Current concepts in immune derangement due to undernutrition

Protein-calorie malnutrition (PCM) adversely affects more or less all immune competent cells. Nonspecific immunity is impaired, particularly adherence and chemotaxis of phagocytes, although the responsiveness of circulating cells may not be the same as that of noncirculating cells. PCM results in numerical and functional impairment in lymphocytes. PCM markedly affects IgG class antibodies which have the highest affinity when directed against T-dependent antigens. These impairments are interrelated, since cooperation between T-helper cell and B-cells is depressed, and the antigen presentation to T-helper cells by macrophages is deficient.     

Digoxin cannot account for the reported association of EKG abnormalities and rhegmatogenous retinal detachment

The prevalence of cardiovascular disease (by EKG criteria) in patients with rhegmatogenous retinal detachments has been reported to be more than four times that found in age-matched controls. Adhesion between the retinal pigment epithelium (RPE) and the photoreceptors is facilitated by RPE transport. Because RPE transport is driven by a Na-K ATPase, it has been suggested that the correlation of EKG abnormalities and retinal detachment may be due to clinical use of digoxin, a Na-K ATPase inhibitor frequently given to patients with cardiovascular disease. The prevalence of EKG abnormalities in 299 consecutive patients with primary retinal detachment is about the same as that reported previously. However, 92% of these patients with EKG abnormalities did not take digoxin. Therefore, clinical use of digoxin cannot account for the reported association of EKG abnormalities and rhegmatogenous retinal detachment.     

Adhesion molecules and their ligands in nasal polyps of aspirin-hypersensitive patients.

BACKGROUND: Chronic inflammation with tissue eosinophilia plays a key role in the pathogenesis of asthma and nasal polyps in patients with aspirin hypersensitivity. OBJECTIVE: To evaluate the expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule I (ICAM-1) and their ligands (the integrins lymphocyte function-associated antigen 1 and very late-activation antigen 4 [VLA-4]) in nasal polyps of patients with aspirin hypersensitivity compared with aspirin-tolerant individuals. METHODS: Immunohistochemical studies were performed using a peroxidase method and monoclonal antibodies on 6-microm-thick cryostat sections cut from frozen polyps collected during elective surgery from 21 aspirin-sensitive and 23 aspirin-tolerant patients. RESULTS: The mean +/- SD values of the semiquantitatively evaluated immunoexpression of ICAM-1, VCAM-1, and VLA-4 were significantly increased in patients with aspirin hypersensitivity compared with aspirin-tolerant patients (1.7 +/- 0.8 vs 0.9 +/- 0.8, P < .003; 1.8 +/- 0.8 vs 0.8 +/- 0.8, P < .001; and 2.2 +/- 0.7 vs 1.3 +/- 0.7, P < .001, respectively), whereas the mean +/- SD values of the expression of lymphocyte function-associated antigen 1 did not differ significantly (2.4 +/- 0.5 vs 2.2 +/- 0.9; P = .57). We found a correlation between the immunoexpression of VCAM-1 and its ligand VLA-4 in all studied tissue samples (r = 0.4; P < .02). CONCLUSIONS: In nasal polyps of aspirin-hypersensitive patients, up-regulation of the adhesion molecules ICAM-1 and VCAM-1 and the integrin VLA-4 may play an important role in the development of chronic eosinophilic inflammation.     

Nerve growth factor (NGF) promotes angiogenesis in the quail chorioallantoic membrane.

Angiogenesis, the formation of new blood vessels, is tightly regulated by growth factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). The authors hypothesize that nerve growth factor (NGF), a well known neurotrophin, may play a direct angiogenic role. To test this hypothesis, the authors measured the effects of NGF on the natural vascularization of the quail chorioallantoic membrane (CAM). The angiogenic effect of NGF was compared to that of human recombinant VEGF165 (rhVEGF) and basic FGF (rhbFGF). In comparison to phosphate-buffered saline-treated controls, NGFs from different biological sources (mouse, viper, and cobra) increased the rate of angiogenesis in a dose-dependent fashion from 0.5 to 5 microg. For quantitative morphometry, grayscale images of the blood vessels end points of the CAM arteries were binarized for visualization and skeletonized for quantization by fractal analysis. In mouse NGF-treated embryos the fractal dimension (Df), indicative of arterial vessel length and density, increased to 1.266 +/- 0.021 compared to 1.131 +/- 0.018 (p < .001) for control embryos. This effect was similar to that of 0.5 microg rhVEGF (1.290 +/- 0.021, p < .001) and 1.5 microg rhbFGF (1.264 +/- 0.028, p < .001). The mouse NGF-induced angiogenic effect was blocked by 1 microM K252a (1.149 +/- 0.018, p < .001), an antagonist of the NGF/trkA receptor, but not by 1 microM SU-5416 (1.263 +/- 0.029, p < .001), the VEGF/Flk1 receptor antagonist, indicating a direct, selective angiogenic effect of NGF via quail embryo trkA receptor activation. These results confirm previous observations that NGF has angiogenic activity and suggest that this neurotrophin may also play an important role in the cardiovascular system, besides its well-known effects in the nervous system. The angiogenic properties of NGF may be beneficial in engineering new blood vessels and for developing novel antiangiogenesis therapies for cancer.     

Further studies on the aberrant crossed visual corticotectal pathway in rats

Summary An aberrant crossed corticotectal pathway can be generated by removal of one visual cortex and the contralateral superior colliculus from newborn rats. This aberrant crossed corticotectal projection arises from the pyramidal neurons located in layer V of the visual cortex and terminates in a spatially orderly manner in the appropriate laminae of the cortically deafferented contralateral colliculus. Comparable results cannot be reproduced by unilateral collicular lesions alone. The significance of these findings and the possible mechanisms involved in the formation of the aberrant pathway are discussed and compared with the retinotectal system.The research was supported by USPHS Grant EY-00596 from the National Institutes of Health     

Reduction of soluble adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor levels in serum of rheumatoid arthritis patients following multiple intravenous infusions of infliximab

INTRODUCTION: The purpose of this study was to determine the effect of repeated infusions of infliximab, a chimeric anti-tumor necrosis factor (anti-TNF)-alpha antibody, on the levels of soluble adhesion molecules and vascular endothelial growth factor (VEGF) in patients with active rheumatoid arthritis (RA). MATERIALS AND METHODS: The treatment design consisted of 9 infusions of infliximab (3 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter. All patients had been receiving methotrexate (MTX; 7.5-20 mg/week). Serum levels of soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, E-selectin (sE-selectin), and VEGF were measured by ELISA at weeks 0, 2, 6, 14, and 38 prior to infusion, and at week 62. RESULTS: A remarkable decrease in serum sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01) and VEGF (p<0.001) levels was observed in RA patients after the initial dose of infliximab. The second administration of the drug was followed by an even more significant suppression of serum sICAM-1, sVCAM-1, sE-selectin, and VEGF (p<0.001 in all cases). Further infliximab infusions also significantly reduced serum soluble adhesion molecules and VEGF concentrations, although these were less effective. Infliximab treatment induced a significant decrease in the number of monocytes observed until the end of the study. CONCLUSIONS: Our study, besides a rapid suppression of disease activity, showed that serum soluble adhesion molecules and VEGF concentrations are down-regulated following anti-TNF-alpha antibody therapy combined with MTX. Repeated doses of infliximab sustained the reductions in the soluble adhesion molecules and VEGF concentrations, although they were less effective than the first and second infusions of infliximab.     

Transitions to parenthood: his,hers, and theirs

This study explores marital processes that may underlie the apparent decline in satisfaction with marriage in partners becoming parents for the 1st time. The study assessed 47 couples expecting a 1st child and 15 couples not yet decided about having a child at pretest, post 1 (6 months post partum of 9 months after pretest) and post 2 (18 months postpartum or 21 months after pretest). Questionnaires examined: 1) psychological sense of self; 2) partners' role arrangements and communication; 3) parenting ideology; 4) perceptions of the family of origin; and 5) social support and life stress, including parents' work patterns. Parenthood seems to bring more change, and more negative change, in each of the 5 domains of family life that were investigated for comparable couples not having a 1st child experience over a similar period of time. Quantitative data support this conclusion in 4 of the 5 domains (individuals sense of self, marital, parent-child, and outside the family). Interview data suggest that new parents' relationships with their families of origin also undergo change at this time. Although shifts within domains often showed patterns similar to change in overall satisfaction with the marriage, the connection between the 2 was not linear and direct, especially for women. Men and women in transition to parenthood become increasingly different from one another; the results suggest that increased gender differentiation accompanying the transition to parenthood is a factor in accounting for marital satisfaction decline.     

Global versus local processing: Is there a hemispheric dichotomy?

A major dichotomy proposed for lateralized information processing is that the right and left cerebral hemispheres are "global" and "analytic" processors respectively. Here three experiments employed a tachistoscopic recognition paradigm with letter patterns varying in size and composition. No visual field asymmetries in RT were found in the first two experiments, although statistical power was high and a Stroop-like effect ("global precedence") was supported. Experiment 3 resulted in a right field advantage for vocal naming responses yet no asymmetry for manual responses, suggesting that both hemispheres can recognize global and local patterns, but that introduction of a laterally controlled response independently determines asymmetry.     

Proanthocyanidins and Flavan-3-ols in the Prevention and Treatment of Periodontitis—Immunomodulatory Effects,Animal and Clinical Studies

This paper continues the systematic review on proanthocyanidins and flavan-3-ols in the prevention and treatment of periodontal disease and covers the immunomodulatory effects, and animal- and clinical studies, while the other part discussed the direct antibacterial properties. Inflammation as a major response of the periodontal tissues attacked by pathogenic microbes can significantly exacerbate the condition. However, the bidirectional activity of phytochemicals that simultaneously inhibit bacterial proliferation and proinflammatory signaling can provide a substantial alleviation of both cause and symptoms. The modulatory effects on various aspects of inflammatory and overall immune response are covered, including confirmed and postulated mechanisms of action, structure activity relationships and molecular targets. Further, the clinical relevance of flavan-3-ols and available outcomes from clinical studies is analyzed and discussed. Among the numerous natural sources of flavan-3-ols and proanthocyanidins the most promising are, similarly to antibacterial properties, constituents of various foods, such as fruits of Vaccinium species, tea leaves, grape seeds, and tannin-rich medicinal herbs. Despite a vast amount of in vitro and cell-based evidence of immunomodulatory there are still only a few animal and clinical studies. Most of the reports, regardless of the used model, indicated the efficiency of these phytochemicals from cranberries and other Vaccinium species and tea extracts (green or black). Other sources such as grape seeds and traditional medicinal plants, were seldom. In conclusion, the potential of flavan-3-ols and their derivatives in prevention and alleviation of periodontal disease is remarkable but clinical evidence is urgently needed for issuing credible dietary recommendation and complementary treatments.