New phenylisoxazole quinoxalin-2-amine hybrids 5a-i were successfully synthesised with yields of 53-85% and characterised with various spectroscopy methods. The synthesised hybrids underwent in vitro α-amylase and α-glucosidase inhibitory assays, with acarbose as the positive control. Through the biological study, compound 5h exhibits the highest α-amylase inhibitory activity with IC50 = 16.4 ± 0.1 μM while compounds 5a-c, 5e and 5h exhibit great potential as α-glucosidase inhibitors, with 5c being the most potent (IC50 = 15.2 ± 0.3 μM). Among the compounds, 5h exhibits potential as a dual inhibitor for both α-amylase (IC50 = 16.4 ± 0.1 μM) and α-glucosidase (IC50 = 31.6 ± 0.4 μM) enzymes. Through the molecular docking studies, the inhibition potential of the selected compounds is supported. Compound 5h showed important interactions with α-amylase enzyme active sites and exhibited the highest binding energy of -8.9 ± 0.10 kcal mol-1, while compound 5c exhibited the highest binding energy of -9.0 ± 0.20 kcal mol-1 by forming important interactions with the α-glucosidase enzyme active sites. The molecular dynamics study showed that the selected compounds exhibited relative stability when binding with α-amylase and α-glucosidase enzymes. Additionally, compound 5h demonstrated a similar pattern of motion and mechanism of action as the commercially available miglitol.
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.
Faecal incontinence is a debilitating chronic clinical condition which may affect the patient and care givers. Modality of treatment is based on severity of the symptoms as well as the anatomical defect itself, availability of resources and expertise. We describe a modified technique of dynamic graciloplasty as neoanal sphincter for the treatment severe faecal incontinence who has failed previous over lapping sphincteroplasty. In our modified version, instead of using implanted intramuscular electrodes and subcutaneous neurostimulator to provide continuous stimulation, the patient will undergo an external stimulation on the nerve of transplanted gracilis periodically and concurrent biofeedback therapy. We believe the technique is relatively easy to learn and very cost effective without any electrodes or neurostimulator related complications.
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.
RetCam is an excellent screening tool for the detection of retinopathy of prematurity (ROP). However, affordability is a barrier when adopting the use of RetCam in developing countries. We aimed to describe different stages of ROP using ultrasonographic B-scan and to evaluate the association between funduscopic examinations and ultrasonographic B-scan findings in premature neonates with ROP in Malaysia. A descriptive cross sectional study was conducted in 90 eyes of 47 premature neonates with different stages of ROP in three tertiary hospitals in Malaysia. Experienced ophthalmologists performed detailed funduscopic examinations using binocular indirect ophthalmoscopy (BIO). A masked examiner performed a 10 MHz ultrasonographic B-scan evaluation with 12 meridian position images within 48 hours of clinical diagnosis. Data from the clinical examination and ultrasonographic findings were collected and analysed. We recruited 37 eyes (41.1%) with stage 1 ROP, 29 eyes (32.3%) with stage 2, 18 eyes (20.0%) with stage 3, and 3 eyes (3.3%) with stages 4 and 5 based on the clinical assessment. Ultrasonography correctly identified 3 (8.1%) stage 1 eyes, 17 (58.6%) stage 2 eyes, 13 (72.2%) stage 3 eyes, and 3 each (100%) of the stage 4 and 5 eyes. There was a significant association between the funduscopic signs and the ultrasound findings for stage 2 ROP and above (Fisher's exact test, p <0.001). In conclusion, all stages of ROP were detected and described with a 10 MHz ultrasonic B-scan system. A significant association was observed between funduscopic signs and ultrasonographic findings in premature Malaysian neonates with stage 2 ROP and above.