Kenneth Blum, Bernard W Downs, Manashi Bagchi, Steve Kushner, Bruce S Morrison, Jeffrey Galvin, Kourtney Randsdorp, Justin Randsdorp, Rajendra D Badgaiyan, Eric R Braverman, Debasis Bagchi
{"title":"Induction of homeostatic biological parameters in reward deficiency as a function of an iron-free multi-nutrient complex: Promoting hemoglobinization, aerobic metabolism, viral immuno-competence, and neuroinflammatory regulation.","authors":"Kenneth Blum, Bernard W Downs, Manashi Bagchi, Steve Kushner, Bruce S Morrison, Jeffrey Galvin, Kourtney Randsdorp, Justin Randsdorp, Rajendra D Badgaiyan, Eric R Braverman, Debasis Bagchi","doi":"10.15761/JSIN.1000234","DOIUrl":"10.15761/JSIN.1000234","url":null,"abstract":"<p><strong>Background: </strong>A common neurological condition worldwide is Reward Deficiency Syndrome (RDS) leading to both substance and non-substance addictive behaviors, that must be combatted by integrating both central nervous system and peripheral nervous system biological approaches. Integrity of hemoglobin is a crucial determining factor for the overall health functions. Nutrient repletion therapy should be a fundamental strategy to restore the healthy properties of blood. A unique patent-pending iron-free VMP35 formulation was engineered by our laboratory to restore iron-dependent hemoglobin in anemic cells using a proprietary Prodosome<sup>®</sup> absorption technology. This formulation, containing an array of nano-emulsified botanical ingredients rich in bioflavonoids, strengthens the structural integrity of connective tissues, and potentiates immune competence, cellular aerobic metabolism, and enhances efficient regulation of inflammatory events. We discuss the intricate aspects of strong vs. fragile immunity and consequential inflammatory responses to convey a deeper understanding of the varied and overly complex sequela of immunological behaviors and events. The effect of the VMP35 is mediated through highly absorbable nutritional/nutrigenomic repletion enabling improvements in the systemic set of functional behaviors. In fact, the iron-free VMP35 facilitates a \"Systems Biology Approach\" which restores hemoglobin status, reverses anaerobic hypoxia, improves competent immune responsivity, and regulates appropriate and controlled activation of general and neuro-inflammatory sequela. Under these pathogenic circumstances, iron-deficiency anemia has been misconceptualized, and a new nosological term, Chronic Anemia Syndrome, is proposed. The comparative therapeutic rationale of Reductionist vs. Systems Biology approaches is also explained in detail.</p><p><strong>Methods: </strong>The efficacy of the novel therapeutic iron-free VMP35 liquid nutraceutical is detailed in restoring iron-dependent hemoglobin to RBCs and boosting cellular morphology, viability, and immune competence, thereby reducing the need for prolonging inflammatory sequela.</p><p><strong>Results: </strong>This was demonstrated in a previous IRB approved multi-subject human study. In addition, two recent case studies report dramatic restorative benefits of nutrient repletion therapy of the VMP35 on subjects having experienced near-fatal events, which confirmed the findings explained in this manuscript.</p><p><strong>Conclusions: </strong>This novel iron-free VMP35 modulates an array of homeostatic biological parameters such as enhanced hemoglobinization, aerobic metabolism, viral immuno-competence, and inflammatory regulation. Further research, examining mechanistic and beneficial effects in athletic performance, is in progress. Importantly, during these troubled immune challenging times, modulating an array of homeostatic immunological and inflammatory dysfunctions are","PeriodicalId":87318,"journal":{"name":"Journal of systems and integrative neuroscience","volume":"7 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8793786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39572912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kenneth Blum, Lisa Lott, David Baron, David E Smith, Rajendra D Badgaiyan, Mark S Gold
{"title":"Improving naltrexone compliance and outcomes with putative pro- dopamine regulator KB220, compared to treatment as usual.","authors":"Kenneth Blum, Lisa Lott, David Baron, David E Smith, Rajendra D Badgaiyan, Mark S Gold","doi":"10.15761/JSIN.1000229","DOIUrl":"https://doi.org/10.15761/JSIN.1000229","url":null,"abstract":"<p><p>A recent analysis from Stanford University suggested that without any changes in currently available treatment, prevention, and public health approaches, we should expect to have 510,000 deaths from prescription opioids and street heroin from 2016 to 2025 in the US. In a recent review, Mayo Clinic Proceedings (October 2019), Gold and colleagues at Mayo Clinic reviewed the available medications used in opioid use disorders and concluded that in private and community practice adherence is more important as a limiting factor to retention, relapse, and repeat overdose. It is agreed that the primary utilization of known opioid agonists like methadone, buprenorphine and naloxone combinations, while useful as a way of reducing societal harm, is limited by 50% of more discontinuing treatment within 6 months, their diversion, and addiction liability. Opioid agonists may have other unintended consequences, like continuing the down regulation of dopamine systems. While naltrexone would be expected to have opposite effects, adherence is also low even after detoxification and long acting naltrexone injections. Recent studies have shown Naltrexone is beneficial by attenuation of craving via \"psychological extinction\" and reducing relapse. Buprenorphine is the MAT of choice currently but injectable Naltrexone plus an agent to improve dopaminergic function and tone may renew interest amongst addiction physicians and patients. Understanding this dilemma there is increasing movement to opt for the non-addicting narcotic antagonist Naltrexone. Even with extended injectable option there is still poor compliance. As such, we describe an open label investigation in humans showing improvement of naltrexone compliance and outcomes with dopamine augmentation with the pro- dopamine regulator KB220 (262 days) compared to naltrexone alone (37days). This well studied complex consists of amino-acid neurotransmitter precursors and enkephalinase inhibitor therapy compared to treatment as usual. Consideration of this novel paradigm shift may assist in not only addressing the current opioid epidemic but the broader question of reward deficiency in general.</p>","PeriodicalId":87318,"journal":{"name":"Journal of systems and integrative neuroscience","volume":"7 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38384238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B W Downs, K Blum, D Bagchi, S Kushner, M Bagchi, J M Galvin, McG Lewis, D Siwicki, R Brewer, B Boyett, D Baron, J Giordano, R D Badgaiyan
{"title":"Molecular neuro-biological and systemic health benefits of achieving dopamine homeostasis in the face of a catastrophic pandemic (COVID- 19): A mechanistic exploration.","authors":"B W Downs, K Blum, D Bagchi, S Kushner, M Bagchi, J M Galvin, McG Lewis, D Siwicki, R Brewer, B Boyett, D Baron, J Giordano, R D Badgaiyan","doi":"10.15761/JSIN.1000228","DOIUrl":"https://doi.org/10.15761/JSIN.1000228","url":null,"abstract":"<p><p>In the face of the global pandemic of COVID 19, approaching 1.75 Million infected worldwide (4/12/2020) and associated mortality (over 108, 000 as of 4/12/2020) as well-as other catastrophic events including the opioid crisis, a focus on brain health seems prudent [1] (https://www.coronavirus.gov). This manuscript reports on the systemic benefits of restoring and achieving dopamine homeostasis to reverse and normalize thoughts and behaviors of Reward Deficiency Syndrome (RDS) dysfunctional conditions and their effects on behavioral physiology; function of reward genes; and focuses on digestive, immune, eye health, and the constellation of symptomatic behaviors. The role of nutrigenomic interventions on restoring normal brain functions and its benefits on these systems will be discussed. We demonstrate that modulation of dopamine homeostasis using nutrigenomic dopamine agonists, instead of pharmaceutical interventions, is achievable. The allied interlinking with diverse chronic diseases and disorders, roles of free radicals and incidence of anaerobic events have been extensively highlighted. In conjunction, the role of dopamine in aspects of sleep, rapid eye movement and waking are extensively discussed. The integral aspects of food indulgence, the influence of taste sensations, and gut-brain signaling are also discussed along with a special emphasis on ocular health. The detailed mechanistic insight of dopamine, immune competence and the allied aspects of autoimmune disorders are also highlighted. Finally, the integration of dopamine homeostasis utilizing a patented gene test and a research-validated nutrigenomic intervention are presented. Overall, a cutting-edge nutrigenomic intervention could prove to be a technological paradigm shift in our understanding of the extent to which achieving dopamine homeostasis will benefit overall health.</p>","PeriodicalId":87318,"journal":{"name":"Journal of systems and integrative neuroscience","volume":"7 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489293/pdf/nihms-1595404.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38384239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mark S Gold, Jean Lud Cadet, David Baron, Rajendra D Badgaiyan, Kenneth Blum
{"title":"Calvin klein (CK) designer cocktail, new \"Speedball\" is the \"grimm reaper\": Brain dopaminergic surge a potential death sentence.","authors":"Mark S Gold, Jean Lud Cadet, David Baron, Rajendra D Badgaiyan, Kenneth Blum","doi":"10.15761/JSIN.1000227","DOIUrl":"https://doi.org/10.15761/JSIN.1000227","url":null,"abstract":"On June 18th the world lost a fabulous 17-year-old violinist prodigy a Carnegie Hall sensation, Katya Tsukanova, due to a fatal overdose of the designer drug named Calvin Klein (CK). The CK drug is so named because it contains a combination of both cocaine and ketamine. It is therefore appropriately categorized as a “polydrug.” CK (sometimes called CK1 or cable) has become a real party drug not only in England but also in other parts of the world including New York’s nightclub scenes. The feeling experienced from using CK is akin to that induced by the famous sex-inked, Molly, in the 60s and 70s. People taking this drug, mostly by snorting it, suggest that the mixture of the two-produce powerful euphoric highs coupled with a hallucinogenic feeling caused by ecstasy.","PeriodicalId":87318,"journal":{"name":"Journal of systems and integrative neuroscience","volume":"7 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38384237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cortical activation during imitative behavior: An fMRI study","authors":"Pierpaoli C, Fabri M, Polonara G","doi":"10.15761/JSIN.1000226","DOIUrl":"https://doi.org/10.15761/JSIN.1000226","url":null,"abstract":"A previous behavioural study on healthy subjects and callosotomized patients showed that subjects imitated mainly in mirror mode when free to choose the imitation mode, using the right limb to copy a left limb gesture of the facing model; when asked to use the same limb as the model, patients still perform in mirror mode, but controls imitated in anatomical mode, using the right limb for imitating a right limb gesture. These data suggest that the anatomical mode of imitation recruites both hemispheres, being linked to the integrity of the corpus callosum. The present study aims at investigating with fMRI the neural correlates of imitative perspective-taking, specially the anatomical mode. Functional MRI was performed in 10 control subjects of the previously tested groups, asked to Observe or Imagine-to-Imitate-with-the-same-limb , in separete runs, intransitive gestures. Different cortical activation in the two conditions were observed: opercular part of left inferior frontal gyrus, left inferior parietal lobule, right temporo-parietal junction and bilateral parietal opercular cortices were activated in Imagine-to-Imitate condition only. Present data confirm previous behavioural observations and indicate that neural circuitry underpinning the anatomical imitation of intransitive gesture likely requires the cooperation of both hemispheres, and therefore the integrity of the corpus callosum.","PeriodicalId":87318,"journal":{"name":"Journal of systems and integrative neuroscience","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67485513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Tsialios, E. Karavasilis, I. Karanasiou, A. Bonakis, G. Velonakis, E. Efstathopoulos, N. Kelekis, M. Papathanasiou
{"title":"Left Temporal Lobe Epilepsy Patients Without Hippocampal Sclerosis: a DTI and VBM Study","authors":"P. Tsialios, E. Karavasilis, I. Karanasiou, A. Bonakis, G. Velonakis, E. Efstathopoulos, N. Kelekis, M. Papathanasiou","doi":"10.15761/jsin.1000237","DOIUrl":"https://doi.org/10.15761/jsin.1000237","url":null,"abstract":"","PeriodicalId":87318,"journal":{"name":"Journal of systems and integrative neuroscience","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67485633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Bouadel, M. El Hassani, M. Y. Oudrhiri, S. Kabbaj, M. Jiddane, A. El Ouahabi
{"title":"Brain mapping optimization: DES characterization towards improved sensitivityA. Bouadel","authors":"A. Bouadel, M. El Hassani, M. Y. Oudrhiri, S. Kabbaj, M. Jiddane, A. El Ouahabi","doi":"10.15761/jsin.1000231","DOIUrl":"https://doi.org/10.15761/jsin.1000231","url":null,"abstract":"Improving the functional mapping quality means overcoming the effect of boundary conditions affecting its sensitivity under the false negative impact without forgetting the manageable impact of false positives on its specificity. This is a simulation study of the functional brain mapping has been done by neuronal computational modeling in correlation with a comparative retrospective analysis. However, the results show the optimization of the parameters threshold in DES, as intensity threshold, its increase by the CSF resistivity and the extremum duration of the electrical signal in direct application. Therefore, the awake surgery becomes not only a revolutionary technique; because of the extent of the resection, which is currently done according to functional imperative, unlike the onco-anatomical limits during the classical paradigm; but to free up new therapeutic perspective towards a functional, personalized and maximalist surgical neuro-oncology without malignant transformation.","PeriodicalId":87318,"journal":{"name":"Journal of systems and integrative neuroscience","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67486044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Improved executive functioning in healthy older adults after multifactorial cognitive training targeting controlled processes","authors":"C. Chambon, B. Alescio-Lautier","doi":"10.15761/JSIN.1000218","DOIUrl":"https://doi.org/10.15761/JSIN.1000218","url":null,"abstract":"Among the different cognitive training approaches tested in healthy older adults, multifactorial programs, which target higher-order processes such as memory and attention, best promote the transfer of learning to untrained cognitive processes. Objective: In the present study, we investigated the effects of a multifactorial cognitive training program on executive functions in older adults. Method: This training was developed to embed the processing of executive information in memory and attention training tasks, and mnemonic and executive strategies were implemented progressively throughout training. Results: The results showed that this training program (24 sessions, 2 sessions per week) improved executive functions in older adults (n=15; mean age=74.5±2.1). Significant improvements were found for the switching and inhibition of irrelevant stimuli. We also report enhanced performance in the efficiency of a dual-task activity. Additionally, we report that these benefits were present at the 6-month follow-up without any additional training. Conclusion: Taken together with previous results obtained with the same training protocol, the present results showed that the multifactorial training program we developed is an efficient tool to positively act on memory-related and executive aspects of the cognitive decline found in normal aging.","PeriodicalId":87318,"journal":{"name":"Journal of systems and integrative neuroscience","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67485551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gut acellular matrix for the in vitro study of Enteric Nervous System cells","authors":"Schrenk S, Piccione M, Tasso A, D. R., Conconi Mt","doi":"10.15761/JSIN.1000217","DOIUrl":"https://doi.org/10.15761/JSIN.1000217","url":null,"abstract":"Enteric nervous system (ENS) cells respond to the intestinal extracellular matrix (ECM) signals changing their proliferation rate, migration and differentiation. In this study, we explored in vitro the adaptive response of primary ENS cell cultures to the stimulation of gut acellular matrix (AM) defining the gene expression profile of neuronal functionality markers. Scanning electron microscopy was used to detect the acquisition of specific morphological features. Intestinal AM was prepared using an enzyme-detergent treatment. Primary rat enteric cells were isolated from the myenteric plexus of postnatal rats using an enzymatic method and seeded on intestinal AM in the presence of exogenous neurotrophic factors. The morphological properties and the expression of specific differentiation markers were evaluated by Scanning Electron Microscopy (SEM) and wholemount fluorescent staining. In order to verify the synergic activity of soluble factors and AM, the gene expression of neurotransmitter receptors was evaluated by qPCR in ENS cells cultured in SM conditions in the presence or not of AM. The development of interconnected ganglion-like structures and the expression of neurotransmitter receptors suggested that gut matrix engineered with ENS cells could be useful for medical applications of regenerative medicine or for the in vitro assessment of tridimensional culture system of ENS.","PeriodicalId":87318,"journal":{"name":"Journal of systems and integrative neuroscience","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67485478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Tsikouras, Konstantinos Paraskevopoulos, A. Bothou, Nikoletta Pastelli, X. Anthoulaki, A. Chalkidou, S. Michalopoulos, Ioannis Tsirkas, F. Gaitatzi, M. Koutsogiannis, Stavroglou Athanasia, Panagiotis Petsidis, Stefanos Zervvoudis, N. Nikolettos, K. Vahtsevanos
{"title":"Tongue cancer and Pregnancy: Report of two cases in association with HPV infection and literature review. Is HPV vaccination necessary to prevent of tongue cancer?","authors":"P. Tsikouras, Konstantinos Paraskevopoulos, A. Bothou, Nikoletta Pastelli, X. Anthoulaki, A. Chalkidou, S. Michalopoulos, Ioannis Tsirkas, F. Gaitatzi, M. Koutsogiannis, Stavroglou Athanasia, Panagiotis Petsidis, Stefanos Zervvoudis, N. Nikolettos, K. Vahtsevanos","doi":"10.15761/jsin.1000236","DOIUrl":"https://doi.org/10.15761/jsin.1000236","url":null,"abstract":"The detailed research for more information on the very important area of tongue cancer is the purpose of the present study. We report two cases of pregnant women suffering from tongue cancer during pregnancy, the treatment of tongue cancer and information on the outcome of pregnancy. Pregnancy should not be considered an obstacle to the proper treatment of a mother's tongue malignancy. The epidemiological trend in recent years is to increase the overall survival of patients and keep them free of disease for a longer period of time. The reported pregnant women were in the third trimester of pregnancy with tongue cancer symptoms at 37 and 32 weeks, respectively. After detailed information, the cesarean section was performed and the two women treated according to the proposed protocols which were as following: surgical removal of tumors, lymph node dissection in 5 levels and postoperative radiotherapy. The first case of these recurred 3 months later, underwent surgical removal of the tumor and subsequently underwent chemotherapy and immunotherapy. She died one year after the primary diagnosis of tongue cancer. The perinatal effect was perfect in both cases. The lack of systematic randomized prospective studies and the difficulties in carrying them out in general, make bibliographic review even more useful in guidelines, retrospective studies, series of events and individual cases for future scientific studies to be performed in order to establish treatment protocols.","PeriodicalId":87318,"journal":{"name":"Journal of systems and integrative neuroscience","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67486009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}