Comparison of Ophiopogon japonicus and Liriope spicata var. prolifera from Different Origins Based on Multi-Component Quantification and Anticancer Activity.

The tuberous root of Ophiopogon japonicus (Thunb.) Ker-Gawl. is a well-known Chinese medicine also called Maidong (MD) in Chinese. It could be divided into "Chuanmaidong" (CMD) and "Zhemaidong" (ZMD), according to the geographic origins. Meanwhile, the root of Liriope spicata (Thunb.) Lour. var. prolifera Y. T. Ma (SMD) is occasionally used as a substitute for MD in the market. In this study, a reliable pressurized liquid extraction and HPLC-DAD-ELSD method was developed for the simultaneous determination of nine chemical components, including four steroidal saponins (ophiopojaponin C, ophiopogonin D, liriopesides B and ophiopogonin D'), four homoisoflavonoids (methylophiopogonone A, methylophiopogonone B, methylophiopogonanone A and methylophiopogonanone B) and one sapogenin (ruscogenin) in CMD, ZMD and SMD. The method was validated in terms of linearity, sensitivity, precision, repeatability and accuracy, and then applied to the real samples from different origins. The results indicated that there were significant differences in the contents of the investigated compounds in CMD, ZMD and SMD. Ruscogenin was not detected in all the samples, and liriopesides B was only found in SMD samples. CMD contained higher ophiopogonin D and ophiopogonin D', while the other compounds were more abundant in ZMD. Moreover, the anticancer effects of the herbal extracts and selected components against A2780 human ovarian cancer cells were also compared. CMD and ZMD showed similar cytotoxic effects, which were stronger than those of SMD. The effects of MD may be due to the significant anticancer potential of ophiopognin D' and homoisoflavonoids. These results suggested that there were great differences in the chemical composition and pharmacological activity among CMD, ZMD and SMD; thus, their origins should be carefully considered in clinical application.

Long-Term Trends and Predictors of Medical Resource Utilization and Medical Outcomes in Inguinal Hernia Repair: A Nationwide Cohort Study.

BACKGROUND: Few studies have comprehensively and systematically analyzed nationwide samples. This study purposed to explore temporal trends and predictors of medical resource utilization and medical outcomes in these patients to obtain data that can be used to improve healthcare policies and to support clinical and administrative decision-making. METHODS: This study used nationwide population data contained in the Longitudinal Health Insurance Database of Taiwan. The 14,970 inguinal hernia repair patients were enrolled in this study (age range, 18-100 years) from 1997 to 2013 in Taiwan. After temporal trends analysis of demographic characteristics, clinical characteristics, and institutional characteristics, predictors of postoperative medical resource utilization and medical outcomes were evaluated through multiple linear regression analysis and Cox regression analysis. RESULTS: The prevalence of inguinal hernia repair per 100,000 population significantly decreased from 195.38 in 1997 to 39.66 in 2013 (p < 0.05). Demographic characteristics, clinical characteristics, and institutional characteristics were significantly associated with postoperative medical resource utilization and medical outcomes (p < 0.05). Of these characteristics, both surgeon volume and hospital volume had the strongest association. CONCLUSIONS: The inguinal hernia repair prevalence rate gradually decreased during the study period. Demographic characteristics, clinical characteristics, and institutional characteristics had strong associations with postoperative medical resource utilization and medical outcomes. Furthermore, hospital volume and surgeon volume had the strongest associations with postoperative medical resource utilization and medical outcomes. Additionally, providing the education needed to make the most advantageous medical decisions would be a great service not only to patients and their families, but also to the general population.

Ophiopogon japonicus--A phytochemical, ethnomedicinal and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiopogonis Radix (Maidong in Chinese), the root of Ophiopogon japonicus, is widely used in local medicines of China, Japan and some south-eastern Asian countries. According to the traditional Chinese medicine (TCM) principle, Ophiopogonis Radix nourishes the yin, promotes body fluid production, moistens the lung, eases the mind and clears away heart fire. This review summarizes the achievements of the investigations in botany, phytochemistry, quality control, traditional uses, pharmacological activities and clinical studies on O. japonicus; this review also describes the shortcomings of studies on this herbal drug and thus serves as the basis of further scientific research and development of this traditional herbal drug. MATERIALS AND METHODS: O. japonicus-related information was collected from various resources, including books on Chinese herbs and the Internet databases, such as Google Scholar, SciFinder, Web of Science, Elsevier, ACS, PubMed and China Knowledge Resource Integrated (CNKI). RESULTS: O. japonicus is widely distributed in East Asia, especially in China. Numerous compounds were identified from this plant. The main components of O. japonicus include steroidal saponins, homoisoflavonoids and polysaccharides, which exhibited various pharmacological activities, such as cardiovascular protection, anti-inflammation, anticancer, anti-oxidation, immunomodulation, cough relief, antimicrobial, and anti-diabetes. CONCLUSIONS: O. japonicus is a common traditional Chinese herbal drug used as the main ingredient in many prescriptions. Modern researches verified that O. japonicus can be used either as a healthy food or a therapeutic agent for disease prevention and treatment. The molecular mechanisms and chemical principles of this herbal medicine should be further explored.

Comparing characteristics of adverse drug events between older and younger adults presenting to a Taiwan emergency department.

To compare the proportion, seriousness, preventability of adverse drug events (ADEs) between the older adults (≥ 65 years old) and younger adults (<65 years old) presenting to the emergency department (ED), we conducted a prospective observational cohort study of patients 18 years and older presenting to the ED. For all ED visits between March 1, 2009, and Feb 28, 2010, investigators identified ADEs and assessed cases using the Naranjo adverse drug reaction probability scale. Outcomes (proportion, seriousness, and preventability of ADE, length of ED stay, and hospitalization) and associated variables were measured and compared between younger and older adults. The results showed that of 58,569 ED visits, 295 older adults, and 157 younger adults were diagnosed as having an ADE and included in our analysis. The proportion of ADEs leading to ED visits in the older group, 14.3 per 1000  (295/20,628), was significantly higher than the younger group of 4.1 per 1000  (157/37,941). The older group with ADE had a longer ED stay (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.9-6.4 for stay ≥ 24 hours) and larger proportion of preventable ADEs (OR 2.2, 95% CI 1.4-3.6) than the younger group, but there was no significant difference in terms of serious ADEs (OR 0.6, 95% CI 0.3-1.3 for fatal and life threatening) and hospitalization (OR 1.5, 95% CI 0.9-2.6) between the 2 groups. In addition, patients in the older group were more likely to be male, to have symptoms of fatigue or altered mental status, to involve cardiovascular, renal, and respiratory systems, and to have higher Charlson comorbidity index scores, higher number of prescription medications, and higher proportion of unintentional overdose. In conclusion, the proportion of ADE-related ED visits in older adults was higher than younger adults, and many of these were preventable. The most common drug categories associated with preventable ADEs in the older adults were antithrombotic agents, antidiabetic agents, and cardiovascular agents.

Cellular mechanism underlying hydrogen sulfide induced mouse tracheal smooth muscle relaxation: role of BKCa.

Recent studies have suggested that hydrogen sulfide (H2S), an important endogenous signaling gaseous molecule, participates in relaxation of smooth muscle. Nevertheless, the mechanism of this relaxation effect on respiratory system is still unclear. The present study aims to investigate the physiological function as well as cellular mechanism of H2S in tracheal smooth muscle. Application of the H2S donor, sodium hydrosulphide (NaHS) and the precursor of H2S, l-cysteine (l-Cys) induced mouse tracheal smooth muscle (TSM) relaxation in an epithelium-independent manner. The relaxation of TSM induced by NaHS was abrogated by iberiotoxin (IbTX), the large conductance calcium activated potassium channel (BKCa) blocker. In primary cultured mouse TSM cells, NaHS remarkably increased potassium outward currents in whole-cell patch clamp, hyperpolarized TSM cells and inhibited the calcium influx. All of these effects were significantly blocked by IbTX. Consistent with the results in vitro, administration of NaHS in vivo also reduced airway hyperresponsiveness in Ovalbumin (OVA)-challenged asthmatic mice. Our present study indicates that NaHS can induce mouse TSM relaxation by activating BKCa. These observations reveal the physiological function of H2S in airway, which provides a promising pharmacological target for the treatment of asthma and other respiratory diseases associated with over-contraction of TSM.

Layer-by-layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing.

Efficient and safe delivery systems for siRNA therapeutics remain a challenge. Elevated secreted protein, acidic, and rich in cysteine (SPARC) protein expression is associated with tissue scarring and fibrosis. Here we investigate the feasibility of encapsulating SPARC-siRNA in the bilayers of layer-by-layer (LbL) nanoparticles (NPs) with poly(L-arginine) (ARG) and dextran (DXS) as polyelectrolytes. Cellular binding and uptake of LbL NPs as well as siRNA delivery were studied in FibroGRO cells. siGLO-siRNA and SPARC-siRNA were efficiently coated onto hydroxyapatite nanoparticles. The multilayered NPs were characterized with regard to particle size, zeta potential and surface morphology using dynamic light scattering and transmission electron microscopy. The SPARC-gene silencing and mRNA levels were analyzed using ChemiDOC western blot technique and RT-PCR. The multilayer SPARC-siRNA incorporated nanoparticles are about 200 nm in diameter and are efficiently internalized into FibroGRO cells. Their intracellular fate was also followed by tagging with suitable reporter siRNA as well as with lysotracker dye; confocal microscopy clearly indicates endosomal escape of the particles. Significant (60%) SPARC-gene knock down was achieved by using 0.4 pmole siRNA/µg of LbL NPs in FibroGRO cells and the relative expression of SPARC mRNA reduced significantly (60%) against untreated cells. The cytotoxicity as evaluated by xCelligence real-time cell proliferation and MTT cell assay, indicated that the SPARC-siRNA-loaded LbL NPs are non-toxic. In conclusion, the LbL NP system described provides a promising, safe and efficient delivery platform as a non-viral vector for siRNA delivery that uses biopolymers to enhance the gene knock down efficiency for the development of siRNA therapeutics.

Risk factors associated with adverse drug events among older adults in emergency department.

BACKGROUND: Little is known about the emergency department (ED) visits from drug-related injury among older adults in Taiwan. This study seeks to identify risk factors associated with adverse drug events (ADEs) leading to ED visits. METHODS: We prospectively conducted a case-control study of patients 65years and older presenting to the ED. ED visits between March 1, 2009 and Feb 28, 2010 identified by investigators for suspected ADEs were further assessed by using the Naranjo Adverse Drug Reaction probability scale. For each patient with an ADE, a control was selected and time-matched from the ED population of the study hospital. The association between the risk of adverse drug events and triage, age, gender, serum alanine transaminase (ALT), serum creatinine, number of medications, and Charlson Comorbidity Index scores were analyzed using logistic regression. RESULTS: Of 20,628 visits, 295 ADEs were physician-documented in older adults. Independent risk factors for ADEs included number of medications (adjusted odds ratio [OR]=4.1; 95% confidence interval [CI] 2.4-6.9 for 3-7 drugs; adjusted OR=6.4; 95% CI 3.7-11.0 for 8 or more drugs) and increased concentration of serum creatinine (adjusted OR=1.5; 95% CI 1.1-2.2). Diuretics, analgesics, cardiovascular agents, anti-diabetic agents and anticoagulants were the medications most commonly associated with an ADE leading to ED visits. CONCLUSIONS: This study suggests that prevention efforts should be focused on older patients with renal insufficiency and polypharmacy who are using high risk medications such as anticoagulants, diuretics, cardiovascular agents, analgesics, and anti-diabetic agents.

Involvement of CFTR in oviductal HCO3- secretion and its effect on soluble adenylate cyclase-dependent early embryo development.

BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) plays a critical role in electrolyte and fluid transport in epithelial cells, and women with cystic fibrosis (CF), caused by CFTR gene mutations, have a higher incidence of infertility. METHODS: In the present study, we investigated the expression of CFTR in porcine oviduct and its functional role in oviductal HCO(3)(-) secretion and embryo development with RT-PCR, western blot, patch-clamp, short-circuit current (I(sc)), pH measurement and embryo culture. RESULTS: RT-PCR and western blot analysis showed the expression of CFTR mRNA and protein in the oviduct with its localization demonstrated by immunohistochemistry. The whole-cell patch-clamp recording revealed a forskolin (FSK)-activated current with electrophysiological and pharmacological characteristics of CFTR. The I(sc) measurement showed that FSK-stimulated an increase in the I(sc), which could be significantly reduced by CFTR inhibitor or removal of both CO(2) and HCO(3)(-). pH measurement showed a FSK stimulated alkalization at the apical surface, which could be inhibited by CFTR inhibitor, indicating CFTR-mediated HCO(3)(-) secretion. Mouse embryo development from 2-cell to morula or blastocyst stage was significantly inhibited in the absence of HCO(3)(-) or when co-cultured with HCO(3)(-) secretion-deficient CFTR mutant cells as compared with the wild-type. RT-PCR, western blot and immunostaining showed the expression of soluble adenylate cyclase (sAC), the known HCO(3)(-) sensor, in embryos. Treatment with its inhibitors, 2-hydroxyestradiol and KH7, prevented the HCO(3)(-) dependent embryo development. CONCLUSION: The present results suggest that CFTR-mediated oviductal HCO(3)(-) secretion may be vital for sAC-dependent early embryo development, a defect of which may contribute to the reduced fertility seen in women with CF.

The cystic fibrosis transmembrane conductance regulator in reproductive health and disease.

The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel regulated by cAMP-dependent phosphorylation, which is expressed in epithelial cells of a wide variety of tissues including the reproductive tracts. Mutations in the gene encoding CFTR cause cystic fibrosis, a common genetic disease in Caucasian populations with a multitude of clinical manifestations including infertility/subfertility in both sexes. However, the physiological role of CFTR in reproduction and its involvement in the pathogenesis of reproductive diseases remain largely unknown. This review discusses the role of CFTR in regulating fluid volume and bicarbonate secretion in the reproductive tracts and their importance in various reproductive events. We also discuss the contribution of CFTR dysfunction to a number of pathological conditions. The evidence presented is consistent with an important role of CFTR in reproductive health and disease, suggesting that CFTR might be a potential target for the diagnosis and treatment of reproductive diseases including infertility.

Cellular mechanisms of carbachol-stimulated Cl- secretion in rat epididymal epithelium.

Neurotransmitter-controlled Cl- secretions play an important role in maintenance of the epididymal microenvironment for sperm maturation. This study was carried out to investigate the effect of carbachol (CCH) on the cultured rat epididymal epithelium and the signal transduction mechanisms of this response. In normal K-H solution, CCH added basolaterally elicited a biphasic Isc response consisting of a transient spike followed by a second sustained response. Ca2+ activated Cl- channel blocker disulfonic acid stilbene (DIDS, 300 microM) only inhibited part of the CCH-induced Isc response, while nonselective Cl- channel blocker diphenylamine-dicarboxylic acid (DPC, 1 mM) reduced all, indicating the involvement of different conductance pathways. Both peaks of the CCH-induced Isc response could be significantly inhibited by pretreatment with an adenylate cyclase inhibitor, MDL12330A (50 microM). An increase in intracellular cAMP content upon stimulation of CCH was measured. All of the initial peak and part of the second peak could be inhibited by pretreatment with Ca2+-chelating agent BAPTA/AM (50 microM) and an endoplasmic reticulum Ca2+ pump inhibitor, Thapsigagin (Tg, 1 microM). In a whole-cell patch clamp experiment, CCH induced an inward current in the single cell. Two different profiles of currents were found; the first component current exhibited an outward rectifying I-V relationship in a time and voltage-dependent manner, and the current followed showed a linear I-V relationship. The carbachol-induced current was found to be partially blockable by DIDS and could be completely blocked by DPC. The above results indicate that the CCH-induced Cl- secretion could be mediated by Ca2+ and cAMP-dependent regulatory pathways.

Detection of chromosome aberrations in the second trimester using genetic amniocentesis: experience during 1995-2004.

OBJECTIVE: To retrospectively investigate the 10-year experience of prenatal diagnosis of fetal chromosome aberrations by second-trimester amniocentesis. METHODS: Data were collected at Taichung Veterans General Hospital between 1995 and 2004 from cytogenetic analyses of cultured amniocytes from second-trimester amniocentesis. The main indications for amniocentesis included advanced maternal age, abnormal maternal serum screening results, and abnormal ultrasound findings. Chromosome aberrations included autosomal aneuploidies, sex chromosome aneuploidies, polyploidies, and rearrangements. Variant chromosomes were considered to be normal and excluded. RESULTS: A total of 7,028 amniocenteses were performed and analyzed for chromosome aberrations. Among these, 4,026 (57.29%) were for advanced maternal age, 1,500 (21.34%) for abnormal maternal serum screening results, 553 (7.87%) for abnormal ultrasound findings, and 949 (13.50%) for other reasons. The highest detection rate of chromosome aberrations was in cases undergoing amniocentesis for abnormal ultrasound findings (8.86%), followed by other reasons (2.74%), abnormal maternal serum screening results (2.60%), and advanced maternal age (2.31%). Chromosome aberrations were detected in 207 cases (2.90%), including fetuses of 93 older mothers, 39 mothers with abnormal serum screening results, 49 mothers with abnormal ultrasound findings, and 26 mothers with other reasons for amniocentesis. Of fetuses with chromosome aberrations, 144 (69.56%) had trisomy 13, trisomy 18, trisomy 21, or sex chromosome disorder. The other 63 cases (30.44%) included balanced translocation, unbalanced abnormality, inversion, and marker chromosome. CONCLUSION: For daily practice, our data could offer a database for proper genetic counseling, such as termination issues and future pregnancies.

A multiple logistic regression analysis of risk factors in different subtypes of gastric ulcer.

BACKGROUND/AIMS: To elucidate the relationship among disparate ulcer risk factors in 3 subtypes of gastric ulcer. METHODOLOGY: One hundred and fifty-nine age-matched controls, 30 patients with ulcer craters in the gastric body (GU-I), 55 with coexistent gastroduodenal ulcer (GU-II), and 69 with ulcer craters in the prepyloric region (GU-III) were examined for potential risk factors. These included cigarette smoking, nonsteroidal anti-inflammatory drug use, Helicobacter pylori infection, gender and ABO blood group. Using multiple logistic regression analysis, Odds ratios of relevant risk factors associated with different subtypes of gastric ulcer were reported. RESULTS: Among all gastric ulcer subsets, cigarette smoking, nonsteroidal anti-inflammatory drugs use and H. pylori infection were independent ulcer risk factors. For GU-I, smoking (OR: 3.98; 95% CI: 1.44-11.0) and nonsteroidal anti-inflammatory drugs use (OR: 4.33; 95% CI: 1.10-17.1) raised the likelihood of ulceration. For GU-II and GU-III, smoking, nonsteroidal anti-inflammatory drug use and H. pylori infection were identified as risk factors. H. pylori infection carried the strongest association with gastroduodenal ulcer (OR: 9.29; 95% CI: 3.11-27.7) in GU-II, and nonsteroidal anti-inflammatory drug use generated the highest possibility of GU-III (OR: 11.3; 95% CI: 3.49-36.5). Nonsteroidal anti-inflammatory drug use also markedly raised the likelihood of multiple gastric ulcers (OR: 17.0; 95% CI: 4.21-68.9). CONCLUSIONS: Stratification analysis showed differential influences of risk factors on separate subtypes of gastric ulcer. These data support the hypothesis that peptic ulcer disease is heterogeneous in etiology and pathogenesis.