This led to a re-expression of the MDRD formulas. The chronic diseases itself or the effects of the chronic diseases may alter serum creatinine levels without affecting GFR itself. In patients with chronic heart failure, a cardiovascular disease, the effective circulating volume is reduced, blood pressure is low and therefore renal perfusion pressure is reduced, leading to reduced filtration rate in viable nephrons and probably also to reduced excretion of creatinine. The tubuli, however, are still capable of secreting creatinine actively. In addition, the cornerstone in heart failure therapy are renin-angiotensin-aldosterone-system inhibitors, which also may reduce glomerular filtration pressure and therefore excretion of creatinine. These different mechanisms may influence serum creatinine levels. In addition, patients with heart failure are often immobile and therefore at risk for having lower serum creatinine levels. In cancer and COPD unknown mechanisms may influence creatinine levels without affecting GFR, but reduced muscle mass and malnourishment may also be present. This latter may result in low serum creatinine levels and therefore in overestimation of the GFR. In diabetes mellitus, the choice of drugs or dosages is influenced by GFR. Finally, we searched for articles about 8) other chronic diseases in which reduced muscle mass can be present, which may render the MDRD formula less valid. Such diseases include neuromuscular diseases, rheumatoid arthritis, cystic fibrosis, human immunodeficiency virus and liver diseases. In certain liver diseases the production of serum creatinine is also reduced to approximately one half of the rate of patients with normal hepatic function. Hyperbilirubinemia is also common among patients with liver diseases. Elevated serum bilirubine levels interfere with the Jaffe method to measure creatinine, which might lead to misleadingly low serum creatinine levels. Ever since human embryonic stem cells cells were first TWS119 isolated from the inner cell mass of a human blastocyst, they have been viewed as a ‘holy grail’ of medical promise. Because they have the ability to self-renew indefinitely and differentiate into any cell type of the body, they are potentially an unlimited source of cells for patients in need of cellular therapy. Moreover, due to their provenance, hES cells are an ideal system to study cellular fate decisions in early human development. More recently, Yamanaka and colleagues devised a method to convert fully differentiated somatic cells into an embryonic-like state, known as induced pluripotent stem cells, through the over-expression of certain transcription factors. Collectively, we refer to hES cells and iPS cells as human pluripotent stem cells. A major branch of therapeutic stem cell research is aimed at understanding how pluripotent cells acquire their ultimate fate as a defined tissue. Considerable effort has gone into developing directed differentiation protocols by empirically adding or removing inductive signals to the differentiating cell population.