Rapid hypertensinogenic effect of lead: studies in the spontaneously hypertensive rat.

Chronic lead exposure may cause hypertension in normotensive rats. This hypertensinogenic effect has been attributed to perturbations in the renin-angiotensin axis, the contractile response of the vascular smooth muscle, or the intracellular Ca2+ homeostasis as a consequence of the inhibition of Na(+)-K(+)-ATPase activity. In this study we examined the short-term effect of lead exposure on blood pressure, plasma renin activity, vascular contractility, and renal Na(+)-K(+)-ATPase activity and abundance in the spontaneously hypertensive rat. Our data indicate that modest lead exposure caused blood pressure elevation within two weeks in this rat strain that is genetically susceptible to the development of hypertension. This rapid blood pressure-elevating effect did not appear to depend on the mechanisms described in hypertension associated with more chronic lead exposure listed above. This acute model provides an additional approach to the study of lead-induced hypertension.     

Eales' disease presenting as stroke in the young adult

Eales' disease is an uncommon idiopathic disorder characterized by retinal perivasculitis and recurrent vitreous hemorrhages in young males. Associated neurological involvement is rare. We report a 38-year-old man who presented with stroke attributed to Eales' disease.     

Role of IL-2 in rat fetal thymocyte development

Early during rat thymus ontogeny, an important proportion of thymocytes expresses IL-2R and contains IL-2 mRNA. To investigate the role of the IL-2-IL-2R complex in rat T cell maturation, we supplied either recombinant rat IL-2 or blocking anti-CD25 mAb to rat fetal thymus organ cultures (FTOC) under several experimental conditions. The IL-2 treatment initially stimulated the growth of thymocytes and, as a result, induced T cell differentiation, but the continuous addition of IL-2 to rat FTOC, as well as the anti-CD25 administration, resulted in cell number decrease and inhibition of thymocyte maturation. These results indicate that immature rat thymocytes bear functional high- affinity IL-2R and that IL-2 promotes T cell differentiation as a consequence of its capacity to stimulate cell proliferation. Modifications in TCR alpha beta repertoire and increased numbers of NKR- P1+ cells, largely NK cells, were also observed in IL-2-treated FTOC. Furthermore, IL-2-responsiveness of different thymocyte subsets changed throughout thymic ontogeny. Immature CD4-CD8-cells responded to IL-2 in two stages, early in thymus development and around birth, in correlation with the maturation of two distinct waves of thymic cell progenitors. Mature CD8+ thymocytes maximally responded to IL-2 around birth, supporting a role for IL-2 in the increased proliferation of mature thymocytes observed in vivo in the perinatal period. Taken together, these findings support a role for IL-2 in rat T cell development.      

The influence of high dietary aluminum on brain microtubule polymerization in mice

One of the possible mechanisms that has been proposed to underlie the deleterious effects of excess aluminum on brain function is an impairment in the normal formation of the cytoskeletal network. Based on recent reports that aluminum can promote the in-vitro polymerization of purified tubulin, in the present study we characterized the effects of high dietary aluminum on in-vitro microtubule formation in brain supernatants. Mice were fed diets containing aluminum 25-1000 micrograms/g for up to 10 weeks. Tubulin polymerization in high-speed brain supernatants was not found to be affected by dietary aluminum. However, we observed that the addition of aluminum in vitro stimulated microtubule assembly in brain supernatants from mice fed control diets, as had been previously reported. Thus, impaired brain microtubule function is not an early general biochemical lesion in aluminum toxicosis.     

Enhanced saliva-mediated bacterial aggregation and decreased bacterial adhesion in caries-resistant versus caries-susceptible individuals.

A study of saliva-mediated aggregation and adhesion has been carried out in a group of caries-resistant (CR) and caries-susceptible (CS) individuals. The submandibular saliva of the CS group had a much greater potency, as determined by dilution, in promoting adherence to hydroxyapatite beads than did the saliva of CR group. In contrast, the CR group demonstrated a twofold enhancement of saliva-mediated aggregation compared with the CS group. These observations support the hypothesis that saliva-mediated aggregation and adherence are important factors in caries resistance.     

Tetracycline administration restores osteoblast structure and function during experimental diabetes.

Osteopenia is a recognized complication of diabetes mellitus in humans and experimental animals. We recently found that tetracyclines prevent osteopenia in the streptozotocin-induced diabetic rat and that this effect was associated with a restoration of defective osteoblast morphology (Golub et al., 1990). The present study extends these initial ultrastructural observations by assessing osteoblast function in the untreated and tetracycline-treated diabetic rats. After a 3-week protocol, non-diabetic control and diabetic rats, including those orally administered a tetracycline, minocycline (MC), or a non-antimicrobial tetracycline analog (CMT), were perfusion-fixed with an aldehyde mixture; the humeri were dissected and processed for ultracytochemical localization of alkaline phosphatase (ALPase) and Ca-ATPase activities. Some rats from each experimental group received an intravenous injection of 3H-proline as a radioprecursor of procollagen, and the humeri were processed for light microscopic autoradiography. In addition, the osteoid volume in each experimental group was quantitatively examined by morphometric analysis of electron micrographs. During the diabetic state, active cuboidal osteoblasts in the endosteum of control rats were replaced by flattened bone-lining cells that contained few cytoplasmic organelles for protein synthesis (Golgi-RER system), and active transport (mitochondria). Treating diabetic rats with MC, and even more so with CMT, appeared to "restore" osteoblast structure. During diabetes, bone-lining cells incorporated little 3H-proline or secreted little labeled protein and produced only a very thin osteoid layer. Tetracycline administration to the diabetics increased both the incorporation of 3H-proline by osteoblasts and their secretion of labeled protein toward the osteoid matrix, in a pattern similar to that seen in the non-diabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic marginal iron intakes during early development in mice alter brain iron concentrations and behavior despite postnatal iron supplementation

The objective of this study was to investigate the behavioral and cognitive outcomes associated with chronic marginal iron (Fe) intakes during early development. Offspring (3 males and 3 females/litter) of Swiss-Webster female mice who had been fed a control Fe diet (75 microg Fe/g diet) or marginal Fe diet (14 microg Fe/g diet) for 9 wk before mating were weaned on postnatal (PND) 21. Offspring of marginal Fe dams were fed either the marginal Fe diet (marginal group) or a control diet (replete group) from PND 21 throughout the duration of the study, whereas offspring of control dams consumed the control diet ad libitum (control group). On PND 30, 45 and 60, one male and female per litter underwent grip strength and auditory startle testing. A Morris maze was used to assess cognitive function in males starting at PND 50. Marginal Fe mice consistently demonstrated significantly lower grip strength, which was independent of differences in body weight. In addition, marginal Fe males demonstrated attenuated startle responsiveness, as well as altered performance in the Morris water maze. These differences in performance were found in association with lower brain Fe concentrations. Postnatal Fe supplementation did not reverse all of these disturbances because differences in brain Fe concentrations and maze learning persisted. This study demonstrates that chronic marginal Fe intakes during early development can result in persistent biochemical and behavioral changes in mice.