Vitamins, Macroelements, and Trace Metals
Stephen C. Cunnane in Zinc: Clinical and Biochemical Significance, 2018
In the search to define the biological role of zinc, the interaction of zinc with vitamins, minerals, and trace metals has sometimes been overlooked. Nevertheless, it is quite clear that zinc depletion in both humans and animals profoundly influences the biological activity of other essential nutrients. Some of these interactions are discussed in this chapter. The chapter details the relationship between zinc and vitamin A. Zinc has important effects on the metabolism of vitamin A in relation to retinol-binding protein. With vitamins B6 and E, zinc seems to have similar, possibly synergistic effects, especially involving essential fatty acids and antioxidant effects/membrane stability, respectively. The most significant interactions of zinc with the macroelements are with calcium, nitrogen, and sulfur. With two of the essential trace elements, copper and iron, zinc has a largely competitive association. The role of zinc with the toxic trace metals (cadmium, aluminum, and lead) appears to be one of competitive inhibition of their uptake.
Possible Mechanisms of Hla and Disease Associations:Sex Prevalence
William E. Braun in HLA and Disease: A Comprehensive Review, 2019
The major mechanisms proposed for HLA and disease association are as follows. First, there may be molecular mimicry, or cross-reactivity, between a pathogen and a histocompatibility or disease-association antigen so that normal immune surveillance mechanisms fail to eliminate the pathogen because it resembles a “self” antigen. Second, a form of molecular mimicry which is nonimmunologic and actually more like competitive inhibition has been hypothesized by A. Svejgaard. Third, the antigen in question may actually be a receptor for a microbial pathogen or other pathogenic substance. A fourth possibility focuses on the histocompatibility restriction for lymphocytes cytotoxic to virus-infected target cells. A fifth and highly promising mechanism is linkage and linkage disequilibrium between the HLA loci and Ir loci for disease susceptibility. The vast majority of such disease associations are with HLA-B and D-series antigens. Finally, HLA antigens may act as differentiation antigens that can alter cell-cell interaction.
Flumazenil (Flumazepil)
Louis A. Pagliaro, Ann Marie Pagliaro in Psychologists’ Psychotropic Drug Reference, 2020
This chapter describes trade name, classification, approved indications for psychological disorders, available dosage forms, storage, and compatibility, usual dosage and administration, relative contraindications, and clinically significant drug interactions of flumazenil. The manufacturer recommends that flumazenil be administered intravenously by a physician who has experience in anesthesiology and that patients have an established airway and intravenous access before intravenous flumazenil pharmacotherapy is initiated. Flumazenil pharmacotherapy always should be administered with concurrent emergency symptomatic medical treatment for acute overdosage. Flumazenil is a benzodiazepine antagonist that acts at the benzodiazepine receptors by means of competitive inhibition. The efficacy of flumazenil for reversing the sedation and respiratory depression associated with benzodiazepine overdosage is greatest in relation to sedation but may be limited or incomplete in relation to respiratory depression. Excessive or rapid administration of flumazenil to patients who are addicted to benzodiazepines may induce the benzodiazepine withdrawal syndrome.
Decreased semantic competitive inhibition in Parkinson's disease: Evidence from an investigation of word search performance
Published in International Journal of Speech-Language Pathology, 2010
Wendy L. Arnott, Helen J. Chenery, Anthony J. Angwin, Bruce E. Murdoch, Peter A. Silburn, David A. Copland
Aberrant semantic competitive inhibition has been reported in Parkinson's disease (PD). Whether PD-related alterations cause an increase or a decrease in lateral inhibition, however, remains unclear. Accordingly, the present study aimed to examine semantic inhibition during lexical-semantic processing in non-demented people with PD. Twenty-two people with PD and 18 matched controls completed a computerized word search task in which both the relationship between the background items and the target (related or unrelated) and the search type (open e.g., any dog or closed e.g., collie) were manipulated. It was hypothesized that decreased semantic inhibition would be evidenced by abnormally short response times for open searches among words related to the target, while increased inhibition would lead to abnormally long response times. Analysis of the results revealed that control participants performed open searches faster for unrelated vs related word lists. In contrast, the PD group recorded similar response times regardless of background items. Hence, the present findings are consistent with the notion of decreased semantic competitive inhibition in PD and suggest that an impaired ability to inhibit unwanted information during lexical retrieval may underlie observed deficits on semantic tasks such as verbal fluency.
Design, synthesis, and evaluation of curcumin analogues as potential inhibitors of bacterial sialidase
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Bo Ram Kim, Ji-Young Park, Hyung Jae Jeong, Hyung-Jun Kwon, Su-Jin Park, In-Chul Lee, Young Bae Ryu, Woo Song Lee
Sialidases are key virulence factors that remove sialic acid from the host cell surface glycan, unmasking receptors that facilitate bacterial adherence and colonisation. In this study, we developed potential agents for treating bacterial infections caused by Streptococcus pneumoniae Nan A that inhibit bacterial sialidase using Turmeric and curcumin analogues. Design, synthesis, and structure analysis relationship (SAR) studies have been also described. Evaluation of the synthesised derivatives demonstrated that compound 5e was the most potent inhibitor of S. pneumoniae sialidase (IC50 = 0.2 ± 0.1 µM). This compound exhibited a 3.0-fold improvement in inhibitory activity over that of curcumin and displayed competitive inhibition. These results warrant further studies confirming the antipneumococcal activity 5e and indicated that curcumin derivatives could be potentially used to treat sepsis by bacterial infections.
Synthesis and tyrosinase inhibitory properties of novel isoquinoline urea/thiourea derivatives
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2014
Hayriye Genç, Mustafa Zengin, Emre Yavuz, Nahit Gençer, Oktay Arslan
A new series of isoquinoline urea/thiourea derivatives (1–11) were synthesized, and their inhibitory effects on tyrosinase were evaluated. Isoquinoline urea/thiourea derivatives were obtained as a result of the reaction of 5-aminoisoquinoline with isocyanates or isothiocyanates. The result showed that all the synthesized compounds inhibited the tyrosinase enzyme activity. Among the compounds synthesized, 1-(4-chlorophenyl)-3-(isoquinolin-5-yl)thiourea (3) was found to be the most active one (Ki = 119.22 μM), and the inhibition kinetics analyzed using Lineweaver–Burk double reciprocal plots revealed that compound 3 was a competitive inhibitor. We also calculated HOMO-LUMO energy levels, some selected the synthesized compounds (1, 4, 11, 3, 6, 2) using Gaussian software.