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.
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 series of 2-methoxypyridine-3-carbonitrile (5a-i)-bearing aryl substituents were successfully synthesized in good yields by the condensation of chalcones (4a-i) with malononitrile in basic medium. The condensation process, in most cases, offers a route to a variety of methoxypyridine derivatives (6a-g) as side products in poor yields. All new compounds were fully characterized using different spectroscopic methods. Mass ESI-HMRS measurements were also performed. Furthermore, these compounds were screened for their in vitro cytotoxicity activities against three cancer cell lines; namely, those of the liver (line HepG2), prostate (line DU145) and breast (line MBA-MB-231). The cytotoxicity assessment revealed that compounds 5d, 5g, 5h and 5i exhibit promising antiproliferative effects (IC50 1-5 µM) against those three cancer cell lines.
This paper reports the optical properties of zinc oxide nanofilm fabricated by using organic natural products from Salvia officinalis leaves (SOL) extract and discusses the effect of the nanocrystal (NC) structure (nanoyarn and nanomat-like structure) on nanofilm optical properties. The surface-active layer of the nanofilm of ZnO nanoparticles (ZnO NPs) was passivated with natural organic SOL leaves hydrothermally, then accumulated on zinc oxide nanorods (ZnO NRs). The nanofilms were fabricated (with and without PEO) on glass substrate (at 85 °C for 16 h) via chemical solution deposition (CSD). The samples were characterized by UV-vis, PL, FESEM, XRD, and TEM measurements. TEM micrographs confirmed the nucleation of ZnO NPs around 4 nm and the size distribution at 1.2 nm of ZnO QDs as an influence of the quantum confinement effect (QCE). The nanofilms fabricated with SOL surfactant (which works as a capping agent for ZnO NPs) represent distinct optoelectronic properties when compared to bulk ZnO. FESEM images of the nanofilms revealed nanoyarn and nanomat-like structures resembling morphologies. The XRD patterns of the samples exhibited the existence of ZnO nanocrystallites (ZnO NCs) with (100), (002), and (101) growth planes. The nanofilms fabricated represented a distinct optical property through absorption and broad emission, as the optical energy band gap reduced as the nanofilms annealed (at 120 ℃). Based on the obtained results, it was established that phytochemicals extracted from organic natural SOL leaves have a distinct influence on zoic oxide nanofilm fabrication, which may be useful for visible light spectrum trapping. The nanofilms can be used in photovoltaic solar cell applications.
Previous in vitro and in vivo studies have reported that 1'-S-1'-acetoxychavicol acetate (ACA) isolated from rhizomes of the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) induces apoptosis-mediated cell death in tumour cells via dysregulation of the NF-κB pathway. However there were some clinical development drawbacks such as poor in vivo solubility, depreciation of biological activity upon exposure to an aqueous environment and non-specific targeting of tumour cells. In the present study, all the problems above were addressed using the novel drug complex formulation involving recombinant human alpha fetoprotein (rhAFP) and ACA.
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
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.
Resveratrol, a natural stilbene found in grapes and wines exhibits a wide range of pharmacological properties. Resveratrol is also known as a good chemopreventive agent for inhibiting carcinogenesis processes that target kinases, cyclooxygenases, ribonucleotide reductase and DNA polymerases. A total of 19 analogues with an amide moiety were synthesized and the cytotoxic effects of the analogues on a series of human cancer cell lines are reported. Three compounds 6d, 6i and 6n showed potent cytotoxicity against prostate cancer DU-145 (IC50=16.68 µM), colon cancer HT-29 (IC50=7.51 µM) and breast cancer MCF-7 (IC50=21.24 µM), respectively, which are comparable with vinblastine. The resveratrol analogues were synthesized using the Heck method.
A phytochemical investigation of the methanolic extract of the bark of Endiandra kingiana led to the isolation of seven new tetracyclic endiandric acid analogues, kingianic acids A-G (1-7), together with endiandric acid M (8), tsangibeilin B (9) and endiandric acid (10). Their structures were determined by 1D- and 2D-NMR analysis in combination with HRMS experiments. The structure of compounds 9 and 10 were confirmed by single-crystal X-ray diffraction analysis. These compounds were screened for Bcl-xL and Mcl-1 binding affinities and cytotoxic activity on various cancer cell lines. Compound 5 showed moderate cytotoxic activity against human colorectal adeno-carcinoma (HT-29) and lung adenocarcinoma epithelial (A549) cell lines, with IC50 values in the range 15-17 µM, and compounds 3, 6 and 9 exhibited weak binding affinity for the anti-apoptotic protein Mcl-1.
A retrospective analysis of 15 cases intracanalicular acoustic neuroma that undergone tumour excision by translabyrinthine approach spanning from August 1996 until December 2002 is presented. The main presenting complaints are unilateral hearing loss (100%) and tinnitus (86.7%). The mean age of presentation was 48.5 years old. Magnetic resonance imaging is the most important investigation tool to diagnose acoustic neuroma. At six months post operatively, the facial nerve was normal or near normal (grade I and II) in 46.6%, grade III to IV in 46.6% and grade V to VI in 6.7% of the cases respectively. There were also four cases of post operative cerebrospinal fluid leak, which was successfully managed with conservative measures. The translabyrinthine approach is the most familiar surgical technique employed by otologist. It is the most direct route to the cerebellopontine angle and internal auditory canal. It requires minimum cerebellar retraction. However, it sacrifices any residual hearing in the operated ear.
A phytochemical study of the EtOAc-soluble part of the methanolic extract of the bark of Endiandra kingiana led to the isolation of three new pentacyclic kingianins as racemic mixtures, kingianins O-Q (1-3), together with the known kingianins A, F, K, L, M and N (4-9), respectively. The structures of the new kingianins 1-3 were determined by 1D and 2D NMR analysis in combination with HRESIMS experiments. Kingianins A-Q were assayed for Mcl-1 binding affinity. Kingianins G and H were found to be potent inhibitors of Mcl-1/Bid interaction. A structure-activity relationship study showed that potency is very sensitive to the substitution pattern on the pentacyclic core. In addition, in contrast with the binding affinity for Bcl-xL, the levorotatory enantiomers of kingianins G, H and J exhibited similar binding affinities for Mcl-1 than their dextrorotatory counterparts, indicating that the two anti-apoptotic proteins have slightly different binding profiles.
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
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.
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.
Crouzon syndrome (CS) is the most common craniosynostosis syndrome and requires a comprehensive management strategy for the optimization of care and functional rehabilitation. This report presents a case series of 6 pediatric patients diagnosed with CS who were treated with distraction osteogenesis (DO) to treat serious functional issues involving severe orbital proptosis, an obstructed nasopharyngeal airway, and increased intracranial pressure (ICP). Three boy and 3 girls were 8 months to 6 years old at the time of the operation. The mean skeletal advancement was 16.1 mm (range, 10 to 27 mm) with a mean follow-up of 31.7 months (range, 13 to 48 months). Reasonable and successful outcomes were achieved in most patients as evidenced by adequate eye protection, absence of signs and symptoms of increased ICP, and tracheostomy tube decannulation except in 1 patient. Complications were difficult fixation of external stabilizing pins in the distraction device (n = 1) and related to surgery (n = 4). Although DO can be considered very technical and can have potentially serious complications, the technique produces favorable functional and clinical outcomes in treating severe CS.
Medicinal plants containing active natural compounds have been used as an alternative treatment for cancer patients in many parts of the world especially in Asia (Itharat et al. 2004). In this report, we describe the cytotoxic and apoptotic properties of 1'S-1'-acetoxyeugenol acetate (AEA), an analogue of 1'S-1'-acetoxychavicol acetate (ACA), isolated from the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) on human breast cancer cells. Data from MTT cell viability assays indicated that AEA induced both time- and dose-dependent cytotoxicity with an IC(50) value of 14.0 μM within 36 h of treatment on MCF-7 cells, but not in HMEC normal control cells. Both annexin V-FITC/PI flow cytometric analysis and DNA fragmentation assays confirmed that AEA induced cell death via apoptosis. AEA was also found to induce cell cycle arrest in MCF-7 cells at the G(0)/G(1) phase with no adverse cell cycle arrest effects on HMEC normal control cells. It was concluded that AEA isolated from the Malaysian tropical ginger represents a potential chemotherapeutic agent against human breast cancer cells with higher cytotoxicity potency than its analogue, ACA.
Furopyridine III, namely 1-(3-amino-4-(4-(tert-butyl)phenyl)-6-(p-tolyl)furo[2,3-b]pyridin-2-yl)ethan-1-one, synthesized from 4-(4-(tert-butyl)phenyl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile I in two steps. The title compound is characterized by NMR, MS and its X-ray structure. The molecular structure consists of planar furopyridine ring with both phenyl rings being inclined from the furopyridine scaffold to a significant different extent. There are three intramolecular hydrogen bonds within the structure. The lattice is stabilized by N-H…O, H2C-H …π and π…π intermolecular interactions leading to three-dimensional network. Compound III exhibits fluorescent properties, which are investigated. Antimicrobial potential and antioxidant activity screening studies for the title compound III and the heterocyclic derivatives, I and II, show no activity towards neither bacterial nor fungal strains, while they exhibited weak to moderate antioxidant activity compared to reference.
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.
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.
A 24 year-old Malay lady presented with high grade fever, myalgia, generalized rashes, severe headache and was positive for dengue serology test. Her lowest platelet count was 45 × 10(9) cells/L. She complained of sudden onset of painlessness, profound loss of vision bilaterally 7 days after the onset of fever. On examination, her right eye best corrected vision was 6/30 and left eye was 6/120. Her anterior segment examination was unremarkable. Funduscopy revealed there were multiple retinal haemorrhages found at posterior pole of both fundi and elevation at fovea area with subretinal fluid. Systemic examination revealed normal findings except for residual petechial rashes. She was managed conservatively. Her vision improved tremendously after 2 months. The retinal hemorrhages and foveal elevation showed sign of resolving. Ocular manifestations following dengue fever is rare. However, bilateral visual loss can occur if both fovea are involved.