Occurrence of Infusion-Related Reactions due to Obinutuzumab Therapy for Follicular Lymphoma.

BACKGROUND: Obinutuzumab is used to treat follicular lymphoma in Japan. Its characteristic adverse event is infusion- related reactions(IRRs). Although interruption of administration improves many IRRs, serious symptoms can occur; thus, timing the interruption to correspond with the onset of these symptoms is necessary. However, the specific symptoms and timing of IRRs caused by obinutuzumab remain unclear. Therefore, the purpose of this study was to clarify the specific symptoms and timing of the onset of IRRs with obinutuzumab treatment. METHODS: Thirty patients were administered obinutuzumab for one year from October 2018 to September 2019. The frequency of IRRs, expression time, severity, symptoms, and correspondence were investigated. RESULTS: IRRs occurred in 13 patients(43.3%), and all occurred after the first dosing. In 9 of 13 cases(69.2%), IRRs occurred within 90 min of the first dosage. Grade 3 symptoms were expressed in 1 of 13 cases (7.7%). The symptoms of IRRs were throat discomfort, breathing difficulty, skin rash, chills, and fever. CONCLUSIONS: Most IRRs due to obinutuzumab occurred within 90 min of the first dosage. They were mostly Grade 2 or lower, and the frequency of serious IRRs was low. Thus, careful observation of symptoms during treatment with obinutuzumab is necessary.

Protective Effects of Mekabu Aqueous Solution Fermented by Lactobacillus plantarum Sanriku-SU7 on Human Enterocyte-Like HT-29-luc Cells and DSS-Induced Murine IBD Model.

Most wakame Undaria pinnatifida, a brown algae, products are made from the frond portion. In this study, the polysaccharide content and antioxidant property of aqueous extract solutions (AESs) of the four parts (frond: wakame, stem of the frond: kuki-wakame, sporophyll: mekabu, and kuki-mekabu) of wakame were investigated. Polysaccharide content was high in both the wakame and mekabu. Superoxide anion (O2-) radical-scavenging capacities were high in the mekabu. These AESs could be fermented by Lactobacillus plantarum Sanriku-SU7. The O2- radical-scavenging activity of the kuki-wakame, mekabu, and kuki-mekabu were increased by the fermentation. Fermented mekabu clearly showed a protective effect on human enterocyte-like HT-29-luc cells and in a mouse model of dextran sodium sulphate-induced inflammatory bowel disease (IBD). These results suggest that the mekabu fermented by L. plantarum Sanriku-SU7 has anti-IBD effect related to O2- radical-scavenging.

Anti-glycation properties of the aqueous extract solutions of dried algae products and effect of lactic acid fermentation on the properties.

The antioxidant and anti-glycation properties in aqueous extract solutions (AESs) of 11 dried algae products were investigated. AESs of brown algae Ecklonia kurome (kurome) and Ecklonia stolonifera (tsuruarame) showed a strong DPPH radical-scavenging capacity and Fe-reducing power with high total phenolic compound content. On the other hand, superoxide anion radical-scavenging capacities of Porphyra sp. (iwanori, red alga), sporophyll of Undaria pinnatifida (mekabu, brown alga), and Gelidiaceae sp. (tengusa, red alga) were also high. Anti-glycation activities in BSA-fructose and BSA-methylglyoxal glycation were also high in kurome, while iwanori showed high activity. Results of the BSA-fructose model agreed with those of superoxide anion radical-scavenging. On the other hand, those of the BSA-methylglyoxal model agreed with those of the phenolic content, DPPH radical-scavenging capacity, and Fe-reducing power. Anti-glycation activities of iwanori, U. pinnatifida (wakame), and mekabu in the BSA-fructose model were clearly increased by fermentation with Lactobacillus plantarum AN6.

Induction of the superoxide anion radical scavenging capacity of dried 'funori'Gloiopeltis furcata by Lactobacillus plantarum S-SU1 fermentation.

To understand the beneficial properties of edible algae obtained from the north-eastern (Sanriku) Satoumi region of Japan, the antioxidant properties of hot aqueous extract solutions (AES) obtained from 18 dried algal products were determined. The samples included 4 Ceratophyllum demersum (matsumo), 5 Undaria pinnatifida (wakame), 5 Laminaria japonica (kombu), and 2 each of Gloiopeltis furcate (funori) and G. tenax (funori). Of these products, the total phenolic content and Fe-reducing power were highest in matsumo. On the other hand, the polysaccharide content, viscosity, and superoxide anion radical (O2˙(-))-scavenging capacity were highest in funori. Lactobacillus plantarum S-SU3, isolated from the intestine of Japanese surfperch, and Lb. plantarum S-SU1, isolated from salted squid, could ferment the AES of matsumo and funori, respectively. Although the Fe-reducing power of the matsumo solution was reduced due to fermentation, the O2˙(-)-scavenging capacity of the funori solution was increased by fermentation. Furthermore, the fermented funori suspension protected Saccharomyces cerevisiae, a live cell model, against H2O2 toxicity. These results suggest that the fermented funori is a promising functional food material that is capable of protecting against reactive oxygen species.

Anti-inflammatory properties of fermented soy milk with Lactococcus lactis subsp. lactis S-SU2 in murine macrophage RAW264.7 cells and DSS-induced IBD model mice.

Six lactic acid bacteria strains (four Lactobacillus plantarum strains and one each of Lactococcus lactis subsp. lactis and Pediococcus pentosaceus) have been isolated and shown to possess anti-oxidant activity. In this study, we determined their acid, bile, salt resistance, and adhesion activity on human enterocyte-like HT-29-Luc and Caco-2 cells. An isolate Lc. lactis S-SU2 showed highest bile resistance and adhesion activity compared to type strains. S-SU2 could ferment both 10% skimmed milk and soy milk while the type strain could not ferment soy milk. Soy milk fermented with S-SU2 showed an increased nitric oxide (NO) secretion in the mouse macrophage RAW264.7 cells without bacterial lipopolysaccharide (LPS). Furthermore, the inhibitory effects of the fermented soy milk on Escherichia coli O111 LPS-induced NO secretion were higher than those of fresh soy milk. Inflammatory bowel disease (IBD) was induced in mice fed either 5% (w/v) dextran sodium sulfate (DSS) in drinking water or 50% soy milk in drinking water. Shortening of colon length, breaking of epithelial cells, lowering liver and thymus weights, and enlargement of spleen are some of the characteristics observed in the IBD, which were prevented by the use of soy milk fermented with Lc. lactis S-SU2.

In vitro antioxidant and anti-inflammation properties of lactic acid bacteria isolated from fish intestines and fermented fish from the Sanriku Satoumi region in Japan.

The Ministry of the Environment, Government of Japan, defines a Satoumi as a coastal area where biological productivity and biodiversity has increased through human interaction. As a way to identify new starters and probiotics, we isolated and screened lactic acid bacteria (LAB) with acid, bile, and salt resistance from the intestines of 23 fish and 11 fermented fish samples obtained from the northeastern (Sanriku) Satoumi region of Japan. Of the 301 isolates, 75 strains were selected as LAB, 6 of which clearly showed increased antioxidant activities (DPPH and O2- radical scavenging and Fe-reducing power) in their cultured broth. Four isolates (S-SU1, 3-5) were identified as Lactobacillus plantarum. The two other strains (S-SU2, 6) identified were Lactococcus lactis and Pediococcus pentosaceus. In these in vitro assays, Lc. lactis S-SU2, isolated from sea pineapple kimchi showed the highest radical scavenging capacity. Moreover, the protective effect of heat-killed cells against the toxicity of 3mM H2O2 on Saccharomyces cerevisiae was the highest for Lb. plantarum S-SU1 isolated from a salted squid product, followed by P. pentosaceus S-SU6 isolated from the intestines of blue mackerel. Furthermore, Lb. plantarum S-SU5 showed inhibitory effect against the toxicity of 3mM H2O2 in human enterocyte-like HT-29-luc cells and on nitrite (NO) production in mouse RAW264.7 macrophage cells, which was induced by Escherichia coli O111 lipopolysaccharide (LPS). These results suggest that the selected LAB strains are potential starters and/or functional components with antioxidant and anti-inflammatory properties.

[Preventive effect of polaprezinc suspension dispersed in sodium alginate solution (P-AG) for stomatitis induced by Docetaxel/Cisplatin/Fluorouracil (DCF) chemotherapy in patients with head and neck cancer].

We measured the effectiveness of the prophylactic administration of a polaprezinc suspension dispersed in sodium alginate solution (P-AG) by dividing it into two courses in the same patients, and measured the stomatitis induced by Docetaxel/Cisplatin/Fluorouracil (DCF) chemotherapy. We then evaluated the results. We defined the therapeutic course as the course where P-AG was given therapeutically for stomatitis induced after DCF chemotherapy. We defined the prophylactic course as when P-AG was prophylactically given before any incidences of stomatitis after the therapeutic course. We compared the incidences of stomatitis in the prophylactic courses with those of the therapeutic courses. The incidences of stomatitis that were higher than Grade 1 were 17 out of 17 patients (100%) in the therapeutic course. On the other hand, they were 15 out of 17 patients (88. 2%) in the prophylactic course. Compared with the mean of the Grade of Stomatitis by the Common Terminology Criteria for Adverse Events version 3. 0 (CTCAE v. 3. 0), the maximal Grade of stomatitis significantly decreased in the prophylactic courses compared to those of the therapeutic courses(p<0. 05). Therefore, these results suggested that we were able to decrease the severity of stomatitis by using P-AG prophylactically, as opposed to using P-AG therapeutically.