Urea And Uric Acid Adsorption By Nanoporous Biomaterials

Kelemahan hemodialisis zaman ini telah menjadi punca penyelidikan dan pembangunan beberapa prototaip ginjal buatan mudah alih. Komponen utama model mudah alih ini (berbanding hemodialisis) ialah sistem dialisat tertutup. Secara tipikalnya, model-model ini biasanya menggunakan karbon teraktif sebagai bahan penjerap. Penggunaan bahan penjerap yang lebih unggul, jumlah dialisat yang diperlukan untuk penyingkiran toksin uremik boleh dikurangkan dan dikitar semula. Motivasi utama bagi penyelidikan ini ialah kekurangan pemilihan bahan untuk bahan penjerap dalam model-model ini. Oleh itu, objektif projek ini ialah sintesis dan penilaian tiga jenis biobahan berliang nano yang baru, iaitu gentian karbon teraktif berongga (ACF), silika berliang meso (MS) dan hidroksiapatit berliang meso, dengan sasaran untuk penyingkiran konstituen utama toksin uremik, iaitu urea dan asid urik. ACF telah diperolehi melalui kaedah pengaktifan asid dengan menggunakan asid-asid yang berbeza; asid bukan organic sulfurik, nitrik dan fosforik; asid organik asetik dan sitrik. MS dan HAp telah disintesis melalui kaedah templat lembut dengan surfaktan Pluronics. Keputusan awal penjerapan urea telah menunjukkan bahawa MS dengan kumpulan berfungsi amina dan ACF terawat asid sulfuric adalah sangat baik (550 mg/g) berbanding dengan karbon teraktif komersil (CAC). Ujian kinetik penjerapan urea telah mendedahkan mekanisma penjerapan urea oleh ACF (jerapan fizikal) dan MS (jerapan kimia). MS amina dan diamina menjerap lebih daripada 30 molekul per nm2 (jerapan kimia yang kuat) berbanding MS biasa, CAC dan pelbagai ACF, yang telah menjerap kurang daripada 10 molekul per nm2 (jerapan fizikal). Faktor-faktor utama yang mempengaruhi kapasiti jerapan ialah keliangan dan kimia permukaan yang sesuai, yang mana kedua-duanya dipunyai oleh MS amina dan diamina. Kebolehubahan permukaan berfungsi bagi MS merupakan asas untuk ujian jerapan urik asid seterusnya. Satu hipotesis peningkatan jerapan asid urik oleh MS terfungsi amina merupakan melalui tindak balas kimia asid-amina. Jerapan asid urik oleh MS tidak mengikut keluk jerapan teori. Analisa yang mendalam dengan menggunakan aplikasi MATLAB menunjukkan bahawa MS telah menjalani jerapan dan nyahrepan serentak, dengan kadar jerapan permulaan setinggi 20.3 mg/g/s berbanding gel silica dengan kadar jerapan hanya 0.39 mg/g/s. Sebagai kesimpulan, secara keseluruhannya, keputusan jerapan urea dan asid urik MS dan ACF lebih baik berbanding CAC dan gel silika komersil. ________________________________________________________________________________________________________________________ The limitations of the present hemodialysis have led towards the research and development of several wearable artificial kidney prototypes. The most important component of the miniaturised model is the closed-system dialysate, achieved through the utilisation of solid activated carbon as adsorbents. With the application of superior alternative adsorbents, the amount of dialysate required could be reduced due to efficient regeneration. The main motivation for this project is the lack of adsorbent materials selection. Thus, this project aims to synthesise and evaluate three emerging nanoporous biomaterials, i.e. hollow activated carbon fibre (ACF), mesoporous silica (MS) and mesoporous hydroxyapatite (HAp), targeting major uremic toxin constituent urea and uric acid. ACF was obtained though the acid activation route, with variation in acid used; inorganic acids sulphuric, nitric and phosphoric; organic acids acetic and citric. MS and HAp was synthesised through soft templating route using Pluronics surfactant. Results show that amine functionalised MS and sulphuric acid treated ACF performed well in the preliminary urea adsorption capacity evaluation (550 mg/g), as compared to the control commercial activated carbon (CAC) (350 mg/g). Subsequent urea kinetics study revealed better understanding of urea adsorption mechanism by ACF and MS, whereby ACF and MS operate through physisorption and chemisorption respectively. Amine and diamine MS adsorbed more than 30 molecules per nm2 (strong chemisorption interaction) compared to bare MS, CAC and various ACF, which adsorbed less than 10 molecules per nm2 (physisorption). The most important factors which govern adsorption capacity are porosity and suitable surface chemistry, both which are possessed by amine and diamine MS. The flexibility of surface functionalisation of MS is the basis of subsequent uric acid adsorption kinetics test. Amine functionalised MS is hypothesised to improve uric acid adsorption through acid-amine reaction. Uric acid adsorption by MS did not follow theoretical adsorption curve. Further analysis using MATLAB curve fit revealed that MS underwent simultaneous adsorption-desorption, with initial adsorption rates as high as 20.3 mg/g/s compared to commercial silica gel, with initial adsorption rate of 0.39 mg/g/s. As a conclusion, on a whole, MS and ACF performed better than the benchmarked CAC and commercial silica gel in terms of urea and uric acid adsorption

The influence of OLR1 and PCSK9 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

It has been reported that both OLR1 and PCSK9 genes are related to various vascular diseases such as atherosclerosis, cardiovascular disease, peripheral artery disease and stroke, in particular ischemic stroke. The prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between OLR1 rs11053646 and PCSK9 rs505151 polymorphisms and the risk of ischemic stroke remains unclear and inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of genetic polymorphisms on ischemic stroke, by analyzing the complete coverage of all relevant studies. All eligible case-control and cohort studies that met the search term were retrieved in multiple scientific databases. Data of interest such as demographic data and genotyping methods were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. A total of seven case-control studies encompassing 1897 ischemic stroke cases and 2119 healthy controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR=1.33. 95%CI:1.11-1.58) and co-dominant models (OR=1.24, 95%CI:1.02-1.51) were significantly associated with ischemic stroke. For PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR=1.36, 95%CI:1.01-1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G>C and PCSK9 rs505151 A>G may contribute to the susceptibility risk of ischemic stroke

Association of NOTCH3 gene polymorphisms with ischemic stroke and its subtypes: A meta-analysis

Background and objectives: NOTCH3 gene variations play a significant role in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, the role of NOTCH3 gene polymorphisms in the risk of ischemic stroke, and its subtypes such as atherothrombotic or lacunar strokes, remains unclear. Aims: Hence, we carried out a meta-analysis to examine whether the NOTCH3 rs1043994, rs1044009 and rs3815188 polymorphisms are associated with ischemic stroke and its major subtypes. Materials and Methods: All relevant studies were systematically screened and meta-analyzed using Review Manager (Revman) version 5.3. The strength of the association between NOTCH3 polymorphisms and ischemic stroke risk and its subtypes were measured as odds ratios and 95% confidence intervals, under different genetic models. Results: A total of ten studies were identified, five of which considered NOTCH3 rs1043994 (2077 cases/2147 controls), five of which considered NOTCH3 rs1044009 (2315 cases/3053 controls), and nine of which considered NOTCH3 rs3815188 (2819 cases/2769 controls). These studies were meta-analyzed for their association with ischemic stroke risk. Four studies (874 cases/2002 controls) of the NOTCH3 rs3815188 polymorphism and three studies of the NOTCH3 rs1043994 (643 cases/1552 controls) polymorphism were meta-analyzed for lacunar stroke risk. Three studies (1013 cases/1972 controls) of the NOTCH3 rs3815188 polymorphism were meta-analyzed for atherothrombotic stroke risk. The meta-analysis results showed a lack of association between all of the studied polymorphisms and the risk of ischemic stroke and its major subtypes (i.e., atherothrombotic and lacunar). Conclusions: NOTCH3 polymorphisms are not significantly associated with the risk of ischemic stroke and its subtypes (p < 0.05).</p

The impact of APOA5 , APOB , APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

<b>BACKGROUND AND AIMS</b>\ud \ud Genetic studies have been reported on the association between APOA5, APOB, APOC3 and ABCA1 gene polymorphisms and ischemic stroke, but results remain controversial. Hence, this meta-analysis aimed to infer the causal relationships of APOA5 (rs662799, rs3135506), APOB (rs693, rs1042031, rs1801701), APOC3 (rs4520, rs5128, rs2854116, rs2854117) and ABCA1 rs2230806 with ischemic stroke risk.\ud \ud <b>METHODS</b>\ud \ud A systematic review was performed for all the articles retrieved from multiple databases, up until March 2017. Data were extracted from all eligible studies, and meta-analysis was carried out using RevMan 5.3 and R package 3.2.1. The strength of association between each studied polymorphism and ischemic stroke risk was measured as odds ratios (ORs) and 95% confidence intervals (CIs), under fixed- and random-effect models.\ud \ud <b>RESULTS</b>\ud \ud A total of 79 studies reporting on the association between the studied polymorphisms and ischemic stroke risk were identified. The pooled data indicated that all genetic models of APOA5 rs662799 (ORs = 1.23-1.43), allelic and over-dominant models of APOA5 rs3135506 (ORs = 1.77-1.97), APOB rs1801701 (ORs = 1.72-2.13) and APOB rs1042031 (ORs = 1.66-1.88) as well as dominant model of ABCA1 rs2230806 (OR = 1.31) were significantly associated with higher risk of ischemic stroke. However, no significant associations were observed between ischemic stroke and the other five polymorphisms, namely ApoB (rs693) and APOC3 (rs4520, rs5128, rs2854116 and rs2854117), under any genetic model.\ud \ud <b>CONCLUSIONS:</b>\ud \ud The present meta-analysis confirmed a significant association of APOA5 rs662799 CC, APOA5 rs3135506 CG, APOB rs1801701 GA, APOB rs1042031 GA and ABCA1 rs2230806 GG with increased risk of ischemic stroke

Prevalence of drug-related problems and complementary and alternative medicine use in Malaysia:A systematic review and meta-analysis of 37,249 older adults

Drug-related problems (DRPs) in the elderly include polypharmacy, potentially inappropriate medications, nonadherence, and drug-related falls. In this systematic review and meta-analysis, the prevalence of DRPs and complementary and alternative medicine (CAM) use among the Malaysian elderly was estimated. PubMed, Scopus, Web of Science, and Google Scholar databases were searched to identify studies published since their inception up to 24 August 2020. A random-effects model was used to generate the pooled prevalence of DRPs along with its corresponding 95% confidence interval (CI). The heterogeneity of the results was estimated using the I2 statistics, and Cochran’s Q test and sensitivity analyses were performed to confirm the robustness of the results. We identified 526 studies, 23 of which were included in the meta-analysis. (n = 29,342). The pooled prevalence of DRPs among Malaysian elderly was as follows: (1) polypharmacy: 49.5% [95% CI: 20.5–78.6], (2) potentially inappropriate medications: 28.9% [95% CI: 25.4–32.3], (3) nonadherence to medications: 60.6% [95% CI: 50.2–70.9], and (4) medication-related falls 39.3% [95% CI: 0.0–80.8]. Approximately one in two Malaysian elderly used CAM. The prevalence of polypharmacy and potentially inappropriate medications among the Malaysian elderly population was high, calling for measures and evidence-based guidelines to ensure the safe medication use

Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and Ischemic Stroke: Meta-Analysis

Introduction The association between ischemic stroke and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR; 677C>T and 1298A>C), endothelial nitric oxide synthase (eNOS; -786T>C, +894G>T, and variable number tandem repeat [VNTR]), phosphodiesterase 4D (PDE4D; SNPs 83 and 87), angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) 235M>T, paraoxonase 1 (PON1) 192Q>R, and apolipoprotein E (ApoE) ε2ε3ε4 remains inconclusive. Therefore, this updated meta-analysis aimed to clarify the presumed influence of genetic polymorphisms on ischemic stroke by meta-analyzing the comprehensive coverage of all individual association studies. Methods All case-control studies published in different languages such as English, Japanese, Korean, Spanish, Chinese, Hungarian, Ukrainian, or Russian were identified from databases. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated via fixed- and random-effect models. Sensitivity analysis, heterogeneity test, Hardy Weinberg Equilibrium, and Egger's regression analyses were performed in this study. Results A total of 490 case-control studies with 138,592 cases and 159,314 controls were included in this meta-analysis. Pooled ORs from all the genetic models indicated that MTHFR 677TT and 1298CC, eNOS +894TT and VNTR, PDE4D SNP 83, ACE DD, AGT 235TT, PON1 192RR, and ApoE ε4 polymorphisms were increasing the risks of ischemic stroke. Nevertheless, PDE4D SNP 87 and eNOS -786T>C polymorphisms are not associated with ischemic stroke risks. Conclusions Hence, the evidence from this meta-analysis concluded that MTHFR (677C>T and 1298A>C), eNOS (+894G>T and VNTR), PDE4D SNP 83, ACE I/D, AGT 235M>T, PON1 192Q>R, and ApoE ε2ε3ε4 polymorphisms predispose individuals to ischemic stroke

SLC17A3 rs9379800 and Ischemic Stroke Susceptibility at the Northern Region of Malaysia

Objectives: The relationships of Paired Like Homeodomain 2 (PITX2), Ninjurin 2 (NINJ2), TWIST-Related Protein 1 (TWIST1), Ras Interacting Protein 1 (Rasip1), Solute Carrier Family 17 Member 3 (SLC17A3), Methylmalonyl Co-A Mutase (MUT) and Fer3 Like BHLH Transcription Factor (FERD3L) polymorphisms and gene expression with ischemic stroke have yet to be determined in Malaysia. Hence, this study aimed to explore the associations of single nucleotide polymorphisms (SNPs) and gene expression with ischemic stroke risk among population who resided at the Northern region of Malaysia. Materials and methods: Study subjects including 216 ischemic stroke patients and 203 healthy controls were recruited upon obtaining ethical clearance. SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism assays. Gene expression levels were quantified by real-time polymerase chain reaction assays. Statistical and genetic analyses were conducted with SPSS version 22.2, PLINK version 1.07 and multifactor dimensionality reduction software. Results: Study subjects with G allele, CG or GG genotypes of SLC17A3 rs9379800 demonstrated increased risk of ischemic stroke with the odds ratios ranging from 1.76-fold to 3.14-fold (p<0.05). When stratified study subjects according to the ethnicity, SLC17A3 rs9379800 G allele and CG genotype contributed to 2.14- and 2.96-fold of ischemic stroke risk among Malay population significantly, in the multivariate analysis (p<0.05). However, no significant associations were observed for PITX2, NINJ2, TWIST1, Rasip1, and MUT polymorphisms with ischemic stroke risk in the multivariate analysis for the pooled cases and controls as well as when stratified them according to the ethnicity. Lower mRNA expression levels of Rasip1, SLC17A3, MUT and FERD3L were observed among cases (p<0.05). After FDR adjustment, the mRNA level of SLC17A3 remained significantly associated with ischemic stroke among Malay population (q=0.034). Conclusion: In conclusion, this study suggests that SLC17A3 rs9379800 polymorphism and its gene expression contribute to significant ischemic stroke risk among Malaysian population, particularly the Malay who resided at the Northern Region of the country. Our findings can provide useful information for the future diagnosis, management and treatment of ischemic stroke patients.</p