European journal of clinical investigation
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Eur. J. Clin. Invest. · May 2005
ReviewVitamin D and calcium deficits predispose for multiple chronic diseases.
There is evidence from both observational studies and clinical trials that calcium malnutrition and hypovitaminosis D are predisposing conditions for various common chronic diseases. In addition to skeletal disorders, calcium and vitamin D deficits increase the risk of malignancies, particularly of colon, breast and prostate gland, of chronic inflammatory and autoimmune diseases (e.g. insulin-dependent diabetes mellitus, inflammatory bowel disease, multiple sclerosis), as well as of metabolic disorders (metabolic syndrome, hypertension). The aim of the present review was to provide improved understanding of the molecular and cellular processes by which deficits in calcium and vitamin D cause specific changes in cell and organ functions and thereby increase the risk for chronic diseases of different aetiology. 1,25-Dihydroxyvitamin D(3) and extracellular Ca(++) are both key regulators of proliferation, differentiation and function at the cellular level. ⋯ Calcium malnutrition eventually causes a decrease in calcium concentration in extracellular fluid compartments, resulting in organ-specific modulation of calcium-sensing receptor activity. Hence, attenuation of signal transduction from the ligand-activated vitamin D receptor and calcium-sensing receptor seems to be the prime mechanism by which calcium and vitamin D insufficiencies cause perturbation of cellular functions in bone, kidney, intestine, mammary and prostate glands, endocrine pancreas, vascular endothelium, and, importantly, in the immune system. The wide range of diseases associated with deficits in calcium and vitamin D in combination with the high prevalence of these conditions represents a special challenge for preventive medicine.
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Eur. J. Clin. Invest. · Apr 2005
Cancer immunotherapy by fusions of dendritic and tumour cells and rh-IL-12.
Vaccination with fusion cells (FCs) comprising dendritic cells and tumour cells as well as administration of interleukin-12 (IL-12) showed a significant therapeutic effect against established tumours in mouse experimental models. We conducted immunotherapy against various malignant tumours using the FCs and rhIL-12, and investigated the safety and efficacy of the therapy. ⋯ Immunotherapy using a FC vaccine and rhIL-12 induced no serious adverse reactions, and provided good therapeutic responses in some of the patients with a brain tumour.
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Eur. J. Clin. Invest. · Mar 2005
ReviewThe 'precautionary principle' as a guide for future drug development.
During the last decade, the 'precautionary principle' health has gained importance. It is an approach to manage uncertain risks and to prevent any damage to the environment or human. A key element is to take action, even if some cause and effect relationships are not fully established scientifically. ⋯ With the approval of fondaparinux, the first synthetic, selective factor Xa, a first alternative to the porcine-derived heparin has become available. In addition, other synthetic antithrombotics are currently in clinical development. In principle, it is thus possible that the prophylaxis and therapy of thromboembolic diseases will become completely independent of animal-derived drugs, which would be in line with the precautionary principle.
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Eur. J. Clin. Invest. · Mar 2005
Randomized Controlled Trial Clinical TrialHigh-dose glucose-insulin-potassium treatment reduces myocardial apoptosis in patients with acute myocardial infarction.
Several clinical trials have suggested that a metabolic cocktail of glucose-insulin-potassium (GIK) decreases mortality rates in patients with acute myocardial infarction (AMI). It has also been reported that Fas-mediated apoptosis plays an important role in ischaemic/reperfusion injury in the rat model. This study was designed to evaluate the interaction of ischaemic/reperfusion and reperfusion therapy coadministered with high-dose GIK treatment on soluble Fas/APO-1 (sFas) and Fas ligand (sFasL) plasma concentration in patients with AMI. ⋯ These results indicate that the sFas and sFasL in patients with AMI increased significantly compared with NC. Owing to the cardioprotective effects reported here and by others, a high-dose GIK infusion co-administered with the timely re-establishment of nutritive perfusion should be strongly considered as a treatment of choice for AMI. Additionally, sFas may be a valuable marker of the physiological response to ischaemic/reperfusion injury and reperfusion associated with high-dose GIK treatment.