Different mechanisms between premitotic apoptosis and postmitotic apoptosis in X-irradiated U937 cells

PURPOSE: Apoptosis is currently being evaluated for its importance as a pathway of radiation-induced cell death. However, the difference in the mechanisms between premitotic and postmitotic apoptosis following X-irradiation remains not well understood. We show here that the human monoblastoid cell line U937 can be induced to undergo these two different types of apoptosis. METHODS AND MATERIALS: U937 cells were irradiated at a dose of 5 or 20 Gy, and the DNA fragmentation rate was measured by both flow cytometric analysis and gel electrophoresis. Activation of caspase-3 was detected by Western blot analysis and fluorogenic assay using acetyl-Asp-Glu-Val-Asp-7-amino-4-methyl-coumarin (Ac-DEVD-AMC). Detection of mitochondrial transmembrane potential (DeltaPsi) was performed by using Rho123. Chasing of S-phase fraction following X-irradiation was performed after labeling with 5-bromo-2'-deoxyuridine (BrdU). Thymidine was used for synchronization of the cells. Inhibition of caspase-3 activity was achieved by Acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO). RESULTS: Time courses of the apoptotic rates, caspase activation, and DeltaPsi indicated that two different types of cell death were induced by the different X-ray doses. High-dose X-ray (20 Gy) induced a rapid and strong apoptosis, whereas low-dose X-ray (5 Gy) induced a slow and mild apoptosis. Cell-cycle analyses revealed that there was cell death before cell division in the former apoptosis but the cells must be dying after cell division in the latter apoptosis. By means of cell-cycle synchronization, the S-phase cells proved to be the most sensitive fraction to premitotic apoptosis, but an obvious difference in the susceptibility to cell death among the cell-cycle phases was not observed in postmitotic apoptosis. Ac-DEVD-CHO treatment effectively blocked caspase activity and premitotic apoptosis, but it failed to block postmitotic apoptosis. CONCLUSIONS: Irradiation of U937 cells at different X-ray doses induced two different types of apoptotic cell death, premitotic apoptosis and postmitotic apoptosis, which are characterized by the time course and cell-cycle specificity. Decision concerning these two types of apoptotic cell death may be made by the difference in the magnitude of cell damage following X-irradiation.     

Influence of synthetic and natural food dyes on activities of CYP2A6, UGT1A6, and UGT2B7

Synthetic or natural food dyes are typical xenobiotics, as are drugs and pollutants. After ingestion, part of these dyes may be absorbed and metabolized by phase I and II drug-metabolizing enzymes and excreted by transporters of phase III enzymes. However, there is little information regarding the metabolism of these dyes. It was investigated whether these dyes are substrates for CYP2A6 and UDP-glucuronosyltransferase (UGT). The in vitro inhibition of drug-metabolizing enzymes by these dyes was also examined. The synthetic food dyes studied were amaranth (food red no. 2), erythrosine B (food red no. 3), allura red (food red no. 40), new coccine (food red no. 102), acid red (food red no. 106), tartrazine (food Yellow no. 4), sunset yellow FCF (food yellow no. 5), brilliant blue FCF (food blue no. 1), and indigo carmine (food blue no. 2). The natural additive dyes studied were extracts from purple sweet potato, purple corn, cochineal, monascus, grape skin, elderberry, red beet, gardenia, and curthamus. Data confirmed that these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. Only indigo carmine inhibited CYP2A6 in a noncompetitive manner, while erythrosine B inhibited UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone). In the natural additive dyes just listed, only monascus inhibited UGT1A6 and UGT2B7.     

New procedure for purse-string suture in thoracoscopic esophagectomy with intrathoracic anastomosis

Background In endoscopic surgery, one of the greatest problems is the difficulty with the reconstructive procedure. This problem frequently makes operating times longer. The authors have performed thoracoscopic esophagectomy and intrathoracic esophagogastric anastomosis for reconstruction using a circular stapler for the esophageal cancer. Although the circular stapler is a useful device for gastrointestinal anastomosis, it was difficult to place a purse-string suture and to fixate the anvil into the proximal esophagus endoscopically.Methods The authors devised a new procedure for the placement of the purse-string suture by using an Endo-Stitch device along with a new method to incise the esophageal wall and thereby facilitate fixation of the anvil.Results The authors attempted this procedure for five patients. The anastomoses were performed successfully.Conclusions The new procedure can make endoscopic intrathoracic anastomosis feasible and safe. In addition, this procedure can be applied widely to other endoscopic reconstructions.     

The clinical evaluation of ceftizoxime suppositories in the pediatric field

Clinical evaluation of ceftizoxime suppository (CZX-S), a new antibiotic rectal suppository, was performed in 5 cases with bacterial infections in pediatric field (2 with acute bronchitis, 1 with acute tonsillitis, UTI and pertussis, respectively) and the following results were obtained; Blood levels of CZX at 10-20 minutes after administration of CZX-S at a dose of 10.0-26.3 mg/kg in 5 cases were 3.26-23.3 micrograms/ml and the urinary excretion rates within 6 hours were 15.2, 60.1, 60.2% in 3 of 5 cases measured respectively. Clinical effects were excellent in 3 and good in 2 cases. Slight elevation of GOT and GPT was observed in 1 case. No other side effects were observed. The patients' tolerability against rectal suppository was good. From the above results, we concluded that CZX-S is useful for treating the pediatric patients with various infections.     

Biological transmission of arboviruses: reexamination of and new insights into components, mechanisms, and unique traits as well as their evolutionary trends

Among animal viruses, arboviruses are unique in that they depend on arthropod vectors for transmission. Field research and laboratory investigations related to the three components of this unique mode of transmission, virus, vector, and vertebrate host, have produced an enormous amount of valuable information that may be found in numerous publications. However, despite many reviews on specific viruses, diseases, or interests, a systematic approach to organizing the available information on all facets of biological transmission and then to interpret it in the context of the evolutionary process has not been attempted before. Such an attempt in this review clearly demonstrates tremendous progress made worldwide to characterize the viruses, to comprehend disease transmission and pathogenesis, and to understand the biology of vectors and their role in transmission. The rapid progress in molecular biologic techniques also helped resolve many virologic puzzles and yielded highly valuable data hitherto unavailable, such as characterization of virus receptors, the genetic basis of vertebrate resistance to viral infection, and phylogenetic evidence of the history of host range shifts in arboviruses. However, glaring gaps in knowledge of many critical subjects, such as the mechanism of viral persistence and the existence of vertebrate reservoirs, are still evident. Furthermore, with the accumulated data, new questions were raised, such as evolutionary directions of virus virulence and of host range. Although many fundamental questions on the evolution of this unique mode of transmission remained unresolved in the absence of a fossil record, available observations for arboviruses and the information derived from studies in other fields of the biological sciences suggested convergent evolution as a plausible process. Overall, discussion of the diverse range of theories proposed and observations made by many investigators was found to be highly valuable for sorting out the possible mechanism(s) of the emergence of arboviral diseases.     

Evaluation of the elimination and safety of gadodiamide injection in patients with hemodialysis

We performed this study to evaluate the safety and elimination of gadodiamide injection in patients with hemodialysis (HD). The subjects were 10 patients on maintenance HD therapy, after receiving gadodiamide injection for magnetic resonance imaging (MRI) examination. The patients' mean age was 59.4 +/- 3.5 years, and their mean hemodialysis period was 70.6 +/- 20.4 months. Diseases for MRI examination were liver tumor (n=2), gallbladder tumor (n=1), renal tumor (n=3), pancreas tumor (n=1), abdominal aortic aneurysm (n=1), and arteriosclerosis obliterans (n=2). HD was performed routinely three times a week for 4 hours. Cellulose triacetate (CTA) membranes were used for 5 patients, polysulphone (PS) for 3 patients and polyester-polymer alloy (PEPA) for 2 patients. Serum levels of gadodiamide were analyzed before and after the first and second HD, and before the third and fourth HD. At the first HD, the concentration of gadodiamide in dialysate was analyzed every hour. Gadodiamide was eventually eliminated over time; 74.1% of the gadodiamide was dialyzed after the first HD and 98.8% after the third HD. There were no significant changes in the removal rate and laboratory parameters between each membrane. The present study suggests that gadodiamide could be removed by HD therapy efficiently thereby indicating that gadodiamide injection is possible in patients with HD.     

Dietary canola and soybean oil fed to SHRSP rat dams differently affect the growth and survival of their male pups

Canola oil (Can), as well as some other oils, shortens the survival of SHRSP rats compared with soybean oil (Soy). Although detrimental factors other than phytosterols have not been identified, they are likely to be hydrophobic and transmissible to pups. To test this possibility, female SHRSP rats (F0) were fed a diet supplemented with Can or Soy and mated at 11 wk of age. The growth of suckling pups (F1) from the Can-fed dams was significantly retarded compared with that of pups from the Soy-fed dams. Half of the male pups (F1) were weaned to the same diet as their dams (Can-->Can and Soy-->Soy groups) and the rest were weaned to the other diet (Can-->Soy and Soy-->Can groups). The survival rate of the male pups (F1) was significantly lower in the Can-->Can group than in the Soy-->Can group, and in the Can-->Soy group than in the Soy-->Soy group, indicating that the oils fed to dams differently affected the growth and survival of pups. There were fewer pups per dam in the Can-fed dams (F0) than in the Soy-fed dams, and in the dams (F1) of the Can-->Can and Soy-->Can groups than in those of the Can-->Soy and Soy-->Soy groups. Although Can is nutritionally detrimental to SHRSP rats compared with Soy, no direct evidence has been obtained thus far relating these observations to human nutrition.