Dimethyl Fumarate Ameliorated Cardiorenal Anemia Syndrome and Improved Overall Survival in Dahl/Salt-Sensitive Rats.

Cardiovascular disease, chronic kidney disease, and anemia are known to adversely affect each other. Inflammation is commonly involved in these diseases. Cardiorenal anemia syndrome (CRAS) is the name given to this mutually harmful condition. Dimethyl fumarate (DMF) is a Food and Drug Administration-approved antioxidant and anti-inflammatory agent. The purpose of this study was to investigate the effects of DMF on Dahl/salt-sensitive (DS) rats as a CRAS model. Six-week-old DS rats were divided into three groups: the control group, the high-salt (HS) group, and the HS+DMF group. The HS and HS+DMF groups were fed a high-salt diet (8% NaCl) from 6 weeks of age. In the HS+DMF group, DMF (90 mg/kg per day) was orally administered from 6 to 15 weeks of age. Systolic blood pressure was measured every 2 weeks. The heart and renal injuries were assessed with histopathological analysis. The heart and renal expression of mRNAs was assessed by reverse-transcription polymerase chain reaction. DMF significantly improved overall survival, which was shortened by HS in DS rats. Systolic blood pressure increased in the HS group compared with the control group, and DMF tended to suppress this change. DMF ameliorated the cardiac and renal abnormalities confirmed in the HS group by histopathological analysis. Furthermore, the changes in mRNA expressions associated with disease exacerbation in the HS group were suppressed by DMF. DMF also improved anemia. This study suggests that DMF improves overall survival in DS rats through organ-protective effects and is effective against cardiorenal anemia syndrome. SIGNIFICANCE STATEMENT: Dimethyl fumarate was found to improve overall survival in Dahl/salt-sensitive rats, associated with its ability to ameliorate anemia and induce cardioprotective and renoprotective effects through anti-inflammatory and antifibrotic effects.

A Recurrent Case of Adult-onset Still's Disease with Concurrent Acalculous Cholecystitis and Macrophage Activation Syndrome/Hemophagocytic Lymphohistiocytosis Successfully Treated with Combination Immunosuppressive Therapy.

We herein report the case of 21-year-old female diagnosed with adult-onset Still's disease (AOSD) three years earlier who presented with fever and right upper abdominal pain. She was diagnosed with acute acalculous cholecystitis (AAC) based on hepatic dysfunction, elevated C-reactive protein, and gallbladder wall thickening on abdominal ultrasound. Based on the presence of pancytopenia, hyperferritinemia, and hemophagocytosis by a bone marrow examination, she was diagnosed with macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH) which was refractory to glucocorticoid pulse therapy. The combination of intravenous cyclosporine A with glucocorticoids was able to successfully control the disease activity of AOSD-related AAC and MAS/HLH.

Effect of Bifidobacterium animalis subsp. lactis GCL2505 on the physiological function of intestine in a rat model.

Bifidobacterium animalis ssp. lactis GCL2505 has been shown to proliferate in the human intestine. The intestinal dynamics and physiological effects of GCL2505 as well as the mechanism underlying proliferation in the gut were investigated. GCL2505 showed markedly higher resistance to free bile acids (cholic and deoxycholic acids) than other bifidobacterial species. The intestinal dynamics of GCL2505 and B. longum ssp. longum JCM1217T was compared. The level of B. animalis ssp. lactis in the GCL2505-administered group was remarkably higher than that of B. longum in the JCM1217T-administered group. The distribution of B. animalis ssp. lactis through the intestine of the GCL2505-administered group revealed that GCL2505 proliferated in the cecum. The physiological effects of GCL2505 and JCM 1217T were investigated. The cecal IgA level in the GCL2505-administered group was significantly higher than that in the nontreated control group. In contrast, the JCM 1217T-administered group did not manifest any change in the cecal IgA level. Mucin excretion in the GCL2505-administered group was significantly higher than that in the JCM 1217T-administered group. The thickness of the sulfomucin layer of the colon in the GCL2505-administered group tended to be higher than that in the JCM 1217T-administered group. In a loperamide-induced constipation model, fecal excretion in the GCL2505-administered group was significantly increased compared with that in the loperamide-treated control group. Short-chain fatty acid concentration in the GCL2505-administered group was significantly higher than that in the loperamide-treated control group. These results indicate that the level of proliferation of probiotics in the intestine correlates with the magnitude of host physiological responses, such as IgA production and mucin secretion, which possibly affect gastrointestinal functions such as bowel movement to counteract constipation. GCL2505 exhibits high tolerance to secondary bile acids, which partially explains its higher rate of proliferation in the large intestine.

Copper- and Silver-Catalyzed Diastereo- and Enantioselective Conjugate Addition Reaction of 1-Pyrroline Esters to Nitroalkenes: Diastereoselectivity Switch by Chiral Metal Complexes.

syn-Diastereoselective conjugate addition of 1-pyrroline esters to nitroalkenes in good yields with an excellent enantioselectivity by using CuOAc/Me-FcPHOX catalyst in the presence of pyridine. In contrast, AgOAc/tBu-ThioClickFerrophos catalyzed the anti diastereoselective conjugate addition with a high enantioselectivity without additional base. Thus, the preparation of chiral 1-pyrroline derivatives bearing diverse stereochemistry could be achieved. The diastereoselective reduction of the imine group in the conjugate adduct could afford the 2,5-cis-proline ester derivative.