The streptozotocin-induced diabetic (STZ-DB) rat model is associated with fetal hyperglycemia, but with low to normal plasma insulin concentration. Because surfactant protein (SP) mRNA content in fetal rat lung is decreased in STZ-DB pregnancy, we investigated the effect of increasing concentrations of glucose on SP gene expression in lung organ cultures. SP mRNA content (SP-A, SP-B, SP-C) was assessed by Northern blot analysis in fetal day 20 lung explants (term = 22 days) cultured for 44 hours in medium containing 10, 25, 50, or 100 mM glucose. Our findings were (1) No consistent alteration in SP-A mRNA content was observed at different glucose concentrations (P > .05); (2) SP-B and SP-C mRNA content were reduced in a dose-dependent manner when glucose concentration was increased from 10 mM to 100 mM. The mRNA content, compared to 10 mM glucose, decreased to 50-60% at 25 mM glucose, to 20-25% at 50 mM glucose, and to lower than 10% at 100 mM glucose (P < .01). These findings indicate that the decrease in SP-B and SP-C mRNA in fetuses of STZ-DB rats may be, in part, due to a direct effect of hyperglycemia, whereas the decrease in SP-A mRNA content in STZ-DB rats appears to be due to other effects of diabetes in pregnancy.

Because surfactant protein (SP) mRNA levels in rat fetuses are increased by maternal dexamethasone (dex) treatment and decreased in streptozotocin-induced diabetic (STZ-DB) pregnancy, we investigated the in vivo effects of dex on SP gene expression in STZ-DB pregnancy. 2) a 2-3-fold increase in SP-C mRNA levels was observed in response to dex in d 18 and 20 fetuses; 3) the increase in transcription of SP-A and SP-B in d 20 fetuses after dex is 68 and 60%, respectively, of the increase in their mRNA levels whereas in STZ-DB, the decrease in transcription compared with mRNA levels is 3.67-fold for SP-A and 2.42 fold SP-B; and 4) changes in SP-C transcription in either in vivo model, dex-treated or STZ-DB, correspond well with changes in mRNA levels. Together, these findings indicate that dex can enhance SP expression in STZ-DB immature lungs and support differential regulation of fetal SP genes in the models studied. (Pediatr Res 38: 870-877, 1995)

It would be convenient to be able to measure airway responsiveness to bronchodilator drugs with a sequential use of oscilloresistometry and spirometry, which may allow the comparison of the response to bronchodilator at two different states of respiratory mechanics i.e. resting tidal breathing at functional residual capacity (FRC) versus forced expiratory manoeuvre from total lung capacity to residual volume. The evaluation of airway resistance and forced expiratory volume at 1 s (FEV₁) may thus assist in the interpretation of bronchial responsiveness tests (BRT) to pick up responders among non-responders to administered bronchodilator. Such a concept was verified in 54 patients with respiratory disease before and 10 min after inhalation of 200 μg of salbutamol. Within 10 min following salbutamol challenge the increase for forced vital capacity (FVC), FEV₁ and peak expiratory flow rate (PEFR) was 23, 27 and 39% in 27 asthmatic patients of group A (p < 0.005). On the other hand, 27 patients with chronic obstructive pulmonary disease in group B did not show any significant change in FEV₁ and PEFR (p > 0.05). However, they showed a decrease in airway resistance of 30% (p < 0.005) during normal tidal breathing at FRC. Twenty-two normal controls in group C showed values of airway resistance and expiratory flow rates to be within the normal range and the response to administered salbutamol inhalation was not significant (p > 0.05). It may be concluded that the airway responsiveness to bronchodilators using only FEV₁ as an index of BRT should be interpreted with caution in non-responders because they may not be able to tolerate the mechanical challenge in the form of an FCV manoeuvre but show a significant decrease in airway resistance during resting tidal breathing at FRC.