Biomedical subjects

R Harding

Publications and source records attributed to R Harding.

At least 19 recordsLinked to original sources

PubMed2001

Restriction of prenatal gas exchange impairs memory consolidation in the chick.

Our aim was to assess the effects of restricting gas exchange during incubation on postnatal memory formation and growth in the chick. Gas exchange across the eggshell was restricted by covering 50% of the eggshell with an impermeable membrane for 4 or 8 days, commencing at days 14 and 10, respectively, of a 21-day incubation. Memory formation was examined postnatally at 1-2 days using a one-trial discriminated bead task, and at 5-6 days using a discriminated wheat task. For both tasks, chicks from eggs wrapped from days 14 to 18 had impaired memory retention at 60 min after training, although learning and labile memory were not impaired. Chicks from eggs wrapped from days 10-18 appeared to be poorer in their ability to form memories, and did not discriminate as well as controls in any of the tasks. Body weights of chicks from wrapped eggs were reduced from 2 days after hatching; chicks from eggs wrapped from day 10 had lower body weights at hatching. We conclude that a period of altered prenatal gas exchange can impair memory consolidation in the chick soon after hatching. The ability to form memories may be permanently altered, as this impairment is still apparent at 5-6 days after hatching. Pre- and postnatal growth was also impaired in the chicks from wrapped eggs. Our results suggest that the extent to which postnatal neurological function and growth is impaired depends on the timing and possibly the duration of the prenatal insult.

Animals↗

PubMed2001

Hierarchical self-assembly of chiral rod-like molecules as a model for peptide beta -sheet tapes, ribbons, fibrils, and fibers.

A generic statistical mechanical model is presented for the self-assembly of chiral rod-like units, such as beta-sheet-forming peptides, into helical tapes, which with increasing concentration associate into twisted ribbons (double tapes), fibrils (twisted stacks of ribbons), and fibers (entwined fibrils). The finite fibril width and helicity is shown to stem from a competition between the free energy gain from attraction between ribbons and the penalty because of elastic distortion of the intrinsically twisted ribbons on incorporation into a growing fibril. Fibers are stabilized similarly. The behavior of two rationally designed 11-aa residue peptides, P(11)-I and P(11)-II, is illustrative of the proposed scheme. P(11)-I and P(11)-II are designed to adopt the beta-strand conformation and to self-assemble in one dimension to form antiparallel beta-sheet tapes, ribbons, fibrils, and fibers in well-defined solution conditions. The energetic parameters governing self-assembly have been estimated from the experimental data using the model. The 8-nm-wide fibrils consist of eight tapes, are extremely robust (scission energy approximately 200 k(B)T), and sufficiently rigid (persistence length l(fibril) approximately 20-70 microm) to form nematic solutions at peptide concentration c approximately 0.9 mM (volume fraction approximately 0.0009 vol/vol), which convert to self-supporting nematic gels at c > 4 mM. More generally, these observations provide a new insight into the generic self-assembling properties of beta-sheet-forming peptides and shed new light on the factors governing the structures and stability of pathological amyloid fibrils in vivo. The model also provides a prescription of routes to novel macromolecules based on a variety of self-assembling chiral units, and protocols for extraction of the associated energy changes.

Models, Molecular↗

PubMed2001

An evaluation of a thicker versus a standard condom with gay men.

OBJECTIVES: Although thicker (stronger) condoms are advocated in western Europe for anal intercourse between men, empirical evidence supporting their greater efficacy is lacking. The present study aimed to determine whether a thicker condom is less likely to fail (break or slip off) than a standard (regular thickness) condom, and to establish factors associated with condom failure among gay men. DESIGN: A total of 283 homosexual couples participated in a double-blind, randomized, controlled trial of a standard and a thicker condom. METHODS: Each couple was allocated nine of either condom type. Data were collected on user characteristics, and a questionnaire completed immediately after the use of each condom. The thicker and the standard condoms were used by 142 and 141 couples, respectively. RESULTS: No significant differences were found between the two condom types with respect to either clinical or non-clinical definitions of failure (breakage and slippage). With instances of inappropriate use removed, failure rates for the standard and the thicker condom were low at 2.5 and 2.3%, respectively. User characteristics associated with breakage were lower educational achievement, lack of confidence in condom use, and a history of condom breakage. Behaviours associated with breakage were unrolling the condom before fitting to the penis, longer penis length, absence of additional lubricant, the use of inappropriate lubricant, and longer duration of intercourse. CONCLUSION: Breakage and slippage rates were low for both condom types. There is no evidence from the present investigation to support the use of stronger (thicker) condoms over standard strength condoms among gay men. The appropriate use of additional lubricant should be encouraged.

Adult↗

PubMed2001

Effects of fetal growth restriction on lung development before and after birth: a morphometric analysis.

Our aim was to determine the effects of fetal growth restriction (FGR) during late gestation on the structure of the lungs in the fetus near term and at 8 weeks after birth. The studies were performed using two groups of pregnant sheep and their offspring. In both groups, FGR was induced by umbilico-placental embolisation (UPE); for fetal studies, UPE was performed from 120 days of gestation until 140 days (term, approximately 146 days), when fetuses were killed for tissue analysis. For postnatal studies, UPE continued from 120 days until delivery at term; postnatal lambs were killed at 8 weeks after birth for tissue analysis. UPE led to a thicker pulmonary blood-air barrier at 140 days of gestation and this difference, which was due to a thickened basement membrane, was still present at 8 weeks after birth. At 8 weeks, we also observed a smaller number of alveoli per respiratory unit, thicker interalveolar septa, and a greater volume density of lung tissue in FGR lambs compared to controls. These changes would be expected to impair gas exchange and alter the mechanical properties of the lungs. Our data show that structural alterations in the lungs induced by placental insufficiency were more evident at 8 weeks of postnatal age than near term, indicating that the effects of FGR on the lung may become more serious with age and may affect respiratory health later in life.

Animals↗

PubMed2001

Stimulation of lung growth in fetuses with lung hypoplasia leads to altered postnatal lung structure in sheep.

Increased lung expansion in the fetus stimulates lung growth and is being trialed clinically to reverse severe fetal lung hypoplasia. Our aim was to examine the effects of increased fetal lung expansion in the presence of lung hypoplasia on lung structure in sheep at term and 8 weeks after birth. Lung hypoplasia was induced in 15 fetal sheep by continuous drainage of tracheal fluid, commencing at approximately 113 days of gestation (term, approximately 148 days). In 10 of these fetuses, tracheal obstruction (TO) was performed from 137-147 days of gestation (treated lung hypoplasia, TLH), while lung liquid drainage continued until term in the remaining 5 fetuses (untreated lung hypoplasia, ULH). Lung tissues were obtained from 5 TLH, 5 ULH, and 5 control lambs at birth, and from 5 TLH and 5 control lambs at 8 weeks after birth. At birth, alveolar number, surface area, and interalveolar wall thickness were not different between TLH and control lambs, whereas airspace diameter was greater in TLH lambs (72.7 +/- 3.0 microm) than in controls (58.4 +/- 4.3 microm). Diameters of airspaces were not different between ULH and control lambs; however, alveolar numbers and surface area were reduced, while interalveolar wall thickness was increased in ULH lambs compared to controls. At 8 weeks after birth, alveolar number (928.0 +/- 66.1 x 10(6)) and surface area (30.3 +/- 2.2 m(2)) in TLH lambs were lower, whereas interalveolar wall thickness (83.0 +/- 3.1 microm) was greater than in control lambs (2,263.6 +/- 261.6 x 10(6), 46.7 +/- 4.8 m(2), and 68.6 +/- 2.1 microm, respectively). Our data show that TO restores most aspects of lung structure to normal in fetuses with lung hypoplasia but leads to altered alveolar development. The presence of fewer, larger alveoli in postnatal TLH animals may predispose these animals to respiratory complications during later life.

Analysis of Variance↗

PubMed2001

Working with ambivalence: informal caregivers of patients at the end of life.

Informal caregivers of patients at the end of life perform a crucial role in maintaining and supporting patients at home. They provide a high level of demanding care, and as a consequence have been shown to have high-level information and support needs themselves. However, they are less often identified as recipients of services than as providers, and little research has addressed how services should be developed to meet their needs. This study aimed to address obstacles in the access to and provision of targeted, appropriate interventions. Eighteen informal carers participated in this qualitative study, which used a grounded approach to the analysis and generation of concepts. The data showed that while recognising their stress, anxiety and need for a caregivers' service, caregivers were highly ambivalent with regard to their own needs. The design and delivery of an intervention aimed at caregivers should take account of their high level of ambivalence by addressing their lack of identification with their role, enhancing existing coping strategies, and ensuring that interventions are accessible and acceptable.

Adaptation, Psychological↗

PubMed2001

Ventilatory and arousal responses to respiratory stimuli of full term, intrauterine growth restricted lambs.

We aimed to determine the effect of intrauterine growth restriction (IUGR) on the control of breathing and arousal in sleeping postnatal animals. We measured ventilatory and arousal responses to respiratory challenges during sleep in normally grown (birthweight 5.17+/-0.48 kg) and IUGR (2.64+/-0.19 kg) full term lambs. During wakefulness, IUGR lambs had significantly lower arterial pH and higher Pa(CO(2)) levels. During quiet sleep, but not active sleep, end tidal CO(2) was elevated in IUGR lambs (P=0.08). During active and quiet sleep, minute ventilation (per kg body weight) was significantly higher in IUGR lambs than controls. Ventilatory responses to hypercapnia and/or hypoxia were not different between control and IUGR lambs during active and quiet sleep but end tidal CO(2) at arousal was consistently higher in IUGR lambs; other indices of arousal were not affected by IUGR. Our findings suggest IUGR lambs require an elevated level of ventilation to maintain respiratory homeostasis and that alterations in lung function are likely consequences of IUGR.

Animals↗

PubMed2001

Postnatal outcomes in term and preterm lambs following fetal growth restriction.

1. Epidemiological evidence indicates that low birthweight increases the risk of a number of adult-onset diseases. It is now apparent that many babies with a low birthweight may have been subjected to a combination of reduced growth rates in utero as well as preterm birth. However, the long-term effects of preterm birth following intra-uterine growth restriction (IUGR) are unknown. Thus, our objectives were: (i) to identify prenatal factors associated with preterm birth in IUGR fetuses; and (ii) to characterize postnatal effects of preterm birth following IUGR. 2. We studied pregnant sheep and their offspring, in which fetal growth was restricted by umbilico-placental embolization during late gestation. Some of these animals were born at term (146 +/- 1 days) and some were born prematurely (139 +/- 1 days). In both groups, we have conducted longitudinal studies of postnatal respiratory function, cardiovascular function and learning ability up to 6-8 weeks of age. 3. Before birth, IUGR fetuses born prematurely (P-IUGR) were more hypoxaemic and acidaemic and had higher haemoglobin concentrations than both control fetuses and IUGR fetuses born at term (T-IUGR). In P-IUGR fetuses, plasma cortisol concentrations increased earlier than in the two other groups. The P-IUGR lambs had lower birthweights than T-IUGR lambs and both groups of IUGR lambs remained lighter than controls for 8 weeks. 4. After birth, P-IUGR lambs were hypoxaemic compared with T-IUGR and control lambs. Pulmonary diffusing capacity (adjusted for lung volume) was significantly lower in both groups of IUGR lambs than in controls, with P-IUGR lambs having lower values than T-IUGR lambs. Lung compliance (adjusted for lung volume), was not different between P-IUGR and control lambs, but values were higher in T-IUGR lambs than in control and P-IUGR lambs. Chest wall compliance (adjusted for lung volume) was higher in both groups of IUGR lambs than in controls. 5. During the 8 week postnatal study period, both groups of IUGR lambs had lower mean arterial pressures than control lambs; this relative hypotension was greatest in P-IUGR lambs. 6. In tests of learning ability, P-IUGR lambs took longer to complete a simple maze task at all ages and, in the second postnatal week, made a greater number of errors compared with controls. In an obstacle course, P-IUGR lambs recorded longer trial durations; they also made more errors than control lambs. 7. We conclude that preterm birth in the presence of late- gestational placental insufficiency and IUGR can result in specific effects on respiratory and cardiovascular development after birth, in addition to the effects of IUGR alone.

Animals↗

PubMed2001

Effects of intrauterine growth restriction on lung liquid dynamics and lung development in fetal sheep.

OBJECTIVE: The aim of this study was to determine the effects of intrauterine growth restriction on fetal lung liquid and lung development. STUDY DESIGN: Intrauterine growth restriction was induced in 7 fetal sheep from 120 to 140 days' gestation (term, approximately 147 days' gestation) by umbilicoplacental embolization. We used 6 control fetuses. Volumes and production rates of fetal lung liquid were measured, and lungs were removed post mortem (140 days' gestation) for analysis of concentrations of deoxyribonucleic acid, protein, and messenger ribonucleic acid for surfactant proteins A, B, and C. RESULTS: Umbilicoplacental embolization induced fetal hypoxemia, hypoglycemia, and intrauterine growth restriction. At 140 days' gestation lung weight was reduced by 34%, and the fetal lung liquid production rate (15.9 +/- 1.8 mL/h for intrauterine growth restriction vs 24.8 +/- 3.9 mL/h for control) and volume (110.9 +/- 16.3 mL for intrauterine growth restriction vs 178.1 +/- 11.9 mL for control) were reduced in the intrauterine growth restriction group. After adjustment for body weight, however, values were not different from those in the control group. Pulmonary deoxyribonucleic acid and plasma cortisol concentrations were elevated by intrauterine growth restriction, but levels of messenger ribonucleic acid for surfactant proteins were unchanged. CONCLUSION: In intrauterine growth restriction, lung liquid and lung growth were proportionate to body weight, and surfactant protein expression was unaffected. Alterations in lung deoxyribonucleic acid concentrations suggest that the lungs may be structurally immature.

Animals↗

PubMed2001

Motivational interviewing for HIV risk reduction among gay men in commercial and public sex settings.

The present paper addresses the feasibility of combining motivational interviewing and cognitive interventions to HIV risk reduction in commercial venues and public sex environments (PSEs). The logic for these two approaches is considered and an intervention combining key elements of the two is presented. The intervention uses a questionnaire format to encourage individuals to compare their desired versus actual behaviour (i.e. chosen personal risk reduction strategy versus 'slip-ups'/unwanted risk taking), and to recognize their risk-related cognitions. High-risk individuals are identified, and health-focused conversations developed from the brief schedule. The structure and key design issues in the development of a feasible, acceptable and evidence-based tool are reviewed. The limitations of more complex, focused interventions in the context of commercial and PSE settings are discussed.

Cognitive Behavioral Therapy↗

PubMed2001

Programming effects in sheep of prenatal growth restriction and glucocorticoid exposure.

Our aim was to determine the postnatal effects of single and repeated glucocorticoid injections during late gestation. Repeated (104, 111, 118, 125 days) or single (104 days) injections of betamethasone or saline were given to the ewe or by ultrasound guided injection to the fetus (term 150 days). Lambs were born spontaneously and studied at 3 and 6 mo and 1 yr of age. Arterial pressure was measured at each age, and we performed intravenous glucose tolerance tests at 6 mo and 1 yr. Repeated maternal, but not single maternal or fetal, betamethasone injections prolonged gestation, reduced weight at birth and 3 mo, and was associated with low arterial pressure at 3 mo but not at 6 mo and 1 yr. Glucose metabolism was altered in all betamethasone treatment groups, regardless of the number or route of injections. Our data demonstrate that glucocorticoid-induced fetal growth restriction is associated with a transient reduction in postnatal arterial pressure, but glucocorticoid exposure with or without growth restriction alters glucose metabolism.

Aging↗

PubMed2001

Compromised respiratory function in postnatal lambs after placental insufficiency and intrauterine growth restriction.

Epidemiologic studies have shown persistent effects of low birth weight on respiratory function and lung health, but underlying mechanisms are not understood. Our aim was to determine the effects of intrauterine growth restriction (IUGR), a major cause of low birth weight, on postnatal respiratory function. IUGR was induced by umbilico-placental embolization during late gestation in chronically catheterized sheep. Umbilico-placental embolization was performed between 120 d of gestation and term ( approximately 146 d) during which fetuses were hypoxemic and hypoglycemic relative to controls. Umbilico-placental embolization led to a 48% reduction in birth weight compared with controls, and throughout the postnatal study period IUGR lambs (n = 8) remained lighter than controls (n = 8). Respiratory function was repeatedly studied in lambs for 8 wk after birth; during this period, IUGR lambs were mildly hypoxemic and tended to be hypercapnic compared with controls. In IUGR lambs, relative to controls, O(2) consumption (mL/min/kg) and minute ventilation (mL/kg) were increased and pulmonary diffusing capacity (adjusted for functional residual capacity) was decreased. Functional residual capacity, measured by helium dilution, and total lung capacity (measured at 30 cm H(2)O) were smaller in IUGR lambs than in controls. When adjusted for functional residual capacity, static lung compliance was reduced and chest wall compliance was increased in IUGR lambs. At 8 wk, pulmonary DNA and protein concentrations were decreased in IUGR lambs relative to controls. We conclude that restriction of fetal growth by placental insufficiency induces alterations in the lungs and chest wall that result in persistent impairments in respiratory function during early postnatal life.

Animals↗

PubMed2001

Effect of increased lung expansion on surfactant protein mRNA levels in lambs.

Increased fetal lung expansion profoundly inhibits surfactant protein gene expression and stimulates cellular proliferation in the fetal lung. Our aim was to determine whether increased expansion of the lung after birth, by the application of a continuous positive airway pressure (CPAP) for 12 h, inhibits surfactant protein gene expression and stimulates cell division in lambs. Two week-old lambs were randomly divided into 2 groups (n = 5 for each), sedated, and exposed to either no CPAP (controls) or 10 cm H(2)O of CPAP during a 12-hour treatment period. After 2 h of the treatment, (3)H-thymidine was administered to each lamb (iv) to measure pulmonary DNA synthesis rates over the following 10 h of treatment. To assess the increase in lung expansion, functional residual capacity (FRC) was measured before the start of the treatment period and again at 6 and 12 h. Compared with control lambs, a CPAP of 10 cm H(2)O increased FRC from 26.8 +/- 3.8 mL/kg to 62.9 +/- 19.7 mL/kg at 6 h and it remained elevated at 12 h (56.2 +/- 5.7 mL/kg). Despite this large increase in end expiratory lung volume (FRC), the mRNA levels for SP-A, SP-B, and SP-C and DNA synthesis rates in lung tissue were not altered. The results of this study indicate that, in contrast to the fetus, an increase in end expiratory lung volume of approximately 100% does not affect surfactant protein gene expression or pulmonary DNA synthesis rates in 2 week old lambs. Thus, the response of the lung to increases in lung expansion varies markedly before and after birth.

Animals↗

PubMed2000

The compromised intra-uterine environment: implications for future lung health.

1. Epidemiological studies of infants, children and adults indicate that prenatal compromises that restrict fetal growth and cause low birthweight increase the risk of respiratory deficiencies after birth. 2. It is apparent that the lung has a limited ability to recover from early developmental compromises and that altered development can permanently impair lung architecture. 3. Lung development in utero can be adversely affected by factors associated with fetal growth restriction, namely fetal hypoxaemia, reduced substrate supply and hypercortisolaemia. 4. We have conducted a series of studies of respiratory development in chronically catheterized ovine fetuses and postnatal lambs in which growth restriction was induced during late gestation by embolizing the umbilico-placental vascular bed, a technique that replicates key aspects of human placental insufficiency. 5. During late gestation, restricting the growth of the ovine fetus did not alter lung weight or lung liquid secretion or volume when each factor was related to bodyweight, but it did lead to increased lung DNA concentrations and an increased thickness of the air-blood barrier. Expression of pulmonary surfactant proteins A, B and C were not altered and, hence, it was unlikely that surfactant protein synthesis had been impaired by growth restriction. 6. When growth restriction continued to term, lambs were born with a low birthweight and remained small compared with controls for 8 weeks after birth. Low-birthweight lambs were mildy hypoxaemic and compliances of their lungs and chest wall were, respectively, decreased and increased relative to controls. Pulmonary surfactant proteins A, B and C were not deficient, indicating that decreased lung compliance most likely had a structural basis.

Animals↗

PubMed2000

Relation between damage to the placenta and the fetal brain after late-gestation placental embolization and fetal growth restriction in sheep.

OBJECTIVE: Our aim was to determine the effects of 30 days of placental insufficiency on fetal brain development and to relate placental damage to the degree of fetal brain injury. STUDY DESIGN: Umbilicoplacental embolization was induced from 110 to 140 days of gestation (term, 147 days) in 7 fetal sheep, such that fetal arterial oxygen saturation was maintained at 50% of pre-umbilicoplacental embolization values. Six control fetuses were used. At 140 days the fetal brains and placentas were subjected to structural and histochemical analysis. RESULTS: During umbilicoplacental embolization, fetal arterial oxygen saturation, PaO(2), and pH were reduced (P <.05). Thirty days of umbilicoplacental embolization caused a decrease in cross-sectional area of the placentome (P <.05), with 20% of tissue showing damage. All umbilicoplacental embolization fetuses were growth restricted and had brain damage, most prominently in the cerebral white matter. There was no relation between the extent of placental damage and the severity of fetal brain damage. CONCLUSIONS: The absence of a correlation between damage to the placenta and fetal brain is likely to be caused by variations between individuals in (1) the amount of placenta that is required to be functionally damaged to achieve the prescribed level of hypoxemia and (2) the response of the fetal brain to that level of hypoxemia.

Animals↗

PubMed2000

Changes in lung structure and cellular division induced by tracheal obstruction in fetal sheep.

Increased expansion of the fetal lung, caused by obstruction of the fetal trachea, is a potent stimulus for growth and structural development of the fetal lung. Our aim was to analyze the changes in lung structure induced by fetal tracheal obstruction and to identify cell types that contribute to the growth response. Fetal sheep were exposed to 2, 4, or 10 days of tracheal obstruction (TO) and on day 128 of gestation (term "147 d"), were injected with 3H-thymidine 8 hours before tissues were collected. The right lung was fixed at 20 cm H2O and prepared for stereological and autoradiographic analysis. Alveolar wall thickness (7.8 +/- 0.3 microns vs 5.5 +/- 0.4 microns) and percent tissue space (27.9 +/- 0.9% vs 21.4 +/- 2.8%) were increased at 2 days of TO, but were not different from control at 4 and 10 days. The luminal surface area of the right lung increased gradually from 2.4 +/- 0.2 m2/kg in control fetuses to 3.6 +/- 0.4 m2/kg following 10 days of TO and this increase was accompanied by an increase in alveolar number (control: 808 x 10(6) +/- 81.9 x 10(6) vs 10d obstruct: 1254 x 10(6) +/- 63 x 10(6). Alveolar diameter increased at 2 days of TO (51.8 +/- 1.4 microns vs 43.8 +/- 1.9 microns), but was not increased further at 4 or 10 days. The percentage of dividing cells was increased at 2 days of TO (12.64 +/- 3.39% vs 1.73 +/- 0.31%), remained elevated at 4 days (5.01 +/- 0.27%), but had returned to control by day 10. The increase at 2 days was due to division of type II epithelial cells, fibroblasts, and endothelial cells. We conclude that increased expansion of the fetal lung induces time-dependent changes in lung structure and cell division rates; these include a transient increase in alveolar wall thickness, a rapid increase in alveolar number, and a gradual increase in luminal surface area. The latter is probably caused by an increase in alveolar number rather than an increase in the alveolar size.

Animals↗

PubMed2000

Increased lung expansion alters the proportions of type I and type II alveolar epithelial cells in fetal sheep.

Type I and type II alveolar epithelial cells (AECs) are derived from the same progenitor cell, but little is known about the factors that regulate their differentiation into separate phenotypes. An alteration in lung expansion alters the proportion type II AECs in the fetal lung, indicating that this may be a regulatory factor. Our aim was to quantify the changes in the proportion of type I and type II AECs caused by increased fetal lung expansion and to provide evidence for transdifferentiation of type II into type I cells. Lung tissue samples were collected from ovine fetuses exposed to increased lung expansion induced by 2, 4, or 10 days of tracheal obstruction (TO). The identities and proportions of AEC types were determined with electron microscopy. The proportion of type II cells was reduced from 28.5 +/- 2.2% in control fetuses to 9.4 +/- 2.3% at 2 days of TO and then to 1.9 +/- 0.8% at 10 days. The proportion of type I AECs was not altered at 2 days of TO (63.1 +/- 2.3%) compared with that of control cells (64.8 +/- 0.5%) but was markedly elevated (to 89.4 +/- 0.9%) at 10 days of TO. The proportion of an intermediate AEC type, which displayed characteristics of both type I and type II cells, increased from 5.7 +/- 1.3% in control fetuses to 23.8 +/- 5.1% by 2 days of TO and was similar to control values at 10 days of TO (7.7 +/- 0.9%). Our data show that increases in fetal lung expansion cause time-dependent changes in the proportion of AEC types, including a transient increase in an intermediate cell type. These data provide the first evidence to support the hypothesis that increases in fetal lung expansion induce differentiation of type II into type I AECs via an intermediate cell type.

Animals↗

PubMed2000

Ventilatory and arousal responses of sleeping lambs to respiratory challenges: effect of prenatal maternal anemia.

We have examined the effects of exposure to chronic maternal anemia, throughout the final one-third of gestation, on postnatal ventilatory and arousal responses to hypoxia, hypercapnia, and combined hypoxia-hypercapnia in sleeping lambs. While resting quietly awake, lambs from anemic ewes had higher arterial PCO(2) levels than control animals during the first 2-3 postnatal wk, but pH, arterial PO(2), and arterial O(2) saturation were not different. During active and quiet sleep lambs from anemic ewes had higher end-tidal CO(2) levels than control animals when breathing room air and at the time of spontaneous arousal or when aroused by progressive hypercapnia or by combined hypoxia-hypercapnia. Ventilation and arterial O(2) saturation during uninterrupted sleep and ventilatory responsiveness to hypoxia (inspiratory O(2) fraction, 10%), progressive hypercapnia, and combined hypoxia/hypercapnia were not significantly affected by exposure to maternal anemia. Our findings show that maternal anemia results in elevated PCO(2) levels in the offspring. This effect may be due, at least in part, to altered pulmonary function.

Anemia↗