Therapeutic effects of 10 mg/day rabeprazole administration on reflux esophagitis was not influenced by the CYP2C19 polymorphism

BACKGROUND: The acid suppressive effects of omeprazole (OPZ) and lansoprazole (LPZ) are influenced by the CYP2C19 polymorphism. On the other hand, some investigators have reported that acid suppressive effect of rabeprazole (RPZ) was not significantly affected by CYP2C19. The present study was designed to investigate whether the CYP2C19 genotype is related to the healing of reflux esophagitis (RE) in treatment with RPZ 10 mg. METHODS: One hundred and three Japanese patients with RE were treated with daily oral administration of 10 mg RPZ. At 4 and 8 weeks after the start of treatment, healing of RE was evaluated endoscopically. The CYP2C19 genotype was investigated before the treatment. RESULTS: At 4 weeks after the start of treatment, the healing rates for homo-extensive metabolizer, hetero-extensive metabolizer, and poor metabolizer patients were 83.3% (15/18), 77.3% (17/22), and 88.9% (8/9) [corrected] respectively, and at 8 weeks after the start of treatment, the healing rates were 86.1% (31/36), 92.0% (46/50), and 82.4% (14/17), respectively. There were no significant differences in the healing rate of RE among the three genotypes at either 4 or 8 weeks after the start of treatment. CONCLUSIONS: The therapeutic effects of 10 mg/day RPZ administration on RE may be uninfluenced by the CYP2C19 polymorphism.     

Insulin resistance and low sympathetic nerve activity in the Tsumura Suzuki obese diabetic mouse: a new model of spontaneous type 2 diabetes mellitus and obesity

Tsumura Suzuki obese diabetic (TSOD) mouse is a new model of type 2 diabetes mellitus and obesity. The TSOD mice had hypoadiponectinemia. To assess the glucose utilization and insulin sensitivity, we examined the effect of insulin (1U/kg) on peripheral tissue glucose uptake in vivo in the TSOD and Tsumura Suzuki nonobese mouse using 2-deoxy-d-[(3)H]glucose. The rates constant of glucose uptake in basal condition without insulin were similar in the peripheral tissues in both strains. Insulin-stimulated glucose uptake by skeletal muscles and adipose tissues in vivo was diminished in the TSOD mice. In addition, we assessed norepinephrine turnover in brown adipose tissue and adrenal epinephrine (E) content and E turnover because disturbances in the sympathetic activities relate to many features in obese and diabetic syndrome. In these mice, the rate of norepinephrine turnover was decreased, and adrenal E content was at most one half of the Tsumura Suzuki nonobese mice and E turnover had extremely low rates. The TSOD mice showed hypercorticosteronemia. These results suggest that TSOD mice have insulin resistance and both low sympathetic nervous activities and low adrenomedullary activity, and have high adrenocortical activity, which are significant features of the TSOD mouse.     

Immunoselection by natural killer cells of PIGA mutant cells missing stress-inducible ULBP

The mechanism by which paroxysmal nocturnal hemoglobinuria (PNH) clones expand is unknown. PNH clones harbor PIGA mutations and do not synthesize glycosylphosphatidylinositol (GPI), resulting in deficiency of GPI-linked membrane proteins. GPI-deficient blood cells often expand in patients with aplastic anemia who sustain immune-mediated marrow injury putatively induced by cytotoxic cells, hence suggesting that the injury allows PNH clones to expand selectively. We previously reported that leukemic K562 cells preferentially survived natural killer (NK) cell-mediated cytotoxicity in vitro when they acquired PIGA mutations. We herein show that the survival is ascribable to the deficiency of stress-inducible GPI-linked membrane proteins ULBP1 and ULBP2, which activate NK and T cells. The ULBPs were detected on GPI-expressing but not on GPI-deficient K562 cells. In the presence of antibodies to either the ULBPs or their receptor NKG2D on NK cells, GPI-expressing cells were as less NK sensitive as GPI-deficient cells. NK cells therefore spared ULBP-deficient cells in vitro. The ULBPs were identified only on GPI-expressing blood cells of a proportion of patients with PNH but none of healthy individuals. Granulocytes of the patients partly underwent killing by autologous cytotoxic cells, implying ULBP-associated blood cell injury. In this setting, the lack of ULBPs may allow immunoselection of PNH clones.     

A case of primary Sjögren's syndrome complicated by chronic progressive myositis

The patient was a 64-year-old woman with a nearly 20-year history of sicca symptoms, having been given a diagnosis of primary Sj?gren's syndrome. Three years previously, she experienced difficulty in walking up a slope and had leg malaise, which insidiously progressed to an inability to go up and down stairs. This disability brought her to our hospital, where her muscle strength was examined by manual muscle testing, and she was found to have reduced muscle strength in proximal muscles like the thigh muscles and the neck flexor muscles. Blood studies revealed elevated ESR, increased serum IgG, mildly increased myogenic enzymes, and positive results for anti-SS-A and -SS-B antibodies. MRI scans disclosed extensive muscle atrophy as well as fatty degeneration in the thigh. A biopsy of the quadriceps femoris muscle provided a diagnosis of myositis based on the finding of muscle fibers of unequal size, nuclear centralization, and inflammatory cell infiltration into muscle fibers. CD4-positive lymphocytes were the predominant inflammatory cells. We diagnosed the case as myositis in primary Sj?gren's syndrome based on the clinical course and laboratory findings. She recovered well with steroid medication. It is noteworthy that myositis associated with primary Sj?gren's syndrome presents with mild symptoms and unremarkable laboratory data but may run a chronic progressive course.     

Morphology of the lingual papillae in the raccoon dog and fox

The dorsal lingual surfaces of the raccoon dogs (Nyctereutes procyonoides) and fox (Vulpes vulpes japonica) were examined by scanning electron microscopical (SEM) observations. The distribution and type of the lingual papillae found in the raccoon dog were similar to those in the fox. Filiform, fungiform, foliate and vallate papillae were observed. The filiform papillae were distributed over the entire dosal surface of the tongue. Each filiform papilla on the apical surface of the tongue had several pointed processes. The filiform papillae of the lingual body consisted of a main papilla and some secondary papillae. The fungiform papillae were present rounded bodies, and more densely distributed on the lingual apex. The foliate papillae were seen on the dorsolateral aspect of the tongue. The vallate papillae were located on both sides of the posterior end of the lingual body. Each papilla was surrounded by groove and crescent pad. On the periphery of the papillae, large conical papillae were observed.     

Antithrombin III for portal vein thrombosis in patients with liver disease: A randomized,double‐blind,controlled trial

Aim

Portal vein thrombosis (PVT) is one of the most critical disorders in liver disease patients. These patients have the imbalance of coagulation and coagulation inhibition resulting from decreased levels of coagulation inhibitory factors, such as protein C, protein S, and antithrombin III (AT‐III). We designed this randomized, double‐blind, placebo‐controlled trial comparing the safety and efficacy of AT‐III for PVT in liver disease patients with those who received no treatment.

Methods

Eligible patients were diagnosed with the association of thrombus, without tumor thrombus, and thrombus in more than 50% of the cross‐sectional lumen of the portal vein. Patients with 70% or less serum level of AT‐III were included. The study drug was given up to three times in a 5‐day consecutive infusion interval if the thrombus decreased in size. Efficacy was evaluated by contrast enhanced computed tomography using a five‐grade scale (complete response, partial response, slight response, no response, and progression). From October 2014 through to March 2016, 36 patients were randomly assigned to the AT‐III group and 37 patients to the placebo group.

Results

The proportion of patients with complete response or partial response of PVT was significantly higher in the AT‐III group (55.6%; 20/36 patients; 95% confidence interval, 38.1–72.1) than in the placebo group (19.4%; 7/36 patients, 95% confidence interval, 8.2–36.0) (P = 0.003). The overall incidence of adverse events and adverse drug reactions did not differ significantly between the two groups.

Conclusion

Antithrombin III is one of the essential therapies for patients with PVT in cases with lower concentration levels of AT‐III.