Displaying publications 1 - 20 of 24 in total

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  1. Hamid SS, Cheah SH
    Hybridoma (Larchmt), 2011 Apr;30(2):137-43.
    PMID: 21529286 DOI: 10.1089/hyb.2010.0091
    Breast mucin is secreted by breast tumor cells and serves as a marker for breast cancer. Thus, antibodies against breast mucin will be valuable in the development of immunotherapy and laboratory diagnostic tests. Monoclonal antibodies (MAbs) against breast cancer-associated antigen were generated and characterized. Balb/c mice were immunized with breast cancer-associated antigen CA15-3, and subsequently splenocytes from immunized mice were fused with myeloma cells. After fusion, culture supernatants from hybridomas surviving HAT medium were screened by enzyme-linked immunosorbent assay (ELISA). A total of eight hybridomas producing MAbs against breast cancer showed significant levels of antibody activity against CA15-3. Two selected stable hybridomas were adapted into CELLine CL 350 bioreactors, and the MAbs produced were characterized for their subclass, specificity, and affinity. The MAbs were of high specificity and affinity as shown by ELISA. The MAbs produced may represent a powerful tool and are considered promising reagents for use in diagnosis and detection of early stage of the disease.
  2. Mat MC, Mohamed AS, Hamid SS
    Lipids Health Dis, 2011;10:216.
    PMID: 22104447 DOI: 10.1186/1476-511X-10-216
    Oxidized low density lipoprotein plays an important role in development of foam cells in atherosclerosis. The study was focused on regulation of primary human monocyte growth and CD11b expression in presence of Nigella sativa oil.
  3. Motaghed M, Al-Hassan FM, Hamid SS
    Pharmacognosy Res, 2013 Jul;5(3):200-6.
    PMID: 23900121 DOI: 10.4103/0974-8490.112428
    Nigella sativa or black seed extract has been reported to show various medicinal benefits. Thymoquinone which is an active compound of its seed has been reported to contain anti-cancer properties.
  4. Motaghed M, Al-Hassan FM, Hamid SS
    Int. J. Mol. Med., 2014 Jan;33(1):8-16.
    PMID: 24270600 DOI: 10.3892/ijmm.2013.1563
    New drugs are continuously being developed for the treatment of patients with estrogen receptor-positive breast cancer. Thymoquinone is one of the drugs that exhibits anticancer characteristics based on in vivo and in vitro models. This study further investigates the effects of thymoquinone on human gene expression using cDNA microarray technology. The quantification of RNA samples was carried out using an Agilent 2100 Bioanalyser to determine the RNA integrity number (RIN). The Agilent Low Input Quick Amplification Labelling kit was used to generate cRNA in two-color microarray analysis. Samples with RIN >9.0 were used in this study. The universal human reference RNA was used as the common reference. The samples were labelled with cyanine-3 (cye-3) CTP dye and the universal human reference was labelled with cyanine-5 (cye-5) CTP dye. cRNA was purified with the RNeasy Plus Mini kit and quantified using a NanoDrop 2000c spectrophotometer. The arrays were scanned data analysed using Feature Extraction and GeneSpring software. Two-step qRT-PCR was selected to determine the relative gene expression using the High Capacity RNA-to-cDNA kit. The results from Gene Ontology (GO) analysis, indicated that 8 GO terms were related to biological processes (84%) and molecular functions (16%). A total of 577 entities showed >2-fold change in expression. Of these entities, 45.2% showed an upregulation and 54.7% showed a downregulation in expression. The interpretation of single experiment analysis (SEA) revealed that the cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and UDP glucuronosyltransferase 1 family, polypeptide A8 (UGT1A8) genes in the estrogen metabolic pathway were downregulated significantly by 43- and 11‑fold, respectively. The solute carrier family 7 (anionic amino acid transporter light chain, xc-system), member 11 (SLC7A11) gene in the interferon pathway, reported to be involved in the development of chemoresistance, was downregulated by 15‑fold. The interferon-induced protein with tetratricopeptide repeats (IFIT)1, IFIT2, IFIT3, interferon, α-inducible protein (IFI)6 (also known as G1P3), interferon regulatory factor 9 (IRF9, ISGF3), 2'-5'-oligoadenylate synthetase 1, 40/46 kDa (OAS1) and signal transducer and activator of transcription 1 (STAT1) genes all showed changes in expression following treatment with thymoquinone. The caspase 10, apoptosis-related cysteine peptidase (CASP10) gene was activated and the protein tyrosine phosphatase, receptor type, R (PTPRR) and myocyte enhancer factor 2C (MEF2C) genes were upregulated in the classical MAPK and p38 MAPK pathways. These findings indicate that thymquinone targets specific genes in the estrogen metabolic and interferon pathways.
  5. Shaarani S, Hamid SS, Mohd Kaus NH
    Pharmacognosy Res, 2017 Jan-Mar;9(1):12-20.
    PMID: 28250648 DOI: 10.4103/0974-8490.199774
    BACKGROUND: This study reports on hydrophobic drug thymoquinone (TQ), an active compound found in the volatile oil of Nigella sativa that exhibits anticancer activities. Nanoformulation of this drug could potentially increase its bioavailability to specific target cells.

    OBJECTIVE: The aim of this study was to formulate TQ into polymer micelle, Pluronic F127 (5.0 wt %) and Pluronic F68 (0.1 wt %), as a drug carrier to enhance its solubility and instability in aqueous media.

    MATERIALS AND METHODS: Polymeric micelles encapsulated TQ were prepared by the microwave-assisted solvent evaporation technique. Fourier transform infrared spectroscopy and ultraviolet-visible spectrophotometer were utilized for qualitative confirmation of micelles encapsulation. The surface morphology and mean particle size of the prepared micelles were determined by using transmission electron microscopy (TEM). Cytotoxicity effect was studied using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay.

    RESULTS: Dynamic laser light scattering (DLS) technique showed hydrodynamic size distribution of optimized micelles of 50 nm, which was in close agreement with the mean particle size obtained from TEM of about 51 nm. Drug release study showed the maximum percentage of TQ release at 61% after 72 h, while the entrapment efficiency of TQ obtained was 46% using PF127. The cytotoxic effect of PF127-encapsulated TQ was considerably higher compared to PF68-encapsulated TQ against MCF7 cells, as they exhibited IC50value of 8 μM and 18 μM, respectively.

    CONCLUSION: This study suggests higher molecular weight Pluronic polymer micelles (F127) with hydrophilic-hydrophobic segments which could be used as a suitable candidate for sustainable delivery of TQ. However, comprehensive studies should be carried out to establish the suitability of Pluronic F127 as a carrier for other drugs with similar challenges as TQ.

    SUMMARY: There is a rising interest in integrating nanotechnology with medicine, creating a nanomedicine aiming for high efficiency and efficacy of disease diagnosis and treatment. In drug delivery, the term nanomedicine describes the nanometer-sized range (1-1000 nm) of a multi-component drug for disease treatments. As such, liposome-based nanoparticulate delivery vehicles have been approved by the Food and Drug Administration (FDA) for clinical applications. The main purpose of introducing nanoscale drug delivery is to improve the pharmacological and pharmacokinetic profiles of therapeutic molecules. Drug or therapeutic molecules can be either released through the cleavage of a covalent linkage between drug molecules and polymers (conjugation) or through the diffusion from a drug and polymer blended matrix (physical encapsulation). Polymers play an important role in the design of nanocarriers for therapeutic deliveries. In Asia, Nigella sativa seed oil has been used traditionally for its various medicinal benefits. One of its most potent compound which is thymoquinone has been intensively investigated for its anti-cancer effects in colorectal carcinoma, breast adenocarcinoma, osteosarcoma, ovarian carcinoma, myeloblastic leukemia, and pancreatic carcinoma. In addition, it is reported to show anti-inflammatory potential, antidiabetic, antihistaminic effects, as well as the ability to alleviate respiratory diseases, rheumatoid arthritis, multiple sclerosis, and Parkinson's disease. This study aims to formulate and characterize different pluronic-based thymoquinone nanocarrier and investigate its effect against breast cancer cells Abbreviations Used: ATR-IR: Attenuated Total Reflectance-Infrared Spectroscopy, CH3CN: Acetonitrile, DLS: Dynamic Light Scattering, MTS: [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, NPs: Nanoparticles, PF127/TQ: Pluronic F127 encapsulated TQ, PF68/TQ: Pluronic F68 encapsulated TQ, PLGA: Poly-(D,L-lactide-co-glycolide), PVA: Poly-vinylalcohol, TQ: Thymoquinone, UV/VIS: Ultravioletvisible spectrophotometry.
  6. Ab Hamid SS, Zahari NK, Yusof N, Hassan A
    Cell Tissue Bank, 2014 Mar;15(1):15-24.
    PMID: 23187886 DOI: 10.1007/s10561-012-9353-x
    Human amniotic membrane that has been processed and sterilised by gamma irradiation is widely used as a biological dressing in surgical applications. The morphological structure of human amniotic membrane was studied under scanning electron microscopy (SEM) to assess effects of gamma radiation on human amniotic membrane following different preservation methods. The amniotic membrane was preserved by either air drying or submerged in glycerol before gamma irradiated at 15, 25 and 35 kGy. Fresh human amniotic membrane, neither preserved nor irradiated was used as the control. The surface morphology of glycerol preserved amnion was found comparable to the fresh amniotic membrane. The cells of the glycerol preserved was beautifully arranged, homogonous in size and tended to round up. The cell structure in the air dried preserved amnion seemed to be flattened and dehydrated. The effects of dehydration on intercellular channels and the microvilli on the cell surface were clearly seen at higher magnifications (10,000×). SEM revealed that the changes of the cell morphology of the glycerol preserved amnion were visible at 35 kGy while the air dried already changed at 25 kGy. Glycerol preservation method is recommended for human amniotic membrane as the cell morphological structure is maintained and radiation doses lower than 25 kGy for sterilization did not affect the appearance of the preserved amnion.
  7. Banabilh SM, Asha'ari ZA, Hamid SS
    Sleep Breath, 2008 Aug;12(3):269-74.
    PMID: 17978839 DOI: 10.1007/s11325-007-0154-6
    Snoring is considered as the most common clinical symptom of obstructive sleep apnea-hypopnea syndrome. However, many snoring studies were done in western population, and data from around Asia is scarce. Therefore, the purposes of this study were to determine the prevalence of snoring among Malaysian children from hospital-based medical clinic population setting and to compare the craniofacial features of children with and without snoring using cephalometric analysis. A cross-sectional study among children aged 7-15 years were carried out in Hospital Kuala Terengganu. Sleep behavior questionnaire (Berlin questionnaire) was given to 500 children. The respondents were divided into snoring and non-snoring groups. Thirty children from each group were randomly selected to undergo a cephalometric X-ray. For each lateral cephalometric radiograph, 17 parameters consisting bony, soft tissue, and angular measurements were recorded using computer software VixWin2000. Independent t test was used to analyze the data. The results indicated that the whole questionnaire respondents were 317 (46 snoring and 271 non-snoring), hence, the prevalence of snoring in our survey population was 14.51%. The cephalometric X-ray showed that the snoring children manifested a significant different craniofacial features, such as narrow airway at the level of the soft palate and oropharynx (p < 0.05), more inferiorly positioned hyoid bone (p < 0.05), longer vertical airway length from posterior nasal spine to the base of epiglottis (p < 0.05), more protruding maxilla, and anterior-posterior discrepancy of maxilla and mandible (p < 0.05). In conclusion, our snorer children exhibit significant craniofacial differences compared to non-snorer groups.

    Study site: ACC at Hospital Kuala Terengganu, MalaysiaThe ACC is a daycare center consisting of
    various specialty clinics such as Pediatrics, Orthopedics,
    Otorhinolaryngology, Dental, Oral-maxillofacial, General
    Surgery, General Medical, Ophthalmology, Psychiatry, and
    Obstetrics and Gynecology clinics.
  8. Yatim RM, Kannan TP, Ab Hamid SS
    Cell Tissue Bank, 2016 Dec;17(4):643-651.
    PMID: 27535136
    Human amniotic membrane (HAM) due to its high biocompatibility, low immunogenicity, anti-microbial, anti-viral properties as well as the presence of growth factors has been used in various clinical applications. The growth factors play an important role in wound healing. The current study aimed to explore the effect of 15 kGy gamma radiation dose on selected growth factors and receptors mRNA present in HAM. Eight growth factors, namely, EGF, HGF, KGF, TGF-α, TGF-β1, TGF-β2, TGF-β3 and bFGF and two growth factor receptors, HGFR and KGFR were evaluated in this study. The total RNA was extracted and converted to complimentary DNA using commercial kits. Subsequently, the mRNA expressions of these growth factors were evaluated using real-time PCR and the results were statistically analyzed using REST-MCS software. This study confirmed the presence of these mRNA growth factors and receptors in fresh, glycerol cryopreserved and irradiated glycerol cryopreserved HAM. In glycerol cryopreserved HAM, the results showed up-regulation of HGF and bFGF and down-regulation of EGF, HGFR, KGF, KGFR, TGF-α, TGF-β1, TGF-β2 and TGF-β3 relative to the fresh HAM which acted as the control, whereas in irradiated glycerol cryopreserved HAM, the results showed up-regulation of EGF, HGF, KGF, KGFR, TGF-β1, TGF-β2 and TGF-β3 and down-regulation of HGFR, TGF-α and bFGF relative to the glycerol cryopreserved HAM which acted as the control. However, these mRNA expressions did not show any statistical significant difference compared to the control groups. This study concluded that a dose of 15 kGy of gamma radiation did not affect the mRNA expression for the growth factors' and receptors' in the glycerol cryopreserved HAM.
  9. Loo SK, Ab Hamid SS, Musa M, Wong KK
    Pathol. Res. Pract., 2018 Jan;214(1):134-143.
    PMID: 29137822 DOI: 10.1016/j.prp.2017.10.005
    Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR) <0.05]. Cell cycle progression and DNA replication were among the significantly enriched biological processes (FDR <0.05). Expression of genes involved in the activation of cell cycle and DNA replication (e.g. CDK1, CCNA2, E2F2, PCNA, RFC5 and POLD3) were highly correlated (r>0.8) with DNMT1 expression and significantly downregulated (log fold-change
  10. Yusoff NH, Alshehadat SA, Azlina A, Kannan TP, Hamid SS
    Trop Life Sci Res, 2015 Apr;26(1):21-9.
    PMID: 26868590 MyJurnal
    In the past decade, the field of stem cell biology is of major interest among researchers due to its broad therapeutic potential. Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Stem cells can be classified into two main types: adult stem cells (adult tissues) and embryonic stem cells (embryos formed during the blastocyst phase of embryological development). This review will discuss two types of adult mesenchymal stem cells, dental stem cells and amniotic stem cells, with respect to their differentiation lineages, passage numbers and animal model studies. Amniotic stem cells have a greater number of differentiation lineages than dental stem cells. On the contrary, dental stem cells showed the highest number of passages compared to amniotic stem cells. For tissue regeneration based on animal studies, amniotic stem cells showed the shortest time to regenerate in comparison with dental stem cells.
  11. Omar NS, Kannan TP, Ismail AR, Abdullah SF, Samsudin AR, Hamid SS
    Int. J. Toxicol., 2011 Aug;30(4):443-51.
    PMID: 21540334 DOI: 10.1177/1091581811399474
    This study aimed to evaluate the in vitro cytotoxic effects of locally produced processed natural coral (PNC) using human osteoblasts (HOS). Cytotoxicity was not observed when HOS cells were cultured with PNC, as assessed by (3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyl tetrazolium bromide; MTT) and Neutral Red (NR) assays at concentration up 200 mg/mL for up to 72 hours. Flow cytometry (FCM) analysis showed that PNC (200 mg/mL) did not decrease viability of HOS cells after 48 and 72 hours of treatment. In a cell attachment study, the HOS cells attached to the edge of the PNC disc, and later grew into the pores of the PNC disc. All results from these studies indicate that locally produced PNC material is noncytotoxic and favors the growth of HOS cells.
  12. Abdullah B, Rajet KA, Abd Hamid SS, Mohammad WM
    Sleep Breath, 2011 Dec;15(4):747-54.
    PMID: 20957444 DOI: 10.1007/s11325-010-0431-7
    OBJECTIVES: We aimed to evaluate the severity of upper airway obstruction at the retropalatal and retroglossal regions in obstructive sleep apnea (OSA) patients.

    METHODOLOGY: This is a descriptive cross-sectional study at the Sleep Clinic, Department of Otorhinolaryngology-Head and Neck Surgery. Flexible nasopharyngolaryngoscopy was performed in seated erect and supine position. Retropalatal and retroglossal regions were continuously recorded during quiet breathing and Mueller's maneuver in both positions. Captured images were measured using Scion Image software and narrowing rate was calculated. Level of each site was classified based on Fujita classification and severity of obstruction using Sher scoring system for Mueller's maneuver.

    RESULTS: A total of 59 patients participated in this study. Twenty-nine (49.2%) participants had type 1 (retropalatal) obstruction, 23 (38.9%) had type 2 (retropalatal and retroglossal), and seven (11.9%) in type 3 (retroglossal) obstruction. Fifty (84.7%) of the patients have severe obstruction at the retropalatal region in supine position (SRP) followed by 35 (59.3%) at retropalatal region in erect position (ERP), 27 (45.8%) at retroglossal region in supine position (SRG) and eight (13.5%) at retroglossal region in erect position (ERG). The average oxygen saturation showed significant association in ERP (P = 0.012) and SRP (P < 0.001), but not significant in ERG and SRG.

    CONCLUSIONS: Videoendoscopy utilizing flexible nasopharyngolaryngoscopy and Scion Image software is reliable, minimally invasive, and useful as an office procedure in evaluating the multilevel obstruction of upper airway in OSA patients. The retropalatal region has more severe obstruction compared with retroglossal region either in erect or supine position.

  13. Abdullah B, Shibghatullah AH, Hamid SS, Omar NS, Samsuddin AR
    Cell Tissue Bank, 2009 Aug;10(3):205-13.
    PMID: 18975136 DOI: 10.1007/s10561-008-9111-2
    This study was performed to determine the microscopic biological response of human nasal septum chondrocytes and human knee articular chondrocytes placed on a demineralized bovine bone scaffold. Both chondrocytes were cultured and seeded onto the bovine bone scaffold with seeding density of 1 x 105 cells per 100 microl/scaffold and incubated for 1, 2, 5 and 7 days. Proliferation and viability of the cells were measured by mitochondrial dehydrogenase activity (MTT assay), adhesion study was analyzed by scanning electron microscopy and differentiation study was analyzed by immunofluorescence staining and confocal laser scanning electron microscopy. The results showed good proliferation and viability of both chondrocytes on the scaffolds from day 1 to day 7. Both chondrocytes increased in number with time and readily grew on the surface and into the open pores of the scaffold. Immunofluorescence staining demonstrated collagen type II on the scaffolds for both chondrocytes. The results showed good cells proliferation, attachment and maturity of the chondrocytes on the demineralized bovine bone scaffold. The bovine bone being easily resourced, relatively inexpensive and non toxic has good potential for use as a three dimensional construct in cartilage tissue engineering.
  14. Asnawi AW, Sathar J, Mohamed R, Deraman R, Kumaran S, Hamid SS, et al.
    Indian J Hematol Blood Transfus, 2016 Jun;32(Suppl 1):251-3.
    PMID: 27408406 DOI: 10.1007/s12288-014-0495-9
    Clinical manifestations of sickle cell disease (SCD) arise from the tendency of the sickle haemoglobin to polymerize and deform red blood cells into the characteristic sickle shape. Sickle cell crisis is a devastating complication that may occur in patients with SCD. If not managed properly permanent organ damage and even death may be the final outcome. A case of a 32-year-old Nigerian lady, Gravida 1 Para 0 in her first trimester, with SCD who developed signs and symptoms of delayed haemolytic transfusion reaction after receiving packed red cell transfusion is demonstrated. Multiple red cell alloantibodies were detected in the patient's plasma; anti-Fy a, anti-Jk b and anti-E. The patient miscarriaged and succumbed to complications of hyperhaemolysis with delayed haemolytic transfusion reaction, acute chest syndrome and renal failure. There is an urgent need for mandatory red cell antibody screen and identification especially in high-risk cases. Prevention of alloimmunization by supplying phenotype-specific red cells is also required.
  15. Roslinah M, Wan Hitam WH, Md Salleh MS, Abdul Hamid SS, Shatriah I
    Cureus, 2019 Jan 25;11(1):e3954.
    PMID: 30956907 DOI: 10.7759/cureus.3954
    We aimed to compare clinical and pathological reactions towards locally synthesized bovine bone derived from hydroxyapatite (bone docosahexaenoic acid (dHA)) and commercially available porous polyethylene (Medpor®, Porex Surgical Incorporation, Georgia, USA) orbital implants in animal models. An experimental study was performed on 14 New Zealand white rabbits. Group A (n=7) was implanted with bovine bone dHA and group B (n=7) was implanted with Medpor®. Clinical examinations were performed on Days 1, 7, 14, 28, and 42 post-implantation. The implanted eyes were enucleated on Day 42 and were sent for pathological evaluation. Serial clinical examinations included urine color and odor; feeding and physical activity demonstrated normal wellbeing in all the subjects. Localized minimal infection was observed in both groups during the first two weeks following implantation, and the subjects responded well to topical moxifloxacin. Both groups exhibited evidence of wound breakdown. No signs of implant migration or extrusion were observed in either group. The histopathological examination revealed no statistically significant difference in inflammatory cell reactions and fibrovascular tissue maturation between both types of implants. However, all (100%) of the bovine bone dHA implants displayed complete fibrovascular ingrowth compared to Medpor® implants (57.1%) at six weeks post-implantation (p=0.001). In conclusion, bovine bone dHA and Medpor® orbital implants were well-tolerated clinically and displayed similar inflammatory reactions and fibrovascular tissue maturation. Locally synthesized bovine bone dHA orbital implants displayed significantly greater complete fibrovascular ingrowth in comparison with Medpor® implants.
  16. Zakaria ZA, Yahya F, Mamat SS, Mahmood ND, Mohtarrudin N, Taher M, et al.
    BMC Complement Altern Med, 2016;16(1):175.
    PMID: 27287196 DOI: 10.1186/s12906-016-1110-4
    Methanol extract of Bauhinia purpurea L. (family Fabaceae) (MEBP) possesses high antioxidant and anti-inflammatory activities and recently reported to exert hepatoprotection against paracetamol (PCM)-induced liver injury in rats. In an attempt to identify the hepatoprotective bioactive compounds in MEBP, the extract was prepared in different partitions and subjected to the PCM-induced liver injury model in rats.
  17. Zakaria ZA, Kamisan FH, Omar MH, Mahmood ND, Othman F, Abdul Hamid SS, et al.
    BMC Complement Altern Med, 2017 May 18;17(1):271.
    PMID: 28521788 DOI: 10.1186/s12906-017-1781-5
    BACKGROUND: The present study investigated the potential of methanolic extract of Dicranopteris linearis (MEDL) leaves to attenuate liver intoxication induced by acetaminophen (APAP) in rats.

    METHODS: A group of mice (n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats (n = 6) were used and each received as follows: Group 1 (normal control; pretreated with 10% DMSO (extract's vehicle) followed by treatment with 10% DMSO (hepatotoxin's vehicle) (10% DMSO +10% DMSO)), Group 2 (hepatotoxic control; 10% DMSO +3 g/kg APAP (hepatotoxin)), Group 3 (positive control; 200 mg/kg silymarin +3 g/kg APAP), Group 4 (50 mg/kg MEDL +3 g/kg APAP), Group 5 (250 mg/kg MEDL +3 g/kg APAP) or Group 6 (500 mg/kg MEDL +3 g/kg APAP). The test solutions pre-treatment were made orally once daily for 7 consecutive days, and 1 h after the last test solutions administration (on Day 7th), the rats were treated with vehicle or APAP. Blood were collected from those treated rats for biochemical analyses, which were then euthanized to collect their liver for endogenous antioxidant enzymes determination and histopathological examination. The extract was also subjected to in vitro anti-inflammatory investigation and, HPLC and GCMS analyses.

    RESULTS: Pre-treatment of rats (Group 2) with 10% DMSO failed to attenuate the toxic effect of APAP on the liver as seen under the microscopic examination. This observation was supported by the significant (p 

  18. Zakaria ZA, Zainol AS, Sahmat A, Salleh NI, Hizami A, Mahmood ND, et al.
    Pharm Biol, 2016 May;54(5):812-26.
    PMID: 26452435 DOI: 10.3109/13880209.2015.1085580
    Muntingia calabura L. (family Muntingiaceae) and Melastoma malabathricum L. (family Melastomaceae) are traditionally used to treat gastric ulcer.
  19. Choudhury A, Jindal A, Maiwall R, Sharma MK, Sharma BC, Pamecha V, et al.
    Hepatol Int, 2017 Sep;11(5):461-471.
    PMID: 28856540 DOI: 10.1007/s12072-017-9816-z
    BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models.

    METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922).

    RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001).

    CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

  20. Choudhury A, Kumar M, Sharma BC, Maiwall R, Pamecha V, Moreau R, et al.
    J. Gastroenterol. Hepatol., 2017 Dec;32(12):1989-1997.
    PMID: 28374414 DOI: 10.1111/jgh.13799
    BACKGROUND AND AIM: Systemic inflammatory response syndrome (SIRS) is an early marker of sepsis and ongoing inflammation and has been reported in large proportion of acute-on-chronic liver failure (ACLF) patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, the study investigated the course and outcome of ACLF patients without SIRS/sepsis.

    METHODS: Consecutive ACLF patients were monitored for the development of SIRS/sepsis and associated complications and followed till 90 days, liver transplant or death.

    RESULTS: Of 561 patients, 201 (35.8%) had no SIRS and 360 (64.2%) had SIRS with or without infection. New onset SIRS and sepsis developed in 74.6% and 8% respectively in a median of 7 (range 4-15) days, at a rate of 11% per day. The cumulative incidence of new SIRS was 29%, 92.8%, and 100% by days 4, 7, and 15. Liver failure, that is, bilirubin > 12 mg/dL (odds ratio [OR] = 2.5 [95% confidence interval {CI} = 1.05-6.19], P = 0.04) at days 0 and 4, and renal failure at day 4 (OR = 6.74 [95%CI = 1.50-13.29], P = 0.01), independently predicted new onset SIRS. Absence of SIRS in the first week was associated with reduced incidence of organ failure (20% vs 39.4%, P = 0.003), as was the 28-day (17.6% vs 36%, P = 0.02) and 90-day (27.5% vs 51%,P = 0.002) mortality. The 90-day mortality was 61.6% in the total cohort and that for those having no SIRS and SIRS at presentation were 42.8% and 65%, respectively (P 

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