Comparative actions of biologic and synthetic leukotrienes on isolated human bronchus and rat mast cells

The effects of biologically prepared leukotriene C4 (LTCb) and leukotriene D4 (LTDb), obtained from rat monocytes stimulated with the calcium ionophore A23187, were compared with those of chemically synthetized leukotrienes (LTCs and LTDs) using two in vitro systems. All four leukotriene preparations (10(-10) to 6 X 10(-6) M) showed equal activity upon human bronchi, inducing slow, sustained contractions. LTCb alone (10(-7) to 6.9 X 10(-7) M) elicited histamine release and enhanced compound 48/80-induced release in a dose-dependent manner from rat mast cells. In contrast, LTDb alone was without effect but inhibited release caused by 48/80. FPL 55712 failed to block the LTCb and LTDb effects on the release process. The synthetic leukotrienes neither caused histamine release nor modulated 48/80-induced release from rat mast cells. We conclude that biologic and synthetic leukotrienes exhibit comparable contractile activity on isolated human bronchi but only biologic preparations modulate histamine release by previously unappreciated substances that isolate with the biologic leukotrienes.     

Involvement of the RE V3 gene in the methylated base-excision repair system. Co-operation of two DNA polymerases, δ and Rev3p, in the repair of MMS-induced lesions in the DNA of Saccharomyces cerevisiae

The ability of four yeast DNA polymerase mutant strains to carry out the repair of DNA treated with MMS was studied. Mutation in DNA polymerase Rev3, as well as the already known mutation in the catalytic subunit of DNA polymerase δ, were both found to lead to the accumulation of single-strand breaks, which indicates defective repair. A double-mutant strain carrying mutations in DNA polymerase δ and a deletion in the REV3 gene had a complete repair defect, both at permissive (23°C) and restrictive (38°C) temperatures, which was not observed in other pairwise combinations of tested polymerase mutants. Other polymerases are not involved in the repair of exogenous DNA methylation damage, since neither mutation in the DNA polymerase ɛ, nor deletion in the DNA polymerase IV (β₇₀) gene, caused defective repair. The data obtained suggest that DNA polymerases δ and Rev3p are both necessary to perform repair synthesis in the base-excision repair of methylation damage. The results are discussed in the light of current concepts on the role of DNA polymerase Rev3 in mutagenesis. Received: 18 November / 10 December 1996     

The expression of B7-H1 on keratinocytes in chronic inflammatory mucocutaneous disease and its regulatory role

PD-1 and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, have been identified recently as CD28-B7 family molecules that are implicated in immune regulation. Lichen planus (LP) is a T cell-mediated chronic inflammatory mucocutaneous disease. We investigated the expression and function of PD-1 and its two ligands in LP. Immunohistochemical examination revealed the abundant expression of PD-1 and B7-H1 in infiltrating T cells and macrophages, and lower-level expression of B7-DC on macrophages in the subepithelium. Interestingly, substantial expression of B7-H1 on keratinocytes (KCs) was found close to the numerous T cell infiltrates in the subepithelium. Unstimulated cultured KCs expressed both B7-H1 and B7-DC, and their expression was upregulated by proinflammatory cytokines, particularly IFN-gamma. The T-cell proliferative responses and IFN-gamma production that were induced by IFN-gamma-treated KCs were augmented preferentially by anti-B7-H1 mAb, but not by anti-B7-DC mAb. These results indicate the regulatory role of B7-H1 on KCs in the interactions with T cells. Our results suggest that the induction of B7-H1 on KCs may play an important role in tolerance induction in the inflamed oral mucosa and skin.     

Running-related injury prevention through barefoot adaptations

A number of reports indicate an extremely low running-related injury frequency in barefoot populations in contrast to reports about shod populations. It is hypothesized that the adaptations which produce shock absorption, an inherent consequence of barefoot activity and a mechanism responsible for the low injury frequency in unshod populations, are related to deflection of the medial longitudinal arch of the foot on loading. It is also hypothesized that the known inability of this arch of the shod foot to deflect without failure (foot rigidity) is responsible for the high injury frequency in shod populations. To evaluate these hypotheses, 17 recreational runners were analyzed to study the adaptive pattern of the medial longitudinal arch of the foot due to increased barefoot weight-bearing activity. Changes occurred in the medial longitudinal arch which allowed deflection of this arch on loading which substantiated the hypotheses. Other evidence suggests that sensory feedback largely from the glabrous epithelium of the foot is the element of barefoot activity which induced these adaptations. The sensory insulation inherent in the modern running shoe appears responsible for the high injury frequency associated with running. The injuries are considered "pseudo-neuropathic" in nature.     

Care-Seeking Behavior for Newborns in Rural Zambia

Maternal and Child Health Journal - Mothers in resource-limited areas face barriers in initiating care for ill newborns, leading to delays that may contribute to newborn mortality. This qualitative...     

Primary Prevention of Food Allergy—Environmental Protection beyond Diet

A food allergy is a potentially life-threatening disease with a genetic and environmental background. As its prevalence has increased significantly in recent years, the need for its effective prevention has been emphasized. The role of diet modifications and nutrients in food allergy reduction has been extensively studied. Much less is known about the role of other environmental factors, which can influence the incidence of this disease. Changes in neonates gut microbiome by delivery mode, animal contact, inhalant allergens, oral and then cutaneous allergen exposure, air pollution, smoking, infections and vaccinations can be the potential modifiers of food allergy development. There is some data about their role as the risk or preventive factors, but yet the results are not entirely consistent. In this paper we present the current knowledge about their possible role in primary prevention of food allergies. We discuss the mechanisms of action, difficulties in designing accurate studies about food allergy and the potential biases in interpreting the connection between environmental factors and food allergy prevention. A better understanding of the role of environmental factors in food allergies development may help in implementing practical solutions for food allergy primary prevention in the future.     

Esofaguectomía «tubeless»: menos es más

The esophageal cancer surgery is a complex procedure with elevated rates of both morbidity and mortality, which is why, in order to achieve adequate results, it should be performed in high volume centers, where complete multidisciplinary support is available and recent clinical guidelines are applied. We describe the initial experience and the technique of “tubeless” esophagectomy where esophageal resection and mediastinal lymphadenectomy are performed and no drains nor tubes of any kind are placed, with the aim to decrease the level of surgical aggression, enhance the postoperative comfort and accelerate the patient?s recovery.