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Pancreas deficiency modifies bone development in the ovine fetus near term.
Full text linkHormones have an important role in the regulation of fetal growth and development, especially in response to nutrient availability in utero. Using micro-CT and an electromagnetic three-point bend test, this study examined the effect of pancreas removal at 0.8 fraction of gestation on the developing bone structure and mechanical strength in fetal sheep. When fetuses were studied at 10 and 25 days after surgery, pancreatectomy caused hypoinsulinaemia, hyperglycaemia and growth retardation which was associated with low plasma concentrations of leptin and a marker of osteoclast activity and collagen degradation. In pancreatectomized fetuses compared to control fetuses, limb lengths were shorter, and trabecular (Tb) bone in the metatarsi showed greater bone volume fraction, Tb thickness, degree of anisotropy and porosity, and lower fractional bone surface area and Tb spacing. Mechanical strength testing showed that pancreas deficiency was associated with increased stiffness and a greater maximal weight load at fracture in a subset of fetuses studied near term. Overall, pancreas deficiency in utero slowed the growth of the fetal skeleton and adapted the developing bone to generate a more compact and connected structure. Maintenance of bone strength in growth-retarded limbs is especially important in a precocial species in preparation for skeletal loading and locomotion at birth
Developmental regulation of hepatic and renal gluconeogenic enzymes by thyroid hormones in fetal sheep during late gestation
No full textTissue glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) activities were investigated in sheep fetuses after experimental manipulation of thyroid hormone status. Increments in hepatic and renal G6P and PEPCK activities seen between 127-130 and 140-145 days of gestation (term, 145 ± 2 days) were abolished when the normal prepartum rise in plasma triiodothyronine (T3), but not cortisol, was prevented by fetal thyroidectomy (TX). At 127-130 days, hepatic and renal G6P, and renal PEPCK, activities were similar in intact and TX fetuses; however, hepatic PEPCK was increased by TX. At 140-145 days, tissue G6P and PEPCK activities in TX fetuses were lower than in intact fetuses. In immature fetuses infused with cortisol (2-3 mg (kg body wt)-1 day-1) for five days, hepatic and renal enzyme activities were increased to those seen in mature fetuses near term. After five days of T3 infusion (8-12 µg (kg body wt)-1 day-1), G6P and PEPCK activities in the liver and kidney were greater than in saline-infused fetuses, but only renal G6P and PEPCK increased to the level seen close to term. Therefore, in fetal sheep, thyroid hormones are important for the prepartum rises in G6P and PEPCK activities in the liver and kidney and may mediate, in part, the maturational effects of cortisol
Ontogeny of pulmonary and renal angiotensin-converting enzyme in pigs
No full textThe present study investigated the ontogeny of pulmonary and renal angiotensin-converting enzyme (ACE) in foetal and postnatal pigs, and examined the effect of cortisol on tissue ACE in utero. Data were compared with those in sheep at similar ages. Under anaesthesia, tissues and umbilical blood were collected from pig foetuses between 81–115 days of gestation (term, 115±2 days). Twelve foetuses delivered at 97±2 days were infused with saline or cortisol (3–6 mg kg?1 day?1) using osmotic mini-pumps implanted 6 days previously. Tissues were collected from newborn piglets, and from pigs at 2–4 weeks, 10–12 weeks and 10–12 months of age. Unlike in sheep, gestational age and exogenous cortisol had no effect on pulmonary or renal ACE in pigs. After birth, pulmonary ACE decreased to a nadir at 2–4 weeks and remained low thereafter. Renal ACE increased between 10–12 weeks and 10–12 months. Postnatal changes in tissue ACE may have consequences for cardiovascular, pulmonary and renal function in pigs
Developmental control of plasma leptin and adipose leptin messenger ribonucleic acid in the ovine fetus during late gestation: role of glucocorticoids and thyroid hormones
No full textIn developed countries, the increasing incidence of obesity is a serious health problem. Leptin exposure in the perinatal period affects long-term regulation of appetite and energy expenditure, but control of leptin production in utero is unclear. This study investigated perirenal adipose tissue (PAT) and placental leptin expression in ovine fetuses during late gestation and after manipulation of plasma glucocorticoid and thyroid hormone concentrations. Between 130 and 144 d of gestation (term at 145 ± 2 d), plasma leptin and PAT leptin mRNA levels increased in association with increments in plasma cortisol and T3. Fetal adrenalectomy prevented these developmental changes, and exposure of intact 130 d fetuses to glucocorticoids, by cortisol infusion or maternal dexamethasone treatment, caused premature elevations in plasma leptin and PAT leptin gene expression. Fetal thyroidectomy increased plasma leptin and PAT leptin mRNA abundance, whereas intravenous T3 infusion to intact 130 d fetuses had no effect on circulating or PAT leptin. Leptin mRNA expression was low in the ovine placenta. Therefore, in the sheep fetus, PAT appears to be a primary source of leptin in the circulation, and leptin gene expression is regulated by both glucocorticoids and thyroid hormones. Developmental changes in circulating and PAT leptin may mediate the maturational effects of cortisol in utero and have long-term consequences for appetite regulation and the development of obesity
Effects of hypothyroidism on the structure and mechanical properties of bone in the ovine fetus
No full textThyroid hormones are important for normal bone growth and development in postnatal life. Little is known, however, about the role of thyroid hormones in the control of bone development in the fetus. Using computed-tomography and mechanical testing, the structure and strength of metatarsal bones were measured in sheep fetuses in which thyroid hormone levels were altered by thyroidectomy or adrenalectomy. In intact fetuses, plasma concentrations of total calcium and the degradation products of C-terminal telopeptides of Type I collagen increased between 100 and 144 days of gestation (term 145 ± 2 days), in association with various indices of bone growth and development. Thyroid hormone deficiency induced by thyroidectomy at 105-110 days of gestation caused growth retardation of the fetus and significant changes in metatarsal bone structure and strength when analysed at both 130 and 144 days of gestation. In hypothyroid fetuses, trabecular bone was stronger with thicker, more closely spaced trabeculae despite lower bone mineral density. Plasma osteocalcin was reduced by fetal thyroidectomy. Removal of the fetal adrenal gland at 115-120 days of gestation, and prevention of the prepartum rises in cortisol and triiodothyronine, had no effect on bodyweight, limb lengths, metatarsal bone structure or strength, or circulating markers of bone metabolism, in the fetuses studied near term. This study demonstrates that hypothyroidism in utero has significant effects on the structure and strength of bone, with different consequences for cortical and trabecular bone<br/
Sex- and bone-specific responses in bone structure to exogenous leptin and leptin receptor antagonism in the ovine fetus.
Full text linkWidespread expression of leptin and its receptor in developing cartilage and bone suggests that leptin may regulate bone growth and development in the fetus. Using microcomputed tomography, this study investigated the effects of exogenous leptin and leptin receptor antagonism on aspects of bone structure in the sheep fetus during late gestation. From 125 to 130 days of gestation (term ~145 days), chronically catheterized singleton sheep fetuses were infused intravenously for 5 days with either saline (0.9% saline, n = 13), recombinant ovine leptin at two doses (0.6 mg·kg-1·day-1 LEP1, n = 10 or 1.4 mg·kg-1·day-1 LEP2, n = 7), or recombinant superactive ovine leptin receptor antagonist (4.6 mg·kg-1·day-1 SOLA, n = 6). No significant differences in plasma insulin-like growth factor-I, osteocalcin, calcium, inorganic phosphate, or alkaline phosphatase were observed between treatment groups. Total femur midshaft diameter and metatarsal lumen diameter were narrower in male fetuses treated with exogenous leptin. In a fixed length of femur midshaft, total and bone volumes were reduced by the higher dose of leptin; nonbone space volume was lower in both groups of leptin-treated fetuses. Leptin infusion caused increments in femur porosity and connectivity density, and vertebral trabecular thickness. Leptin receptor antagonism decreased trabecular spacing and increased trabecular number, degree of anisotrophy, and connectivity density in the lumbar vertebrae. The increase in vertebral porosity observed following leptin receptor antagonism was greater in the malecompared with female, fetuses. Therefore, leptin may have a role in the growth and development of the fetal skeleton, dependent on the concentration of leptin, sex of the fetus, and bone type examined
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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