Induction of apoptosis and cell cycle arrest by imexon in human pancreatic cancer cell lines

Imexon is an aziridine-containing small molecule currently in Phase I clinical trials. This agent has been shown to bind to thiols and increase intracellular oxidants, inducing apoptosis in hematologic cancer cells. Pancreatic cancers are known to be sensitive to oxidation, suggesting this disease may be an appropriate target for this agent. The current report examines the activity of imexon in pancreatic cells. Imexon induced concentration-dependent and time-dependent apoptosis in a panel of six human pancreatic carcinoma cell (PCC) lines. The mean IC₅₀ (SD) for growth inhibition by the SRB assay was 200 (101) µM for a 48 h exposure with a range of 64–358 µM. Cell killing was schedule-dependent, favoring exposure times ≥48 h. Imexon-treated MiaPaCa-2 cells underwent non-lethal growth arrest following exposure to concentrations ≤200 µM for 48 h. When concentrations were increased to 300 µM for ≥48 h, the MiaPaCa-2 cells arrested in G₂ phase and activated caspases 3, 8, and 9 were detected. After a 72 h exposure to the IC₈₀ concentration of imexon, cells exhibited a loss of mitochondrial membrane potential detected by CMXRos staining. However, there was no loss of reduced cellular thiols unless very high concentrations of ≥400 µM were used. In contrast, reactive oxygen species (ROS) were elevated in a dose-dependent fashion, starting at very low imexon concentrations. Imexon also significantly inhibited MiaPaCa-2 tumor growth in SCID mice at 100 mg/kg/d for 9 d. The tumor growth inhibition (% T/C) was 27% of control, and the tumor growth delay was 21 d, indicating an active agent by NCI standards. The levels of imexon that are cytotoxic in human PCC’s are achievable based on the preliminary results of the ongoing Phase I trial. Imexon appears to be active against PCCs in vitro and has an entirely novel mechanism of action involving G₂ arrest, accumulation of ROS, and the induction of apoptosis.     

Immunogenicity of oil-based contagious bovine pleuropneumonia vaccine in cattle

The effects on the immunity in cattle of dosage and storage of oil-based inactivated vaccine incorporating the Gladysdale strain were examined. Storage at 4°C for 12 or 24 months was found not to have any marked effect on the immunity conferred in the vaccinated cattle. A dosage of 0.5 ml was found to be as effective as dosages at 1 and 2 ml of the inactivated vaccine. To assess the potency of the inactivated vaccine in cattle two methods were used: antibody response to the vaccine using the complement fixation test and the challenge test in cattle by contact using a virulent strain at 2 and 6 months after vaccination.     

Long-term PM2.5 exposure before diagnosis is associated with worse outcome in breast cancer

Breast Cancer Research and Treatment - Many patients seek breast reconstruction following mastectomy. Debate exists regarding the best reconstructive option. The authors evaluate outcomes comparing...     

Self-reported yeast symptoms compared with clinical wet mount analysis and vaginal yeast culture in a specialty clinic setting

OBJECTIVE: To determine the validity of patients' self-reported symptoms of vulvovaginal candidiasis and the accuracy of clinical wet mount examinations compared with vulvovaginal yeast culture results in a specialty clinic. STUDY DESIGN: A retrospective chart review of new patients seen at the Saint Louis University Vulvar and Vaginal Disease Clinic from January 2005 to March 2006 was performed. Patients' age, medication use, symptom scores on a rating scale for vaginal/vulvar pain, burning, itching, dyspareunia and wet mount analyses were compared with yeast culture results. RESULTS: Of 153 patients, 40 had positive yeast cultures (prevalence rate 26.1%). Compared with yeast cultures, self-reported symptom scores >4 resulted in high sensitivity (90%) and low specificity (7%). Positive wet mount result showed low sensitivity (18%) and high specificity (99%). Patient symptom scores were a poor predictor of yeast infections based on yeast culture results. No correlation was found among wet mount, self-reported symptoms and yeast culture results. No significant difference between age or symptom scores to culture result was found. CONCLUSION: Wet mount analysis for recurrent or persistent patient symptoms should be reevaluated. Self-reported symptoms are not reliable for diagnosis. Wet mount analysis resulted in low sensitivity. Yeast cultures should be considered the gold standard for identification of vulvovaginal candidiasis in persistent or recurrent cases.     

Patterns of injuries: accident or abuse

This study uses two types of independent variables, age and the location of the physical wound, to develop a model of injury patterning that identifies violent behavior without direct observation of the assault. In this research, domestic violence injuries are compared to accidental injuries. The results indicate that there are specific and predictable injury patterns that separate abuse from other kinds of wounds. A logistic regression model was developed to identify the regions of the body most susceptible to injury from domestic assault. Using the age of the victim and the injury regions, probabilities were calculated to determine which wounds were caused by abuse.     

INTRA-STOMACHAL AND INTRA-INTESTINAL INOCULATIONS OF TRYPANOSOME VIRUS WITH TESTS FOR IMMUNITY

In nearly 50 per cent. of the cases, virulent trypanosome virus inoculated directly through the stomach wall of rats failed to infect these animals. The percentage of infections after inoculation of this kind seemed to vary with the virus. Surra of India proved to be the most virulent, and caderas the least. Nagana and dourine occupied intermediate positions. The rats that escaped infection showed no trace of immunity when tested with small quantities of the same virus between the twelfth and the twenty-eighth days after the intra-stomachal inoculations. The majority of the rats tested for immunity with surra of India and nagana seemed to have acquired, instead of an immunity, a certain hypersensitiveness to infection. Five of the seven nagana rats died before their controls. The results of testing the vitality of the trypanosomes of caderas, dourine, and nagana introduced directly into the stomachs and intestines of living rats seem to show that both motility and virulence are usually lost in less than two hours. Surra of India proved exceptionally resistant to the harmful influences of the stomach, for in one case, surra trypanosomes introduced into the intestines were found to be sluggishly motile in the stomach one hour and fifty-five minutes later, and in another instance, surra parasites injected into the stomach were found, when removed from that organ two hours later, to be actively motile and infectious.     

Trends in dietary fiber intake in Japan over the last century

Summary. Background: Insufficient intake of dietary fiber (DF) is currently a major problem in the overall promotion of health in the general population in Japan. Aim of the study: To analyze the time trends in DF intake, including DF density (total DF intake/1,000 kcal), and the ratio of water-insoluble fiber to water-soluble fiber (IS ratio) in Japan. Methods: The time trend in DF intake in Japan was calculated from data compiled in the Japanese National Nutrition Survey. Results: The mean daily DF intake (total DF intake) in 1952 was 20.5 g/day, which rapidly declined to about 70 % of the 1952 level in 1970, after which there was little change to 1998. DF density in 1952 was 9.7 g/1000 kcal, which declined by about 30 % in 1970, and remained at about the same level to 1998. The IS ratio has remained stable over this period. Whereas total DF intake and DF density in Japan are similar to those in Western countries, the IS ratios are higher in Japan. Therefore, the higher incidence of, and mortality from, colon diverticulosis, coronary heart disease, hyperlipidemia, etc., which are all thought to be related to fiber deficiency, in Western countries compared to Japan might be due to the differences in the IS ratio. Conclusions: A decline in total DF intake and DF density is predicted for Japan in the future, because these parameters were lower among the younger generation. This may be due to the marked changes in the dietary habits of the younger generation, and is a problematic trend for Japanese health. Received: 26 April 2002, Accepted: 22 August 2002 Correspondence to: Shigeyuki Nakaji, MD, PhD