Institut Perubatan & Pergigian Termaju - Tesis
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- PublicationRed Blood Cell Transfusion Among Neonatal Sepsis Patients At Hospital Usm(2022-05)Misran, Siti MarlinaINTRODUCTION: The prevalence of neonatal sepsis varies in different countries. It is one of the most common reasons for admission to NICU, and it remains a significant cause of neonatal morbidity and mortality. Neonates represent a frequent group of recipients receiving red blood cell (RBC) transfusion. However, there is limited information about the impact of RBC transfusion among neonates with sepsis in Malaysia. The risk and potential adverse associations with RBC transfusions are poorly described in neonates. This study aimed to explore the clinical characteristics of neonatal sepsis, evaluate the outcomes related to RBC transfusion and assess the factors associated with mortality in neonatal sepsis. METHODS: This case-control retrospective study involved 220 neonates admitted with sepsis in NICU Hospital USM from 2014 until 2019. The association between patients' demographics, clinical characteristics and RBC transfusion with mortality was analysed by logistic regression. RESULTS: Only half (59.5%) of the neonates were delivered prematurely with a gestational age of fewer than 3 7 weeks. Low birth weight neonates were found to have a higher risk for RBC transfusion, with a mean birth weight of2.34 kg. Among 55 (25.0%) neonates who had proven blood culture positive, 43 (39.1 %) of them had RBC transfusion. There were two (1.8%) reported cases of acute transfusion reaction among neonatal sepsis with RBC transfusion. The mean length of stay in NICU for neonatal sepsis with RBC transfusion was prolonged, up to 15 days compared to neonatal sepsis without RBC transfusion, up to 8 days only. About 71 (32.2%) neonates died during hospitalization in the NICU, of which 55 (50.0%) of them were among neonatal sepsis in transfuse group. Mortality among neonatal sepsis was significantly associated with proven positive blood culture, neonatal birth weight and the total number of RBC transfusions, either with two or more than two RBC transfusions (p<0.05). CONCLUSION: Our study was able to prove that proven positive blood culture, neonatal birth weight and the total number of RBC transfusions were significantly associated with mortality among neonatal sepsis. This information can be utilised by clinicians to ensure that any blood transfusion decision is made judiciously in neonates. Regular clinical audit on blood transfusion and appropriate Patient Blood Management among neonates able to reduce neonatal sepsis morbidity and mortality
- PublicationThiolated Alginate- Poly(Lactic-co-glycolic Acid) Aptamer-functionalised As A Tamoxifen-curcumin Nanocarrier Against Resistant Breast Cancer Cell(2023-12)Hock Ing, ChiuBreast cancer therapy often fails due to the development of multidrug resistance (MDR), which is commonly mediated by the overexpression of P glycoprotein (P-gp), a drug efflux transporter presents in the membrane. Traditional drug delivery methods for single-drug chemotherapy have limitations such as low bioavailability, fast clearance, and MDR. Combination chemotherapy has reduced MDR and side effects, but toxicity issues remain a challenge. Targeted drug delivery systems have been developed to overcome drug resistance and improve cancer therapy effectiveness and safety. These systems are safer than conventional therapies and allow for greater drug doses, which is essential for improving efficacy and reducing toxicity. The objective of this project is to create thiolated alginate nanoparticles with the surface fabrication of poly(lactic-co-glycolic acid) (PLGA) and AS1411 aptamer for targeted delivery of tamoxifen (TAM) and curcumin (CUR) to resistant breast cancer cells. The thiolated alginate nanoparticles were prepared under the self-assembly process and further coated with PLGA for biofunctionalisation and a drug protection layer. TAM and CUR were entrapped into AS1411 aptamer and PLGA fabricated thiolated alginate nanoparticles (ACDL and ATDL). ACDL and ATDL nanoparticles showed particle sizes of -16 mV, showing stable nano-sized particles with narrow size distribution. Herein, the entrapment efficiencies of TAM and CUR in ACDL and ATDL nanoparticles were ~40% and 10%, respectively, indicating that the co-entrapment of TAM and CUR in the ACDL and ATDL nanoparticles was successful. The conjugation efficiency of AS1411 aptamer was recorded as >26%, providing cancer targeting for the nanoparticles. The cumulative release of CUR (>44%) and TAM (>65%) reached a plateau at 72 h in ACDL and ATDL nanoparticles, indicating that the ACDL and ATDL nanoparticles exhibited sustained drug release. In vitro studies were performed using MCF-7, MCF-7/TAMR-1, and MCF-7/10A cells. The viability of MCF 7/TAMR-1 cells was significantly lower than MCF-7/10A cells 72 h post treatment with ACDL and ATDL nanoparticles, proving that the nanoparticles were selective against cancer cells over normal cells. ACDL and ATDL nanoparticles also induced early apoptosis and cell cycle arrest at the G0/G1 phase in MCF-7/TAMR-1 cells, showing that the nanoparticles were effectively suppressed the growth of resistant breast cancer cells. The cellular uptake of ACDL and ATDL nanoparticles showed time- and dose-dependent results, with an optimum 2 h incubation and concentration as low as 6.3 µg/mL via nucleolin receptor- and clathrin-mediated endocytosis. ACDL and ATDL nanoparticles suppressed P-gp expression and ATP activity while improving intracellular tamoxifen accumulation and retention. In conclusion, the results suggest that ACDL and ATDL nanoparticles have the potential to be effective anticancer agents for resistant breast cancer therapy by improving drug retention and reducing P-gp expression and ATP activity
- PublicationEvaluation Of Colour Stability, Gloss, Microhardness And Surface Roughness Between Microhybrid And Nano-Based Light Cured Composites In Different Ph Solutions(2024-12)Jasin, Naziah Binti MdNanotechnology in dentistry is not something new. The application of nanotechnology provides many advantages and benefits especially in the production of high-quality restorative materials. Research and continuous improvement are conducted to ensure that the newly developed composite resins have superior characteristics that are resistant to mechanical challenges to remain and sustain in the oral environment for a lifetime. This study aims to evaluate the influence of various types of beverages that are widely used in malaysia on colour stability, surface gloss, microhardness, and surface roughness of contemporary composite resins. A total of 450 samples were fabricated from the three types of composites tested; filtektm 250; filtektm 250 xt; filtektm 350 xt (n=150). All samples were immersed in five immersion solutions consisting of distilled water, artificial saliva, soft drink, energy drink and instant black coffee for 100 days. Findings of this study was analysed using one-way anova and post-hoc test at significant level of p<0.05. The results of the study showed that all the composites immersed in various ph levels experienced a significant change in colour and gloss after the assessment periods of 24 hours, d10, d20, d30, d60 and d100 using a colorimeter and gloss meter. Evaluations of the microhardness level using vickers hardness test was performed at 24 hours, d30 and d100 found that nanofilled composites present a higher strength against mechanical stress compared to microhybrid composites.
- PublicationThe Effects Of Nannochloropsis Sp. Methanolic Extract On Prevention Of Dna Damage In L929 Cells(2023-01)Zainoddin, Ahmad HazwanNannochloropsis and Spirulina are some of microalgae species that have been found to have a wide range of biological activities such as antioxidant and anti-DNA damage properties. Unfortunately, there is still lack of study on the effect of both microalgae especially Nannochloropsis species. Hence, this study was carried out to determine the effect of Nannochloropsis sp. extract on prevention of DNA damage in L929 cell line. The phytochemicals of both microalgae were extracted using 100% methanol. The extractions were then screened with HPLC to detect the presence of targeted compounds. HPLC analysis revealed that Nannochloropsis sp. methanolic extracts had caffeic acid, p-Coumaric acid, naringenin and hesperetin while Spirulina sp. methanolic extract had caffeic acid, quercetin and naringenin. The extracts were then tested for Total Phenolic Content (TPC) and Total Flavonoid Content (TFC). Results revealed that the extracts for both TPC and TFC for Nannochloropsis sp. were higher than Spirulina sp. with 58.43 mg GAE/g and 19.64 mg GAE/g, and 79.87 mg QE/g and 11.19 mg QE/g respectively. The study was then proceeded by evaluating the antioxidant activities of the microalgae extracts using DPPH-HPLC analysis. Nannochloropsis sp. methanolic extract exhibit greater percentage of DPPH inhibition compared to Spirulina sp. extract. A negative correlation existed between TPC and TFC with the EC50 of DPPH antioxidant inhibition activity. In this study, Spirulina sp. and Nannochloropsis sp. showed moderate toxicity toward L929 cell lines with IC50 1.701 mg/mL and 1.134 mg/mL respectively. In DNA damage analysis with Nannochloropsis sp., the result revealed that the methanolic extract are able to prevent and reduce DNA damage activity. Thus, microalgae can be proposed as one of alternative form in medical and pharmaceutical industry.
- PublicationInvestigation On The Radiation Dose Distribution In High Dose Rate (Hdr) Gynaecological Brachytherapy Treatment Using Monte Carlo Calculation(2025-07)Azahari, Ahmad NaqiuddinThis study addresses the research gap by evaluating the influence of tissue heterogeneity and geometric factors on dose distribution, while exploring alternative methods for more accurate dose verification. The purpose of this study was to evaluate dosimetric accuracy in endometrial HDR brachytherapy through experimental and simulation approaches. Specifically, the study aimed to: (1) assess suitable materials for phantom development representing organs at risk (OARs), (2) investigate dose distribution using the constructed phantom, (3)validate Monte Carlo (MC) modelling against experimental measurements, and (4)estimate tissue inhomogeneity correction factors to complement the TG-43 formalism.