Clinical pharmacology and translational medicine最新文献

{"title":"Ivermectin as a potential therapeutic in COVID-19.","authors":"Juan Segura-Aguilar, Yousef Tizabi","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":87235,"journal":{"name":"Clinical pharmacology and translational medicine","volume":"4 1","pages":"160-161"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993655/pdf/nihms-1665991.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25526052","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":"Overexpression of Vesicular Monoamine Transporter-2 may Block Neurotoxic Metabolites from Cytosolic Dopamine: a Potential Neuroprotective Therapy for Parkinson's Disease.","authors":"Segura-Aguilar,&nbsp;David Sulzer,&nbsp;Fabio A Zucca,&nbsp;Luigi Zecca","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The loss of nigrostriatal dopaminergic neurons containing neuromelanin underlies the motor symptoms of Parkinson's disease. Neuromelanin accumulation into autophagic lysosomes is evidence of ongoing cytosolic dopamine stress in these neurons during normal aging. The formation of neuromelanin is likely neuroprotective, as oxidation of cytosolic dopamine to quinones and aldehydes, as reviewed here, can produce a host of neurotoxic sequela. In addition to sequestration of dopamine and its metabolites in autophagic lysosomes, the uptake of dopamine into monoaminergic neurons mediated by vesicular monoamine transporter-2 (VMAT- 2), prevents dopamine oxidation. Dopamine is stable in monoaminergic vesicles due to their low pH, and thus overexpression of VMAT-2 may provide a target for potential neuroprotective therapy in Parkinson's disease.</p>","PeriodicalId":87235,"journal":{"name":"Clinical pharmacology and translational medicine","volume":"3 1","pages":"143-148"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454000/pdf/nihms-1621354.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38326356","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":"Effects of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Gut Microbiota in a Rat Model of Depression.","authors":"Bruk Getachew,&nbsp;Yousef Tizabi","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background/aims: </strong>It is now well established that imbalance or dysbiosis in the gut microbiota (GM) plays a significant role in neuropsychiatric/neurodegenerative disorders. Recently it has been reported that the C-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) may not only act as a neuroprotectant but may also exhibit antidepressant effects in Wistar-Kyoto (WKY) rats, a putative animal model of treatment-resistant depression. The aim of this study was to determine whether Hc-TeTx may also interact with GM implicated in mood regulation in these rats.</p><p><strong>Methods: </strong>Adult male WKY rats (5/group) were injected intramuscularly (IM) with 60 μg/kg Hc-TeTx or saline. Twenty-four hours after the injection, the animals were sacrificed, intestinal stools were collected and stored at -80°C. DNA was extracted from the samples for 16S rRNA gene-based microbiota analysis using 16S Metagenomics application.</p><p><strong>Results: </strong>Abundance of several bacteria at different taxonomic levels were distinguished between Hc-TeTx group and the control. At species-level, 11 operational taxonomic units (OTUs), particularly <i>Bifidobacterium cholerium</i>, a bacterium with a strong ability to degrade resistant starch, were enriched (69 fold) in the Hc-TeTx group. In addition, 5 species of probiotic <i>Lactobacillus</i>, two butyrate-forming species S<i>arcina, Butyrivibro proteovlasticus</i> a<i>nd Roseburia faecis</i>, were enhanced by a minimum of 2-fold in Hc-TeTx group. In contrast, 24 species including five species of pathogenic <i>Provettela</i> (5-14 fold), two mucin-degrading <i>Akkermansia muciniphila and Mucispirillum schaedleri</i>, and four species of pathogenic <i>Ruminoccus</i> were reduced by a minimum of 2-fold by Hc-TeTx treatment.</p><p><strong>Conclusion: </strong>Hc-TeTx enhanced probiotic species and suppressed the opportunistic pathogens. Since overall effect of Hc-TeTx appears to be promoting GM associated with mood enhancement (e.g. <i>Bifidobacterium, Butyrivibro, and Lactobacillus</i>) and suppressing GM associated with mood dysregulation (e.g. <i>Mucispirillum, Provettela, and Ruminoccus</i>) a novel mechanism of beneficial effects of Hc-TeTx may involve normalization of dysbiosis.</p>","PeriodicalId":87235,"journal":{"name":"Clinical pharmacology and translational medicine","volume":"3 2","pages":"152-159"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063687/pdf/nihms-1065711.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37727476","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":"Natural Products in the Promotion of Healthspan and Longevity.","authors":"M. Niso-Santano, R. González-Polo, Marta Paredes-Barquero, J. M. Fuentes, M. Aschner","doi":"10.31700/2572-7656.000123","DOIUrl":"https://doi.org/10.31700/2572-7656.000123","url":null,"abstract":"patterns has been shown to have similar beneficial effects on health and longevity. These therapeutic fasting include intermittent fasting (IF) or periodic fasting (PF) or among others. CR and IF may have a number of beneficial effects on health including improved cardiovascular health, reduced inflammation, improved mitochondrial function, reduced insulin resistance and delayed the onset and progression of age-related metabolic diseases. One key mechanism responsible for many of these beneficial effects appears to be the induction of autophagy. In","PeriodicalId":87235,"journal":{"name":"Clinical pharmacology and translational medicine","volume":"3 1 1","pages":"149-151"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69666022","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":"Botulinum Neurotoxin, an Example of Successful Translational Research.","authors":"Juan Segura-Aguilar,&nbsp;Yousef Tizabi","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":87235,"journal":{"name":"Clinical pharmacology and translational medicine","volume":"2 3","pages":"125-126"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384007/pdf/nihms-1001211.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36996052","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":"Nicotinic Receptor Intervention in Parkinson's Disease: Future Directions.","authors":"Yousef Tizabi, Bruk Getachew","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Sufficient preclinical and epidemiological data are available to justify nicotinic intervention in Parkinson's disease (PD). Although use of nicotine patch has been suggested in some neurodegenerative disorders, including PD, the key for success with nicotinic intervention, particularly in PD, appears to rely not only on the dose but also on the mode of nicotine administration. Our aim in this short review is to provide justification for such contention. Thus, following a short introduction of nicotinic receptor pharmacology, the potential of nicotine in alleviating not only the motor symptoms, but also the mood disorders (e.g. depression) and mild cognitive impairments that are commonly co-morbid with PD will be presented. Moreover, since current PD therapy is associated with dyskinesia, the effectiveness of nicotine in ameliorating levodopa (L-Dopa)-induced dyskinesia will also be discussed. It is suggested that pulsatile nicotine administration (e.g. via inhalation or nasal spray) may be the optimal route in nicotinic intervention in PD.</p>","PeriodicalId":87235,"journal":{"name":"Clinical pharmacology and translational medicine","volume":"1 1","pages":"14-19"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975393/pdf/nihms931112.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40528677","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":"Neuroprotective and Therapeutic Strategies for Manganese-Induced Neurotoxicity.","authors":"A P Marreilha Dos Santos,&nbsp;V Andrade,&nbsp;M Aschner","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Manganese (Mn) is an essential element required for growth, development and general maintenance of health. However, chronic or high occupational and environmental exposure to excessive levels of Mn has long been known to lead to a progressive neurological disorder similar to Parkinsonism. Manganism patients display a variety of symptoms, including mental, cognitive and behavioural impediments, as well as motor dysfunctions that are associated with basal ganglia dysfunction. Taking into account the pharmacokinetics and Mn-related toxicity mechanisms, several neuroprotective compounds and therapeutic approaches have been investigated to assess their efficacy in mitigating its neurotoxicity. Here, we will briefly address some of the toxic mechanisms of Mn, followed by neuroprotective strategies and therapeutic approaches aiming to reduce or treat Mn induced neurotoxicity. Natural and synthetic antioxidants, anti-inflammatory compounds, ATP/ADP ratio protectors and glutamate protectors have been introduced in view of decreasing Mn-induced neurotoxicity. In addition, the efficacy and mechanisms of several therapeutic interventions such as levodopa, ethylene-diamine-tetraacetic acid (EDTA) and para-aminosalicylic acid (PAS), aimed at ameliorating Mn neurotoxic symptoms in humans, will be reviewed.</p>","PeriodicalId":87235,"journal":{"name":"Clinical pharmacology and translational medicine","volume":"1 2","pages":"54-62"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402347/pdf/nihms-984937.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37217097","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}