Research in Malaysia

Recent research output from Malaysia (via PubMed). Updated automatically.

A positive urine pregnancy test (UPT) with adnexal mass; ectopic pregnancy is not the ultimate diagnosis.

Horm Mol Biol Clin Investig. 2018 Mar 20;:

Authors: Ahmad MF, Abu MA, Chew KT, Sheng KL, Zakaria MA

A positive urine pregnancy test (UPT) with adnexal mass in ectopic pregnancy is not the ultimate diagnosis. The incidence of ectopic pregnancy is about 27 per 1000 pregnancies [1]. On average, about 6-16% will present to an emergency department with first-trimester bleeding and abdominal pain [2]. On presenting with these symptoms with the simultaneous presence of an adnexal mass and an empty uterus, a UPT is of paramount importance to determine whether the symptoms are pregnancy related or not. When the UPT is positive, an ectopic pregnancy is not the only diagnosis as the rare entity of non-gestational ovarian choriocarcinoma (NGOC) should be considered. Here we present two case reports of NGOC, which were initially diagnosed as ectopic pregnancy. The first case is a 16-year-old girl, with vaginal bleeding and an adnexal mass due to an ovarian choriocarcinoma, She underwent unilateral oophorectomy and received multiple courses of chemotherapy. She is disease free without evidence of recurrence or metastasis after 12 months of follow-up. The second patient is also 16 years old and presented with an acute abdomen. She was diagnosed as a ruptured luteal cyst and underwent partial oophorectomy. When the pathologist diagnosed a choriocarcinoma she received multiple courses of chemotherapy, but thereafter an advanced disease was diagnosed with evidence of distant metastasis.

PMID: 29558344 [PubMed - as supplied by publisher]

Severity of Pain and Sleep Problems during Kratom (Mitragyna speciosa Korth.) Cessation among Regular Kratom Users.

J Psychoactive Drugs. 2018 Mar 20;:1-9

Authors: Singh D, Narayanan S, Vicknasingam BK, Prozialeck WC, Ramanathan S, Zainal H, Harun SN

Kratom (Mitragyna speciosa Korth.) is traditionally used in Southeast Asia for its medicinal value and psychoactive properties. Nonetheless, cessation from regular kratom use is reported to cause unpleasant dose-dependent withdrawal symptoms. This study aims to evaluate the severity of pain and sleep problems following the cessation of kratom tea/juice consumption among regular kratom users. A total of 170 regular users were recruited through snowball sampling for this cross-sectional study. The Brief Pain Inventory (BPI) and Pittsburgh Sleep Quality Index (PSQI) scales were administered to assess the severity of pain and sleep problems. Most participants experienced moderate pain intensity (84%) and moderate pain interference (70%) during kratom cessation; 46% experienced more sleep problems during kratom cessation. Individuals who consumed ≥4 glasses of kratom tea/juice (about 76-115 mg of mitragynine) daily had higher odds of reporting some pain interference (OR: 2.0; CI: 1.04-3.93: p < .028), and sleep problems during kratom cessation (OR: 2.0; CI: 1.08-3.68: p < .020), as compared to those who consumed 1-3 glasses of kratom tea/juice daily. However, the effects were still relatively mild. Cessation from regular kratom tea/juice consumption is not associated with prolonged pain and sleep problems, as compared to those reported for opioid analgesics.

PMID: 29558272 [PubMed - as supplied by publisher]

Upper Instrumented Vertebrae (UIV) Tilt Angle is an Important Postoperative Radiological Parameter that Correlates With Postoperative Neck and Medial Shoulder Imbalance.

Spine (Phila Pa 1976). 2018 Mar 19;:

Authors: Chan CYW, Chiu CK, Ler XY, Ng YH, Chian XH, Tan PH, Kwan MK

STUDY DESIGN: Retrospective study.
OBJECTIVE: To investigate the association between postoperative upper instrumented vertebra (UIV) Tilt Angle with postoperative medial shoulder and neck imbalance.
SUMMARY OF BACKGROUND DATA: Studies had found that current recommendations for UIV selection were not predictive of good postoperative shoulder balance.
METHODS: 98 AIS patients with Lenke 1/2 curves who underwent posterior spinal fusion between 2013 and 2014 with minimum follow up of 2 years were recruited. Radiological parameters: UIV Tilt Angle, T1 Tilt, Cervical Axis and Clavicle Angle were measured preoperatively, postoperatively and at final follow-up.
RESULTS: Mean age was 16.2 ± 6.2 years. Mean follow-up was 37.9 ± 6.5 months. There were 73.5% Lenke 1 and 26.5% Lenke 2 curves. Significant factors affecting postoperative T1 Tilt were postoperative UIV Tilt Angle, preoperative T1 Tilt and preoperative UIV Tilt Angle. Postoperative UIV Tilt Angle and preoperative Cervical Axis were significant factors affecting Cervical Axis at final follow up. UIV level was not significant independent factor that affected post-operative T1 Tilt and Cervical Axis. There was strong correlation between postoperative UIV Tilt Angle and T1 Tilt for the whole cohort (p < 0.001), when UIV was at T2 (p < 0.001), T3(p < 0.001) and T4 (p < 0.001). Postoperative UIV Tilt Angle also had significant correlation with Cervical Axis when UIV was at T2 (p = 0.021) and T3(p = 0.009).
CONCLUSIONS: Postoperative UIV Tilt Angle was an independent factor which had significant correlation with postoperative T1 Tilt and Cervical Axis measurement. There was strong correlation between postoperative UIV Tilt Angle and T1 Tilt for the whole cohort, when UIV was at T3 and T4. There was very strong correlation between post-operative UIV Tilt Angle and T1 Tilt when UIV was at T2. There was also moderate and significant correlation between postoperative UIV Tilt Angle and Cervical Axis for the whole cohort.

PMID: 29557927 [PubMed - as supplied by publisher]

Physical activity, but not sedentary time, influences bone strength in late adolescence.

Arch Osteoporos. 2018 Mar 20;13(1):31

Authors: Tan VP, Macdonald HM, Gabel L, McKay HA

Physical activity is essential for optimal bone strength accrual, but we know little about interactions between physical activity, sedentary time, and bone outcomes in older adolescents. Physical activity (by accelerometer and self-report) positively predicted bone strength and the distal and midshaft tibia in 15-year-old boys and girls. Lean body mass mediated the relationship between physical activity and bone strength in adolescents.
PURPOSE: To examine the influence of physical activity (PA) and sedentary time on bone strength, structure, and density in older adolescents.
METHODS: We used peripheral quantitative computed tomography to estimate bone strength at the distal tibia (8% site; bone strength index, BSI) and tibial midshaft (50% site; polar strength strain index, SSIp) in adolescent boys (n = 86; 15.3 ± 0.4 years) and girls (n = 106; 15.3 ± 0.4 years). Using accelerometers (GT1M, Actigraph), we measured moderate-to-vigorous PA (MVPAAccel), vigorous PA (VPAAccel), and sedentary time in addition to self-reported MVPA (MVPAPAQ-A) and impact PA (ImpactPAPAQ-A). We examined relations between PA and sedentary time and bone outcomes, adjusting for ethnicity, maturity, tibial length, and total body lean mass.
RESULTS: At the distal tibia, MVPAAccel and VPAAccel positively predicted BSI (explained 6-7% of the variance, p < 0.05). After adjusting for lean mass, only VPAAccel explained residual variance in BSI. At the tibial midshaft, MVPAAccel, but not VPAAccel, positively predicted SSIp (explained 3% of the variance, p = 0.01). Lean mass attenuated this association. MVPAPAQ-A and ImpactPAPAQ-A also positively predicted BSI and SSIp (explained 2-4% of the variance, p < 0.05), but only ImpactPAPAQ-A explained residual variance in BSI after accounting for lean mass. Sedentary time did not independently predict bone strength at either site.
CONCLUSION: Greater tibial bone strength in active adolescents is mediated, in part, by lean mass. Despite spending most of their day in sedentary pursuits, adolescents' bone strength was not negatively influenced by sedentary time.

PMID: 29556801 [PubMed - in process]

Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines.

Chem Cent J. 2018 Mar 19;12(1):31

Authors: Zamrus SNH, Akhtar MN, Yeap SK, Quah CK, Loh WS, Alitheen NB, Zareen S, Tajuddin SN, Hussin Y, Shah SAA

BACKGROUND: Curcumin is one of the leading compound extracted from the dry powder of Curcuma longa (Zingiberaceae family), which possess several pharmacological properties. However, in vivo administration exhibited limited applications in cancer therapies.
RESULTS: Twenty-four curcumin derivatives have synthesized, which comprises cyclohexanone 1-10, acetone 11-17 and cyclopentanone 18-24 series. All the curcuminoids were synthesized by the acid or base catalyzed Claisen Schmidt condenstion reactions, in which β-diketone moiety of curcumin was modified with mono-ketone. These curcuminoids 1-24 were screened against HeLa, K562, MCF-7 (an estrogen-dependent) and MDA-MB-231 (an estrogen-independent) cancer cell lines. Among them, acetone series 11-17 were found to be more selective and potential cytotoxic agents. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines. Among the cyclohexanone series, the compound 4 exhibited (IC50 = 11.04 ± 2.80, 6.50 ± 01.80, 8.70 ± 3.10 and 2.30 ± 1.60 µg/mL) potential cytotoxicity against four proposed cancer cell lines, respectively. All the curcucminoids were characterized with the detailed 1H NMR, IR, UV-Vis, and mass spectroscopic techniques. The structure of compound 4 was confirmed by using the single X-ray crystallography. Additionally, we are going to report the first time spectral data of (2E,6E)-2,6-bis(2-methoxybenzylidene)cyclohexanone (1). Structure-activity relationships revealed that the mono-carbonyl with 2,5-dimethoxy substituted curcuminoids could be an essential for the future drugs against cancer diseases.
CONCLUSIONS: Curcuminoids with diferuloyl(4-hydroxy-3-methoxycinnamoyl) moiety with mono carbonyl exhibiting potential cytotoxic properties. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines.

PMID: 29556774 [PubMed]

Biochemical and structural characterization of a novel cold-active esterase-like protein from the psychrophilic yeast Glaciozyma antarctica.

Extremophiles. 2018 Mar 20;:

Authors: Hashim NHF, Mahadi NM, Illias RM, Feroz SR, Abu Bakar FD, Murad AMA

Dienelactone hydrolase, an α/β hydrolase enzyme, catalyzes the hydrolysis of dienelactone to maleylacetate, an intermediate for the Krebs cycle. Genome sequencing of the psychrophilic yeast, Glaciozyma antarctica predicted a putative open reading frame (ORF) for dienelactone hydrolase (GaDlh) with 52% sequence similarity to that from Coniophora puteana. Phylogenetic tree analysis showed that GaDlh is closely related to other reported dienelactone hydrolases, and distantly related to other α/β hydrolases. Structural prediction using MODELLER 9.14 showed that GaDlh has the same α/β hydrolase fold as other dienelactone hydrolases and esterase/lipase enzymes, with a catalytic triad consisting of Cys-His-Asp and a G-x-C-x-G-G motif. Based on the predicted structure, GaDlh exhibits several characteristics of cold-adapted proteins such as glycine clustering in the binding pocket, reduced protein core hydrophobicity, and the absence of proline residues in loops. The putative ORF was amplified, cloned, and overexpressed in an Escherichia coli expression system. The recombinant protein was overexpressed as soluble proteins and was purified via Ni-NTA affinity chromatography. Biochemical characterization of GaDlh revealed that it has an optimal temperature at 10 °C and that it retained almost 90% of its residual activity when incubated for 90 min at 10 °C. The optimal pH was at pH 8.0 and it was stable between pH 5-9 when incubated for 60 min (more than 50% residual activity). Its Km value was 256 μM and its catalytic efficiency was 81.7 s-1. To our knowledge, this is the first report describing a novel cold-active dienelactone hydrolase-like protein.

PMID: 29556723 [PubMed - as supplied by publisher]

Angiogenic and osteogenic potentials of dental stem cells in bone tissue engineering.

J Oral Biol Craniofac Res. 2018 Jan-Apr;8(1):48-53

Authors: Yusof MFH, Zahari W, Hashim SNM, Osman ZF, Chandra H, Kannan TP, Noordin KBAA, Azlina A

Manipulation of dental stem cells (DSCs) using current technologies in tissue engineering unveil promising prospect in regenerative medicine. DSCs have shown to possess angiogenic and osteogenic potential in both in vivo and in vitro. Neural crest derived DSCs can successfully be isolated from various dental tissues, exploiting their intrinsic great differentiation potential. In this article, researcher team intent to review the characteristics of DSCs, with focus on their angiogenic and osteogenic differentiation lineage. Clinical data on DSCs are still lacking to prove their restorative abilities despite extensive contemporary literature, warranting research to further validate their application for bone tissue engineering.

PMID: 29556464 [PubMed]

Knowledge about human papillomavirus (HPV) related oral cancers among oral health professionals in university setting-A cross sectional study.

J Oral Biol Craniofac Res. 2018 Jan-Apr;8(1):35-39

Authors: Arora S, Ramachandra SS, Squier C

Introduction: Scientific literature suggests that human papillomavirus (HPV) infection may be associated with oral squamous cell carcinoma (OSCC). However, knowledge regarding HPV-OSCC link among oral health professionals (OHP) has been insufficient. So, the aim of this study was to assess the knowledge about HPV associated OSCC among OHP working in dental faculties in Malaysia.
Methodology: Ethical committee of the University approved this study. A validated, pre-tested questionnaire was sent electronically to 224 OHP. Questionnaire collected information regarding demography, knowledge about HPV-OSCC link, HPV vaccine, and willingness to educate patients about HPV OSCC link among the participants of this cross-sectional study. Data collected was analysed using "Stata/IC-13" and was summarised using descriptive statistics like frequency, percentage, mean and standard deviation.
Results: Out of 179 participants, around 39% of the participant's opined virus was not a causative factor for OSCC. Around, 44% replied posterior portion of the tongue/oro-pharynx was the commonest site for HPV related OSCC, whereas 29% replied that lateral border of the tongue was the common site for HPV related OSCC. Forty one percent educated patients regarding HPV infection being a causative factor for OSCC. HPV vaccine can prevent OSCC was stated by 70% OHP. Only 12% were aware of the availability of HPV vaccine in Malaysia. Majority (99%), agreed that there is a need to offer continuing education programmes to dentists highlighting advances and preventive strategies in the fight against OSCC.
Conclusion: Substantial increase in awareness is required among OHP regarding HPV-OSCC link.

PMID: 29556461 [PubMed]

Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand.

J Venom Anim Toxins Incl Trop Dis. 2018;24:9

Authors: Charoenpitakchai M, Wiwatwarayos K, Jaisupa N, Rusmili MRA, Mangmool S, Hodgson WC, Ruangpratheep C, Chanhome L, Chaisakul J

Background: Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities of B. candidus venoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats.
Methods: Rats were administered Malayan krait (BC-NE or BC-S) venom (50 μg/kg, i.m.) or 0.9% NaCl solution (50 μL, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity.
Results: Administration of BC-NE or BC-S venom (50 μg/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (100-0.2 μg/mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 = 8 ± 1 μg/mL; at 24 h incubation; n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 = 15 ± 2 μg/mL; at 24 h incubation; n = 4). In addition, the PLA2 activity of BC-NE venom was significantly higher than that of BC-S venom.
Conclusions: This study found that Malayan krait venoms from both populations possess myotoxic, cytotoxic and nephrotoxic activities. These findings may aid in clinical diagnosis and treatment of envenomed patients in the future.

PMID: 29556251 [PubMed]

Anti-nociceptive mechanisms of flavonoids-rich methanolic leaf extract from Terminalia coriacea (Roxb.) Wight & Arn. leaves.

Food Chem Toxicol. 2018 Mar 16;:

Authors: Ali Khan MS, Ahmed N, Misbah, Arifuddin M, Zakaria ZA, Al-Sanea MM, Kulsoom Khundmiri SU, Ahmed I, Ahmed S, Mok PL

In view of the report on anti-nociceptive activity of Leathery Murdah, Terminalia coriacea {Roxb.} Wight & Arn. (Combretaceae) leaves, the present study was conducted to isolate the active constituents and identify the underlying mechanisms. The methanolic extract of T. coriacea leaves (TCLME) at doses 125, 250 and 500 mg/kg orally, was subjected to various in-vivo assays in acetic acid induced writhing and formalin induced paw-licking tests with aspirin (100 mg/kg) and morphine (5 mg/kg) as reference drugs. Three flavonoids, rutin, robinin and gossypetin 3-glucuronide 8-glucoside were isolated and characterized from TCLME for the first time. The extract showed significant (p < 0.001) dose-dependent anti-nociceptive activity in glutamate induced paw licking in mice. The involvement of opioid pathway was confirmed as naloxone (5 mg/kg, i.p) treatment blocked the analgesic activity of the test extract. Similarly, glibenclamide (an ATP - sensitive potassium channel inhibitor) at dose of 10 mg/kg, i.p increased writhing in acetic acid model. It reversed the inhibitory effects of TCLME when administered in combination. Treatment of TCLME alone and in combination with l-arginine (100 mg/kg, i.p) significantly (p < 0.001) reduced writhing while pre-treatment with l-NAME (20 mg/kg, i.p) further enhanced the analgesic action of TCLME indicating involvement of nitric oxide pathway.

PMID: 29555329 [PubMed - as supplied by publisher]

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