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Synthesis and formulation studies of griseofulvin analogues with improved solubility and metabolic stability

Petersen AB, Andersen NS, Konotop G, Hanafiah NH, Raab MS, Krämer A, et al.

Eur J Med Chem, 2017 Apr 21;130:240-247.
PMID: 28258034 DOI: 10.1016/j.ejmech.2017.02.055

Griseofulvin (1) is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Comprehensive SAR studies have led to the identification of 2'-benzyloxy griseofulvin 2, a more potent analogue with low micromolar anticancer potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve the poor pharmacokinetic properties, 11 griseofulvin analogues were synthesized and evaluated for biological activity and physiological stabilities including SGF, plasma, and metabolic stability. Finally, the most promising compounds were investigated in respect to thermodynamic solubility and formulation studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral and intravenous administration. Finally, 2'-benzylamine analogue 10 was confirmed to induce G2/M cell cycle arrest in vitro.
Fulltext Familial primary antiphospholipid syndrome: A report of co-occurrence in three Malaysian family members

Islam MA, Wong KK, Sasongko TH, Gan SH, Wong JS

Eur J Rheumatol, 2016 Sep;3(3):139-141.
PMID: 27733946 DOI: 10.5152/eurjrheum.2015.0068

Here we present a case report of three familial primary antiphospholipid syndrome (PAPS) patients from Malaysia. The three familial patients comprised two females and one male with a mean age of 26.3 years. The first diagnosis was made between 2005 and 2009, and all patients demonstrated deep vein thrombosis, high levels of IgM and IgG anticardiolipin antibodies, and received warfarin treatment international normalized ratio (INR) 2.0-3.0. The patients ceased to show clinical symptoms after treatment. Recently (August 2014), we investigated whether the levels of antiphospholipid antibodies remained elevated, and we found that seronegativity occurred in the patients. We suspect that prolonged anticoagulant treatment might be one of the causes of reduced levels of antiphospholipid antibodies in these familial PAPS patients.
A Randomized, Single-Blind Trial of Clobetasol Propionate 0.05% Cream Under Silicone Dressing Occlusion Versus Intra-Lesional Triamcinolone for Treatment of Keloid

Nor NM, Ismail R, Jamil A, Shah SA, Imran FH

Clin Drug Investig, 2017 Mar;37(3):295-301.
PMID: 27888448 DOI: 10.1007/s40261-016-0484-x

BACKGROUND AND OBJECTIVE: Keloid is conventionally treated with intra-lesional (IL) triamcinolone, which is highly operator dependent and has its own adverse effects. Topical steroid and silicone dressings are a patient friendly and non-invasive treatment alternative. We therefore sought to determine the efficacy and safety of topical clobetasol propionate (Dermovate(®)) 0.05% cream under occlusion with Mepiform(®) silicone dressing compared to IL triamcinolone in the treatment of keloid.
METHODS: This was a prospective, randomised, observer-blinded study. Two keloids on the same site were randomly assigned to receive either daily topical clobetasol propionate 0.05% cream under occlusion with silicone dressing (Scar 1) or monthly IL triamcinolone injection (Scar 2). Efficacy was assessed using patient and observer scar assessment scale (POSAS) at 4-weekly intervals up to 12 weeks. Dimension of keloid and adverse effects were also assessed.
RESULTS: A total of 34 scars from 17 patients completed the study. There was significant improvement of POSAS at 12 weeks compared to baseline within each treatment group. However, there was no statistically significant difference in POSAS at 12 weeks between the two treatments. Keloid dimensions showed a similar trend of improvement by week 12 with either treatment (p = 0.002 in Scar 1, p = 0.005 for Scar 2). However, there was no significant difference between the treatment. In the IL triamcinolone group, all patients reported pain and 70.6% observed necrotic skin reaction. There was a significantly higher rate of adverse effects such as erythema (41.2 vs. 17.6%), hypopigmentation (35.3 vs. 23.5%), telangiectasia (41.2 vs. 17.6%) and skin atrophy (23.5 vs. 5.9%) documented in the IL triamcinolone group when compared to clobetasol propionate 0.05% cream under occlusion with silicone dressing.
CONCLUSION: Clobetasol propionate 0.05% cream under occlusion with silicone dressing is equally effective and has fewer adverse effects compared to IL triamcinolone. Hence, it may be used as an alternative treatment for keloid particularly in patients with low pain threshold, needle phobia and those who prefers home-based treatment.
Anti-Proliferative Effects of Dendrophthoe pentandra Methanol Extract on BCR/ABL-Positive and Imatinib-Resistant Leukemia Cell Lines

Zamani A, Mat Jusoh SA, Al-Jamal HA, Sul'ain MD, Johan MF

Asian Pac J Cancer Prev, 2016 11 01;17(11):4857-4861.
PMID: 28030911

Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R (IC50= 192 μg/mL) compared to K562 (500 μg/ mL) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.
Comprehensive insight into the binding of sunitinib, a multi-targeted anticancer drug to human serum albumin

Kabir MZ, Tee WV, Mohamad SB, Alias Z, Tayyab S

Spectrochim Acta A Mol Biomol Spectrosc, 2017 Jun 15;181:254-263.
PMID: 28376387 DOI: 10.1016/j.saa.2017.03.059

Binding studies between a multi-targeted anticancer drug, sunitinib (SU) and human serum albumin (HSA) were made using fluorescence, UV-vis absorption, circular dichroism (CD) and molecular docking analysis. Both fluorescence quenching data and UV-vis absorption results suggested formation of SU-HSA complex. Moderate binding affinity between SU and HSA was evident from the value of the binding constant (3.04×104M-1), obtained at 298K. Involvement of hydrophobic interactions and hydrogen bonds as the leading intermolecular forces in the formation of SU-HSA complex was predicted from the thermodynamic data of the binding reaction. These results were in good agreement with the molecular docking analysis. Microenvironmental perturbations around Tyr and Trp residues as well as secondary and tertiary structural changes in HSA upon SU binding were evident from the three-dimensional fluorescence and circular dichroism results. SU binding to HSA also improved the thermal stability of the protein. Competitive displacement results and molecular docking analysis revealed the binding locus of SU to HSA in subdomain IIA (Sudlow's site I). The influence of a few common ions on the binding constant of SU-HSA complex was also noticed.
Biological activities of Anastatica hierochuntica L.: A systematic review

Zin SRM, Kassim NM, Alshawsh MA, Hashim NE, Mohamed Z

Biomed Pharmacother, 2017 Jul;91:611-620.
PMID: 28486192 DOI: 10.1016/j.biopha.2017.05.011

Anastatica hierochuntica L. (A. hierochuntica) is a desert plant consumed by people across the globe to treat various medical conditions. This review is aimed at providing a summary of the scientific findings on biological activities of A. hierochuntica and suggests areas in which further research is needed. This systematic review was synthesized from the literature obtained from the following databases; PubMed, Science Direct, Web of Science, Ovid Medline, Scopus, Google Scholar and WorldCat. Previous studies have indicated that the methanolic and aqueous extracts of this plant have antioxidant, antifungal and antimicrobial activities. It was shown to have the ability to activate phagocytes and to possess microbicidal activity, thereby causing increased resistance to infection. Both methanolic and aqueous extracts of this plant were also demonstrated to have a hypoglycaemic property, whilst the methanolic extract significantly exhibited hypolipidaemic effects in diabetic rats. Moreover, the methanolic extract of A. hierochuntica has been suggested to have hepatoprotective properties. This is supported by its ability to significantly decrease transaminase and alkaline phosphatase activities in alloxan-induced diabetic rats. Besides, this desert plant exhibited anti-inflammatory, anti-melanogenic and gastroprotective activities. Even though A. hierochuntica is widely used, studies on this plant are still scarce, thus its reputed biological activities and medical benefits require critical evaluation. Before A. hierochuntica can be used clinically, further studies need to be conducted to increase our understanding of the effects of this plant, its constituents, and possible mechanisms of action.
Comparison of the learning of two notations: A pilot study

Akram A, Fuadfuad MD, Malik AM, Nasir Alzurfi BM, Changmai MC, Madlena M

J Adv Med Educ Prof, 2017 Apr;5(2):67-72.
PMID: 28367462

INTRODUCTION: MICAP is a new notation in which the teeth are indicated by letters (I-incisor, C-canine, P-premolar, M-molar) and numbers [1,2,3] which are written superscript and subscript on the relevant letters. FDI tooth notation is a two digit system where one digit shows quadrant and the second one shows the tooth of the quadrant. This study aimed to compare the short term retention of knowledge of two notation systems (FDI two digit system and MICAP notation) by lecture method.
METHODS: Undergraduate students [N=80] of three schools participated in a cross-over study. Two theory-driven classroom based lectures on MICAP notation and FDI notation were delivered separately. Data were collected using eight randomly selected permanent teeth to be written in MICAP format and FDI format at pretest (before the lecture), post-test I (immediately after lecture) and post-test II (one week after the lecture). Analysis was done by SPSS version 20.0 using repeated measures ANCOVA and independent t-test.
RESULTS: The results of pre-test and post-test I were similar for FDI education. Similar results were found between post-test I and post-test II for MICAP and FDI notations.
CONCLUSION: The study findings indicated that the two notations (FDI and MICAP) were equally mind cognitive. However, the sample size used in this study may not reflect the global scenario. Therefore, we suggest more studies to be performed for prospective adaptation of MICAP in dental curriculum.
Biofilm is associated with chronic streptococcal meningoencephalitis in fish

Isiaku AI, Sabri MY, Ina-Salwany MY, Hassan MD, Tanko PN, Bello MB

Microb Pathog, 2017 Jan;102:59-68.
PMID: 27890651 DOI: 10.1016/j.micpath.2016.10.029

Biofilms are aggregates of attached microbial organisms whose existence on tissues is often recognised as a mechanism for the establishment of most chronic diseases. Herein we investigated the ability of piscine Streptococcus agalactiae, an important aquatic pathogen, for adaptation to this sessile lifestyle in vitro and in the brain of a tilapia fish model. Piscine S. agalactiae exhibited a weak attachment to polystyrene plates and expressed a low biofilm phenotype under the study conditions. Furthermore, fluorescent in situ hybridization and confocal laser scanning microscopy revealed discrete aggregates of attached S. agalactiae within brain tissues and around meningeal surfaces. They were embedded in an exopolysaccharide containing matrix, intractable to inflammatory response and showed some level of resistance to penicillin despite proven susceptibility on sensitivity test. Intracellular bacterial aggregates were also observed, moreover, antibody mediated response was not demonstrated during infection. Nucleated erythrocytes appear to facilitate brain invasion possibly via the Trojan horse mechanism leading to a granulomatous inflammation. We have demonstrated that biofilm is associated with persistence of S. agalactiae and the development of chronic meningoencephalitis in fish.
Influence of alkaline hydrogen peroxide pre-hydrolysis on the isolation of microcrystalline cellulose from oil palm fronds

Owolabi AF, Haafiz MK, Hossain MS, Hussin MH, Fazita MR

Int J Biol Macromol, 2017 Feb;95:1228-1234.
PMID: 27836655 DOI: 10.1016/j.ijbiomac.2016.11.016

In the present study, microcrystalline cellulose (MCC) was isolated from oil palm fronds (OPF) using chemo-mechanical process. Wherein, alkaline hydrogen peroxide (AHP) was utilized to extract OPF fibre at different AHP concentrations. The OPF pulp fibre was then bleached with acidified sodium chlorite solution followed by the acid hydrolysis using hydrochloric acid. Several analytical methods were conducted to determine the influence of AHP concentration on thermal properties, morphological properties, microscopic and crystalline behaviour of isolated MCC. Results showed that the MCC extracted from OPF fibres had fibre diameters of 7.55-9.11nm. X-ray diffraction (XRD) analyses revealed that the obtained microcrystalline fibre had both celluloses I and cellulose II polymorphs structure, depending on the AHP concentrations. The Fourier transmission infrared (FTIR) analyses showed that the AHP pre-hydrolysis was successfully removed hemicelluloses and lignin from the OPF fibre. The crystallinity of the MCC was increased with the AHP concentrations. The degradation temperature of MCC was about 300°C. The finding of the present study showed that pre-treatment process potentially influenced the quality of the isolation of MCC from oil palm fronds.
Fulltext Prediction of incidence and bio-psycho-socio-cultural risk factors of post-partum depression immediately after birth in an Iranian population

Abdollahi F, Zarghami M, Sazlina SG, Zain AM, Mohammad AJ, Lye MS

Arch Med Sci, 2016 Oct 1;12(5):1043-1051.
PMID: 27695496

INTRODUCTION: Post-partum depression (PPD) is the most prevalent mental problem associated with childbirth. The purpose of the present study was to determine the incidence of early PPD and possible relevant risk factors among women attending primary health centers in Mazandaran province, Iran for the first time.
MATERIAL AND METHODS: A longitudinal cohort study was conducted among 2279 eligible women during weeks 32-42 of pregnancy to determine bio-psycho-socio-cultural risk factors of depression at 2 weeks post-partum using the Iranian version of the Edinburgh Postnatal Depression Scale (EPDS). Univariate and hierarchical multiple logistic regression models were used for data analysis.
RESULTS: Among 1,739 mothers whose EPDS scores were ≤ 12 during weeks 32-42 of gestation and at the follow-up study, the cumulative incidence rate of depression was 6.9% (120/1,739) at 2 weeks post-partum. In the multivariate model the factor that predicted depression symptomatology at 2 weeks post-partum was having psychiatric distress in pregnancy based on the General Health Questionnaire (GHQ) (OR = 1.06, (95% CI: 1.04-1.09), p = 0.001). The risk of PPD also lower in those with sufficient parenting skills (OR = 0.78 (95% CI: 0.69-0.88), p = 0.001), increased marital satisfaction (OR = 0.94 (95% CI: 0.9-0.99), p = 0.03), increased frequency of practicing rituals (OR = 0.94 (95% CI: 0.89-0.99), p = 0.004) and in those whose husbands had better education (OR = 0.03 (95% CI: 0.88-0.99), p = 0.04).
CONCLUSIONS: The findings indicated that a combination of demographic, sociological, psychological and cultural risk factors can make mothers vulnerable to PPD.
KEYWORDS: depression; incidence; post-partum
Fulltext Safety and efficacy of tocotrienol supplementation for bone health in postmenopausal women: protocol for a dose-response double-blinded placebo-controlled randomised trial

Shen CL, Mo H, Yang S, Wang S, Felton CK, Tomison MD, et al.

BMJ Open, 2016 12 23;6(12):e012572.
PMID: 28011809 DOI: 10.1136/bmjopen-2016-012572

INTRODUCTION: Osteoporosis is a major health concern in postmenopausal women, and oxidative stress contributes to the development of bone loss. Cellular studies and ovariectomised rat model mimicking bone loss in postmenopausal women show the bone-protective effect of tocotrienols (TTs) with antioxidant capability. We aim to access the safety and efficacy of TT consumption for bone health in postmenopausal women.
METHODS AND ANALYSIS: In this 12-week randomised double-blinded placebo-controlled trial for the effects of dietary TT supplementation in postmenopausal women, postmenopausal women aged 45 years and older with at least 1 year after menopause and bone mineral density T-score at the spine and/or hip 2.5 or more below the reference values will be randomly assigned to 3 daily supplements: (1) placebo group receiving 860 mg olive oil, (2) low TT group receiving 430 mg of 70% pure TTs (containing 300 mg TT) and (3) high TT group receiving 860 mg of 70% pure TTs (600 mg TT). The primary outcome measure will be urinary N-terminal telopeptide. The secondary outcome measures will be serum bone-specific alkaline phosphatase, receptor activator of nuclear factor-κB ligand, osteoprotegerin, urinary 8-hydroxy-2'-deoxyguanosine and quality of life. At 0, 6 and 12 weeks, the following will be assessed: (1) primary and secondary outcome measures; (2) serum TT and tocopherol concentrations; (3) physical activity and food frequency questionnaires. Liver function will be monitored every 6 weeks for safety. 'Intent-to-treat' principle will be employed for data analysis. A model of repeated measurements with random effect error terms will be applied. Analysis of covariance, χ2 analysis and regression will be used for comparisons.
ETHICS AND DISSEMINATION: This study was approved by the Bioethics Committee of the Texas Tech University Health Sciences Center. The findings of this trial will be submitted to a peer-reviewed journal in the areas of bone or nutrition and international conferences.
TRIAL REGISTRATION NUMBER: NCT02058420; results.
Multivariate analysis for source identification of pollution in sediment of Linggi River, Malaysia

Elias MS, Ibrahim S, Samuding K, Rahman SA, Wo YM, Daung JAD

Environ Monit Assess, 2018 Mar 29;190(4):257.
PMID: 29600468 DOI: 10.1007/s10661-018-6632-4

Rapid socioeconomic development in the Linggi River Basin has contributed to the significant increase of pollution discharge into the Linggi River and its adjacent coastal areas. The toxic element contents and distributions in the sediment samples collected along the Linggi River were determined using neutron activation analysis (NAA) and inductively coupled plasma-mass spectrometry (ICP-MS) techniques. The measured mean concentration of As, Cd, Pb, Sb, U, Th and Zn is relatively higher compared to the continental crust value of the respective element. Most of the elements (As, Cr, Fe, Pb, Sb and Zn) exceeded the freshwater sediment quality guideline-threshold effect concentration (FSQG-TEC) value. Downstream stations of the Linggi River showed that As concentrations in sediment exceeded the freshwater sediment quality guideline-probable effect concentration (FSQG-PEC) value. This indicates that the concentration of As will give an adverse effect to the growth of sediment-dwelling organisms. Generally, the Linggi River sediment can be categorised as unpolluted to strongly polluted and unpolluted to strongly to extremely polluted. The correlation matrix of metal-metal relationship, principle component analysis (PCA) and cluster analysis (CA) indicates that the pollution sources of Cu, Ni, Zn, Cd and Pb in sediments of the Linggi River originated from the industry of electronics and electroplating. Elements of As, Cr, Sb and Fe mainly originated from motor-vehicle workshops and metal work, whilst U and Th originated from natural processes such as terrestrial runoff and land erosion.
Fulltext The Study of Drag Reduction on Ships Inspired by Simplified Shark Skin Imitation

Ibrahim MD, Amran SNA, Yunos YS, Rahman MRA, Mohtar MZ, Wong LK, et al.

Appl Bionics Biomech, 2018;2018:7854321.
PMID: 29853998 DOI: 10.1155/2018/7854321

The skin of a fast swimming shark reveals riblet structures that help reduce the shark's skin friction drag, enhancing its efficiency and speed while moving in the water. Inspired by the structure of the shark skin denticles, our team has carried out a study as an effort in improving the hydrodynamic design of marine vessels through hull design modification which was inspired by this riblet structure of shark skin denticle. Our study covers on macroscaled design modification. This is an attempt to propose an alternative for a better economical and practical modification to obtain a more optimum cruising characteristics for marine vessels. The models used for this study are constructed using computer-aided design (CAD) software, and computational fluid dynamic (CFD) simulations are then carried out to predict the effectiveness of the hydrodynamic effects of the biomimetic shark skins on those models. Interestingly, the numerical calculated results obtained show that the presence of biomimetic shark skin implemented on the vessels give about 3.75% reduction of drag coefficient as well as reducing up to 3.89% in drag force experienced by the vessels. Theoretically, as force drag can be reduced, it can lead to a more efficient vessel with a better cruising speed. This will give better impact to shipping or marine industries around the world. However, it can be suggested that an experimental procedure is best to be conducted to verify the numerical result that has been obtained for further improvement on this research.
Fulltext The Effect of Microwave Roasting Over the Thermooxidative Degradation of Perah Seed Oil During Heating

Li KS, Ali MA, Muhammad II, Othman NH, Noor AM

J Oleo Sci, 2018 May 01;67(5):497-505.
PMID: 29628486 DOI: 10.5650/jos.ess17203

The impact of microwave roasting on the thermooxidative degradation of perah seed oil (PSO) was evaluated during heating at a frying temperature (170°C). The roasting resulted significantly lower increment of the values of oxidative indices such as free acidity, peroxide value, p-anisidine, total oxidation (TOTOX), specific extinctions and thiobarbituric acid in oils during heating. The colour L* (lightness) value dropped gradually as the heating time increased up to 12 h, whereas a*(redness) and b* (yellowness) tended to increase. The viscosity and total polar compound in roasted PSO was lower as compared to that in unroasted one at each heating times. The tocol retention was also high in roasted samples throughout the heating period. The relative contents of polyunsaturated fatty acids (PUFAs) were decreased to 94.42% and saturated fatty acids (SFAs) were increased to 110.20% in unroasted sample, after 12 h of heating. On the other hand, in 3 min roasted samples, the relative contents of PUFAs were decreased to 98.08% and of SFAs were increased to 103.41% after 12 h of heating. Outcome from analyses showed that microwave roasting reduced the oxidative deteriorations of PSO during heating.
Fulltext A side-effect free method for identifying cancer drug targets

Ashraf MI, Ong SK, Mujawar S, Pawar S, More P, Paul S, et al.

Sci Rep, 2018 04 27;8(1):6669.
PMID: 29703908 DOI: 10.1038/s41598-018-25042-2

Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.
Fulltext Optimization of a closed rat tibial fracture model

Handool KO, Ibrahim SM, Kaka U, Omar MA, Abu J, Yusoff MSM, et al.

J Exp Orthop, 2018 May 02;5(1):13.
PMID: 29721763 DOI: 10.1186/s40634-018-0128-6

BACKGROUND: The use of a closed fracture model has become the preferred model to study the fracture healing process, given that the periosteum and the soft tissue surrounding the fracture site play an important role in the fracture healing process. Some techniques like osteotomy, drilling the long bones and the use of the guillotine-like apparatus to induce fracture are characterized by some undesirable effects and complications. The aim of this study is to optimize and evaluate an in vivo fracture model using three-point bending pliers that can be used to study secondary bone fracture healing in rats.
METHODS: Modified three-point bending pliers were used as a device to create the closed rat tibial bone fracture that was prefixed with an intramedullary pin (23 G × 11/2″) in rats. The exact location of the induced closed fracture was along the long bone. The presence of bone comminution, and the fracture bone alignment were immediately examined after the induction of the fracture until the 6th week.
RESULTS: All fractures induced were transverse, located in the middle to proximal one third of the tibia, and they all healed without complications. Bone union as shown radiographically occurred within 2-3 weeks postoperative. The average angle of the fracture line with the axis of the tibia was 89.41 ± 2.11°. The lateral and anterio-posterior pin angulation views were 167.33 ± 3.67° and 161.60 ± 4.87° respectively. The average length of proximal end of the fractured bone in comparison with the whole length of intact bone was 41.02 ± 3.27%. There was a significant difference in percentage of the gross callus area and gross callus index, while there was no significant difference in X-ray callus index. There was no significant difference of the gross callus area between slight comminution (n = 4) and non comminution (n = 21).
CONCLUSION: The optimized rat tibial fracture model resulted in mainly transverse tibial mid-shaft fractures with minimal bone comminution and absence of surrounding soft tissue damage. The size area of consequent soft callus formation and the extent to which the closed fracture model was reproducible are very good outcomes making it feasible for in vivo laboratory research use.
Effects of standardized quassinoid-rich Eurycoma longifolia extract in a rat model of osteoporosis due to testosterone deficiency: A densitometric, morphometric and biomechanical study

Jayusman PA, Mohamed IN, Alias E, Dom SM, Shuid AN

J Xray Sci Technol, 2018;26(4):643-656.
PMID: 29689767 DOI: 10.3233/XST-17366

BACKGROUND: Eurycoma longifolia (EL) is a well-known aphrodisiac herb for men. Recently, the crude extract of EL was reported to possess anti-osteoporotic activities.
OBJECTIVE: This study aims to determine the bone protective effects of the standardized quassinoid-rich EL extract in testosterone-deficient rat model.
METHODS: Ninety-six intact male Sprague-Dawley rats were randomized into baseline, sham, orchidectomized, and chemically castrated groups. Chemical castration was performed via subcutaneous injection of degarelix at 2 mg/kg. The orchidectomized and degarelix-induced rats were administered with vehicle, intramuscularly injected with testosterone once a week, or orally supplemented with EL extract at doses of 25 mg/kg, 50 mg/kg or 100 mg/kg daily for 10 weeks. Bone mass, microarchitecture and strength were analyzed by dual-energy x-ray absorptiometry (DEXA), micro-CT and three-point bending test.
RESULTS: Whole body bone mineral density and femoral bone mineral content significantly increased in testosterone groups (p < 0.05). Micro-CT analysis revealed that trabecular bone volume, number, separation and connectivity density were significantly improved by testosterone administration. However, the structural model index was only improved in degarelix group supplemented with 100 mg/kg EL extract (P < 0.05). The improvement of cortical thickness by EL extract was similar to that of testosterone groups (p < 0.05). Biomechanically, EL extract supplementation was able to improve stiffness, strain and modulus of elasticity in degarelix-induced groups, while stress parameter was significantly improved in orchidectomized groups (p < 0.05).
CONCLUSION: Quassinoid-rich EL extract enables to protect against bone loss due to testosterone deficiency. The protective effect on cortical thickness and biomechanical parameters is comparable to testosterone group.
Photoprotection awareness and practices among patients with systemic lupus erythematosus and its association with disease activity and severity

Abdul Kadir WD, Jamil A, Shaharir SS, Md Nor N, Abdul Gafor AH

Lupus, 2018 Jul;27(8):1287-1295.
PMID: 29665756 DOI: 10.1177/0961203318770016

Objective The objective of this paper is to determine photoprotection awareness, knowledge, practices, and its relationship with disease activity and damage in patients with systemic lupus erythematosus (SLE).
Methods A cross-sectional study was performed. Data were acquired from in-person interviews and medical records.
Results A total of 199 (89.6%) females and 23 (10.4%) males were recruited. Median age was 39.00 (interquartile range (IQR) 18) years, disease duration 12.12 (IQR 8) years, Fitzpatrick skin phototype III 119 (53.6%) and IV 81 (36.5%). Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) was 2.95 (IQR 4) while Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-ACR DI) was 1.20 (IQR 2). The majority 205 (92.3%) were aware of sun exposure effects on SLE. Photoprotection methods were shade seeking 209 (94.1%), sun avoidance 212 (95.5%), long pants 168 (75.7%), long sleeves 155 (69.8%), sunscreen 116 (52.3%), sunglasses 114 (51.4%) and head cover 103 (46.4%). Significantly higher photoprotection practice scores (PPS) were observed in females, Malays, and individuals with higher education level and internet accessibility. PPS were not significantly correlated with SLICC-ACR DI and SLEDAI-2 K. Independent predictors for good photoprotection practice (GPP) were ethnicity (OR = 3.66, 95% CI 1.78-7.53), awareness (OR = 3.77, 95% CI 1.09-13.08) and cutaneous involvement (OR = 2.43, 95% CI 1.11-5.28). Photoprotection methods and GPP were not predictors for disease activity or damage.
Conclusion Photoprotection awareness and knowledge was good. Shade seeking and sun avoidance were the common photoprotection methods practised. The use of sunscreen requires improvement. Photoprotection awareness and cutaneous manifestation were predictors for GPP. Neither photoprotection methods nor GPP were associated with disease activity or damage.
Study site: Nephrology, Rheumatology and Dermatology clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Fulltext Subacute Oral Toxicity Assesment of Ethanol Extract of Mariposa christia vespertilionis Leaves in Male Sprague Dawley Rats

Nurul SAS, Hazilawati H, Mohd RS, Mohd FHR, Noordin MM, Norhaizan ME

Toxicol Res, 2018 Apr;34(2):85-95.
PMID: 29686770 DOI: 10.5487/TR.2018.34.2.085

The term Butterfly tea refers to decoction of Mariposa christia vespertilionis leaves which is widely consumed by cancer patients throughout Malaysia and has gained a huge popularity among Malaysians, not only cancer patients but also researchers to discover the real potential of this plant. Herein, the study is aimed at evaluating the possible toxicity in 28-day subacute oral toxicity of ethanolic extract M. christia vespertilionis in male Sprague Dawley rats. The 28-day subacute toxicity study was conducted to detect the no-observed adverse effect level (NOAEL). In this study, a total of 30 rats were divided into the control, 5% DMSO (vehicle), low dose (75 mg/kg), medium dose (125 mg/kg) and high dose (250 mg/kg) groups. The extract was administered daily from day 1 until day 28. At the end of the study, the animals were humanely sacrificed and assessed for the effect extract of Mariposa christia vespertilionis leaves on body weight and relative organ weights and haematological, biochemical and histopathological parameters. The haematological and serum biochemical parameters for the assessment of kidney and liver injuries were carried out. Results of haematological and serum biochemistry results showed no changes in the control and treated groups. In the histopathology, evaluation of kidney tissues in all treated groups showed no significant (p > 0.05) lesions. In contrast to kidney, liver tissues showed significant differences (p < 0.05) in lesions observed in low dose (430 mg), medium dose (700 mg) and high dose (1480 mg) groups with very mild, mild and mild to moderate lesion of hepatic necrosis, in the respective groups, and very mild hepatic degeneration and hepatitis were scored in all three groups.
Efficacy and Safety of Polymer-Free Ultrathin Strut Sirolimus-Probucol Coated Drug-Eluting Stents for Chronic Total Occlusions: Insights from the Coroflex ISAR 2000 Worldwide Registry

Mahmood Zuhdi AS, Krackhardt F, Waliszewski MW, Ismail MD, Boxberger M, Wan Ahmad WA

Cardiol Res Pract, 2018;2018:8053168.
PMID: 29686890 DOI: 10.1155/2018/8053168

Objective: Coronary revascularization in chronic total occlusion (CTO) is associated with improved clinical outcomes. The choice of the coronary stent is crucial in maintaining long-term vessel patency after CTO revascularization. We investigated the efficacy and safety of polymer-free ultrathin strut sirolimus-probucol coated drug-eluting stents (PF-SES) for CTO lesions.
Methods: Patients with CTO lesions treated with PF-SES were identified from the prospective multicenter international ISAR 2000 registry. The primary endpoint was clinically driven target lesion revascularization (TLR) at 9 months. Secondary endpoints were 9-month major adverse cardiac events (death, myocardial infarction, or TLR) (MACE) and the occurrence of stent thrombosis.
Results: A total of 111 patients with CTO lesions (n=127) were available for analysis. The 9-month clinical follow-up rate was 91%. The mean reference vessel diameter and lesion length were 2.76 mm ± 0.40 and 26.8 mm ± 13.1, respectively. The overall DAPT duration was 9.7 ± 2.8 months. Only one (1%) in-hospital MI was reported. The TLR and MACE rates at 9 months were 2% (2/101) and 5.9% (6/101), respectively. The 9-month accumulated rates of definite or probable stent thrombosis was 0% (0/101).
Conclusion: Revascularizations for CTO with PF-SES are associated with low rates of TLR and MACE at 9 months with no stent thrombosis. These initial findings need to be compared with results of other new generation DES of larger studies.

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