Medical hypotheses
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Diabetic retinopathy is a common and potentially devastating microvascular complication in diabetes and is a leading cause of acquired blindness among the people of occupational age. However, therapeutic options for the treatment of proliferative diabetic retinopathy, photocoagulation and vitrectomy, are limited by considerable side effects. Therefore, to develop novel therapeutic strategies that specifically target diabetic retinopathy is desired for patients with diabetes. ⋯ By blocking the protein prenylation, cerivastatin completely prevented the AGE-RAGE-elicited angiogenesis via suppression of vascular endothelial growth factor (VEGF). These observations let us to speculate that statins might be a promising remedy for treating patients with diabetic retinopathy by acting as a potential inhibitor of the AGE-RAGE signaling pathway in microvascular endothelial cells. In this paper, we would like to propose the possible ways of testing our hypotheses. (1) Does treatment with statins decrease the risk for the development and progression of diabetic retinopathy in patients with normocholesterolemia? (2) If the answer is yes, is this beneficial effect of statins superior to that of other cholesterol-lowering agents with equihypolipidemic properties? (3) Does statin treatment suppress retinal VEGF expression in diabetic patients? (4) Does treatment with pyridoxamine, a post-Amadori inhibitor of AGE formation, attenuate the beneficial effects of statins on diabetic retinopathy? These clinical studies could clarify whether the use of statins is of benefit in patients with AGE-RAGE-related disorders such as diabetic retinopathy, even in the absence of hypercholesterolemia.
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Brain neuronal dysfunction has been implicated in pathogenesis of migraine but direct evidence is lacking. Scintillating scotoma of migraine is generally believed to originate at the visual cortex. While cortical spreading depression is a relatively late physiological alteration in migraine, its protective role in neuronal ischaemia is increasingly being recognized. ⋯ Headache of migraine possibly arises from a similar mechanical deformation of the anterior eye segment followed by antidromic discharge in the trigeminovascular system. Lateralizing negative deficits such as homonymous hemianopia probably reflect vasospastic complications of migraine. A rational explanation for the most characteristic clinical features of migraine and a new template to elucidate the pharmacological basis of anti-migraine drugs is offered.
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Alzheimer's disease (AD) is the most common cause of dementia in developed countries. AD is characterized pathologically by the presence of senile plaques and neurofibrillary tangles (NFTs), the major constituents of which are the amyloid beta protein (Abeta) and tau protein, respectively. Several epidemiological studies have reported moderately increased risks of AD in diabetic patients compared with general population. ⋯ These observations led us to hypothesize that serum or cerebrospinal fluid (CSF) levels of glyceraldehyde-derived AGEs could become a promising biomarker for early detection of AD. We also would like to propose the possible ways of testing our hypothesis. Are the concentrations of glyceraldehyde-derived AGEs in serum or CSF elevated early in the course of dementia? Are these levels correlated with disease severity and progression, especially in patients with diabetes? These clinical studies clarify whether use of serum or CSF levels of glyceraldehyde-derived AGEs as a biomarker for AD might enable more effective diagnosis and treatment of patients with this devastating disorder.
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Symptoms of Gulf War Syndrome and chronic Lyme disease are very similar. Lyme disease is a condition which can be difficult to diagnose since one of the main features of the condition, the erythema migrans rash, may be absent or overlooked and serological testing for Lyme disease may be falsely negative. ⋯ There has been no systematic examination of Gulf War Syndrome sufferers for chronic Lyme disease and it is hypothesized that chronic Lyme disease has been overlooked as a cause of Gulf War Syndrome. To address this it is suggested that sufferers of Gulf War Syndrome or similar illnesses should be examined by physicians who have experience diagnosing and treating large numbers of patients with Lyme disease.
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HIV transmission from the male to the female is a major health problem. A hypothesis proposing an intra vas deferens implant of an antimicrobial compound to prevent the infection spread is presented. Mechanisms of action for the inhibition could include inactivating HIV in sperms passing through the vas deferens; drug release from the implant to destroy HIV entering into semen from genital structures distal to the vas deferens; and sperm acrosome released hyaluronidase mediated reabsorption of HIV. ⋯ A significant reduction in the semen viral load following RISUG administration will validate the hypothesis. Speculated reduced female to male HIV transmission is more difficult to test. Nonspecific indications will come from a population study of the incidence of RISUG treated men becoming HIV positive as compared to that in the general population.