NADH: Ubiquinone Oxidoreductase Inhibitors Block Induction of Ornithine Decarboxylase Activity in MCF-7 Human Breast Cancer Cells*

Abstract: Rotenone is the classical inhibitor of NADH: ubiquinone oxidoreductase and its analogue deguelin is a potent inhibitor of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase mRNA steady state level and enzyme activity in mouse 308 cells (Gerhäuser et al. 1995). In MCF-7 human breast cancer cells, rotenone, deguelin and two structurally-unrelated miticides (pyridaben and fenazaquin) inhibit not only NADH: ubiquinone oxidoreductase but also induced ornithine decarboxylase activity with IC₅₀ values of <1 to 70 nM. Rotenone inhibits ornithine decarboxylase activity equally well as induced by TPA, insulin-like growth factor I and 17β-oestradiol. Pyridaben is the most potent of the four inhibitors not only for NADH: ubiquinone oxidoreductase activity (bovine heart enzyme) and TPA-induced ornithine decarboxylase activity and mRNA steady state level but also for TPA-induced reactive oxygen species. It is therefore proposed that NADH: ubiquinone oxidoreductase inhibitors block multiple and possibly reactive oxygen species-modulated pathways which regulate ornithine decarboxylase activity.     

高效液相色谱法测定血浆中洛美沙星浓度及其在人体内药代动力学

建立了人血浆洛美沙星的反相离子对高效液相色谱测定方法。该法简便易行,精密度好,方法回收率95～102%,日内、日间RSD为2.1～7.8%,血药浓度在0.125～5.012 μg/ml范围内呈线性关系,相关系数0.9998,当S/N=2时,最小检测浓度为25 ng/ml。健康志愿者口服400 mg洛美沙星,药代动力学过程符合一室模型,消除相半衰期为5.5 h。     

An amorphous selenium based positron emission mammography camera with avalanche gain

Early diagnosis of breast cancer is crucial for effective treatment, and the need exists for greater detection ability and specificity than possible by screening x-ray mammography (currently the primary imaging technique for the detection of breast lesions). Positron Emission Tomography (PET) using the radiotracer 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) offers a noninvasive, highly sensitive method for the diagnosis of breast cancer. Images from PET contain unique metabolic information that is not available from anatomical imaging techniques. We propose a Positron Emission Mammography (PEM) imaging system that maintains the established high specificity of FDG PET while providing improved collection efficiency for the radiotracer signal and the potential for images with better spatial resolution. This PEM system will enable detection of lesions that are considerably smaller than those that can be visualized using whole body PET imaging. The compact dual-head PEM camera will be based on an amorphous selenium (a-Se) avalanche photodetector and the scintillator lutetium oxyorthosilicate (LSO). The camera promises high collection efficiency by combining the fast scintillation light decay and high light yield of LSO with the excellent quantum efficiency, large avalanche gain, and rapid response time of a-Se. We have measured the gain and readout time of an 8 microm a-Se layer and demonstrated the feasibility of the proposed PEM camera.     

Difficulties in Immunohaematology : The Weak D Antigen

Background

The Rh blood system is one of the most polymorphic and immunogenic systems known to humans. The expression of Rh blood group antigen is complex. The Rh D antigen is the most important of the antigens that constitute the Rh antigen system. In most cases, D antigen can easily be detected. However, due to variability of expression, weak forms antigen are encountered. The reactivity of weak D with antisera is variable and presents as a problem in blood banking.

Methods

A retrospective analysis for a five-year period was done. Blood samples that were negative for Rh D by immediate spin tube method were tested for weak D antigen by additional lab tests.

Result

Of 34932 serial Rh grouping tests done in our Blood Bank, the incidence of weak D Rh antigen was 0.189%. All these were confirmed by the antiglobulin test.

Conclusion

These patients present as a problem for the blood banker and a curiosity to the clinician. Although uncommon, all health care workers should be aware of this entity to avoid anti D alloimmunisation.Key Words: Weak D, Rh Blood Group     

A lesson learnt: the importance of modelling in randomized controlled trials for complex interventions in primary care

BACKGROUND: The Randomised Controlled Trial (RCT) is recognised as the 'gold standard' in quantitative research. However RCTs testing health care interventions can be difficult to design and implement. Health care interventions are often complex in themselves and are always applied in complex settings. Such interventions require a process of careful 'modelling' to maximize the chances of successful trials that will add to knowledge. OBJECTIVES: To describe the terms 'complex' and 'modelling' as used in the setting of randomised controlled trials of complex interventions. To give a practical example of an RCT involving a complex intervention applied in a health care setting to illustrate how this might take place in practice. METHODS: We describe an RCT designed and conducted by the authors. We then use our trial as an example to illustrate how complex interventions such as ours might benefit from modelling during the design of the intervention and the setting within which the intervention is to be tested. RESULTS: Our project was designed and tested before current guidance on complex interventions was published; our RCT was therefore not 'modelled' but was based on the outcome of a single quantitative pilot study. As part of our study we ran a parallel qualitative study, which highlighted several areas of complexity both in our intervention, and in the setting within which we applied it. In this paper we show how modelling might have allowed us to recognise these complexities at an early stage and might therefore have resulted in a study more likely to have demonstrated useful outcomes. CONCLUSION: Careful modelling of complex interventions is an essential step in designing trials of innovations in health care and health care services. Such a process ensures that interventions fit with and reflect the complexities of the settings within which interventions will be applied, and should ensure that the outcomes chosen are those most appropriate to demonstrate any benefits or risks.     

Transjugular intrahepatic portosystemic stent shunt: 11 years' experience at a regional referral centre

OBJECTIVES: Transjugular intrahepatic portosystemic stent shunt (TIPSS) is now widely used in the treatment of uncontrolled and recurrent variceal haemorrhage. This study reports the outcome and long-term follow-up of 125 patients who were referred to a single centre for TIPSS. METHODS: One hundred and twenty-five patients were referred to undergo TIPSS. All but 10 had variceal haemorrhage. The 10 patients referred with refractory ascites were excluded from the analysis. Our follow-up protocol was to assess shunt patency only if bleeding recurred or there was a clinical indication. The mean age was 51.5 years (range 18-87 years) and 64 patients (56%) were male. The commonest aetiology for chronic liver disease was alcohol (80%). At referral, 19 patients (16%) were Child-Pugh class A, 26 patients (23%) were Child-Pugh class B and 70 patients (61%) were Child-Pugh class C. The mean follow-up period was 20.4 months (range 0-95 months). RESULTS: TIPSS was successfully placed in 108 of 115 patients (94%). The thirty-day mortality was 30%. One-year and 2-year overall cumulative survival was 52% (survival ratio, 0.525; 95% confidence interval, 0.432-0.619) and 43% (survival ratio, 0.436; 95% confidence interval, 0.340-0.532), respectively. CONCLUSION: TIPSS is effective in the treatment of uncontrolled or recurrent variceal bleeding. In comparison with previously published studies, our study suggests no value in regular or routine shunt surveillance to reduce rebleeding episodes or mortality, but this needs to be further assessed in prospective randomized studies.