There is strong evidence for an association between H pylori infection and antral gastritis and duodenal ulcer disease in children; however, data from randomized, double-blind, placebo-controlled treatment trials are required. There is weak evidence for an association with gastric ulcer and weak or no evidence for an association with recurrent abdominal pain.
1. Blood-cerebrospinal fluid (CSF) transfer of various exogenous albumins has been investigated in developing Monodelphis domestica (South American grey short-tailed opossum) and compared with the steady-state CSF: plasma ratios for endogenous (Monodelphis) albumin. Ratios for Monodelphis albumin and human albumin were similar and were the highest at postnatal day 5 (P5) (48-2 + 4-4 and 40-6 + 4 5%, respectively). The ratio for bovine albumin was similar to the steady-state ratio for Monodelphis albumin at P7-8 but became consistently lower than the Monodelphis albumin ratio at all other ages until P32-36 when all albumins tested attained a similar low ratio. The CSF: plasma ratio of chemically modified (succinylated) bovine albumin was always significantly lower than that of other albumins, except at the oldest age examined (P32-36). 2. Immunocytochemistry showed that within the brain, albumin was confined to the lumen and endothelial cells of blood vessels. In the choroid plexus only a small proportion (0*2-1X7% of the total cell number) of epithelial cells was positive for albumin, both endogenous and exogenous, at all ages studied (except the 3rd ventricle where cells were only positive from P8). The CSF was strongly positive for all albumins. The peak proportion of positive cells and of albumin concentrations in CSF occurred at P8. These findings suggest that the primary route for penetration of albumin into CSF is directly across the choroid plexus rather than via the brain. 3. Double-labelling immunocytochemistry revealed that the same epithelial cells contained both endogenous (Monodelphis) and exogenous (human) albumin. In contrast, for succinylated albumin, at P7 only about 35% (lateral ventricle) and 50% (4th ventricle) of Monodelphis albumin-positive cells were also positive for succinylated albumin, but by P30 this proportion increased to 90 % at both sites. 4. Thus the developing choroid plexus distinguishes between different albumins. Chemical modification of albumin (succinylation) disrupts this mechanism. It is proposed that in older animals (P32-36) all of the albumin in the CSF is derived from plasma by diffusion (as in adult animals). At earlier stages of development, a proportion of the albumin in CSF also appears to be transferred from the plasma by diffusion with an additional component transferred by a mechanism that can distinguish between different species of albumin. The main route of entry of albumin to CSF seems likely to be via the choroid plexus epithelial cells.
The commonly held belief that the fetal blood-brain and blood-CSF barriers are immature is reviewed. Results obtained from carefully conducted experiments with horseradish peroxidase and optimal freeze-fracturing suggest that the chick, rat and monkey brain barrier systems to proteins are tight from the earliest stages of development. Previous studies are reviewed in the light of new information on retrograde axonal transport, circumventricular organs, the proper use of horseradish peroxidase, freeze-fracturing, immunocytochemistry and plasma protein gene expression in the developing human brain. Original data on the development of human brain barrier systems are included. Tight junctions between cerebral endothelial and choroid plexus epithelial cells form the morphological basis for these systems. CSF in the fetus contains a remarkably high concentration of protein in contrast to adult CSF which is characterized by a very low protein concentration. This has previously been interpreted as due to immaturity of barriers in the fetal brain. Tight junctions between cerebral endothelial cells and between choroid plexus epithelial cells have been investigated in human embryos and fetuses by freeze fracture and thin section electron microscopy. As soon as the choroid plexus and the brain capillaries differentiated they exhibited well formed tight junctions. These junctions were very complex at early stages of development. A new barrier consisting of 'strap junctions' was found in the developing germinal matrix. The very high concentration of protein in early human fetal CSF cannot be accounted for by a lack of tight junctions in the developing brain barrier systems. Some transfer of proteins from blood to CSF, possibly via an intracellular route, has been demonstrated in immature experimental animals, but it seems that an important contribution to CSF proteins in the fetus may be synthesis by the developing brain and choroid plexuses with subsequent release into the CSF.
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