Biomedical subjects

K M Dziegielewska

Publications and source records attributed to K M Dziegielewska.

At least 19 recordsLinked to original sources

PubMed2006

Blood-CSF barrier function in the rat embryo.

Blood-cerebrospinal fluid (CSF) barrier function and expansion of the ventricular system were investigated in embryonic rats (E12-18). Permeability markers (sucrose and inulin) were injected intraperitoneally and concentrations measured in plasma and CSF at two sites (lateral and 4th ventricles) after 1 h. Total protein concentrations were also measured. CSF/plasma concentration ratios for endogenous protein were stable at approximately 20% at E14-18 and subsequently declined. In contrast, ratios for sucrose (100%) and inulin (40%) were highest at the earliest ages studied (E13-14) and then decreased substantially. Between E13 and E16 the volume of the lateral ventricles increased over three-fold. Decreasing CSF/plasma concentration ratios for small, passively diffusing molecules during embryonic development may not reflect changes in permeability. Instead, increasing volume of distribution appears to be important in this decline. The intracellular presence of a small marker (3000 Da biotin-dextranamine) in plexus epithelial cells following intraperitoneal injection indicates a transcellular route of transfer. Ultrastructural evidence confirmed that choroid plexus tight junctions are impermeable to small molecules at least as early as E15, indicating the blood-CSF barrier is morphologically and functionally mature early in embryonic development. Comparison of two albumins (human and bovine) showed that transfer of human albumin (surrogate for endogenous protein) was 4-5 times greater than bovine, indicating selective blood-to-CSF transfer. The number of plexus epithelial cells immunopositive for endogenous plasma protein increased in parallel with increases in total protein content of the expanding ventricular system. Results suggest that different transcellular mechanisms for protein and small molecule transfer are operating across the embryonic blood-CSF interface.

Albumins↗

PubMed2005

Aquaporin-1 in the choroid plexuses of developing mammalian brain.

The normal brain develops within a well-controlled stable internal "milieu" protected by specialised mechanisms referred to collectively as blood-brain barriers. A fundamental feature of this environment is the control of water flow in and out of the developing brain. Because of limited vascularisation of the immature brain, choroid plexuses, via the cerebrospinal fluid, have been proposed as the main route of fluid exchange between the blood and brain interfaces. We describe the temporal expression and appearance of aquaporin-1 (AQP1) which is important for water transfer across adult choroid plexuses. AQP1 expression was studied in rat embryos using real time reverse transcription/polymerase chain reaction. mRNA for AQP1 was present in rat brain at embryonic day 12 (E12) one day before the protein was detectable in the fourth ventricular choroid plexus (the first plexus to appear); its relative levels increased at E13-E14 when more AQP1-immunoreactive cells appeared in all plexuses. The presence of AQP1 was determined immunocytochemically in five different mammalian species (rat, mouse, human, sheep and opossum) in all four choroid plexuses from their earliest appearance. In all five species studied, the appearance of AQP1 immunoreactivity followed the same developmental sequence: the fourth, lateral and, finally, third ventricular choroid plexus. The stage of choroid plexus development when AQP1 was first detected in all five species and in all four choroid plexuses corresponded to the transition between Stages I and II. The cellular localisation of AQP1 in all choroid plexuses, as soon as it was detectable, had the characteristic apical membrane distribution previously described in the adult; a basolateral membrane localisation was also observed.

Animals↗

PubMed2005

Breakdown of the blood-brain barrier to proteins in white matter of the developing brain following systemic inflammation.

Compromised blood-brain barrier permeability resulting from systemic inflammation has been implicated as a possible cause of brain damage in fetuses and newborns and may underlie white matter damage later in life. Rats at postnatal day (P) 0, P8 and P20 and opossums (Monodelphis domestica) at P15, P20, P35, P50 and P60 and adults of both species were injected intraperitoneally with 0.2-10 mg/kg body weight of 055:B5 lipopolysaccharide. An acute-phase response occurred in all animals. A change in the permeability of the blood-brain barrier to plasma proteins during a restricted period of postnatal development in both species was determined immunocytochemically by the presence of proteins surrounding cerebral blood vessels and in brain parenchyma. Blood vessels in white matter, but not grey matter, became transiently permeable to proteins between 10 and 24 h after lipopolysaccharide injection in P0 and P8 rats and P35-P60 opossums. Brains of Monodelphis younger than P35, rats older than P20 and adults of both species were not affected. Permeability of the blood-cerebrospinal fluid (CSF) barrier to proteins was not affected by systemic inflammation for at least 48 h after intraperitoneal injection of lipopolysaccharide. These results show that there is a restricted period in brain development when the blood-brain barrier, but not the blood-CSF barrier, to proteins is susceptible to systemic inflammation; this does not appear to be attributable to barrier "immaturity" but to its stage of development and only occurs in white matter.

Animals↗

PubMed2005

Long-term changes in blood-brain barrier permeability and white matter following prolonged systemic inflammation in early development in the rat.

Epidemiological evidence in human fetuses links inflammation during development with white matter damage. Breakdown of the blood-brain barrier has been proposed as a possible mechanism. This was investigated in the present study by inducing a prolonged inflammatory response in newborn rats, with intraperitoneal injections of lipopolysaccharide (LPS; 0.2 mg/kg) given at postnatal (P) day 0, P2, P4, P6 and P8. An acute phase response was present over the whole period of injections. Changes in blood-brain barrier permeability were determined for small (sucrose and inulin) and large (protein) molecules. During and immediately after the inflammatory response, plasma proteins were detected in the brain only within white matter tracts, indicating an increased permeability of the blood-brain barrier to protein during this period. The alteration in permeability to protein was transient. In contrast, the permeability of the blood-brain barrier to 14C-sucrose and 14C-inulin was significantly higher in adult animals that had received serial LPS injections during development. Adult animals receiving a single 1 mg/kg LPS injection at P0 showed no alteration in blood-brain barrier permeability to either small or larger molecules. A significant decrease in the volume of CNPase immunoreactive presumptive white matter tracts occurred in the external capsule and corpus callosum at P9. These results demonstrate that a prolonged systemic inflammatory response in the early postnatal period in rats causes size selective increases in blood-brain barrier permeability at different stages of brain development and results in changes in white matter volume.

Animals↗

PubMed2001

Permeability and route of entry for lipid-insoluble molecules across brain barriers in developing Monodelphis domestica.

1. We have studied the permeability of blood-brain barriers to small molecules such as [(14)C]sucrose, [(3)H]inulin, [(14)C]L-glucose and [(3)H]glycerol from early stages of development (postnatal day 6, P6) in South American opossums (Monodelphis domestica), using a litter-based method for estimating steady-state cerebrospinal fluid (CSF)/plasma and brain/plasma ratios of markers that were injected I.P. 2. Steady-state ratios for L-glucose, sucrose and inulin all showed progressive decreases during development. The rate of uptake of L-glucose into the brain and CSF, in short time course experiments (7-24 min) when age-related differences in CSF production can be considered negligible also decreased during development. These results indicate that there is a significant decrease in the permeability of brain barriers to small lipid-insoluble molecules during brain development. 3. The steady-state blood/CSF ratio for 3000 Da lysine-fixable biotin-dextran following I.P. injection was shown to be consistent with diffusion from blood to CSF. It was therefore used to visualise the route of penetration for small lipid-insoluble molecules across brain barriers at P0-30. The proportion of biotin-dextran-positive cells in the choroid plexuses declined in parallel with the age-related decline in permeability to the small-molecular-weight markers; the paracellular (tight junction) pathway for biotin-dextran appeared to be blocked, but biotin-dextran was easily detectable in the CSF. A transcellular route from blood to CSF was suggested by the finding that some choroid plexus epithelial cells contained biotin-dextran. 4. Biotin-dextran was also taken up by cerebral endothelial cells in the youngest brains studied (P0), but in contrast to the CSF, could not be detected in the brain extracellular space (i.e. a significant blood-brain barrier to small-sized lipid-insoluble compounds was already present). However, in immature brains (P0-13) biotin-dextran was taken up by some cells in the brain. These cells generally had contact with the CSF, suggesting that it is likely to have been the source of their biotin-dextran. Since the quantitative permeability data suggest that biotin-dextran behaves similarly to the radiolabelled markers used in this study, it is suggested that these markers in the more immature brains were also present intracellularly. Thus, brain/plasma ratios may be a misleading indicator of blood-brain barrier permeability in very immature animals. 5. The immunocytochemical staining for biotin-dextran in the CSF, in contrast to the lack of staining in the brain extracellular space, together with the quantitative permeability data showing that the radiolabelled markers penetrated more rapidly and to a much higher steady-state level in CSF than in the brain, suggests that lipid-insoluble molecules such as sucrose and inulin reach the immature brain predominantly via the CSF rather than directly across the very few blood vessels that are present at that time.

Algorithms↗

PubMed2001

Development of the choroid plexus.

Mammalian choroid plexuses develop at four sites in the roof of the neural tube shortly after its closure, in the order IVth, lateral, and IIIrd ventricles. Bone morphogenetic proteins and tropomyosin are involved in early specification of these sites and in early plexus growth. Four stages of lateral ventricular plexus development have been defined, based on human and sheep fetuses; these depend mainly on the appearance of epithelial cells and presence or absence of glycogen. Other plexuses and other species are probably similar, although marsupials may lack glycogen. Choroid plexuses form one of the blood-brain barrier interfaces that control the brain's internal environment. The mechanisms involved combine a structural diffusion restraint (tight junctions between the plexus epithelial cells) and specific exchange mechanisms. In this review, it is argued that barrier mechanisms in the developing brain are different in important respects from those in the adult brain, but these differences do not necessarily reflect immaturity of the system. Absence of a barrier mechanism or presence of one not found in the adult may be a specialisation that is appropriate for that stage of brain development. Emphasis is placed on determining which mechanisms are present in the immature brain and relating them to brain development. One mechanism unique to the developing brain transfers specific proteins from blood to cerebrospinal fluid (CSF), via tubulocisternal endoplasmic reticulum in plexus epithelial cells. This results in a high concentration of proteins in early CSF. These proteins do not penetrate into brain extracellular space because of "strap" junctions between adjacent neuroependymal cells, which disappear later in development, when the protein concentration in CSF is much lower. Functions of the proteins in early CSF are discussed in terms of generation of a "colloid" osmotic pressure that expands the ventricular system as the brain grows; the proteins may also act as specific carriers and growth factors in their own right. The pathway for low molecular weight compounds, which is much more permeable in the developing choroid plexuses, appears also to be a transcellular one, rather than paracellular via tight junctions. There is thus good evidence to support a novel view of the state of development and functional significance of barrier mechanisms in the immature brain. It grows in an environment that is different from that of the rest of the fetus/neonate and that is also different in some respects from that of the adult. But these differences reflect developmental specialisation rather than immaturity.

Animals↗

PubMed2001

Fetuin in human bone marrow: detection in foetal tissue and patients with mastocytosis.

Fetuin, a foetal protein of unknown function, has been shown to be expressed in both the immune and nervous systems, especially during development. Here, we show for the first time, that fetuin is abundantly present in many cells of the foetal human bone marrow, but is restricted to cells of the monocytic lineage in the adult. Fetuin's immunoreactivity increased considerably in adult human bone marrow in some pathological conditions, particularly in mastocytosis and was also increased in bone marrows in some cases of acute leukaemias, especially in acute myeloid leukaemia. This increase in the presence of fetuin in neoplastic bone marrows is not reflected by an increased level of circulating fetuin. This last observation contradicts earlier suggestions that fetuin is specifically reduced in cancer patients. A consistent increase in fetuin immunoreactivity in bone marrow of most cases of mastocytosis, as demonstrated in this paper, could become a useful tool in the diagnosis of this disease.

Adult↗

PubMed2000

Fetuin in the developing neocortex of the rat: distribution and origin.

Immunocytochemical distribution of the fetal protein fetuin in the neocortex of developing rat brain and the presence of its mRNA, as detected by using reverse transcriptase-polymerase chain reaction analysis, was studied in fetuses at embryonic day 15 (E15) through E22, in neonates at postnatal day 0 (P0) through P20, and in adults. Quantitative estimates of fetuin in cerebrospinal fluid (CSF) and plasma were obtained over the same period. Exogenous (bovine) fetuin injected intraperitoneally into fetal and postnatal rats was used to study the uptake of fetuin into CSF and brain and its distribution compared with endogenous fetuin; bovine albumin was used as a control. Fetuin was identified immunocytochemically in the cortical plate and subplate cells of the developing neocortex. In the rat fetus, fetuin first was apparent at E17, mainly in cell processes, but a few subplate cells also were positive. By E18, there was strong staining in subplate neurons and in inner cells of the cortical plate. At E21, these inner cells of the cortical plate were beginning to differentiate into layer VI neurons, many of which were positive for fetuin. By P0-P1, more layer VI neurons and some layer V neurons had become positive for fetuin. Fetuin immunoreactivity generally was weaker at P1, and, by P2-P3, it had disappeared from all of the layers of the developing neocortex. Bovine fetuin (but not albumin), probably taken up through CSF over the neocortical dorsal surface, had a cytoplasmic distribution; endogenous rat fetuin was both cytoplasmic and membrane bound. Thus, much of this fetuin can be accounted for by uptake, although the presence of fetuin mRNA indicates that in situ synthesis may also contribute.

Animals↗

PubMed2000

Acute-phase cytokines IL-1beta and TNF-alpha in brain development.

The nervous and the immune systems share several molecules that control their development and function. We studied the temporal and spatial distribution of the immunoreactivity of two acute-phase cytokines, TNF-alpha and IL-1beta, in the developing sheep neocortex and compared it with the well-described distribution of fetuin, a fetal glycoprotein also known to modulate the production of cytokines by lipopolysaccharide (LPS)-stimulated monocytes and macrophages. TNF-alpha was present first at embryonic day 30 (E30) (term is 150 days in sheep) as a faint band of immunoreactivity between the ventricular zone and the primordial plexiform layer (preplate). IL-1beta was detected at the first appearance of the cortical plate (E35-E40). Both cytokines were present on both sides of the cortical plate, which contained fetuin-positive cells, but was free from cytokine staining. By E60, TNF-alpha immunoreactivity was less prominent than that of IL-1beta and was confined to the marginal zone and outer developing white matter; IL-1beta was present in the marginal zone and in two bands of immunoreactive cells, one at the border of the cortical plate/developing layer VI (cells of neuronal morphology) and the other at the border of layer V and the developing white matter (identified as microglia). By E80, TNF-alpha staining had disappeared and IL-1beta-immunopositive microglia were no longer detectable. By E100-E140 only a few immunoreactive cells were identified in layers V-VI; these did not co-localize with fetuin-positive cells. The differences in distribution between fetuin and the two cytokines suggest that the opsonizing role of fetuin, proposed for monocyte production of cytokines, is probably not present in the developing brain. However, early in neocortical development TNF-alpha and IL-1beta were present in the subplate zone at a time of intense synaptogenesis.

Acute-Phase Reaction↗

PubMed2000

The nature and composition of the internal environment of the developing brain.

1. The fetal brain develops within its own environment, which is protected from free exchange of most molecules among its extracellular fluid, blood plasma, and cerebrospinal fluid (CSF) by a set of mechanisms described collectively as "brain barriers." 2. There are high concentrations of proteins in fetal CSF, which are due not to immaturity of the blood-CSF barrier (tight junctions between the epithelial cells of the choroid plexus), but to a specialized transcellular mechanism that specifically transfers some proteins across choroid plexus epithelial cells in the immature brain. 3. The proteins in CSF are excluded from the extracellular fluid of the immature brain by the presence of barriers at the CSF-brain interfaces on the inner and outer surfaces. These barriers are not present in the adult. 4. Some plasma proteins are present within the cells of the developing brain. Their presence may be explained by a combination of specific uptake from the CSF and synthesis in situ. 5. Information about the composition of the CSF (electrolytes as well as proteins) in the developing brain is of importance for the culture conditions used for experiments with fetal brain tissue in vitro, as neurons in the developing brain are exposed to relatively high concentrations of proteins only when they have cell surface membrane contact with CSF. 6. The developmental importance of high protein concentrations in CSF of the immature brain is not understood but may be involved in providing the physical force (colloid osmotic pressure) for expansion of the cerebral ventricles during brain development, as well as possibly having nutritive and specific cell development functions.

Amino Acids↗

PubMed2000

Barriers in the immature brain.

1. The term "blood-brain barrier" describes a range of mechanisms that control the exchange of molecules between the internal environment of the brain and the rest of the body. 2. The underlying morphological feature of these barriers is the presence of tight junctions which are present between cerebral endothelial cells and between choroid plexus epithelial cells. These junctions are present in blood vessels in fetal brain and are effective in restricting entry of proteins from blood into brain and cerebrospinal fluid. However, some features of the junctions appear to mature during brain development. 3. Although proteins do not penetrate into the extracellular space of the immature brain, they do penetrate into cerebrospinal fluid by a mechanism that is considered in the accompanying review (Dziegielewska et al., 2000). 4. In the immature brain there are additional morphological barriers at the interface between cerebrospinal fluid and brain tissue: strap junctions at the inner neuroependymal surface and these and other intercellular membrane specializations at the outer (piaarachnoid) surface. These barriers disappear later in development and are absent in the adult. 5. There is a decline in permeability to low molecular weight lipid-insoluble compounds during brain development which appears to be due mainly to a decrease in the intrinsic permeability of the blood-brain and blood-cerebrospinal fluid interfaces.

Animals↗

PubMed1999

Fetuin in neurons of the retina and cerebellum during fetal and postnatal development of the rat.

Although long known to be a liver-derived fetal plasma glycoprotein, fetuin has more recently been shown to be present in sub-populations of neurons in the developing nervous system of a number of mammalian species. We have extended these observations to examine the fetuin immunoreactivity (IR) in developing rat retina and cerebellum. Fetuin-IR was first seen in the retina on embryonic day (E)19 in a sub-population of cells in the retinal ganglion cell layer and a small proportion of cells in the neuroblastic layer. The proportion of cells in the ganglion layer exhibiting fetuin-IR increased until postnatal day (P)10 when all cells in this layer were strongly immunoreactive. From P14 onwards fetuin-IR was absent or very weak and restricted to a small proportion of ganglion cells. In the developing cerebellum, the outer and inner granule cell layers, the deep nuclei and cells in the sub-cortical white matter exhibited fetuin-IR from E19 to P10. There was little fetuin-IR in the cerebellum at ages P14 and older, and Purkinje cells did not exhibit fetuin-IR at any time. The results show that fetuin appears in many neurons in the retina and cerebellum that are differentiating during the period from E19 to P10. The concentration of fetuin in cerebrospinal fluid is at its highest in this same period which suggests that some sub-populations of neurons could obtain fetuin from extracellular fluid during this period; however, the lack of fetuin-IR in other neuronal populations suggests that fetuin uptake is not a general property of developing neurons.

Animals↗

PubMed1999

Barrier mechanisms in the brain, I. Adult brain.

1. The adult brain functions within a well-controlled (internal) environment that is separate from that of the internal environment of the rest of the body as a whole. 2. The underlying mechanism of control of the brain's internal environment lies in the presence of tight junctions between the cerebral endothelial cells at the blood-brain interface (blood-brain barrier) and between choroid plexus epithelial cells (blood-cerebrospinal fluid (CSF) barrier). 3. The effect of tight junctions at the blood-brain and blood-CSF barriers is to convert the properties of the individual endothelial and epithelial cells into properties of these interfaces as a whole. 4. Superimposed on the diffusion restriction provided by the tight junctions in the blood-brain and blood-CSF barriers is a series of transport mechanisms into and out of the brain and CSF that determine and control the internal environment of the brain with respect to a wide range of molecules, such as electrolytes, amino acids, glucose, vitamins and peptides. 5. The physical characteristics of drugs, together with their interaction with the properties of the barriers between blood, brain and CSF, determine the extent to which drugs penetrate into the brain. 6. Drugs can be targeted to the brain by making use of knowledge of this interaction between the physical properties of a drug (which can be modified by manipulation of the structure of the molecule in predictable ways) and the influx/efflux mechanisms present in the blood-CSF and blood-brain interfaces.

Adult↗

PubMed1999

Barrier mechanisms in the brain, II. Immature brain.

1. It is widely believed that 'the' blood-brain barrier is immature in foetuses and newborns. 2. Much evidence in support of this belief is based on experiments that were unphysiological and likely to have disrupted fragile blood vessels of the developing brain. Some confusion about barrier development arises from insufficient recognition that the term 'blood-brain barrier' describes a complex series of mechanisms controlling the internal environment of the brain. 3. We present evidence showing that the brain develops within an environment that, particularly with respect to protein, is different from that of the rest of the body and that possesses a number of unique features not present in the adult. 4. Barriers to protein at blood-brain and blood-cerebrospinal fluid (CSF) interfaces (tight junctions) are present from very early in development; immunocytochemical and permeability data show that proteins are largely excluded from extracellular space in developing brain. 5. Cerebrospinal fluid in developing brain contains high concentrations of proteins largely derived from plasma. This protein is transferred from blood by an intracellular mechanism across the epithelial cells of the immature choroid plexus. Only a small proportion of choroid plexus cells is involved. The route is an intracellular system of tubulo-endoplasmic reticulum continuously connected across the epithelial cells only early in brain development. 6. High concentrations of proteins in CSF in developing brain are largely excluded from the brain's extracellular space by barriers at the internal and external CSF-brain interfaces. These consist of membrane specializations between surfaces of cells forming these interfaces (neuroependyma on the inner surface; radial glial end feet on the outer surface). In contrast with tight junctions present at the blood-brain and blood-CSF barriers, at the CSF-brain barriers of the immature brain, other junctional types are involved: strap junctions in the neuroependyma and a mixture of junctions at the outer CSF-brain barrier (plate junctions, strap junctions and wafer junctions). These barriers are not present in the adult. 7. Permeability to small lipid-insoluble molecules is greater in developing brain; more specific mechanisms, such as those involved in transfer of ions and amino acids, develop sequentially as the brain grows.

Adult↗

PubMed1998

Modification of macrophage response to lipopolysaccharide by fetuin.

The physiological role(s) of fetuin, a protein present in plasma and many tissues of developing animals at levels much higher than in the adult, is unknown. Here we show that fetuin can modify the responses of macrophages to lipopolysaccharide (LPS) stimulation. At concentrations of fetuin in the medium, corresponding to fetal levels of this protein in plasma, the production and secretion of interleukin 1beta (IL-1beta) and nitric oxide (NO) is almost abolished, tumour necrosis factor-alpha (TNF-alpha) reduced, while that of IL-6 is not affected. On the other hand, concentrations of fetuin corresponding to adult plasma levels (i.e. 40-60 mg/100 ml) were without much effect on macrophage synthesis and secretion of these cytokines.

Animals↗

PubMed1998

The acute phase response of plasma proteins in the polyprotodont marsupial Monodelphis domestica.

In eutherians, patterns of plasma protein levels in blood change during the acute phase response to trauma and inflammation. Until now, such an acute phase response has not been characterised in a noneutherian species. Here we describe the acute phase response in a marsupial species, the South American polyprotodont marsupial Monodelphis domestica, after brain surgery or injection of lipopolysaccharide. Several days after brain surgery, transthyretin was not detected in plasma. For 48 hr following injection of lipopolysaccharide, the concentration of haptoglobin in plasma increased, that of transthyretin decreased, and the concentration of albumin in plasma did not change significantly. The American polyprotodont marsupials are probably more closely related to the common ancestor marsupial than the Australian marsupials are. It is most likely that the transthyretin gene was not expressed in the liver of this common ancestor. As the transthyretin gene is expressed in the liver of M. domestica, it seems that as soon as transthyretin is synthesised by the liver, it is under negative acute phase control.

Acute-Phase Reaction↗

PubMed1998

Permeability of the developing and mature blood-brain barriers to theophylline in rats.

1. In the present study, the uptake of theophylline and L-glucose into the adult and neonatal rat brain has been investigated. Steady state cerebrospinal fluid (CSF) and brain concentrations of theophylline were reached within 1 h following a single intraperitoneal (i.p.) injection, whereas steady state CSF and brain concentrations of L-glucose were not approached until after 5 h. 2. Steady state brain:plasma and CSF:plasma concentration ratios for theophylline and L-glucose in neonatal rats were significantly higher than ratios in adult rats. Erythrocyte:plasma ratios for theophylline in neonatal rats were also significantly higher than ratios in adult rats. Steady state ratios for theophylline were significantly higher than those for L-glucose in both neonatal and adult rats. 3. Respiratory acidosis (pH 6.9-7.0) did not affect steady state CSF:plasma or brain:plasma ratios for theophylline in neonatal or adult rats. In contrast, steady state CSF:plasma and brain:plasma ratios for L-glucose were increased by respiratory acidosis. 4. The lower steady state CSF:plasma, brain:plasma and erythrocyte:plasma ratios for theophylline in adult rats are likely to be due to a higher concentration of plasma proteins in adult blood compared with neonates, with a greater retention of protein-bound (non-exchangeable) theophylline in adult blood, and are unlikely to be due to p-glycoprotein-mediated efflux of theophylline at the adult blood-brain barrier.

Acidosis, Respiratory↗

PubMed1998

The fetal glycoprotein, fetuin, counteracts ill-effects of the bacterial endotoxin, lipopolysaccharide, in pregnancy.

We show that fetuin, a fetal glycoprotein present in fetal plasma in concentrations substantially higher than in the adult, can exert a protective function against ill-effects of the bacterial endotoxin, lipopolysaccharide (LPS), in pregnancy. The concentration of fetuin in plasma of pregnant rats (E17 gestation) was artificially increased by repeated intraperitoneal administration of this protein. This was followed by an injection of a standard dose of LPS, a dose that produced in control animals (no additional fetuin) nearly 50% abortions and 40% maternal deaths. None of the females exposed to increased fetuin died following LPS injection. Nine out of 10 multigravida animals carried their pregnancy to full term but all primagravidas aborted.

Abortion, Spontaneous↗