PURPOSE: In a previous study, we have shown that anticancer agents inhibiting topoisomerases improve survival of tumor cells under hypoxic condition. In the present study, we evaluated whether and how cell survival effect of the anticancer agents under hypoxic conditions could be eliminated by the addition of nitroimidazoles, a class of bioreductive agents. METHODS: Human hepatocellular carcinoma cells (HepG2) were incubated with different combinations of pimonidazole (1~1,000 microg/ml) and doxorubicin (0.1 or 1 microg/ml) concentrations under different O2 concentrations [1, 3, 5, 10 and 21 O2]. Then cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured, and DNA fragmentation assay was performed. Finally, different combinations of nitroimidazoles, such as pimonidazole, misonidazole, etanidazole, tinidazole, metronidazole, ornidazole or dimetridazole, and anticancer agents, such as doxorubicin, campothecin, epirubicin, dactinomycin, etoposide or mitomycin C was added to the cell culture medium under hypoxic conditions (1% O2). RESULTS: Pimonidazole at a concentration of 100 microg/ml eliminated cell survival effect of doxorubicin at the concentrations of 0.1 and 1 microg/ml under hypoxic condition (1% O2) by promoting apoptosis. Almost all the cells died even after 24 hours of incubation for all the oxygen concentrations at a combination of 100 microg/ml pimonidazole and 1 microg/ml doxorubicin. Finally, pimonidazole at a concentration of 100 microg/ml, and misonidazole or etanidazole at a concentration of 1,000 microg/ml eliminated cell survival effect of all the anticancer agents tested under hypoxic condition. CONCLUSION: Combination therapy of doxorubicin (adriamycin) with pimonidazole can maximize dororubicin efficacy by eliminating cell survival effect of doxorubicin under hypoxic conditions in treating solid tumors, such as breast cancer.
Anoxia ; Antineoplastic Agents ; Apoptosis ; Breast Neoplasms ; Carcinoma, Hepatocellular ; Cell Count ; Cell Culture Techniques ; Cell Survival ; Dactinomycin ; Dimetridazole ; DNA Fragmentation ; Doxorubicin ; Epirubicin ; Etanidazole ; Etoposide ; Glucose ; Humans ; Lactic Acid ; Metronidazole ; Misonidazole ; Mitomycin ; Nitroimidazoles ; Ornidazole ; Oxygen ; Tinidazole

Noninvasive imaging of molecular and biological processes in living subjects with positron emission tomography (PET) provides exciting opportunities to monitor metabolism and detect diseases in humans. Measuring these processes with PET requires the preparation of specific molecular imaging probes labeled with 18F-fluorine. In this review we describe recent methods and novel trends for the introduction of 18F-fluorine into molecules which in turn are intended to serve as imaging agents for PET study. Nucleophilic 18F-fluorination of some halo- and mesyloxyalkanes to the corresponding 18F-fluoroalkanes with 18F-fluoride obtained from an 18O(p,n)18F reaction, using novel reaction media system such as an ionic liquidor tert-alcohol, has been studied as a new method for 18F-fluorine labeling. Ionic liquid method is rapid and particularly convenient because 18F-fluoride in H2O can be added directly to the reaction media, obviating the careful drying that is typically required for currently used radiofluorination methods. The nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with 18F-fluorine for PETimaging, and it is illustrated by the synthesis of 18F-fluoride radiolabeled molecular imaging probes, such as 18F-FDG, 18F-FLT, 18F-FP-CIT, and 18F-FMISO, in high yield and purity and in shorter times compared to conventional syntheses
Biological Processes ; Dideoxynucleosides ; Fluorides ; Fluorodeoxyglucose F18 ; Halogenation ; Humans ; Imidazoles ; Misonidazole ; Molecular Imaging ; Nitro Compounds ; Organothiophosphorus Compounds ; Positron-Emission Tomography ; Radiopharmaceuticals ; Solvents

No abstract available.
Metronidazole

OBJECTIVE: To evaluate the therapeutic effects of acupoint autohemotherapy (A-AHT) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in mice focusing on regulating T helper 1/T helper 2 (Th1/Th2) immune responses. METHODS: Thirty BALB/c mice were divided into 5 groups by a random number table, including normal control (NC), AD model (AD), A-AHT, sham A-AHT (sA-AHT), and acupoint injection of normal saline (A-NS) groups, 6 mice per group. Mice were challenged by DNCB for the establishment of experimental AD model. On the 8th day, except for the NC and AD groups, the mice in the other groups received management once every other day for a total of 28 days. For the A-AHT and sA-AHT groups, 0.05 mL of autologous whole blood (AWB) was injected into bilateral Zusanli (ST 36) and Quchi (LI 11) and sham-acupoints (5 mm lateral to ST 36 and LI 11), respectively. The A-NS group was administrated with 0.05 mL of normal saline by acupoint injection into ST 36 and LI 11. Dermatitis severity for dorsal skin of mice was determined using the Severity Scoring of Atopic Dermatitis (SCORAD) every week. The total immunoglobulin E (IgE), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) cytokine levels in serum were examined by enzyme-linked immunosorbent assay (ELISA). Spleen Th1/Th2 expression were analyzed via flow cytometry and immunohistochemical assay was used to detect T-box expressed in T cell (T-bet) and GATA-binding protein 3 (GATA3) expressions in skin lesions of mice. RESULTS: Compared with the AD group, both A-AHT and sA-AHT reduced the SCORAD index and serum IgE level (P<0.05 or P<0.01); A-AHT, sA-AHT and A-NS down-regulated serum IL-4 level and upregulated IFN-γ/IL-4 ratio (P<0.05 or P<0.01); A-AHT regulated the Th1/Th2 shift specifically and increased the related transcription factors such as T-bet expression and T-bet/GATA3 ratio (P<0.05). CONCLUSION A-AHT showed significant effectiveness on the AD model mice, through regulating Th1/Th2 immune responses.
Acupuncture Points ; Animals ; Dermatitis, Atopic/therapy* ; Dinitrobenzenes ; Dinitrochlorobenzene ; Immunoglobulin E ; Interferon-gamma ; Interleukin-4 ; Mice ; Mice, Inbred BALB C ; Saline Solution

Child ; Dinitrobenzenes ; poisoning ; Humans

Tolerance to contact hypersensitivity was induced by feeding of different DNCB doses in mice. A total of 40 mice were divided into 4 groups(control group, 6 mg feeding group, 10 mg feeding group, 14 mg feeding group) in experiment I, Degree of tolerance to contact hypersensitivity was rneasured by incremert rate of ear swelling after challenge with DNFB. Experiment 2 was performed in the same method of cxperiment: I with addition of 3 mg DNCB feeding group. The increment ratee were significantly decreased in DNCB feeding groups in experirnent 1 and 2(p<0.0l). But there were no differences statisticalIy between increment rates of DNCB feeding groups.
Animals ; Dermatitis, Contact ; Dinitrochlorobenzene* ; Dinitrofluorobenzene ; Ear ; Mice*

PURPOSE: The use of prophylactic antibiotics is the current standard of care after elective colorectal surgery. The aim of this study was to compare the efficacy of antibiotic prophylaxis with dual antibiotic therapy and triple antibiotic therapy after elective colorectal surgery. METHODS: We studied consecutive patients underwent elective colorectal surgery from January to June, 2007. Patients of triple-therapy group were administered second cephalosporin, metronidazole, and aminoglycoside for early 3 mo and dual-therapy group were administered second cephalosporin and metronidazole for next 3 mo. The prophylactic antibiotics were administered 2-3 doses for 24 hr after surgery. The surgery for diverticulitis, inflammatory bowel disease, and colon obstruction were excluded. Wound conditions were checked on alternate days during the hospital stay and follow up at least for 30 days after discharge. RESULTS: Over 6 mo, 110 patients were enrolled (59 dual-therapy group, 51 triple-therapy group). In two group, sex, age, American Society of Anesthesiology score, body mass index, combined diseases, and location of disease were similar. Wound infection rate were 1.7% in dual-therapy group and 2.0% in triple-therapy group (P=1.0). Anastomotic leakage rate were 5.1% in dual-therapy group and 2.0% in triple-therapy group (P=0.622). CONCLUSION: The addition of aminoglycoside to dual antibiotic therapy, second cephalosporin-metronidazole showed on advantage in prevention of postoperative wound complications. Further studies are required to establish appropriate guideline of antibiotic prophylaxis after elective colorectal surgery.
Anastomotic Leak ; Anesthesiology ; Anti-Bacterial Agents ; Antibiotic Prophylaxis ; Body Mass Index ; Colon ; Colorectal Surgery ; Diverticulitis ; Follow-Up Studies ; Humans ; Imidazoles ; Inflammatory Bowel Diseases ; Length of Stay ; Metronidazole ; Nitro Compounds ; Standard of Care ; Wound Infection

The aims of this study were to investigate the changing pattern of Helicobacter pylori antibiotic resistance in Jinju over a 15-year period. H. pylori strains were isolated from 170 adults living in Jinju from 1985-1989, 1990-1994 and 1995-1999, and from 23 adults living in Cheongju from 1995 to 1999. Susceptibility to erythromycin, clarithromycin, azithromycin, amoxicillin, tetracycline, metronidazole, furazolidone, levofloxacin, ciprofloxacin, moxifloxacin, and rifabutin was tested using the serial two-fold agar dilution method. Moxifloxacin resistance significantly increased in Jinju from 1985-1989 (0%) to 1995-1999 (14.9%) (p < 0.0001). Resistance to amoxicillin was increasesed trend to decreased trend from 1985 to 1999 (p = 0.033), whereas metronidazole resistance decreased from 37.5% to 21.3%. Resistance to furazolidone was greater from 1985-1989 (9.4%) than in 1995-1999 (2.1%). In comparing Jinju and Cheongju, minimal inhibitory concentrations (MICs) of tetracycline and levofloxacin among H. pylori isolated from Jinju were lower than for isolates from Cheonju (p < 0.05). The levofloxacin resistance rate was higher in Cheongju than in Jinju (p = 0.02). No macrolide resistance was observed in Cheongju. Overall, we did not observe any remarkable antimicrobial resistance increase of H. pylori strains isolated from Jinju over 15 years. The MIC distributions of antimicrobials and antimicrobial resistant rates were time- and region-specific among different strains. Future anti-H. pylori eradication regimens should be designed based on the changing patterns of antimicrobial resistance according to the resident area.
Adult ; Agar ; Amoxicillin ; Anti-Infective Agents ; Aza Compounds ; Azithromycin ; Ciprofloxacin ; Clarithromycin ; Drug Resistance, Microbial ; Erythromycin ; Furazolidone ; Helicobacter ; Helicobacter pylori ; Humans ; Metronidazole ; Ofloxacin ; Quinolines ; Rifabutin ; Tetracycline

The diagnosis of a bony fracture by the use of ultrasound is not common. However, with the advantage of the use of a real time examination and recent technical advances, the use of ultrasound has gradually been on the increase. In this pictorial review, we demonstrate the sonographic findings of various kinds of bony fractures where an ultrasound examination was effective in the diagnosis of a fracture. The use of ultrasound is compared with the use of other imaging modalities.
Imidazoles ; Nitro Compounds

BACKGROUND: Repeating a QC that is outside 2SD from the mean (1:2s rule) appears to be a common practice. Although this form of repeat-sampling is frowned on by many, the comparative power of the approach has not been formally evaluated. METHODS: We computed power functions mathematically and by computer simulation for 4 different 1:2s repeat-sampling strategies, as well as the 1:2s rule, the 1:3s rule, and 2 common QC multirules. RESULTS: The false-rejection rates for the repeat-sampling strategies were similarly low to those of the 1:3s QC rule. The error detection rates for the repeat-sampling strategies approached those of the 1:2s QC rule for moderate to large out-of-control error conditions. In most cases, the power of the repeat-sampling strategies was superior to the power of the QC multirules we evaluated. The increase in QC utilization rate ranged from 4% to 13% for the repeat-sampling strategies investigated. CONCLUSIONS: The repeat-sampling strategies provide an effective tactic to take advantage of the desirable properties of both the 1:2s and 1:3s QC rules. Additionally, the power of the repeat-sampling strategies compares favorably with the power of 2 common QC multirules. These improvements come with a modest increase in the average number of controls tested.
Computer Simulation ; Imidazoles ; Nitro Compounds