Displaying publications 1 - 20 of 68 in total

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  1. Ramanathan S, Gopinath SCB, Arshad MKM, Poopalan P, Anbu P
    Mikrochim Acta, 2019 07 18;186(8):546.
    PMID: 31321546 DOI: 10.1007/s00604-019-3696-y
    A genomic DNA-based colorimetric assay is described for the detection of the early growth factor receptor (EGFR) mutation, which is the protruding reason for non-small cell lung cancer. A DNA sequence was designed and immobilized on unmodified gold nanoparticles (GNPs). The formation of the respective duplex indicates the presence of an EGFR mutation. It is accompanied by the aggregation of the GNPs in the presence of monovalent ions, and it indicates the presence of an EGFR mutation. This is accompanied by a color change from red (520 nm) to purple (620 nm). Aggregation was evidenced by transmission electron microscopy, scanning electron microscopy and atomic force microscopy. The limit of detection is 313 nM of the mutant target strand. A similar peak shift was observed for 2.5 μM concentrations of wild type target. No significant peak shift was observed with probe and non-complementary DNA. Graphical abstract Schematic representation of high-specific genomic DNA sequence on gold nanoparticle (GNP) aggregation with sodium chloride (NaCl). It illustrates the detection method for EGFR mutation on lung cancer detection. Red and purple colors of tubes represent dispersed and aggregated GNP, respectively.
  2. Gopinath SCB, Ramanathan S, More M, Patil K, Patil SJ, Patil N, et al.
    Curr Med Chem, 2023 Sep 12.
    PMID: 37702170 DOI: 10.2174/0929867331666230912101634
    The engineering of nanoscale materials has broadened the scope of nanotechnology in a restricted functional system. Today, significant priority is given to immediate health diagnosis and monitoring tools for point-of-care testing and patient care. Graphene, as a one-atom carbon compound, has the potential to detect cancer biomarkers and its derivatives. The atom-wide graphene layer specialises in physicochemical characteristics, such as improved electrical and thermal conductivity, optical transparency, and increased chemical and mechanical strength, thus making it the best material for cancer biomarker detection. The outstanding mechanical, electrical, electrochemical, and optical properties of two-dimensional graphene can fulfil the scientific goal of any biosensor development, which is to develop a more compact and portable point-of-care device for quick and early cancer diagnosis. The bio-functionalisation of recognised biomarkers can be improved by oxygenated graphene layers and their composites. The significance of graphene that gleans its missing data for its high expertise to be evaluated, including the variety in surface modification and analytical reports. This review provides critical insights into graphene to inspire research that would address the current and remaining hurdles in cancer diagnosis.
  3. Ramanathan S, Karupiah S, Nair NK, Olliaro PL, Navaratnam V, Wernsdorfer WH, et al.
    PMID: 16046285
    A new approach using a simple solid-phase extraction technique has been developed for the determination of pyronaridine (PND), an antimalarial drug, in human plasma. After extraction with C18 solid-phase sorbent, PND was analyzed using a reverse phase chromatographic method with fluorescence detection (at lambda(ex)=267 nm and lambda(em)=443 nm). The mean extraction recovery for PND was 95.2%. The coefficient of variation for intra-assay precision, inter-assay precision and accuracy was less than 10%. The quantification limit with fluorescence detection was 0.010 microg/mL plasma. The method described herein has several advantages over other published methods since it is easy to perform and rapid. It also permits reducing both, solvent use and sample preparation time. The method has been used successfully to assay plasma samples from clinical pharmacokinetic studies.
  4. Parthasarathy S, Ramanathan S, Murugaiyah V, Hamdan MR, Said MI, Lai CS, et al.
    Forensic Sci Int, 2013 Mar 10;226(1-3):183-7.
    PMID: 23385139 DOI: 10.1016/j.forsciint.2013.01.014
    Mitragyna speciosa, a native plant of Thailand and Malaysia known as 'ketum', is a plant of considerable interest. It exhibits strong antinociceptive effect and yet, acts like a psychostimulant. Due to the affordability and its ease of availability, the abuse of this plant as a substitute for other banned narcotics has become a major concern in many societies. In countries such as Thailand, Myanmar, Australia and Malaysia, the use of ketum is illegal. However, for a person to be charged for possessing or selling ketum, a reliable analytical method is needed in order to detect and identify the plant and its products. Mitragynine is the major alkaloid of ketum. This compound manifests its antinociceptive effects by acting on the opioid receptors. Since M. speciosa contain large quantity of mitragynine and it is exclusive to the species, the present analytical method is developed and validated for the purpose of screening ketum products based on this unique compound as the analytical marker. The method uses a HPLC-DAD system with Inertsil C8 (4.6 mm × 150 mm, 5 μm) as the column and a mixture of acetonitrile and formic acid, 50:50 (v/v), as the mobile phase. This method not only detects mitragynine, it can also be used to quantify the amount of mitragynine in the sample. The limit of detection is 0.25 μg/ml, while the limit of quantification is 0.50 μg/ml. The method is quick, simple and reliable with an accuracy of 97.27-101.74% and coefficient of variations of between 0.91 and 3.96%. The method has been tested and found suitable for the identification and quantification of mitragynine in dried plants, a variety of ketum extracts, as well as ketum drink obtained from the market.
  5. Nagaya D, Ramanathan S, Ravichandran M, Navaratnam V
    J Integr Neurosci, 2012 Mar;11(1):117-22.
    PMID: 22744787
    Drug addiction is an important social problem in many countries. Genetic and environmental factors contribute to the predisposition of drug addiction. Genetic variations at the μ opioid receptor (OPRM1) gene locus have been associated with opiate addiction. The present study aims to delineate the frequency of A118G allele of OPRM1 among Malaysian subjects. The frequency of A allele and G allele were 51% and 49%, respectively for addicts and about 73% and 27% respectively for healthy volunteers. The frequency of G allele was 1.77-fold higher in addicts by odds ratio calculation at 95% Cl, which indicate the G allele to be strongly associated with addiction X(2) = 15.31,P < 0.0001; odds ratio 2.51; 95% Cl (1.575-3.994), compared to healthy volunteers. A significant association was observed between A118G polymorphism in μ opioid receptor gene and drug addiction.
  6. Goh YS, Karunakaran T, Murugaiyah V, Santhanam R, Abu Bakar MH, Ramanathan S
    Molecules, 2021 Jun 17;26(12).
    PMID: 34204457 DOI: 10.3390/molecules26123704
    Mitragyna speciosa Korth (kratom) is known for its psychoactive and analgesic properties. Mitragynine is the primary constituent present in kratom leaves. This study highlights the utilisation of the green accelerated solvent extraction technique to produce a better, non-toxic and antinociceptive active botanical extract of kratom. ASE M. speciosa extract had a dry yield (0.53-2.91 g) and showed a constant mitragynine content (6.53-7.19%) when extracted with organic solvents of different polarities. It only requires a shorter extraction time (5 min) and a reduced amount of solvents (less than 100 mL). A substantial amount of total phenolic (407.83 ± 2.50 GAE mg/g and flavonoids (194.00 ± 5.00 QE mg/g) were found in ASE kratom ethanol extract. The MTT test indicated that the ASE kratom ethanolic leaf extract is non-cytotoxic towards HEK-293 and HeLa Chang liver cells. In mice, ASE kratom ethanolic extract (200 mg/kg) demonstrated a better antinociceptive effect compared to methanol and ethyl acetate leaf extracts. The presence of bioactive indole alkaloids and flavonols such as mitragynine, paynantheine, quercetin, and rutin in ASE kratom ethanolic leaf extract was detected using UHPLC-ESI-QTOF-MS/MS analysis supports its antinociceptive properties. ASE ethanolic leaf extract offers a better, safe, and cost-effective choice of test botanical extract for further preclinical studies.
  7. Ramanathan S, Gopinath SCB, Arshad MKM, Poopalan P, Anbu P, Lakshmipriya T, et al.
    Sci Rep, 2019 11 19;9(1):17013.
    PMID: 31745155 DOI: 10.1038/s41598-019-53573-9
    Lung cancer is one of the most serious threats to human where 85% of lethal death caused by non-small cell lung cancer (NSCLC) induced by epidermal growth factor receptor (EGFR) mutation. The present research focuses in the development of efficient and effortless EGFR mutant detection strategy through high-performance and sensitive genosensor. The current amplified through 250 µm sized fingers between 100 µm aluminium electrodes indicates the voltammetry signal generated by means of the mutant DNA sequence hybridization. To enhance the DNA immobilization and hybridization, ∼25 nm sized aluminosilicate nanocomposite synthesized from the disposed joss fly ash was deposited on the gaps between aluminium electrodes. The probe, mutant (complementary), and wild (single-base pair mismatch) targets were designed precisely from the genomic sequences denote the detection of EGFR mutation. Fourier-transform Infrared Spectroscopy analysis was performed at every step of surface functionalization evidences the relevant chemical bonding of biomolecules on the genosensor as duplex DNA with peak response at 1150 cm-1 to 1650 cm-1. Genosensor depicts a sensitive EGFR mutation as it is able to detect apparently at 100 aM mutant against 1 µM DNA probe. The insignificant voltammetry signal generated with wild type strand emphasizes the specificity of genosensor in the detection of single base pair mismatch. The inefficiency of genosensor in detecting EGFR mutation in the absence of aluminosilicate nanocomposite implies the insensitivity of genosensing DNA hybridization and accentuates the significance of aluminosilicate. Based on the slope of the calibration curve, the attained sensitivity of aluminosilicate modified genosensor was 3.02E-4 A M-1. The detection limit of genosensor computed based on 3σ calculation, relative to the change of current proportional to the logarithm of mutant concentration is at 100 aM.
  8. Ramanathan S, Gopinath SCB, Md Arshad MK, Poopalan P, Anbu P, Lakshmipriya T
    Sci Rep, 2020 02 25;10(1):3351.
    PMID: 32099019 DOI: 10.1038/s41598-020-60208-x
    An incredible amount of joss fly ash is produced from the burning of Chinese holy joss paper; thus, an excellent method of recycling joss fly ash waste to extract aluminosilicate nanocomposites is explored. The present research aims to introduce a novel method to recycle joss fly ash through a simple and straightforward experimental procedure involving acidic and alkaline treatments. The synthesized aluminosilicate nanocomposite was characterized to justify its structural and physiochemical characteristics. A morphological analysis was performed with field-emission transmission electron microscopy, and scanning electron microscopy revealed the size of the aluminosilicate nanocomposite to be ~25 nm, while also confirming a uniformly spherical-shaped nanostructure. The elemental composition was measured by energy dispersive spectroscopy and revealed the Si to Al ratio to be 13.24 to 7.96, showing the high purity of the extracted nanocomposite. The roughness and particle distribution were analyzed using atomic force microscopy and a zeta analysis. X-ray diffraction patterns showed a synthesis of faceted and cubic aluminosilicate crystals in the nanocomposites. The presence of silica and aluminum was further proven by X-ray photoelectron spectroscopy, and the functional groups were recognized through Fourier transform infrared spectroscopy. The thermal capacity of the nanocomposite was examined by a thermogravimetric analysis. In addition, the research suggested the promising application of aluminosilicate nanocomposites as drug carriers. The above was justified by an enzyme-linked apta-sorbent assay, which claimed that the limit of the aptasensing aluminosilicate-conjugated ampicillin was two-fold higher than that in the absence of the nanocomposite. The drug delivery property was further justified through an antibacterial analysis against Escherichia coli (gram-negative) and Bacillus subtilis (gram-positive).
  9. Mustaffa F, Indurkar J, Ismail S, Mordi MN, Ramanathan S, Mansor SM
    Pharmacognosy Res, 2010 Mar;2(2):76-81.
    PMID: 21808545 DOI: 10.4103/0974-8490.62952
    Cinnomomum iners standardized leaves methanolic extract (CSLE) was subjected to analgesic, toxicity and phytochemical studies. The analgesic activity of CSLE was evaluated using formalin, hot plate and tail flick tests at doses of 100, 200 and 500 mg/kg. CSLE showed significant activity (P < 0.05) in the formalin model (late phase) on the rats at doses of 200 and 500 mg/kg. However, CSLE did not show activity in the hot plate and tail flick tests. The results obtained suggest that CSLE acts peripherally to relieve pain. For the toxicity study, CSLE was orally administered to the Swiss albino mice according to the Organization for Economic Co-Operation and Development (OECD) guideline 423. There was no lethality or toxic symptoms observed for all the tested doses throughout the 14-day period. Phytochemical screening of CSLE showed the presence of cardiac glycoside, flavonoid, polyphenol, saponin, sugar, tannin and terpenoid.
  10. Perumal S, Mahmud R, Ramanathan S
    Nat Prod Res, 2015;29(18):1766-9.
    PMID: 25571920 DOI: 10.1080/14786419.2014.999242
    Euphorbia hirta (L.) plant is traditionally used in Malaysia for the treatment of gastrointestinal, bronchial and respiratory ailments caused by nosocomial infectious agents. Bioactivity-guided fractionation of the methanol extract of the aerial parts of E. hirta and analysis using high-performance liquid chromatography have led to the isolation of two antibacterial compounds. These compounds were identified as caffeic acid (CA) and (-)-epicatechin 3-gallate (ECG) based on spectroscopic analyses and comparison with previously published data. Using broth microdilution method, both ECG and CA had demonstrated significant minimum inhibitory concentration of 15.6 and 31.3 μg/mL respectively, against Pseudomonas aeruginosa. Time-kill assessment of ECG and CA displayed bactericidal effect on P. aeruginosa cells.
  11. Torey A, Sasidharan S, Latha LY, Sudhakaran S, Ramanathan S
    Pharm Biol, 2010 Oct;48(10):1119-23.
    PMID: 20738154 DOI: 10.3109/13880200903490505
    To investigate the in vitro antioxidant activity of methanol extracts of Ixora coccinea L. (Rubiaceae) flower, leaf and stem.
  12. Hazim AI, Ramanathan S, Parthasarathy S, Muzaimi M, Mansor SM
    J Physiol Sci, 2014 May;64(3):161-9.
    PMID: 24464759 DOI: 10.1007/s12576-014-0304-0
    The effects of mitragynine on anxiety-related behaviours in the open-field and elevated plus-maze tests were evaluated. Male Sprague-Dawley rats were orally treated with mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) 60 min before behavioural testing. Mitragynine doses used in this study were selected on the basis of approximately human equivalent doses with reference to our previous literature reports. Acute administration of mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) increased central zone and open arms exploration in the open-field and elevated plus-maze tests respectively. These anxiolytic-like effects of mitragynine were effectively antagonized by intraperitoneal administration of naloxone (2 mg/kg), flumazenil (10 mg/kg), sulpiride (0.5 mg/kg) or SCH 23390 (0.02 mg/kg) 15 min before mitragynine treatments. These findings reveal that the acute administration of mitragynine produces anxiolytic-like effects and this could be possibly attributed to the interactions among opioidergic, GABAergic and dopaminergic systems in brain regions involved in anxiety.
  13. Ramanathan S, Gopinath SCB, Ismail ZH, Md Arshad MK, Poopalan P
    Biosens Bioelectron, 2022 Feb 01;197:113735.
    PMID: 34736114 DOI: 10.1016/j.bios.2021.113735
    In an aim of developing portable biosensor for SARS-CoV-2 pandemic, which facilitates the point-of-care aptasensing, a strategy using 10 μm gap-sized gold interdigitated electrode (AuIDE) is presented. The silane-modified AuIDE surface was deposited with ∼20 nm diamond and enhanced the detection of SARS-CoV-2 nucleocapsid protein (NCP). The characteristics of chemically modified diamond were evidenced by structural analyses, revealing the cubic crystalline nature at (220) and (111) planes as observed by XRD. XPS analysis denotes a strong interaction of carbon element, composed ∼95% as seen in EDS analysis. The C-C, CC, CO, CN functional groups were well-refuted from XPS spectra of carbon and oxygen elements in diamond. The interrelation between elements through FTIR analysis indicates major intrinsic bondings at 2687-2031 cm-1. The aptasensing was evaluated through electrochemical impedance spectroscopy measurements, using NCP spiked human serum. With a good selectivity the lower detection limit was evidenced as 0.389 fM, at a linear detection range from 1 fM to 100 pM. The stability, and reusability of the aptasensor were demonstrated, showing ∼30% and ∼33% loss of active state, respectively, after ∼11 days. The detection of NCP was evaluated by comparing anti-NCP aptamer and antibody as the bioprobes. The determination coefficients of R2 = 0.9759 and R2 = 0.9772 were obtained for aptamer- and antibody-based sensing, respectively. Moreover, the genuine interaction of NCP aptamer and protein was validated by enzyme linked apta-sorbent assay. The aptasensing strategy proposed with AuIDE/diamond enhanced sensing platform is highly recommended for early diagnosis of SARS-CoV-2 infection.
  14. Sahgal G, Ramanathan S, Sasidharan S, Mordi MN, Ismail S, Mansor SM
    Pharmacognosy Res, 2010 Jul;2(4):215-20.
    PMID: 21808570 DOI: 10.4103/0974-8490.69107
    The seeds of Swietenia mahagoni have been applied in folk medicine for the treatment of hypertension, diabetes, malaria, amoebiasis, cough, chest pain, and intestinal parasitism. Here we are the first to report on the toxicity of the Swietenia mahagoni crude methanolic (SMCM) seed extract.
  15. Tan SA, Goya L, Ramanathan S, Sulaiman SF, Alam M, Navaratnam V
    Food Res Int, 2014 Oct;64:387-395.
    PMID: 30011665 DOI: 10.1016/j.foodres.2014.06.040
    Extract from papaya leaves, a waste material from fruit farms in Malaysia was previously reported to possess remarkable antioxidative activities. In this study, papaya leaf extract was separated into fractions of different polarities [petroleum ether (PE), ethyl acetate (EA), n-butanol (NB) and water (W) fractions]. The aim of this research was to determine the most active fraction in terms of its chemopreventive effects towards oxidative stress and the chemical constituents involved. The cytoprotective nature of the papaya fractions was observed against t-BOOH-induced oxidative stress on HepG2 liver cell line. ROS assay indicated that only PE and EA effectively reduced the increment of radical due to the pro-oxidant, t-BOOH. Nevertheless, PE was a stronger ROS scavenger by demonstrating ROS reducing activity in a dose-dependent manner to the basal level. This fraction was also found to inhibit cell death caused by t-BOOH toxicity, attenuating lactate dehydrogenase enzyme leakage by more than 90% (p<0.05). In addition, gene expression of phase II antioxidant enzymes (hmox-1 and nqo-1) and their transcription factor (nrf-2) were shown to be upregulated upon PE treatment during a time-course study. A GC-MS fingerprint of the active fraction was subsequently obtained with standardization using the marker compound; α-tocopherol, a well known antioxidant. However, this pure compound was not as effective as its corresponding PE concentrations in ROS reduction. Hence, PE of papaya leaf extract was a strong antioxidant and cytoprotectant with tremendous potential to be harnessed into the next therapeutic remedy against oxidative stress of the liver.
  16. Damodaran T, Tan BWL, Liao P, Ramanathan S, Lim GK, Hassan Z
    J Ethnopharmacol, 2018 Oct 05;224:381-390.
    PMID: 29920356 DOI: 10.1016/j.jep.2018.06.020
    ETHNOPHARMACOLOGICAL RELEVANCE: Clitoria ternatea L. (CT), commonly known as Butterfly pea, is used in Indian Ayurvedic medicine to promote brain function and treat mental disorders. Root of CT has been proven to enhance memory, but its role in an animal model of chronic cerebral hypoperfusion (CCH), which has been considered as a major cause of brain disorders, has yet to be explored.

    AIM OF THE STUDY: To assess the motor and cognitive effects of acute oral administration of CT root methanolic extract and hippocampal long-term plasticity in the CA1 region of the CCH rat model.

    MATERIALS AND METHODS: Male Sprague Dawley rats (200-300 g) were subjected to permanent bilateral occlusion of common carotid arteries (PBOCCA) or sham operation. Then, these rats were given oral administration of CT root extract at doses of 100, 200 or 300 mg/kg on day 28 post-surgery and tested using behavioural tests (open-field test, passive avoidance task, and Morris water maze) and electrophysiological recordings (under urethane anaesthesia).

    RESULTS: Treatment with CT root extract at the doses of 200 and 300 mg/kg resulted in a significant enhancement in memory performance in CCH rats induced by PBOCCA. Furthermore, CCH resulted in inhibition of long-term potentiation (LTP) formation in the hippocampus, and CT root extract rescued the LTP impairment. The CT root extract was confirmed to improve the glutamate-induced calcium increase via calcium imaging using primary cultured rat neurons. No significance difference was found in the CaMKII expression. These results demonstrated that CT root extract ameliorates synaptic function, which may contribute to its improving effect on cognitive behaviour.

    CONCLUSIONS: Our findings demonstrated an improving effect of CT root extract on memory in the CCH rat model suggesting that CT root extract could be a potential therapeutic strategy to prevent the progression of cognitive deterioration in vascular dementia (VaD) and Alzheimer's disease (AD) patients.

  17. Domnic G, Jeng-Yeou Chear N, Abdul Rahman SF, Ramanathan S, Lo KW, Singh D, et al.
    J Ethnopharmacol, 2021 Oct 28;279:114391.
    PMID: 34224811 DOI: 10.1016/j.jep.2021.114391
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) or kratom is a medicinal plant indigenous to Southeast Asia. The leaf of M. speciosa is used as a remedy in pain management including cancer related pain, in a similar way as opioids and cannabis. Despite its well-known analgesic effect, there is a scarce of information on the cancer-suppressing potential of M. speciosa and its active constituents.

    AIM OF THE STUDY: To assess the potential applicability of M. speciosa alkaloids (mitragynine, speciociliatine or paynantheine) as chemosensitizers for cisplatin in Nasopharyngeal carcinoma (NPC) cell lines.

    MATERIALS AND METHODS: The cytotoxic effects of the extracts, fractions and compounds were determined by conducting in vitro cytotoxicity assays. Based on the cytotoxic screening, the alkaloid extract of M. speciosa exhibited potent inhibitory effect on the NPC cell line NPC/HK1, and therefore, was chosen for further fractionation and purification. NPC cell lines NPC/HK1 and C666-1 were treated with combinations of cisplatin and M. speciosa alkaloids combinations in 2D monolayer culture. The effect of cisplatin and mitragynine as a combination on cell migration was tested using in vitro wound healing and spheroid invasion assays.

    RESULTS: In our bioassay guided isolation, both methanolic and alkaloid extracts showed mild to moderate cytotoxic effect against the NPC/HK1 cell line. Both NPC cell lines (NPC/HK1 and C666-1) were insensitive to single agent and combination treatments of the M. speciosa alkaloids. However, mitragynine and speciociliatine sensitized the NPC/HK1 and C666-1 cells to cisplatin at ~4- and >5-fold, respectively in 2D monolayer culture. The combination of mitragynine and cisplatin also significantly inhibited cell migration of the NPC cell lines. Similarly, the combination also of mitragynine and cisplatin inhibited growth and invasion of NPC/HK1 spheroids in a dose-dependent manner. In addition, the spheroids did not rapidly develop resistance to the drug combinations at higher concentrations over 10 days.

    CONCLUSION: Our data indicate that both mitragynine and speciociliatine could be potential chemosensitizers for cisplatin. Further elucidation focusing on the drug mechanistic studies and in vivo studies are necessary to support delineate the therapeutic applicability of M. speciosa alkaloids for NPC treatment.

  18. Damodaran T, Chear NJ, Murugaiyah V, Mordi MN, Ramanathan S
    Front Pharmacol, 2021;12:714918.
    PMID: 34489704 DOI: 10.3389/fphar.2021.714918
    Background: Kratom (Mitragyna speciosa Korth), a popular opioid-like plant holds its therapeutic potential in pain management and opioid dependence. However, there are growing concerns about the safety or potential toxicity risk of kratom after prolonged use. Aim of the study: The study aimed to assess the possible toxic effects of kratom decoction and its major alkaloids, mitragynine, and speciociliatine in comparison to morphine in an embryonic zebrafish model. Methods: The zebrafish embryos were exposed to kratom decoction (1,000-62.5 μg/ml), mitragynine, speciociliatine, and morphine (100-3.125 μg/ml) for 96 h post-fertilization (hpf). The toxicity parameters, namely mortality, hatching rate, heart rate, and morphological malformations were examined at 24, 48, 72, and 96 hpf, respectively. Results: Kratom decoction at a concentration range of ≥500 μg/ml caused 100% mortality of zebrafish embryos and decreased the hatching rate in a concentration-dependent manner. Meanwhile, mitragynine and speciociliatine exposure resulted in 100% mortality of zebrafish embryos at 100 μg/ml. Both alkaloids caused significant alterations in the morphological development of zebrafish embryos including hatching inhibition and spinal curvature (scoliosis) at the highest concentration. While exposure to morphine induced significant morphological malformations such as pericardial oedema, spinal curvature (lordosis), and yolk edema in zebrafish embryos. Conclusion: Our findings provide evidence for embryonic developmental toxicity of kratom decoction and its alkaloids both mitragynine and speciociliatine at the highest concentration, hence suggesting that kratom consumption may have potential teratogenicity risk during pregnancy and thereby warrants further investigations.
  19. Shahrir NF, Aziz NRA, Ahmad FL, Muzaid NA, Samat F, Syed Ghazaili SNA, et al.
    Malays Fam Physician, 2022 Nov 30;17(3):53-63.
    PMID: 36606172 DOI: 10.51866/oa.122
    INTRODUCTION: Microalbuminuria presents significant health risks for the progression of endstage renal-failure (ESRF) among type 2 diabetes mellitus (T2DM) patients. This study aims to determine the proportion and associated factors of microalbuminuria among T2DM patients in Kuala Selangor district, Malaysia.

    METHOD: A retrospective cross-sectional study was conducted from December 2020 to February 2021 using secondary data from the National Diabetic Registry (NDR), Malaysia, and reviewed patients' diabetic records for the year 2020. All T2DM patients aged >18 years who were registered with the NDR in 2020 and fulfilled the inclusion and exclusion criteria were included in the study. Descriptive statistics and multiple logistic regression analysis were performed. Data were analysed using SPSS version 26.0. A total of 343 samples were included in this study for the determination of the proportion of microalbuminuria and its associated factors.

    RESULTS: Of 343 respondents, 34.4% had microalbuminuria. HbAlc >7.0% (AdjOR 2.19, 95% CI: 1.35, 3.55, p=0.001), HDL <1.04 mmol/L (AdjOR 2.44, 95% CI: 1.323, 4.52, p=0.004), dyslipidaemia (AdjOR 1.90, 95% CI: 1.03, 3.48, p=0.039), and peripheral neuropathy (AdjOR 3.01, 95% CI: 1.02, 8.93, p=0.047) were significantly associated with microalbuminuria. Conclusion: Microalbuminuria is a modifiable risk factor in preventing the progression of ESRF among T2DM patients. Therefore, identification of factors associated with microalbuminuria among this high-risk group is important to facilitate early screening and prompt treatment to prevent progression of diabetic kidney disease to ESRF.

  20. Ramanathan S, Nair NK, Mansor SM, Navaratnam V
    J. Chromatogr., 1993 Jun 02;615(2):303-7.
    PMID: 8335708
    A rapid and selective high-performance liquid chromatographic assay for simultaneous quantitative determination of a new antifilarial drug (UMF-058, I) and mebendazole (MBZ) is described. After a simple extraction from whole blood, both compounds were analysed using a C18 Nova Pak reversed-phase column and a mobile phase of methanol-0.05 M ammonium dihydrogenphosphate (50:50, v/v) adjusted to pH 4.0, with ultraviolet detection at 291 nm. The average recoveries of I and MBZ over a concentration range of 25-250 ng/ml were 92.0 +/- 7.7 and 84.4 +/- 4.4%, respectively. The minimum detectable concentrations in whole blood for I and MBZ were 7 and 6 ng/ml, respectively. This method was found to be suitable for pharmacokinetic studies.
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