MyMedR

Displaying all 4 publications

Abstract:

Sort:

Fulltext The Effect of a Setting Accelerator on the Physical and Mechanical Properties of a Fast-set White Portland Cement Mixed with Nano-zirconium Oxide

Chen YZ, Yong MJ, Tan VY, Kong SLS, Elnawawy HMA, Yahya NA, et al.

Eur Endod J, 2023 May;8(3):215-224.
PMID: 37257037 DOI: 10.14744/eej.2023.36449

OBJECTIVE: This study compared the effects of calcium chloride dihydrate (CaCl2.2H2O) on the physical properties and push-out bond strength of white Mineral Trioxide Aggregate (WMTA) and an experimental Malaysian Portland cement mixed with nano-zirconium oxide (nano-ZrO) [(radiopaque Malaysian Portland cement (RMPC). Mineral Trioxide Aggregate (MTA) was the first calcium silicate cement (CSC) introduced in dentistry, but up to date, it is an expensive cement with long setting time and causes tooth discolouration. Although Portland cement has been introduced as a potential substitute to MTA, it still faces some challenges such as long setting time and lack of sufficient radiopacity.
METHODS: Four groups [WMTA, RMPC, fast-set WMTA (FS-WMTA) and fast-set RMPC (FS-RMPC)] were prepared. Initial setting time was evaluated using Vicat apparatus. The pH was measured at seven-day intervals. For discolouration potential, cements were packed in the pulp chamber of 46 extracted maxillary incisors. Spectrophotometric readings were obtained at seven-day intervals, and the rate of colour change (ΔE) was recorded. For the push-out bond strength testing, cements were applied in 48 sectioned root samples, and the test was performed using universal testing machine at crosshead speed of 0.5 mm/min until bond failure. Statistical analysis was done according to the nature of each group of data using SPSS 26.
RESULTS: Addition of CaCl2.2H2O decreased the initial setting times of both RMPC and WMTA significantly (p<0.05). The pH values of FS-WMTA and FS-RMPC were comparable to their non-accelerated counterparts ranging from 10 to 12. Discolouration effect was more obviously observed with WMTA and FS-WMTA with time compared to RMPC formulations. Push-out bond strength of the two materials also showed an increase with the addition of the accelerator, however, only FS-WMTA showed statistically significant difference compared to WMTA (p<0.05).
CONCLUSION: The addition of CaCl2.2H2O improves the physical and mechanical properties of the newly formulated RMPC and WMTA. The RMPC formulation overcomes the discolouration potential of WMTA. (EEJ-2022-12-155).
Fulltext Discovery of indolylpiperazinylpyrimidines with dual-target profiles at adenosine A2A and dopamine D2 receptors for Parkinson's disease treatment

Shao YM, Ma X, Paira P, Tan A, Herr DR, Lim KL, et al.

PLoS One, 2018;13(1):e0188212.
PMID: 29304113 DOI: 10.1371/journal.pone.0188212

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects. In this study, new chemical entities targeting both human A2A adenosine receptor and dopamine D2 receptor were designed and evaluated. Two computational methods, namely support vector machine (SVM) models and Tanimoto similarity-based clustering analysis, were integrated for the identification of compounds containing indole-piperazine-pyrimidine (IPP) scaffold. Subsequent synthesis and testing resulted in compounds 5 and 6, which acted as human A2A adenosine receptor binders in the radioligand competition assay (Ki = 8.7-11.2 μM) as well as human dopamine D2 receptor binders in the artificial cell membrane assay (EC50 = 22.5-40.2 μM). Moreover, compound 5 showed improvement in movement and mitigation of the loss of dopaminergic neurons in Drosophila models of PD. Furthermore, in vitro toxicity studies on compounds 5 and 6 did not reveal any mutagenicity (up to 100 μM), hepatotoxicity (up to 30 μM) or cardiotoxicity (up to 30 μM).
Fulltext Design, Synthesis and Evaluation of New Indolylpyrimidylpiperazines for Gastrointestinal Cancer Therapy

Tan A, Babak MV, Venkatesan G, Lim C, Klotz KN, Herr DR, et al.

Molecules, 2019 Oct 11;24(20).
PMID: 31614517 DOI: 10.3390/molecules24203661

Human A3 adenosine receptor hA3AR has been implicated in gastrointestinal cancer, where its cellular expression has been found increased, thus suggesting its potential as a molecular target for novel anticancer compounds. Observation made in our previous work indicated the importance of the carbonyl group of amide in the indolylpyrimidylpiperazine (IPP) for its human A2A adenosine receptor (hA2AAR) subtype binding selectivity over the other AR subtypes. Taking this observation into account, we structurally modified an indolylpyrimidylpiperazine (IPP) scaffold, 1 (a non-selective adenosine receptors' ligand) into a modified IPP (mIPP) scaffold by switching the position of the carbonyl group, resulting in the formation of both ketone and tertiary amine groups in the new scaffold. Results showed that such modification diminished the A2A activity and instead conferred hA3AR agonistic activity. Among the new mIPP derivatives (3-6), compound 4 showed potential as a hA3AR partial agonist, with an Emax of 30% and EC50 of 2.89 ± 0.55 μM. In the cytotoxicity assays, compound 4 also exhibited higher cytotoxicity against both colorectal and liver cancer cells as compared to normal cells. Overall, this new series of compounds provide a promising starting point for further development of potent and selective hA3AR partial agonists for the treatment of gastrointestinal cancers.
Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis

Bousquet J, Melén E, Haahtela T, Koppelman GH, Togias A, Valenta R, et al.

Allergy, 2023 Feb 17.
PMID: 36799120 DOI: 10.1111/all.15679

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.