Outpatient ablation treatment with two doses of 30 mCi of radioactive iodine for non-low-risk papillary thyroid cancer.

Outpatient ablation therapy with low-dose radioactive iodine (RAI) is applied to non-low-risk papillary thyroid cancer patients due to a chronic shortage of inpatient RAI treatment wards in Japan. We used the maximum dosage available for outpatient therapy of 30 mCi of RAI for ablation and diagnostic (Dx) whole-body scintigraphy (WBS). This study aimed to examine the significance of the second dose of 30 mCi. DxWBS was performed 6 months after ablation, and assessment of success or failure was performed 12 months after ablation. A second WBS was performed in the remaining RAI accumulation cases in the neck on DxWBS. The criteria for successful ablation was negative cervical accumulation on WBS, thyroid stimulating hormone-suppressed thyroglobulin (sup-Tg) below 1.0 ng?/?mL, and no increase in thyroglobulin antibody (TgAb) level. At the time of DxWBS, 35?/?68 cases met the successful criteria, and 45 cases achieved success at assessment. Sup-Tg values decreased significantly after ablation and decreased further after DxWBS in successful ablation cases, whereas those were not changed in ablation failure cases. Findings indicated that RAI used in DxWBS had therapeutic effects. It makes sense to use 30 mCi for DxWBS, given the current difficulty of inpatient ablation therapy with high-dose RAI. J. Med. Invest. 70 : 17-21, February, 2023.

Betuletol, a Propolis Component, Suppresses IL-33 Gene Expression and Effective against Eosinophilia.

Propolis, a resinous substance produced by honeybees, has been used in folk medicine since ancient times due to its many biological benefits such as antitumor, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory effects. Propolis contains flavonoids, terpenoids, aromatic aldehydes, and alcohols, which vary with different climate and environmental conditions. In our study, we examined the antiallergic activity of Brazilian green propolis (BGP) and isolated the active compound that can suppress an allergy-sensitive gene, IL-33, expression and eosinophilia. Ethanolic extract of BGP freeze-dried powder was fractionated with several solvent systems, and the active fractions were collected based on activity measurement. The single active compound was found by thin-layer chromatography. Using column chromatography and NMR, the active compound was isolated and identified as 3,5,7-trihydroxy-6,4'-dimethoxyflavone, also known as betuletol. Further, the antiallergic activity of that has been examined in PMA-induced up-regulation of IL-33 gene expression in Swiss 3T3 cells. Our data showed the IL-33 gene suppression both by BGP and the isolated active compound, betuletol. We also found that betuletol suppressed ERK phosphorylation, suggesting it could be effective in suppressing IL-33 mediated eosinophilic chronic inflammation and will provide new insights to develop potent therapeutics against allergic inflammations.

Effects of sublingual immunotherapy with tablets or drops containing Japanese cedar pollen antigens on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis.

OBJECTIVE: We examined the effects of SLIT with tablets containing JCP antigens on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis during pollen dispersal season. METHODS: A total of 128 patients with Japanese cedar pollinosis were categorized into four groups:19 one-year SLIT with tablets group, 16 two-year SLIT with drops group, 19 antihistamine group, and 74 untreated group. The scores of nasal symptoms and sleep disturbance were evaluated based on the Japanese guidelines for allergic rhinitis and the Athens Insomnia Scale. RESULTS: The scores of nasal symptoms and sleep disturbance at the peak cedar pollen period in the two-year SLIT with drop group and the one-year SLIT with tablets group were significantly lower than those in untreated group. Additionally, these scores were significantly lower in the one-year SLIT with tablets group than those in the antihistamine group. CONCLUSION: It is suggested that SLIT with JCP tablets improved both nasal symptoms and sleep disturbances at peak pollen period in patients with Japanese cedar pollinosis. SLIT with JCP tablets for one year was more effective than SLIT with JCP drops for two years and prophylactic treatment with antihistamines. J. Med. Invest. 69 : 97-100, February, 2022.

Clinical trials of Cry j 1 and Cry j 2 T-cell epitope peptide-expressing rice in patients with Japanese cedar pollinosis.

BACKGROUND: In allergic models, administration of rice that expresses a hybrid peptide consisting of 7 major T cell epitopes of Cry j 1 and Cry j 2 (7Crp), suppressed allergic symptoms, IgE elevation and specific T cell response to Japanese cedar pollen. OBJECTIVE: To evaluate the efficacy and safety of 7Crp-expressing rice in patients with Japanese cedar pollinosis. METHODS: A 24-week randomized, double-blind, placebo-controlled study was performed to see the efficacy of 7Crp on allergic symptoms using scoring systems, in which 45 patients were assigned to take either 5 g, 20 g test rice, or placebo daily. A 96-week open study was also conducted to determine its inhibitory effect on serum IgE and T cell proliferative response for Japanese cedar pollen, in which 10 patients consumed 5 g test rice daily. RESULTS: No adverse events associated with the test rice occurred, and the intake rate was more than 96%. The test rice did not show suppression of symptoms related to Japanese cedar pollinosis within 24 weeks. However, intake of 5 g test rice led to a significant decrease in T cell response to Japanese cedar pollen during and after the second disperse season in a 96-week open trial, whereas the specific IgE titer remained unchanged. CONCLUSIONS: Tolerability and safety of 7Crp-expressing rice was accepted. Daily intake of up to 20 g transgenic rice did not provide beneficial effects on Japanese cedar pollinosis within 24 weeks, however, continuous intake of 5 g rice might reduce allergen specific T cell response.

Patho-Pharmacological Research of Anti-allergic Natural Products Targeting Antihistamine-Sensitive and -Insensitive Allergic Mechanisms.

Histamine H1 receptor (H1R) has a special up-regulation mechanism by the stimulation of H1R, mediated by protein kinase C-delta (PKCδ) signaling and H1R gene expression, resulting increase in H1R signaling. Increase in H1R mRNA in nasal mucosa was induced after the provocation of nasal hypersensitivity model rats and suppressed by the pre-treatment of antihistamines. Improvement of nasal symptoms and suppression of H1R mRNA expression in nasal mucosa were also observed by the pre-treatment of antihistamines in pollinosis patients. Elucidation of a correlation between symptoms and H1R mRNA level suggests that H1R gene is an allergic disease (AD)-susceptibility gene, targeted by antihistamines. Similar to antihistamines, pre-treatment of Kujin extract, an anti-allergic Kampo medicine improved nasal symptoms and suppressed H1R mRNA expression in nasal hypersensitivity model rats. (-)-Maackiain targeting heat shock protein 90 (Hsp90) was isolated as an inhibitor of PKCδ signaling-mediated H1R gene expression from Kujin extract. In addition to H1R-mediated activation of H1R gene expression as the first mechanism, nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression is suggested to participate to allergic symptoms as the second mechanism insensitive to antihistamines. Pyrogallol and proanthocyanidin suppressing IL-9 gene expression were discovered from Awa-tea and lotus root knots, respectively. Combination therapy using medicines suppressing both H1R gene expression and IL-9 gene expression is promising for outstanding alleviation of AD. Multifactorial diseases involving H1R gene expression may be treated by the combination therapy with antihistamine and complementary drugs, and diseases involving PKCδ signaling may be treated by drugs targeting Hsp90.

Dietary supplementation with monosodium glutamate with dietary balance such as protein, salt and sugar intake with increasing T1R3 taste receptor gene expression in healthy females.

We previously showed that chemotherapy-induced dysgeusia was associated with lingual taste receptor gene expression, and monosodium glutamate (MSG) improved dysgeusia by upregulating taste 1 receptor 3(T1R3) gene expression. In recent years, decreased taste sensitivity has also been reported in some young people, and these are partly due to their disordered eating habits. From these background, we investigated the effects of MSG supplementation on taste receptor expression and dietary intake in healthy females. Fifteen young healthy volunteers were enrolled for the present crossover study and divided in two groups (dietary supplementation with MSG at 2.7 g / day or 0.27 g / day). The relative expression of T1R3, a subunit of both umami and sweet taste receptors, in the tongue was assessed by quantitative PCR analysis. Food intake was assessed by food frequency questionnaire (FFQg), and body composition was measured using Omron HBF-701. T1R3 expression levels in the tongue and taste sensitivity increased significantly in participants who consumed <10 g of MSG daily, whereas no alteration was observed in participants who consumed >10 g of MSG daily. Furthermore, protein, fat, and carbohydrate (PFC) balance and salt and sugar intake improved by MSG supplementation. In conclusion, MSG supplementation increased T1R3 expression in the tongue and improved dietary balance. J. Med. Invest. 68 : 315-320, August, 2021.

Dietary Supplementation with Monosodium Glutamate Suppresses Chemotherapy-Induced Downregulation of the T1R3 Taste Receptor Subunit in Head and Neck Cancer Patients.

(Background) We investigated the effect of dietary supplementation with monosodium glutamate (MSG) on chemotherapy-induced downregulation of the T1R3 taste receptor subunit expression in the tongue of patients with advanced head and neck cancer. (Methods) Patients undergoing two rounds of chemoradiotherapy were randomly allocated to a control or intervention group (dietary supplementation with MSG at 2.7 g/day during the second round of chemotherapy). The relative expression of T1R3, a subunit of both umami and sweet taste receptors, in the tongue was assessed by quantitative polymerase chain reaction analysis. Dysgeusia was assessed with a visual analog scale and daily energy intake was evaluated. (Results) T1R3 expression levels in the tongue, taste sensitivity, and daily energy intake were significantly reduced after the first round of chemotherapy compared with before treatment. Furthermore, these parameters significantly decreased after the second round of chemotherapy, but the extent of decrease was significantly attenuated in the MSG group compared with the control group. (Conclusions) MSG supplementation suppresses chemotherapy-induced dysgeusia, possibly due to the inhibition of the T1R3-containing taste receptor downregulation in the tongue, thereby increasing energy intake in patients with advanced head and neck cancer.

Effects of narrow-band UVB on nasal symptom and upregulation of histamine H1 receptor mRNA in allergic rhinitis model rats.

BACKGROUND: Phototherapy with narrow-band ultraviolet B (narrow-band UVB) is clinically effective treatment for atopic dermatitis. In the present study, we examined the effects of intranasal irradiation with narrow-band UVB on nasal symptom, upregulation of histamine H1 receptor (H1R) gene expression and induction of DNA damage in the nasal mucosa of allergic rhinitis (AR) model rat. METHODS: AR model rats were intranasally irradiated with 310 nm of narrow-band UVB. Nasal mucosal levels of H1R mRNA were measured using real-time quantitative reverse transcriptase (RT)-PCR. DNA damage was evaluated using cyclobutane pyrimidine dimer (CPD) immunostaining. RESULTS: In toluene 2,4-diisocyanate (TDI)-sensitized rats, TDI provoked sneezes and H1R gene expression in the nasal mucosa. Intranasal pre-irradiation with 310 nm narrow-band UVB at doses of 600 and 1400, but not 200 mJ/cm2 significantly inhibited the number of sneezes and upregulation of H1R gene expression provoked by TDI. CPD-positive cells appeared in the nasal mucosa after intranasal narrow-band UVB irradiation at a dose of 1400, but not 200 and 600 mJ/cm2. The suppression of TDI-provoked sneezes and upregulation of H1R gene expression lasted 24 hours, but not 48 hours, after narrow-band UVB irradiation with a dose of 600 mJ/cm2. CONCLUSIONS: Intranasal pre-irradiation with narrow-band UVB dose-dependently inhibited sneezes and upregulation of H1R gene expression of the nasal mucosa in AR model rats, suggesting that the inhibition of nasal upregulation of H1R gene expression suppressed nasal symptom. The suppression after narrow-band UVB irradiation at a dose of 600 mJ/cm2 was reversible without induction of DNA damage. These findings indicated that low-dose narrow-band UVB phototherapy could be effectively and safely used for AR treatment in a clinical setting. LEVEL OF EVIDENCE: NA.

Effects of sublingual immunotherapy on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis.

OBJECTIVE: Japanese cedar (JC) pollinosis is the most common seasonal allergic rhinitis (AR) in Japan. AR reduces the quality of life not only because of nasal symptoms but also because of sleep disturbance. In the present study, we investigated the effects of sublingual immunotherapy (SLIT) with a standardized JC pollen extract on nasal symptoms and AR-related sleep disturbance in patients with JC pollinosis. METHODS: In the present non-randomized controlled study, we assigned thirty-one patients with JC pollinosis who received SLIT into the SLIT group, and another thirty-eight patients with JC pollinosis who visited our hospital without treatment into the untreated group. We evaluated nasal symptoms and sleep disturbance using the classification of the severity of AR symptoms and the Athens Insomnia Scale, respectively. RESULTS: The nasal symptom scores and the Athens Insomnia Scale scores of patients in the SLIT group were both significantly lower than those of patients in the untreated group. There was a significant correlation between total nasal symptom scores and the Athens Insomnia Scale scores. CONCLUSIONS: These findings suggested that SLIT with JC pollen extract suppressed nasal symptoms in patients with JC pollinosis, leading to improvements in AR-related sleep disturbance and daytime troubles with daily life.

Identification of pyrogallol from Awa-tea as an anti-allergic compound that suppresses nasal symptoms and IL-9 gene expression.

As the expression level of allergic disease sensitive genes are correlated with the severity of allergic symptoms, suppression of these gene expressions could be promising therapeutics. We demonstrated that protein kinase Cδ / heat shock protein 90-mediated H1R gene expression signaling and nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression signaling are responsible for the pathogenesis of pollinosis. Treatment with Awa-tea combined with wild grape hot water extract suppressed these signaling and alleviated nasal symptoms in toluene-2,4-diisocyanate (TDI)-sensitized rats. However, the underlying mechanism of its anti-allergic activity is not elucidated yet. Here, we sought to identify an anti-allergic compound from Awa-tea and pyrogallol was identified as an active compound. Pyrogallol strongly suppressed ionomycin-induced up-regulation of IL-9 gene expression in RBL-2H3 cells. Treatment with pyrogallol in combination with epinastine alleviated nasal symptoms and suppressed up-regulation of IL-9 gene expression in TDI-sensitized rats. Pyrogallol itself did not inhibit calcineurin phosphatase activity. However, pyrogallol suppressed ionomycin-induced dephosphorylation and nuclear translocation of NFAT. These data suggest pyrogallol is an anti-allergic compound in Awa-tea and it suppressed NFAT-mediated IL-9 gene expression through the inhibition of dephosphorylation of NFAT. This might be the underlying mechanism of the therapeutic effects of combined therapy of pyrogallol with antihistamine. J. Med. Invest. 67 : 289-297, August, 2020.

Electroneurography cannot predict when facial synkinesis develops in patients with facial palsy.

The objective of this study is to clarify when facial palsy patients with lower value of Electroneurography (ENoG) should begin the rehabilitation to prevent the development of facial synkinesis. For this purpose, we examined the relationship between the value of ENoG measured 10-14 days after facial palsy onset and the onset day of the development of oral-ocular synkinesis. Sixteen patients with facial palsy including 11 with Bell's palsy and 5 with Ramsay Hunt syndrome (7 men and 9 women ; 15-73 years old ; mean age, 41.6 years) were enrolled in this study. There was no correlation between ENoG value and the onset day of the development of oral-ocular synkinesis (ρ = .09, p = .73). Oral-ocular synkinesis began to develop in 4.0 ±â€…0.7 months (mean ±â€…SD ; range : 3.1-5.0 months) after facial palsy onset regardless of ENoG value. In conclusion, ENoG value cannot predict when facial synkinesis develops in patients with facial palsy. We recommend that facial palsy patients with a high risk for the development of synkinesis begin the biofeedback rehabilitation with mirror to prevent the development of facial synkinesis 3 months after facial palsy onset. J. Med. Invest. 67 : 87-89, February, 2020.

Aural stimulation with capsaicin prevented pneumonia in dementia patients.

OBJECTIVE: In the present study, we examined the effects of daily application of capsaicin ointment to the external auditory canal for 6 months on the development of pneumonia in elderly dementia patients at high risk of aspiration. METHODS: Twenty-nine oldest-old bedridden dementia inpatients at high risk of aspiration were enrolled in the present study. Ointment containing 0.025% capsaicin was applied to each external auditory canal with a cotton swab alternatively once a day for 6 months. RESULTS: The incidence of pneumonia during the 6 months before the intervention was 1.80±0.37 in these patients. However, this incidence significantly decreased to 0.40±0.29 (p<0.01) during the 6 months of the alternative application of capsaicin ointment to each auditory canal. No adverse effect such as otalgia was observed. CONCLUSION: These findings suggest that daily long-term aural stimulation with capsaicin ointment enhanced the cough reflex via Arnold's ear-cough reflex as a glottis protective measure, resulting in the reduction of incidence of pneumonia in elderly dementia patients at high risk of aspiration. The daily aural stimulation with capsaicin ointment may be a safe and promising intervention to prevent aspiration pneumonia in elderly people, especially those who cannot undergo swallowing exercise.

Effect of wild grape on the signaling of histamine H1 receptor gene expression responsible for the pathogenesis of allergic rhinitis.

As expression level of allergic disease-sensitive genes are correlated with allergic symptom severity, suppression of these gene expressions could be good therapeutics. We have demonstrated that PKCδ signaling and NFAT signaling, involve in histamine H1 receptor (H1R) and IL-9 gene expressions, respectively, are responsible for the pathogenesis of allergic rhinitis. We explore anti-allergic compounds that suppress these signaling pathways and found that wild grape (WG) contains such compounds. Here, we investigated the effect of WG hot water extract (WGE) on the signaling pathways for PKCδ-mediated H1R and NFAT-mediated IL-9 gene expressions. WGE suppressed histamine/PMA-induced H1R gene up-regulation in HeLa cells. Toluene-2,4-diisocyanate (TDI)-induced H1R mRNA elevation in TDI-sensitized rats was also suppressed by WGE treatment. Treatment with WGE in combination with Awa-tea, suppresses NFAT signaling-mediated IL-9 gene, markedly alleviated nasal symptoms. Furthermore, WGE suppressed PMA-induced IL-33 gene up-regulation in Swiss 3T3 cells. Data suggest that combination of WGE, suppresses PKCδ signaling with Awa-tea, suppresses NFAT signaling would have distinct clinical and therapeutic advantages as a substitute for anti-allergic drugs. In addition, as the expression level of IL-33 mRNA was correlated with the blood eosinophils number in patients with pollinosis, WG could alleviate eosinophilic inflammation through the suppression of IL-33 gene expression. J. Med. Invest. 65:242-250, August, 2018.

Effects of irradiation with narrowband-ultraviolet B on up-regulation of histamine H1 receptor mRNA and induction of apoptosis in HeLa cells and nasal mucosa of rats.

Narrowband-ultraviolet B (NB-UVB) phototherapy is used for the treatment of atopic dermatitis. Previously, we reported that irradiation with 200 mJ/cm2 of 310 nm NB-UVB suppressed phorbol-12-myristate-13-acetate (PMA)-induced up-regulation of histamine H1 receptor (H1R) gene expression without induction of apoptosis in HeLa cells. However, the effect of NB-UVB irradiation on nasal symptoms is still unclear. Here, we show that low dose irradiation with 310 nm NB-UVB alleviates nasal symptoms in toluene 2,4-diisocyanate (TDI)-sensitized allergy model rats. Irradiation with 310 nm NB-UVB suppressed PMA-induced H1R mRNA up-regulation in HeLa cells dose-dependently at doses of 75-200 mJ/cm2 and reversibly at a dose of 150 mJ/cm2 without induction of apoptosis. While, at doses of more than 200 mJ/cm2, irradiation with 310 nm NB-UVB induced apoptosis. Western blot analysis showed that the suppressive effect of NB-UVB irradiation on H1R gene expression was through the inhibition of ERK phosphorylation. In TDI-sensitized rat, intranasal irradiation with 310 nm NB-UVB at an estimated dose of 100 mJ/cm2 once a day for three days suppressed TDI-induced sneezes and up-regulation of H1R mRNA in nasal mucosa without induction of apoptosis. These findings suggest that repeated intranasal irradiation with low dose of NB-UVB could be clinically used as phototherapy of AR.

Aural stimulation with capsaicin ointment improved swallowing function in elderly patients with dysphagia: a randomized, placebo-controlled, double-blind, comparative study.

OBJECTIVE: The aim of this study was to assess whether aural stimulation with ointment containing capsaicin improves swallowing function in elderly patients with dysphagia. STUDY DESIGN: A randomized, placebo-controlled, double-blind, comparative study. SETTINGS: Secondary hospital. PATIENTS AND METHODS: Twenty elderly dysphagic patients with a history of cerebrovascular disorder or Parkinson's disease were randomly divided into two groups: 10 receiving aural stimulation with 0.025% capsaicin ointment and 10 stimulated with placebo. The ointments were applied to the external auditory canal with a cotton swab. Then, swallowing of a bolus of blue-dyed water was recorded using transnasal videoendoscopy, and the swallowing function was evaluated according to both endoscopic swallowing scoring and Sensory-Motor-Reflex-Clearance (SMRC) scale. RESULTS: The sum of endoscopic swallowing scores was significantly decreased 30 and 60 min after a single administration in patients treated with capsaicin, but not with placebo. Reflex score, but not Sensory, Motion and Clearance scores, of the SMRC scale was significantly increased 5, 30 and 60 min after single administration in patients treated with capsaicin, but not with placebo. No patient showed signs of adverse effects. CONCLUSION: As capsaicin is an agonist of the transient receptor potential vanilloid 1 (TRPV1), these findings suggest that improvement of the swallowing function, especially glottal closure and cough reflexes, in elderly dysphagic patients was due to TRPV1-mediated aural stimulation of vagal Arnold's nerve with capsaicin, but not with a nonspecific mechanical stimulation with a cotton swab.

Complementary and alternative medicine for allergic rhinitis in Japan.

BACKGROUND: Complementary and alternative medicine (CAM) is extensively used in patients with allergic diseases worldwide. The purpose of this study was to investigate the actual situation of CAM practice in the treatment of allergic rhinitis. METHODS: We distributed questionnaires to otolaryngologists at 114 facilities in Japan. The subjects who participated in this study included children <16 years of age and adults ≥16 years of age diagnosed with allergic rhinitis by otolaryngologists. The survey was performed in the period from September 2007 to August 2009. Furthermore, we performed the same investigation out of the hospital setting, such as during general health examinations. All questionnaires were returned to Chiba University and analyzed. RESULTS: The proportions of patients who had ever experimented with CAM in the hospital survey were 7.1% (225/3170) and 19.2% (1416/7363) of children and adults, respectively. Approximately 36.2% of the adult patients thought that the treatments were effective. The main reasons for CAM use were safety, convenience and low price. However, the group who spent more than $1000 on CAM felt more dissatisfaction and anxiety related to treatment at the hospital. The situation of CAM practice was not consistent and was instead influenced by the backgrounds of the subjects. CONCLUSIONS: Many patients who receive CAM report feeling that the effects of treatment provided by hospitals are insufficient and have concerns about the side effects of such treatments. Information regarding standard treatments, as described in the guidelines, should become widely known and diffused, and strong communication with patients should be considered.

Efficacy of proton pump inhibitor in combination with rikkunshito in patients complaining of globus pharyngeus.

OBJECTIVE: Globus pharyngeus (GP) is a common symptom of laryngopharyngeal reflux disease (LPRD), and proton pump inhibitor (PPI) and rikkunshito, a traditional Japanese medicine having prokinetic effect improve LPRD symptoms. In the present study, we examined the efficacy of high-dose PPI in combination with rikkunshito in patients complaining of GP. METHODS: 106 patients complaining of GP without any organic endoscopic findings were enrolled. RESULTS: Patients were first administrated with high-dose PPI alone for 4 to 8 weeks and the symptom was improved in 65 patients. Among 41 patients with PPI-refractory GP, 22 patients were administrated with high-dose PPI in combination with rikkunshito, and the symptom was improved in 14 of 22 patients 4 weeks later. The average value of a modified reflux symptom index of the responders was similar to that of non-responders. Only a few patients had positive values in reflux finding scores in both groups. CONCLUSION: The present findings suggest the existence of a high prevalence of LPRD in patients complaining of GP. The data also suggest that gastroesophageal dysmotility is involved in GP, in addition to excessive acid reflux. The pre-therapeutic laryngopharyngeal symptoms and endoscopic findings could not predict the efficacy of the treatment for GP. J. Med. Invest. 63: 227-229, August, 2016.

Irradiation with narrowband-ultraviolet B suppresses phorbol ester-induced up-regulation of H1 receptor mRNA in HeLa cells.

Conclusion These findings suggest that low dose irradiation with 310 nm NB-UVB specifically suppressed the up-regulation of H1R gene expression without inducing apoptosis and that UVB of shorter or longer wavelength than 310 nm NB-UVB had no such effects. Objective To develop a narrowband-ultraviolet B(NB-UVB) phototherapy for allergic rhinitis, this study investigated the effects of irradiation with NB-UVB at wavelength of 310 nm on phorbol-12-myristate-13-acetate (PMA)-induced up-regulation of histamine H1 receptor (H1R) mRNA in HeLa cells. Methods The mRNA levels of H1R in HeLa cells were measured using real-time RT-PCR. Apoptosis were evaluated with DNA fragmentation assay. Results PMA induced a significant increase in H1R mRNA expression in HeLa cells. Irradiation with 305 nm UVB and 310 nm NB-UVB, but not with 315 nm UVB at doses of 200 and 300 mJ/cm(2) significantly suppressed PMA-induced up-regulation of H1R mRNA. At a dose of 200 mJ/cm(2), irradiation with 305 nm UVB, but not with 310 nm NB-UVB, induced apoptosis, although exposure of the cells to both 305 and 310 nm UVB induced apoptosis at a dose of 300 mJ/cm(2) after PMA treatment in HeLa cells. Conversely, irradiation with 315 nm UVB at doses of 200 and 300 mJ/cm(2) did not induce apoptosis.

Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit.

In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders.