Medical hypotheses
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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.
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Endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) is an early step in the course of atherosclerotic cardiovascular disease (CVD). NO is synthesized from L-arginine via the action of NO synthase (NOS), which is known to be blocked by endogenous L-arginine analogues such as asymmetric dimethylarginine (ADMA). ADMA is a naturally occurring amino acid found in plasma and various types of tissues. ⋯ Since ADMA is mainly metabolized by dimethylarginine dimethylaminohydrolase (DDAH), it is conceivable that the impairment of DDAH actions by AGEs could be one possible molecular mechanism of the ADMA elevation in diabetic patients. 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 levels of ADMA 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, also reduce the levels of ADMA and subsequently improve endothelial dysfunction in diabetic patients? Are the ADMA-lowering effects of these agents associated with an increase of DDAH expression and/or activity in endothelial cells? These clinical studies could clarify whether AGEs are involved in the elevation of ADMA in patients with diabetes via suppression of DDAH expression and/or activity, thus providing a novel molecular mechanism for accelerated atherosclerosis in diabetes.
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Elderly surgical patients constitute a unique surgical group. They require special consideration in order to preempt the long term adverse effects of anesthesia. This paper examines the proposition that general anesthesia causes harm to elderly patients with its impact being felt long after the anesthetic agents are cleared from the body. ⋯ Its' occurrence may herald an increase in morbidity and mortality. Based on both human and animal data, this paper outlines a unitary theoretical framework to explain these phenomena. If this hypothesis proves to be correct, anesthesiologist should consider regional rather than general anesthesia for equivalent surgical procedures to reduce POCD and consequently achieving superior patient outcome.