Biochemical and antitumor activity of trimidox,a new inhibitor of ribonucleotide reductase

Trimidox (3,4,5-trihydroxybenzamidoxime), a newly synthesized analog of didox (N,3,4-trihydroxybenzamide) reduced the activity of ribonucleotide reductase (EC 1.17.4.1) in extracts of L1210 cells by 50% (50% growth-inhibitory concentration, IC₅₀) at 5 M, whereas hydroxyurea, the only ribonucleotide reductase inhibitor in clinical use, exhibited an IC₅₀ of 500 M. Ribonucleotide reductase activity was also measured in situ by incubating L1210 cells for 24 h with trimidox at 7.5 M, a concentration that inhibits cell proliferation by 50% (IC₅₀) or at 100 M for 2 h; these concentrations resulted in a decrease in enzyme activity to 22% and 50% of the control value, respectively. Trimidox and hydroxyurea were cytotoxic to L1210 cells with IC₅₀ values of 7.5 and 50 M, respectively. Versus ribonucleotide reductase, trimidox and hydroxyurea yielded IC₅₀ values of 12 and 87 M, respectively. A dose-dependent increase in life span was observed in mice bearing intraperitoneally transplanted L1210 tumors. Trimidox treatment (200 mg/kg; q1dx9) significantly increased the life span of mice bearing L1210 leukemia (by 82 in male mice and 112% in female mice). The antitumor activity appeared more pronounced in female mice than in male mice. Viewed in concert, these findings suggest that trimidox is a new and potent inhibitor of ribonucleotide reductase and that it is a promising candidate for the chemotherapy of cancer in humans.Abbreviations Didox N,3,4-trihydroxybenzamide - MTT {3-[4,5-dimethyl-thiazo-2yl]}-2,5-diphenyl tetrazolium bromide - PBS phosphate-buffered saline - trimidox 3,4,5-trihydroxybenzamidoxime HCl     

抗真菌药物的研究II.C-端含氧代赖氨酸二肽的合成及抗白念珠菌活性

引用违法传递概念设计合成了11个C-末端含氧代赖氨酸二肽,进行抗深部致病菌-白念珠菌活性试验,体外实验结果显示极强的抑菌活性,MIC在12.5～0.8μg/disk之间,较母体氧化赖氨酸大50～135倍(克分子比。     

Differentiation of pulmonary parenchymal consolidation from pleural disease using the sonographic fluid bronchogram

The nature of pleural-based thoracic collections may be sonographically confusing. To help lessen this confusion, the fluid bronchogram, a useful sonographic sign of pulmonary parenchymal consolidation, is described. Bronchi containing fluid in consolidated lung can be identified using ultrasound.     

Modulation of responses to optic flow in area 7a by retinotopic and oculomotor cues in monkey

Perception of two- and three-dimensional optic flow critically depends upon extrastriate cortices that are part of the 'dorsal stream' for visual processing. Neurons in area 7a, a sub-region of the posterior parietal cortex, have a dual sensitivity to visual input and to eye position. The sensitivity and selectivity of area 7a neurons to three sensory cues - optic flow, retinotopic stimulus position and eye position - were studied. The visual response to optic flow was modulated by the retinotopic stimulus position and by the eye position in the orbit. The position dependence of the retinal and eye position modulation (i.e. gain field) were quantified by a quadratic regression model that allowed for linear or peaked receptive fields. A local maximum (or minimum) in both the retinotopic fields and the gain fields was observed, suggesting that these sensory qualities are not necessarily linearly represented in area 7a. Neurons were also found that simply encoded the eye position in the absence of optic flow. The spatial tuning for the eye position signals upon stationary stimuli and optic flow was not the same, suggesting multiple anatomical sources of the signals. These neurons can provide a substrate for spatial representation while primates move in the environment.      

Synthetic or natural surfactants

Surfactant replacement therapy is one of the most studied interventions in neonatal medicine, with many thousands of infants having been enrolled in randomized clinical trials. It is clear that surfactant therapy reduces neonatal mortality and the risk of pulmonary air leaks in babies with or at risk of developing respiratory distress syndrome. Yet some doubts linger over other aspects of this therapy, despite it having been an acceptable and proven therapy for the past 7–10 years. As regards timing of treatment, the earlier the better, with true prophylaxis being reserved for babies of less than 28 weeks' gestation. Natural surfactant preparations containing surfactant proteins B and C act more rapidly than their synthetic protein-free counterparts and probably also have a greater impact on reducing neonatal mortality and pulmonary air leaks. Fears raised about immunological effects, prion transmission and chemical contamination of natural surfactants have not been substantiated. Long-term follow-up studies do not show any differences in outcome between treated and non-treated infants, except that the incidence and severity of retinopathy of prematurity might be reduced by treatment with natural surfactant. Further research is needed and this will include more detailed follow-up studies, newer indications for surfactant therapy and the testing of newer preparations with synthetic peptides or protein analogues added.     

Orthotopic cardiac transplantation: evaluation with CT

As cardiac transplantation has become widely available, computed tomography (CT) of the chest has played a useful role in the examination of patients after heart transplantation. To determine anatomic features related to the procedure, the authors evaluated 59 scans in 46 patients who had undergone orthotopic cardiac transplantation. Aortic anastomosis (seen in 98% of scans) and altered spacing between the great vessels (83%) proved to be the most common and most reliable findings. Other features including atrial anastomosis, high main pulmonary artery segment, remnant superior vena cava, and cardiac reorientation were also seen. Accurate interpretation of adenopathy, mediastinal abscess, and pericardial effusion will be enhanced in these patients through a better understanding of the cardiovascular-pericardial complex, which is afforded by CT.     

Experiences of special gynaecological services for children and adolescents: a descriptive study

Gynaecological examination of girls during childhood is undertaken somewhat infrequently. These genital examinations should not be taboo or a frightening experience for the girl, for her parents or for the physician. Studies of children suspected of sexual abuse have paid attention to the wide variety of gynaecological conditions already present in childhood. In 1988 we founded a special gynaecological outpatient clinic for girls under 16 y of age at a university hospital to develop the special knowledge and skills needed in children's gynaecology. In this gynaecological clinic for children and adolescents we were able to gain and offer expert knowledge of the problems of this age group. In this special clinic for children, gynaecological examination by special techniques and sonography led to a diagnosis in 71% of the patients without any instrumentation. Children and adolescent girls in need of special gynaecological care should be recognized specifically. Particular attention should be paid to the gynaecological care of victims of child sexual abuse and mentally or physically handicapped girls. In good co-operation with the girl, a gynaecological examination can become a positive experience during the development of female identity.     

Morphological determinants of femoral strength in growth hormone-deficient transgenic growth-retarded (Tgr) rats.

The extent to which childhood GHD affects adult fracture risk is unclear. We measured femoral strength in adult transgenic growth-retarded rats as a model of GHD. Long-term, moderate GHD was accompanied by endocrine and morphometric changes consistent with a significant reduction in femoral strength. INTRODUCTION: Childhood growth hormone deficiency (GHD) is associated with osteopenia, but little is known about its effects on subsequent adult bone strength and fracture risk. MATERIALS AND METHODS: We have therefore measured femoral strength (failure load measured by three-point bending) in a new model of moderate GHD, the transgenic growth-retarded (Tgr) rat at 15, 22-23, and 52 weeks of age, and have quantified potential morphological and endocrine determinants of bone strength. RESULTS: Skeletal growth retardation in Tgr rats was accompanied by a sustained reduction in the anterior-posterior diameter of the femoral cortex, whereas mid-diaphyseal cortical wall thicknesses were largely unaltered. Total femoral strength was significantly impaired in Tgr rats (p < 0.01), and this impairment was more pronounced in males than females. Compromised bone strength in Tgr rats could not be accounted for by the reduction in mechanical load (body weight) and was not caused by impairment of the material properties of the calcified tissue (ultimate tensile stress), despite marked reductions in femoral mineral density (areal bone mineral density; p < 0.001). Microcomputerized tomographical analysis revealed significant modification of the architecture of trabecular bone in Tgr rats, with reductions in the number and thickness of trabeculae (p < 0.05) and in the degree of anisotropy (p < 0.01). The marked reduction in plasma insulin-like growth factor-1 in Tgr rats was accompanied by the development of high circulating leptin levels (p < 0.01). CONCLUSION: These results show that the changes in endocrinology and bone morphology associated with long-term moderate GHD in Tgr rats are accompanied by changes consistent with a significant reduction in the threshold for femoral fracture.