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Generation of a novel ex-vivo model to study re-endothelialization

Azman SS, Yazid MD, Abdul Ghani NA, Raja Sabudin RZA, Abdul Rahman MR, Sulaiman N

Artif Cells Nanomed Biotechnol, 2023 Dec;51(1):408-416.
PMID: 37584645 DOI: 10.1080/21691401.2023.2245456

Endothelial dysfunction initiates the pathogenesis of a myriad of cardiovascular diseases, yet the precise underlying mechanisms remain unclear. Current model utilises mechanical denudation of arteries resulting in an arterial-injury model with onset of intimal hyperplasia (IH). Our study shows that 5 min enzymatic denudation of human umbilical artery (hUA) lumen at 37 °C efficiently denudes hUA while maintaining vessel integrity without significantly increase intima-media thickness after 7 days in culture. This ex-vivo model will be a valuable tool in understanding the mechanism of re-endothelialization prior to smooth muscle cells (SMC) activation thus placating IH at an early stage.
Visual loss after long-haul flight

Abdul Ghani NA, Mohd Abdullah AAB, Abdul Hamid S, Yuhana MY, Ramli N

Eur J Ophthalmol, 2020 Oct 19.
PMID: 33070639 DOI: 10.1177/1120672120965499

BACKGROUND: Deep cerebral venous sinus thrombosis is a reversible yet potentially serious thromboembolic event. A number of reports suggest a relationship between long-haul flights and thromboembolic events, mainly deep venous thrombosis (DVT) and pulmonary embolism (PE). It is rarely reported to cause deep cerebral venous sinus thrombosis. We report a case of a bilateral papilledema after long-haul flight secondary to deep cerebral venous sinus thrombosis with subsequent complete recovery post corticosteroid and anticoagulant therapy.
CASE: A case of a 21-year-old woman with no known medical illness who presented with gradual painless bilateral visual loss is described. She had a history of travelling on a long-haul flight 3 weeks prior to presentation. Examination showed presence of bilateral papilloedema, no vitritis, choroiditis and retinitis. Blood investigations showed raised international normalised ratio (INR). Otherwise, workup for infectious causes of optic disc swelling, connective tissue disease screening were normal. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) of the brain showed loss of flow signal in the right transverse sinus and the left sigmoid sinus. Blood workup for preexisting hypercoagulable state was normal. She was diagnosed with deep cerebral venous sinus thrombosis and showed complete recovery with oral corticosteroid and anticoagulant therapy.
CONCLUSION: Deep cerebral venous sinus thrombosis is a potentially serious consequence of long-haul flights. A high index of suspicion along with radiological techniques is needed for early detection and initiation of anticoagulation for this reversible condition.
Fulltext Comparison between AmniSure placental alpha microglobulin-1 rapid immunoassay and standard diagnostic methods for detection of rupture of membranes

Ng BK, Lim PS, Shafiee MN, Ghani NA, Ismail NA, Omar MH, et al.

Biomed Res Int, 2013;2013:587438.
PMID: 24073412 DOI: 10.1155/2013/587438

Objective. To determine the diagnostic accuracy of placental alpha microglobulin-1 assay and standard diagnostic methods for detecting rupture of membrane. Study Design. Prospective diagnostic study, between June 2011 to November 2011 at a tertiary centre. Initial evaluation included both the standard diagnostic methods for rupture of membranes and placental alpha microglobulin-1 immunoassay. The actual rupture of membranes was diagnosed on review of the medical records after delivery (absence of membrane or a positive pad chart). Main Outcome Measures. Placental alpha microglobulin-1 immunoassay and standard diagnostic methods for diagnosis of rupture of membrane. Results. A total of 211 patients were recruited. At initial presentation, 187 patients (88.6%) had ruptured membranes, while 24 patients (11.4%) had intact membranes. Placental alpha microglobulin-1 immunoassay confirmed rupture of membranes at initial presentation with a sensitivity of 95.7% (179 of 187), specificity of 100% (24 of 24), positive predictive value of 100% (179 of 179), and negative predictive value of 75.0% (24 of 32). By comparison, the conventional standard diagnostic methods had a sensitivity of 78.1% (146 of 187), specificity of 100% (24 of 24), positive predictive value of 100% (146 of 146), and negative predictive value of 36.9% (24 of 65) in diagnosing rupture of membrane. Conclusion. Placental alpha-microglobulin-1 immunoassay is a rapid and accurate method for confirming the diagnosis of rupture of membrane. It was superior to conventional standard diagnostic methods (pooling, nitrazine, and ferning), the nitrazine test alone or fern test alone.
Fulltext Health-related quality of life of female patients with congenital adrenal hyperplasia in Malaysia

Zainuddin AA, Grover SR, Abdul Ghani NA, Wu LL, Rasat R, Abdul Manaf MR, et al.

Health Qual Life Outcomes, 2020 Aug 01;18(1):258.
PMID: 32738912 DOI: 10.1186/s12955-020-01515-9

BACKGROUND: This study investigates the health-related quality of life (HRQOL) of female patients with congenital adrenal hyperplasia (CAH) in Malaysia. The objectives were to attain socio-demographic and medical data on these Malaysian females with CAH and establish their health-related quality of life (HRQOL) in comparison to age matched diabetic controls.
METHODS: A cross-sectional study was conducted over 6 months in the two main tertiary centres for CAH patients in Malaysia. Participants including 59 female-raised CAH patients (mean age ± SD = 16.3 ± 4.2 years, range 10-28 years) compared to 57 age-matched female diabetic patients (mean age ± SD = 16.5 ± 3.4 years, range 10-26 years). Socio-demographic and medical profiles was obtained through semi-structured interviews. HRQOL of participants were evaluated utilising validated, Malay translated questionnaires which were age appropriate: Pediatric Quality of Life Inventory (PedsQL v4.0) scales for Child (8-12) and Adolescent (13-18) and Medical Outcome Survey 36-item Short Form version. These were then compared to the diabetic controls.
RESULTS: The CAH participants consisted of children (ages 10-12 years, n = 12), adolescents (ages 13-17 years, n = 29) and adults (≥ 18 years, n = 18). The majority were Malays (64.4%) and had salt-wasting CAH (67.8%). There were no significant differences between the total mean score of the HRQOL of the combined children and adolescents CAH group (total mean score ± SD = 81.6 ± 17.9, 95% CI = 75.6-87.6) when compared to age-matched diabetic patients (total mean score ± SD = 80.8 ± 11.0, 95% CI = 77.0-84.5, P = 0.81, effect size = 0.05); no significant difference between the adult CAH and diabetic controls in the physical [median score (IQR) CAH vs diabetics; 49.3 (11.4) vs. 50.2 (6.1), P = 0.60, effect size = 0.09] and the mental composite scores [median score (IQR) CAH vs. diabetics; 47.8 (14.1) vs. 50.0 (10.8), P = 0.93, effect size = 0.01].
CONCLUSIONS: The HRQOL of the Malaysian CAH cohort were comparable to the diabetic controls.
Ionic liquids toxicity on fresh water microalgae, Scenedesmus quadricauda, Chlorella vulgaris &Botryococcus braunii; selection criterion for use in a two-phase partitioning bioreactor (TPPBR)

Quraishi KS, Bustam MA, Krishnan S, Aminuddin NF, Azeezah N, Ghani NA, et al.

Chemosphere, 2017 Oct;184:642-651.
PMID: 28624742 DOI: 10.1016/j.chemosphere.2017.06.037

A promising method of Carbon dioxide (CO2) valorization is to use green microalgae photosynthesis to process biofuel. Two Phase Partitioning Bioreactors (TPPBR) offer the possibility to use non-aqueous phase liquids (NAPL) to enhance CO2 solubility; thus making CO2 available to maximize algae growth. This requires relatively less toxic hydrophobic Ionic Liquids (ILs) that comprise a new class of ionic compounds with remarkable physicochemical properties and thus qualifies them as NAPL candidates. This paper concerns the synthesis of ILs with octyl and butyl chains as well as different cations containing aromatic (imidazolium, pyridinium) and non-aromatic (piperidinum, pyrrolidinium) rings for CO2 absorption studies. The authors measured their respective toxicity levels on microalgae species, specifically, Scenedesmus quadricauda, Chlorella vulgaris and Botryococcus braunii. Results revealed that octyl-based ILs were more toxic than butyl-based analogues. Such was the case for bmim-PF6 at double saturation with an absorbance of 0.11, compared to Omim-PF6 at 0.17, bmim-NTf2 at 0.02, and Omim-NTf2 at 0.14, respectively. CO2 uptake results for ILs bearing octyl-based chains compared to the butyl analog were 54% (nCO2/nIL) (i.e., moles of CO2 moles of IL) and 38% (nCO2/nIL), respectively. Conclusively, 1-butyl-1-methylpiperidinium absorbed 13% (nCO2/nIL) and appeared the least toxic, having an absorbance of 0.25 at 688 nm (double saturation at 7 d) compared to 1-butyl-3-methylimidazolium, which showed the highest toxicity with zero absorbance. Accordingly, these findings suggest that 1-butyl-1-methylpiperidinium is capable of transporting CO2 to a system containing green microalgae without causing significant harm; thus allowing its use in TPPBR technology.
Reviewing the role of progesterone therapy in endometriosis

Abdul Karim AK, Shafiee MN, Abd Aziz NH, Omar MH, Abdul Ghani NA, Lim PS, et al.

Gynecol Endocrinol, 2019 Jan;35(1):10-16.
PMID: 30044157 DOI: 10.1080/09513590.2018.1490404

Endometriosis is a benign, chronic inflammatory condition characterized by the presence and growth of endometrial implants outside the uterine cavity. The cause of endometriosis is multifactorial. It is due to the diversity of hypothesis and plausibility of hormonal alterations which could play a major role. Evidence has shown that progesterone resistance is a key factor for endometriosis sufferers. Medical therapy can avoid surgical intervention, which may lead to a reduced in ovarian reserve, and its effects of earlier menopause and reduced fecundity. Progesterone receptor isoform has provided new insight as the potential treatment. Progestin, anti-progestin and selective progesterone receptor modulators usage, which target these receptors, could avoid hypo-estrogenic side effects, which can be debilitating. Numerous types of these medications have been used on and off labeled to treat endometriosis with varying success. This review aims to consolidate series of clinical trials using progestins in endometriosis.
Fulltext Vitamin E improved bone strength and bone minerals in male rats given alcohol

Zakaria S, Mat-Husain SZ, Ying-Hwey K, Xin-Kai K, Mohd-Badawi A, Abd-Ghani NA, et al.

Iran J Basic Med Sci, 2017 Dec;20(12):1360-1367.
PMID: 29238472 DOI: 10.22038/IJBMS.2017.9610

Objectives: Alcohol consumption induces oxidative stress on bone, which in turn increases the risk of osteoporosis. This study determined the effects of vitamin E on bone strength and bone mineral content in alcohol-induced osteoporotic rats.
Materials and Methods: Three months old Sprague Dawley male rats were randomly divided into 5 groups: (I) control group; (II) alcohol (3g/kg) + normal saline; (III) alcohol (3g/kg) + olive oil; (IV) alcohol (3g/kg) + alpha-tocopherol (60mg/kg) and (V) alcohol (3g/kg) + palm vitamin E (60mg/kg). The treatment lasted for three months. Following sacrifice, the right tibia was subjected to bone biomechanical test while the lumbar (fourth and fifth lumbar) and left tibia bones were harvested for bone mineral measurement.
Results: Alcohol caused reduction in bone biomechanical parameters (maximum force, ultimate stress, yield stress and Young's modulus) and bone minerals (bone calcium and magnesium) compared to control group (P<0.05). Palm vitamin E was able to improve bone biomechanical parameters by increasing the maximum force, ultimate stress and Young's modulus (P<0.05) while alpha-tocopherol was not able to. Both alpha-tocopherol and palm vitamin E were able to significantly increase tibia calcium and magnesium content while only alpha-tocopherol caused significant increase in lumbar calcium content (P<0.05).
Conclusion: Both palm vitamin E and alpha-tocopherol improved bone mineral content which was reduced by alcohol. However, only palm vitamin E was able to improve bone strength in alcohol treated rats.
Management Options and Outcome of Cerebral Arteriovenous Malformation in Pregnancy: Case Series

Teik CK, Basri NI, Abdul Karim AK, Azrai Abu M, Ahmad MF, Abdul Ghani NA, et al.

Arch Iran Med, 2019 06 01;22(6):340-343.
PMID: 31356101

Cerebral arteriovenous malformation (AVM) is a rare entity with an estimated prevalence of 0.01-0.05% in the general population. We reviewed hospital obstetric records during 2010-2017 and reported a case series of six patients with cerebral AVM in pregnancy, of which five patients had successful pregnancy, and one maternal mortality.
Palatability of black soldier fly larvae in valorizing mixed waste coconut endosperm and soybean curd residue into larval lipid and protein sources

Lim JW, Mohd-Noor SN, Wong CY, Lam MK, Goh PS, Beniers JJA, et al.

J Environ Manage, 2019 Feb 01;231:129-136.
PMID: 30340132 DOI: 10.1016/j.jenvman.2018.10.022

The black soldier fly larvae (BSFL) have been widely extolled for the application in managing various solid organic wastes. Owing to the saprophagous nature of BSFL, a rapid valorization of solid organic wastes can be accomplished with the simultaneous production of valuable biochemical compounds derived from larval biomass. In the present works, the mixed waste coconut endosperm (w-CE) and soybean curd residue (SC-r) substrates with increasing protein nutritional constituent were administered to BSFL. The correlations between protein from larval feed substrates and nutritional profiles of BSFL biomasses were ultimately unveiled. The protein from larval feed substrates could be increased by increasing of SC-r portion against w-CE. At the w-CE:SC-r ratio of 3:2, the highest larval total weight gained and growth rate were attained; indicating an optimum protein nutritional constituent in mixed organics (12.4%) that could enhance the BSFL palatability. Further increment of protein nutritional constituent in mixed organics was found acidifying the residual larval feed substrate progressively, undermining the growth of BSFL. By feeding the BSFL with optimum mixed organics, the maximum accumulations of larval lipid and protein could be achieved. Transesterification of extracted lipid had demonstrated high in monounsaturated fatty acids (73%) which was suitable for biodiesel. The BSFL palatability was finally confirmed from the bioconversion viewpoint of mixed organic wastes. Again, achieving the highest bioconversion efficiency of 14% into larval biomass after accounting the metabolic loss of 54%. Therefore, a total of 68% of mixed w-CE and SC-r could be successfully bioconverted.
The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome--a proof-of-concept study

Shafiee MN, Malik DA, Yunos RI, Atiomo W, Omar MH, Ghani NA, et al.

Gynecol Endocrinol, 2015 Apr;31(4):286-90.
PMID: 25495168 DOI: 10.3109/09513590.2014.989982

The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS). A total of 40 women, aged between 21 and 45 years with PCOS (Rotterdam criteria) were recruited. The participants were assessed at pre- and 3-month-post-Metformin therapy for the menstrual regularities, weight reduction, Ferriman Galway scores, fasting blood glucose (FBG), total cholesterol, LDL, HDL and p53, BCL-2 and cyclin D2 gene expression. Five participants conceived spontaneously after the initial recruitment. Majority (68%) resumed regular menstrual cycles after Metformin. There were significant reduction in BMI (p = 0.001), weight (p = 0.001) and Ferriman Galway scores (p = 0.001). A significant improvement was seen in mean FBG (p = 0.002), total cholesterol (p = 0.001), LDL (p = 0.003) and HDL cholesterol levels (p = 0.015). Tumor suppressor gene (p53) was significantly up-regulated after Metformin (10 out of 14 women), with p value 0.016. BCL-2 and cyclin D2 (oncogenes) were slightly up-regulated without significant difference (p = 0.119 and 0.155, respectively). In conclusion, Metformin therapy improved clinical and metabolic parameters in women with PCOS and up-regulated p53 tumor suppressor gene significantly. Further studies are however required to independently validate our findings.

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