Biomedical subjects
Publications and source records attributed to V Chechani.
A 39-year-old man with AIDS presented with cough, chest pain, dyspnea on exertion, fever, and a cavitary lesion in the upper lobe of the left lung. The cavity increased in size over the next five months with disease involvement limited to the left upper lobe. Pneumocystis carinii infection was then diagnosed. Symptoms and cavity resolved with trimethoprim/sulfamethoxazole therapy.
Recent experimental evidence suggests that a combination of glucocorticoid and thyroid hormone may be more effective than either hormone alone in accelerating morphologic as well as biochemical mammalian fetal lung maturation. We have demonstrated that IM administration of T3 to the rabbit doe is associated with enhanced functional fetal lung maturation. We investigated the effect of simultaneous administration of T3 and betamethasone on the development of functional fetal lung maturation and the duration of survival after premature delivery. On day 25 and 26 of pregnancy, T3 (175 micrograms/kg/dose) betamethasone (85 micrograms/kg/dose), T3 plus betamethasone or the appropriate amount of the vehicles were injected. The functional fetal pulmonary maturity and the duration of survival after premature delivery were assessed on day 27 of gestation. Although enhanced functional fetal lung maturation was observed after T3 or betamethasone administration, there was no additive effect after simultaneous administration of both. The duration of survival on premature delivery was enhanced in betamethasone but not T3 or T3 plus betamethasone group when compared to control. Further animal experimentation seems necessary before a clinical trial of T3 plus betamethasone therapy is considered.
We have recently demonstrated that intramuscular administration of triiodothyronine (T3) or thyroxine (T4) to the rabbit doe results in its transfer across the placenta. In this study we investigated the effect of maternally administered T3 upon the functional and morphologic fetal lung maturation. T3 (175 micrograms/kg) or the vehicle was injected intramuscularly into the New Zealand White rabbit does on days 25 and 26 of gestation. On day 27 of pregnancy, the does were killed and the fetuses were delivered. Maternal and fetal plasma T3, glucose and insulin and fetal plasma corticosteroid concentrations were determined. The functional pulmonary maturity was assessed by performing the pressure-volume hysteresis while morphologic maturity was established by histologic techniques. Enhanced functional as well as morphologic fetal lung maturation was observed in female as well as male fetuses in T3-treated animals. However, there was a significant increase in the fetal mortality after T3 treatment, and the duration of survival in the extrauterine environment on premature delivery was not prolonged.
Although rabbit has been used as a convenient animal model in understanding the role of thyroid hormones during the perinatal development, ontogenetic changes in plasma-free thyroxine or triiodothyronine concentration has not been studied in this species. We delineated the ontogeny of immunoreactive plasma-free thyroxine and triiodothyronine concentration during the perinatal period. It is generally believed that thyroid hormones do not cross the placenta from the mother to the fetus in sufficient concentrations to exert biological effects in the fetus. We administered 250 micrograms/kg of thyroxine (T4) or 125 micrograms/kg of triiodothyronine (T3) intramuscularly to the rabbit doe on the 25th and 26th day of gestation. Maternal and fetal plasma-free T4, T3 and glucose concentration and fetal liver glycogen content were quantitated on the 27th day of gestation. Maternal and fetal plasma-free T4 and T3 concentration was significantly higher than the control in T4-treated animals. Maternal and fetal plasma T3 concentration was higher and free T4 concentration lower than the control in T3-treated animals. T3 or T4 treatment resulted in fetal hyperglycemia and depletion of fetal hepatic glycogen content. We conclude that T4 or T3 cross the rabbit placenta and exert thyromimetic effects in the fetus. A convenient animal model to investigate in utero effects of T4 or T3 in mammalian fetal development is proposed.
Although the role of thyroid hormones in enhancing lung and brain maturation during the perinatal period is well established, the cellular mechanisms involved in these processes are incompletely understood. Hypothyroidism retards the development of fetal pulmonary insulin, neonatal pulmonary beta-adrenergic and neonatal brain insulin receptors. In this study, we investigated the effect of hypo- or hyperthyroidism on the development of neonatal brain and lung epidermal growth factor (EGF) receptors. The rabbit pups were rendered hypothyroid by adding 0.05% propylthiouracil to the drinking water starting at 23 days of gestation and thereafter. The neonatal hyperthyroid state was achieved by intramuscular administration of 100 micrograms/kg of synthroid to the rabbit doe on the 29th and 30th day of pregnancy. Neonatal plasma free thyroxine (T4) concentrations were quantitated by a radioimmunoassay. Brain and lung plasma membranes were isolated by differential centrifugation. EGF receptor characteristics were studied using 125I-EGF binding assays and Scatchard analysis. The plasma free T4 concentrations were 0.36 +/- (SEM) 0.02 (n = 6), p less than 0.01 (n = 7) and 1.76 +/- 0.1 (n = 6) ng/dl in the control, hypothyroid and hyperthyroid pups, respectively. The percent specific binding of 125I-EGF to 200 micrograms of brain plasma membrane (BPM) protein was significantly lower in the hypothyroid (0.62 +/- 0.03, n = 7, p less than 0.01), and higher in the thyroxine-treated (1.58 +/- 0.08, n = 6, p less than 0.01) group when compared to control (1.08 +/- 0.06, n = 6) animals. However, the percent specific binding of 125I-EGF to 100 micrograms of lung plasma membrane (LPM) protein was similar in all three groups (2.24 +/- 0.28, control; 2.01 +/- 0.5, hypothyroid, and 2.26 +/- 0.3, hyperthyroid). The number of EGF receptors per milligram of BPM protein (X 10(-10] were lower in the hypothyroid (2.24 +/- 0.03, n = 5) and higher in the hyperthyroid (6.6 +/- 0.02, n = 4) group when compared to control (4.4 +/- 0.05, n = 4) with no apparent difference in Kd. There was no difference in the number of EGF binding sites per milligram of LPM protein (X 10(-10] within the groups (6.6 +/- 0.8, n = 6, control; 7.9 +/- 0.4, n = 4, hypothyroid, and 7.3 +/- 0.3, n = 4, hyperthyroid). Presence of high affinity receptors for EGF in the neonatal brain as well as lung supports the hypothesis that EGF may play an important role in neonatal brain and lung maturation.(ABSTRACT TRUNCATED AT 400 WORDS)