Red ginseng prevents doxorubicin-induced cardiomyopathy by inhibiting cell death via activating the Nrf2 pathway.

BACKGROUND: Doxorubicin (DXR) is an effective chemotherapeutic agent. DOX-induced cardiomyopathy (DICM), a major limitation of DXR, is a complication with limited treatment options. We previously reported that Red Ginseng (steamed and dried the root of Panax Ginseng cultivated for over six years; RGin) is beneficial for the treatment of DICM. However, the mechanism underlying the action of RGin remains unclear. In this study, we investigated the mechanism of action underlying the efficacy of RGin in the treatment of DICM. METHODS: Four-week-old DBA/2 mice were divided into: vehicle, DXR, RGin, and DXR + RGin (n = 10/group). Mice were treated with DXR (4 mg/kg, once a week, accumulated 20 mg/kg, i.p.) or RGin (0.5 g/kg, three times a week, i.p.). To evaluate efficacy, the survival rate and left ventricular ejection fraction (LVEF) were measured as a measure of cardiac function, and cardiomyocytes were subjected to Masson trichrome staining. To investigate the mechanism of action, western blotting was performed to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, transferrin receptor (TfR), and other related proteins. Data were analyzed using the Easy R software. Between-group comparisons were performed using one-way analysis of variance and analyzed using a post-hoc Tukey test. Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test. P < 0.05 was considered statistically significant in all analyses. RESULTS: RGin treatment prolongs survival and protects against reduced LVEF. In the DXR group, Nrf2 was not activated and cell death was accelerated. Furthermore, there was an increase in the TfR levels, suggesting abnormal iron metabolism. However, the DXR + RGin group showed activation of the Nrf2 pathway and suppression of myocardial cell death. Furthermore, there was no increase in TfR expression, suggesting that there were no abnormalities in iron metabolism. Therefore, the mechanism of action of RGin in DICM involves an increase in antioxidant activity and inhibition of cell death through activation of the Nrf2 pathway. CONCLUSION: RGin is a useful therapeutic candidate for DICM. Its efficacy is supported by the activation of the Nrf2 pathway, which enhances antioxidant activity and inhibits cell death.

A case of pyloric gland adenoma with high-grade dysplasia in the duodenum arising from heterotopic gastric mucosa observed over 5 years.

Pyloric gland adenoma (PGA) in the duodenum is a rare gastric phenotype duodenal neoplasm. Although heterotopic gastric mucosa in the duodenum has been recognized as a benign lesion, it is a potential precursor of PGA and gastric phenotype adenocarcinoma. Herein, we present a case follow-up of endoscopic and histological changes in the PGA in the duodenum from low-grade to high-grade dysplasia. PGA was considered to arise from the heterotopic gastric mucosa, because the heterotopic gastric mucosa was observed in the initial examination. It is difficult to distinguish heterotopic gastric mucosa from PGAs, both endoscopically and histologically. This increase in size may be useful for their differentiation. Therefore, endoscopists should not underestimate the growth of the heterotopic gastric mucosa compared to that in the previous examination.

[A case of difficult to diagnose duodenal gastrinoma].

A 42-year-old man, after remission of MALT lymphoma of the small intestine, was repeatedly hospitalized because of abdominal pain and severe dehydration caused by frequent vomiting and watery diarrhea. His symptoms would improve quickly every time when he was fasted and inserted a nasogastric tube. We were unable to find abnormalities on endoscopic examination and computed tomography. He was suspected to have gastrinoma because of active bleeding from a duodenal ulcer. High-level serum gastrin, endoscopic ultrasound, somatostatin receptor scintigraphy, and selective arterial calcium injection test were done. He was diagnosed with pancreatic gastrinoma in the pancreatic head by endoscopic ultrasound fine needle aspiration and subsequently underwent pancreatoduodenectomy. Histopathologic findings showed a 3-mm neuroendocrine tumor located in the duodenal submucosal layer. The presence of metastasis was confirmed in one of the peripancreatic lymph nodes. The pancreatic gastrinoma in the pancreatic head that we initially diagnosed was a lymph node metastasis behind the pancreas. Because additional resection was performed on the duodenum, we were able obtain a diagnosis of duodenal gastrinoma.

Evaluating the effect of aromatherapy on a stress marker in healthy subjects.

BACKGROUND/PURPOSE: Chemotherapy is important for cancer treatment, but patients' physical and mental stress may lead to unfavorable pain control, an increase in the risk of relapse, and a reduction in the quality of life (QOL). Recently, aromatherapy has been performed in addition to palliative care in many countries, such as Japan and the United States, but scientific evidence remains insufficient. To investigate the usefulness of aromatherapy as complementary and alternative medicine, we evaluated its influence on the immune and autonomic nervous systems. METHODS: We instructed healthy volunteers to inhale aroma oil at bedtime for 6 weeks, and measured changes in the salivary level of secretory immunoglobulin A (s-IgA). Furthermore, blood was collected in addition to saliva in some healthy volunteers, and the blood level of noradrenaline (NA) was measured to examine its relationship to changes in the salivary s-IgA level. RESULTS: Aromatherapy with lavender and grapefruit oils significantly increased the salivary s-IgA level: lavender oil increased 3.5-fold (p = 0.03), and grapefruit oil increased 2.55-fold (p = 0.04). On lavender oil inhalation, there was a weak, positive correlation between changes in the salivary s-IgA level and those in the blood NA level (R2 = 0.24). CONCLUSION: The results showed that aromatherapy with lavender and grapefruit oils reduced stress by acting on the immune and autonomic nervous systems in healthy volunteers. In the future, its clinical usefulness must be investigated through similar examination in patients in whom the stress level may be high.

ß-mannosyl linkages inhibit CAWS arteritis by negatively regulating dectin-2-dependent signaling in spleen and dendritic cells.

AIMS: CAWS, Candida albicans water-soluble fraction, is an extracellular mannoprotein produced by C. albicans NBRC1385. It is a ligand of dectin-2, the C-type lectin receptor for innate immunity, and has strong potency for induction of vasculitis in DBA/2 mice. The structure of this mannoprotein is known to be modulated by the culture conditions. To clarify the structure required for vasculitis, CAWSs were prepared in the two culture conditions with or without pH control, and biological properties were compared. METHODS: CAWSs prepared by the standard protocol and pH controlled at 7.0 were designated as CAWS and CAWS727, respectively. The antigenicity was detected by the anti-Candida mannan IgG. These chemical structures were assessed by nuclear magnetic resonance analysis and the lectin array system. The in vitro activity of CAWSs was tested by tumor necrosis factor-α (TNF-α) induction using bone marrow-derived dendritic cells and spleen cell cultures. RESULTS: The antigenicity of CAWS727 was similar to CAWS but the nuclear magnetic resonance analysis showed a higher ratio of ß-mannosyl linkages were detected in CAWS727. The lectin array showed relative affinities of CAWS727 to α-mannosyl specific lectins were weaker than those of CAWS. CAWS induced severe vasculitis in DBA/2 mice while CAWS727 did not. CAWS significantly induced TNF-α but CAWS727 did slightly. In addition, CAWS-induced TNF-α production was inhibited by mixing with CAWS727 in a concentration dependent manner. CONCLUSION: The α-mannosyl linkages of Candida mannan is a key molecule for the immunotoxicity. CAWS727, which conatins ß-mannosyl linkages, competitively bound to lectin receptors, and resulted in reductions in the inflammatory response.

[Successful treatment of duodenal Crohn disease with infliximab: report of 3 cases].

We present 3 patients with Crohn disease (CD) of the duodenum with progressive symptoms. A 31-year-old man with Crohn ileocolitis presented epigastralgia. A 32-year-old man with Crohn ileocolitis presented upper GI bleeding. In both patients, endoscopy revealed duodenal stenosis. A 33-year-old man was given a diagnosis of CD by gastroduodenal endoscopy. They received an infliximab infusion and had symptomatic relief and macroscopic healings without any adverse effects. Several treatments for upper GI lesions of the CD patients have been tried, but there is no high-quality level evidence-based data to guide the medical management of gastroduodenal CD. Our experience with 3 patients suggests that infliximab is a safe and effective treatment for duodenal CD and it may be appropriate for early use to avoid surgery or balloon dilatation.

Proliferation of immature plasma cells in pouchitis mucosa in patients with ulcerative colitis.

BACKGROUND: Pouchitis is the most common complication of restorative proctocolectomy in patients with ulcerative colitis (UC). The etiology of pouchitis is not known. We have previously reported the specific and significant proliferation of immature plasma lineage cells in the ulcer bases and inflamed mucosa of UC. In the present study we report the results of a phenotypic study of ileal pouch mucosa. METHODS: Biopsy samples were taken from the ileal pouch of 22 patients with UC (12 with pouchitis, 10 with a normal pouch) and 5 patients with familial adenomatous polyposis (FAP) (with a normal pouch) who underwent restorative proctocolectomy, and normal ileum of 10 patients with UC yet to undergo pouch surgery. Frozen sections were cut from fixed samples and reacted with various lymphocyte markers and anti-Ki-67 antibodies. Ki-67+ cells, CD19+ cells, and CD138+ cells were significantly increased in the pouchitis mucosa of patients with UC. RESULTS: Immunological double staining revealed significantly increased numbers of CD19+Ki-67+ cells and CD138+Ki-67+ cells in the pouchitis mucosa of patients with UC compared to noninflamed UC pouch, FAP pouch, and normal ileum of UC patients. The number of CD19+CD138+ cells was significantly increased in inflamed pouch mucosa. The increased number of CD19+CD138+ cells we observed represents proliferation of immature plasma cells. Moreover, the increase in labeling for Ki-67 among CD19 cells and CD138 cells suggests proliferative activity of these cells, consistent with their immaturity. CONCLUSIONS: Proliferation of these immature plasma cells suggests the possibility of involvement of UC-derived abnormality in the pathogenesis of pouchitis.

A case of mucosa-associated lymphoid tissue lymphoma forming multiple lymphomatous polyposis in the small intestine.

A 50-year old woman suffering from diabetes had a CT scan that revealed a diffuse thickening of small intestinal wall and swollen paraaortic lymph nodes. An esophagogastroduodenoscopy (EGD) confirmed multiple polypoid lesions in the duodenum and small intestine, and conventional histological testing revealed non-specific inflammatory changes. Further examinations including the immunohistochemical profiles of the biopsied specimens led us to diagnose the lesion as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type, forming multiple lymphomatous polyposis sequentially spreading from duodenal bulb to terminal ileum. According to Lugano's classification, its staging was clinically diagnosed as stage II. Two courses of a standard CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and predonisolone) regimen with rituximab reduced the lesion and the patient had a almost complete response. A 5-year follow-up EGD and histological examinations detected no recurrence of the disease.