Advantages of histamine H4 receptor antagonist usage with H1 receptor antagonist for the treatment of murine allergic contact dermatitis

Histamine facilitates development of eczematous lesions in chronic allergic contact dermatitis. In addition to the well-known corticosteroid treatments, H1 receptor (H1R) antagonists also have been used. This study observed effects of histamine H4 receptor (H4R) antagonist usage with H1R antagonist in a murine chronic allergic contact dermatitis model, developed by repeated percutaneous challenge to the dorsal skin with 2,4,6-trinitro-1-chlorobenzene (TNCB). The H1R antagonist olopatadine hydrochloride and/or the H4R antagonist JNJ7777120 was then administered. Combination therapy was more effective than H1R antagonist monotherapy. Serum IgE and levels of interleukin (IL)-4, IL-5 and IL-6 (Th2 cytokines) in eczematous lesions decreased with combined therapy. Combined therapy with H1R and H4R antagonists counteracts the disadvantages of each as monotherapeutic agents and potentially represents a new strategy for the treatment of chronic allergic contact dermatitis.     

MiR-23a regulates TGF-β-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells

Transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) has been shown to be related to the pathogenesis of various diseases including lung cancer. Recently, microRNAs (miRNA) have been recognized as a new class of genes involved in human tumorigenesis. MiR-23a/24/27a is a miRNA cluster located in chromosome 19p13.12, which can function as an oncogene in several human cancers. In this study, we analyzed miR-23a/24/27a expression in 10 non-small cell cancer (NSCLC) cell lines by real-time PCR analysis. Correlation between expression of these miRNAs and TGF-β/Smad signaling was evaluated. We found that miR-23a could be regulated by TGF-β1 in a Smad-dependent manner in A549 lung adenocarcinoma cells showing the EMT phenomenon. Knockdown of miR-23a partially restored E-cadherin expression under conditions of TGF-β1 stimulation. In contrast, overexpression of miR-23a could suppress E-cadherin expression and stimulate EMT. Furthermore, A549 cells with overexpressed miR-23a were more resistant to gefitinib compared to the parental cells. These findings suggest that miR-23a regulates TGF-β-induced EMT by targeting E-cadherin in lung cancer cells and may be useful as a new therapeutic target in NSCLC.     

Gas Volume Analysis and Postoperative Bowel Functional Disorders in Patients Who Received Anterior Resection for Rectal Cancer

PURPOSE: Colon gas analysis using abdominal radiography has been reported as a reliable method for assessing functional bowel disorders. The aim of this study was to clarify the relevance of colon gas distribution in postoperative disorders such as constipation and feelings of incomplete evacuation following rectal cancer operation. METHODS: Colon gas volume score was calculated using plain abdominal radiographs and evaluated in 50 patients who had received low anterior resections. Twenty-one constipated patients who required laxatives and 29 patients who did not were compared in terms of colon gas distribution. In addition, 32 patients with postoperative feelings of incomplete evacuation and 18 patients without such feelings were assessed in similar fashion. RESULTS: Left colon gas scores in patients who required laxatives were significantly higher (2.82 ± 3.23 percent) than in nonusers (1.21 ± 0.96 percent; P < 0.01). Patients with feelings of incomplete evacuation displayed significantly higher left side colon gas scores (2.51 ± 2.66 percent) than those without such feelings (0.77 ± 0.81 percent; P < 0.0001). CONCLUSION: Patients with postoperative functional bowel disorders such as constipation or feelings of incomplete evacuation may experience relatively high volumes of gas in the left colon.     

Successful Treatment with Afatinib after Osimertinib-induced Interstitial Lung Disease in a Patient with EGFR-mutant Non-small-cell Lung Cancer

Osimertinib is the standard treatment for epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer. However, drug-induced interstitial lung disease (ILD) is recognized as a serious adverse event associated with EGFR-tyrosine kinase inhibitors (TKIs). We herein report a 78-year-old woman with stage IV lung adenocarcinoma harboring an EGFR L858R mutation on exon 21 who received rechallenge treatment with afatinib after osimertinib-induced ILD with an organizing pneumonia pattern. This is the first report of successful rechallenge with afatinib after osimertinib-induced ILD. Treatment with other EGFR-TKIs after osimertinib-induced ILD may be an option for subsequent therapy.     

Rheological properties of erythrocytes in recombinant human erythropoietin-administered normal rat

Recombinant human erythropoietin [rhEPO (180 iu/micrograms); 1 or 10 micrograms polypeptide equivalent/kg] was intravenously administered daily to 6-week-old normal rats for 1 week. Rheologically, (1) blood viscosity at shear rate of 40-380 s-1 increased in a manner entirely dependent upon the haematocrit, (2) no change in erythrocyte deformability was detected by high shear rheoscopy, and (3) the velocity of rouleau formation in autologous plasma (at 7.5 s-1) decreased. Haematologically, rhEPO administration induced considerable polycythaemia with reticulocytosis in a dose-dependent manner, accompanying increased cell volume and decreased intracellular haemoglobin concentration, thus the density distribution of erythrocytes shifted towards low specific gravity. Plasma viscosity and plasma protein composition were unaffected by rhEPO-administration. In erythrocyte metabolism, no drastic alteration in the level of 2.3-DPG or ATP was detected.     

Microscopic polyangiitis accompanying interstitial pneumonia with aluminum lung]

A 67-year-old man who had worked as an aluminum grinder had been given a diagnosis of pneumoconiosis. Ten years later, he was admitted with fever, dyspnea on exertion, and numbness. Chest roentgenograms showed linear-reticular shadows in both lower lung fields. ELISA-based tests were positive for perinuclear anti-neutrophil cytoplasmic antibody (P-ANCA). Renal biopsy specimens disclosed crescentic glomerulonephritis and angiitis of small arteries. Our diagnosis was microscopic polyangiitis accompanying interstitial pneumonia with aluminum lung. The results of high-energy dispersion X-ray microanalysis indicated that the patient's lungs contained aluminum. His general condition improved with the administration of corticosteroid and immunosuppressive agents, and his chief symptoms disappeared.