Nerve growth factor-induced differentiation of PC12 cells is accompanied by elevated adenylyl cyclase activity.

Rat pheochromocytoma (PC12) cells characteristically undergo differentiation when cultured with nerve growth factor (NGF). Here we show that NGF dramatically increased the adenylyl cyclase-activating property of forskolin in PC12 cells. This effect of NGF was well maintained even when NGF was removed after 4 days, even though the morphological features of neuronal differentiation were rapidly lost on removal of NGF. The enhanced cAMP production in response to forskolin could be due to a synergistic interaction between forskolin and endogenously released agonists acting on G(s)-coupled receptors. However, responses to forskolin were not attenuated by antagonists of adenosine A2 receptors or pituitary adenylate cyclase-activating polypeptide (PACAP) receptors, suggesting that adenosine and PACAP were not involved. Adenylyl cyclases 3, 6 and 9 were the predominant isoforms expressed in PC12 cells, but we found no evidence for NGF-induced changes in expression levels of any of the 9 adenylyl cyclase isoforms, nor in the expression of Gα(s). These findings highlight that NGF has a subtle influence on adenylyl cyclase activity in PC12 cells which may influence more than the neurite extension process classically associated with neuronal differentiation.

Gallium Nitride (GaN) High-Electron-Mobility Transistors with Thick Copper Metallization Featuring a Power Density of 8.2 W/mm for Ka-Band Applications.

Copper-metallized gallium nitride (GaN) high-electron-mobility transistors (HEMTs) using a Ti/Pt/Ti diffusion barrier layer are fabricated and characterized for Ka-band applications. With a thick copper metallization layer of 6.8 µm adopted, the device exhibited a high output power density of 8.2 W/mm and a power-added efficiency (PAE) of 26% at 38 GHz. Such superior performance is mainly attributed to the substantial reduction of the source and drain resistance of the device. In addition to improvement in the Radio Frequency (RF) performance, the successful integration of the thick copper metallization in the device technology further reduces the manufacturing cost, making it extremely promising for future fifth-generation mobile communication system applications at millimeter-wave frequencies.

Advancing pedagogy of undergraduate nursing students' cultural awareness through internationalization webinars: A qualitative study.

In today's world, nurses increasingly care for individuals from different cultures. Because culturally sensitive care can improve patient satisfaction in care, nurses need to develop cultural competence in their practice. To develop cultural competence, one option is to build cultural awareness by exposing students to nursing practices in other cultures through online internationalization-at-home activities. However, little is known about the process of cultural awareness development through internationalization activities. Therefore, this qualitative study aimed to identify the development process of cultural awareness in nursing students, who participated in a series of internationalization-at-home activities. A total of 31 nursing students from Australia, Hong Kong, and Sweden volunteered to participate in student-led learning groups. Groups consisted of two to four students from each university, who engaged in four weekly webinars and online reflections about nursing practice based on a case scenario. Data were collected from participants' ongoing reflective journal entries, and after the webinars ended, from three focus groups. A semi-structured interview guide was used to understand how the internationalization-at-home activities impacted their cultural awareness and knowledge of nursing. Data were analyzed using interpretive description. Following four levels of thematic analysis (i.e., comprehension, synthesis, theorizing, reconceptualization), we identified four themes in the development of cultural awareness: 1) nurturing reciprocity through comparisons of nursing culture; 2) discovering common ethical values of the nursing profession; 3) developing cultural awareness in nursing ideology and practice; and 4) transforming understanding of nursing in the context of their healthcare systems. By the end of the internationalization activities, students appeared to have developed relational skills to facilitate their own inner dialogue about ethical ideals of "self" and "other" in the context of being part of the global nursing community. Future research should develop and assess teaching strategies that can further facilitate the four themes in cultural awareness development.

Clinical trial: percutaneous acetic acid injection vs. percutaneous ethanol injection for small hepatocellular carcinoma--a long-term follow-up study.

BACKGROUND: The long-term outcome of percutaneous acetic acid injection (PAI) and percutaneous ethanol injection (PEI) for treating small hepatocellular carcinoma (HCC) remains unclear. AIM: To compare the long-term outcome of PAI vs. PEI for treating small HCC. METHODS: From July 1998 to July 2004, 125 patients with small HCC were enrolled. Seventy patients receiving PAI and 55 patients receiving PEI were enrolled. There were no significant differences in the clinical characteristics between the two groups. Tumour recurrence and survival rates were assessed. RESULTS: Mean follow-up time was 43 months. The local recurrence rate and new tumour recurrence rate were similar between the PAI and PEI groups. The PAI group had significantly better survival than the PEI group (P = 0.027). Multivariate analysis revealed that PAI was the significant factor associated with overall survival [PAI vs. PEI, RR: 0.639, 95% CI: (0.419-1.975), P = 0.038]. The treatment sessions required to achieve complete tumour necrosis were significantly fewer in the PAI group than in the PEI group (2.4 +/- 1.0 vs. 2.9 +/- 1.3, P = 0.018). CONCLUSION: Percutaneous acetic acid injection required fewer treatment sessions than PEI and provided better survival after long-term follow-up.

Quadruple rescue therapy for Helicobacter pylori infection after two treatment failures.

BACKGROUND: A standard third-line therapy for Helicobacter pylori infection is lacking, and antimicrobial sensitivity data for patients who failed eradication therapy are often unavailable in clinical practice. We therefore designed the prospective study to assess the efficacy of levofloxacin, amoxicillin, bismuth and rabeprazole quadruple therapy as a third-line treatment for H. pylori infection. PATIENTS AND METHODS: From September 2005 to August 2007, 37 consecutive H. pylori-infected patients who had failed standard first-line and second-line treatments underwent a 10-day quadruple therapy comprising rabeprazole (20 mg b.i.d.), bismuth subcitrate (300 mg q.d.s.), amoxicillin (500 mg q.d.s.) and levofloxacin (500 mg o.d.). Follow-up endoscopy with rapid urease test, histological examination and culture was performed at 6 weeks after the end of treatment to evaluate the response to therapy. RESULTS: Helicobacter pylori was successfully eradicated in 31 out of 37 patients (84% by both intention-to-treat analysis and per-protocol analysis). All patients complied with the eradication therapies, and only seven patients (19%) complained of mild-to-moderate adverse events. Amoxicillin- and levofloxacin-resistant strains were observed in 17% and 22% of the patients, respectively. There were no significant differences between H. pylori eradication rates and antibiotic resistances. CONCLUSIONS: The 10-day levofloxacin- and amoxicillin-based quadruple therapy is well tolerated and achieves a high eradication rate as a third-line empirical treatment for H. pylori infection.

A prospective, randomized controlled trial of transjugular intrahepatic portosystemic shunt versus cyanoacrylate injection in the prevention of gastric variceal rebleeding.

BACKGROUND AND STUDY AIMS: Both endoscopic obturation and transjugular intrahepatic portosystemic shunts (TIPSs) have proven to be effective in preventing rebleeding from gastric varices. This study compared the efficacy and complications of these modalities. PATIENTS AND METHODS: Cirrhotic patients with acute bleeding from gastric varices were considered for inclusion. After initial control, eligible patients were randomly allocated to two groups: TIPS (n = 35) and obturation using cyanoacrylate (n = 37). In the cyanoacrylate group, treatment was repeated regularly until gastric varices were obliterated. Patients of both groups received regular follow-up. The end points were gastric variceal rebleeding or death. RESULTS: Stent shunt insertion was successful in all TIPS patients, and mean portal pressure gradient decreased from 21.4 +/- 7.5 mm Hg to 7.5 +/- 3.5 mm Hg ( P < 0.001). Variceal obliteration was achieved in 19 patients in the cyanoacrylate group (51 %) compared with seven TIPS patients (20 %) ( P < 0.02). After a median follow up of 33 months, upper gastrointestinal bleeding occurred in 15 TIPS patients (43 %) and 22 cyanoacrylate patients (59 %) ( P = 0.12). Rebleeding from gastric varices was encountered in four TIPS patients (11 %) and 14 cyanoacrylate patients (38 %) ( P = 0.014; odds ratio 3.6, 95 %CI 1.2 - 11.1). Blood transfusion requirements were lower in the TIPS group than in the cyanoacrylate group ( P < 0.01). Survival and frequency of complications were similar in both groups. CONCLUSIONS: TIPS proved more effective than glue injection in preventing rebleeding from gastric varices, with similar survival and frequency of complications.

Characterization of contamination in and toxicities of a shipyard area in Hong Kong.

This is the first integrated study on the contaminant characterization and toxicities of a shipyard area. This site in Hong Kong contained 3.6-33.4 mg kg(-1) dichlorodiphenyltrichloroethane and 5-79 g kg(-1) oil and grease. Other pollutants exceeding the Dutch intervention values were total polyaromatic hydrocarbons, total petroleum hydrocarbons, and metals Cu, Pb and Zn. These pollutants persisted partially owing to the poor fertility with <125 mg N kg(-1) and <530 mg P kg(-1) typical of coastal soil. Sediments collected within 100 m also showed contamination exceeding the China and Hong Kong intervention levels. The shipyard soil killed two bacteria Pseudomonas stutzeri and Acinetobacter sp. isolated from a clean coastal soil, inhibited germination of three exogenous plants Triticum aestivum, Brassica chinense and Lolium perenne, and inhibited proliferation of three indigenous bacteria: Methylobacterium sp., Pseudomonas aeruginosa and Bacillus cereus. Thus, ex situ remediation was needed.

Eradication of Helicobacter pylori prevents ulcer development in patients with ulcer-like functional dyspepsia.

BACKGROUND: Although the eradication of Helicobacter pylori infection benefits patients with gastric or duodenal ulcers, the value of eradicating the infection in the patients with functional dyspepsia (FD) remains controversial. AIMS: To determine whether eradicating H. pylori can prevent the subsequent development of ulcers or relieve the symptoms of functional dyspepsia patients. METHODS: In a double-blind, placebo-controlled trial, 161 patients infected with H. pylori who had functional dyspepsia were randomly assigned to 7 days of treatment with a lansoprazole-based triple therapy or placebo and then followed for 1 year. The main outcome measures were the development of peptic ulcers and the resolution of symptoms. RESULTS: H. pylori was eradicated in 63 out of 81 patients (78%) in the treatment group and none of the 80 patients (0%) in the placebo group. During the follow-up period, two patients in the treatment group and six patients in the placebo group developed peptic ulcers at repeat endoscopy (2.5% vs. 7.5%; 95% CI: -12 to 2). The reduction in ulcer rates was statistically significant in the 'ulcer-like' sub-group (0% vs. 16.7%; 95% CI: -32 to -2), but not in the 'dysmotility-like' and 'unclassifiable' sub-groups. Regarding symptom response, the resolution rates of symptoms were similar between the treatment and placebo groups (58.0% vs. 55.0%, 95% CI: -12 to 18). Additionally, no significant differences existed in the symptom responses between the treatment and control arms in each of the dyspepsia sub-groups. CONCLUSIONS: Eradicating H. pylori can prevent the subsequent development of peptic ulcers in the patients with 'ulcer-like' functional dyspepsia. However, this approach does not significantly reduce the symptoms of functional dyspepsia patients.

Risks of interleukin-1 genetic polymorphisms and Helicobacter pylori infection in the development of gastric cancer.

BACKGROUND: The host genetic factors that determine the clinical outcomes of Helicobacter pylori-infected individuals remain unclear. AIM: To elucidate the risks of host interleukin-1 (IL-1) genetic polymorphisms and H. pylori infection in the development of gastric cancer. METHODS: In a case-control study of 164 controls and 142 patients with gastric cancer, the IL-1B-511 biallelic polymorphisms and the IL-1RN penta-allelic variable number of tandem repeats were genotyped. RESULTS: The carriage of IL-1RN*2, male gender, old age and H. pylori infection independently increased the risk of gastric cancer, with odds ratios of 3.3 [95% confidence interval (CI), 1.4-7.7], 2.1 (95% CI, 1.2-3.8), 5.3 (95% CI, 3.1-9.0) and 2.2 (95% CI, 1.3-3.8), respectively. H. pylori-infected individuals who were carriers of IL-1RN*2 showed increased risks of both intestinal and diffuse types of gastric cancer, with odds ratios of 11.0 and 8.7, respectively. In addition, these individuals also had a higher score of intestinal metaplasia in the corpus than did uninfected non-carriers. CONCLUSIONS: This study is the first to verify IL-1RN*2 as an independent factor governing the development of gastric cancer in Asian individuals. A combination of H. pylori testing and host genotyping may target the eradication of H. pylori to high-risk individuals.

Phase II study of mitoxantrone in unresectable primary hepatocellular carcinoma following hepatitis B infection.

A total of 20 patients with histologically proven primary hepatocellular carcinoma (PHC) received mitoxantrone IV at a dose of 10-16 mg/m2 every 3 weeks. All patients had previous hepatitis B infection. None underwent remission after treatment; 2 had stable disease and 18 progressive disease. The median overall survival was 13 weeks (range, 1-59 weeks). There was no evidence of significant antitumor activity for mitoxantrone in our patients with PHC. Hematotoxicity occurred in 100% of the patients with grades 2-4 leukopenia, 89% of those with grades 1-4 anemia, and 26% of those with grades 2-3 thrombocytopenia. Cardiotoxicity occurred in 20% of the patients after 14-30 mg/m2 mitoxantrone; these included complete heart block with fatal outcome in one case, decreased ventricular ejection fraction in one, and sinus tachycardia in two. Nausea, vomiting, fever, diarrhea, and alopecia were mild and occurred in 15%-45% of the patients Therefore, patients with PHC following hepatitis B infection may be less tolerant to mitoxantrone, resulting in the apparent increase in toxicities.

Transcatheter arterial chemoembolization for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) was treated with transcatheter arterial chemoembolization (TACE) in a sample of 129 patients. The cumulative survival rate was 49% at 1 year and 22% at 2 years. The median survival time was 11.9 months. The survival rates at 1 year of 84 patients in Child's group A and 27 in Child's group B were 56% and 40%; out of 52 HCC patients with portal vein patent and 77 with portal vein invasion 75% and 40% survived, and the 1-year survival rates for 33 HCC patients with capsule intact, 14 with capsule broken and 82 with no capsule were 85%, 65% and 40% respectively. From the above results there were statistically significant differences in survival time in those with good clinical performance status by Child's classification, those showing patency of the portal vein and those where the capsule was present. Therefore, we would like to recommend, TACE of HCC in well-selected patients presenting with good clinical status, patency of the portal vein and without broken capsule, in order to achieve better clinical results.

Implications of serum basic fibroblast growth factor levels in chronic liver diseases and hepatocellular carcinoma.

Angiogenesis occurs in response to tissue damage, and is of vital importance for tumor growth and metastasis. Basic fibroblast growth factor (bFGF), a well-known angiogenic factor, has been suggested to be a useful diagnostic marker in certain hypervascular tumors. However, the relevance of its detection has not been well evaluated in patients with hepatocellular carcinoma (HCC) and benign chronic liver diseases. In the current study, immunoassay of bFGF was performed on serum samples from 39 patients with HCC, 21 with liver cirrhosis, 22 with chronic hepatitis and 40 normal subjects. The serum bFGF level was significantly increased in patients with liver cirrhosis and HCC when compared with those with chronic hepatitis or normal subjects (all p-values < 0.001). However, no difference was observed between the groups with liver cirrhosis and HCC (p > 0.05). If we set 9.6 pg/ml (mean + 3 standard deviations of bFGF in the control group) as the upper limit of normal serum level of bFGF, elevated bFGF concentrations were noted in 9.1%, 42.9% and 51.3% of patients with chronic hepatitis, liver cirrhosis and HCC respectively. In non-cancer patients, the coexistence of acute illness (p = 0.000) was an independent factor related to the elevation of serum bFGF. On the other hand, a multivariate analysis demonstrated that both advanced stage of cancer (p = 0.026) and coexistence of acute illness (p = 0.000) influence the serum level of bFGF in patients with HCC. We conclude that serum bFGF levels are significantly higher in patients with HCC and are positively correlated with advanced tumor stage. Nevertheless, elevation of serum bFGF may also be observed in a significant number of patients with liver cirrhosis. Therefore, measurement of serum bFGF alone cannot be satisfactory as a tumor marker for diagnosis of HCC. In addition, it is important to point out that coexistence of acute illness may be a crucial confounding factor in the diagnosis or monitoring of any cancer by the estimation of serum bFGF.

Impact of bacterial eradication on the cell proliferation and p53 protein accumulation in Helicobacter pylori-associated gastritis.

BACKGROUND: This study investigates the cell proliferation and the expression of p53 protein in Helicobacter pylori (H. pylori)-associated gastritis and assesses the effect of bacterial eradication on these epithelial factors. MATERIAL AND METHODS: Seventy-nine patients with H. pylori-associated gastritis were randomized into the control group (n = 38) and anti-H. pylori group (n = 41). Each patient received endoscopic examinations with gastric biopsy before and 8 weeks after the treatment. The specimens from gastric antrum were immunostained for monoclonal antibodies against the proliferating cell nuclear antigen (PCNA) and p53 protein. RESULTS: In the control group, the total labeling index (L.I.) of PCNA and the positive index (P.I.) of p53 in the whole foveolar epithelium were unchanged after treatment. In the anti-H. pylori group, 35 of 41 cases (85.3%) achieved eradication of H. pylori. Amongst the H. pylori-eradicated cases, the total L.I. of PCNA in the whole foveolar epithelium did not meaningfully alter after H. pylori elimination (p > 0.05). However, a significant reduction of L.I. was observed in the middle compartments of the gastric pits (before vs. after treatment: 14.0 vs. 7.3, p < 0.05). With regard to the p53 expression, the P.I.s were significantly decreased in the whole foveolar epithelium (before vs. after treatment: 0.57 vs. 0.17, p < 0.05) and in each compartment of the gastric pits (before vs. after treatment: [upper compartment]: 0.34 vs. 0.15, p < 0.05; [middle compartment]: 0.67 vs. 0.23, p < 0.05; [lower compartment]: 0.71 vs. 0.20, p < 0.05) after eradication of H. pylori. CONCLUSIONS: Bacterial eradication reverses the hyperproliferating status of the foveolar epithelium in patients with H. pylori gastritis and leads to a decrease in p53 accumulation in the epithelial cells.

Endoscopic balloon dilatation is a safe method in the management of common bile duct stones.

BACKGROUNDS AND AIMS: Endoscopic sphincterotomy is a widely accepted treatment for patients with common bile duct stones. Despite improvement in this technique, endoscopic sphincterotomy is still associated with some biliary complications. Endoscopic balloon dilatation is a less traumatic and sphincter preserving method for removal of common bile duct stones. However, the results of controlled studies in comparison with these two methods are contradictory. The aim of this study is to compare the safety and efficacy of endoscopic balloon dilatation and endoscopic sphincterotomy in Chinese patients. PATIENTS AND METHODS: A total of 104 patients with common bile duct stones on endoscopic retrograde cholangiopancreatography were enrolled. They were randomly assigned to endoscopic balloon dilatation or endoscopic sphincterotomy. Endoscopic balloon dilatation was performed by using a balloon dilator to dilate the sphincter for 5 min. The common bile duct stones were then removed by a Dormia basket after endoscopic balloon dilatation or endoscopic sphincterotomy. Mechanical lithotripsy was performed if the stones were difficult to remove by Dormia basket. After discharge, patients were regularly followed up for biliary complications. RESULTS: The successful bile duct stone clearance rate was 94.1% in endoscopic balloon dilatation group and 100% in endoscopic sphincterotomy group. Post-procedural significant haemorrhage was higher in endoscopic sphincterotomy group than in endoscopic balloon dilatation group (14/53 versus 1/48, P < 0.001). The bleeding patient from endoscopic balloon dilatation group was a case of uremia and bleeding occurred 48 h after endoscopic balloon dilatation. All the patients with post-procedural haemorrhage were controlled endoscopically. The post-procedural serum amylase level showed no significant difference in both groups and none of them developed clinical pancreatitis. After a mean 16 months follow-up, three patients (6.3%) in endoscopic balloon dilatation group and four patients (7.5%) in endoscopic sphincterotomy group developed recurrent common bile duct stones. The recurrent common bile duct stones were multiple and muddy in consistency. They were successfully removed endoscopically. CONCLUSION: Both endoscopic balloon dilatation and endoscopic sphincterotomy are safe and effective techniques for the treatment of common bile duct stones. Endoscopic balloon dilatation can be safely applied in patients with coagulopathy and does not increase the incidence of pancreatitis or bleeding.

Endoscopic 13C-urea breath test for the diagnosis of Helicobacter pylori infection.

BACKGROUND: Endoscopic 13C-urea breath test may avoid contamination of oral urease and rapidly discriminate Helicobacter pylori-positive and Helicobacter pylori-negative patients. AIMS: To compare the accuracy of endoscopic 13C-urea breath test with conventional invasive methods in diagnosis of Helicobacter pylori infection. PATIENTS: One hundred patients who attended for routine upper gastrointestinal endoscopy were included. METHODS: 13C-urea was applied to the stomach through the working channel of endoscope at the end of endoscopic examination. Breath samples were collected before endoscopy and 2, 4, 6, 8, 10 min after consumption of 100 or 50 mg 13C-urea. Helicobacter pylori infection was defined as those with positive culture or positive results of both histology and CLO test. RESULTS: The accuracy of 100 mg endoscopic 13C-urea breath test was significantly higher than that of culture and CLO test (100% vs. 88% and 92%, p = 0.02 and 0.03, respectively). The accuracy of 50 mg endoscopic 13C-urea breath test was higher than that of histology and CLO test (98% vs. 90% and 96%, respectively), although the differences were not statistically significant. CONCLUSIONS: Endoscopic 13C-urea breath test has a higher accuracy compared with biopsy-based modalities. It may be a good choice to diagnose Helicobacter pylori infection if endoscopy is indicated for a dyspeptic patient.

Efficacy of quantitative cholescintigraphy in the diagnosis of sphincter of Oddi dysfunction.

The diagnostic efficacy of time-activity curves (TAC) and common bile duct dynamics (CBDD) derived from quantitative cholescintigraphy (QC) was assessed in patients with suspected sphincter of Oddi dysfunction (SOD). Quantitative cholescintigraphy was performed on 34 cholecystectomized individuals with suspected SOD and 26 asymptomatic controls. Each patient with suspected SOD underwent endoscopic retrograde cholangiography and sphincter of Oddi manometry (SOM). After exclusion of eight patients because of failure of manometry, the final diagnoses of the remaining 26 patients were taken as the gold standard by which to determine the detectability of TAC and CBDD. The sensitivity of TAC reached 68.8%. Common bile duct dynamics showed equal sensitivity but was more specific than TAC. The sensitivity improved to 87.5% when TAC and CBDD were combined. We conclude that non-invasive QC provides good sensitivity and specificity in evaluating cholecystectomized patients with suspected SOD.

Impact of a severe acute respiratory syndrome outbreak in the emergency department: an experience in Taiwan.

OBJECTIVES: To evaluate the impact of a severe acute respiratory syndrome (SARS) outbreak in the emergency department (ED). METHODS: Computerised records of all ED visits in January and May 2003 were analysed and compared, representing before and during the SARS epidemic respectively. Data were grouped into two categories. Group 1 was the indicators of impact on patients, including visitor's condition classification, number of patients that died on arrival (DOA), received cardiopulmonary resuscitation, underwent endotracheal intubation, needed mechanical ventilation, discharged against medical advice (AAD), died in the ED, and the admission rate to wards. Group 2 was the indicators of impact on the quality of medical care, including number of visits that returned within 72 hours (early returns), underwent chest radiography, upper abdomen sonography or computed tomography, and the length of stay. RESULTS: There were 6650 and 3901 consecutive encounters in January and May 2003 respectively. There were significant differences on condition classifications (p = 0.000), increased rate of patients that underwent endotracheal intubation (p = 0.003), needed mechanical ventilation (p = 0.020), and admission (p = 0.000). The rate of AAD decreased significantly (p = 0.024). There was no significant difference on early returns, although the length of stay in the ED increased (p = 0.043). The number of visits that underwent chest radiological examination increased (p = 0.000) and upper abdomen sonography (p = 0.007) decreased significantly in May. CONCLUSIONS: SARS had an impact on the medical service system and decreased visits by 40% in the ED. Patients visiting the ED had more severe conditions than before. The impact of SARS on quality of medical care can be minimised when adequate infection control measures are applied.

Gi-coupled prostanoid receptors are the likely targets for COX-1-generated prostanoids in rat pheochromocytoma (PC12) cells.

Cyclooxygenase-1 (COX-1) behaves as a delayed response gene in rat pheochromocytoma (PC12) cells exposed to nerve growth factor (NGF). To investigate the possible targets for COX-1 generated prostanoids in the early stages of neuronal differentiation, we have examined the expression of prostanoid receptors by PC12 cells using functional assays. Prostanoid receptor-specific agonists failed to activate adenylyl cyclase in undifferentiated and NGF-treated PC12 cells; neither did they stimulate phospholipase C activity. EP3 receptor agonists and PGF(2alpha) were the only active ligands, able to inhibit forskolin-stimulated adenylyl cyclase activity. PC12 cells expressed EP3 and FP receptor mRNA, but only the responses to EP3 receptor agonists were inhibited by the EP3 receptor antagonist ONO-AE3-240. The functional role of NGF-stimulated COX-1 remains to be determined since we found no strong evidence of a role for EP3 receptors in the morphological changes induced by NGF during the early stages of differentiation of PC12 cells.

High-dose versus low-dose esomeprazole-based triple therapy for Helicobacter pylori infection.

BACKGROUND: This prospective, randomized, controlled study was conducted to compare the efficacies of high-dose and low-dose esomeprazole-based triple therapies for Helicobacter pylori eradication in Taiwan. MATERIALS AND METHODS: From January 2004 to June 2006, 240 H. pylori-infected patients were randomly assigned to undergo high-dose (40 mg b.d.) or low-dose (40 mg o.d.) esomeprazole combined with clarithromycin (500 mg b.d.) and amoxicillin (1 g b.d.) for one week. Follow-up endoscopy was performed at eight weeks after the end of treatment to evaluate the response to therapy. RESULTS: Intention-to-treat analysis demonstrated no differences between eradication rates of high-dose and low-dose groups (92% vs. 90%, respectively, P > 0.05). Per-protocol analysis yielded comparable results (95% vs. 93%). Both groups exhibited similar frequencies of adverse events (13% vs. 11%) and drug compliance (96% vs. 93%). Multivariate analysis indicated that only good compliance (odds ratio: 10.3, 95% CI, 3.0-35.7) was an independent predictor of treatment success. CONCLUSIONS: This work demonstrates that low-dose esomeprazole-based triple therapy yields a similar eradication rate as high-dose esomeprazole-based therapy in Taiwan. Since the cost of the low-dose regime is lower than that of the high-dose regime, low-dose esomeprazole-based triple therapy can reasonably be recommended for the first-line eradication of H. pylori for Taiwanese and probably most Asians.

Randomized comparison of two rescue therapies for Helicobacter pylori infection.

BACKGROUND: Bismuth salts are not available worldwide. It remains unknown whether clarithromycin can replace bismuth salts as an adjuvant agent in the rescue regimens for Helicobacter pylori infection. We therefore designed the prospective study to compare the efficacies of two rescue therapies for H. pylori infection after standard triple therapies. PATIENTS AND METHODS: Ninety-three patients who failed H. pylori eradication using proton pump inhibitor plus clarithromycin and amoxicillin were randomly assigned to undergo rescue therapy with esomeprazole, clarithromycin, tetracycline and metronidazole (ECTM group, n = 46) or esomeprazole, bismuth subcitrate, tetracycline and metronidazole (EBTM group, n = 47). Follow-up endoscopy was performed at 8 weeks after the end of treatment to assess the treatment response. RESULTS: Intention-to-treat analysis demonstrated both groups had similar eradication rates (ECTM 74% vs. EBTM 77%; P = 0.76) and drug compliance (ECTM 94% vs. EBTM 96%; P = 0.68). However, the frequency of adverse events in the ECTM group was higher than that in EBTM group (ECTM 57% vs. EBTM 36%, P = 0.05). In the EBTM group, eradication rate of metronidazole-resistant strains was lower than that of metronidazole-susceptible strains (67%[8/12] vs. 100%[9/9], P = 0.05). However, eradication rates were similar between metronidazole-susceptible and metronidazole-resistant strains in ECTM group (69%[9/13] vs. 70%[7/10], P = 1.00). CONCLUSIONS: The new ECTM second-line therapy can achieve similar eradication rate as standard EBTM therapy. It may be very useful in countries where bismuth salts are not available.