UHPLC-HRMS study of Anti-Alzheimer’s drug candidates: metabolism of 7-MEOTA-tryptophan hybrids hampers their passage into brain
Publication date: Available online 24 May 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): M. Mžik, J. Karasová-Žďárová, K. Chalupová, J Korábečný, V. Palička, V. ŠestákAbstractBeing among the top five causes of death in the developed world, Alzheimer’s disease represents a major socio-economic issue. We administered a single intramuscular dose of two new hybrid anti-Alzheimer’s compounds, with 7-methoxytacrine (7-MEOTA; acetylcholinesterase inhibitor) and tryptophan (inhibitor of amyloid accumulation) in their structure, to rats.Using validated ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) methods, we uncovered their inability to enter the site of action – the brain. We discuss four possible explanations: i) physico-chemical properties, ii) lack of active/facilitated transport, iii) effective efflux and/or iv) extensive metabolism.Extensive high-resolution mass spectrometric analyses proved that the compounds are easily hydrolysed at amide bond between tryptophan and the linker both in vitro and in vivo using. Contrary to the parent compounds these metabolites – analogues of 7-MEOTA – can enter the brain in significant amounts.
Publication date: Available online 17 July 2019Source: Journal of Integrative MedicineAuthor(s): Pierre Watcho, Ismaelle Rosine Mpeck, Patrick Brice Defo Deeh, Modeste W.eu-Nya, Esther Ngadjui, Georges Romeo Fozin Bonsou, Pierre Kamtchouing, Albert KamanyiAbstractObjectiveCyclophosphamide (CP) is commonly used to treat some cancers, but its clinical efficacy is also linked with testicular toxicity. We investigated the effects of aqueous extract (AE) and methanolic extract (ME) of Helichrysum odoratissimum for reducing CP-induced reproductive toxicity in male rats.MethodsIn addition to a normal control (group 1), drugs or v...
This study used Oswestry Disability Index (ODI)-self-comparison and showed that acupuncture treatments for lumber disc herniation and sciatica demonstrated significant improvement in long term clinical outcomes. A total of 112 lumbar disc herniation and sciatica cases were treated with electric acupuncture for pain relief and function improvement from July 1998 to December 2006.ResultsAll the 112 cases filled out the ODI forms prior to receiving treatment. Among the 112 patients, 23 of them did not finish the 6-week treatments. 89 cases were evaluated with ODI after 6-week acupuncture treatments. Of those 89 cases, 67 case...
ConclusionsThe therapeutic effect of acupuncture and moxibustion by soothing liver and regulating mind can obviously improve the quality of life of depression elders.
ConclusionRV Dysfunction according to our definition in first Anterior MI occurred in (55%) of the study population. Independent predictors for Abnormal RV function were; LCX mid or proximal affection, eventful procedure, occurrence of no reflow, Glucose level, LVESD, LVEDD and LV EF.
Publication date: Available online 17 July 2019Source: Global HeartAuthor(s): Jessica Ying-Yi Xie, Matthew R. Solomons, Mahmood Ahmad
Publication date: Available online 18 July 2019Source: American Heart JournalAuthor(s): Nwora Lance Okeke, Allison R. Webel, Hayden B. Bosworth, Angela Aifa, Gerald S. Bloomfield, Emily Choi, Sarah Gonzales, Sarah Hale, Corrilynn O. Hileman, Virginia Kidwell, Charles Muiruri, Megan Oakes, Julie Schexnayder, Valerie Smith, Rajesh Vedanthan, Chris T. Longenecker
Conclusion: Experiences of being sexually harassed correlate among adolescents with high social anxiety but also with high self-esteem. Sexual harassment among adolescents may partly be explained as inept ways of showing interest, but it may nevertheless have detrimental effects on the well-being of the those subjected to it. PMID: 31311376 [PubMed - as supplied by publisher]
Publication date: Available online 17 July 2019Source: Journal of Geriatric OncologyAuthor(s): Mina S. Sedrak, Daneng Li, Louise C. Walter, Karen Mustian, Kevin P. High, Beverly Canin, Supriya G. Mohile, William Dale, Can-Lan Sun
Publication date: Available online 17 July 2019Source: Journal of Geriatric OncologyAuthor(s): Melisa L. Wong, Stuart M. Lichtman, Gary R. Morrow, John Simmons, Tomma Hargraves, Cary P. Gross, Jennifer L. Lund, Lisa M. Lowenstein, Louise C. Walter, Cara L. McDermott, Supriya G. Mohile, Harvey Jay Cohen
ConclusionIn a cohort of 40 older adults with newly diagnosed multiple myeloma, three frailty indices have differing approaches to operationalizing frailty resulting, in different patients being categorized as frail. Little agreement existed between the models. Further studies are needed to explore the utility of these models in predicting treatment toxicity and prognosis.