Successful Treatment of Anti-Factor H Antibody-Associated Atypical Hemolytic Uremic Syndrome.

Anti-complement factor H (CFH) autoantibody (Ab)-associated atypical hemolytic uremic syndrome (aHUS) has a poor prognosis in terms of frequent relapses. Although eculizumab is an effective treatment for this type of aHUS, the method of eculizumab discontinuation is not yet established. Herein, we report a case of anti-CFH Ab-associated aHUS in a 6-year-old boy. Eculizumab induction therapy following plasma exchange improved his condition. After 14 months, eculizumab was discontinued because of meningococcal bacteremia. After 6 months of eculizumab cessation, prednisolone (20 mg/alternate days) and mycophenolate mofetil (500 mg/day) were initiated. There were no relapses or increases in anti-CFH Ab titers for 26 months after treatment initiation. We believe that eculizumab induction therapy, following plasma exchange and maintenance therapy with immunosuppressants after eculizumab discontinuation are effective treatments for anti-CFH Ab-related aHUS.

Dual Biological Functions of a Cytoprotective Effect and Apoptosis Induction by Bioavailable Marine Carotenoid Fucoxanthinol through Modulation of the Nrf2 Activation in RAW264.7 Macrophage Cells.

In this study, the function of fucoxanthinol (FxOH) as a bioavailable marine carotenoid together with the pre-metabolite, fucoxanthin (Fx), was examined through the Nrf2-ARE pathway. The antioxidant activity in the low concentration range of the compounds (1-4 µM) with a peroxyl radical scavenging capacity was proved by the ORAC (Oxygen Radical Absorbance Capacity) method and an ESR study. Similar concentrations of the compound also activated the Nrf2-ARE signaling with the Nrf2 translocation into the nuclear, then the expression of the antioxidant protein HO-1 increased. On the other hand, the high concentrations of both compounds (>10 µM) induced apoptosis with caspase 3/7 activation during suppression of the anti-apoptotic proteins, such as Bcl-XL and phosphorous Akt (pAkt). The Nrf2 expression was then activated in the nuclear, indicating that the Nrf2 plays a significant role in the cytoprotective effect against the toxicity of the compounds. These results indicated that the compounds have the dual functions of a cytoprotective effect and the apoptosis induction dependent on the treated concentrations through the Nrf2 activation. In addition, the results of all the assays involved in our previous studies suggested that the metabolite FxOH having a higher activity than the Fx, will be a bioavailable compound in biological systems.

Dual biological functions of the apoptotic activity and anti-inflammatory effect by alcyonolide congeners from the Okinawan soft coral, Cespitularia sp.

In our current study, alcyonolide and its congeners isolated from the Okinawan soft coral, Cespitularia sp., have shown an antitumor activity in HCT116 colon cancer cells. This study investigated the biological activities of these compounds (1-12) for the apoptotic activity in the HCT116 cells and the anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. As a result, the apoptotic cells with a nuclear condensation were detected by treatment with these compounds. The apoptotic cells dependent on the caspase 3/7 activation was also induced in the low concentration range of 2.5-10 µM. While a similar concentration of the compounds inhibited the NO production in the LPS-stimulated inflammatory RAW264.7 cells, the pro-inflammatory gene expressions of the iNOS and COX-2 mRNA were also suppressed. The structurally unique alcyonolides (5, 12) having the dual biological activity of apoptotic activity and anti-inflammatory effect could be a potential development as pharmaceutical agents.

Successful treatment with mycophenolate mofetil and tacrolimus in juvenile severe lupus nephritis.

Lupus nephritis (LN) of juvenile onset often has severe disease presentation. Despite aggressive induction therapy, up to 20% of patients with LN are resistant to initial therapy and up to 44% suffer a renal relapse. However, there is no consensus on an appropriate therapeutic regimen for refractory LN. We report a 13-year-old girl with recurrent LN who was not taking her medications. At age of 11 years, she was diagnosed with LN classified as International Society of Nephrology/Renal Pathology Society (ISN/RPS) class IV G (A) + V. She was treated with prednisolone and MMF after nine methylprednisolone pulses. Nineteen months later, she was admitted to the hospital with generalized edema. Her symptoms were nephrotic syndrome and acute renal dysfunction. She received three methylprednisolone pulses for 3 days, followed by oral prednisolone and MMF. Twenty-seven days after the three methylprednisolone pulses, her acute renal dysfunction was improved, but the nephrotic syndrome was not improved. A second biopsy showed diffuse lupus nephritis classified as the predominant finding of ISN/RPS class V. We added tacrolimus to the MMF. Four months after adding tacrolimus, the nephrotic syndrome improved. We conclude that adding tacrolimus to the treatment regimen for LN resistant to MMF is effective.

Antioxidant capacity of betacyanins as radical scavengers for peroxyl radical and nitric oxide.

This study was designed to assess the antioxidant capacity of betacyanins as indole derived plant pigments, such as betanin, phyllocactin and betanidin. The antioxidant capacity of the betacyanins was evaluated as an index of radical scavenging ability using the peroxyl radical generating system in the presence of AAPH and NO generating system using NOR3 as an NO donor. The peroxyl radical scavenging capacity was dose-dependent in the low concentration range (25-100 nM). The mol-Trolox equivalent activity/mol compound (mol-TEA/mol-compound) as an index of the antioxidant capacity indicated the following order at 10.70 ± 0.01, 3.31 ± 0.14 and 2.83 ± 0.01 mol-TEA/mol-compound for betanidin, betanin and phyllocactin, respectively. In addition, betacyanins reduced the nitrite-level in the low concentration range of 2.5-20 µM. The IC50 values (µM) of nitrogen radical scavenging activity were 24.48, 17.51 and 6.81 for betanin, phyllocactin and betanidin. ESR studies provided evidence that the compounds directly scavenged NO. These results indicated that betacyanins have a strong antioxidant capacity, particularly betanidin with a catechol group had higher activity than those of the glycoside of betacyanins. This study demonstrated that the betacyanins will be useful as natural pigments to provide defence against oxidative stress.

Inhibition of the ß-catenin/Tcf signaling by caffeoylquinic acids in sweet potato leaf through down regulation of the Tcf-4 transcription.

Sweet potato leaves contain the highest levels of functional polyphenols. In this study the effects of the sweet potato leaf extract and its contents, such as mono (3, 4, and 5)-caffeoylquinic acid (CQA), di-CQA (4,5-diCQA, 3,5-diCQA, and 3,4-diCQA) and caffeic acid (CA), were evaluated on the ß-catenin/Tcf-4 signaling in human colorectal cancer HCT116 cells. The extract and the CQA derivatives inhibited the ß-catenin/Tcf-4 signaling, and the inhibition of the di-CQA (with two caffeoyl groups) was higher than that of the mono-CQA (one-caffeoyl group) and CA, suggesting that the caffeoyl structure in the presence of a catechol group plays a significant role in interfering with the ß-catenin/Tcf-4 signaling. In addition, the CQA derivatives had no effect on the ß-catenin protein expression, but all test compounds inhibited the expression of the Tcf-4 transcription, and the inhibition of the di-CQA derivatives was stronger than those of the mono-CQA derivatives as well as the ß-catenin/Tcf-4 transcriptional activity. These compounds can modulate the downstream Wnt signaling pathway, suggesting that sweet potato leaves can be a protective food for colorectal cancer.