Knowledge, attitudes, and practices regarding tick-borne diseases among an at-risk population living in Niigata prefecture, Japan.

OBJECTIVE: This study examined the knowledge, attitudes, and practices (KAP) of an at-risk population living in Niigata prefecture regarding tick-borne diseases (TBDs) and preventive strategies. METHODS: A cross-sectional questionnaire-based study was conducted to assess the KAP of the community. RESULTS: In total, 186 responses were received. Among the respondents, 130 (69·9%) were men, and the mean age was 51.1 (14·3). Nine (4·8%) respondents reported having experienced tick bites. Of the respondents, 44 (23.7%) knew about both scrub typhus and severe fever with thrombocytopenia syndrome, while 156 (83·9%) and 71 (38·2%) recognized limiting skin exposure and use of insect repellents as preventive measures, respectively. The attitudes towards TBDs: being worried about tick bites (p = 0·018) and interested in preventing TBDs (p = 0·001), were significantly higher among women than men. About 75% of the respondents reported taking preventive measures against tick bites, and limiting skin exposure was the most frequently applied method (69·9%). Insect repellents were used by 58 (31·2%) respondents. Age (p = 0·049), being worried about tick bites (p = 0·046), and knowledge of ticks score (p = 0·024) were the significant independent predictors of practicing countermeasures. CONCLUSION: We identified gaps in knowledge and practices regarding TBDs. Public health interventions should be implemented to improve public awareness of TBDs.

Hormetic response of cultured normal and tumor cells to 2-aminotropone derivatives.

We have recently reported that out of twenty benzo[b]cyclohept[e][1,4]oxazines and their S-analogs, and 2-aminotropone derivatives, 7-bromo-2-(4-hydroxyanilino) tropone and 4-isopropyl-2-(2-hydroxyanilino)tropone showed the highest tumor-specificity in human oral squamous cell carcinoma cell lines. To gain more insight into the anti-tumor actions of these compounds, whether they induce the growth stimulation effect observed at low concentrations, known as hormesis, was investigated using a total of ten human normal and tumor cultured cells. The tumor-specificity of both compounds became apparent 48 hours after the start of treatment of the cells with these compounds and reached a maximum level at 72 and 96 hours. On the other hand, their growth stimulatory effects were most prominent at 24 hours, especially in normal skin and lung fibroblasts, but rapidly disappeared with prolonged incubation time (48-96 hours). These data suggest the occurrence of a hormetic response only at restricted times and concentrations as has been previously reported, although the biological significance is yet to be elucidated.

Inhibition of NO production in LPS-stimulated mouse macrophage-like cells by benzo[b]cyclohept[e] [1,4]oxazine and 2-aminotropone derivatives.

The aim of this study was to investigate whether a total of twenty benzo[b]cyclohept[e][1,4]oxazines and their S-analogs, and 2-aminotropone derivatives affect the function of activated macrophages. These compounds inhibited the production of pro-inflammatory substances such as nitric oxide (NO) by lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells to different extents. Among them, benzo[b]cyclohept[e][1,4]oxazin-6(11H)-one [5] and 7-bromo-2-(4-hydroxyanilino)tropone [16] showed the highest inhibitory effects at concentrations that did not affect cellular viability (selectivity index=74.89 and 54.15, respectively). Western blot and RT-PCR analyses showed that [16] inhibited the expression of both inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 at both protein and mRNA levels, whereas [5] inhibited only iNOS protein expression. Electron-spin resonance (ESR) spectroscopy revealed that both [5] and [16] scavenged nitric oxide (generated from NOC-7) and superoxide anion (generated by HX-XOD reaction) only at much higher concentration. These data suggest that [16] but not [5] exerts its anti-inflammatory action against macrophages via the inhibition of iNOS and COX-2 protein expressions.

Tumor-specific cytotoxicity and type of cell death induced by benzo[b]cyclohept[e][1,4]oxazine and 2-aminotropone derivatives.

A total of twenty benzo[b]cyclohept[e] [1,4]oxazines and their S-analogs, and 2-aminotropone derivatives were investigated for their cytotoxicity against three human normal cells and four tumor cell lines. These compounds showed moderate tumor-specific cytotoxicity. The cytotoxicity was enhanced by bromination at the tropone ring and replacement by formylbenzene. The cytotoxicity of 2-(2-hydroxyanilino) tropone was enhanced by introduction of bromine or isopropyl group to the tropone ring. The presence of a hydroxyl group at ortho or para-position should be necessary for the appearance of cytotoxicity and tumor-specificity. The highly active derivatives, 7-bromo-2-(4-hydroxyanilino)tropone [16] and 4-isopropyl-2-(2-hydroxyanilino)tropone [20], induced internucleosomal DNA fragmentation and caspase-3, -8 and -9 activation in human promyelocytic leukemia HL-60 cells, but only at concentrations twice or four times higher than CC(50) values. These compounds induced no discernible DNA fragmentation, and activated caspases much more weakly in human oral squamous cell carcinoma HSC-2 cells. Both [16] and [20] failed to induce the production of acidic organelles, a marker of autophagy, in contrast to the nutritional starvation. These data demonstrated that 2-aminotropones showed relatively higher tumor-specificity than benzo[b]cyclohept[e] [1,4]oxazine, and that 2-aminotropones induced little or no apoptotic cell death in oral squamous cell carcinoma, in contrast to HL-60 cells.