Medical hypotheses
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The incidence of sensorineural hearing loss often caused by direct damage to the cochlear hair cells is by far more frequent and more serious than disorders affecting the external ear or the middle ear. Mechanisms that are discussed to be relevant for the genesis of tinnitus and acquired hearing impairment are hair cell loss, signal transduction disturbances in the region of the outer and inner hair cells and the spiral ganglion, impairment of cochlear blood flow, mechanical disturbance, and hypoxia and ischemia. The present model surveys the possible cellular and molecular biological causes of peripherally developing hearing loss and tinnitus. ⋯ Moreover, the hypoxia inducible factor-1 may have an important role to play as a key transcription factor in the cells' adaptation to hypoxia and ischemia. An impairment of the cochlear blood flow may be induced by the expression of target genes like nitrogen monoxide synthase and endothelin-1 resulting in tinnitus. The paper discusses consequences resulting from the present model for the medical treatment of peripherally developing tinnitus and hearing loss.
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The likelihood of successful defibrillation in patients with sustained ventricular fibrillation (VF) is increased after administering thrombolytics during cardiopulmonary resuscitation (CPR). While dissolution of coronary artery thrombosis resolves the underlying cause of myocardial infarction in the majority of patients, improved microcirculatory reperfusion and alteration of the electrical activity of the fibrillation process may increase the likelihood of restoring spontaneous circulation in cardiac arrest patients. Electrocardiography is a sensitive means of displaying current myocardial perfusion in VF using changes in the frequency and amplitude of fibrillation. Our hypothesis postulates that thrombolytic therapy during CPR increases fibrillation frequency, fibrillation amplitude and amplitude spectrum area, thus improving ventricular fibrillation status and the chance of successful defibrillation.
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B-type natriuretic peptide (BNP) is released from cardiac ventricles in response to increased wall tension in patients with heart failure. It has been used as a biochemical marker for the diagnosis of congestive heart failure. BNP is also increased in patients with acute myocardial infarction, and is associated with an increased risk of cardiovascular mortality in those with impaired left ventricular function after myocardial infarction. We hypothesized that an increase in BNP soon after acute myocardial infarction is an independent predictor for long-term prognosis in patients with no clinical signs of left ventricular function.
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In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs-their receptor (RAGE) interactions are involved in the development and progression of diabetic retinopathy. Bisphosphonates are potent inhibitors of bone resorption and are widely used drugs for the treatment of osteoporosis and osteolytic bone metastasis. ⋯ NADPH oxidase-derived reactive oxygen species (ROS) generation is required for the AGE-RAGE signaling in vascular wall cells, and small G protein Rac is a critical component of vascular NADPH oxidase complex. These observations let us to speculate that minodronate, a newly developed nitrogen-containing bisphosphonate, might be a promising remedy for treating patients with diabetic retinopathy by inhibiting the AGE-RAGE signaling pathways through suppression of ROS generation via inhibition of Rac prenylation. In this paper, we like to propose the possible ways of testing our hypotheses: (1) Does treatment with minodronate decrease the risk for the development and progression of diabetic retinopathy in osteoporotic patients? (2) If the answer is yes, is this beneficial effect of minodronate superior to that of other nitrogen-noncontaining bisphosphonates with equihypolipidemic properties? (3) Does minodronate treatment suppress NADPH oxidase-mediated ROS generation in retinas of diabetic animals? (4) Does treatment with pyridoxamine, a post-Amadori inhibitor of AGE formation, attenuate these beneficial effects of minodronate on diabetic retinopathy? These clinical and animal studies could clarify whether the use of minodronate is of benefit in patients with AGE-RAGE-related disorders such as diabetic retinopathy, even in the absence of osteoporosis.