Medical hypotheses
-
Diabetic foot ulcers (DFUs) consist of an interaction of neuropathy, ischemia and infection. Neuropathy affects sensory, motor and autonomic pathways. Pathogenic factors for neuropathy include hyperglycemia, nonenzymatic glycosylation, oxidative stress, ischemic and hypoxic factors, nerve growth factor anomalies, activation of polyol pathway and immunologic abnormalities. ⋯ In addition, recent in vivo and in vitro investigations have evidenced that statins have a favorable effect on diabetic peripheral neuropathy independent of its lipid-lowering effect by demonstrating restoration or preservation of microcirculation of the sciatic nerve. We hypothesized that statins can be useful for the prevention and treatment of diabetic foot. Possible mechanisms include the reduction of neuropathy and ischemia or through growth factors, the effectiveness of which has been shown for fracture healing in animal models.
-
This article complements Dr. Charlton's follow-up of David Horrobin's suggestion in Nature two decades ago to offer sizeable prizes for practical approaches to either eliminate a problem in medicine or reduce the cost of its solution. Examples from the 20th and 21st centuries illustrate that prizes--small and big--have generated sustained and successful attacks on defined problems in biology, physics and, lately, mathematics. Provided that glittering prizes are offered and awarded with care, they can lead to effective problem-solving in medicine and related biomedical sciences as well.
-
Vascular calcification is a common feature in advanced atherosclerosis and also a predictor of future cardiovascular events such as unstable angina and myocardial infarction, especially in diabetes. There is a growing body of evidence that advanced glycation end products (AGEs), senescent macroprotein derivatives formed at an accelerated rate in diabetes, exist within atherosclerotic lesions, thereby being implicated in the pathogenesis of accelerated atherosclerosis in diabetes. Indeed, we have previously shown that AGE - their receptor (RAGE) interaction could induce angiogenesis through autocrine production of vascular endothelial growth factor, suggesting its role for plaque formation and enlargement in diabetes. ⋯ Since we, along with others, have shown that nifedipine inhibits glycation of low-density lipoprotein in vitro and blocks the AGE-induced RAGE expression in endothelial cells through its anti-oxidative properties, nifedipine could inhibit vascular calcification by blocking the AGE formation or the downstream signaling in diabetes. In this paper, we would like to propose the possible ways of testing our hypothesis. Does nifedipine treatment slow down the progression of coronary calcification in diabetic patients? If the answer is yes, is this beneficial effect of nifedipine superior to that of other DHPs with equihypotensive properties? Does nifedipine treatment decrease expression levels of AGEs and RAGE in diabetic atherosclerosis? Is the unique effect of nifedipine on vascular calcification correlated with its AGE or RAGE-suppressing properties? These prospective studies will provide further valuable information whether nifedipine could prevent vascular calcification in diabetic atherosclerosis by blockade the AGE-RAGE signaling in vascular wall cells.
-
The clinical assessment of sarcoidosis has been confounded by its inexact diagnostic criteria, multiorgan involvement, and effects of therapy. In this manuscript an instrument, the Sarcoidosis Three-Dimensional Assessment Instrument (STAI), is proposed to assess the clinical state of sarcoidosis. The instrument examines each organ involved with sarcoidosis separately. ⋯ Severity is based both on the decline from normal capacity as well as physical and psychosocial limitation. Disease activity takes into account changes in organ function as well as changes in therapy. Although this instrument is presently not validated, it is hoped that it will undergo study as it rationally accounts for several problems of previous assessment instruments.
-
People often suggest that scientists should have a specific personality type, usually conscientious and self-critical. But this is a mistake. Science as a social system needs to be conscientious and self-critical, but scientists as people do not necessarily have to conform to that stereotype. ⋯ But the modern science superstar is more like the Nutty Professor's alter ego, nightclub singer 'Buddy Love': a sharp-suited, good-looking and charismatic charmer. While Nutty was dull but impartial, Buddy is compelling but self-seeking. Our attitude towards public scientific pronouncements should be adjusted accordingly.