Intraperitoneal Phototherapy Suppresses Inflammatory Reactions in a Surgical Model of Peritonitis.

BACKGROUND: Standard treatment for diffuse peritonitis due to colorectal perforation may be insufficient to suppress inflammatory reaction in sepsis. Thus, developing new treatments is important. This study aimed to examine whether intraperitoneal irradiation by artificial sunlight suppresses inflammatory reaction in a lipopolysaccharide (LPS)-induced peritonitis model after surgical treatments. MATERIALS AND METHODS: Mice were divided into naive, nontreatment (NT), and phototherapy (PT) groups. In the latter two groups, LPS was intraperitoneally administered to induce peritonitis and removed by intraperitoneal lavage after laparotomy. The PT group was irradiated with artificial sunlight intraperitoneally. We evaluated the local and systemic inflammatory reactions. Murine macrophages were irradiated with artificial sunlight after stimulation by LPS, and cell viability and expression of tumor necrotizing factor-α (TNF-α) were evaluated. RESULTS: As a local inflammatory reaction, the whole cell count, the expression of interleukin-6 and TNF-α in the intra-abdominal fluid, and the peritoneal thickness were significantly lower in the PT group than in the NT group. As a systematic inflammatory reaction, the expression of serum TNF-α, granulocyte macrophage colony-stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1α, and MIP-1ß were significantly lower in the PT group than in the NT group. Irradiation by artificial sunlight suppressed the expression of TNF-α in murine macrophages without affecting cell viability. CONCLUSIONS: Intraperitoneal irradiation by artificial sunlight could suppress local and systemic inflammatory reactions in the LPS-induced peritonitis murine model. These effects may be associated with macrophage immune responses.

The utility of DHL-HisZnNa, a novel antioxidant, against anticancer agent-induced alopecia in breast cancer patients: a multicenter phase II clinical trial.

PURPOSE: Chemotherapy-induced alopecia (CIA) is a distressing adverse effect of anticancer drugs; however, there are currently no mechanisms to completely prevent CIA. In this study, we performed a clinical trial to examine whether sodium N-(dihydrolipoyl)-l-histidinate zinc complex (DHL-HisZnNa), an alpha-lipoic acid derivative, prevents CIA in patients with breast cancer. METHODS: Between July 2014 and May 2015, we performed a multi-center, single arm, clinical trial involving 103 breast cancer patients who received adjuvant chemotherapy at three medical institutions in Japan. During chemotherapy, a lotion containing 1% DHL-HisZnNa was applied daily to the patients' scalps. The primary endpoint was the incidence of grade 2 alopecia; the secondary endpoints were the duration of grade 2 alopecia, alopecia-related symptoms, and drug-related adverse events. Alopecia was evaluated by three independent reviewers using head photographs taken from four angles. RESULTS: Safety analysis was performed for 101 patients who started the protocol therapy. After excluding one patient who experienced disease progression during treatment, 100 patients who received at least two courses of chemotherapy underwent efficacy analysis. All original 101 patients developed grade 2 alopecia, the median durations of which were 119 days (112-133 days) and 203 days (196-212 days) in the groups treated with four and eight courses of chemotherapy, respectively. Mild or moderate adverse events potentially related to DHL-HisZnNa were observed in 11 patients. Alopecia-related symptoms were observed in 53 patients (52%). CONCLUSIONS: The application of 1% DHL-HisZnNa to the scalp did not prevent CIA. However, this drug may promote recovery from CIA. TRIAL REGISTRATION NUMBER: UMIN000014840.