The effect of vitamin E supplementation on an experimental Haemonchus contortus infection in lambs.

The objective of this study was to investigate the effect of vitamin E supplementation on an experimental Haemonchus contortus infection in lambs. Twenty lambs were stratified into two treatment groups based on fecal egg count. Worm-free lambs, 28-32 weeks of age, were supplemented with vitamin E (d-α-tocopherol) for 12 weeks following the recommendations of the National Research Council for the minimum daily requirement (control; 5.3 IU/kg body weight (BW)/day (d), n=10) or the requirement for optimal immune function (VE10; 10 IU/kg BW/d, n=10). Five weeks following initiation of vitamin E supplementation, lambs were infected with 10,000 H. contortus third stage larvae. Samples were taken weekly to quantify serum α-tocopherol, serum total non-specific immunoglobulin (Ig)G, whole worm antigen specific IgG, packed cell volume (PCV), and fecal egg count (FEC). Expression of cytokine genes IFN-λ and IL-4 were measured in peripheral blood collected prior to slaughter. Lambs were necropsied six weeks after infection and the α-tocopherol concentration of liver, muscle and lymph node were measured as well as abomasal worm burden and histologic evaluation of the abomasum for inflammation and enumeration of eosinophils and globule leukocytes. The livers of VE10 lambs contained slightly more α-tocopherol than control lambs. No differences were observed in serum, muscle or lymph node α-tocopherol concentration, serum IgG or peripheral mRNA expression of IL-4 or IFN-λ between control and VE10 lambs. However, lambs supplemented at 10IU/kg BW/d had a lower PCV reduction, FEC and worm burden 49% less than control lambs. Worm burden was negatively correlated with eosinophil (-0.720, P<0.05) and globule leukocyte count (-0.867, P<0.05). Strong positive correlations were observed within the inflammatory cell response in VE10 lambs that was absent in control lambs. These data indicate that additional vitamin E supplementation resulted in lower worm burden and greater recruitment of innate effector cells to the site of infection. Further studies are necessary to elucidate the mechanism by which vitamin E affects greater recruitment of innate effector cells to the abomasum during gastrointestinal nematode infection of lambs.

Solubility of molecular crystals: polymorphism in the light of solubility theory.

The thermodynamic theory of solubility of molecular crystals in solvents is reviewed with an emphasis on solutes showing polymorphism as in case of many pharmaceuticals. The relation between solubility and binary phase diagrams of the solute solvent system is treated. The astonishing variety of possible solubility curves as a function of temperature is explained using simple models for the solution thermodynamics assuming no mixing between the solvent and solute in the solid phase, though including the case of solvates or pseudo polymorphs. In passing a new method is introduced that allows to estimate the transition temperature of enantiotropically related polymorphs from melting temperatures and enthalpies of the polymorphs.

Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice.

Receptor for advanced glycation end-products (RAGE), and two of its ligands, AGE and EN-RAGEs (members of the S100/calgranulin family of pro-inflammatory cytokines), display enhanced expression in slowly resolving full-thickness excisional wounds developed in genetically diabetic db+/db+ mice. We tested the concept that blockade of RAGE, using soluble(s) RAGE, the extracellular ligand-binding domain of the receptor, would enhance wound closure in these animals. Administration of sRAGE accelerated the development of appropriately limited inflammatory cell infiltration and activation in wound foci. In parallel with accelerated wound closure at later times, blockade of RAGE suppressed levels of cytokines; tumor necrosis factor-alpha; interleukin-6; and matrix metalloproteinases-2, -3, and -9. In addition, generation of thick, well-vascularized granulation tissue was enhanced, in parallel with increased levels of platelet-derived growth factor-B and vascular endothelial growth factor. These findings identify a central role for RAGE in disordered wound healing associated with diabetes, and suggest that blockade of this receptor might represent a targeted strategy to restore effective wound repair in this disorder.

Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model.

Although hyperhomocysteinemia (HHcy) is a well-known risk factor for the development of cardiovascular disease, the underlying molecular mechanisms are not fully elucidated. Here we show that induction of HHcy in apoE-null mice by a diet enriched in methionine but depleted in folate and vitamins B6 and B12 increased atherosclerotic lesion area and complexity, and enhanced expression of receptor for advanced glycation end products (RAGE), VCAM-1, tissue factor, and MMP-9 in the vasculature. These homocysteine-mediated (HC-mediated) effects were significantly suppressed, in parallel with decreased levels of plasma HC, upon dietary supplementation with folate and vitamins B6/B12. These findings implicate HHcy in atherosclerotic plaque progression and stability, and they suggest that dietary enrichment in vitamins essential for the metabolism of HC may impart protective effects in the vasculature.

Naka-Rushton equation parameters in electroretinogram analysis of daunomycin effects on retinal function.

Intraocular daunomycin may inhibit intravitreal cellular proliferation in proliferative vitreoretinopathy after rhegmatogenous retinal detachments and retinal reattachment surgery. Doses of 15 nmol or more have shown histological retinal toxicity when injected into the intact vitreous of rabbit eyes. We injected 30, 20, 10 and 0 nmol doses of daunomycin into rabbit eyes with gas-compressed vitreous to better simulate the clinical conditions in which it would be used. We then evaluated effects on retinal function by examining scotopic b-wave amplitudes, measured for a four log unit set of intensities. We used the three independent parameters Rmax, log K, and n of the Naka-Rushton equation to measure changes in retinal function. All three doses of daunomycin failed to measurably depress retinal function (i.e., there were no dose-related losses of Rmax, log K or n) in this experimental model. We used this approach to monitor alterations in retinal function since it can show selective changes in each parameter. This selectivity is an advantage over monitoring retinal function with single intensities or comparisons limited solely to electroretinogram amplitudes.

Effects of stress and social supports on mother-child interactions in single- and two-parent families.

Social networks, coping abilities, life stresses, and mother-child interaction were studied in 28 mother-child pairs--14 single mothers and their preschool children and 14 matched married women and children. Questionnaires were used to measure the mothers' social network, coping abilities, and life stress; a mother-child interaction situation was used to measure maternal control, maternal maturity demands, maternal nurturance, mother-child communication, and child compliance. Single parents tended to be more socially isolated than married parents. They worked longer hours and received less emotional and less parental support. They tended to have less stable social networks and experience more potentially stressful life changes. Only in the household area did single mothers report more difficulties coping than 2-parent mothers. No significant differences were found in any of the 5 mother-child interaction variables. Different variables predicted mother-child interaction in the 2 samples. Predicting optimal mother-child interaction in single-parent families were fewer stressful life events, reduced social contact, increased parenting support, and hours maternal employment. Predicting optimal interaction in 2-parent families were fewer stressful life events, satisfaction with emotional support, and the availability of household help. Social contacts, household help, and employment differentially predicted mother-child interactions in the 2 groups. Implications of these differences for descriptions of the effect of social networks and maternal adjustment on child development are considered, as are implications for intervention.

The Stiles--Crawford function of an albino observer.

Stiles--Crawford functions (SCF's) were measured for both eyes of an albino observer with a marked pendular nystagmus using an eye position monitoring system. Both eyes demonstrated directional sensitivity as revealed by their SCF's. The directional sensitivity of both eyes was less than that of either the foveal or parafoveal region of normal observers. In addition, there was a significant difference between the SCF's for the albino observer's two eyes. Our results suggest that the psychophysical SCF is predominantly the result of the orientational distribution of groups of receptors on the retina.