Displaying publications 1 - 20 of 38 in total

Abstract:
Sort:
  1. Yusoh NA, Leong SW, Chia SL, Harun SN, Rahman MBA, Vallis KA, et al.
    ACS Chem. Biol., 2020 02 21;15(2):378-387.
    PMID: 31898884 DOI: 10.1021/acschembio.9b00843
    There is a need to improve and extend the use of clinically approved poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi), including for BRCA wild-type triple-negative breast cancer (TNBC). The demonstration that ruthenium(II) polypyridyl complex (RPC) metallointercalators can rapidly stall DNA replication fork progression provides the rationale for their combination alongside DNA damage response (DDR) inhibitors to achieve synergism in cancer cells. The aim of the present study was to evaluate use of the multi-intercalator [Ru(dppz)2(PIP)]2+ (dppz = dipyrido[3,2-a:2',3'-c]phenazine, PIP = (2-(phenyl)imidazo[4,5-f][1,10]phenanthroline, Ru-PIP) alongside the PARPi olaparib and NU1025. Cell proliferation and clonogenic survival assays indicated a synergistic relationship between Ru-PIP and olaparib in MDA-MB-231 TNBC and MCF7 human breast cancer cells. Strikingly, low dose Ru-PIP renders both cell lines hypersensitive to olaparib, with a >300-fold increase in olaparib potency in TNBC, the largest nongenetic PARPi enhancement effect described to date. A negligible impact on the viability of normal human fibroblasts was observed for any combination tested. Increased levels of DNA double-strand break (DSB) damage and olaparib abrogation of Ru-PIP-activated pChk1 signaling are consistent with PARPi-facilitated collapse of Ru-PIP-associated stalled replication forks. This results in enhanced G2/M cell-cycle arrest, apoptosis, and decreased cell motility for the combination treatment compared to single-agent conditions. This work establishes that an RPC metallointercalator can be combined with PARPi for potent synergy in BRCA-proficient breast cancer cells, including TNBC.
  2. Yusoh NA, Tiley PR, James SD, Harun SN, Thomas JA, Saad N, et al.
    J Med Chem, 2023 May 25;66(10):6922-6937.
    PMID: 37185020 DOI: 10.1021/acs.jmedchem.3c00322
    Synergistic drug combinations can extend the use of poly(ADP-ribose) polymerase inhibitors (PARPi) such as Olaparib to BRCA-proficient tumors and overcome acquired or de novo drug resistance. To identify new synergistic combinations for PARPi, we screened a "micro-library" comprising a mix of commercially available drugs and DNA-binding ruthenium(II) polypyridyl complexes (RPCs) for Olaparib synergy in BRCA-proficient triple-negative breast cancer cells. This identified three hits: the natural product Curcumin and two ruthenium(II)-rhenium(I) polypyridyl metallomacrocycles. All combinations identified were effective in BRCA-proficient breast cancer cells, including an Olaparib-resistant cell line, and spheroid models. Mechanistic studies indicated that synergy was achieved via DNA-damage enhancement and resultant apoptosis. Combinations showed low cytotoxicity toward non-malignant breast epithelial cells and low acute and developmental toxicity in zebrafish embryos. This work identifies RPC metallomacrocycles as a novel class of agents for cancer combination therapy and provides a proof of concept for the inclusion of metallocompounds within drug synergy screens.
  3. Yaghi AR, Shaheed HS, Harun SN, Hyder Ali IA, Khan AH
    Adv Respir Med, 2022 Nov 14;90(6):467-482.
    PMID: 36412638 DOI: 10.3390/arm90060054
    BACKGROUND: Multidrug resistance TB (MDR-TB) has emerged as a public health issue worldwide, and the mortality rate is worrying. Therefore, this study was conducted to investigate the factors related to MDR-TB occurrence and the survival experience of TB patients.

    METHODS: A retrospective cohort study was conducted at Hospital Pulau Pinang in Malaysia. Medical records of active TB patients from 2014-2018 were reviewed. Cox regression was used to identify the factors associated with MDR-TB development and mortality among TB patients.

    RESULTS: The patients had a mean age of 48.84 ± 16.713 years, and a majority of the Chinese race (46.4%). Out of 351 TB patients, 325 (92.6%) were drug-susceptible TB, and 26 (7.4%) were diagnosed with MDR-TB. Among drug-susceptible TB patients, 245 (75.4%) achieved successful outcomes, and 73 (22.5%) passed away. In multivariable Cox regression, drug addiction, levels of white blood cells, urea, platelets, and albumin were significantly associated with death. Relapsed TB, alcohol consumption, and being single were significant risk factors for MDR-TB development.

    CONCLUSION: Patients achieved a success rate of 75.4%, which is encouraging but still far below the WHO target (at least an 85% success rate) and has room for further improvement.

  4. Singh D, Narayanan S, Vicknasingam BK, Prozialeck WC, Ramanathan S, Zainal H, et al.
    J Psychoactive Drugs, 2018 03 20;50(3):266-274.
    PMID: 29558272 DOI: 10.1080/02791072.2018.1443234
    Kratom (Mitragyna speciosa Korth.) is traditionally used in Southeast Asia for its medicinal value and psychoactive properties. Nonetheless, cessation from regular kratom use is reported to cause unpleasant dose-dependent withdrawal symptoms. This study aims to evaluate the severity of pain and sleep problems following the cessation of kratom tea/juice consumption among regular kratom users. A total of 170 regular users were recruited through snowball sampling for this cross-sectional study. The Brief Pain Inventory (BPI) and Pittsburgh Sleep Quality Index (PSQI) scales were administered to assess the severity of pain and sleep problems. Most participants experienced moderate pain intensity (84%) and moderate pain interference (70%) during kratom cessation; 46% experienced more sleep problems during kratom cessation. Individuals who consumed ≥4 glasses of kratom tea/juice (about 76-115 mg of mitragynine) daily had higher odds of reporting some pain interference (OR: 2.0; CI: 1.04-3.93: p 
  5. Siddiqui S, Zainal H, Harun SN, Sheikh Ghadzi SM
    Clin Nutr ESPEN, 2019 02;29:213-223.
    PMID: 30661689 DOI: 10.1016/j.clnesp.2018.10.002
    BACKGROUND: The contribution of dietary factors in the development and progression of pre-diabetes has been increasingly recognized. However, due to high variability in dietary habits measurement of dietary intake remains one of the most challenging tasks in this population. Food frequency questionnaire (FFQ) which investigates usual dietary intake can be used to identify frequent consumption of foods such as dietary fat, fiber, grains that are linked to the risk of pre-diabetes.

    METHOD: This systematic review was conducted to identify and describe FFQs that measure dietary intake of pre-diabetic patients and to examine their relative validity and reliability. The systematic search was done through electronic databases such as PubMed, CINAHL, PsycINFO, ProQuest and Scopus. Methodological quality of included studies and results of study outcome was also summarized in this review.

    RESULT: The search identified 445 papers, of which 18 studies reported 15 FFQs, met inclusion criteria. Most of the FFQs (n = 12) were semi-quantitative while three were frequency measures with portion size estimation of selected food items. Test-retest reliability of FFQ was reported in 7 (38.3%) studies with the correlation coefficient of 0.33-0.92. Relative validity of FFQ was reported in 16 (88.8%) studies with the range of correlation coefficient of 0.08-0.83. Dietary patterns rich in carbohydrate, fat, animal protein and n-3 fatty acids were associated with increased risk of pre-diabetes.

    CONCLUSION: No well-established disease-specific FFQ identified in the literature. Development of a valid, practical and reliable tool is needed for better understanding of the impact of diet in pre-diabetic population.

  6. Siddiqui S, Zainal H, Harun SN, Sheikh Ghadzi SM, Ghafoor S
    Diabetes Metab Syndr, 2020 07 08;14(5):1243-1252.
    PMID: 32688241 DOI: 10.1016/j.dsx.2020.06.069
    BACKGROUND: Prediabetes is a risk state for the future development of type 2 diabetes. Previously, it was evident that the risk factors for diabetes differ by gender. However, conclusive evidence regarding the gender difference in modifiable risk factors associated with the presence of pre-diabetes is still lacking.

    AIMS: To systematically identify and summarize the available literature on whether the modifiable risk factors associated with prediabetes displays similar relationship in both the genders.

    METHODS: A systematic search was performed on electronic databases i.e. PubMed, EBSCOhost, and Scopus using "sex", "gender", "modifiable risk factors" and "prediabetes" as keywords. Reference list from identified studies was used to augment the search strategy. Methodological quality and results from individual studies were summarized in tables.

    RESULTS: Gender differences in the risk factor association were observed among reviewed studies. Overall, reported association between risk factors and prediabetes apparently stronger among men. In particular, abdominal obesity, dyslipidemia, smoking and alcohol drinking habits were risk factors that showed prominent association among men. Hypertension and poor diet quality may appear to be stronger among women. General obesity showed stringent hold, while physical activity not significantly associated with the risk of prediabetes in both the genders.

    CONCLUSIONS: Evidence suggests the existence of gender differences in risk factors associated with prediabetes, demands future researchers to analyze data separately based on gender. The consideration and the implementation of gender differences in health policies and in diabetes prevention programs may improve the quality of care and reduce number of diabetes prevalence among prediabetic subjects.

  7. Siddiqui S, Zainal H, Harun SN, Ghadzi SMS
    Clin Nutr ESPEN, 2020 10;39:165-172.
    PMID: 32859312 DOI: 10.1016/j.clnesp.2020.06.022
    BACKGROUND: Diabetes mellitus is a leading cause of preventable deaths and becomes a major public health concern in Malaysia. Multiple studies have reported the association between diet quality and glycemic parameters among known diabetic subjects. Its influence in individuals with borderline diabetes (i.e. pre-diabetes) or unknown diabetes is still unclear.

    OBJECTIVE: The objective of this study was to assess the association between diet quality evaluated by healthy eating index (HEI) with the glucose outcome in individuals with distinct diabetes progression stages, as well as to identify causal factors in relation to their diabetes status.

    METHOD: A cross-sectional study was conducted at clinical care setting in Universiti Sains Malaysia (USM) between October 2018-March 2019. Normoglycemic controls (n = 47), at-risk of pre-diabetes (n = 58), pre-diabetes (n = 24) as well as individuals with undiagnosed diabetes (n = 18) were queried about their habitual diet by using Food Frequency Questionnaire (FFQ). Correlation analyses were performed to examine the relationship between HEI score and 1) Fasting plasma glucose (FPG) 2) postprandial blood glucose (2-HPP) and glycosylated hemoglobin (HbA1c). Multinomial regression was performed to identify predictors associated with diabetes status of study participants.

    RESULT: Overall, diet quality of study participants was unsatisfactory with the mean score of 58.05 ± 9.07 that need improvement. Total HEI score was negatively correlated with the 2-HPP levels in pre-diabetic patients (r = - 0.45, p = 0.05). No significant association was revealed between glycemic parameters and total HEI score among other groups. Age, body mass index (BMI), triglycerides and female gender were positively correlated with the risk of pre-diabetes, at-risk of pre-diabetes and undiagnosed diabetes (p 

  8. Siddiqui S, Harun SN, Ghadzi SMS, Wahid NA, Hassan AB, Zainal H
    PMID: 38213389 DOI: 10.51866/oa.125
    INTRODUCTION: Diabetes is closely linked to cardiovascular diseases, with diabetic dyslipidaemia serving as an established marker of the acceleration of complications, contributing to an increased cardiovascular risk among patients. Timely detection and early characterization of lipid abnormalities can help clinicians in implementing effective preventive measures. This study aimed to determine the patterns and associated factors of dyslipidaemia among Malaysian subjects with borderline diabetes.

    METHODS: A retrospective study was conducted among subjects with borderline diabetes aged ≥18 years who visited a primary healthcare centre at Universiti Sains Malaysia from January 2017 to December 2018. Sociodemographic, clinical and laboratory data were obtained from electronic medical records. Data were analysed using SPSS version 25.

    RESULTS: A total of 250 participants with borderline diabetes were included in the analysis. Of them, 93.6% (n=234) had lipid abnormalities. Isolated dyslipidaemia characterised by a high low-density lipoprotein cholesterol (LDL-C) level (38.8%, n=97) was the most common pattern found, followed by combined dyslipidaemia of high LDL-C and triglyceride (TG) levels (22.8%, n=57). The male sex was found to be significantly associated with hypertriglyceridemia (adjusted odds ratio [AOR] = 1.86, 95% confidence interval [CI] =1.09-3.1)(P=0.02). Diastolic blood pressure ≥90mmHg was significantly associated with a low HDL-C level (A0R=2.09, 95% CI=1.0-4.1) (P=0.03).

    CONCLUSION: The majority of subjects with borderline diabetes have lipid abnormalities. Specifically, isolated dyslipidaemia characterised by a high LDL-C level is alarmingly prevalent. Further large-scale robust studies are needed to confirm the present findings.

  9. Rehman AU, Hassali MAA, Muhammad SA, Harun SN, Shah S, Abbas S
    Eur J Health Econ, 2020 Mar;21(2):181-194.
    PMID: 31564007 DOI: 10.1007/s10198-019-01119-1
    OBJECTIVES: To find the economic burden of COPD and to identify the key cost drivers in the management of COPD patients across different European countries.

    BACKGROUND: COPD is a major cause of mortality and morbidity and is associated with considerable economic burden on the individual and society. It limits the daily activities and working ability of the patients.

    METHODOLOGY: We conducted a systematic search of PUBMED, SCIENCE DIRECT, Cochrane CENTRAL, SCOPUS, Google Scholar and SAGE Premier Databases to find scientific research articles evaluating the cost of COPD management from patient and societal perspective.

    RESULTS: Estimated per patient per year direct cost in Norway, Denmark, Germany, Italy, Sweden, Greece, Belgium, and Serbia was €10,701, €9580, €7847, €7448, €7045, €2896, €1963, and €2047, respectively. Annual per patient cost of work productivity loss was highest in Germany as €5735 and lowest in Greece as €998. It was estimated as €4824, €2033 and €1298 in Bulgaria, Denmark and Sweden, respectively. Several factors found associated with increasing cost of COPD management that include but not limited to late diagnosis, severity of disease, frequency of exacerbation, hospital readmissions, non-adherence to the therapy and exposure to COPD risk factors.

    CONCLUSION: Minimizing the COPD exacerbations and controlling the worsening of symptoms may potentially reduce the cost of COPD management at any stage.

  10. Rehman AU, Hassali MAA, Harun SN, Abbas S, Muneswarao J, Ali IABH, et al.
    Health Qual Life Outcomes, 2020 May 13;18(1):138.
    PMID: 32404113 DOI: 10.1186/s12955-020-01393-1
    BACKGROUND: Cultural differences affect the administration and results of health status questionnaires. "Cross cultural adaptation" ensures retention of psychometric properties such as validity and reliability at an item and/or scale level.

    OBJECTIVE: To develop a Malaysian version of St George's respiratory COPD specific questionnaire (SGRQ-CM), to evaluate the full spectrum of psychometric properties (reliability, validity and responsiveness), to test the factor structure and to assess minimum clinically important difference for the SGRQ-CM, to be used in population of Malaysia.

    METHODOLOGY: SGRQ-C was translated to Bahasa Malaysia using a standard protocol. 240 COPD patients were included in the study. All patients were followed-up for six months. Construct validity, internal consistency, item convergent validity, test-retest ability, responsiveness, factor analysis and MCID of the Malaysian version of SGRQ-C to be used in population of Malaysia were evaluated.

    RESULTS: The Cronbach alpha coefficient and intraclass correlation coefficients (ICC) for SGRQ-CM were reported as 0.87, and 0.88 respectively. Correlation of SGRQ-CM with CAT, EQ-5D-5 L, mMRC dyspnea scales and FEV1%predicted were reported as 0.86, - 0.82, 0.72 and - 0.42 respectively. Correlation coefficient between the subscales and other clinical and health status measures ranged from r = - 0.35 to r = - 0.87. The MCID was reported as 5.07 (- 2.54-12.67).

    CONCLUSION: The Malaysian version of SGRQ-C has a good psychometric property comparable to those of the original version and has a strong evidence of validity, reliability and responsiveness towards disease severity in Malaysian COPD patients. It can be recommended as a reliable quality of life measure for future research.

  11. Rehman AU, Shah S, Abbas G, Harun SN, Shakeel S, Hussain R, et al.
    Sci Rep, 2021 Jun 30;11(1):13578.
    PMID: 34193949 DOI: 10.1038/s41598-021-92968-5
    Compromised lung function is a common feature of COPD patients, but certain factors increase the rate of lung function decline in COPD patients. The objective of the current study was to investigate the effect of different clinically important factors responsible for rapid deterioration of lung function quantified as ≥ 60 ml decline in FEV1 over a period of one year. COPD patients recruited from the chest clinic of Penang hospital were followed-up for one year from August 2018 to August 2019. Rapid deterioration of lung function was defined as greater than 60 ml/year decline in force expiratory volume in one second. Among 367 included patients 73.84% were male, with mean age 65.26 (9.6) years and % predicted FEV1 51.07 (11.84). 30.27% patients showed mean decline of ≥ 60 ml in FEV1. The regression analysis showed that current smoking relative risk (RR) = 2.38 (1.78-3.07), p 
  12. Phaisal W, Albitar O, Chariyavilaskul P, Jantarabenjakul W, Wacharachaisurapol N, Ghadzi SMS, et al.
    PMID: 38661209 DOI: 10.1093/jac/dkae059
    OBJECTIVES: Twelve weekly doses of rifapentine and isoniazid (3HP regimen) are recommended for TB preventive therapy in children with TB infection. However, they present with variability in the pharmacokinetic profiles. The current study aimed to develop a pharmacokinetic model of rifapentine and isoniazid in 12 children with TB infection using NONMEM.

    METHODS: Ninety plasma and 41 urine samples were collected at Week 4 of treatment. Drug concentrations were measured using a validated HPLC-UV method. MassARRAY® SNP genotyping was used to investigate genetic factors, including P-glycoprotein (ABCB1), solute carrier organic anion transporter B1 (SLCO1B1), arylacetamide deacetylase (AADAC) and N-acetyl transferase (NAT2). Clinically relevant covariates were also analysed.

    RESULTS: A two-compartment model for isoniazid and a one-compartment model for rifapentine with transit compartment absorption and first-order elimination were the best models for describing plasma and urine data. The estimated (relative standard error, RSE) of isoniazid non-renal clearance was 3.52 L·h-1 (23.1%), 2.91 L·h-1 (19.6%), and 2.58 L·h-1 (20.0%) in NAT2 rapid, intermediate and slow acetylators. A significant proportion of the unchanged isoniazid was cleared renally (2.7 L·h-1; 8.0%), while the unchanged rifapentine was cleared primarily through non-renal routes (0.681 L·h-1; 3.6%). Participants with the ABCB1 mutant allele had lower bioavailability of rifapentine, while food prolonged the mean transit time of isoniazid.

    CONCLUSIONS: ABCB1 mutant allele carriers may require higher rifapentine doses; however, this must be confirmed in larger trials. Food did not affect overall exposure to isoniazid and only delayed absorption time.

  13. Mustafa ZU, Khan AH, Salman M, Harun SN, Meyer JC, Godman B, et al.
    J Hosp Infect, 2023 Nov;141:142-151.
    PMID: 37774930 DOI: 10.1016/j.jhin.2023.09.011
    BACKGROUND: Healthcare-associated infections (HAIs) increase morbidity, mortality and costs. The overall prevalence of HAIs is greater in low- and middle-income countries due to poor resources and infrastructure, with the incidence of HAIs greater among neonates and children. There is a need to understand the current situation in Pakistan including key drivers to improve future care.

    METHODS: Point prevalence survey (PPS) of HAIs in the children's wards of 19 public sector secondary- and tertiary-care hospitals of Pakistan and associated key drivers.

    RESULTS: A total of 1147 children were included in the PPS. 35.7% were neonates with 32.8% aged >1-5 years. 35.2% were admitted to the intensive care units (ICUs). Peripheral, central venous and urinary catheters were present in 48%, 2.9% and 5.6% of the patients, respectively. A total of 161 HAIs from various pathogens were observed in 153 cases, giving a prevalence of 13.3%. The majority of HAIs were caused by Staphylococcus aureus (31.7%) followed by Klebsiella pneumoniae (22.9%) and Escherichia coli (17.4%). Bloodstream infections were identified in 42 cases followed by lower-respiratory-tract infections in 35. Increased length of hospital stays and being admitted to the ICU, 'rapidly fatal' patients under the McCabe and Jackson criteria, central and peripheral catheterization, and invasive mechanical ventilation were, associated with higher HAIs (P<0.001). 99.7% of HAI patients fully recovered and were discharged from the hospital.

    CONCLUSION: There is a high prevalence of HAIs among neonates and children admitted to health facilities in Pakistan. Infection prevention and control measures should be implemented to help prevent future HAIs.

  14. Javed S, Mohamed Noor DA, Md Hanafiah NH, Javed U, Mustafa T, Rehman AU, et al.
    J Surg Res, 2024 May 07;299:85-93.
    PMID: 38718688 DOI: 10.1016/j.jss.2024.04.001
    INTRODUCTION: The relationship between type 2 diabetes mellitus (T2DM) and pathological responses after neoadjuvant chemotherapy (NACT) is controversial. In this study, we aim to determine the association of pathological responses in breast cancer women with T2DM after receiving NACT.

    METHODS: Medical records of breast cancer women with T2DM who received NACT from January 2016 to January 2021 at the medical center in the Gujranwala Institute of Nuclear Medicine and Radiotherapy, Pakistan, were identified and retrieved retrospectively. Variables, including pathological responses, diabetes status, and other clinical data, were collected. Patients were grouped as diabetic and nondiabetic based on the doctor's diagnosis or the diabetic's medication history recorded upon the breast cancer diagnosis. Factors influencing the pathological complete response (pCR) were determined using multivariate logistic regression utilizing IBM SPSS Statistics (version 20).

    RESULTS: A total of 1372 patient files who received NACT and breast cancer surgery from January 2016 to January 2021 were selected. Out of 1372 breast cancer women receiving NACT, 345 (25.1%) had pre-existing diabetes, while 1027 (74.85%) were without pre-existing diabetes. The most common molecular subtypes of breast cancer were luminal A and B. Two hundred fifty-eight patients (18.8%) had a pCR after receiving NACT. The pCR in diabetic patients was 3.9%, and in nondiabetes, 14.9%. Most women had a pathological partial response (pPR) after the NACT 672 (48.9%). The pPR in diabetic patients was 11.0%, and in nondiabetic patients, it was 38.0%. In nondiabetics, the odds of achieving pPR increase more than pathological no response after the NACT with odd ratio: 1.71 (95% confidence interval: 1.24-2.37). The probability of pCR in patients with luminal B was 1.67 times higher than that in patients with triple-negative breast cancer with odd ratio: 1.67, 95% confidence interval (1.00-2.79), P = 0.05.

    CONCLUSIONS: The results of the study show that T2DM may have an adverse impact on pCR and pPR following NACT and surgery. Further investigation is needed to explore how changes in blood glucose levels over time impact pathological responses.

  15. Harun SN, Wainwright C, Klein K, Hennig S
    Paediatr Respir Rev, 2016 Sep;20:55-66.
    PMID: 27259460 DOI: 10.1016/j.prrv.2016.03.002
    A systematic review was performed (i) to describe the reported overall rate of progression of CF lung disease quantified as FEV1%predicted decline with age, (ii) to summarise identified influencing risk factors and (iii) to review methods used to analyse CF lung disease progression data. A search of publications providing FEV1%predicted values over age was conducted in PUBMED and EMBASE. Baseline and rate of FEV1%predicted decline were summarised overall and by identified risk factors. Thirty-nine studies were included and reported variable linear rates of lung function decline in patients with CF. The overall weighted mean FEV1%predicted over age was graphically summarised and showed a nonlinear, time-variant decline of lung function. Compared to their peers, Pseudomonas aeruginosa infection and pancreatic insufficiency were most commonly associated with lower baseline and more rapid FEV1%predicted declines respectively. Considering nonlinear models and drop-out in lung disease progression, analysis is lacking and more studies are warranted.
  16. Harun SN, Holford NHG, Grimwood K, Wainwright CE, Hennig S, Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study group
    Thorax, 2019 08;74(8):740-748.
    PMID: 31203197 DOI: 10.1136/thoraxjnl-2018-211548
    BACKGROUND: While Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown.

    AIM: To determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years.

    METHODS: Cross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting Aspergillus at age 5 years. A parametric repeated time-to-event model quantitatively described the risk and factors associated with acquiring Aspergillus and Pseudomonas aeruginosa from birth until age 5 years.

    RESULTS: Cross-sectional analysis found that the number of P. aeruginosa eradication courses increased the odds of detecting Aspergillus at age 5 years (OR 1.61, 95% CI 1.23 to 2.12). The median (IQR) age for the first P. aeruginosa positive culture was 2.38 (1.32-3.79) years and 3.69 (1.68-4.74) years for the first Aspergillus positive culture. The risk of P. aeruginosa and Aspergillus events changes with time after the first year of study entry. It also decreases for P. aeruginosa after completing P. aeruginosa eradication (HR 0.15, 95% CI 0.00 to 0.79), but increases for Aspergillus events (HR 2.75, 95% CI 1.45 to 5.41). The risk of acquiring both types of events increases after having had a previous event.

    CONCLUSION: In young children with CF, completing P. aeruginosa eradication therapy and previous Aspergillus events are associated with increased risk of acquiring Aspergillus.

  17. Harun SN, Ahmad H, Lim HN, Chia SL, Gill MR
    Pharmaceutics, 2021 Jan 24;13(2).
    PMID: 33498795 DOI: 10.3390/pharmaceutics13020150
    The ruthenium polypyridyl complex [Ru(dppz)2PIP]2+ (dppz: dipyridophenazine, PIP: (2-(phenyl)-imidazo[4,5-f ][1,10]phenanthroline), or Ru-PIP, is a potential anticancer drug that acts by inhibiting DNA replication. Due to the poor dissolution of Ru-PIP in aqueous media, a drug delivery agent would be a useful approach to overcome its limited bioavailability. Mesoporous silica nanoparticles (MSNs) were synthesized via a co-condensation method by using a phenanthrolinium salt with a 16 carbon length chain (Phen-C16) as the template. Optimization of the synthesis conditions by Box-Behnken design (BBD) generated MSNs with high surface area response at 833.9 m2g-1. Ru-PIP was effectively entrapped in MSNs at 18.84%. Drug release profile analysis showed that Ru-PIP is gradually released, with a cumulative release percentage of approximately 50% at 72 h. The release kinetic profile implied that Ru-PIP was released from MSN by diffusion. The in vitro cytotoxicity of Ru-PIP, both free and MSN-encapsulated, was studied in Hela, A549, and T24 cancer cell lines. While treatment of Ru-PIP alone is moderately cytotoxic, encapsulated Ru-PIP exerted significant cytotoxicity upon all the cell lines, with half maximal inhibitory concentration (IC50) values determined by MTT (([3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide]) assay at 48 h exposure substantially decreasing from >30 µM to <10 µM as a result of MSN encapsulation. The mechanistic potential of cytotoxicity on cell cycle distribution showed an increase in G1/S phase populations in all three cell lines. The findings indicate that MSN is an ideal drug delivery agent, as it is able to sustainably release Ru-PIP by diffusion in a prolonged treatment period.
  18. Harun SN, Hanafiah MM, Aziz NIHA
    Environ Manage, 2021 Jan;67(1):146-161.
    PMID: 33001258 DOI: 10.1007/s00267-020-01365-7
    This study aims to assess the environmental impacts of conventional and organic rice cultivations and proposes a sustainable conceptual framework of rice farming based on the life cycle assessment (LCA) approach. A cradle-to-gate LCA was performed by using the ReCiPe 2016 method and SimaPro 8.5 software. The functional unit was one ton of rice grains harvested. Primary data were obtained from the farmer, while secondary data were collected from Ecoinvent 3.0, the Agri Footprint 3.0 database and the literature. The total characterization factors for global warming potential (GWP), water consumption potential (WCP) and fossil fuel depletion potential (FFP) were 457.89 kg CO2-eq, 98.18 m3 and 84.56 kg oil-eq, respectively, at the midpoint level for conventional rice, while the impacts for organic rice were 140.55 kg CO2-eq, 29.45 m3 and 22.25 kg oil-eq, respectively. At the endpoint level, the total characterization factors for human health damage (HH), ecosystem damage (ED) and resource availability (RA) for conventional rice were 9.63 × 10-4 DALY, 5.54 × 10-6 species.year and 30.98 Dollar, respectively, while for organic rice, the impacts were 2.60 × 10-4 DALY, 2.28 × 10-6 species.year and 8.44 Dollar, respectively. Rice cultivation impacted the environment, particularly in relation to three impact categories: GWP, WCP and FFP. The cultivation phase of rice production was the main contributor to environmental impacts due to the production and application of fertilizer and pesticides. It can be concluded that the application of LCA in agricultural sector is able to provide information and responses for policy makers in understanding the potential environmental impacts at various spatial levels.
  19. Harun SN, Nordin SA, Gani SSA, Shamsuddin AF, Basri M, Basri HB
    Int J Nanomedicine, 2018;13:2571-2584.
    PMID: 29731632 DOI: 10.2147/IJN.S151788
    Background and aim: Drugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood-brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered.

    Methods: The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties.

    Results: The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of -46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0-
    t
    , prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0-
    t
    , prolonged half-life, and lower clearance as compared to free cefuroxime solution.

    Conclusion: Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.

  20. Harun SN, Wainwright CE, Grimwood K, Hennig S, Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study group
    Thorax, 2019 02;74(2):125-131.
    PMID: 30275132 DOI: 10.1136/thoraxjnl-2018-211550
    BACKGROUND: The impact of Aspergillus on lung disease in young children with cystic fibrosis is uncertain.
    AIMS: To determine if positive respiratory cultures of Aspergillus species are associated with: (1) increased structural lung injury at age 5 years; (2) accelerated lung function decline between ages 5 years and 14 years and (3) to identify explanatory variables.
    METHODS: A cross-sectional analysis of association between Aspergillus positive bronchoalveolar lavage (BAL) cultures and chest high-resolution CT (HRCT) scan findings at age 5 years in subjects from the Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study was performed. A non-linear mixed-effects disease progression model was developed using FEV1% predicted measurements at age 5 years from the ACFBAL study and at ages 6-14 years for these subjects from the Australian Cystic Fibrosis Data Registry.
    RESULTS: Positive Aspergillus BAL cultures at age 5 years were significantly associated with increased HRCT scores for air trapping (OR 5.53, 95% CI 2.35 to 10.82). However, positive Aspergillus cultures were not associated with either FEV1% predicted at age 5 years or FEV1% predicted by age following adjustment for body mass index z-score and hospitalisation secondary to pulmonary exacerbations. Lung function demonstrated a non-linear decline in this population.
    CONCLUSION: In children with cystic fibrosis, positive Aspergillus BAL cultures at age 5 years were associated contemporaneously with air trapping but not bronchiectasis. However, no association was observed between positive Aspergillus BAL cultures on FEV1% predicted at age 5 years or with lung function decline between ages 5 years and 14 years.
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links