First evidence of tick-borne encephalitis (TBE) outside of Hokkaido Island in Japan.

Tick-borne encephalitis (TBE) is an infection of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is endemic in parts of Europe and Asia. TBEV is transmitted to humans primarily by Ixodes ticks. There have been 5 TBE cases identified in Japan, all on the northern island of Hokkaido. Rodents with TBEV antibodies and Ixodes ticks have been identified throughout Japan, indicating that TBEV infection might be undiagnosed in Japan. Residual serum and cerebrospinal fluid (CSF) collected in 2010-2021 from 520 patients ≥1 year-of-age previously hospitalized with encephalitis or meningitis of unknown etiology at 15 hospitals (including 13 hospitals outside of Hokkaido) were screened by ELISA for TBEV IgG and IgM antibodies; TBEV infection was confirmed by the gold standard neutralization test. Residual serum was available from 331 (63.6%) patients and CSF from 430 (82.6%) patients; both serum and CSF were available from 189 (36.3%). Two patients were TBE cases: a female aged 61 years hospitalized for 104 days in Oita (2000 km south of Hokkaido) and a male aged 24 years hospitalized for 11 days in Tokyo (1200 km south of Hokkaido). Retrospective testing also identified a previous TBEV infection in a female aged 45 years hospitalized for 12 days in Okayama (1700 km south of Hokkaido). TBEV infection should be considered as a potential cause of encephalitis or meningitis in Japan. TBE cases are likely undiagnosed in Japan, including outside of Hokkaido, due to limited clinical awareness and lack of availability of TBE diagnostic tests.

Effects of various polyphenolics on hydrogen peroxide-induced p53 activity in NIH3T3 cells.

A cell-based assay system was developed to evaluate the potential antioxidant and pro-oxidant effects of various dietary polyphenolic compounds based on the induction of p53 activity by hydrogen peroxide. A p53-luciferase reporter vector was stably transfected into NIH3T3 cells. Individual clones were isolated, and one clone (number 33) was selected that showed the highest induction levels with different generators of free radicals. Clone 33 was preincubated for 1 hour with 0, 0.1, 1.0, 10, 50, and 100 microM genistein, resveratrol, naringenin, quercetin, epicatechin gallate, and epigallocatechin-3-gallate and then treated with 40 microM hydrogen peroxide or left untreated for 4 hours. Cell lysates were prepared and assayed for luciferase activity. Results show that the effects on p53 activity by the different polyphenolics varied depending on the compound and concentration. Quercetin and genistein reduced p53 activity at 1.0 microM, whereas the other four compounds did not attenuate p53 activity. With the exception of naringenin, the other compounds increased p53 at the higher (50 microM or 100 microM) amounts, without added hydrogen peroxide, suggesting that these compounds can act as pro-oxidants or possibly stimulate p53 activity by another mechanism.