Increased mucosal inflammatory cytokines in children with Helicobacter pylori-associated gastritis

The concentrations of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1-β in tissue homogenates of gastric mucosal biopsy specimens, and in gastric juice samples from Helicobacter pylori-positive and -negative children, were determined. The study population comprised 30 children with recurrent abdominal pain attending upper gastrointestinal endoscopy. Of these patients 18 were infected with H. pylori. Cytokine concentrations in gastric biopsy homogenate supernatants and in gastric juice were measured by enzyme-linked immunosorbent assay (ELISA). TNF-α levels in gastric juice and in gastric biopsy homogenate supernatants in patients with H. pylori-positive gastritis were found to be significantly higher than those in children without H. pylori infection. IL-6 levels were also higher in H. pylori -infected subjects, but the difference in IL-6 concentrations measured in gastric juice and biopsy homogenate supernatants did not reach statistical significance. IL-1-β concentrations in both specimens showed no significant difference between the two groups of children. It was suggested that increased levels of inflammatory cytokines, especially TNF-α and IL-6 generated locally within the gastric mucosa might be implicated in the pathogenesis of H. pylori-associated gastritis in childhood.     

Occupational Rhinosinusitis and Upper Airway Disease: The World Trade Center Experience

The World Trade Center disaster and its recovery work involved a range of hazardous occupational exposures that have not been fully characterized but that can be reasonably assumed to have the potential to cause mucosal inflammation, preferentially (but not exclusively) in the upper airway. A high prevalence of rhinosinusitis and upper airway disease (UAD) symptoms was reported by several early surveys. Clinical studies demonstrated objective, clinically significant, and persistent chronic perennial rhinosinusitis and UAD—with or without seasonal exacerbation—in a large proportion of patients. Demonstration of an association between UAD and available exposure indicators has been limited. Atopy seemed to be associated with increased UAD symptom severity and to be a risk factor for upper, but not lower, airway disease. World Trade Center-related UAD is considered an irritant-induced disease but not, in many cases, of acute onset. No data thus far suggest an increased upper airway cancer incidence.     

Red cell membrane stiffness in iron deficiency

The purpose of this study was to characterize red blood cell (RBC) deformability by iron deficiency. We measured RBC deformability to ektacytometry, a laser diffraction method for determining the elongation of suspended red cells subjected to shear stress. Isotonic deformability of RBC from iron-deficient human subjects was consistently and significantly lower than that of normal controls. In groups of rats with severe and moderate dietary iron deficiency, RBC deformability was also reduced in proportion to the severity of iron deficiency. At any given shear stress value, deformability of resealed RBC ghosts from both iron-deficient humans and rats was lower than that of control ghosts. However, increase of applied shear stress resulted in progressive increase in ghost deformation, indicating that ghost deformability was primarily limited by membrane stiffness rather than by reduced surface area-to-volume ratio. This was consistent with the finding that iron-deficient cells had a normal membrane surface area. In addition, the reduced mean corpuscular hemoglobin concentration (MCHC) and buoyant density of the iron-deficient rat cells indicated that a high hemoglobin concentration was not responsible for impaired whole cell deformability. Biochemical studies of rat RBC showed increased membrane lipid and protein crosslinking and reduced intracellular cation content, findings that are consistent with in vivo peroxidative damage. RBC from iron-deficient rats incubated in vitro with hydrogen peroxide showed increased generation of malonyldialdehyde, an end-product of lipid peroxidation, compared to control RBC. Taken together, these findings suggest that peroxidation could contribute in part to increased membrane stiffness in iron- deficient RBC. This reduced membrane deformability may in turn contribute to impaired red cell survival in iron deficiency.     

A novel phospholipid in irreversibly sickled cells: evidence for in vivo peroxidative membrane damage in sickle cell disease

In individuals with sickle cell disease, a variable number of irreversibly sickled cells (ISC) is present that may contribute to the pathophysiology of sickle cell anemia. The present study was undertaken to determine the possible role of membrane lipid peroxidation in the genesis of ISC. After 24 hr of simple aerobic incubation, sickle cells accumulated 2-3 times more malonyldialdehyde (MDA), an end product of lipid peroxidation, than normal cells. To assess the possibility of peroxidative damage in ISC in vivo, ISC were separated from sickle blood using Stractan density gradients. Lipid extracts of the untreated ISC-enriched fraction of sickle blood showed significant fluorescence and contained a novel phospholipid:MDA adduct that was not seen in control cells. Taken together, these observations suggest that ISC have previously undergone lipid peroxidative damage and the accumulation of MDA in vivo.