Medical hypotheses
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Reducing sugars can react non-enzymatically with amino groups of protein to form Amadori products. These early glycation products undergo further complex reaction such as rearrangement, dehydration, and condensation to become irreversibly cross-linked, heterogeneous fluorescent derivatives, termed advanced glycation end products (AGEs). The formation and accumulation of AGEs in various tissues has been known to progress at an accelerated rate under hyperglycemic conditions in diabetes. ⋯ Since several lines of evidence have shown anti-atherogenic effects of Chlorella on animal models, we hypothesize here that the beneficial aspects of Chlorella on atherosclerosis could be ascribed, at least in part, to its AGE inhibitory property and that Chlorella may have therapeutic potentials in treatment of patients with other AGE-related disorders such as diabetic microangiopathy and Alzheimer's disease. In this paper, we would like to propose the possible ways of testing our hypotheses. Does daily intake of Chlorella reduce the risk of the incidence and progression of diabetic vascular complications including atherosclerosis? Does Chlorella treatment prevent the development of Alzheimer's disease and/or improve the cognitive impairment of patients with this disorder? If the answers are yes, are plasma or tissue levels of AGE in these patients actually suppressed by Chlorella treatment? And, does the extent of the AGE reduction by Chlorella predict the beneficial effects of Chlorella on these disorders? These prospective studies will provide further valuable information whether blockade by Chlorella of the AGE formation could be clinically relevant.
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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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Osteoporosis, one of the most prevalent metabolic bone diseases in developed countries, is a major public health problem through its association with fragility fractures. Several epidemiological studies have reported moderately increased risks of osteoporotic bone fractures in diabetic patients compared with general population. However, the underlying molecular link between diabetes and osteoporosis remains to be elucidated. ⋯ These observations let us to hypothesize that AGEs could explain the molecular link between diabetes and osteoporosis. In this paper, we would like to propose the possible ways of testing our hypotheses. Does treatment with metformin, which has a potential effect on the inhibition of glycation reactions in vivo, decrease the risk for osteoporotic bone fractures in diabetic patients? If the answer is yes, is this beneficial effect of metformin superior to that of other anti-diabetic agents with equihypoglycemic properties? Does treatment with pyridoxamine, a post-Amadori inhibitor (so-called Amadorins) of AGE formation, reduce the risk for osteoporotic bone fractures as well? Furthermore, are increased levels of AGEs and RAGE in bone tissues associated with high risk for bone fractures in patients with diabetes? These clinical studies could clarify whether the AGEs-RAGE interactions serve as a causal link between diabetes and osteoporosis.
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Alzheimer's disease [AD] is the most common cause of dementia among people age 65 and older. One of the biggest stumbling blocks in developing effective drug therapy for Alzheimer's disease has been the lack of a comprehensive hypothesis that explains the mechanism behind all of the histopathological changes seen in patients suffering from Alzheimer's disease. An overview of the currently popular 'amyloid' and 'vascular' hypotheses for AD demonstrates that neither hypothesis by itself can explain all the known histopathological and biochemical lesions seen in Alzheimer's disease. ⋯ According to the hypothesis, beta amyloid peptides are necessary if not sufficient to cause AD, VaD and mixed senile dementias. The hypothesis, therefore, proposes the term Beta Amyloid Dementias [BAD] to describe the conditions currently covered by the diagnoses of 'AD', 'VaD' and 'Mixed [senile] Dementias'. Finally, the ABSENT hypothesis tries to put forth a direct chemical mechanism behind the apparent synergy and increased association between old age, pre- and coexisting vascular disease, diabetes and AD.
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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.