villi hydropic degenerations were more frequent in placentae of pre-term newborns appropriate for gestational age. Chronic infections had a tendency to be greater in placentae from infants with diminished intrauterine growth. Term newborns small for gestational age had greater proportions of placental abnormalities than the other groups.

Alkaline ribonuclease activity in maternal serum and in serum of newborns from birth up to thirty days of age. A study made with full-term appropriate-, full-term small- and preterm appropriate-for-gestational-age infants

We have studied the alkaline ribonuclease (RNase) activity in maternal serum and serum of full-term small- (T-SGA), full-term appropriate- (T-AGA) and preterm appropriate-for-gestational age (PT-AGA) newborns. A significantly lower level of RNase was observed in T-AGA and T-SGA newborns on the 30th day of age and in PT-AGA newborns on the 15th and 30th days of age, as compared to other T-AGA, T-SGA and PT-AGA groups of infants at birth. RNase activity was significantly higher in cord blood than in the maternal blood in all categories studied. Moreover, in preterm newborns, RNase activity in cord blood was significantly higher in those presenting a lower gestational age. We did not observe any significant difference in RNase levels in the cord blood of newborns from the 3 categories studied. The same results were observed concerning maternal blood. We, therefore, conclude that RNase activity in cord blood or in maternal blood is not a very statisfactory indicator of fetal malnutrition.

Effects of cigarette smoke on the Meckel's cartilage of rat fetus : Morphologic, morphometric and stereologic study

The purpose of this study was to investigate the effects of cigarette smoke on the development of the embryo mandible (Meckel's) cartilage in rat fetuses. When inhaled by female Wistar rats between the 9th and the 12th day of pregnancy, cigarette smoke (5 cigarettes a day) caused intrauterine growth retardation, providing smaller fetuses and placentas. In fetuses from the experimental group, the histopathologic examination revealed a poorly developed Meckel' s cartilage with smaller chondroblasts showing a scanty cytoplasm with spherical and paler central nuclei, as well as more abundant cartilage matrix. Morphometric analysis revealed that Meckel's cartilage lacunae were smaller in the fetuses from the experimental group, although not showing any remarkable alteration in shape. The results suggested that inhalation of cigarette smoke by pregnant rats during the organogenic period induced growth retardation and delayed cellular differentiation in rat fetal Meckel's cartilage.