PURPOSE: Anti-tumor necrosis factor-alpha (TNF-alpha) medications represent a major advancement in the management of chronic inflammatory diseases. However, these agents are associated with increased risks of tuberculosis (TB) and other serious infections. The aim of this study was to evaluate the incidences of such disease among tertiary hospitals in Korea. MATERIALS AND METHODS: We retrospectively studied patients who received anti-TNF-alpha therapy; we reviewed serious infections including TB that developed within 6 months after initiation of anti-TNF-alpha therapy. Data concerning patient demographics, types of anti-TNF-alpha agents, concomitant immunosuppressive drugs use, and infection details were collected. RESULTS: A total 175 patients treated with infliximab (n=72) or adalimumab (n=103) with the following conditions were enrolled: Crohn's disease, 34 (19.4%); ulcerative colitis, 20 (11.4%); ankylosing spondylitis, 82 (46.9%); and rheumatoid arthritis, 39 (22.2%). There were 18 cases (6.0%) of serious infections. The most common site of serious infection was the intra-abdomen (n=6), followed by TB (n=3), skin and soft tissue (n=3), bone and joints (n=2), ocular neurons (n=2), lower respiratory tract (n=1), and urinary tract (n=1). Of the 175 patients, only 3 cases showed development of TB. Furthermore, of all those who developed TB, none had taken anti-TB chemoprophylaxis prior to treatment with an anti-TNF agent due to negative screening results. CONCLUSION: Serious infections with anti-TNF-alpha therapy were uncommon among tertiary hospitals in Korea; TB was the second most frequent infection. Nevertheless, there were no TB reactivations after anti-TB chemoprophylaxis. Accordingly, physicians should be aware of TB in subjects undergoing anti-TNF-alpha therapy, especially in countries with a high prevalence of TB.
Arthritis, Rheumatoid ; Chemoprevention ; Colitis, Ulcerative ; Crohn Disease ; Demography ; Humans ; Incidence* ; Joints ; Korea ; Mass Screening ; Methods ; Necrosis* ; Neurons ; Prevalence ; Respiratory System ; Retrospective Studies ; Skin ; Spondylitis, Ankylosing ; Tertiary Care Centers ; Tuberculosis* ; Tumor Necrosis Factor-alpha ; Urinary Tract

OBJECTIVETo discover new chemopreventive agents, a drug screening cell model based on reporter gene and antioxidative response element (ARE) has been established.

METHODFour repeas of ARE DNA binding conserved sequences were synthesized and cloned into a GFP expression vector. This construct was stably transfected into HepG2 cells in vitro. The cell model was tested with known chemopreventive agents and the effects of resveratrol, protocatechuic aldehyde, ursolic acid and oleanolic acid at different concentration (0, 12.5, 25, 50, 100, 200 micromol x L(-1)) were observed by determining reporter gene GFP activity.

RESULTThe induce level of GFP was regulated by ARE and the dose-dependence in a certain range was observed. The induce level of GFP by resveratrol was significantly increased.

CONCLUSIONThe method can be used to screening of chemopreventive agents from Chinese traditional medicine by measurement of luminescent value of expressed GFP in wells of microtiter plate.

Antineoplastic Agents ; pharmacology ; Chemoprevention ; Drug Screening Assays, Antitumor ; methods ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression ; drug effects ; Genes, Reporter ; drug effects ; Green Fluorescent Proteins ; genetics ; metabolism ; Hep G2 Cells ; Humans ; Models, Biological ; Neoplasms ; drug therapy ; prevention & control

Opisthorchis viverrini infection causes inflammation and liver injury leading to periductal fibrosis. Little is known about the pathological alterations in bile canaliculi in opisthorchiasis. This study aimed to investigate bile canalicular alterations in O. viverrini-infected hamsters and to examine the chemopreventive effects of curcumin on such changes. Hamsters were infected with O. viverrini and one group of animals was fed with 1% dietary curcumin supplement. Animals were examined during the acute infection phase, days 21 and 30 post-infection (PI) and chronic infection phase (day 90 PI). Scanning electron microscopy revealed that in the infected group fed with a normal diet, bile canaliculi became slightly tortuous by 30 day PI and more tortuous at day 90 PI. Transmission electron microscopy showed a reduction in microvilli density of canaliculi starting at day 30 PI, with a marked loss of microvilli at day 90 PI. These ultrastructral changes were slightly seen at day 21 PI, which was similar to that found in infected animals fed with 1% curcumin-supplemented diet. Notably, curcumin treatment prevented the reduction of microvilli density, reduced the dilation of bile canaliculi, and decreased the tortuosity of the bile canaliculi relative to non-infected animals on a normal diet at days 30 and 90 PI. These results suggest that curcumin reduces alteration of bile canaliculi and may be a promising agent to prevent the onset of bile duct abnormalities induced by O. viverrini infection.
Animals ; Anthelmintics/*administration & dosage ; Bile Canaliculi/*pathology/ultrastructure ; Chemoprevention/methods ; Cricetinae ; Curcumin/*administration & dosage ; Disease Models, Animal ; Electrons ; Liver/pathology/ultrastructure ; Male ; Mesocricetus ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Opisthorchiasis/parasitology/*pathology/*prevention & control ; Opisthorchis/*growth & development

Vivax malaria was endemic on the Korean peninsula for many centuries until the late 1970's when the Republic of Korea (ROK) was declared "malaria free". Since its re-emergence in 1993, the number of malaria cases in the military increased exponentially through 2000 near the demilitarized zone. Chemoprophylaxis with chloroquine and primaquine has been used in the ROK Army since 1997 in an attempt to reduce the number of the malaria cases throughout the ROK. Data show that chemoprophylaxis contributed, in part, to the decrease in the number of malaria cases among military personnel. However, mass chemoprophylaxis on a large scale in the ROK Army is unprecedented and extensive supervision and monitoring is warranted to determine its effectiveness and to monitor the appearance of chloroquine tolerant/resistant strains of Plasmodium vivax.
Antimalarials/therapeutic use ; Chemoprevention/methods/statistics and numerical data ; Chloroquine/*therapeutic use ; Disease Outbreaks/*prevention and control/*statistics and numerical data ; Humans ; Incidence ; Korea/epidemiology ; Malaria, Vivax/*epidemiology/*prevention and control ; Military Personnel/*statistics and numerical data ; Outcome Assessment (Health Care) ; Prevalence ; Primaquine/*therapeutic use ; Research Support, Non-U.S. Gov't ; Risk Assessment/methods ; Risk Factors ; Treatment Outcome

Cancer is the main cause of death in developed countries. However, in underdeveloped countries infections and parasitic diseases are the main causes of death. There are raising scientific evidences indicating that parasitic infections induce antitumor activity against certain types of cancers. In this study, the effects of Toxoplasma gondii and Toxocara canis egg antigens in comparison with Bacillus Calmette Guerin (BCG) (known to have anticancer distinctive) on WEHI-164 fibosarcoma transplanted to BALB/c mice was investigated. Groups of 6 male BALB/c mice injected with T. gondii antigen, BCG, or T. canis egg antigen as case groups and alum alone as control groups. All mice were then challenged with WEHI-164 fibrosarcoma cells. The mice were examined for growth of the solid tumor and the tumor sizes were measured every other day up to 4 wk. The mean tumor area in T. gondii, BCG, or alum alone injected mice in 4 different days of measurements was 25 mm2, 23 mm2, and 186 mm2 respectively. Also the mean tumor area in T. canis injected mice in 4 different days was 25.5 mm2 compared to the control group (alum treated) which was 155 mm2. T. gondii parasites and T. canis egg antigens induced inhibition of the tumor growth in the fibrosarcoma mouse model. We need further study to clarify the mechanisms of anti-cancer effects.
Animals ; Antigens, Helminth/isolation & purification/pharmacology/*therapeutic use ; Antigens, Protozoan/isolation & purification/pharmacology/*therapeutic use ; Antineoplastic Agents/isolation & purification/pharmacology/*therapeutic use ; Chemoprevention/*methods ; Female ; Fibrosarcoma/pathology/*prevention & control ; Male ; Mice ; Mice, Inbred BALB C ; Mycobacterium bovis ; Toxocara canis/*chemistry ; Toxoplasma/*chemistry

OBJECTIVETo find out the anticancer effect of Indigofera aspalathoides (I. aspalathoides) on 20-methylcholanthrene induced fibrosarcoma in rats.

METHODSFibrosarcoma was induced in Wistar strain male albino rats by 20-methylcholanthrene. Intraperitoneous (i.p.) administration of 250 mg/kg body weight/day of aqueous extract of I. aspalathoides for 30 d effectively suppressed chemically induced tumors. Parameters such as body weight, liver and kidney weight, tumor weight, mean survival time, behavioral changes, blood glucose, blood glycogen and marker enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), acid phosphatase (ACP) and 5'-nucleiotidase (5'-NT) in serum, liver and kidney and lipid profiles such as total cholesterol, phospholipids, free fatty acids in liver and kidney of control and experimental animals were studied.

RESULTSFibrosarcoma bearing animals were ferocious and anxious. The mean survival time was found to increase after the treatment. The body weights were significantly decreased (P<0.001) in group II fibrosarcoma animals which steadily increased after the treatment with I. aspalathoides. The liver and kidney weights were significantly increased whereas the tumor weights decreased as compared to the weights in untreated fibrosarcoma bearing rats. The blood glucose and the liver and kidney glycogen levels were found to decrease significantly (P<0.001) in group II animals. Elevated activities of marker enzymes were observed in serum, liver and kidney of fibrosarcoma bearing Group II animals which were normalize after I. aspalathoides treatment. In the liver and kidney of Group II animals the total cholesterol increased whereas the phospholipids and free fatty acid levels decreased (P<0.001) which were normalized after treatment.

CONCLUSIONSThe treatment by I. aspalathoides on fibrosarcoma bearing rats has improved the levels of various parameters indicating its antiproliferative and anticancer activity.

Animals ; Antineoplastic Agents ; pharmacology ; Chemoprevention ; Fibrosarcoma ; drug therapy ; pathology ; Indigofera ; chemistry ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Liver Neoplasms, Experimental ; chemically induced ; pathology ; prevention & control ; Male ; Methylcholanthrene ; Phytotherapy ; methods ; Plant Extracts ; pharmacology ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Rats ; Rats, Wistar ; Seeds ; chemistry