Ming-Chih Chou

Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study.

Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double‐blind, placebo‐controlled study for 6u2003months. Patients (aged 6–12u2003yr) with mild‐to‐moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7u2003mg of D.p. and 3.0u2003mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6u2003months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (pu2003<u20030.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1u2003s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (pu2003<u20030.05). No severe adverse effects were reported. Our results revealed that treatment for 6u2003months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild‐to‐moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.

Randomized placebo‐controlled trial comparing montelukast and cetirizine for treating perennial allergic rhinitis in children aged 2–6 yr

Leukotriene receptor antagonists (LTRAs) were recently added to the method of treating allergic rhinitis (AR). However, in children under 6u2003yr old, there has been no study about its efficacy in treating AR. We aim to compare the clinical efficacy of montelukast, cetirizine and placebo in the treatment of children from 2 to 6u2003yr old with perennial allergic rhinitis (PAR), to see if there are any significant differences. Sixty children were selected and treated with montelukast, or cetirizine, or placebo once daily. The efficacy of the three agents was compared with the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Total Symptom Score (TSS) by diary. In addition, we also examined serum IgE, serum eosinophil cationic protein (ECP), blood eosinophil counts, nasal airway resistance (NAR) and eosinophil percentage in nasal smears. The results revealed that both montelukast and cetirizine were significantly efficacious compared with placebo in NAR, eosinophil percentage in nasal smears, PRQLQ, TSS and all symptom items except nasal itching, throat itching and tearing. For nasal itching, only cetirizine was significantly efficacious. On the other hand, for night sleep quality, montelukast was significantly superior to cetirizine.

Tannic acid-induced apoptosis and -enhanced sensitivity to arsenic trioxide in human leukemia HL-60 cells.

Tannic acid (TA), a glucoside of gallic acid polymer, has been shown to possess anti-bacterial, anti-enzymatic, anti-tumor and astringent properties. However, the anti-cancer activity of TA in leukemia is still obscure. In this study, we showed TA-induced apoptotic death in acute myeloid leukemia (AML) HL-60 cells via dose- and time-dependent manner as well as increase of sub-G1 fraction, chromosome condensation, and DNA fragmentation. Further analysis demonstrated the involvement of activation of caspase cascade, cleavage of poly (ADP-ribose) polymerase (PARP), disruption of mitochondrial membrane potential, and release of Cytochrome C, in TA-induced apoptosis. These effects were probably associated with the increase of intracellular superoxide in mitochondrial signaling pathway which attributed to the down-regulation of superoxide dismutase (SOD). Notably, a low dose of TA is sufficient to aggravate arsenic trioxide (As(2)O(3))-induced cytotoxicity in HL-60 cells. Altogether, this study suggested the effects of TA to induce apoptosis in HL-60 and therapeutic potential in AML by being an adjunct to As(2)O(3).

Evaluation of internal consistency and re-test reliability of Bath ankylosing spondylitis indices in a large cohort of adult and juvenile spondylitis patients in Taiwan

The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Score (BAS-G) have been recommended for evaluating function and disability in patients with ankylosing spondylitis (AS). The aim of this study was to develop a Chinese version of the BASDAI, BASFI, and BAS-G and assess their reliability and validity. The Chinese version was obtained after a translation and back-translation process. A total of 447 patients with adult and juvenile AS were assessed using these three instruments. Reliability was tested by internal consistency and test–retest reliability. Internal consistency of the instrument was given as Cronbach’s alpha. Test–retest reliability was assessed by intraclass correlation coefficient. To assess the sensitivity to change, 153 patients were included in an 8-week follow-up study. In our analysis, the reliability of these three instruments—the BASDAI, BASFI, and BAS-G—for a 24-h test–retest showed acceptable intraclass correlation coefficients (0.92–0.94). Our Chinese versions of the BASDAI, BASFI, and BAS-G also showed 0.87, 0.94, and 0.90, respectively, with Cronbach’s alpha coefficient, indicating good reliability. For sensitivity to change in 8-week follow-up, all three instruments showed 5.0 to 5.4% changes. Our Chinese versions of the BASDAI, BASFI, and BAS-G showed adequate reliability, validity, and responsiveness to clinical change. Thus, disease activity and functional status in Chinese-speaking patients with AS may be adequately evaluated with these versions of the original instruments.

Anti-herpes simplex virus effects of berberine from Coptidis rhizoma, a major component of a Chinese herbal medicine, Ching-Wei-San

Berberine is an alkaloid extracted from Coptidis rhizome. Among the individual herbal components of a Chinese herb medicine, Ching-Wei-San, Coptidis Rhizoma has the most potent antimicrobial activity. By high-pressure liquid chromatography, the quantitative analysis of berberine from 6.25-mg/mL (w/v) Coptidis rhizome extract or 50.00-mg/mL (w/v) Ching-Wei-San was determined to be 0.26xa0mg/mL. To explore the potential use of Ching-Wei-San against herpes simplex virus (HSV) infection, the cytotoxicity, anti-HSV-1 and anti-HSV-2 activity in Vero cells were assayed. The selectivity index of berberine was about 1.2–1.5 times higher than that of Coptidis rhizome extract and Ching-Wei-San. Moreover, the antiviral activities correspond to the content of berberine in the aqueous solution. Berberine may interfere with the viral replication cycle after virus penetration and no later than the viral DNA synthesis step, and its activities were not affected by the preparation processes. Berberine, the natural plants that contain this component, including Coptidis rhizome, and Ching-Wei-San have all shown anti-HSV effects.

Upregulation of Heme Oxygenase-1 Expression in Areca-quid-chewing-associated Oral Squamous Cell Carcinoma

BACKGROUND/PURPOSEnHeme oxygenase-1 (HO-1) is known as an oxidative stress responsive protein that is upregulated by various physiologic and endogenous stimuli. HO-1 has been proposed to provide an important cellular response that protects cells against oxidative damage. Areca quid chewing is a major risk factor in the development and further progression of oral squamous cell carcinoma (OSCC). The aim of the present study was to investigate the difference in HO-1 expression in normal human oral epithelium and OSCC, and further explore the potential mechanism that may lead to HO-1 expression.nnnMETHODSnThirty-five OSCC and 10 normal epithelium specimens were examined by immunohistochemistry and analyzed by clinicopathologic profiles. The oral epithelial GNM cell line was challenged with arecoline, a major areca nut alkaloid, by reverse-transcriptase polymerase chain reaction. Furthermore, tobacco smoke carcinogen benzo[a]pyrene (BaP) and glutathione (GSH) precursor N-acetyl-L-cysteine were added to find the possible regulatory mechanisms.nnnRESULTSnHO-1 expression was significantly higher in OSCC specimens (p < 0.05). No significant difference in HO-1 expression was observed with respect to age, sex, T category, and stage (p > 0.05). The high HO-1 expression was associated with lymph node metastasis (p = 0.005). In addition, arecoline was found to elevate HO-1 mRNA in a dose-dependent manner (p < 0.05). The addition of BaP enhanced arecolineinduced HO-1 expression (p < 0.05). Moreover, addition of NAC markedly inhibited arecoline-induced HO-1 expression (p < 0.05).nnnCONCLUSIONnTaken together, these results suggest that HO-1 expression is significantly upregulated in OSCC from areca quid chewers, and arecoline may be responsible for enhanced HO-1 expression in vivo. The compounds of cigarette smoke may act synergistically in the pathogenesis of areca-quid-chewing-associated OSCC. The regulation of HO-1 expression induced by arecoline is critically dependent on intracellular GSH concentration.

Therapeutic effects of cantharidin analogues without bridging ether oxygen on human hepatocellular carcinoma cells.

Previous research indicates that cantharidin, norcantharidin and their analogues exhibit anticancer activity due to their inhibition of cancer cell lines such as HL60, HT29 and L1210. The anticancer activities of cantharidin, norcantharidin and their analogues involve the suppression of serine/threonine protein phosphatases (PPs) activity. However, cantharidin is not suitable for cancer therapy because of its high cytotoxicity in vitro (IC(50) = 21 microM in primary cultured rat hepatocytes). In this study, synthetic cantharidin analogues with a structure of aminothiazole compounds 3-9 and a structure of anhydride compounds 10-12 were screened for anticancer activities and cytotoxic effects on human hepatocellular carcinoma cell (HCC) lines HepG2, Sk-Hep1, and primary cultured rat hepatocytes. Experimental results indicated that compounds 3-9 did not perform as expected with regard to anticancer activity and exhibited lower cytotoxicity. Compound 10 promoted apoptosis in HepG2 (IC(50) = 62 microM) and SK-Hep1(IC(50) = 151 microM) cell lines. Compounds 11 and 12 had anticancer potential similar to that of compound 10. After treatment with compounds 3-12, primary cultured rat hepatocytes exhibited no cytotoxicity (IC(50) > 200 microM). By investigating the structure-activity relationship (SAR) of these analogues as a whole, this study suggests that the anhydride ether oxygen such as in cantharidin, norcantharidin and compounds 10-12 may be correlated with HCC survival suppression. The results further suggest that the elimination of bridging ether oxygen on the ring, such as in compounds 10-12, can decrease cytotoxicity.

ACE gene polymorphism might disclose why some Taiwanese children with allergic rhinitis develop asthma symptoms but others do not.

Although allergic asthma and allergic rhinitis have recently been considered to be a single disease, many questions remain unanswered. Why do some atopic patients develop asthma symptoms and others develop allergic rhinitis symptoms? Which factors play a role in the development of different allergic phenotypes? We hypothesized that angiotensin‐converting enzyme (ACE) gene polymorphism might play a role in the development of asthma phenotypes in children with allergic rhinitis. The study sample included 106 children with allergic rhinitis, but no asthma, and 105 age‐ and gender‐matched children with allergic rhinitis and asthma. Subjects of both groups exhibited the same systemic immunologic changes and allergen sensitivities. Controls consisted of 102 healthy children. The ACE genotype was determined by polymerase chain reaction. The serum total immunoglobulin E (IgE) level, allergen‐specific IgE sensitivity, and eosinophil count were also measured. The frequencies of the DD genotype were significantly higher in the children with both allergic rhinitis and asthma than in the children with allergic rhinitis but no asthma [pu2003=u20030.018; odds ratio (OR)u2003=u20033.257; (1.222–8.680)]. Results of this study suggest that ACE gene polymorphism DD genotype might play a role in the development of the asthma phenotype in children with allergic rhinitis.

The significance of altered gelatinase expression in the synovium of patient with arthritic effusions

In this study we quantified the levels of matrix metalloproteinase-2 and 9 (MMP-2 and 9) in effusions and serial synovial cultures of patients with arthritis of the knee in order to investigate the correlations between MMP and cell counts in effusions as well as the possible roles of the synovium. In 49 patients with arthritis of the knee (series I) we examined the cell counts and the amounts of MMP-2 and 9 in 51 effusions. In 20 knee samples of series I of patients who received arthroscopy (series II), we examined the amounts of MMP-2 and 9 in effusions and serial synovial organ cultures. We also compared the gene expressions of MMP-2 and 9 and MT1-MMP in serial synovial cultures using RT-PCR. In series I, significantly more proMMP-9 appeared in effusions from the inflammatory group than in the non-inflammatory and hemorrhagic group (p <0.001). The levels of proMMP-9 correlated with the neutrophil counts in the effusions (p <0.001). In series II synovial cultures, the activities of latent and activated forms of MMP-2 and 9 in lesional areas were all higher than that in paralesional ones (p <0.05). In RT-PCR analysis, MMP-2, -9 and membrane type 1 MMP mRNA levels of lesional areas also showed increased expression. Our data suggest that the analysis of MMP-9 indicates the inflammatory condition of the joints and that additional synovectomy may be beneficial for patients with inflammatory synovitis, compared with non-inflammatory and hemorrhagic arthritis.

Plasma homocysteine status in patients with ankylosing spondylitis

Homocysteine (Hcy), a sulfur-containing amino acid, is eliminated through B vitamins-dependent pathways. Hyperhomocysteinemia has been found to be an independent risk factor for atherosclerotic cardiovascular, cerebrovascular, and peripheral vascular diseases. Recently, psoriasis, lupus, and rheumatoid arthritis were reported to be associated with hyperhomocysteinemia. This study was aimed to evaluate the changes of plasma Hcy level before and after sulfasalazine and MTX therapy in patients with ankylosing spondylitis (AS). One hundred and two patients with AS and ten normal controls were enrolled in the cross-sectional case-control study. Fasting plasma Hcy levels were determined by ELISA kits (IMX, Abbott). Hcy levels were compared to their Bath AS disease activity index (BASDAI) and the usage of sulfasalazine and/or MTX. Active disease was defined by BASDAI as more than 3 in a 10-cm scale with ESR >20xa0mm/h. For those patients with plasma Hcy ≥15xa0μmol/l, a perspective trial of daily supplement of vitamin B-12 0.5xa0mg, B-6 50xa0mg, and folic acid 5xa0mg for 2xa0weeks were also tested for the efficacy. Plasma Hcy level increased significantly in AS patients under sulfasalazine (10.4±3.8xa0μmol/l, p<0.05), MTX (11.9±4.7, p<0.05) and sulfasalazine/MTX combination treatment (11.2±2.6, p<0.05) compared with normal controls (8.6±1.2xa0μmol/l) and AS patients without DMARD(9.4± 2.6μmol/l). No correlation between disease activity and plasma Hcy level was found. Daily supplement of vitamin B-12 0.5xa0mg, B-6 50xa0mg, and folic acid 5xa0mg can lower Hcy level in 2xa0weeks (32.3±24.0 vs 15.6±11.1xa0μmol/l, p=0.007). Plasma homocysteine level did significantly increase in AS patients under sulfasalazine or MTX treatment. B-vitamins should be considered as a routine supplementation for patients who underwent sulfasalazine and/or MTX treatment. Further longitudinal studies are required to confirm the conclusions.