We report a case of diffuse unilateral subacute neuroretinitis in a young boy with no clinical visualization of nematode. The diagnosis was made based on clinical findings and detection of Toxocara immunoglobulin G by Western blot test. An 11-year-old Malay boy presented with progressive blurring of vision in the left eye for a duration of 1 year. It was associated with intermittent floaters. Visual acuity in the left eye was 6/45 and improved to 6/24 with pinhole. There was positive relative afferent pupillary defect, impaired color vision, and presence of red desaturation in the left eye. There were occasional cells in the anterior chamber with no conjunctiva injection. Posterior segment examination revealed mild-to-moderate vitritis and generalized pigmentary changes of the retina with attenuated vessels. The optic disk was slightly hyperemic with mild edema. There was presence of multiple, focal, gray-white subretinal lesions at the inferior part of the retina. Full blood picture results showed eosinophilia with detection of Toxocara immunoglobulin G by Western blot test. Investigations for other infective causes and connective tissue diseases were negative. The diagnosis of diffuse unilateral subacute neuroretinitis secondary to Toxocara was made based on clinical findings and laboratory results. He was treated with oral albendazole 400 mg daily for 5 days and oral prednisolone 1 mg/kg with tapering doses over 6 weeks. At 1 month follow-up, the inflammation had reduced, and multiple, focal, gray-white subretinal lesions were resolved; however there was no improvement of vision.
Although there are various treatments available for depression, some patients may experience resistance to treatment or encounter adverse effects. Centella asiatica (C. asiatica) is an ancient medicinal herb used in Ayurvedic medicine for its rejuvenating, neuroprotective and psychoactive properties. This study aims to explore the antidepressant-like effects of the major constituents found in C. asiatica, i.e., asiatic acid, asiaticoside, madecassic acid, and madecassoside at three doses (1.25, 2.5, and 5mg/kg, i.p), on the behavioural and cortisol level of unpredictable chronic stress (UCS) zebrafish model. Based on the findings from the behavioural study, the cortisol levels in the zebrafish body after treatment with the two most effective compounds were measured using enzyme-linked immunosorbent assay (ELISA). Furthermore, a molecular docking study was conducted to predict the inhibitory impact of the triterpenoid compounds on serotonin reuptake. The in vivo results indicate that madecassoside (1.25, 2.5, and 5mg/kg), asiaticoside and asiatic acid (5mg/kg) activated locomotor behaviour. Madecassoside at all tested doses and asiaticoside at 2.5 and 5mg/kg significantly decreased cortisol levels compared to the stressed group, indicating the potential regulation effect of madecassoside and asiaticoside on the hypothalamic-pituitary-adrenal axis overactivity. This study highlights the potential benefits of madecassoside and asiaticoside in alleviating depressive symptoms through their positive effects on behaviour and the hypothalamic-pituitary-adrenal (HPA)- axis in a chronic unpredictable stress zebrafish model. Furthermore, the in silico study provided additional evidence to support these findings. These promising results suggest that C. asiatica may be a valuable and cost-effective therapeutic option for depression, and further research should be conducted to explore its potential benefits.
Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.
A new antimalarial sterol, kaimanol (1), along with a known sterol, saringosterol (2) was isolated from the Indonesian Marine sponge, Xestospongia sp. The chemical structure of the new compound was determined on the basis of spectroscopic evidences and by comparison to those related compounds previously reported. Isolated compounds, 1 and 2 were evaluated for their antiplasmodial effect against Plasmodium falciparum 3D7 strains. Compounds 1 and 2 exhibited antiplasmodial activity with IC50 values of 359 and 0.250 nM, respectively.
The Aglaia genus, a member of the Meliaceae family, is generally recognized to include a number of secondary metabolite compounds with diverse structures and biological activities, including triterpenoids. Among the members of this genus, Aglaia cucullata has been reported to have unique properties and thrives exclusively in mangrove ecosystems. This plant is also known to contain various metabolites, such as flavaglines, bisamides, and diterpenoids, but there are limited reports on the isolation of triterpenoid compounds from its stem bark. Therefore, this research attempted to isolate and elucidate seven triterpenoids belonging to dammarane-type (1-7) from the stem bark of Aglaia cucullata. The isolated compounds included 20S,24S-epoxy-3α,25-dihydroxy-dammarane (1), dammaradienone (2), 20S-hydroxy-dammar-24-en-3-on (3), eichlerianic acid (4), (20S,24RS)-23,24-epoxy-24-methoxy-25,26,27-tris-nor dammar-3-one (5), 3α-acetyl-cabraleahydroxy lactone (6), and 3α-acetyl-20S,24S-epoxy-3α,25-dihydroxydammarane (7). Employing spectroscopic techniques, the chemical structures of the triterpenoids were identified using FTIR, NMR, and HRESITOF-MS. The cytotoxic activity of compounds 1-7 was tested with the PrestoBlue cell viability reagent against MCF-7 breast cancer, B16-F10 melanoma, and CV-1 normal kidney fibroblast cell lines. The results displayed that compound 5 had the highest level of bioactivity compared to the others. Furthermore, the IC50 values obtained were more than 100 μM, indicating the low potential of natural dammarane-type triterpenoids as anticancer agents. These findings provided opportunities for further studies aiming to increase their cytotoxic activities through semi-synthetic methods.
A new seco-A tirucallane triterpenoid named excelxylin A (1), along with two known seco-A triterpenoids (2-3), were isolated from the n-hexane extract of Dysoxylum excelsum (Spreng.) Blume ex G.Don stem bark. The structure and stereochemistry configuration of compounds 1-3 was established by NMR, IR, and HR-ESI-MS spectroscopic data analyses and comparison of their NMR data with literatures. The compounds exhibited the carbon framework for seco-A ring tirucallane triterpenoid, first reported in the Dysoxylum genus. All compounds were tested for their cytotoxicity against human cervical HeLa cells.
A total of five new mexicanolides (1-5), namely alliaxylines A-E, together with two known limonoids 6 and 7, were isolated and identified from Dysoxylum alliaceum (Blume) Blume ex. A.Juss. (Meliaceae). The structures of these compounds were elucidated based on extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D, and 2D NMR, as well as theoretical stimulation of NMR shifts with the DP4 + algorithm. Consequently, this study aimed to examine cytotoxic activities of these compounds against MCF-7 and A549 cell lines. The results implied that compound 2 was the most potent against the two tested cells, with IC50 values of 34.95 ± 0.21 and 44.39 ± 1.03 µM.
A new limonoid, pentandricine (1), along with three known limonoids, ceramicine B (2), 6-de(acetyloxy)-23-oxochisocheton (3), 6-de(acetyloxy)-23-oxo-7-O-deacetylchisocheton (4), have been isolated from the stembark of Chisocheton pentandrus. The chemical structures of the new compound were elucidated on the basis of spectroscopic evidence. All of the compounds were tested for their cytotoxic effects against MCF-7 breast cancer cells. Compounds 1-4 showed weak and no cytotoxicity against MCF-7 breast cancer cells with IC50 values of 369.84, 150.86, 208.93 and 120.09 μM, respectively.
Two new azadirone-type limonoids, namely lasiocarpine A (1) and lasiocarpine B (2) were isolated from the fruit of Chisocheton lasiocarpus along with three known limonoids (3-5). UV, IR, one- and two- dimensional NMR, and mass spectrometry were used to determine the chemical structure of the isolated compounds. Furthermore, their cytotoxic activity against breast cancer cell line MCF-7 was evaluated using PrestoBlue reagent. From these compounds, lasiocarpine A (1) showed the strongest activity with an IC50 value of 43.38 μM.
Chisocarpene A (1) is a new tirucallane-type triterpenoid together with odoratone (2) and 24-methylenecycloartanol (3), isolated from the stem bark of Chisocheton lasiocarpus. The chemical structures of compounds 1-3 were elucidated through a detailed analysis of their spectroscopic data (IR, MS, 1 D, and 2 D NMR). The isolated compounds were evaluated for cytotoxic activity against the MCF-7 breast cancer cell line using a resazurin-based assay. Compound 1 showed the most potent activity (IC50 26.56 ± 1.01 µM) and was two-fold more active than the positive control.
Three new dammarane-type triterpenoids, namely elliptaglin A-C (1-3) were isolated from the stem bark of Aglaia elliptica (C.DC.) Blume along with three known derivatives, namely (20S)-hydroxydammar-24-en-3-on (4), cabralealactone (5), and E-25-hydroperoxydammar-23-en-20-ol-3-one (6). Subsequently, their chemical structures were determined using HR-ESI-MS, FTIR, 1D and 2D-NMR spectroscopic analysis as well as comparison with previous studies. The cytotoxicity activities of the isolated compounds against MCF-7 breast cancer and B16-F10 melanoma cell lines were then tested using PrestoBlue reagent. The analysis results showed that elliptaglin B (2) had the strongest activity against both cell lines with IC50 values of 60.98 and 51.83 µM, respectively.
Hyphema and orbital apex syndrome occurring concurrently in a patient with herpes zoster ophthalmicus have not been reported previously. We present a case with these unique findings and discuss the pathogenesis of these conditions and their management.
Many studies have shown the effectiveness of educational modules on increasing colorectal cancer screening uptake at individual level but not adjusted for potential clustering effect such as workplace. Longitudinal studies on workplace colorectal cancer screening require a series of analysis under different conditions due to heterogeneity of workplace population. To achieve this, a sensitivity analysis based on Generalized Estimating Equations was conducted to determine the robustness of the predictive performance of health education module in increasing screening uptake. Materials and Method: A parallel, single blind, cluster randomized trial was conducted among 15 organizations in Kuantan, Pahang. Intervention group received a complex Health Education Module comprising of group education, practical session on fecal occult blood test usage and WhatsApp group follow-up, while control group received standard colorectal cancer screening brochure. Sensitivity analyses using intention to treat analysis with interaction term, compatibility term, behavioral intention term and key assumption term were performed. Data were imputed and analysed using generalized estimating equation with IBM SPSS version 23. Pooled adjusted odds ratio was calculated using random effect model with inverse variance weighting using RevMan version 3.5. Results: A total of 166 participants from 15 organizations were recruited in the study. Intervention and control group were comparable at baseline (P>0.05). Health Education Module given in intervention group significantly increased the uptake of FOBT by nearly 5 times compared to control group in sensitivity analyses (pooled adjusted OR=4.60, 95% CI=2.65-7.99, I2=47%, P
Herein, we report our experience in treating extensive traumatic submacular hemorrhage with a single dose of intravitreal ranibizumab. A 23-year-old healthy Malay man presented with a progressive reduction of central vision in the left eye of 2 days' duration following a history of blunt trauma. Visual acuity was reduced to counting fingers. Examination revealed infero-temporal subconjunctival hemorrhage, traumatic anterior uveitis, and an extensive sub-macular hemorrhage with suspicion of a choroidal rupture in the affected eye. He was initially treated conservatively with topical prednisolone acetate 1%. The subconjunctival hemorrhage and anterior uveitis resolved but his vision remained poor with minimal resolution of the submacular hemorrhage at 1 week follow-up (day 12 post-trauma). In view of the poor resolution of submacular hemorrhage, he was treated with a single dose of 0.5 mg intravitreal ranibizumab at day 20 post-trauma. At 4 weeks post-intravitreal ranibizumab, there was an improvement in visual acuity (from counting fingers to 6/45) and complete resolution of the submacular hemorrhage with presence of a choroidal rupture scar temporal to the fovea, which was not seen clearly at presentation due to obscuration by blood. His visual acuity further improved to 6/18 at 3 months post-trauma. Although this single case had a favorable outcome, a large population cohort study is needed to establish the effectiveness of intravitreal ranibizumab in treating extensive traumatic submacular hemorrhage.
We would like to report two cases of preretinal haemorrhage from two different aetiology courses of bleeding being treated with intravitreal ranibizumab and its outcome. Our first case was a 39-year-old man with a diagnosis of severe aplastic anaemia that presented with bilateral premacular haemorrhages in both eyes. His right eye vision was 6/45 and it was counting finger in the left eye. He was treated with intravitreal ranibizumab once to the right eye and twice to the left eye. Right eye showed complete resolution of premacular haemorrhage and minimal residual premacular haemorrhage in the left eye at 3 months after initial presentation. Our second case was a 32-year-old healthy teacher that presented with preretinal haemorrhage at superotemporal region extending to macular area in left eye secondary to valsalva retinopathy. Her left vision was counting finger. She was treated with single intravitreal ranibizumab to the left eye. There was significant reduction of premacular haemorrhage and her left eye vision improved to 6/6 at 10 weeks after injection. Both cases had favourable outcome with intravitreal ranibizumab and can be considered as nonsurgical treatment option in treating premacular haemorrhage.
Neuropathy is frequently a late complication of diabetes mellitus. Auditory neuropathy and microangiopathy of inner ear are the possible causes of hearing loss in diabetics. To study the correlation between glycaemic control and hearing threshold in patients with type 2 diabetes mellitus and to determine the differences of hearing threshold between groups treated with different modality. This single blind randomized controlled study was performed at the Department of Medicine and Department of Otorhinolaryngology, Hospital Universiti Kebangsaan Malaysia (UKM) between 1st May 2003 and 31st September 2004. This study was approved by Research Ethics Committee (code number FF-137). Subjects were randomized into two groups. Group 1 were patients treated with conventional oral hypoglycemic agents. The patients in group 2 were those treated with insulin injection. The subjects were seen 4 weekly for 3 months. Audiometric test were performed in all subjects at each visit. Blood were taken for fasting blood glucose, Hb1Ac, and fructosamine at every visit to determine the glycaemic controls of the subject. They were 11 patients (22 ears) treated with oral hypoglycemic agents and 17 patients treated (34 ears) with subcutaneous insulin. There is no significant difference between mean pure tone threshold before and after treatment at all frequencies in both groups. There is also no significance different in fasting glucose level and fructosamine. However, there is significant difference HbA1c levels between the two groups after treatment (P
Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1'S-1'-acetoxychavicol acetate (ACA), a component of Malaysian ginger traditionally used for various medicinal purposes.
The aims of this study were to investigate the combined effects of a natural compound 1'S-1'-acetoxychavicol acetate (ACA) with cisplatin (CDDP) on HPV-positive human cervical carcinoma cell lines (Ca Ski-low cisplatin sensitivity and HeLa-high cisplatin sensitivity), and to identify microRNAs (miRNAs) modulated in response toward ACA and/or CDDP. It was revealed that both ACA and CDDP induced dose- and time-dependent cytotoxicity when used as a stand-alone agent, while synergistic effects were observed when used in combination with a combination index (CI) value of 0.74 ± 0.01 and 0.85 ± 0.01 in Ca Ski and HeLa cells, respectively. A total of 25 miRNAs were found to be significantly differentially expressed in response to ACA and/or CDDP. These include hsa-miR-138, hsa-miR-210, and hsa-miR-744 with predicted gene targets involved in signaling pathways regulating apoptosis and cell cycle progression. In conclusion, ACA acts as a chemosensitizer which synergistically potentiates the cytotoxic effect of CDDP in cervical cancer cells. The altered miRNA expression upon administration of ACA and/or CDDP suggests that miRNAs play an important role in anticancer drug responses, which can be manipulated for therapeutic purposes.
1'-(S)-1'-Acetoxychavicol acetate (ACA) isolated from the Malaysian ethno-medicinal plant Alpinia conchigera Griff. was investigated for its potential as an anticancer drug. In this communication, we describe the cytotoxic and apoptotic properties of ACA on five human tumour cell lines. Data from MTT cell viability assays indicated that ACA induced both time- and dose-dependent cytotoxicity on all tumour cell lines tested and had no adverse cytotoxic effects on normal cells. Total mortality of the entire tumour cell population was achieved within 30 hrs when treated with ACA at 40.0 µM concentration. Flow cytometric analysis for annexin-V and PI dual staining demonstrated that cell death occurred via apoptosis, followed by secondary necrosis. The apoptotic effects of ACA were confirmed via the DNA fragmentation assay, in which consistent laddering of genomic DNA was observed for all tumour cell lines after a 24 hrs post-treatment period at the IC(50) concentration of ACA. A cell cycle analysis using PI staining also demonstrated that ACA induced cell cycle arrest at the G(0)/G(1) phase, corresponding to oral tumour cell lines. In conclusion, ACA exhibits enormous potential for future development as a chemotherapeutic drug against various malignancies.
In this study, the apoptotic mechanism and combinatorial chemotherapeutic effects of the cytotoxic phenylpropanoid compound 1'S-1'-acetoxyeugenol acetate (AEA), extracted from rhizomes of the Malaysian ethnomedicinal plant Alpinia conchigera Griff. (Zingiberaceae), on MCF-7 human breast cancer cells were investigated for the first time. Data from cytotoxic and apoptotic assays such as live and dead and poly-(ADP-ribose) polymerase cleavage assays indicated that AEA was able to induce apoptosis in MCF-7 cells, but not in normal human mammary epithelial cells. A microarray global gene expression analysis of MCF-7 cells, treated with AEA, suggested that the induction of tumor cell death through apoptosis was modulated through dysregulation of the nuclear factor-kappaB (NF-κB) pathway, as shown by the reduced expression of various κB-regulated gene targets. Consequent to this, western blot analysis of proteins corresponding to the NF-κB pathway indicated that AEA inhibited phosphorylation levels of the inhibitor of κB-kinase complex, resulting in the elimination of apoptotic resistance originating from NF-κB activation. This AEA-based apoptotic modulation was elucidated for the first time in this study, and gave rise to the proposal of an NF-κB model termed the 'Switching/Alternating Model.' In addition to this, AEA was also found to synergistically enhance the proapoptotic effects of paclitaxel, when used in combination with MCF-7 cells, presumably by a chemosensitizing role. Therefore, it was concluded that AEA isolated from the Malaysian tropical ginger (A. conchigera) served as a very promising candidate for further in-vivo development in animal models and in subsequent clinical trials involving patients with breast-related malignancies.