Ethyl acetate extract of Nepenthes adrianii x clipeata induces antiproliferation,apoptosis, and DNA damage against oral cancer cells through oxidative stress

Nepenthes plants are regarded as a kind of Traditional Chinese Medicine for several diseases but its anticancer activity remain unclear. The subject of this study is to evaluate the antiproliferation effects on oral cancer cells by Nepenthes plants using ethyl acetate extract of Nepenthes adrianii x clipeata (EANA). Cell viability was detected using MTS assay. Its detailed mechanisms including cell cycle, apoptosis, oxidative stress, and DNA damage were explored by flow cytometry or western blotting. For 24 hours EANA treatment, five kinds of oral cancer cells (CAL 27, Ca9‐22, OECM‐1, HSC‐3, and SCC9) show IC₅₀ values of cell viability ranging from 8 to 17 μg/mL but the viability of normal oral cells (HGF‐1) remains over 80%. Subsequently, CAL 27 and Ca9‐22 cells with high sensitivity to EANA were chosen to investigate the detailed mechanism. EANA displays the time course and concentration effects for inducing apoptosis based on flow cytometry (subG1 and annexin V analyses) and western blotting [cleaved poly (ADP‐ribose) polymerase (c‐PARP)]. Oxidative stress and DNA damage were induced by EANA treatments in oral cancer cells through reactive oxygen species (ROS), mitochondrial membrane potential disruption, mitochondrial superoxide, and γH2AX. All these changes of EANA treatments in oral cancer cells were reverted by the ROS scavenger N‐acetylcysteine pretreatment. Therefore, EANA induces preferential killing, apoptosis, and DNA damage against oral cancer cells through oxidative stress.     

Hypothermia and prostaglandin E(1) produce synergistic attenuation of ischemia-reperfusion lung injury.

Current methods of preserving lung tissue for transplantation are inadequate. In this study, we tested whether the combination of hypothermia plus prostaglandin E(1) (PGE(1)) treatment would have synergistic attenuation on ischemia-reperfusion (I/R) lung injury. Isolated rat lung experiments with ischemia for 1 h then reperfusion for 1 h, were conducted using six different perfusates: (1) University of Wisconsin solution (UW) at 30 degrees C (n = 5), (2) UW at 22 degrees C (n = 5), (3) UW at 10 degrees C (n = 4), (4) UW+PGE(1) at 30 degrees C (n = 4), (5) UW+PGE(1) at 22 degrees C (n = 4), and (6) UW+PGE(1) at 10 degrees C (n = 4). Hemodynamic changes, lung weight gain, capillary filtration coefficients, and lung pathology were analyzed to evaluate the I/R injury. Compared with 30 degrees C UW, animals treated with 22 degrees C UW and 10 degrees C UW had less I/R lung injury, with the groups receiving 22 degrees C UW showing superior results to group receiving 10 degrees C UW. The addition of PGE(1) to UW solution produced more attenuation of I/R injury than did UW alone. Among the six groups, 10 degrees C UW+PGE(1) produced the most reduction of I/R injury. This study has shown that hypothermia can attenuate I/R injury with the optimal flushing temperature being near 22 degrees C. PGE(1) also has a protective effect on I/R. Furthermore, hypothermia and PGE(1) have synergistic attenuation of I/R lung injury. We propose that pulmonary artery flushed with cooling UW+PGE(1) might improve lung preservation and improve results in lung transplantation.     

Will Helicobacter pylori affect short-term rebleeding rate in peptic ulcer bleeding patients after successful endoscopic therapy?

OBJECTIVE: Helicobacter pylori (H. pylori) can augment the pH-increasing effect of omeprazole in patients with peptic ulcer. A high intragastric pH may be helpful in preventing recurrent hemorrhage by stabilizing the blood clot at the ulcer base of bleeding peptic ulcer patients. Therefore, we hypothesized that omeprazole may reduce short-term rebleeding rate in these patients with H. pylori infection after initial hemostasis had been obtained. METHODS: Between July 1996 and December 1998, 65 bleeding peptic ulcer patients (24 gastric ulcer, 41 duodenal ulcer) who had obtained initial hemostasis with endoscopic therapy were enrolled in this trial. Thirty (46.2%) of them were found to have H. pylori infection by a rapid urease test and pathological examination. For all studied patients, omeprazole was given 40 mg intravenously every 6 h for 3 days. Thereafter, omeprazole was given 20 mg per os (p.o.) once daily for 2 months. A pH meter was inserted in the fundus of each patient under fluoroscopic guidance after intravenous omeprazole had been administered. The occurrence of rebleeding episode was observed for 14 days. RESULTS: In patients with H. pylori infection, intragastric pH (median, 95% confidence interval [CI]: 6.54, 5.90-6.68) was higher than in those without H. pylori infection (6.05, 5.59-6.50, p < 0.001). However, the patients with rebleeding (2 vs 3), volume of blood transfusion (median, range: 1000 ml, 0-2250 vs 750, 0-2000), number of operations (0 vs 1), mortality caused by bleeding (0 vs 0), and hospital stay (median, range: 6 days, 3-14 vs 7, 5-16) were not statistically different from those without H. pylori infection. CONCLUSIONS: Omeprazole does increase intragastric pH in bleeding peptic ulcer patients with H. pylori infection. However, the presence of H. pylori infection does not affect the short-term rebleeding rate in these patients.     

Diabetic nephropathy and risk factors for peripheral artery disease in Chinese with type 2 diabetes mellitus

The risk for peripheral arterial disease (PAD) is increased in patients with chronic kidney disease. We investigated the effects of renal function on PAD in Chinese with type 2 diabetes mellitus. This study enrolled a total of 2983 (1342 men and 1641 women) Chinese adults with diabetes. The mean age was 63.2 ± 11.9 years. Peripheral arterial disease was diagnosed by an ankle-brachial index less than 0.9. Renal function was evaluated by serum creatinine (SCr), estimated glomerular filtration rate, and urinary albumin-creatinine ratio (ACR). Risk factors for PAD were evaluated using multiple logistic regression analysis. Age, cholesterol, and high-density lipoprotein cholesterol (HDL-C) (inverse association) were significant risk factors in men, whereas age, body mass index (inverse association), low-density lipoprotein cholesterol, and HDL-C (inverse association) were significant risk factors for diabetic women. After adjustment for age, body mass index, blood pressure, glycosylated hemoglobin, cholesterol, HDL-C, low-density lipoprotein cholesterol, and triglyceride levels, we found that SCr levels greater than 1.5 mg/dL, estimated glomerular filtration rate less than 60 mL/min, and urinary ACR greater than 30 mg/g were independent risk factors for PAD in diabetic men and that SCr levels greater than 1.4 mg/dL and urinary ACR greater than 30 mg/g were independently associated with PAD in diabetic women. The risk factors for PAD are somewhat different between men and women with diabetes in Chinese population in Taiwan. Diabetic nephropathy is significantly associated with PAD in this patient population.     

Superior Vena Cava Syndrome Revisited

A clinical review with analysis of prognostic factors, includingthe impact of the initial management modality, was conductedon 137 patients with superior vena cava syndrome (SVCS) seenat the Veterans General Hospital-Taipei between 1989 and 1993.Malignant diseases account for most of the SVCS in our Chinesepatients. Patients received diagnostic intervention for theirunderlying diseases without obvious complications. Whether ornot there is a development of SVCS in lung cancer patients,showed prognostic significance in non-small cell lung cancer(NSCLQ 'and no significance in small cell lung cancer (SCLQ.Those with SVCS as the initial manifestation of malignant diseasehad a poor prognosis compared to those who developed SVCS later.Survival is best in lymphoma/leukemia patients, followed bymalignant thymoma and SCLC, and worst in NSCLC and metastaticcancer. The rapid onset of symptoms from SVCS had a short mediansurvival in lung cancer and significantly compromised survivalin SCLC. The overall survival of SCLC with SVCS was not affected,regardless of whether the initial therapy had been radiotherapyor chemotherapy     

Application of stent placement or nasojejunal feeding tube placement in patients with malignant gastric outlet obstruction: A retrospective series of 38 cases

BackgroundMalignant gastric outlet obstruction (MGOO), a late complication of advanced carcinoma of the stomach, duodenum, periampulla or pancreas, causes significant malnutrition and morbidity. The current treatment for MGOO is palliative in nature, with the goal of maintaining the best quality of life possible during the terminal phase of the illness.MethodsA total of 38 patients with MGOO were enrolled in our institute from January 2007 to December 2011; 18 patients received nasojejunal (NJ) feeding tube placement, and 20 patients received duodenal stent placement. Food intake, measured by the gastric outlet obstruction scoring system (GOOSS), survival, complications, recurrent obstructive symptoms, and reintervention were evaluated in both groups.ResultsNo significant differences were noted with regard to patient characteristics, survival rate (NJ group: 140 days vs. stent group: 186 days, p = 0.617), and complication rate. Recurrent obstructions developed more frequently in patients treated with NJ feeding tube placement than in those treated with duodenal stent placement [12 (66.7%) vs. 5 (25%), p = 0.014]. The duration for patency was shorter in the NJ group than in the stent group (median: 40 days vs. 130 days, p = 0.009). The GOOSS score was significantly better in the stent group than in the NJ group.ConclusionNJ tube placement and duodenal stent placement are both effective and safe treatments for patients with MGOO. Both groups had similar complication rates and survival rates. While NJ tube placement is associated with lower costs, stent placement has a longer duration of patency, superior oral intake, and a lower reintervention rate. We suggest that stent placement should be considered first in patients who are able to afford the related costs.     

The influence of intravenous omeprazole on intragastric pH and outcomes in patients with peptic ulcer bleeding after successful endoscopic therapy--a prospective randomized comparative trial.

BACKGROUND/AIMS: The role of omeprazole in preventing rebleeding in patients with peptic ulcer bleeding after successful endoscopic therapy has been controversial. In this study, we used 3 different formulas of intravenous omeprazole in the above patients. We wished to compare the intragastric pH and outcomes among them. METHODOLOGY: Between July 1996 and May 1997, after having obtained initial hemostasis with endoscopic therapy, a total of 20 patients with peptic ulcer bleeding (spurting/oozing/non-bleeding visible vessel: 6/4/10) received intravenous bolus of omeprazole 20 mg every 3 hours; 20 patients (3/5/12) received intravenous bolus of omeprazole 40 mg every 6 hours; and, 20 patients (5/4/11) received intravenous bolus of omeprazole 80 mg every 12 hours for 3 days. One intragastric pH meter (Gastrograph Mark III, Medical Instruments Corp. Switzerland) was used to record 24-hour intragastic pH. RESULTS: The intragastric pH in the patients receiving omeprazole 20 mg every 3 hours was 6.1, 6.0-6.2 (mean: 95% CI); in patients receiving omeprazole 40 mg every 6 hours it was 6.4, 6.2-6.5; and, in patients receiving omeprazole 80 mg every 12 hours it was 5.8, 5.7-5.9. The duration of intragastric pH > 6.0 in omeprazole 20 mg every 3 hours was 70.9%, 57.3%-84.4% (mean: 95% CI); in omeprazole 40 mg every 6 hours it was 83.1%, 73.1%-93.1%; and, in omeprazole 80 mg every 12 hours it was 66%, 51.5%-80.4%. Patients with peptic ulcers receiving omeprazole 40 mg intravenous bolus every 6 hours had the highest intragastric pH as compared with the other 2 groups (p < 0.0001). There were no significant differences concerning rebleeding rates, volume of blood transfusion, hospital stay, numbers of operation and mortality among the 3 groups. CONCLUSIONS: After initial hemostasis had been obtained, patients with peptic ulcer bleeding receiving 40 mg intravenous bolus every 6 hours had the highest intragastric pH. However, they had similar outcomes with the other 2 groups.     

Eight-month prospective study of 14 patients with hospital-acquired severe acute respiratory syndrome

OBJECTIVE: To define the clinical characteristics and clinical course of hospital-acquired severe acute respiratory syndrome (SARS). PATIENTS AND METHODS: This 8-month prospective study of 14 patients with hospital-acquired SARS in Taipei, Taiwan, was conducted from April through December 2003. RESULTS: The most common presenting symptoms in our 14 patients with hospital-acquired SARS were fever, dyspnea, dizziness, malaise, diarrhea, dry cough, muscle pain, and chills. Lymphopenia and elevated serum levels of lactate dehydrogenase (LDH) and C-reactive protein (CRP) were the most common Initial laboratory findings. Initial chest radiographs revealed various pattern abnormalities and normal results. Five of the 14 patients required mechanical ventilation. The need for mechanical ventilation was associated with bilateral lung involvement on the initial chest radiograph and higher peak levels of LDH and CRP. Clinical severity of disease varied from mild to severe. At 8 months after disease onset, patients with mild or moderate SARS had normal findings or only focal fibrosis on chest high-resolution computed tomography. However, bilateral fibrotic changes remained in the 4 patients who had recovered from severe SARS, 1 of whom had mild restrictive ventilatory impairment. One patient with severe SARS died; she was elderly and had other comorbidities. Five additional patients had reduced diffusing capacity. CONCLUSION: The clinical picture of our patients presenting with hospital-acquired SARS revealed atypical pneumonia associated with lymphopenia, elevated serum levels of LDH, rapid clinical deterioration, and lack of response to empirical antibiotic therapy. Substantially elevated levels of LDH and CRP correlated with severe illness requiring mechanical ventilatory support. In those receiving mechanical ventilation, pulmonary function was only mildly reduced at 6 to 8 months after acute illness, consistent with the natural history of acute respiratory distress syndrome due to other causes.     

Palliative MEFLEP therapy in advanced pancreatic cancer: excellent response in a patient with Her-2/neu amplification

INTRODUCTION: Patients with pancreatic cancer often present initially in advanced disease with many compromising factors, and yet they may still be responsive to chemotherapy. AIMS: The response of 23 patients with advanced pancreatic cancer to continuous infusion therapy was investigated. METHODOLOGY: From September 1995 to February 1998, 23 patients with advanced pancreatic cancer, many with compromising factors, were treated with a MEFLEP regimen: biweekly 24-hour infusions of etoposide, 5-fluorouracil, leucovorin, epirubicin, and cisplatin, all given through an infusion pump, plus megestrol acetate, 160 mg/d, taken daily. A total of 145 courses were given. Overall response rate was 21% (4/19) for assessable chemo-naive patients; median survival for all 23 patients was 6 months; 22% of patients were alive at 1 year; and a clinical response benefit was attained in 35%. RESULTS: Toxicity was manageable; grade 3 or 4 leukopenia occurred in 1 patient each, 1 patient had fever and grade 3 infection, and grade 3 and 4 hyperammonemic encephalopathy developed in 3 and 1 patients, respectively. All four of the latter patients recovered uneventfully within 2 days of initiation of therapy. Nine patients were evaluated by fluorescence in situ hybridization for the Her-2/neu oncogene, but for only one patient did amplification of the gene occur. She attained complete remission with treatment and lived for 26.7 months after diagnosis. CONCLUSION: Biweekly MEFLEP is an active and manageable regimen for patients with advanced pancreatic cancer with compromised clinical status.