Selective activation of ceruloplasmin promoter in ovarian tumors: potential use for gene therapy

Gene therapy provides a novel treatment approach to cancer patients. Ideally, expression of therapeutic genes driven by cancer-specific promoters would only target tumors resulting in minimal toxicity to normal tissues. While there is a need of more effective and tolerable treatments for ovarian cancer patients, we aimed to identify gene promoters with high activity in ovarian tumors that can be potentially used in gene therapy to drive the expression of a therapeutic gene in tumors. To identify such promoters, a literature search was performed to reveal genes that are preferentially expressed in ovarian cancer compared with normal ovarian tissue. We found that the ceruloplasmin promoter drove up to 30-fold higher luciferase expression in ovarian cancer cells compared with immortalized normal cells. Furthermore, deletion studies revealed an activator protein-1 (AP-1) site in the ceruloplasmin promoter to be critical for optimal ceruloplasmin promoter activity. Ceruloplasmin promoter activity was significantly activated by 1-O-tetradecanoyl phorbol-13-acetate, a c-jun activator, and conversely suppressed by SP600125, a c-jun inhibitor. Consistently, the ceruloplasmin AP-1 site was specifically recognized by c-jun both in vitro and in vivo. Immunohistochemical analyses of human ovarian cancer specimens showed a direct correlation (r = 0.7, P = 0.007) between expression levels of c-jun and ceruloplasmin. In nude mice carrying SKOV3.ip1 xenografts, the ceruloplasmin promoter demonstrated significantly higher activities in tumors compared with normal organs. Together, these results suggest that the ceruloplasmin promoter activity is significantly enhanced in ovarian cancer and therefore may be exploited as a promising cancer-specific promoter in developing new gene therapy strategies for ovarian cancer.     

Screening postpartum depression with the Taiwanese version of the Edinburgh Postnatal Depression scale

This study is intended to develop the Taiwanese version of the Edinburgh Postnatal Depression Scale (EPDS-T), to evaluate its validity, and to estimate the prevalence of postpartum depressive disorders (PPD) among Taiwanese women. A prospective cohort of 203 subjects who completed the EPDS-T, the Beck Depression Inventory (BDI-II), and postpartum questionnaire at 6 weeks after giving birth were assessed with the Mini-International Neuropsychiatric Interview (MINI) and DSM-IV to establish their psychiatric diagnoses. We tested the validity of EPDS-T against the clinical diagnoses and compared its applicability with BDI-II. We found that the Taiwanese version of EPDS-T had satisfactory sensitivity and better specificity than BDI-II, that the 12/13 cutoff point was the best for screening PPD, and that 10.3% of the study population suffered from depressive disorders at 6 weeks postpartum. Based on the findings of this study, we suggest that PPD prevalence among Taiwanese women is not lower than that among most Western populations and that the validated EPDS-T can be used for early detection and management of postpartum depression in Taiwan.     

Eikenella corrodens in subgingival plaque: relationship to age and periodontal condition

BACKGROUND: The purpose of this study was to determine the prevalence and distribution of Eikenella corrodens (E. corrodens) in subgingival plaque in different age and periodontitis groups and to examine whether its presence is related to periodontal diseases. METHODS: A total of 273 subgingival plaque samples from 213 periodontitis patients and 60 healthy subjects were assessed. Smears from each plaque sample were made and E. corrodens was detected by means of indirect immunofluorescent technique. Mean percentage of E. corrodens per total bacteria (distribution) was calculated in each sample. The prevalence (% of positive samples) and distribution of E. corrodens were statistically analyzed based on age or diagnosis by means of Fisher's exact test and analysis of variance (ANOVA). RESULTS: Prevalence of E. corrodens decreased by age in the healthy control group; however, prevalence did not change in periodontitis groups. Distribution of E. corrodens was highest in juvenile periodontitis (JP) (2.3 +/- 1.5%) followed by post-JP (1.7 +/- 2.1%), prepubertal periodontitis (1.4 +/- 1.1%), rapidly progressive periodontitis (0.8 +/- 0.7%), adult periodontitis (0.7 +/- 0.6%), and healthy subjects (0.3 +/- 0.3%) (ANOVA, P<0.0001). The <20-year-old age group with periodontitis showed the highest distribution of E. corrodens (2.2 +/- 1.6%) compared to the older age groups who were either healthy or had periodontitis (ANOVA, P<0.0001). CONCLUSIONS: Since the distribution of E. corrodens is significantly higher in JP, post-JP, and PP, E. corrodens might play an important role in the occurrence or progression of periodontitis in young patients.     

Assessment of genetic damage by methyl methacrylate employing in vitro mammalian test system

Methyl methacrylate (MMA) is a volatile liquid widely used in the manufacture of acrylic polymers. In modern dentistry, MMA is the mainstream material in denture bases. MMA has been implicated as primary irritant and sensitizer, which can cause allergic eczematous reaction on the oral mucosa as well as skin. To date, there is growing concern that MMA may produce genetic damage by inducing mutation. In this study, colony forming efficiency, DNA synthesis, and cytogenetic assays were performed to investigate the adverse effects of MMA in cultured CHO cells. MMA was found to decrease colony formation in a dose- and time-dependent manner (P<0.05). MMA also inhibited DNA synthesis in a dose-dependent manner (P<0.05). The chromosome aberrations induced by MMA were the chromatid-type aberrations in the treated cultures. Moreover, the gaps and breaks were the most common type of aberrations observed. The sister-chromatid exchange frequencies were found to increase in the concentration of MMA. In this study, MMA was found to be not only a cytotoxic agent but also a genotoxic agent. The effects observed following treatment with low dose for longer duration is of relevance to the condition of the oral mucosa of the denture wears. Denture base resin could constantly release MMA extended periods, possibly causing moderate toxic reactions and possibly contributing to adverse effects on the mucosa.     

Hormone replacement therapy and menopause: a review of randomized,double-blind,placebo-controlled trials

Hormone replacement therapy (HRT) is frequently prescribed to healthy women to ameliorate menopausal symptoms. HRT is used long term (> or = 1 year) to prevent chronic disease in older women. The objective of this study was to review the benefits and risks of HRT and studies of menopause or HRT in Taiwan via a MEDLINE search. Recommendations are provided for future HRT research in Taiwan. Randomized, double-blind, placebo-controlled clinical trials are considered the gold standard of scientific evidence. A MEDLINE literature search (January 1966-July 2002) identified 23 papers on trials (> or = 1 year) that met the inclusion criteria. The results showed that various HRT regimens used for more than 1 year caused more harm than good in healthy menopausal women and that there was no benefit for women with coronary artery disease, Alzheimer's disease, hysterectomy, hysterosalpingo-oophorectomy, and ischemic stroke. None of this research was conducted in Taiwan. A MEDLINE search using the key words "estrogen replacement therapy and menopause in Taiwan" identified 16 studies. There was only one, short-term, HRT trial. No evidence suggested benefits from long-term HRT in menopausal women in Taiwan.     

Determinants of inorganic arsenic methylation capability among residents of the Lanyang Basin,Taiwan: arsenic and selenium exposure and alcohol consumption

The objective of this study was to assess individual variation in inorganic arsenic methylation capability and the association between selenium levels in urine and blood, and inorganic arsenic methylation capability among residents of the Lanyang Basin who drank groundwater and were exposed to high concentrations of inorganic arsenic. According to the arsenic concentration of their drinking water, they were equally and randomly classified into four groups of 252 persons. It turned out that the higher the concentration of arsenic in well water was and thus the cumulative arsenic exposure, the higher the total inorganic arsenic metabolites in urine (total As(i)) and the overall inorganic and organic arsenic in urine (overall As(i+o)) were. The percentage of inorganic arsenic significantly decreased and the DMA percentage significantly increased as the concentration of urinary selenium and serum alpha-tocopherol increased. It appeared that urinary selenium levels increased the metabolism by methylation of arsenic, a finding that requires further investigation.     

Ion release from NiTi orthodontic wires in artificial saliva with various acidities

NiTi orthodontic wire products from different manufacturers would have different corrosion resistance. We assayed the corrosion resistance, in terms of ion release, of different NiTi orthodontic wires in artificial saliva with various acidities. Four types of as-received commercial NiTi orthodontic wires were immersed in artificial saliva (37 degrees C) at pH 2.5-6.25 for different periods (1-28d). The amount of Ni and Ti ions released from NiTi wires was determined using an atomic adsorption spectrophotometer. Surface morphology and roughness of wires were related to the corrosion resistance. Results showed that the manufacturer, pH value, and immersion period, respectively, had a significantly statistical influence on the release amount of Ni and Ti ions. The amount of Ni ions released in all test solutions was well below the critical value necessary to induce allergy and below daily dietary intake level. The amount of Ti ions released in pH>/=3.75 solution was mostly not detectable, representing that the TiO(2) film on NiTi wires exhibited a good protection against corrosion. Pre-existed surface defects on NiTi wires might be the preferred locations for corrosion. The NiTi wire with the highest release amount of metal ions had the maximal increase in surface roughness after immersion test, while a rougher surface did not correspond to a higher metal ion release.     

Accidental subdural catheterization due to complication of epidural anesthesia--a case report

Although accidental subdural injection is a well-recognized complication of epidural block, only a mere handful cases have been substantially proven by radiological evidence. Here we report a case of subdural catheterization during the attempt of epidural anesthesia for a gynecological procedure. Its clinical course and radiological findings are compared with those of the cases previously reported in literature. Whenever there is the occurrence of widespread of sensory block together with respiratory distress and hemodynamic unstability following epidural injection of local anesthetic, a subdural injection should be considered in spite of a negative confirmation. Repeated subdural injection of a local anesthetic at the same site may predispose patients to serious morbidity. Therefore, we recommend that when a subdural injection is evident or suspected, reinsertion of the catheter in the epidural space via another entry or contemplation of a switch to another anesthetic technique is mandatory.