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Biomedical subjects

D E de Mello

Publications and source records attributed to D E de Mello.

4 recordsLinked to original sources

Effect of prenatal glucocorticoid on fetal lung ultrastructural maturation in hyt/hyt mice with primary hypothyroidism.

Glucocorticoids (GC) and thyroid hormones (TH) accelerate fetal lung maturation. Though GC are used clinically, the mechanisms of GC-induced fetal lung maturity remain unclear. Prenatal GC increase fetal TH activity in humans and in animals. Thus, it is possible that increased fetal TH activity after prenatal GC plays a role in accelerating fetal lung maturation. However, this hypothesis has remained untested due to the lack of a suitable animal model. In the hyt/hyt mouse primary hypothyroidism occurs due to a point mutation in the beta subunit of the thyroid-stimulating hormone receptor of the thyroid gland, and it is transmitted in an autosomal recessive manner. We studied the effect of maternal betamethasone on fetal lung ultrastructure in hyt/hyt (hypothyroid) and Balb-c (euthyroid) mice. Hypothyroid mice were made euthyroid by T3 supplementation and mated to carry hypothyroid pups. Vehicle (n = 6) or betamethasone (n = 6) was injected intraperitoneally twice daily into the doe on days 16 and 17 of gestation. Fetal lungs on 18 days of gestation were subjected to ultrastructural morphometric analysis. The number of lamellar bodies per type II cell increased after betamethasone in Balb-c (2.10+/-0.31 vs. 3.43+/-0.37) and hyt/hyt (0.77+/-0.28 vs. 3.85+/-0.26) mice. The alveolar-to-parenchymal ratio was less in the vehicle-treated hyt/hyt (0.082+/-0.024) as compared with the vehicle-treated Balb-c (0.30+/-0.05) mice, while prenatal betamethasone increased the alveolar-to-parenchymal ratio in the hyt/hyt (0.227+/-0.034) but not in the Balb-c (0.26+/-0.04) mice. The glycogen-to-nucleus ratio was higher in betamethasone-treated hyt/hyt mice (1.46+/-0.20) when compared to vehicle-treated hyt/hyt (0.89+/-0.14) or Balb-c (1.01+/-0.17) or betamethasone-treated Balb-c (0.81+/-0.13) mice. Though tubular myelin was readily apparent in the airspace lumen of betamethasone-treated Balb-c mice, it was absent in betamethasone-treated hyt/hyt fetal lungs. We conclude that fetal thyroid plays an important role in accelerating some aspects of fetal lung ultrastructural maturation from GC stimulation.

Animals↗

Type II fiber predominance with motor neuron dysfunction.

Several variations in the muscle fiber distribution and differentiation have been described. Different hypotheses, including maturational dysfunction of motor neurons have been postulated. We present a 28 year-old male with proximal weakness, and negative family history. Motor strength was 4-/5 proximally and 4+/5 distally in the extremities. He was areflexic with trace triceps jerks. Electrophysiological studies showed motor neuron dysfunction. Marked type II fiber predominance 97% was noted without group atrophy on a vastus-lateralis muscle biopsy. Type 2A were the largest with type 2B and 2C smaller than type 1. A deltoid muscle biopsy and electrophysiological studies performed nine years earlier depicted the same changes. With electrophysiological studies consistent with static motor neuron dysfunction and clinical and pathological presentation of myopathy, we propose a functional abnormality of motor neuron in-utero leading to abnormal muscle fiber differentiation and growth.

Adult↗