Leukotriene C4 contents,synthase and catabolic activity in human meningiomas

Abstract

Leukotriene has been proposed as a factor of tumour induced brain oedema. Independently of its size, meningioma occasionally shows various extents of peritumoural oedema. We investigated LTC₄ tissue contentsLTC₄ catabolic and synthetic activity in 12 human meningiomas and their correlation with peritumoural oedema was studied. LTC₄ contents were varied from 0.01 to 8.21 pg/mg tissue. When LTA4/ an unstable expoxide intermediate was incubated with tumour homogenate, LTC₄ was rapidly synthesized. However; LTC₄ levels generated by incubating LTA4 with each homogenate were much different in each case. Degradation of LTC₄ to LTD4, LTE4, and other polar materials was also rapid by incubation with tumour homogenates. Approximately 70% of added UC₄ was transformed to LTD4/ LTE4 nor 6-trans LTB4 diastereoisomers during 30 min incubation at 37 °C. The results suggested that there were significant LTC₄ tissue contents and LTC₄ synthetic and catabolic activity in meningiomas. Oedema index ranged from 1.0 (no peritumoural oedema) to 67.5. No significant correlationi, however', was observed not only between the LTC₄ tissue contents and LTC₄ synthetic or catabolic activities but also between each of these three parameters and peritumoural oedema. Thus, these results do not support a significant correlation of sulfidopeptide LTs with oedema formation in meningioma patients. Since leukotrienes are extremely unstable compounds, LTC₄ tissue contents should be carefully discussed along with a consideration of rapid LTC₄ synthesis and catabolism. Further role of leukotrienes in meningioma tissue should be studied.     

Impact of next generation sequencing on diagnostics in a genetic skin disease clinic

Individuals with inherited skin diseases often pose one of the most difficult diagnostic challenges in dermatology. The hunt for the underlying molecular pathology may involve candidate gene screening or linkage analysis, which is usually determined by the initial history, the physical findings and laboratory tests. Recent technical advances in DNA sequencing, however, are shifting the diagnostic paradigm. Notably, next‐generation sequencing allows a more comprehensive approach to diagnosing inherited diseases, with potential savings of both time and money. In the setting of a paediatric dermatology genetics clinic in Kuwait, we therefore performed whole‐exome sequencing on seven individuals without a priori detailed knowledge of the patients’ disorders: from these sequencing data, we diagnosed X‐linked hypohidrotic ectodermal dysplasia (two cases), acrodermatitis enteropathica, recessive erythropoietic protoporphyria (two siblings) and localized recessive dystrophic epidermolysis bullosa (two siblings). All these groups of disorders are clinically and genetically heterogeneous, but the sequencing data proved inherently useful in improving patient care and avoiding unnecessary investigations. Our observations highlight the value of whole‐exome sequencing, in combination with robust bioinformatics analysis, in determining the precise molecular pathology and clinical diagnosis in patients with genetic skin disorders, notably at an early stage in the clinical evaluation of these often complex disorders and thereby support a new paradigm for future diagnostics.     

Influence of duration of phosphoric acid pre‐etching on bond durability of universal adhesives and surface free‐energy characteristics of enamel

The purpose of this study was to evaluate the influence of duration of phosphoric acid pre‐etching on the bond durability of universal adhesives and the surface free‐energy characteristics of enamel. Three universal adhesives and extracted human molars were used. Two no‐pre‐etching groups were prepared: ground enamel; and enamel after ultrasonic cleaning with distilled water for 30 s to remove the smear layer. Four pre‐etching groups were prepared: enamel pre‐etched with phosphoric acid for 3, 5, 10, and 15 s. Shear bond strength (SBS) values of universal adhesive after no thermal cycling and after 30,000 or 60,000 thermal cycles, and surface free‐energy values of enamel surfaces, calculated from contact angle measurements, were determined. The specimens that had been pre‐etched showed significantly higher SBS and surface free‐energy values than the specimens that had not been pre‐etched, regardless of the aging condition and adhesive type. The SBS and surface free‐energy values did not increase for pre‐etching times of longer than 3 s. There were no significant differences in SBS values and surface free‐energy characteristics between the specimens with and without a smear layer. The results of this study suggest that phosphoric acid pre‐etching of enamel improves the bond durability of universal adhesives and the surface free‐energy characteristics of enamel, but these bonding properties do not increase for phosphoric acid pre‐etching times of longer than 3 s.     

Editorial comments on patch size and mechanics in the surgery for post-infarction ventricular septal perforation

Finite element analysis method (FEM) provides suitable methodology to analyze a target with complex shape such as VSP patch. In this study, by employing the FEM, Ito and colleagues showed the importance of using a large patch to eliminate the dead space between the patch and LV endocardium. Intuitionally many surgeons believed the same way, but it now has been proven mathematically. Although the FEM model has some limitation in part due to too much simplified model, I believe that the study provides useful information to the patch mechanics for VSP closure and that it will help improving the outcome of surgical treatment of VSP.     

Clinical significance of changes in Torque teno virus DNA titer after chemotherapy in patients with primary lung cancer

Background

Several studies have reported that viral infections are related to lung cancer. We previously reported the involvement of Torque teno virus (TTV) in patients with lung cancer and idiopathic pulmonary fibrosis. However, the role of TTV in lung cancer growth, and its influence on changes in TTV DNA titers due to idiopathic pulmonary fibrosis (IPF) in lung cancer patients are poorly understood.

New therapeutic approach for impaired arteriogenesis in diabetic mouse hindlimb ischemia.

BACKGROUND: The combined treatment of sustained-release basic fibroblast growth factor (Sr-bFGF) and a 5-hydroxytryptamine(2A) blocker, sarpogrelate, was evaluated to see whether it reversed the impaired collateral circulation in diabetic (DM) mouse hindlimb ischemia. METHOD AND RESULTS: Diabetic and normal mice with ischemic hindlimb were randomly assigned to 1 of 5 experimental groups (no treatment, sarpogrelate 50 mg . kg(-1) . day(-1), 20 microg or 50 microg Sr-bFGF and a combined treatment of 20 microg Sr-bFGF and sarpogrelate), and treated for 4 weeks. Tissue blood perfusion (TBP), vascular density (angiogenesis) and the number of mature vessels (arteriogenesis) were checked by the use of standard methods. Although angiogenesis was comparable (161+/-14 vs 154+/-12 vessels/mm(2)), the laser Doppler perfusion image index (LDPII) (0.43+/-0.11 (SD) vs 0.63+/-0.08, p<0.05) and arteriogenesis (8+/-3 vs 12+/-4 vessels/mm(2), p<0.05) were significantly lower in DM mice than those in normal mice. The dose of Sr-bFGF for the sufficient number of mature vessels (>or=45 vessels/mm(2)) and LDPII (>or=0.9) was 20 microg for the normal mice, and 50 microg for the DM mice, which was reduced with the aid of sarpogrelate. Conclusions A combined therapy of Sr-bFGF and sarpogrelate is effective for neovascularization to reverse the impaired arteriogenesis and TBP in DM mice.     

Effect of leukotriene C4D4 antagonist on colonic damage induced by intracolonic administration of trinitrobenzene sulfonic acid in rats

We examined the effects of eicosanoid antagonists on colonic damage induced by trinitrobenzene sulfonic acid (TNB) in a rat inflammatory bowel model. TNB (30 mg) dissolved in 0.25 ml of 50% ethanol, was given intrarectally. The appropriate doses of ONO-1078 (a leukotriene C₄D₄ antagonist), ONO-4057 (a leukotriene B₄ antagonist), and OKY-046 (a thromboxane A₂ synthetase inhibitor) were given to obtain the same blood level, either 4 h before (pre-treatment model) or 24 h after (the post-treatment model) the administration of TNB (n=8 in all groups). Drugs were given once daily for 6 days through a gastric feeding tube. Autopsy was performed on the 7th day. Colonie damage was assessed in terms of colonie damage scores, and myeloperoxidase (MPO) activity and eicosanoid concentrations in colonie tissues were measured. Compared with the group given TNB alone, the colonie damage score was reduced to 10% in the pre-treatment model with ONO-1078, but the score was not reduced in other groups, MPO activity was not changed in any group. The concentration of leukotriene C₄ was reduced with ONO-1078 treatment, in both pre- and post-treatment models. These results demonstrated that a leukotriene C₄D₄ antagonist reduced colonie inflammation; however, its anti-inflammatory effect was limited in this colitis model.     

Effect of H. pylori on COX-2 expression in gastric remnant after distal gastrectomy

BACKGROUND/AIMS: Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy. METHODOLOGY: The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically. RESULTS: Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p<0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p<0.001). CONCLUSIONS: H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy.