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An Unusual Case of Adrenocortical Carcinoma with Multiple Facets

Tan JE, Tan FHS, Kuan YC, Chan PL, Yusri Y

J ASEAN Fed Endocr Soc, 2024;39(2):92-96.
PMID: 39620178 DOI: 10.15605/jafes.039.02.16

Adrenocortical carcinoma (ACC) is a rare malignant tumour from the adrenal cortex. Half of the cases are functional, with ACTH-independent autonomous cortisol production being the most common. It is rare for ACC to present with markedly elevated metanephrine levels, characteristic of pheochromocytoma. We report a case of a large functioning adrenal tumour with overlapping biochemical features of ACC and pheochromocytoma. Biopsy confirmed the histopathological diagnosis of metastatic ACC.
Survey of willingness to participate in clinical trials and influencing factors among cancer and non-cancer patients

King TL, Tan SH, Tan SSN, Lai WH, Bujang MA, Voon PJ

Sci Rep, 2025 Jan 10;15(1):1626.
PMID: 39794348 DOI: 10.1038/s41598-024-83626-7

Despite the expanding landscape of clinical trials, there is a lack of study concerning Malaysian patients' participation and perspectives. This study addresses these gaps by assessing patients' willingness, knowledge, perceptions, confidence, and religious barriers related to clinical trial participations at Sarawak General Hospital. We conducted a cross-sectional survey from March to September 2022 on 763 cancer and non-cancer patients. We collected patients' responses and calculated scores for willingness to participate (40.5/100), knowledge (29.9/100), perceived benefits (66.5/100) and risks (72.4/100) of participations, confidence in clinical trial conducts (66.3/100), and religious barriers (49.8/100). The higher scores indicated greater willingness, better knowledge, stronger perceptions of benefits and risk, increased confidence, and stronger religious barriers. Cancer patient demonstrated significantly greater willingness for trials involving new drugs (31.9/100 vs. 27.4/100, p = 0.021) but slightly higher religious barriers compared to non-cancer cohort (51.4/100 vs. 48.3/100, p = 0.006). Multivariable logistic regression identified female gender, unemployment, poor knowledge, low perceived benefits, high perceived risks, and low confidence as significant factors associated with reduced willingness to participate (p
Efficacy of adjunctive octenidine hydrochloride as compared to chlorhexidine and placebo as adjuncts to instrumentation in stage I-II periodontitis: A double-blinded randomized controlled trial

Rath A, Wong M, Li K, Wong A, Tan L, Tan K, et al.

Int J Dent Hyg, 2024 Nov;22(4):802-813.
PMID: 38461488 DOI: 10.1111/idh.12795

OBJECTIVES: This randomized, controlled, double-blinded clinical trial aimed to evaluate the efficacy of octenidine hydrochloride and chlorhexidine mouthwashes as adjuncts to instrumentation in stage I-II periodontitis patients.
METHODS: Forty-five patients with mild-to-moderate periodontitis were randomly allocated to three groups: 0.1% octenidine dihydrochloride (OCT), placebo, and 0.12% chlorhexidine (CHX) mouthwashes. Patients were instructed to use the mouthwash after instrumentation for twice a day up to 3 weeks. Periodontal parameters such as probing pocket depth (PPD), clinical attachment loss (CAL), O'Leary plaque index (PI), Loe and Silness gingival index (GI), Lobene stain index (SI), and oral soft tissue changes were recorded at baseline and once every week for 3 weeks. The visual analogue scale (VAS) was also recorded as a self-administered questionnaire at the end of the study. The one-way ANOVA was used to compare VAS scores between the groups. The repeated measures ANOVA and post hoc Newman-Keuls tests were used to assess the differences in the periodontal parameters between groups at different time intervals. The Kruskal-Wallis test was used to compare the mean SI.
RESULTS: There was a significant reduction in the mean GI of the OCT and CHX groups compared to placebo (p
Neuroinvasion via Peripheral Nerves in Epidemic Viral Encephalitis Caused by Enterovirus, Orthoflavivirus and SARS-Coronavirus

Hooi YT, Fu TL, Tan SH, Ong KC, Tan CY, Wong KT

Neuropathol Appl Neurobiol, 2025 Feb;51(1):e70005.
PMID: 39989030 DOI: 10.1111/nan.70005

Pathogens invade the central nervous system (CNS) and cause infections either through the haematogenous route or via peripheral nerves. Neuroinvasion via peripheral nerves, involving spinal or cranial somatic nerves, is well-established for certain viral encephalitides such as rabies, herpes simplex encephalitis, and poliomyelitis. Advances in understanding emerging and re-emerging viruses that cause epidemic CNS infections have highlighted the growing importance of peripheral nerve pathways in viral neuroinvasion. This review focuses on epidemic viral encephalitides caused by three groups of RNA viruses, viz., enteroviruses (enterovirus A71 and enterovirus D68), orthoflaviviruses (West Nile virus and Japanese encephalitis virus), and severe acute respiratory syndrome coronaviruses (mainly severe acute respiratory coronavirus-2). We examine evidence supporting the hypothesis that peripheral nerve viral transmission may play an increasingly significant if not more critical role than the haematogenous route in neuroinvasion.
Fulltext Parkinson's disease tremor prediction towards real-time suppression: A self-attention deep temporal convolutional network approach

Tan GY, Bakibillah ASM, Chan PY, Tan CP, Nurzaman S

Comput Biol Med, 2025 Apr;188:109814.
PMID: 39978094 DOI: 10.1016/j.compbiomed.2025.109814

Accurate prediction of Parkinson's disease tremor (PDT) is crucial for developing assistive technologies; however, this is challenging due to the nonlinear, stochastic, and nonstationary characteristics of PDT, which substantially vary among patients and their activities. Moreover, most models only have one-step prediction capabilities, which causes delays in real-time applications. This paper proposes a self-attention deep temporal convolutional network (SADTCN) model for the real-time prediction of hand-arm PDT signals from different activities and joint angular motions. The SADTCN can capture both short- and long-term dependencies and complex temporal and spatial dynamics of PDT signals and hence, can effectively adapt to varying tremor characteristics. The performance of the proposed model is evaluated using experimental hand-arm PDT data. The results show that the SADTCN outperforms existing deep learning (DL) models by accurately predicting varying tremor amplitudes and frequencies multi-step ahead. Moreover, we performed spectrum analysis on the measured and predicted signal using the short-time Fourier transform (STFT) as a measure of potential active tremor control and found that SADTCN can accurately determine the transience of tremor amplitude in frequency and time. Finally, we run the Wilcoxon signed-rank statistical test and the results show a statistically significant improvement in the proposed model over the other DL models in all conditions. Therefore, the SADTCN can overcome the nonstationary, nonlinear, and stochastic nature of PDT to perform multi-step prediction with high accuracy, robustness, and generalizability in unseen testing data.
Fulltext Clinical and Radiological Outcomes of Extreme Lateral Interbody Fusion (XLIF) in the Treatment of Lumbar Spondylodiscitis: A Multi-center Study

Tan Y, Mohamed Ramlee FA, Harun MH, Jaapar MS, Tan CN

Cureus, 2024 Dec;16(12):e76356.
PMID: 39866983 DOI: 10.7759/cureus.76356

Introduction Lumbar pyogenic spondylodiscitis is a challenging and rare spinal infection with high morbidity, particularly in patients with comorbidities. While the extreme lateral interbody fusion (XLIF) technique is established in treating degenerative spinal conditions, its efficacy in managing spondylodiscitis is less well-studied. This study aims to evaluate the clinical and radiographic outcomes of the XLIF approach combined with posterior instrumentation in patients with lumbar spondylodiscitis. Method In a multi-center, retrospective cohort study, 15 patients (mean age 66; 62.5% male) diagnosed with pyogenic spondylodiscitis underwent XLIF with posterior percutaneous fixation between January 2018 and December 2022 at two Malaysian hospitals. Patients were selected based on strict inclusion criteria, including a confirmed single-level disc infection and a minimum follow-up of one year. Clinical outcomes, including Visual Analog Scale (VAS) pain scores, infection markers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC)), and fusion rates, were recorded preoperatively and at six weeks, three months, six months, and one year postoperatively. Data were analyzed using appropriate statistical tests, with a significance level set at p<0.05. Results The study demonstrated a significant reduction in VAS scores, from a mean of 7 preoperatively to 1.87 at six weeks postoperatively, representing a 73.3% pain reduction (p<0.005). Mean blood loss was minimal (193.3 mL), and no patients required transfusions. Marked reductions in inflammatory markers were observed, with CRP, ESR, and WBC levels decreasing by 75%, 71.5%, and 38.5%, respectively, within the first six weeks (p<0.005). Radiological assessment showed a 100% fusion rate with a mean fusion time of 4.1 months. Complications were low, with only one case of screw malposition and one surgical site infection, both managed without further morbidity. Conclusion The XLIF approach with posterior instrumentation is a safe and effective intervention for lumbar spondylodiscitis, providing substantial pain relief, infection control, and reliable spinal fusion. These findings suggest XLIF as a viable surgical option for lumbar spondylodiscitis, especially for patients with multiple comorbidities, warranting consideration as a primary surgical strategy for this challenging condition.
Fulltext Assessment of Opuntia ficus-indica supplementation on enhancing antioxidant levels

Zaman R, Tan ESS, Bustami NA, Amini F, Seghayat MS, Ho YB, et al.

Sci Rep, 2025 Jan 28;15(1):3507.
PMID: 39875543 DOI: 10.1038/s41598-025-87680-7

Opuntia ficus-indica (OFi) is a major fruit source prevalent in semiarid and arid regions across various countries worldwide. It is widely recognised for its potential health benefits; however, most studies investigating its effects have been limited to pre-clinical models, highlighting the need for further validation through clinical trials. This study aimed to evaluate the effectiveness of OFi supplementation in enhancing antioxidant levels. Fifty healthy participants, aged 18 years and older, including males and females, received a daily OFi supplement of 1500 mg for 3 months. These findings revealed a significant 48.1% increase in salivary total antioxidant capacity (TAC) (P
Amogel: a multi-omics classification framework using associative graph neural networks with prior knowledge for biomarker identification

Tan CY, Ong HF, Lim CH, Tan MS, Ooi EH, Wong K

BMC Bioinformatics, 2025 Mar 28;26(1):94.
PMID: 40155814 DOI: 10.1186/s12859-025-06111-6

The advent of high-throughput sequencing technologies, such as DNA microarray and DNA sequencing, has enabled effective analysis of cancer subtypes and targeted treatment. Furthermore, numerous studies have highlighted the capability of graph neural networks (GNN) to model complex biological systems and capture non-linear interactions in high-throughput data. GNN has proven to be useful in leveraging multiple types of omics data, including prior biological knowledge from various sources, such as transcriptomics, genomics, proteomics, and metabolomics, to improve cancer classification. However, current works do not fully utilize the non-linear learning potential of GNN and lack of the integration ability to analyse high-throughput multi-omics data simultaneously with prior biological knowledge. Nevertheless, relying on limited prior knowledge in generating gene graphs might lead to less accurate classification due to undiscovered significant gene-gene interactions, which may require expert intervention and can be time-consuming. Hence, this study proposes a graph classification model called associative multi-omics graph embedding learning (AMOGEL) to effectively integrate multi-omics datasets and prior knowledge through GNN coupled with association rule mining (ARM). AMOGEL employs an early fusion technique using ARM to mine intra-omics and inter-omics relationships, forming a multi-omics synthetic information graph before the model training. Moreover, AMOGEL introduces multi-dimensional edges, with multi-omics gene associations or edges as the main contributors and prior knowledge edges as auxiliary contributors. Additionally, it uses a gene ranking technique based on attention scores, considering the relationships between neighbouring genes. Several experiments were performed on BRCA and KIPAN cancer subtypes to demonstrate the integration of multi-omics datasets (miRNA, mRNA, and DNA methylation) with prior biological knowledge of protein-protein interactions, KEGG pathways and Gene Ontology. The experimental results showed that the AMOGEL outperformed the current state-of-the-art models in terms of classification accuracy, F1 score and AUC score. The findings of this study represent a crucial step forward in advancing the effective integration of multi-omics data and prior knowledge to improve cancer subtype classification.
Fulltext A physician-pharmacist partnership intervention for deprescribing (P3iD) among older adults attending a falls and syncope clinic: Protocol for a randomised controlled trial

Goh SSL, Lai PSM, Ramdzan SN, Tan KM, Goh AMC, Tan MP

PLoS One, 2025;20(6):e0324565.
PMID: 40460375 DOI: 10.1371/journal.pone.0324565

BACKGROUND: The concept of deprescribing is gaining traction among clinicians as a formalized approach to improving medication safety for older persons. It has been found to be safe and effective in reducing medication burden. However, its implementation remains challenging. Most research has been conducted in high-income countries, with limited prospective data on deprescribing outcomes in outpatient care settings for older adults in low- and middle-income countries (LMICs). Therefore, evaluating local deprescribing interventions is essential to produce evidence on their effectiveness in older populations. Our study aimed to assess the effectiveness of the Physician-Pharmacist Partnership Intervention for Deprescribing (P3ID) among older persons attending a falls and syncope clinic.
METHODS: This randomised controlled trial will be conducted at a teaching hospital in Kuala Lumpur, Malaysia. Participants will involve individuals aged ≥60 years with at least one chronic disease requiring pharmacological treatment, attending the falls and syncope clinic with ≥1 potentially inappropriate medication (PIM) undergoing systematic multidomain assessment and attending physicians at the clinic. The joint pharmacist-physician intervention comprises five steps: 1) PIM identification, 2) decision on cessation and prioritisation, 3) medication withdrawal, 4) monitoring and support, 5) and documentation.
CONCLUSION: The P3ID trial tests the hypothesis that a jointly led pharmacist-physician intervention in an outpatient will reduce the total number of medications, improve medication adherence, reduce falls and improve patients' and doctors' satisfaction towards pharmacist services. Findings from this study would inform future deprescribing practices, particularly in LMIC, pertaining to fall prevention as well as aid the development of future deprescribing interventions in other settings.
Effects of Phomopsidione on the Viability, Virulence, and Metabolites Profile of Methicillin-Resistant Staphylococcus aureus (MRSA)

Wei YM, Tong WY, Tan JS, Lim V, Leong CR, Tan WN

Curr Microbiol, 2024 Mar 10;81(4):108.
PMID: 38461425 DOI: 10.1007/s00284-024-03627-7

Methicillin-resistant Staphylococcus aureus (MRSA) infections have become one of the most threatening multidrug-resistant pathogens. Thus, an ongoing search for anti-MRSA compounds remains an urgent need to effectively treating MRSA infections. Phomopsidione, a novel antibiotic isolated from Diaporthe fraxini, has previously demonstrated potent anti-candidal activity. The present study aimed to investigate the effects of phomopsidione on the viability, virulence, and metabolites profile of MRSA. MRSA was sensitive to phomopsidione in a concentration-dependent manner. Phomopsidione exhibited minimum inhibitory concentration and minimum bactericidal concentration of 62.5 and 500.00 µg/mL against MRSA on broth microdilution assay. The compound showed significant reduction in virulence factors production including extracellular polymeric substances quantification, catalase, and lipase. An untargeted metabolomics analysis using liquid chromatography-high resolution mass spectrometry revealed a significant difference in the metabolites profile of MRSA with 13 putatively identified discriminant metabolites. The present study suggested the potential of phomopsidione as a promising anti-MRSA agent.
A multi-center cross-sectional comparison of parent-reported quality of life and bowel function between anorectal malformation and Hirschsprung's disease patients with versus those without Down syndrome

Rajasegaran S, Ahmad NA, Tan SK, Lechmiannandan A, Tan YW, Sanmugam A, et al.

Pediatr Surg Int, 2024 Jul 24;40(1):209.
PMID: 39046543 DOI: 10.1007/s00383-024-05792-z

PURPOSE: Down syndrome (DS) is a common abnormality associated with anorectal malformation (ARM) and Hirschsprung's disease (HD). However, quality of life (QOL) in ARM and HD patients with DS is under-researched. This study compares parent-reported QOL and bowel function in ARM and HD patients with DS to those without.
METHODS: Between December 2020 to February 2023, parents of ARM and HD patients with and without DS aged 3-17 years who had undergone surgery > 12 months prior at four tertiary referral centers were recruited. We used the Pediatric Quality of Life Inventory™ (PedsQL™) Generic Core Scales, General Well-Being (GWB) Scale and Family Impact (FI) Module questionnaires, and the Rintala bowel function score (BFS).
RESULTS: There were 101 ARM, 9 (8.9%) of whom had DS; and 87 HD, of whom 6 (6.9%) had DS. Parent-reported Core scores in ARM and HD with DS were comparable to those without DS. However, ARM and HD with DS had worse scores in the FI Module and bowel function than those without DS.
CONCLUSION: Although parent-reported QOL in ARM and HD with DS is similar to those without DS, family impact and BFS are worse. Our findings are limited by small sample size in proportion of DS patients.
Fulltext Optical and Electrical Characteristics of Silicon Nanowires Prepared by Electroless Etching

Hutagalung SD, Fadhali MM, Areshi RA, Tan FD

Nanoscale Res Lett, 2017 Dec;12(1):425.
PMID: 28651386 DOI: 10.1186/s11671-017-2197-3

Silicon nanowires (SiNWs) were fabricated by the electroless etching of an n-type Si (100) wafer in HF/AgNO3. Vertically aligned and high-density SiNWs are formed on the Si substrates. Various shapes of SiNWs are observed, including round, rectangular, and triangular. The recorded maximum reflectance of the SiNWs is approximately 19.2%, which is much lower than that of the Si substrate (65.1%). The minimum reflectance of the SiNWs is approximately 3.5% in the near UV region and 9.8% in the visible to near IR regions. The calculated band gap energy of the SiNWs is found to be slightly higher than that of the Si substrate. The I-V characteristics of a freestanding SiNW show a linear ohmic behavior for a forward bias up to 2.0 V. The average resistivity of a SiNW is approximately 33.94 Ω cm.
An analysis of genetic association in opioid dependence susceptibility

Nagaya D, Zahari Z, Saleem M, Yahaya BH, Tan SC, Yusoff NM

J Clin Pharm Ther, 2018 Feb;43(1):80-86.
PMID: 28656735 DOI: 10.1111/jcpt.12585

WHAT IS KNOWN: Drug addiction is a novelty-seeking personality trait that is associated with the candidate genes OPRD1 (opioid delta receptors), OPRK1 (opioid kappa receptors) and PDYN (prodynorphin). However, associations between single nucleotide polymorphisms (SNPs) rs1042114 (80G>T) of the OPRD1 gene, rs702764 (843 A>G) of the OPRK1 gene, and rs910080 (3' UTR _743T>C), rs1997794 (5' UTR -381A>G) and rs1022563 (3' UTR) of the PDYN gene and novelty seeking remain controversial as reported results have not been reproducible.
OBJECTIVE: The goal of this study was to determine the frequencies of SNPs rs1042114, rs702764, rs1997794, rs1022563 and rs910080 in the Malaysian population and to study their association with opioid dependence in Malaysian Malays.
METHODS: A total of 459 Malay male with opioid dependence and 543 healthy male (controls) subjects were included in this study. SNPs were genotyped using the TaqMan SNP genotyping assay. Statistical analysis was performed using Golden Helix SVS software suite to identify the distribution of allele and genotype frequencies, and SNP-SNP interactions were also analysed in this study.
RESULTS AND DISCUSSION: SNP rs1042114 in the OPRD1 gene is strongly associated with opiate addiction (P=.0001). In individuals homozygous for this risk allele, the likelihood of opiate addiction is increased by a factor 1.62 (95% confidence interval (CI) 1.412-1.875). Polymorphic alleles at SNP rs702764 of OPRK1 were not associated with opioid dependence. A significant association between opioid dependence and SNP rs910080 of PDYN (P=.0217) was detected, but there was no association for SNPs rs199774 and rs1022563. A significant interaction was also identified between homozygous wild-type genotype TT of rs702764 with the risk genotypes TG/GG of rs1042114 (odds ratio (OR)=2.111 (95% CI 1.227-3.631), P=.0069) and with the risk genotypes GA/AA of rs910080 (OR=1.415 (95% CI 1.04-1.912), P=.0239).
WHAT IS NEW AND CONCLUSION: The results indicate that SNPs rs1042114 and rs910080 contribute to vulnerability to opioid dependence in the Malaysian Malay population. These results will help us to understand the effect of the SNPs and the SNP-SNP interaction on opioid dependence and may assist in efforts to screen vulnerable individuals and match them with individually tailored prevention and treatment strategies.
Pattern of skin diseases among patients attending an outpatient dermatology clinic in a tertiary hospital in urban Malaysia

Kwan Z, Wong SM, Robinson S, Tan LL, Ismail R

Australas J Dermatol, 2017 Nov;58(4):e267-e268.
PMID: 28660702 DOI: 10.1111/ajd.12541
Fulltext The Impact of Self-Reported Sleep on Caesarean Delivery in Women Undergoing Induction of Labour: A Prospective Study

Teong ACA, Diong AX, Omar SZ, Tan PC

Sci Rep, 2017 09 26;7(1):12339.
PMID: 28951578 DOI: 10.1038/s41598-017-12410-7

216 women admitted for labour induction were recruited to evaluate sleep duration and other sleep measures on Caesarean delivery risk. The Pittsburgh Sleep Quality Index, Berlin (Obstructive Sleep Apnoea (OSA), Epworth Sleepiness Scale, International Restless Leg Syndrome, Insomnia Symptom Questionnaires were applied. Short sleep duration was defined as reported night sleep length in the previous month below the study population median of 6 hours. After binomial analysis, Caesarean delivery after labour induction is associated with short sleep duration (RR 1.8, 95% CI 1.1-2.9, P = 0.018), nulliparity, Bishop Score, prepregnant BMI and birth weight at P
Call for Caution: Neonatal Portal Vein Thrombosis following Enbucrilate Embolization of Placental Chorioangioma

Voon HY, Amin R, Kok JL, Tan KS

Fetal Diagn Ther, 2018;43(1):77-80.
PMID: 28796996 DOI: 10.1159/000479105

We illustrate a case of giant placental chorioangioma presenting at 20 weeks of gestation. Subsequent monitoring revealed enlargement of the lesion, associated with fetal anemia and cardiac failure, prompting in utero intervention. Amnioreduction followed by percutaneous embolization of the tumour with enbucrilate:Lipiodol Ultra-Fluid™ at a dilution of 1:5 was successfully performed. No repeat intervention or additional supportive measures were required throughout pregnancy and the baby was delivered at 36 weeks of gestation, following spontaneous labour. Due to prolonged neonatal jaundice, further investigations were undertaken, demonstrating subacute right portal vein thrombosis. Other previously reported causes of neonatal portal vein thrombosis such as umbilical vein thrombosis, neonatal umbilical vein catheterization, thrombophilia and sepsis were excluded. There was resolution of the thrombus by 6 months of life. A brief discussion of measures to minimize the risk of such an event and the long-term outcomes of neonatal portal vein thrombosis was included. Whilst the simplicity and efficacy of the procedure has been demonstrated in a handful of patients, judgment on its safety is best deferred. Counselling should be comprehensive, as even rare complications can result in significant postnatal morbidity.
Fulltext Optimization of enzymatic esterification of dihydrocaffeic acid with hexanol in ionic liquid using response surface methodology

Gholivand S, Lasekan O, Tan CP, Abas F, Wei LS

Chem Cent J, 2017 May 26;11(1):44.
PMID: 29086827 DOI: 10.1186/s13065-017-0276-2

BACKGROUND: Developing an efficient lipophilization reaction system for phenolic derivatives could enhance their applications in food processing. Low solubility of phenolic acids reduces the efficiency of phenolic derivatives in most benign enzyme solvents. The conversion of phenolic acids through esterification alters their solubility and enhances their use as food antioxidant additives as well as their application in cosmetics.
RESULTS: This study has shown that lipase-catalyzed esterification of dihydrocaffeic acid with hexanol in ionic liquid (1-butyl-3-methylimidazoliumbis (trifluoromethylsulfonyl) imide) was the best approach for esterification reaction. In order to achieve the maximum yield, the process was optimized by response surface methodology (RSM) based on a five-level and four independent variables such as: dosage of enzyme; hexanol/dihydrocaffeic acid mole ratio; temperature and reaction time. The optimum esterification condition (Y = 84.4%) was predicted to be obtained at temperature of 39.4 °C, time of 77.5 h dosage of enzyme at 41.6% and hexanol/dihydrocaffeic acid mole ratio of 2.1.
CONCLUSION: Finally, this study has produced an efficient enzymatic esterification method for the preparation of hexyl dihydrocaffeate in vitro using a lipase in an ionic liquid system. Concentration of hexanol was the most significant (p
Characterisation, in-vitro and in-vivo evaluation of valproic acid-loaded nanoemulsion for improved brain bioavailability

Tan SF, Kirby BP, Stanslas J, Basri HB

J Pharm Pharmacol, 2017 Nov;69(11):1447-1457.
PMID: 28809443 DOI: 10.1111/jphp.12800

OBJECTIVE: This study was aimed to investigate the potential of formulated valproic acid-encapsulated nanoemulsion (VANE) to improve the brain bioavailability of valproic acid (VPA).
METHODS: Valproic acid-encapsulated nanoemulsions were formulated and physically characterised (osmolarity, viscosity, drug content, drug encapsulation efficiency). Further investigations were also conducted to estimate the drug release, cytotoxic profile, in-vitro blood-brain barrier (BBB) permeability, pharmacokinetic parameter and the concentration of VPA and VANE in blood and brain.
KEY FINDINGS: Physical characterisation confirmed that VANE was suitable for parenteral administration. Formulating VPA into nanoemulsion significantly reduced the cytotoxicity of VPA. In-vitro drug permeation suggested that VANEs crossed the BBB as freely as VPA. Pharmacokinetic parameters of VANE-treated rats in plasma and brain showed F3 VANE had a remarkable improvement in AUC, prolongation of half-life and reduction in clearance compared to VPA. Given the same extent of in-vitro BBB permeation of VPA and VANE, the higher bioavailability of VANE in brain was believed to have due to higher concentration of VANE in blood. The brain bioavailability of VPA was improved by prolonging the half-life of VPA by encapsulating it within the nanoemulsion-T80.
CONCLUSIONS: Nanoemulsion containing VPA has alleviated the cytotoxic effect of VPA and improved the plasma and brain bioavailability for parenteral delivery of VPA.
In Vitro Biodegradation of Hepatotoxic Indospicine in Indigofera spicata and Its Degradation Derivatives by Camel Foregut and Cattle Rumen Fluids

Tan ETT, Al Jassim R, D'Arcy BR, Fletcher MT

J Agric Food Chem, 2017 Aug 30;65(34):7528-7534.
PMID: 28787565 DOI: 10.1021/acs.jafc.7b02492

The known accumulation of the hepatotoxin indospicine in tissues of camels and cattle grazing Indigofera pasture plants is unusual in that free amino acids would normally be expected to be degraded during the fermentation processes in these foregut fermenters. In this study, in vitro experiments were carried out to examine the degradability of indospicine of Indigofera spicata by camel and cattle foregut microbiota. In the first experiment, a 48 h in vitro incubation was carried out using foregut fluid samples that were collected from 15 feral camels and also a fistulated cow. Degradability of indospicine ranged between 97% and 99%, with the higher value of 99% for camels. A pooled sample of foregut fluids from three camels that were on a roughage diet was used in a second experiment to examine the time-dependent degradation of indospicine present in the plant materials. Results indicated that camels' foregut fluids have the ability to biodegrade ∼99% of the indospicine in I. spicata within 48 h of incubation and produced 2-aminopimelamic acid and 2-aminopimelic acid. The time-dependent degradation analysis showed rapid indospicine degradation (65 nmol/h) during the first 8-18 h of incubation followed by a slower degradation rate (12 nmol/h) between 18 and 48 h. Indospicine degradation products were also degraded toward the end of the experiment. The results of these in vitro degradation studies suggest that dietary indospicine may undergo extensive degradation in the foregut of the camel, resulting in trace levels after 48 h. The retention time for plant material in the camel foregut varies depending on feed quality, and the results of this study together with the observed accumulation of indospicine in camel tissues suggest that, although indospicine can be degraded by foregut fermentation, this degradation is not complete before the passage of the digesta into the intestine.
Fulltext Genomic Comparisons Reveal Microevolutionary Differences in Mycobacterium abscessus Subspecies

Tan JL, Ng KP, Ong CS, Ngeow YF

Front Microbiol, 2017;8:2042.
PMID: 29109707 DOI: 10.3389/fmicb.2017.02042

Mycobacterium abscessus, a rapid-growing non-tuberculous mycobacterium, has been the cause of sporadic and outbreak infections world-wide. The subspecies in M. abscessus complex (M. abscessus, M. massiliense, and M. bolletii) are associated with different biologic and pathogenic characteristics and are known to be among the most frequently isolated opportunistic pathogens from clinical material. To date, the evolutionary forces that could have contributed to these biological and clinical differences are still unclear. We compared genome data from 243 M. abscessus strains downloaded from the NCBI ftp Refseq database to understand how the microevolutionary processes of homologous recombination and positive selection influenced the diversification of the M. abscessus complex at the subspecies level. The three subspecies are clearly separated in the Minimum Spanning Tree. Their MUMi-based genomic distances support the separation of M. massiliense and M. bolletii into two subspecies. Maximum Likelihood analysis through dN/dS (the ratio of number of non-synonymous substitutions per non-synonymous site, to the number of synonymous substitutions per synonymous site) identified distinct genes in each subspecies that could have been affected by positive selection during evolution. The results of genome-wide alignment based on concatenated locally-collinear blocks suggest that (a) recombination has affected the M. abscessus complex more than mutation and positive selection; (b) recombination occurred more frequently in M. massiliense than in the other two subspecies; and (c) the recombined segments in the three subspecies have come from different intra-species and inter-species origins. The results lead to the identification of possible gene sets that could have been responsible for the subspecies-specific features and suggest independent evolution among the three subspecies, with recombination playing a more significant role than positive selection in the diversification among members in this complex.

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