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Biomedical subjects

C-C Chen

Publications and source records attributed to C-C Chen.

At least 19 recordsLinked to original sources
PubMed2006

Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels.

Although T-type Ca(2+) channels are implicated in nociception, the function of specific subtypes has not been well defined. Here, we compared pain susceptibility in mice lacking Ca(V)3.2 subtype of T-type Ca(2+) channels (Ca(V)3.2(-/-)) with wild-type littermates in various behavioral models of pain to explore the roles of Ca(V)3.2 in the processing of noxious stimuli in vivo. In acute mechanical, thermal and chemical pain tests, Ca(V)3.2(-/-) mice showed decreased pain responses compared to wild-type mice. Ca(V)3.2(-/-) mice also displayed attenuated pain responses to tonic noxious stimuli such as intraperitoneal injections of irritant agents and intradermal injections of formalin. In spinal nerve ligation-induced neuropathic pain, however, behavioral responses of Ca(V)3.2(-/-) mice were not different from those of wild-type mice. The present study reveals that the Ca(V)3.2 subtype of T-type Ca(2+) channels are important in the peripheral processing of noxious signals, regardless of modality, duration or affected tissue type.

Animals↗
PubMed2006

Long-term inhibition of hepatitis B virus in transgenic mice by double-stranded adeno-associated virus 8-delivered short hairpin RNA.

RNA interference (RNAi) was reported to block hepatitis B virus (HBV) gene expression and replication in vitro and in vivo. However, it remains a technical challenge for RNAi-based therapy to achieve long-term and complete inhibition effects in chronic HBV infection, which presumably requires more extensive and uniform transduction of the whole infected hepatocytes. To increase the in vivo transfection efficiency in liver, we used a double-stranded adeno-associated virus 8-pseudotyped vector (dsAAV2/8) to deliver shRNA. HBV transgenic mice were used as an animal model to evaluate the inhibition effects of the RNAi-based gene therapy. A single administration of dsAAV2/8 vector, carrying HBV-specific shRNA, effectively suppressed the steady level of HBV protein, mRNA and replicative DNA in liver of HBV transgenic mice, leading to up to 2-3 log(10) decrease in HBV load in the circulation. Significant HBV suppression sustained for at least 120 days after vector administration. The therapeutic effect of shRNA was target sequence dependent and did not involve activation of interferon. These results underscore the potential for developing RNAi-based therapy by dsAAV2/8 vector to treat HBV chronic infection, and possibly other persistent liver infections as well.

Animals↗
PubMed2006

Development and evaluation of an air-curtain fume cabinet with considerations of its aerodynamics.

In order to avoid the inherent aerodynamic difficulties of the conventional fume hood, an innovative design--the 'air curtain-isolated fume hood' is developed. The new hood applies a specially designed air curtain (which is generated by a narrow planar jet and a suction slot flow at low velocities) across the sash plane. The hood constructed for the study is full size and transparent for flow visualization. The aerodynamic characteristics are diagnosed by using the laser-light-sheet-assisted smoke flow visualization method. Four characteristic air-curtain flow modes are identified in the domain of jet and suction velocities when the sash remains static. Some of these characteristic flow modes have much improved flow patterns when compared with those of the conventional fume hoods. From the viewpoint of the aerodynamics and mass transport, the results indicate that the air curtain properly setup across the sash opening allows almost no sensible exchange of momentum and mass between the flowfields of the cabinet and the outside environment. Two standard sulfur hexafluoride (SF6) tracer gas concentration measurement methods following the ANSI/ASHRAE 110-1995 standard and the prEN14175 protocol for static test are employed to examine the contaminant leakage levels. Results of the rigorous examinations of leakage show unusually satisfactory hood performance. The leakage of the tracer gas can approach almost null (<0.001 p.p.m.) if the jet and suction velocities are properly adjusted.

Air Movements↗
PubMed2006

Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway.

Epimedium brevicornum Maxim (EbM) has been reputed to have sexual stimulation effects on males. The study is aimed to test the hypothesis that EbM extracts relaxed the corpus cavernosum (CC) smooth muscle through activation of multitargets on nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway. Water extract of EbM and its subfraction (EP-20) were prepared and standardized by high-performance liquid chromatography. Isolated rabbit CC strips were mounted in organ baths and isometric tension was recorded in the presence or absence of specific inhibitors related to NO/cGMP signaling such as L-N(G)-nitro-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor) or phosphodiesterase 5 (PDE 5) inhibitors. cGMP level was determined in EP-20-treated CC strips. The results showed that EP-20 enriched the content of L-arginine in the process of purification and relaxed the CC smooth muscle precontracted with phenylephrine (PE, 1 microM) in a concentration-dependent manner. Besides, EP-20 increased the amount of cGMP production in rabbit CC tissues. Coincubation with EP-20 and L-NAME or ODQ significantly decreased EP-20-induced relaxation whereas EP-20 increased sodium nitroprusside-induced relaxation in PE-precontracted CC strips. Besides, EP-20 increased the potency and the duration of the relaxation effects caused by electrical field stimulation. Finally, EP-20 could potentiate PDE 5 inhibitors in relaxation of PE-precontracted CC strips. We concluded that extract of EbM relax the CC smooth muscle through multitargets in NO/cGMP/PDE 5 pathway and might bring into perspective the treatment strategy for those patients with erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2006

Cancer risks in a population with prolonged low dose-rate gamma-radiation exposure in radiocontaminated buildings, 1983-2002.

PURPOSE: To assess cancer risks in a population that received prolonged low dose-rate gamma-irradiation for about 10 years as a result of occupying buildings containing 60Co-contaminated steel in Taiwan. MATERIALS AND METHODS: The cancer risks were compared with those populations with the same temporal and geographic characteristics in Taiwan by standardized incidence ratios (SIR), adjusted for age and gender. The association of cancer risks with excess cumulative exposure was further evaluated for their relative risks by the Poisson multiple regression analysis. RESULT: A total of 7271 people were registered as the exposed population, with 101,560 person-years at risk. The average excess cumulative exposure was approximately 47.8 mSv (range < 1 - 2,363 mSv). A total of 141 exposed subjects with various cancers were observed, while 95 developed leukemia or solid cancers after more than 2 or 10 years initial residence in contaminated buildings respectively. The SIR were significantly higher for all leukemia except chronic lymphocytic leukemia (n = 6, SIR = 3.6, 95% confidence interval [CI] 1.2 - 7.4) in men, and marginally significant for thyroid cancers (n = 6, SIR = 2.6, 95% CI 1.0 - 5.7) in women. On the other hand, all cancers combined, all solid cancers combined were shown to exhibit significant exposure-dependent increased risks in individuals with the initial exposure before the age of 30, but not beyond this age. CONCLUSIONS: The results suggest that prolonged low dose-rate radiation exposure appeared to increase risks of developing certain cancers in specific subgroups of this population in Taiwan.

Adolescent↗
PubMed2006

Preserving pulpal health of a geminated maxillary lateral incisor through multidisciplinary care.

AIM: To report the multidisciplinary care of an unaesthetic geminated maxillary lateral incisor tooth, which allowed its preservation in the mouth. SUMMARY: Preoperative examination of an unsightly geminated maxillary lateral incisor (tooth 22) demonstrated two pulp chambers and open apices, with normal pulp sensitivity responses. At surgery, a periodontal mucoperiosteal flap was reflected and the distal part of the geminated tooth was removed. The exposed root canal of the preserved tooth was sealed with mineral trioxide aggregate (MTA). The extraction socket and osseous defect was grafted with decalcified freeze-dried bone allograft (DFDBA) before flap closure. During follow-up, distal caries in tooth 22 and a diastema between tooth 22 and 23 were managed with composite resin restorations. Forty-two months postoperatively, normal thermal and electrical pulp sensitivity tests confirmed pulp health. Convincing apexogenesis and dentinogenesis of the developing root was confirmed by radiographic examination. Acceptable periodontal health including 3-4 mm clinical probing depths was achieved. Optimizing aesthetics and occlusion was accomplished without orthodontic treatment.

Aluminum Compounds↗
PubMed2006

Platonin attenuates LPS-induced CAT-2 and CAT-2B induction in stimulated murine macrophages.

BACKGROUND: Platonin, a cyanine photosensitizing dye, is a potent immunomodulator that suppresses acute inflammation. Platonin not only inhibits interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha production but also improves circulatory failure in septic rats. In addition, platonin reduces plasma nitric oxide (NO) formation during sepsis. However, the effects of platonin on inducible NO synthase (iNOS) and cationic amino-acid transporter (including CAT-2, CAT-2 A, and CAT-2B) expressions during sepsis remain uninvestigated. METHODS: Five groups of confluent murine macrophages (RAW264.7 cells) were randomly allocated to receive a 1-h pretreatment of one of five doses of platonin (0.1 microM, 1 microM, 10 microM, 100 microM, or 1000 microM) followed by lipopolysaccharide (LPS; 100 ng ml(-1)). For negative, positive, and platonin control, three other groups of cell cultures were randomly allocated to receive phosphate-buffered saline, LPS, or platonin (1000 microM). The cultures were harvested after exposing them to LPS for 18 h or a comparable duration in those groups without LPS. NO production, L-arginine transport, and expression of the relevant enzymes were then evaluated. RESULTS: Platonin significantly attenuated LPS-induced up-regulation of iNOS expression and NO production in stimulated murine macrophages in a dose-dependent manner. Platonin also significantly inhibited up-regulation of CAT-2 and CAT-2B expression as well as L-arginine transport in LPS-stimulated murine macrophages in a dose-dependent manner. In contrast, CAT-2 A expression in murine macrophages was not affected by LPS and/or platonin. CONCLUSIONS: Platonin attenuates NO production and L-arginine transport in LPS-stimulated murine macrophages possibly through inhibiting iNOS, CAT-2, and CAT-2B expression.

Amino Acid Transport Systems, Basic↗
PubMed2006

Risk stratification of severe sepsis patients in the emergency department.

OBJECTIVE: To determine the efficacy of the Mortality in Emergency Department Sepsis (MEDS) score in the stratification of patients who presented to the emergency department (ED) with severe sepsis. METHODS: Adults who presented to the ED with severe sepsis were retrospectively recruited and divided into group A (MEDS score <12) and group B (MEDS score > or =12). Their outcomes were evaluated with 28 day hospital mortality rate, length of hospital stay, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) analysis. Discriminatory power of the MEDS score in mortality prediction was further compared with the Acute Physiology and Chronic Health Evaluation (APACHE) II model. RESULTS: In total, 276 patients (44.6% men and 55.4% women) were analysed, with 143 patients placed in group A and 133 patients in group B. Patients with MEDS score > or =12 had a significantly higher mortality rate (48.9% v 17.5%, p<0.01) and higher median APACHE II score (25 v 20 points, p<0.01). Significant difference in mortality risk was also demonstrated with Kaplan-Meier survival analysis (log rank test, p<0.01). No difference in the length of hospital stay was found between the groups. ROC analysis indicated a better performance in mortality prediction by the MEDS score compared with the APACHE II score (ROC 0.75 v 0.62, p<0.01). CONCLUSION: Our results showed that mortality risk stratification of severe sepsis patients in the ED with MEDS score is effective. The MEDS score also discriminated better than the APACHE II model in mortality prediction.

APACHE↗
PubMed2005

Pretreatment prognostic factors and treatment outcome in elderly patients with de novo acute myeloid leukemia.

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) generally have an unfavorable clinical course and are under-represented in clinical trials. The aim of this study was to analyze the prognosis and treatment outcome of elderly AML patients. PATIENTS AND METHODS: We studied 205 AML patients aged 65 years or older at our hospital. Prior to study initiation, we designated 13 variables to be analyzed for their impact on complete remission (CR) rate and overall survival (OS). RESULTS: Induction regimen (standard chemotherapy) and good performance status (PS) (Eastern Cooperative Oncology Group PS 0-1) independently influenced the achievement of CR. Multivariate analysis also determined five poor prognostic factors for OS: poor PS (score 2-4), presence of comorbidities, elevated serum lactate dehydrogenase level (> or =2x upper normal limit), extreme leukocytosis (> or =100 x 10(9)/l) and marked thrombocytopenia (< or =20 x 10(9)/l). Age was not an independent contributing factor in terms of either CR attainment or OS duration. Low-risk patients, who possessed one or less non-leukocytosis poor prognostic factor, had significantly longer disease-free survival and OS than their high-risk counterparts. CONCLUSIONS: Elderly AML patients should be risk-stratified at diagnosis. Anthracycline-based induction chemotherapy would be the best therapeutic option for such patients.

Acute Disease↗
PubMed2005

H-Ras oncogene counteracts the growth-inhibitory effect of genistein in T24 bladder carcinoma cells.

Among eight human bladder cancer cell lines we examined, only T24 cells were resistant to the growth inhibition effect of genistein, an isoflavone and potent anticancer drug. Since the T24 cell line was the only cell line known to overexpress oncogenic H-Ras(val 12), we investigated the role of H-Ras(val 12) in mediating drug resistance. Herein, we demonstrate that the phenotype of T24 cells could be dramatically reversed and became relatively susceptible to growth inhibition by genistein if the synthesis of H-Ras(val 12) or its downstream effector c-Fos had been suppressed. The inhibition of Ras-mediated signalling with protein kinase inhibitors, such as PD58059 and U0126 which inhibited MEK and ERK, in T24 cells also rendered the identical phenotypic reversion. However, this reversion was not observed when an inhibitor was used to suppress the protein phosphorylation function of PI3 K or PKC. These results suggest that the signal mediated by H-Ras(val 12) is predominantly responsible for the resistance of the cells to the anticancer drug genistein.

Antineoplastic Agents↗
PubMed2005

The use of gene silencing to study the role of dopa decarboxylase in mosquito melanization reactions.

Mosquito melanization involves hydroxylation of tyrosine to dopa, which then is oxidized to dopaquinone by phenoloxidase, or decarboxylated to dopamine by dopa decarboxlase (DDC). An Armigeres subalbatus cDNA encoding DDC was cloned and real-time PCR analysis revealed increased transcripts in blood-fed and microfilariae (mf)-inoculated mosquitoes. A double subgenomic Sindbis virus was used to silence DDC and assess its role in melanization of mf. DDC transcription and activity were significantly decreased in silenced mosquitoes, as was the degree of mf melanization 48 h postinoculation; however, melanization increased after 72 and 96 h, demonstrating that DDC influences the rate of melanization. DDC-silenced mosquitoes also exhibit high mortality, over-feeding and abnormal movement, consistent with an involvement of DDC in neurotransmission.

Animals↗
PubMed2005

Role of dopachrome conversion enzyme in the melanization of filarial worms in mosquitoes.

Melanization is an effective defence reaction of mosquito hosts against invading parasites. In mosquitoes, the biosynthesis of melanin is initiated by the hydroxylation of tyrosine to DOPA by phenoloxidase (PO). DOPA is a branch point of the melanization reaction; it may be oxidized to dopaquinone by PO or be decarboxylated to dopamine by dopa decarboxylase. Further oxidation of dopaquinone by PO produces dopachrome. Dopachrome is then converted to 5, 6-dihydroxyindole by dopachrome conversion enzyme (DCE) to produce melanin. The conversion of dopachrome is a rate-limiting step of the melanization reaction, and the presence of PO and DCE significantly accelerates melanization reactions. In this study, a cDNA encoding DCE was cloned from the mosquito Armigeres subalbatus. Real-time PCR analysis revealed increased transcripts from haemocytes in microfilariae (mf)-inoculated mosquitoes. Gene silencing using double-stranded RNA was used to elucidate the role of DCE in the melanization reaction of parasites in Ar. subalbatus. The levels of both DCE transcripts and protein in gene knockdown mosquitoes were dramatically reduced. Compared with controls, the degree of melanization of mf in DCE-knockdown mosquitoes was significantly decreased. These results suggest that DCE is a critical enzyme that is required for effective melanization immune responses.

Amino Acid Sequence↗