The role of Piper chaba Hunt. and its pure compound, piperine, on TRPV1 activation and adjuvant effect.

BACKGROUND: Piper chaba Hunt. is used as an ingredient in Thai traditional preparation for arthritis. Its isolated compound is piperine which shows anti-inflammatory activity. Piperine produces a burning sensation because it activates TRPV1 receptor. The TRPV1 activation involved with the analgesic and adjuvant effect. P. chaba Hunt. has not been reported about TRPV1 activation and adjuvant effect. The aim of this study was to investigate the effect of P. chaba extract and piperine on TRPV1 receptor, which is considered as a target for analgesic and their adjuvant effects to support the development of an analgesic drug from herbal medicine. METHODS: The effect of P. chaba extract and piperine on HEK cells expressing TRPV1 channel was examined by calcium imaging assay. Adjuvant effects of P. chaba extract and piperine were investigated by a fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) model in mice. RESULTS: P. chaba extract induced calcium influx with EC50 value of 0.67 µg/ml. Piperine induced calcium influx with EC50 value of 0.31 µg/ml or 1.08 µM. For mouse CHS model, we found that 1% piperine, 5% piperine, 1% P. chaba extract and 5% P. chaba extract significantly enhanced sensitization to FITC as revealed by ear swelling responses. CONCLUSION: P. chaba extract and piperine activated TRPV1 channel and enhanced contact sensitization to FITC.

An Aliphatic Ester Diisopropyl Sebacate Exhibited an Adjuvant Effect on Fluorescein Isothiocyanate-Induced Contact Hypersensitivity Mouse Models.

Alternative plasticizers have become more popular due to health concerns about phthalate esters. We demonstrated that phthalate esters enhanced skin sensitization to fluorescein isothiocyanate (FITC) in mouse contact hypersensitivity models. Alternative plasticizers have not been well studied as to their effect on the immune system. We previously found that diisopropyl adipate (DIPA), an aliphatic dicarboxylic acid ester, enhanced skin sensitization to FITC. Sebacate esters are also widely used as alternative plasticizers. Here we tested diisopropyl sebacate (DIPS), which has the same alcohol with an aliphatic dicarboxylic acid of longer chain, using BALB/c mice. The results showed that DIPS facilitated skin sensitization to FITC and increased FITC-presenting dendritic cell trafficking from the skin to draining lymph nodes. Furthermore, DIPS activated transient receptor potential ankyrin 1 (TRPA1). The latter feature has been commonly observed for phthalate esters and DIPA, which have adjuvant effects. In summary, the adjuvant effect of a sebacate ester was demonstrated in a mouse model.

Adjuvant Effect of an Alternative Plasticizer, Diisopropyl Adipate, on a Contact Hypersensitivity Mouse Model: Link with Sensory Ion Channel TRPA1 Activation.

Due to health concerns about phthalate esters, the use of alternative plasticizers is being considered. Phthalate esters enhance skin sensitization to fluorescein isothiocyanate (FITC) in mouse models. We have demonstrated that phthalate esters stimulate transient receptor potential ankyrin 1 (TRPA1) cation channels expressed on sensory neurons. We also found a correlation between TRPA1 activation and the enhancing effect on FITC-induced contact hypersensitivity (CHS) when testing various types of phthalate esters. Here we investigated the effects of an alternative plasticizer, diisopropyl adipate (DIA). Activation of TRPA1 by DIA was demonstrated by calcium mobilization using Chinese hamster ovary cells expressing TRPA1 in vitro. The effect of DIA was inhibited by a TRPA1-specific antagonist, HC-030031. The presence of DIA or dibutyl phthalate (DBP; positive control) during skin sensitization of BALB/c mice to FITC augmented the CHS response, as revealed by the level of ear-swelling. The enhancing effect of DIA was inhibited by in vivo pretreatment with HC-030031. FITC-presenting CD11c(+) dendritic cell (DC)-trafficking to draining lymph nodes was facilitated both by DIA and by DBP. DBP and DIA were similarly active in the enhancement of interferon-γ production by draining lymph nodes, but the effect on interleukin-4 production was weaker with DIA. Overall, DIA activated TRPA1 and enhanced FITC-induced CHS, as DBP did. The adjuvant effects of adipate esters may need to be considered because they are used as ingredients in cosmetics and drug formulations topically applied to the skin.

Therapeutic barium enema for bleeding colonic diverticula: four case series and review of the literature.

The prevalence of diverticular diseases of the colon, including severe and persistent bleeding in Eastern countries, has increased in the last decades. The bleeding from colonic diverticula is the most common cause of acute lower gastrointestinal bleeding. Herein, we report four cases of severe and persistent bleeding of colonic diverticular disease that could be treated with a high concentration barium enema. These four cases showed a similar pattern of bleeding whose source could not be identified. Colonoscopy revealed fresh blood in the entire colon and many diverticula were noted throughout the colon. No active bleeding source was identified, but large adherent clots in some diverticula were noted. After endoscopic and angiographic therapies failed, therapeutic barium enema stopped the severe bleeding. These patients remained free of re-bleeding in the follow-up period (range 17-35 mo) after the therapy. We report the four case series of therapeutic barium enema and reviewed the literature pertinent to this procedure.

Characterization of pollen dispersion in the neighborhood of Tokyo, Japan in the spring of 2005 and 2006.

The behavior of Japanese cedar (Cryptomeria japonica) and Japanese cypress (Chamaecyparis obtusa) pollens in an urban area was examined through the measurements of the dispersion characteristics at the various sampling locations in both outdoor and indoor environments. Airborne pollens were counted continuously for three months during the Japanese cedar pollen and Japanese cypress seasons in 2005 and 2006 by the use of Durham's pollen trap method in and around Tokyo, Japan. The dispersion of pollens at the rooftop of Kyoritsu Women's University was observed to be at extremely high levels in 2005 compared with previously reported results during the past two decades. As for Japanese cedar pollen, the maximum level was observed as 440 counts cm(-2) day(-1) on 18 March 2005. Japanese cypress pollen dispersed in that area in the latter period was compared with the Japanese cedar pollen dispersions. The maximum dispersion level was observed to be 351 counts cm(-2) day(-1) on 7 April 2005. Total accumulated dispersions of Japanese cedar and Japanese cypress pollens were 5,552 and 1,552 counts cm(-2) for the three months (Feb., Mar. and Apr.) in 2005, respectively. However, the dispersion of both pollens in 2006 was very low. The total accumulated dispersions of Japanese cedar and Japanese cypress pollens were 421 and 98 counts cm(-2) for three months (Feb., Mar. and Apr.) in 2006, respectively. Moreover, the pollen deposition on a walking person in an urban area showed that the pollen counts on feet were observed to be extremely high compared with the ones on the shoulder, back and legs. These findings suggested that pollen fell on the surface of the paved road at first, rebounded to the ambient air and was deposited on the residents again. Furthermore, the regional distribution of the total pollen dispersion in the South Kanto area was characterized on 15-16 March 2005 and on 14-15 March 2006. Although the pollen levels in 2005 were much higher than in 2006, it was commonly observed that higher pollen counts existed in the outlying areas. That is, the pollen counts in an urban area were confirmed to be at a lower level. As for the indoor dispersion of pollens, two cases were evaluated. At the lobby of the main building of Kyoritsu Women's University, the averaged ratio of the indoor to the outdoor pollen count is 4.1%. Another case was at the hospital building of a medical school. The pollen dispersion in the indoor environment was also observed to be low. It was concluded that the indoor pollen would be mainly carried from the outer environment by the movement of air.

[Detection of genetically modified organisms obtained from food samples ].

Genetially modified organisms (GMOs) were explored in food samples obtained from November 2000 to March 2003 in the Tokyo area by using PCR and real-time PCR techniques. The existence of Roundup Ready Soybean (RRS) was surveyed in processed foods derived from soybeans, such as tofu, boiled soybean, kinako, nama-age, abura-age, natto, miso, soymilk and yuba. RRS was detected in 3 of 37 tofu, 2 of 3 nama-age, 2 of 3 yuba and 3 of 3 abura-age samples. The CBH351 in 70 processed corn foods, NewLeaf Plus and NewLeaf Y in 50 processed potato foods, and 55-1 papaya in 16 papayas were surveyed. These GMOs were not detected among the samples. Qualitative and quantitative analyses of RRS and genetically modified (GM) corn were performed in soybean, corn and semi-processed corn products such as corn meal, corn flour and corn grits. RRS was detected in 42 of 178 soybean samples, and the amount of RRS in RRS-positive samples was determined. The content was in the range of 0.1-1.4% in identity-preserved soybeans (non-GMO), and 49.8-78.8% in non-segregated soybeans. On the other hand, GM corns were detected in 8 of 26 samples. The amount of GM corn in GM corn-positive samples was in the range of 0.1-2.0%.

Proteolytic cleavage and cellular toxicity of the human alpha1A calcium channel in spinocerebellar ataxia type 6.

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease caused by small CAG repeat expansion in the alpha1A calcium channel gene. We found that the human alpha1A calcium channel protein expressed in human embryonic kidney 293T cells produces a 75 kDa C-terminal fragment. This fragment is more toxic to cells than the full-length alpha1A calcium channel, regardless of polyglutamine tract length. In cells stably transfected with plasmids of full-length alpha1A calcium channel cDNAs, the C-terminal fragment protein is present in the mutant transformant but not in the wild-type one, indicative that this C-terminal fragment with the expanded polyglutamine tract is more resistant to proteolysis than that with the normal sized polyglutamine tract. We speculate that the toxic C-terminal fragment, in which resistance to proteolysis is rendered by the expanded polyglutamine, has a key role in the pathological mechanism of SCA6.