Hepatic isometallothioneins in mice: induction in adults and postnatal ontogeny

The purpose of this study was to quantitate hepatic metallothionein-I (MT-I) and metallothionein-II (MT-II) in adult mice pretreated with various dosages of selected inorganic and organic compounds and in nonchemically treated neonatal mice. Male CF-1 mice received Zn (0.38-6.0 mmol/kg, sc), Cd (5-80 mumol/kg, sc), dexamethasone (10-1000 mumol/kg, sc), or ethanol (60-180 mmol/kg, po). Liver cytosol was prepared 24 hr after the administration of each compound. In another experiment, liver cytosols were prepared from male and female neonates 1 to 35 days after parturition. MT-I and MT-II in liver cytosols were isolated by high-performance anion-exchange chromatography and quantitated by atomic absorption spectrometry. Hepatic MT-I and MT-II concentrations in adult controls were 5.1 +/- 1.3 and 3.7 +/- 1.0 micrograms/g liver, respectively. All compounds increased hepatic MT levels in a dose-dependent manner over a narrow range of dosages. The lowest dosages of Zn, Cd, dexamethasone, and ethanol that produced a significant increase in total MT content (MT-I plus MT-II) were 0.38, 0.005, 0.3, and 90 mmol/kg, respectively. Maximal induction of total MT following the highest dosages of Zn, Cd, ethanol, and dexamethasone was 58, 34, 24, and 13 times the control value (8.8 +/- 2.4 micrograms total MT/g liver), respectively. The relationship between dose and hepatic MT content was linear following ethanol administration and log-linear following Zn, Cd, and dexamethasone administration. The ratio of MT-I/MT-II was approximately 2.4 following all dosages of metals. Following low and high dosages of organic compounds, the ratio of MT-I/MT-II was approximately 1.0 and 1.5, respectively. Total MT concentration in livers of 1- to 14-day-old mice was approximately 40 times that observed in adult liver (5.5 +/- 1.6 micrograms total MT/g liver) and returned toward adult levels 21 days after parturition. The ratio of MT-I/MT-II was approximately 1.8 during Postpartum Days 1 through 14 and thereafter decreased to approximately 1.0. These results indicate that MT-I is more abundant than MT-II in mouse liver following chemical exposure and during neonatal development.     

环孢菌素A阻断人HL－60抗药性细胞于G_1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的ＨＬ－６０细胞（ＨＲ２０）抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明，环孢菌素Ａ（ＣｓＡ）２０，１０μｇ·ｍｌ￣（－１）诱导ＨＬ－６０细胞发生凋亡，而阻断ＨＲ２０细胞于Ｇ＿１期，就不能诱导细胞发生凋亡。低浓度的ＣｓＡ明显增加柔红霉素在ＨＲ２０细胞内的积聚，其逆转抗药性作用与阻断细胞周期运行无关。ＣｓＡ１０μｇ·ｍｌ￣（－１）处理ＨＲ２０细胞，可引起５０ｋＤａ的蛋白质高度磷酸化。结果提示：环孢菌素Ａ阻断抗三尖杉酯碱的ＨＬ－６０细胞于Ｇ＿１期，而诱导敏感的ＨＬ－６０细胞发生凋亡，其阻断作用与抗药性无关     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Influence of inhaled corticosteroids on growth: a pediatric endocrinologist''s perspective

Given the increasing advocacy for the use of inhaled corticosteroids as a treatment of choice for persistent asthma, growing numbers of children are being exposed to the possible growth-suppressing effects of glucocorticoids. Recent evidence strongly suggests that, when consistently administered at moderate doses, inhaled corticosteroids (IC) are capable of slowing growth in children. Whether such growth suppression would persist and ultimately affect final adult height remains unknown. Therapeutic goals which aim for uninterrupted inflammatory disease control rather than periodic symptom control may increase the occurrence of growth failure in children treated with IC. In this article, current information about the mechanisms of growth suppression by glucocorticoids and the effects of IC on growth is reviewed, and recommendations for designing studies to investigate the effects of drugs on growth are presented.     

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.      

Combination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven hematological cancers

In order to stimulate antigen presentation and T cell activity against cancer, we treated three different tumor models in mice with the monoclonal antibodies anti-CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer model, there was significant enhancement in the survival of mice following BiMab treatment. Anti-CD40 has shown considerable success against lymphoma in previous studies by other investigators, and we also showed in this study that, in a model of Eμ-Myc lymphoma, there was a statistically significant enhancement of survival of mice following BiMab treatment. Following the success of the BiMab treatment in the previous two models, we wished to determine if it would be successful in a mouse model of multiple myeloma. Firstly, we tested a transplantable model of disease in which multiple myeloma cells derived from Vk*MYC mice were injected intravenously. A minor proportion of anti-CD137 and BiMab treated mice experienced prolongation of life beyond 250 days. Then we tested the therapy in a spontaneously occurring multiple myeloma model, in Vk*MYC transgenic mice. The majority of mice treated survived longer than control mice, although statistical significance was not demonstrated.     

In vitro and in vivo trypanocidal effect of lipophilic extracts of medicinal plants from Mali and Burkina Faso

AIM OF THE STUDY: To determine the in vitro and in vivo antitrypanosomal activity of extracts of traditionally used plants. MATERIALS AND METHODS: 47 dichloromethane extracts were tested in vitro in the Long-term Viability Assay (LtVA) on Trypanosoma brucei brucei. The most active ones were also tested in vivo using a standardised mouse test. RESULTS: 13 extracts (28%) were active in vitro with MIC-values相似文献