Platinum-(IV)-derivative satraplatin induced G2/M cell cycle perturbation via p53-p21(waf1/cip1)-independent pathway in human colorectal cancer cells

Platinum-(IV)-derivative satraplatin represents a new generation of orally available anti-cancer drugs that are under development for the treatment of several cancers. Understanding the mechanisms of cell cycle modulation and apoptosis is necessary to define the mode of action of satraplatin. In this study, we investigate the ability of satraplatin to induce cell cycle perturbation, clonogenicity loss and apoptosis in colorectal cancer (CRC) cells.Platinum-(IV)-derivative satraplatin represents a new generation of orally available anti-cancer drugs that are under development for the treatment of several cancers. Understanding the mechanisms of cell cycle modulation and apoptosis is necessary to define the mode of action of satraplatin. In this study, we investigate the ability of satraplatin to induce cell cycle perturbation, clonogenicity loss and apoptosis in colorectal cancer (CRC) cells

Intracoronary versus intravenous abciximab in ST-segment elevation myocardial infarction: rationale and design of the CICERO trial in patients undergoing primary percutaneous coronary intervention with thrombus aspiration

<p>Abstract</p> <p>Background</p> <p>Administration of abciximab during primary percutaneous coronary intervention is an effective adjunctive therapy in the treatment of patients with ST-segment elevation myocardial infarction. Recent small-scaled studies have suggested that intracoronary administration of abciximab during primary percutaneous coronary intervention is superior to conventional intravenous administration. This study has been designed to investigate whether intracoronary bolus administration of abciximab is more effective than intravenous bolus administration in improving myocardial perfusion in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration.</p> <p>Methods/Design</p> <p>The Comparison of IntraCoronary versus intravenous abciximab administration during Emergency Reperfusion Of ST-segment elevation myocardial infarction (CICERO) trial is a single-center, prospective, randomized open-label trial with blinded evaluation of endpoints. A total of 530 patients with STEMI undergoing primary percutaneous coronary intervention are randomly assigned to either an intracoronary or intravenous bolus of weight-adjusted abciximab. The primary end point is the incidence of >70% ST-segment elevation resolution. Secondary end points consist of post-procedural residual ST-segment deviation, myocardial blush grade, distal embolization, enzymatic infarct size, in-hospital bleeding, and clinical outcome at 30 days and 1 year.</p> <p>Discussion</p> <p>The CICERO trial is the first clinical trial to date to verify the effect of intracoronary versus intravenous administration of abciximab on myocardial perfusion in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00927615</p

In Their Own Words: Assessment of Satisfaction with Residential Location among Migrants in Nairobi Slums

Using qualitative data collected from a sample of rural-urban migrants over the age of 15 in two Nairobi slums interviewed in 2008, this paper discusses the migrants’ extent of satisfaction with their residential location and decision to migrate. The study sheds light on why people continue to migrate to, and stay in, the rapidly growing slum settlements despite the high levels of poverty and poor health conditions in these areas. Tenure status is related to satisfaction for all ages. Environmental factors were frequently mentioned as a source of dissatisfaction. Life cycle and ‘age-cohort effects’ may also affect satisfaction for different age groups in terms of who is satisfied as well as the issues that are considered for satisfaction. High levels of dissatisfaction with slum life may be responsible for high out-migration in slum areas, although it does not mean that those who remain do so because they are satisfied. At the same time, challenges associated with slum life do not automatically signify dissatisfaction. Perceived success, as well as conditions in the area of origin can be used to explain and understand satisfaction/dissatisfaction with slum life. Satisfaction with migration and residential location may be related not only to the destination place, but also to events in the area of origin

Cardiac oxygen supply is compromised during the night in hypertensive patients

The enhanced heart rate and blood pressure soon after awaking increases cardiac oxygen demand, and has been associated with the high incidence of acute myocardial infarction in the morning. The behavior of cardiac oxygen supply is unknown. We hypothesized that oxygen supply decreases in the morning and to that purpose investigated cardiac oxygen demand and oxygen supply at night and after awaking. We compared hypertensive to normotensive subjects and furthermore assessed whether pressures measured non-invasively and intra-arterially give similar results. Aortic pressure was reconstructed from 24-h intra-brachial and simultaneously obtained non-invasive finger pressure in 14 hypertensives and 8 normotensives. Supply was assessed by Diastolic Time Fraction (DTF, ratio of diastolic and heart period), demand by Rate-Pressure Product (RPP, systolic pressure times heart rate, HR) and supply/demand ratio by Adia/Asys, with Adia and Asys diastolic and systolic areas under the aortic pressure curve. Hypertensives had lower supply by DTF and higher demand by RPP than normotensives during the night. DTF decreased and RPP increased in both groups after awaking. The DTF of hypertensives decreased less becoming similar to the DTF of normotensives in the morning; the RPP remained higher. Adia/Asys followed the pattern of DTF. Findings from invasively and non-invasively determined pressure were similar. The cardiac oxygen supply/demand ratio in hypertensive patients is lower than in normotensives at night. With a smaller night-day differences, the hypertensives’ risk for cardiovascular events may be more evenly spread over the 24 h. This information can be obtained noninvasively

Guidelines for investigating causality of sequence variants in human disease

The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development

Diastolic time – frequency relation in the stress echo lab: filling timing and flow at different heart rates

A cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been recently validated. Second heart sound can be simultaneously recorded in order to quantify both systole and diastole duration

Advanced glycation end-products, a pathophysiological pathway in the cardiorenal syndrome

The prevalence of heart failure (HF) is increasing. A distinction is made between diastolic HF (preserved left ventricular ejection fraction (LVEF)) and systolic HF (reduced LVEF). Advanced glycation end-products (AGEs) are crystallized proteins that accumulate during ageing, but are particularly increased in patients with diabetes mellitus and in patients with renal failure. Through the formation of collagen crosslinks, and by interaction with the AGE-receptor, which impairs calcium handling and increases fibrosis, AGE-accumulation has pathophysiologically been associated with the development of diastolic and renal dysfunction. Interestingly, diastolic dysfunction is a frequent finding in elderly patients, diabetic patients and in patients with renal failure. Taken together, this suggests that AGEs are related to the development and progression of diastolic HF and renal failure. In this review, the role of AGEs as a possible pathophysiological factor that link the development and progression of heart and renal failure, is discussed. Finally, the role of AGE intervention as a possible treatment in HF patients will be discussed