Displaying publications 21 - 40 of 75 in total

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  1. Eh Suk VR, Chung I, Misran M
    Curr Drug Deliv, 2020;17(4):292-302.
    PMID: 32039684 DOI: 10.2174/1567201817666200210122933
    BACKGROUND: Liposomes are mostly known to be prepared from phospholipids and lipids and have a remarkable capacity to encapsulate both lipophobic and lipophilic molecules. However, there is little research on developing fatty acid liposomes for chemotherapy.

    OBJECTIVE: We have successfully prepared mixed fatty acid liposomes from two monounsaturated fatty acids, namely oleic acid and erucic acid, which stabilised by DOPEPEG2000. The Critical Vesicular Concentration (CVC) of liposomes was found to be within 0.09 to 0.21 mmol dm-3, with an average particle size of 400 nm.

    METHODS: Encapsulation of various anticancer drugs such as folinic acid, methotrexate, doxorubicin, or irinotecan resulted in Encapsulation Efficiency (%EE) of up to 90%. Using a 3-(4, 5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the median Inhibitory Concentration (IC50) values of mixed oleic acid-erucic acid encapsulating hydrophilic drugs was remarkably reduced at the end of 24 hours of incubation with the human lung carcinoma cell line A549.

    RESULTS: The results suggest that mixed oleic acid-erucic acid liposomes are a potential new approach to further develop as an alternative vehicle of various drugs for cancer treatment.

    Matched MeSH terms: Methotrexate/pharmacology; Methotrexate/chemistry
  2. Jain A, Sharma G, Kushwah V, Garg NK, Kesharwani P, Ghoshal G, et al.
    Nanomedicine (Lond), 2017 Aug;12(15):1851-1872.
    PMID: 28703643 DOI: 10.2217/nnm-2017-0011
    AIM: This work was intended to investigate the targeting potential of fructose-tethered lipid-polymeric hybrid nanoparticles (F-BC-MTX-LPHNPs) co-loaded with beta carotene (BC) and methotrexate (MTX) in breast cancer therapeutics and find out the possible protective role of BC on MTX-induced toxicity.

    MATERIALS & METHODS: F-BC-MTX-LPHNPs were fabricated using self-assembled nano-precipitation technique. Fructose was conjugated on the surface of the particles. The in vitro cytotoxicity, sub-cellular localization and apoptotic activity of F-BC-MTX-LPHNPs were evaluated against MCF-7 breast cancer cells. The antitumor potential of F-BC-MTX-LPHNPs was further studied.

    RESULTS & CONCLUSION: Outcomes suggested that F-BC-MTX-LPHNPs induced the highest apoptosis index (0.89) against MCF-7 cells. Following 30 days of treatment, the residual tumor progression was assessed to be approximately 32%, in animals treated with F-BC-MTX-LPHNPs. F-BC-MTX-LPHNPs are competent to selectively convey the chemotherapeutic agent to the breast cancers. Beta carotene ameliorated MTX-induced hepatic and renal toxicity.

    Matched MeSH terms: Methotrexate/pharmacology*; Methotrexate/chemistry
  3. Naqvi AA, Hassali MA, Aftab MT
    J Pak Med Assoc, 2019 Mar;69(3):389-398.
    PMID: 30890833
    OBJECTIVE: The study aimed to evaluate literature on rheumatoid arthritis disease in Pakistani patients, to have an understanding about its epidemiology, clinical aspects and socio-economic determinants.

    METHODS: The review study was conducted from December 2017, to May 2018. An online search was conducted in international and local health databases using appropriate search keywords as well as scanning reference lists of related articles. Literature published after year 2000 that reported epidemiological, demographic, clinical and socioeconomic data of Pakistani rheumatoid arthritis patients was included. Meta-analysis was performed where possible. This systematic review was registered on the international prospective register of systematic reviews PROSPERO (CRD42018090582).

    RESULTS: Of the 334 research articles found, 29 (8.7%) were selected. Patients were mostly females, but no study explored impact of disease on household and family role functioning of rheumatoid arthritis-affected women in Pakistan. Most patients were uneducated (55%) and unemployed; had low disease knowledge (N = 149, 74.5%) and poor adherence to disease-modifying anti-rheumatic drugs (N = 23, 23%). Point prevalence of rheumatoid arthritis reported from Karachi was high at 26.9%. Moderate disease activity, i.e., 4.5}0.7 and mild functional disability (N = 66, 51.6%) were seen in RA patients. Almost half (N = 799, 46.9%) had comorbidities. Almost a fifth proportion of RA patients had dyslipidaemia as a comorbidity (N = 134, 16.77%) and higher cardiovascular risk score as modifiable risk factor. Undiagnosed depression (N = 134, 58.3%) and low bone mineral density (N = 93, 40.6%) were reported in RA patients. Direct monthly treatment cost of disease was significantly high considering patients' socio-economic status, i.e., USD 16.47 - 100.68. Most commonly used drug was methotrexate.

    CONCLUSIONS: There is a paucity of data on Pakistani rheumatoid arthritis patients' demographic and socio-economic parameters, especially the gender element.

    Matched MeSH terms: Methotrexate/economics; Methotrexate/therapeutic use
  4. Suthandiram S, Gan GG, Zain SM, Bee PC, Lian LH, Chang KM, et al.
    Pharmacogenomics, 2014 Aug;15(11):1479-94.
    PMID: 25303299 DOI: 10.2217/pgs.14.97
    Pharmacogenetics of methotrexate (MTX) contributes to interindividual differences in toxicity. We aimed to evaluate the impact of SNPs within the MTX pathway genes on MTX-induced toxicity and MTX plasma levels at 48 h following treatment in Asian adults with acute lymphoblastic leukemia or non-Hodgkin lymphoma.
    Matched MeSH terms: Methotrexate/adverse effects*; Methotrexate/blood; Methotrexate/therapeutic use*
  5. Hong W, Wang Y, Chang Z, Yang Y, Pu J, Sun T, et al.
    Sci Rep, 2015;5:15328.
    PMID: 26471125 DOI: 10.1038/srep15328
    It is an urgent need to develop new drugs for Mycobacterium tuberculosis (Mtb), and the enzyme, dihydrofolate reductase (DHFR) is a recognised drug target. The crystal structures of methotrexate binding to mt- and h-DHFR separately indicate that the glycerol (GOL) binding site is likely to be critical for the function of mt-DHFR selective inhibitors. We have used in silico methods to screen NCI small molecule database and a group of related compounds were obtained that inhibit mt-DHFR activity and showed bactericidal effects against a test Mtb strain. The binding poses were then analysed and the influence of GOL binding site was studied by using molecular modelling. By comparing the chemical structures, 4 compounds that might be able to occupy the GOL binding site were identified. However, these compounds contain large hydrophobic side chains. As the GOL binding site is more hydrophilic, molecular modelling indicated that these compounds were failed to occupy the GOL site. The most potent inhibitor (compound 6) demonstrated limited selectivity for mt-DHFR, but did contain a novel central core (7H-pyrrolo[3,2-f]quinazoline-1,3-diamine), which may significantly expand the chemical space of novel mt-DHFR inhibitors. Collectively, these observations will inform future medicinal chemistry efforts to improve the selectivity of compounds against mt-DHFR.
    Matched MeSH terms: Methotrexate
  6. Albela H, Begum S, Leong KF
    J Dermatolog Treat, 2021 Mar 11.
    PMID: 33706651 DOI: 10.1080/09546634.2021.1899111
    Generalized Pustular Psoriasis (GPP) is a rare, severe, life-threatening form of psoriasis and accounts for up to 13.1% of all childhood psoriasis. Common first-line systemic treatment for pediatric patients with GPP include oral acitretin, cyclosporin and methotrexate which have varying efficacy and side effects but multiple interventions are often needed to induce remission and maintain long term control. Recently, the anti IL 17 A monoclonal antibody secukinumab have been shown to be effective in adult patients with GPP; however, there is lack of evidence of its usage in the pediatric population. We describe a case series of 4 pediatric patients with GPP who were treated with off-label use of secukinumab. All four patients had marked clearance and reduction in Generalized Pustular Psoriasis Area & Severity Score (GPPASI) within first 48 h of first injection with subsequent almost complete to complete clearance of skin lesions by 1 month follow up. In conclusion, secukinumab was found to be successful in inducing remission, with rapid clearance and maintaining remission, with or without combination with other systemic agents for pediatric GPP.
    Matched MeSH terms: Methotrexate
  7. Lin GSS, Abdul Ghani NRN, Ismail NH, Singbal KP, Yusuff NMM
    Eur J Dent, 2020 Jul;14(3):448-455.
    PMID: 32599624 DOI: 10.1055/s-0040-1713951
    OBJECTIVES:  This study aimed to compare the polymerization shrinkage and degree of conversion of new zirconia-reinforced rice husk nanohybrid composite with commercialized microhybrid and nanofilled composites.

    MATERIALS AND METHODS:  Overall, 180 samples were used for polymerization shrinkage (buoyancy and optical methods) and degree of conversion tests in which they were divided into Group 1, nanofilled composite (Filtek-Z350- XT; 3M ESPE, St Paul, MN 55144-1000, USA), Group 2, microhybrid composite (Zmack-Comp), and Group 3, nanohybrid composite (Zr-Hybrid). Polymerization shrinkage test was performed using buoyancy and optical methods. For buoyancy method, samples were weighed in air and water to calculate the shrinkage value, whereas, for optical method, images of nonpolymerized samples were captured under a digital microscope and recaptured again after light-cured to calculate the percentage of shrinkage. Degree of conversion was tested using Fourier-transform infrared spectroscopy spectrometer.

    STATISTICAL ANALYSIS:  Data were analyzed using one-way analysis of variance complemented by post hoc Dunnett's T3 test for polymerization shrinkage and Tukey's honestly significant difference test for degree of conversion. Level of significance was set at p < 0.05.

    RESULTS:  Group 3 demonstrated similar polymerization shrinkage with Group 1, but lower shrinkage (p < 0.05) than Group 2 based on buoyancy method. However, optical method (p < 0.05) showed that Group 3 had the lowest shrinkage, followed by Group 1 and lastly Group 2. Besides, Group 3 showed a significantly higher degree of conversion (p < 0.05) than Group 1 and comparable conversion value with Group 2.

    CONCLUSIONS:  Zirconia-reinforced rice husk nanohybrid composite showed excellent shrinkage and conversion values, hence can be considered as an alternative to commercially available composite resins.

    Matched MeSH terms: Methotrexate
  8. How KN, Yap WH, Lim CLH, Goh BH, Lai ZW
    Front Pharmacol, 2020;11:1105.
    PMID: 32848737 DOI: 10.3389/fphar.2020.01105
    Hyaluronic acid (HA), a major component of extracellular matrix has been widely applied in pharmaceutical and cosmetic industries due to its reported pharmacological properties. Various types of HA drug delivery system including nanoparticles, cryogel-based formulations, microneedle patches, and nano-emulsions were developed. There are studies reporting that several HA-based transdermal delivery systems exhibit excellent biocompatibility, enhanced permeability and efficient localized release of anti-psoriasis drugs and have shown to inhibit psoriasis-associated skin inflammation. Similarly HA is found in abundant at epidermis of atopic dermatitis (AD) suggesting its role in atopic AD pathology. Anti-allergenic effect of atopic eczema can be achieved through the inhibition of CD44 and protein kinase C alpha (PKCα) interaction by HA. Herein, we aim to evaluate the current innovation on HA drug delivery system and the other potential applications of HA in inflammatory skin diseases, focusing on atopic dermatitis and psoriasis. HA is typically integrated into different delivery systems including nanoparticles, liposomes, ethosomes and microneedle patches in supporting drug penetration through the stratum corneum layer of the skin. For instance, ethosomes and microneedle delivery system such as curcumin-loaded HA-modified ethosomes were developed to enhance skin retention and delivery of curcumin to CD44-expressing psoriatic cells whereas methotrexate-loaded HA-based microneedle was shown to enhance skin penetration of methotrexate to alleviate psoriasis-like skin inflammation. HA-based nanoparticles and pluronic F-127 based dual responsive (pH/temperature) hydrogels had been described to enhance drug permeation through and into the intact skin for AD treatment.
    Matched MeSH terms: Methotrexate
  9. Kow CS, Hasan SS
    Drugs Ther Perspect, 2020 Aug 16.
    PMID: 32837197 DOI: 10.1007/s40267-020-00767-1
    Thus far, associations between the presence of systemic rheumatic disease and an increased risk of novel coronavirus disease 2019 (COVID-19) acquisition or a worse prognosis from COVID-19 have not been conclusive. It is not known for certain if there is an association between any pharmacological agent used for rheumatologic treatment, including biological and non-biological disease-modifying antirheumatic drugs (DMARDs), and an increased risk of COVID-19 acquisition or adverse outcomes from COVID-19, although these agents have been associated with an overall higher risk of infections. The pharmacological management of patients with a rheumatic disease without COVID-19 should currently follow usual treatment approaches. Individualized approaches to adjusting DMARD regimens in patients with documented COVID-19 seems prudent, with specific attention paid to the severity of the infection. Patients receiving antimalarials (hydroxychloroquine/chloroquine) may continue treatment with these agents. Treatment with sulfasalazine, methotrexate, leflunomide, immunosuppressants and biological agents other than interluekin-6 receptor inhibitors and JAK inhibitors should be stopped or withheld. It should be reasonable to resume DMARD treatment when patients are no longer symptomatic and at least 2 weeks after documentation of COVID-19, although the decision should be individualized, preferably based on infection severity.
    Matched MeSH terms: Methotrexate
  10. Mohd Faizal, A., Dianie, D.J.K., Suguna, S., Soon, R., Moharzudi, M.
    MyJurnal
    A pure ovarian choriocarcinoma is a very rare disease which can be either pregnancy related (gestational), may not be related (non-gestational), or commonly correlated with different type of germ cell; teratocarcinoma, dysgerminoma or undifferentiated carcinoma. A pure non-gestational primary ovarian choriocarcinoma is astronomically uncommon and we recorded such condition in 14-year-old teenage girl’s ovary. An abdominal operative procedure with the help of a careful histopathology examination revealed choriocarcinoma in absence of other type of germ cell element. Multiple courses of Etoposide/Methotrexate/Actinomycin-D (EMA) regime of chemotherapy were shown to be effective in this case.
    Matched MeSH terms: Methotrexate
  11. Shafiee, M.N., Rahana, A.R., Lim, P.S., Nor Azlin, M.I., Wan Faraliza, Z.A., Isa, M.R., et al.
    MyJurnal
    Morbidly adherent placenta with spontaneous rupture of membrane at extreme prematurity poses poor pregnancy outcome. Various issues on different management modalities still remain perplexed and individual consideration is vital. Two cases of morbidly adherent placenta with symptomatic per vaginal bleeding and spontaneous rupture of membrane at severe prematurity were reviewed and discussed. We found that, active intervention by termination of pregnancy and methotrexate therapy at early gestation can prevent the need of hysterectomy following major obstetrics haemorrhage.
    Matched MeSH terms: Methotrexate
  12. Nirmala, C.K., Lim, P.S., Norzilawati, M.N., Zainul, R.A.Z., Mohd. Hashim, O.
    MyJurnal
    Ectopic pregnancy in the interstitial part of the fallopian tube (cornual pregnancy) is a rare condition but can be fatal. Traditionally, the treatment had been cornual resection or hysterectomy. More conservative approaches had been advocated recently. There is no consensus on the dose or number of methotrexate injections that should be used in the treatment of interstitial pregnancies. Single dose intramuscular methotrexate is one of the treatment options. However, the failure rate is higher if the serum beta-hCG (beta-human chorionic gonadotrophin) level is more than 5000 IU/L. We report a case of cornual ectopic pregnancy with high initial serum beta-hCG level being successfully treated with multiple doses of systemic methotrexate. MRI was used to assess clinical resolution of cornual ectopic pregnancy.
    Matched MeSH terms: Methotrexate
  13. Ghosh A, Tiwari GJ
    3 Biotech, 2018 Aug;8(8):338.
    PMID: 30073123 DOI: 10.1007/s13205-018-1337-5
    In the present study, Karanjin and Pongapin, two important furanoflavone, constituents of Pongamia pinnata were studied in the management of Psoriasis. Presently, we have experimentally studied the free radical quenching property of Karanjin and Pongapin. A modified method was used to estimate the scavenging effect of the Karanjin (the highest activity of 95.60%) and Pongapin (68.05%) compared to the ascorbic acid as standard (11.60%) against nitric oxide. Furthermore, Molecular docking studies were performed using CLC drug discovery workbench software version 3.0 of the studied flavones (Karanjin and Pongapin) with the receptors responsible for psoriasis (viz. IL-17A, IL-17F, IL-23, RORγt, and TLR-7). Docking scores of Karanjin and Pongapin with different studied receptors were found to be comparable to that of Methotrexate, a known drug for treating Psoriasis. Docking results suggest that Karanjin and Pongapin might also help in controlling the disease. Overall, our results indicate that flavones (Karanjin and Pongapin) could be a natural and better alternative in curing psoriasis without any side effects.
    Matched MeSH terms: Methotrexate
  14. Tan T, Ho W
    Malays Orthop J, 2015 Nov;9(3):65-67.
    PMID: 28611915 DOI: 10.5704/MOJ.1511.010
    Stress fractures of the proximal tibia metaphysis are rare in the elderly. We present a case of a 65-year old male who developed sequential proximal tibia stress fractures associated with prolonged usage of methotrexate and prednisolone within a span of 18 months. Magnetic Resonance Imaging revealed an incomplete stress fracture involving the medial proximal tibial region. The patient was treated with stemmed total knee arthroplasty (TKA) bilaterally. Stress fractures should be considered in patients with atypical knee pain who have a history of methotrexate and prednisolone usage. TKA is an effective treatment in stress fractures of the proximal tibia.
    Matched MeSH terms: Methotrexate
  15. Ong PS, Sulaiman W
    Oman Med J, 2011 Sep;26(5):e022.
    PMID: 28845225 DOI: 10.5001/omj.2011.96
    Adult-onset Still's disease (AOSD) is a rare clinical entity with unknown etiology, characterized by arthritis, fever, evanescent rash and other systemic presentations. This report described a 45-year-old male who presented with sore throat, fever, arthritis, evanescent rash, raised liver enzymes and hyperferritinemia. He was diagnosed to have AOSD based on Yamuguchi criteria after the exclusion of other potential diagnoses. The patient partially responded to combined celecoxib and prednisolone. He was also prescribed methotrexate and his symptoms improved.
    Matched MeSH terms: Methotrexate
  16. Tiash S, Othman I, Rosli R, Chowdhury EH
    Curr Drug Deliv, 2014;11(2):214-22.
    PMID: 24328684
    Most of the classical drugs used today to destroy cancer cells lead to the development of acquired resistance in those cells by limiting cellular entry of the drugs or exporting them out by efflux pumps. As a result, higher doses of drugs are usually required to kill the cancer cells affecting normal cells and causing numerous side effects. Accumulation of the therapeutic level of drugs inside the cancer cells is thus required for an adequate period of time to get drugs' complete therapeutic efficacy minimizing the side effects on normal cells. In order to improve the efficacy of chemotherapeutic drugs, nanoparticles of carbonate apatite and its strontium (Sr(2+))-substituted derivative were used in this study to make complexes with three classical anticancer drugs, methotrexate, cyclophosphamide and 5-flurouracil. The binding affinities of these drugs to apatite were evaluated by absorbance and HPLC analysis and the therapeutic efficacy of drug-apatite complexes was determined by cell viability assay. Carbonate apatite demonstrated significant binding affinity towards methotrexate and cyclophosphamide leading to more cellular toxicity than free drugs in MCF-7 and 4T1 breast cancer cells. Moreover, Sr(2+) substitution in carbonate apatite with resulting tiny particles less than 100 nm in diameter further promoted binding of methotrexate to the nanocarriers indicating that Sr(2+)-substituted apatite nanoparticles have the high potential for loading substantial amount of anti-cancer drugs with eventual more therapeutic effectiveness.
    Matched MeSH terms: Methotrexate/administration & dosage*
  17. Sakthiswary R, Suresh E
    Lupus, 2014 Mar;23(3):225-35.
    PMID: 24399812 DOI: 10.1177/0961203313519159
    OBJECTIVE: The objective of this review is to evaluate the evidence for efficacy of methotrexate (MTX) in systemic lupus erythematosus (SLE).
    METHODS: A comprehensive, computerized search was performed in MEDLINE (PubMed), EMBASE and the Cochrane Controlled Trials registry to screen for studies that examined the efficacy of MTX in adult SLE patients. The Jadad scoring system was used to assess study quality, and data were pooled using the random effects model.
    RESULTS: Of the 53 articles that were identified, 44 were excluded. Nine studies (including three randomized controlled and six observational) were eligible for inclusion. All of the included studies predominantly involved patients with arthritis or mucocutaneous features. There was significant reduction of the SLE Disease Activity Index (SLEDAI) among MTX-treated patients when compared with controls (p = 0.001, odds ratio (OR) 0.444, 95% confidence interval (CI) 0.279 to 0.707). There was also significant reduction in the average dose of corticosteroids among MTX-treated patients when compared with controls (p = 0.001, OR 0.335, 95% CI 0.202 to 0.558). The effect of MTX on laboratory and serological markers, including erythrocyte sedimentation rate, anti-dsDNA and complement levels (C3 and C4), could not be determined because of the limited numbers of controlled trials.
    CONCLUSION: The use of MTX is associated with significant reductions in SLEDAI and the average dose of corticosteroids in adult patients with SLE.
    KEYWORDS: SLE; Systemic lupus erythematosus; efficacy; lupus; methotrexate
    Matched MeSH terms: Methotrexate/therapeutic use*
  18. Leong CF, Azma RZ, Cheong SK, Salwati S, Sharifah NA
    Malays J Pathol, 2005 Jun;27(1):45-50.
    PMID: 16676693
    A 25-year-old man was referred to Hospital UKM with a 2-week history of fever, productive cough and loss of appetite. Physical examination revealed an ill-looking, tachypnoeic young man. No obvious lymphadenopathy or organomegaly was noted. Examination of the respiratory system revealed right pleural effusion. Full blood picture demonstrated leukocytosis with 90% blasts, and bone marrow examination confirmed the diagnosis of acute myeloid leukemia (AML) French-American-British (FAB) classification of M4 with eosinophilia. His chromosome karyotyping showed complex karyotypic abnormalities. Cytological examination of the pleural fluid demonstrated numerous blast cells indicating leukemic infiltration of the lungs, which is a rare presentation in AML. He was then started on induction chemotherapy with intravenous daunorubicin and cytarabine. In the midst of treatment, he developed an episode of seizure and cerebro-spinal fluid cytology confirmed central nervous system (CNS) leukaemic infiltration. Additional intrathecal methotraxate was given. Repeat bone marrow examination done on day 15 of chemotherapy showed persistence of excess blasts indicating refractory AML. He was then reinduced with high dose cytarabine but to no avail. The disease progressed and he succumbed about 8 weeks after the initial diagnosis was made. We highlight here a case of AML-M4Eo with complex karyoyptic abnormalities presenting with leukaemic infiltration of the lungs and CNS which had imparted a bad prognosis for this subtype of AML, AML-M4Eo.
    Matched MeSH terms: Methotrexate/therapeutic use
  19. Lin HP, Sinnah D, Menaka N, Cherian R, Singh P
    Med. Pediatr. Oncol., 1983;11(5):327-32.
    PMID: 6579342
    One hundred four children with acute lymphoblastic leukaemia were diagnosed at the University Hospital, Kuala Lumpur, Malaysia, between 1976 and 1982; 87 were evaluable with respect to treatment. They were divided into good prognosis (GP) and bad prognosis (BP) groups based on their initial total white cell count, their treatment differing only during the maintenance phase. Remission was achieved in 82 patients (94%) of whom ten (12%) subsequently died in remission from infection. Twenty-eight (34%) relapsed while on treatment and three while off therapy. Eleven patients ceased treatment after 3 yr of continuous complete remission (CCR). Three of these later relapsed, two within the first year. Survival in CCR was significantly better in the GP group up to 30 months, after which the difference diminished. There was no difference in survival between boys and girls. The overall disease-free survival at 3 yr and 5 yr was 40% and 25%, respectively, with a median follow-up period of 20 months (range 4-69 months). The reasons for the relatively low survival rates as compared with those in developed countries are discussed.
    Matched MeSH terms: Methotrexate/administration & dosage
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