Involvement of nitric oxide in re-innervation of rat molar tooth pulp following transection of the inferior alveolar nerve

The aim of this study was to elucidate whether nitric oxide (NO) is involved in re-innervation of rat molar tooth pulp following transection of the inferior alveolar nerve. The inferior alveolar nerves (IAN) of rats were transected unilaterally under anesthesia with chloral hydrate. The animals received horseradish peroxidase (HRP) application to mandibular molar tooth pulps on both sides and were fixed by transvascular perfusion. The average number of labeled cells on each side of the trigeminal ganglion was not significantly different [101±11 (mean±S.E.M.; n=6, left) and 89±11 (n=6, right)]. With HRP application on postoperative day 3, the ratio of the number of labeled neurons in the transected vs. non-transected (contralateral) sides was 31.5±5.8% (n=11). The i.p. administration of N^ω-nitro-

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-arginine methyl ester (

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-NAME; 100 mg/kg, once a day for a period of 4 days), but not

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-NAME, significantly decreased the ratio of the number of labeled neurons (10.1±7.0%, n=10).

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-Arginine (300 mg/kg, i.p., once a day for a period of 4 days) slightly increased the number of labeled neurons on the transected side. Clonidine (25 μg/kg, i.p., once a day for a period of 4 days) failed to exhibit any significant effect on nerve regeneration. In the trigeminal ganglion ipsilateral to the transected IAN on postoperative day 4, NADPH-diaphorase (NADPH-d)-positive neurons had significantly increased. On the other hand, no changes in NADPH-d were observed in the superficial layers of the subnucleus caudalis of the spinal trigeminal nucleus from where primary neurons innervating the mammalian tooth pulp project. These results suggest that NO is involved in several mechanisms related to neuronal regeneration.     

Cancer chemopreventive activity of 3,5,6,7,8,3',4'-heptamethoxyflavone from the peel of citrus plants

Nobiletin and 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT), isolated from the peel of Citrus plants, were examined for the anti-tumor-initiating activity on two-stage carcinogenesis of mouse skin tumors induced by a nitric oxide donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexenamide, as an initiator and 12-O-tetradecanoylphorbol-13-acetate as a promoter. HPT exhibited the remarkable anti-tumor-initiating effect on mouse skin and it suggested the possibility of HPT being a chemopreventive agent against nitric oxide (NO) carcinogenesis.     

Influence of Previous Interferon Therapy on Recurrence after Resection of Hepatitis C Virus-related Hepatocellular Carcinoma

Interferon (IFN) therapy decreases the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV). One hundred and fifty-nine consecutive patients who underwent liver resection for HCV-related HCC were studied. In 17 (group 1) of the 159 patients, HCC was detected during or after IFN therapy. The incidences of recurrence after surgery in the group 1 patients and the other 142 patients (group 2) were compared. Eight patients had a complete response to IFN, 4 had a partial response, and 5 had no response. The proportion of patients without HCV viremia was significantly higher in the group 1 patients (P<0.0001). The tumor-free survival rate was significantly higher in the group 1 patients (P=0.0010). By multivariate analysis of various risk factors for recurrence, no previous IFN was a significant independent risk factor for recurrence (risk ratio=6.336; 95% CI, 1.512-26.50). The patients with HCC who underwent IFN therapy previously are good candidates for liver resection because recurrence after the operation was rarely observed.     

Relation between breastfeeding and the prevalence of asthma : the Tokorozawa Childhood Asthma and Pollinosis Study.

Many risk factors for asthma have been proposed including age, gender (male), smoking, and family history of asthma. The importance of breastfeeding to childhood asthma is a controversial issue. The present study investigated the relation between breastfeeding and the prevalence of asthma among a childhood population. The subjects were 25,767 students, representing all public elementary and junior high schools in Tokorozawa, Japan (age range, 6--15 years). The study population included 2,315 students with asthma and 21,513 controls. Participants' parents completed the Japanese version of the American Thoracic Society and Division of Lung Diseases, National Heart, Lung, and Blood Institute, questionnaire for children adopted by the Japanese Environmental Agency in 1998. The authors added supplementary questions on the parental history of asthma and feeding patterns from the age of 0--3 months. The risk of breastfeeding for asthma was compared with that of artificial feeding. After adjustment for age, gender, parental smoking status, and parental history of asthma, a significantly higher prevalence of asthma was noted among children who had been breastfed (adjusted odds ratio = 1.198; 95% confidence interval: 1.054, 1.363; p for trend < 0.01). The results indicated that breastfeeding in infancy might be related to the higher prevalence of asthma during preadolescence.     

Development of Langerhans cell histiocytosis associated with chronic active Epstein-Barr virus infection

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by a status of lymphoproliferative disease of EBV-infected cells, resulting in chronic or recurrent infectious mononucleosis-like symptoms. CAEBV is always accompanied by life-threatening complications. We report the case of a 2-year-old female patient with CAEBV who subsequently developed Langerhans cell histiocytosis (LCH) presenting with bilateral exophthalmos, bone, and skin involvement. In situ hybridization for EBER revealed EBV-infected B-cells present in lesional tissue implying that interactions between EBV-infected B-cells and lesional Langerhans cells may be associated with the development of LCH.     

Association study between catechol-O-methyltransferase polymorphisms and uterine leiomyomas in a Japanese population

PURPOSE: To investigate a possible association between uterine leiomyomas and catechol-O-methyltransferase (COMT) polymorphisms in a Japanese population. METHODS: We compared the allele frequencies and genotype distributions of the exon 4 NlaIII restriction site polymorphism (RSP), the P2 promoter HindIII RSP at -1217, and the exon 6 BglI RSP in the COMT gene in 250 leiomyoma cases and 182 controls using polymerase chain reaction-restriction fragment-length polymorphism analysis. RESULTS: No significant differences in allele frequencies and genotype distributions of the exon 4 NlaIII RSP, the P2 promoter HindIII RSP at -1217, and the exon 6 BglI RSP were found between uterine leiomyoma cases and controls. Moreover, no associations were noted between these three polymorphisms in COMT genes and leiomyoma size or a family history of uterine leiomyomas. CONCLUSION: COMT gene polymorphisms are unlikely to be associated with an increased risk of uterine leiomyomas in a Japanese population.     

An inhaled inducible nitric oxide synthase inhibitor reduces damage of Candida-induced acute lung injury

Excessive nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) aggravates acute lung injury (ALI) by producing peroxynitrite. We previously showed by immunostaining that the expression of iNOS was suppressed by inhalation of N(G)-nitro-L-arginine methyl ester in mice with Candida-induced ALI. This study tested the hypothesis that a novel iNOS inhibitor suppresses not only iNOS expression, but also iNOS messenger RNA (mRNA) production by interrupting a positive feedback loop at the time of NO production in Candida-induced ALI. Mice were pretreated by inhalation of saline or ONO-1714, a selective iNOS inhibitor, and were given an intravenous injection of Candida albicans to induce ALI. After inhalation of 1 mM aerosolized ONO-1714, the nitrite-nitrate concentration in bronchoalveolar lavage fluid (BALF) at 24 h was significantly lower than that after inhalation of saline. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels and neutrophils in BALF were decreased by inhalation of ONO-1714. Inhalation of ONO-1714 markedly suppressed nitrotyrosine production and inhibited the expression of iNOS mRNA as well as proteins in the lung. Survival was prolonged by inhalation of ONO-1714. We conclude that pretreatment with inhaled ONO-1714 suppresses the production of peroxinitrite and decreases oxidative stress associated with peroxinitrite in Candida-induced ALI.     

Neurohypophyseal granulomatous germinoma invading the right cavernous sinus: case report and review of the literature

We encountered a rare case of neurohypophyseal germinoma with a prominent granulomatous reaction, which invaded the right cavernous sinus. The neuroimaging and histopathology features in this case were unique, distinguishing it from other types of suprasellar lesions. A 13-year-old boy presented with loss of appetite and polyuria; both symptoms were present for 1 year, and headache, general fatigue and blurred vision present for the prior 2 months. On admission, neurological examination indicated bitemporal hemianopsia and optic atrophy. Endocrinological exam showed panhypopituitarism. Tumor markers such as alpha-fetoprotein, human growth hormone, carcinoembryonic antigen, and placental alkaline phosphatase were negative. Brain CT revealed a suprasellar tumor with calcification. MR T(1)-weighted and T(2)-weighted images showed the tumor to be isointense to normal brain parenchyma and to be enhanced densely. The tumor also involved the right cavernous sinus, so that a biopsy was performed by the transsphenoidal approach. On pathologic examination of the specimen, typical large tumor cells with lymphocytic cell infiltration and prominent granulomatous reaction were observed. Neurohypophyseal granulomatous germinoma was diagnosed. Radiotherapy was performed with a total dose of 51 Gy and the tumor shrank remarkably. The patient returned to school under hormone replacement therapy.