1.Stress- and Aging-Associated Modulation of Macrophage Functions
Takako KIZAKI ; Kenji SUZUKI ; Tomomi OOKAWARA ; Tetsuya IZAWA ; Daizoh SAITOH ; Shuji OH-ISHI ; Keiichiro SUZUKI ; Shukoh HAGA ; Hideki OHNO
Environmental Health and Preventive Medicine 2001;6(4):218-228
Effects of environmental (cold) stress and aging on cells in monocyte/macrophage lineage were investigated. We demonstrated that immune suppressive states seen in acute cold-stressed mice (8-10 weeks of age) is attributable to FcγRIIbright suppressor macrophages. Serum corticosterone levels were markedly increased in acute cold-stressed mice. In addition, expression of glucocorticoids (GC) receptor mRNA was observed in FcγRIIbright cells from these mice. The increase of FcγRIIbright cells in peritoneal exudate cells caused by acute cold stress was inhibited by adrenalectomy or administration of a saturating amount of the GC antagonist RU 38486 (mifepristone). On the contrary, administration of the GC agonist, dexamethasone, markedly increased the proportion of FcγRIIbright cells in peritoneal exudate cells of control mice. These results suggest that the generation of FcγRIIbright suppressor cells of monocyte/macrophage lineage by acute cold stress was mediated by action of GC through the GC receptor. We likewise found that the proportion of FcγRIIbright suppressor macrophages is increased in aged mice (22-24 months of age). Meanwhile, activated macrophages which function as antigen presenting cells were decreased in aged rats. Both the basal corticosterone concentrations in serum and the expression of mRNA for GC receptor in peritoneal macrophages increased significantly in aged animals, suggesting that these populational and functional changes of macrophages in aged animals were mediated, in part, by the increased basal levels of GC. This is probably being responsible for immunosenescence.
Neisseria gonorrhoeae
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Laboratory mice
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Acute
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Macrophages
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receptor
2.Quercetin Enhances Tumorigenicity Induced by N-Ethyl-N'-Nitro-N-Nitrosoguanidine in the Duodenum of Mice*
Yoshizumi MATSUKAWA ; Hoyoku NISHINO ; Mitsunori YOSHIDA ; Hiroyuki SUGIHARA ; Kanade KATSURA ; Tetsurou TAKAMATSU ; Junichi OKUZUMI ; Katsuhiko MATSUMOTO ; Fumiko SATO-NISHIMORI ; Toshiyuki SAKAI
Environmental Health and Preventive Medicine 2001;6(4):235-239
Quercetin, a flavonoid, widely distributed in many fruits and vegetables, is well known to have an anti-tumor effect despite its mutagenicity. In this study, we examined the effect of dietary quercetin on duodenum-tumorigenicity of mice induced by a chemical carcinogen, N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Eight-week-old male C57BL/6 mice were divided into 4 groups; ENNG without quercetin (group A), ENNG with 0.2% quercetin (group B), ENNG with 2% quercetin (group C), and 2% quercetin without ENNG (group D). ENNG was given in drinking water for the first 4 weeks, and thereafter quercetin was given in a mixed diet. At week 20, the average number of duodenal tumors per mouse was significantly higher in group C (mean±SE, 7.26±1.75, p<0.05) than in group A (2.32±0.31). The size of the duodenal tumors increased significantly in group B (1.79±0.09 mm, p<0.001) compared with group A (1.43±0.09 mm). In contrast, no duodenal tumor was induced in group D. The present findings suggest that excessive intake of quercetin occasionally is a risk factor for carcinogenesis of some specific organs such as the upper intestine.
Quercetin
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Upper Case En
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ENNG
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week
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Laboratory mice
3.Eurycoma longifolia extract-artemisinin combination: parasitemia suppression of Plasmodium yoelii-infected mice.
M A R Mohd Ridzuan ; A Sow ; A Noor Rain ; A Mohd Ilham ; I Zakiah
Tropical biomedicine 2007;24(1):111-8
Eurycoma longifolia, locally known as 'Tongkat Ali' is a popular local medicinal plant that possess a lot of medicinal properties as claimed traditionally, especially in the treatment of malaria. The claims have been proven scientifically on isolated compounds from the plant. The present study is to investigate the anti malaria properties of Eurycoma longifolia standardized extract (root) (TA164) alone and in combination with artemisinin in vivo. Combination treatment of the standardized extract (TA164) with artemisinin suppressed P. yoelii infection in the experimental mice. The 4 day suppressive test showed that TA164 suppressed the parasitemia of P. yoelii-infected mice as dose dependent manner (10, 30 and 60 mg/kg BW) by oral and subcutaneous treatment. By oral administration, combination of TA164 at 10, 30 and 60 mg/kg BW each with artemisinin respectively showed a significant increase in the parasitemia suppression to 63, 67 and 80 percent as compared to artemisinin single treatment (31%). Using subcutaneous administration, at 10 mg/kg BW of TA164 in combination with 1.7 mg/kg BW of artemisinin gave a suppression of 80% of infection. This study showed that combination treatment of TA164 with artemisinin gives a promising potential anti malaria candidate using both oral and subcutaneous route, the later being the most potent.
artemisinine
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therapeutic aspects
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Psychological suppression
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Laboratory mice
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Subcutaneous
4.Antimalarial properties of Goniothalamin in combination with chloroquine against Plasmodium yoelii and Plasmodium berghei growth in mice.
M A R Mohd Ridzuan ; U Ruenruetai ; A Noor Rain ; S Khozirah ; I Zakiah
Tropical biomedicine 2006;23(2):140-6
Malaria is a disease which is still endemic and has become a disastrous scourge because of the emergence of antimalarial drug resistant Plasmodium falciparum. A new approach in addressing this is in developing a combination drug. This study is to show the enhancement of antimalarial properties, when single compound, goniothalamin combine with standard drug, chloroquine. Based on 4 Day Test, percentage of parasite growth on treated infected mice were determined. Oral treatment with 1 mg/kg BW of chloroquine on experimental mice suppressed 70% and 76.7% of both Plasmodium yoelii and Plasmodium berghei, respectively. The infection of P. berghei in mice was inhibited less than 50% by goniothalamin individual treatment at all doses in this study. About 27.8% and 18.5% inhibition of infection were observed in P. yoelii infected mice treated with 30 mg/kg and 60 mg/kg of goniothalamin respectively and the suppression exceed more than 50% at higher doses (90 and 120 mg/kg). Combination of 1 mg/kg chloroquine with either 30 mg/kg or 60 mg/kg of goniothalamin decreased the parasitemia of P. yoelii infected mice more than 90% and prolong the survival up to 100% after treatment. Similar treatment to P. berghei infected mice only shows about 60% reduction of parasitemia. The study findings showed that antimalarial property of goniothalamin was enhanced by combination with chloroquine at lower dose of each drug.
Laboratory mice
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Chloroquine
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goniothalamin
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upper case pea
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therapeutic aspects
5.Laboratory animal allergy in laboratory animal workers.
Jae Yeon MOON ; Cheol Woo KIM ; Jae Hee CHO ; Jae Hyeon CHANG ; Soo Young CHOI ; Na Young KWON ; Chein Soo HONG
Journal of Asthma, Allergy and Clinical Immunology 2003;23(3):515-524
BACKGROUND: Laboratory animal workers who are in regular contact with furred animals commonly develop laboratory animal allergy (LAA). LAA is one of the most common occupational allergic diseases. OBJECTIVES: This study was performed to estimate the prevalence of sensitization and symptoms of LAA, and to determine important host factors for the development of LAA. METHOD: Sixteen subjects with laboratory animal workers in one medical research center were enrolled in this study. They responded to a questionnaire about work-related symptoms and underwent allergy skin prick test to common inhalant and laboratory animal allergens. RESULTS: The prevalence of sensitization to laboratory animal allergens was 18.8%, and all sensitized workers were atopic (positive skin reactivity to one or more common inhalant allergens). Prevalence rate of allergy symptoms caused by working with laboratory animals was 31.3%. Positive skin prick responses to dog or cat allergens were highly associated with specific sensitization to laboratory animal allergens, and positive skin responses to laboratory animal allergens were associated with laboratory allergy symptoms. Among sixteen subjects, we found out one case of occupational asthma due to mouse allergy and also reported the case here. CONCLUSION: Some laboratory animal workers showed sensitization to laboratory animal allergens and had allergic symptoms attributed to contact with laboratory animals. Atopy, especially atopy to dogs or cats may be an important host factor for the development of LAA.
Allergens
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Animals
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Animals, Laboratory*
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Asthma, Occupational
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Cats
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Dogs
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Hypersensitivity*
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Mice
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Prevalence
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Skin
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Surveys and Questionnaires
6.Laboratory Rodents Negatively Affected by Construction Environment.
Byeong Han LEE ; Hyun Don JUNG ; Byung Noh LEE ; Kyu Sang PARK ; Jin Soo HAN
Laboratory Animal Research 2010;26(4):425-428
This report describes rodents in a laboratory animal facility that was adversely affected by a noisy environment during construction work. There was much noise and vibration as well as dust caused by the drilling and hammering. The noise levels, frequencies, and length of time when occurring in the drilling and hammering, were all measured. The drilling showed noise levels ranging from 50-90 decibels (dB) (A-filter, A), and the hammering presented 60-70 dB (A). Some researchers raised problems regarding animal experiments, including skin injuries resulted from self-mutilation, and increase of mortality. This gives useful information to people who plan to renovate laboratory animal facilities as it is a very rare case.
Animal Experimentation
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Animal Welfare
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Animals
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Animals, Laboratory
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Dust
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Mandrillus
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Mice
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Noise
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Rats
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Rodentia
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Skin
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Vibration
7.Enhancement of Gene Delivery into Mouse Skeletal Muscle with Microbubble Destruction by Low-Frequency Ultrasound.
Sang Chol LEE ; Sung Soo JUNG ; Seon Woon KIM ; Sung Hoon LIM ; Dae Kyung CHO ; Sung Uk KWON ; Il RHEE ; Jeong Min KIM ; Jung Sun LEE ; Kiick SUNG ; Seung Woo PARK ; Eun Seok JEON ; Duk Kyung KIM ; Sang Hoon LEE ; Kyung Pyo HONG ; Jeong Euy PARK ; Jung Don SEO
Korean Circulation Journal 2006;36(1):32-38
BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the value of microbubble destruction using low-frequency ultrasound for enhancing gene delivery to skeletal muscles of laboratory animals. MATERIALS AND METHODS: Lac-Z gene was injected into 21 mouse anterior tibialis muscles. Seven muscles received the gene only, and seven each received either 20-kHz ultrasound exposure or ultrasound-PESDA (perfluorocarbon-exposed sonicated albumin) destruction, respectively, following the injection; the extent of Lac-Z expression was then compared. Luciferase gene was injected into the muscles (N=80). The muscles were divided into two groups according to the mixture; in the first group saline was used as the mixture solute, with PESDA used in the second group. The groups were subdivided into two groups, one receiv 10 seconds of ultrasound at the injection site after injection, and the other that received no further intervention. Luciferase activities were measured and compared. RESULTS: The proportions of Lac-Z stained cells were 0, 5.7+/-1.2 and 7.7+/-1.7%, respectively, showing a significant stepwise increase microbubble destruction (p<0.05). Luciferase activities were as follows: Luciferase only (Group 1, N=17), 5727+/-2178 RLU/mg; luciferase plus PESDA (Group 2, N=17), 1170+/-470.7 RLU/mg; luciferase plus ultrasound (Group 3, N=17), 16480+/-5239 RLU/mg; and luciferase plus PESDA destruction (Group 4, N=17), 49910+/-16500 RLU/mg. The activity in group 4 was significantly higher than in group 1 (p<0.01), showing an 8.7-fold increase in gene delivery due to microbubble destruction. CONCLUSION: Microbubble destruction using low-frequency ultrasound is an efficient method for increasing the efficacy of direct gene delivery to skeletal muscles.
Animals
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Animals, Laboratory
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Genetic Therapy
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Luciferases
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Mice*
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Microbubbles*
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Muscle, Skeletal*
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Muscles
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Ultrasonography*
8.Mice Lacking Protein Tyrosine Kinase Fyn Develop a T Helper-Type 1 Response and Resist \it{Leishmania major} Infection
Kazuo YAMAKAMI ; Shinkichi AKAO ; Kazuo WAKABAYASHI ; Takushi TADAKUMA ; Nobuyuki YOSHIZAWA
Environmental Health and Preventive Medicine 2001;6(2):132-135
Fyn is a Src family protein tyrosine kinase associated with TCR/CD3 complex. Fyn appears to play a role in the activation of T cells based on its enzymatic activation and tyrosine phosphorylation following the ligation of TCR/CD3, and it also plays a critical role in the calcium flux and interleukin-2 (IL-2) production. The protective response against murine Leishmania major infection is associated with the T helper-type 1 (Th1) responses and the ability to modulate Th1 cytokines such as IL-2 and interferon-γ, respectively. The role of Fyn tyrosine kinase in vivo was directly examined by the response to infection with L. major in C57BL/6 fyn-deficient mice. Despite the absence of Fyn, the mice remained resistant to this infection with only mild lesion development, and, they demonstrated Th1 responses as assessed by the delayed-type hypersensitivity response and cytokine milieu. The findings in the fyn-deficient mice failed to support a relationship between the anticipated functions of Fyn in vitro and the immune response to L. major infection in vivo. As a result, in leishmanial disease, Fyn probably plays a minor role in the protective immune response and is, therefore, not a key factor in such a response.
Infection as complication of medical care
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Role
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Protein-Tyrosine Kinase
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Upper case tea
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Laboratory mice
9.Influence of rice with different amylose contents on postprandial glycemic response
Masayuki Yamasaki ; Mamiko Watanabe ; Toshimi Yoneyama ; Akiko Nogi ; Li Wang ; Kuninori Shiwaku
Journal of Rural Medicine 2006;2(1):51-58
Objective: Clinical studies suggest that maintaining a lower postprandial glycemic response is important for improvement and prevention of metabolic syndrome and type 2 diabetes mellitus. Amylose, an ingredient in many food grains, is a major factor for the lowering of postprandial glycemic and insulinemic response. The aim of the present study was to determine the influence of rice with different level of amylose on postprandial glycemic and insulinemic response in mice and humans.Materials and Methods: The two types of rice used in the study contained 29 wt% (high amylose rice) or 17 wt% (low amylose rice) amylose. In mice and humans, postprandial glycemic and insulinemic responses were measured and then the area under the response curves of both rice groups were compared.Results: In mice, comparisons of postprandial glycemic response showed high amylose rice was lower than that for low amylose rice in all time points. Notably postprandial glycemic responses for high amylose rice at 15, 30, 45 and 60 min were significantly lower (19%, 31%, 16% and 17% respectively). The area under the glycemic response curve for high amylose rice was a remarkably 16% less than for the low amylose rice. In humans, postprandial glycemic response at 30 min and insulinemic response at 60 min for high amylose rice were significantly lower than for low amylose rice (15% and 40% lower, respectively). Furthermore, general linear measurement multivariate analysis after adjustment for eating time and hemoglobin A1c at baseline showed that postprandial glycemic response at 30 and 60 min and insulinemic response at 60 min, and the area under the glycemic response curve for high amylose rice were significantly lower than for low amylose rice in human.Conclusion: The higher amylose content of the rice lowered the postprandial glycemic and insulinemic response, demonstrating the potential to prevent or improve metabolic syndrome and type 2 diabetes mellitus.
Rice
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Minute of time
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Laboratory mice
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Syndrome
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Diabetes Mellitus, Non-Insulin-Dependent
10.A recombinant 19 kDa Plasmodium berghei merozoite surface protein 1 formulated with alum induces protective immune response in mice.
A Wan Omar ; A M Roslaini ; Z U Ngah ; A A Azahari ; M Zahedi ; O Baharudin
Tropical biomedicine 2007;24(1):119-26
We investigated the immunogenicity of recombinant rMSP1 (rPbMSP1) that was generated from Plasmodium berghei. The rPbMSP1 formulated in alum was found to be immunogenic which induced high levels of specific anti-rPbMSP1 antibody. The IgG2a response predominated over IgG1 during the challenge infection in the vaccinated mice. Mice vaccinated with rPbMSP1 in alum mounted significant protective immunity against challenge infection (P < 0.01). On day 121 after the booster, three out of ten mice immunized with rPbMSP1 in PBS survived parasite infection (P < 0.05) and eight out of ten mice vaccinated with r MSP1 in alum did (P < 0.01). Hence, immunization with MSP1 in alum obviously has conferred protective effects, which prevented death from P. berghei lethal infection in mice (P < 0.01). These observations provide an excellent model for clinical assessment of this formulation in human subjects.
aluminum sulfate
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Laboratory mice
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upper case pea
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Infection as complication of medical care
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protect