Medical hypotheses
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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.
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Voltage-dependent calcium channels (VDCCs) are heteromultimeric complexes that mediate calcium influx into cells in response to changes in membrane potential. The alpha1A subunit, encoded by the CACNA1A gene, is the pore-forming subunit specific to the neuronal P/Q-type VDCCs. These are implicated in fast excitatory and inhibitory neurotransmission. ⋯ These drugs improve ataxia in cases of CCA, olivopontocerebellar atrophy and ataxia-telangiectasia. On the basis of the neuropathological identity of SCA 6 with CCA, and given the capacity of gabapentin and pregabalin to decrease P/Q-type VDCCs inactivation, in this paper the authors put forward the hypothesis that the administration of gabapentin and pregabalin might prove beneficial in SCA 6 as the ataxia caused by this disease would be expected to improve. The authors hope that researchers working with this illness will be inspired and encouraged to undertake the appropriate clinical and experimental work.
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Most research is 'normal science' using Thomas Kuhn's term: checking, trial-and-error improvement and incremental extrapolation of already existing paradigms. By contrast, 'revolutionary science' changes the fundamental structures of science by making new theories, discoveries or technologies. Science Nobel prizes (in Physics, Chemistry, Physiology/Medicine and Economics) have the potential to be used as a new metric for measuring revolutionary science. ⋯ Although Nobel science prizes are sporadically won by numerous nations and institutions, it seems that long term national strength in revolutionary science is mainly a result of sustaining and newly-generating multi-Nobel-winning research centres. At present these elite institutions are found almost exclusively in the USA. The USA is apparently the only nation with a research system that nurtures revolutionary science on a large scale.
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Although chronic low back pain (cLBP) is increasingly recognized as a complex syndrome with multifactorial etiology, the pathogenic mechanisms leading to the development of chronic pain in this condition remain poorly understood. This article presents a new, testable pathophysiological model integrating connective tissue plasticity mechanisms with several well-developed areas of research on cLBP (pain psychology, postural control, neuroplasticity). ⋯ Non-invasive measures of connective tissue remodeling may eventually become important tools to evaluate and follow patients with cLBP in research and clinical practice. An integrative mechanistic model incorporating behavioral and structural aspects of cLBP will strengthen the rationale for a multidisciplinary treatment approach including direct mechanical tissue stimulation, movement reeducation, psychosocial intervention and pharmacological treatment to address this common and debilitating condition.
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There are common genetic mechanisms responsible for both drug effects and subsequent seeking behavior. In 1996, we coined the term Reward Deficiency Syndrome (RDS). Past and current treatment of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is considered by most to be inadequate. ⋯ Thus, in the absence of alcohol or other psychoactive drugs (dopamine releasers), especially during recovery or rehabilitation, decreasing, not increasing COMT activity, should result in enhanced synaptic dopamine as physiologically released, thereby proliferating D2 receptors while reducing stress, increasing well-being, reducing craving behavior and preventing relapse. Based on this hypothesis, we believe that adding the COMT inhibitor R. rosea (as Rhodimin) to our amino-acid and chromium combination in DUI offenders and other illegal drug-related crimes, increases the potential for more targeted neurochemical rebalancing and enhanced relapse prevention. Finally, we hypothesize that these data coupled together provide evidence that the combination of enkephalinase inhibition, neurotransmitter precursor loading, brain tryptophan enhancing and COMT inhibition as well as DNA analysis of the individual's genome, may be useful as an adjunct to therapy when used in outpatient recovery, specifically to assist in reducing craving behavior and preventing relapse.