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Displaying publications 61 - 69 of 69 in total

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Chemopreventive effects of standardized papaya leaf fraction on oxidatively stressed human liver cells

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.
Fulltext Prerequisite for COVID-19 Prediction: A Review on Factors Affecting the Infection Rate

Tang SGH, Hadi MHH, Arsad SR, Ker PJ, Ramanathan S, Afandi NAM, et al.

Int J Environ Res Public Health, 2022 Oct 11;19(20).
PMID: 36293576 DOI: 10.3390/ijerph192012997

Since the year 2020, coronavirus disease 2019 (COVID-19) has emerged as the dominant topic of discussion in the public and research domains. Intensive research has been carried out on several aspects of COVID-19, including vaccines, its transmission mechanism, detection of COVID-19 infection, and its infection rate and factors. The awareness of the public related to the COVID-19 infection factors enables the public to adhere to the standard operating procedures, while a full elucidation on the correlation of different factors to the infection rate facilitates effective measures to minimize the risk of COVID-19 infection by policy makers and enforcers. Hence, this paper aims to provide a comprehensive and analytical review of different factors affecting the COVID-19 infection rate. Furthermore, this review analyses factors which directly and indirectly affect the COVID-19 infection risk, such as physical distance, ventilation, face masks, meteorological factor, socioeconomic factor, vaccination, host factor, SARS-CoV-2 variants, and the availability of COVID-19 testing. Critical analysis was performed for the different factors by providing quantitative and qualitative studies. Lastly, the challenges of correlating each infection risk factor to the predicted risk of COVID-19 infection are discussed, and recommendations for further research works and interventions are outlined.
Antioxidant activity and total phenolic content of methanol extracts of Ixora coccinea

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.
Permeability of atenolol and propranolol in the presence of dimethyl sulfoxide in rat single-pass intestinal perfusion assay with liquid chromatography/UV detection

Venkatesh G, Ramanathan S, Nair NK, Mansor SM, Sattar MA, Khan MA, et al.

Biomed Chromatogr, 2007 May;21(5):484-90.
PMID: 17294505

A simple and sensitive RP-HPLC-UV method was developed and validated for simultaneous determination of atenolol and propranolol and subsequently applied to investigate the effect of dimethyl sulfoxide in rat in situ intestinal permeability studies. Atenolol (400 microm) and propranolol (100 microm) were perfused in the small intestine of anaesthetized (pentobarbitone sodium 60 mg/kg, i.p.) male Sprague-Dawley rats either in the presence (1, 3 and 5%) or in the absence of dimethyl sulfoxide. There was no significant alteration (p > 0.05) in the permeability of atenolol and propranolol, which indicated there was no effect of various concentrations of dimethyl sulfoxide (1-5%) on the membrane integrity of the rat intestinal tissues. The analytical method was validated on a C(4) column with a mobile phase comprising ammonium acetate buffer (pH 3.5, 0.02 m) and acetonitrile in the ratio of 30:70 (v/v) at a flow rate of 1.0 mL/min. The validated method was found to be accurate and precise and stability studies were carried out at different storage conditions and both analytes were found to be stable. These findings are applicable for determining the absorbability of water-insoluble drugs and new chemical entities for the purpose of classifying them in the biopharmaceutical classification system.
Development and validation of RP-HPLC-UV method for simultaneous determination of buparvaquone, atenolol, propranolol, quinidine and verapamil: a tool for the standardization of rat in situ intestinal permeability studies

Venkatesh G, Ramanathan S, Mansor SM, Nair NK, Sattar MA, Croft SL, et al.

J Pharm Biomed Anal, 2007 Mar 12;43(4):1546-51.
PMID: 17157469

A simple, sensitive and specific reversed phase high performance liquid chromatographic (RP-HPLC) method with UV detection at 251 nm was developed for simultaneous quantitation of buparvaquone (BPQ), atenolol, propranolol, quinidine and verapamil. The method was applicable in rat in situ intestinal permeability study to assess intestinal permeability of BPQ, a promising lead compound for Leishmania donovani infections. The method was validated on a C-4 column with mobile phase comprising ammonium acetate buffer (0.02 M, pH 3.5) and acetonitrile in the ratio of 30:70 (v/v) at a flow rate of 1.0 ml/min. The retention times for atenolol, quinidine, propranolol, verapamil and BPQ were 4.30, 5.96, 6.55, 7.98 and 8.54 min, respectively. The calibration curves were linear (correlation coefficient > or =0.996) in the selected range of each analyte. The method is specific and sensitive with limit of quantitation of 15 microg/ml for atenolol, 0.8 microg/ml for quinidine, 5 microg/ml for propranolol, 10 microg/ml for verapamil and 200 ng/ml for BPQ. The validated method was found to be accurate and precise in the working calibration range. Stability studies were carried out at different storage conditions and all the analytes were found to be stable. This method is simple, reliable and can be routinely used for accurate permeability characterization.
Optimization and validation of RP-HPLC-UV method with solid-phase extraction for determination of buparvaquone in human and rabbit plasma: application to pharmacokinetic study

Venkatesh G, Majid MI, Ramanathan S, Mansor SM, Nair NK, Croft SL, et al.

Biomed Chromatogr, 2008 May;22(5):535-41.
PMID: 18205140 DOI: 10.1002/bmc.965

A simple, sensitive and specific reversed-phase high-performance liquid chromatographic method with UV detection at 251 nm was developed for quantitation of buparvaquone (BPQ) in human and rabbit plasma. The method utilizes 250 microL of plasma and sample preparation involves protein precipitation followed by solid-phase extraction. The method was validated on a C18 column with mobile phase consisting of ammonium acetate buffer (0.02 m, pH 3.0) and acetonitrile in the ratio of 18:82 (v/v) at a flow rate of 1.1 mL/min. The calibration curves were linear (correlation coefficient>or=0.998) in the selected range. The method is specific and sensitive with limit of quantitation of 50 ng/mL for BPQ. The validated method was found to be accurate and precise in the working calibration range. Stability studies were carried out at different storage conditions and BPQ was found to be stable. Partial validation studies were carried out using rabbit plasma and intra- and inter-day precision and accuracy were within 7%. This method is simple, reliable and can be routinely used for preclinical pharmacokinetic studies for BPQ.
Kratom and Pain Tolerance: A Randomized, Placebo-Controlled, Double-Blind Study

Vicknasingam B, Chooi WT, Rahim AA, Ramachandram D, Singh D, Ramanathan S, et al.

Yale J Biol Med, 2020 06;93(2):229-238.
PMID: 32607084

Background: Kratom has a long history of traditional medicine use in Southeast Asia. Consumption of kratom products has also been reported in the US and other regions of the world. Pain relief is among many self-reported kratom effects but have not been evaluated in controlled human subject research. Methods: Kratom effects on pain tolerance were assessed in a randomized, placebo-controlled, double-blind study. During a 1-day inpatient stay, participants received a randomized sequence of kratom and placebo decoctions matched for taste and appearance. Pain tolerance was measured objectively in a cold pressor task (CPT) as time (seconds) between the pain onset and the hand withdrawal from the ice bath. Health status, vital signs, objective, and subjective indicators of withdrawal symptoms, self-reported data on lifetime kratom use patterns, and assessments of blinding procedures were also evaluated. Results: Twenty-six males with the mean (SD) age 24.3 (3.4) years were enrolled. They reported the mean (SD) 6.1 (3.2) years of daily kratom consumption. Pain tolerance increased significantly 1 hour after kratom ingestion from the mean (SD) 11.2 (6.7) seconds immediately before to 24.9 (39.4) seconds 1 hour after kratom consumption (F(2,53.7)=4.33, p=0.02). Pain tolerance was unchanged after consuming placebo drinks: 15.0 (19.0) seconds immediately before and 12.0 (8.1) seconds 1 hour after consumption of placebo (F(2,52.8)=0.93, p=0.40). No discomfort or signs of withdrawal were reported or observed during 10-20 hours of kratom discontinuation. Conclusions: Kratom decoction demonstrated a substantial and statistically significant increase in pain tolerance. Further rigorous research on kratom pain-relieving properties and a safety profile is needed.
Fulltext Treatment of MOG antibody associated disorders: results of an international survey

Whittam DH, Karthikeayan V, Gibbons E, Kneen R, Chandratre S, Ciccarelli O, et al.

J Neurol, 2020 Dec;267(12):3565-3577.
PMID: 32623595 DOI: 10.1007/s00415-020-10026-y

INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed.
OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD.
METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019).
RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT.
CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.
Fulltext Synchronous Breast and Cervical Carcinoma: A Genetic Point of View

Yahya MM, Ismail MP, Ramanathan S, Kadir MN, Azhar A, Ibrahim NBC, et al.

Biomedicines, 2023 Feb 11;11(2).
PMID: 36831061 DOI: 10.3390/biomedicines11020525

Breast carcinoma is the most common cancer of women in Malaysia. The most common sites of metastasis are the lung, liver, bone and brain. A 45-year-old lady was diagnosed with left invasive breast carcinoma stage IV (T4cN1M1) with axillary lymph nodes and lung metastasis. She was noted to have a cervical mass through imaging, and biopsy showed CIN III. Post chemotherapy, the patient underwent left simple mastectomy with examination under anaesthesia of the cervix, cystoscopy and staging. The cervical histopathological examination (HPE) showed squamous cell carcinoma, and clinical staging was 2A. The breast tissue HPE showed invasive carcinoma with triple receptors positivity. The patient was given tamoxifen and put on concurrent chemoradiotherapy (CCRT) for the cervical cancer. The management of each pathology of this patient involved a multi-disciplinary team that included surgeons, oncologists, gynaecologists, pathologists and radiologists. Due to the complexity of the case with two concurrent cancers, the gene expression profiles may help predict the patient's clinical outcome.