Displaying publications 1 - 20 of 76 in total

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  1. Treatment of skin diseases: recent trends
    Adam BA
    Med J Malaysia, 1973 Mar;27(3):192-4.
    PMID: 4268922
    Matched MeSH terms: Methotrexate/therapeutic use
  2. Fulltext Heterocyclic Substitutions Greatly Improve Affinity and Stability of Folic Acid towards FRα. an In Silico Insight
    Al-Thiabat MG, Saqallah FG, Gazzali AM, Mohtar N, Yap BK, Choong YS, et al.
    Molecules, 2021 Feb 18;26(4).
    PMID: 33670773 DOI: 10.3390/molecules26041079
    Folate receptor alpha (FRα) is known as a biological marker for many cancers due to its overexpression in cancerous epithelial tissue. The folic acid (FA) binding affinity to the FRα active site provides a basis for designing more specific targets for FRα. Heterocyclic rings have been shown to interact with many receptors and are important to the metabolism and biological processes within the body. Nineteen FA analogs with substitution with various heterocyclic rings were designed to have higher affinity toward FRα. Molecular docking was used to study the binding affinity of designed analogs compared to FA, methotrexate (MTX), and pemetrexed (PTX). Out of 19 FA analogs, analogs with a tetrazole ring (FOL03) and benzothiophene ring (FOL08) showed the most negative binding energy and were able to interact with ASP81 and SER174 through hydrogen bonds and hydrophobic interactions with amino acids of the active site. Hence, 100 ns molecular dynamics (MD) simulations were carried out for FOL03, FOL08 compared to FA, MTX, and PTX. The root mean square deviation (RMSD) and root mean square fluctuation (RMSF) of FOL03 and FOL08 showed an apparent convergence similar to that of FA, and both of them entered the binding pocket (active site) from the pteridine part, while the glutamic part was stuck at the FRα pocket entrance during the MD simulations. Molecular mechanics Poisson-Boltzmann surface accessible (MM-PBSA) and H-bond analysis revealed that FOL03 and FOL08 created more negative free binding and electrostatic energy compared to FA and PTX, and both formed stronger H-bond interactions with ASP81 than FA with excellent H-bond profiles that led them to become bound tightly in the pocket. In addition, pocket volume calculations showed that the volumes of active site for FOL03 and FOL08 inside the FRα pocket were smaller than the FA-FRα system, indicating strong interactions between the protein active site residues with these new FA analogs compared to FA during the MD simulations.
    Matched MeSH terms: Methotrexate/chemistry
  3. Successful treatment of paediatric generalized pustular psoriasis with secukinumab: a case series
    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
  4. A Single Institution's Experience with Cytogenetic and MRD Outcomes in Pediatric Acute Lymphoblastic Leukemia
    Amjad A, Wali RM, Anjum S, Mansoor R
    J Coll Physicians Surg Pak, 2019 Jun;29(6):549-552.
    PMID: 31133155 DOI: 10.29271/jcpsp.2019.06.549
    OBJECTIVE: To determine the frequency of cytogenetic type and its significance in the prognostic outcome of the pediatric patients in acute lymphoblastic leukemia (ALL), aged 1 to 15 years, and also determine the importance of minimal residual disease (MRD) in the management of the condition.

    STUDY DESIGN: An observational study.

    PLACE AND DURATION OF STUDY: Pediatric Oncology Ward, Shaukat Khanum Cancer Hospital, Lahore, from January 2015 to July 2017.

    METHODOLOGY: Patients aged 1-15 years, diagnosed with ALL, were included. Studied variables were cytogenetic type and MRD outcome in patients with ALL. Patients under one year of age and more than 15 years, or those having comorbidities, were excluded.

    RESULTS: Total 150 patients' data were retrieved from the Hospital database. One hundred and thirty-three belonged to age 1 to 5 years group (89%) and 17 (11%) were in 5 to 10 years group. The mean age of the patient was 4.3 +3.1 years. One hundred and two (68%) were males; whereas, 48 (32%) were females. Pre B acute lymphoblastic leukemia was diagnosed in 139 (93%) patients and 11(7%) were diagnosed with Pre T acute lymphoblastic leukemia. Standard risk was observed in 120 (80%) patients and 30 (20%) patients were on high risk as per National Cancer Institute (NCI) Guidelines. Regimen A was used in 125 (83.3%), Regimen B in 16 (10.7%), and Regimen C in 9 (6%) patients. BCR-ABL was positive in 2 (1.30%), TEL-AML in 68 (45%), MLL in 5 (3.30%), and normal in 54 (36%). MRD at day 29 was negative in 40 (93%) and positive in 3 (7%). The karyotyping was done in 128 (85%) patients, out of which 68 (53%) were hyperploids, 41 (32%) euploid, and 19 (15%) were hypoploid. Death was observed in 22 (15%) patients. Nineteen (86%) deaths were due to fungal and bacterial sepsis; and disease-related deaths were noted in 3 (14%) patients.

    CONCLUSION: The role of MRD and cytogenetics in risk assessment has improved in the early prognosis determination.

    Matched MeSH terms: Methotrexate
  5. Fulltext More than meets the naked eye: an unusual psoriatic arthritis mimicry and the important role of dermoscopic examination
    Anne LJ, Rahim MJC, Ghazali WSW, Ahmed WAW, Isa SAM
    BMC Rheumatol, 2021 Apr 12;5(1):10.
    PMID: 33840385 DOI: 10.1186/s41927-021-00182-7
    BACKGROUND: Psoriatic arthritis (PsA) can manifest in various forms. This includes mimicry of other diseases. We describe an unusual mimicry of PsA.

    CASE PRESENTATION: We report a case of a middle-aged lady who presented with severe pain and morning stiffness over the small joints of the left hand for 3 months and painless deformity of the affected joints 1 year before. She was under treatment for pruritic rash over her ankles and knees for the past 1 year as well. Physical examination revealed a fixed flexion deformity, swelling and tenderness of the left ring and little fingers' distal interphalangeal (DIP) joints. Left hand radiograph showed sclerotic joint margin, narrowed joint space and marginal osteophytes of the affected DIP joints. Dermoscopic examination showed red- violaceous, flat-topped papules and plaques with minimal scales on both ankles; hyperpigmented scaly plaques over both knees and vertical fingernail ridges. Serum autoimmune screening and inflammatory markers were unremarkable. Left ankle skin biopsy showed features consistent of psoriasis. PsA was diagnosed. Weekly titrated oral methotrexate and topical steroid were started. The patient showed significant improvement after 1 month of treatment.

    CONCLUSION: PsA is a great mimicker. Dermoscopy is an accessible and valuable tool to assess skin lesions in greater detail. Clinicians should be aware of coexisting diseases or misdiagnosis when patients do not respond to treatment.

    Matched MeSH terms: Methotrexate
  6. Fulltext Advances and Opportunities in Passive Wake-Up Radios with Wireless Energy Harvesting for the Internet of Things Applications
    Bello H, Xiaoping Z, Nordin R, Xin J
    Sensors (Basel), 2019 Jul 12;19(14).
    PMID: 31336834 DOI: 10.3390/s19143078
    Wake-up radio is a promising approach to mitigate the problem of idle listening, which incurs additional power consumption for the Internet of Things (IoT) wireless transmission. Radio frequency (RF) energy harvesting technique allows the wake-up radio to remain in a deep sleep and only become active after receiving an external RF signal to 'wake-up' the radio, thus eliminating necessary hardware and signal processing to perform idle listening, resulting in higher energy efficiency. This review paper focuses on cross-layer; physical and media access control (PHY and MAC) approaches on passive wake-up radio based on the previous works from the literature. First, an explanation of the circuit design and system architecture of the passive wake-up radios is presented. Afterward, the previous works on RF energy harvesting techniques and the existing passive wake-up radio hardware architectures available in the literature are surveyed and classified. An evaluation of the various MAC protocols utilized for the novel passive wake-up radio technologies is presented. Finally, the paper highlights the potential research opportunities and practical challenges related to the practical implementation of wake-up technology for future IoT applications.
    Matched MeSH terms: Methotrexate
  7. Fulltext A Case of Linear Scleroderma in a Young Child: A Diagnosis Easily Missed in Primary Care
    Bin Ahmad MZ, Mat Nasir N, Md Yasin M, Yusof ANM, Bakrin IH, Lim SC
    Am J Case Rep, 2023 May 19;24:e940148.
    PMID: 37202915 DOI: 10.12659/AJCR.940148
    BACKGROUND This case illustrates the challenges in diagnosing linear scleroderma (LS) in a child who presented to a primary care setting. Diagnosis of LS is easily missed due to the lack of prominent symptoms, subtle visible skin changes, and under-recognition of this condition. CASE REPORT A 7-year-old boy presented with a linear, painless, non-itchy rash at the center of his forehead, which has been present for 6 months. The rash extends vertically from the hairline to the bridge of the nose. The color gradually evolved from reddish to purplish-grey and shiny within 3 months. He had underlying eczema, allergic rhinitis, and allergic conjunctivitis since birth. His condition remained unrecognized despite consultations with various medical specialties, including family medicine specialist, ophthalmologist, otorhinolaryngologist, and a general pediatrician. Six months after the onset of his lesion, he was subsequently referred to a pediatric dermatologist and pediatric rheumatologist, who made the diagnosis of LS. Laboratory investigations for autoimmune disease showed that negative antinuclear antibodies (ANA) and inflammatory markers, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were normal. Skin biopsy provided a tissue confirmation of the diagnosis. MRI of the lesion showed no extension into the underlying muscle or bone erosions. The patient was initially treated with intravenous (IV) methylprednisolone for 3 days, followed by oral methotrexate weekly and prednisolone. The lesion improved after 1 month of treatment, and after 15 months it was less pigmented and less noticeable. CONCLUSIONS LS is the commonest form of localized scleroderma in children. LS on the forehead can erode into the underlying tissues and is sometimes associated with extensive hemifacial atrophy. Treatment should be instituted early to prevent late irreversible fibrotic sequelae. This report aims to highlight the importance of early diagnosis and treatment of an uncommon but potentially disfiguring condition.
    Matched MeSH terms: Methotrexate/therapeutic use
  8. Fulltext Current trends in the management of oral mucositis related to cancer treatment
    Biswal BM
    Malays J Med Sci, 2008 Jul;15(3):4-13.
    PMID: 22570584 MyJurnal
    Oral mucositis is one of the most common toxicities observed during radiotherapy and chemotherapy treatment for cancers. Mucositis results in sore mouth, altered taste sensation, pain and dysphagia leading to malnutrition. Left untreated, oral mucositis leads to ulceration, orodental infection, bleeding and discontinuation of effective radiotherapy or chemotherapy. Frequent hospitalization, enteral or parenteral nutrition, increased demand for analgesics ultimately account for increased cost of healthcare. Quantification of oral mucositis using standardized grading system is important for appropriate evaluation, reporting and management. In the recent past there is a paradigm shift in the pathobiology of cancer therapy related mucositis. Clear understanding of its pathogenesis is essential for the formulation of effective mucositis care. Numerous drug therapies, radiation techniques and oral care protocols have been tried in the past to reduce oral mucositis, None have proven to be consistently effective. Current trends for the prevention and treatment of oral mucositis is multi-targeted treatment supplemented by aggressive oral hygiene, reactive oxygen species (ROS) inhibitors, growth factors and use of specific topical agents to improve treatment of oral mucositis in future.
    Matched MeSH terms: Methotrexate
  9. Outcome of treatment in adult acute lymphoblastic leukaemia in an Asian population: comparison with previous multicentre German study
    Bosco I, Teh A
    Leukemia, 1995 Jun;9(6):951-4.
    PMID: 7596183
    Reports on the outcome of treatment in ALL in Asian (non-Caucasian) adults have been few, and published results compare very unfavourably with results of treatment from 'Western' centres. Seventy-four newly diagnosed Malaysian patients with ALL between the ages of 15 and 69 were treated from 1986 to 1990. The clinical features and prognostic factors were similar to those reported in 'Western' series. The chemotherapy protocol utilized was adapted from the one used by Hoelzer et al in the multicentre German study. The complete remission rate was 73%. The probability of continuous complete remission at 5 years was 29% with a median duration of remission of 15 months. This compares with Hoelzer's initial results of 77% CR rate and 35% CCR at 5 years. Patients with an initial white cell count of less than 30 x 10(9)/l at presentation were found to have a significantly better disease-free survival than those with a count of more than 30 x 10(9)/l (35 vs 22%, P = 0.026, univariate analysis). There was no difference in leukaemia-free survival according to age, sex, ethnic group, or immunophenotype. These results show that the use of moderately intensive chemotherapy protocols in Asian (non-Caucasian) patients achieves similar results to those used in Caucasians. We also showed that the difficulties in 'curing' approximately 70% of adult patient with ALL are universal.
    Matched MeSH terms: Methotrexate/administration & dosage
  10. Raynaud's phenomenon associated with psoriatic arthritis
    Che Rahim MJ, Lim JA, Wan Ghazali WS
    BMJ Case Rep, 2024 Mar 05;17(3).
    PMID: 38442964 DOI: 10.1136/bcr-2023-258215
    We report a case of Raynaud's phenomenon in a patient with psoriatic arthritis (PsA). A middle-aged right-handed housewife presented with complaints of severely painful hand discolouration for 1 week, which usually worsened with cold exposure. She was diagnosed with PsA 6 months earlier. Her PsA was well controlled with weekly methotrexate. Physical examination showed no features of scleroderma or skin necrosis of her right hand. Both radial pulses were strong and symmetrical. Her nailfolds were visibly normal. The extractable nuclear antigen panel and other blood investigations were negative for scleroderma and other possible causes of secondary Raynaud's phenomenon. Occupational or environmental factors were also excluded. Dermatoscope examination of the nailfolds revealed some areas of dilated capillary loops, areas of vascular sparing and proximal nail fold telangiectasia. The diagnosis of secondary Raynaud's phenomenon was made, and an oral calcium channel blocker was started. The patient had significant improvement in symptoms shortly afterwards.
    Matched MeSH terms: Methotrexate
  11. Clinical profile, morbidity, and outcome of adult-onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia
    Choon SE, Lai NM, Mohammad NA, Nanu NM, Tey KE, Chew SF
    Int J Dermatol, 2014 Jun;53(6):676-84.
    PMID: 23967807 DOI: 10.1111/ijd.12070
    BACKGROUND: Generalized pustular psoriasis (GPP) is a severe but rare variant of psoriasis. Our objective is to review the clinical profile, comorbidities, and outcome of patients with GPP.
    MATERIALS AND METHODS: A retrospective note review of all patients with adult-onset GPP.
    RESULTS: A total of 102 patients with adult-onset GPP were diagnosed between 1989 and November 2011, with a female to male ratio of 2 : 1. The mean age at onset of GPP was 40.9 years (range: 21-81 years). Acute GPP was the most common variant seen (95 cases), followed by four localized variants of GPP and three with annular pustular psoriasis. Fever and painful skin were present in 89% of patients, arthritis in 34.7%, and leukocytosis in 78.4%. Common triggers were systemic steroids (45 cases), pregnancy (17 cases), and upper respiratory tract infections (16 cases). A positive family history of psoriasis and GPP was present in 29% and 11%, respectively. Comorbidities included obesity (42.9%), hypertension (25.7%), hyperlipidemia (25.7%), and diabetes mellitus (23.7%). The mean duration of admission and pustular flare for acute GPP was 10.3 days (range: 3-44 days) and 16 days (range: 7-60 days), respectively. Fifty-four patients responded to systemic retinoid, 21 to methotrexate, eight to cyclosporine, and one to adalimumab, but recurrences were common.
    CONCLUSIONS: Our study confirms the poor response of GPP to currently available anti-psoriatic agents, with frequent flare-ups. There is a need for a more effective targeted therapy for this condition.
    Matched MeSH terms: Methotrexate/therapeutic use*
  12. Efficacy of methotrexate in reducing the risk of bone erosion in patients with rheumatoid arthritis: a systematic review of randomized controlled trials
    Destiani DP, Naja S, Dewi S, Rahmadi AR, Sulaiman SAS, Abdulah R
    Osteoporos Int, 2021 May;32(5):805-816.
    PMID: 33210179 DOI: 10.1007/s00198-020-05743-z
    Even though new drugs for the treatment of rheumatoid arthritis (RA) have been developed, methotrexate (MTX) remains a commonly used drug for RA management. In addition to monitoring disease activity during RA treatment, bone erosion should be closely assessed throughout long-term RA management. In this review article, we present a systematic review of MTX effectiveness in reducing the risk of bone erosion. We reviewed randomized controlled trial studies that involved MTX monotherapy or MTX in combination with placebo. Evaluation of the progression of bone erosion was examined by radiographic assessment such as total Sharp score (TSS) or van der Heijde score (SvdH or vdH TSS), joint space narrowing (JSN), erosion score (ERO), and proportion of radiographic nonprogressors. Several key factors were found to influence the response to MTX treatment, such as gene polymorphism. The exact mechanism of the prevention of bone erosion by MTX remains unclear, which warrants future investigations. The variability of RA disease activity in study subjects resulted in variations in the results reported by individual studies. Collective analysis suggests that MTX could slow down the progression of bone erosion based on a radiographic score of less than 0.5-1/year.
    Matched MeSH terms: Methotrexate/therapeutic use
  13. Fulltext The atypical presentation of rheumatoid arthritis in an elderly woman: a case report
    Devaraj NK
    Ethiop J Health Sci, 2019 Jan;29(1):957-958.
    PMID: 30700964 DOI: 10.4314/ejhs.v29i1.18
    The diagnosis of rheumatologic problem can be difficult, especially if not all the diagnostic criteria or typical clinical features are seen. This includes conditions such as rheumatoid arthritis which needs early diagnosis to start disease modifying drugs (DMARDs) which can improve the prognosis and prevent further joint erosion and organ damage. This case report focused on a similar scenario in an elderly woman initially thought to have osteoarthritis but was diagnosed later with rheumatoid arthritis which brought much relief to her current predicament.
    Matched MeSH terms: Methotrexate/therapeutic use
  14. Mixed Oleic Acid-Erucic Acid Liposomes as a Carrier for Anticancer Drugs
    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
  15. Uterine-conserving approach in ruptured intramyometrial ectopic pregnancy
    Esther LSY, Chew KT, Rahman RA, Zainuddin AA, Hing EY, Kampan N
    Horm Mol Biol Clin Investig, 2020 Mar 13;41(2).
    PMID: 32167930 DOI: 10.1515/hmbci-2020-0001
    Intramyometrial ectopic pregnancy (IMEP) is a rare form of ectopic pregnancy. It is defined as a conceptus implanted within the myometrium and is completely surrounded by myometrium with clear separation from both the uterine cavity and tubes. IMEP possesses not only diagnostic but also therapeutic challenge. The majority of reported cases were managed by hysterectomy. Early management of unruptured IMEP using methotrexate may help to preserve fertility. We, for the first time, report a case of ruptured IMEP managed successfully using suction and curettage followed by Bakri balloon tamponade and avoiding hysterectomy. Post-procedure, the patient received two doses of intramuscular methotrexate 50 mg/m2 due to plateauing serial beta human chorionic gonadotropin (β-hCG) levels and subsequently achieved undetectable level 10 weeks post-methotrexate. She also had complete resolution of the ectopic intramyometrial mass.
    Matched MeSH terms: Methotrexate/therapeutic use
  16. Disease-modifying antirheumatic drugs and organising pneumonia
    Faisal M, Roslan A, Nik Abeed NN, Ban Yu-Lin A
    BMJ Case Rep, 2021 Jan 06;14(1).
    PMID: 33408105 DOI: 10.1136/bcr-2020-238173
    Organising pneumonia (OP) in rheumatoid arthritis (RA) may be part of pulmonary manifestation (disease related) or disease-modifying antirheumatic drugs (DMARDs) related. We report a case series of RA patients with DMARDs related OP. A 65-year-old woman developed OP 3 weeks after initiation of methotrexate (MTX). High-resolution CT (HRCT) scan of the thorax revealed bilateral consolidations in the lung bases. She had complete radiological resolution 6 months after corticosteroid therapy with cessation of MTX. The second case was of a 60-year-old woman on MTX with recent addition of leflunomide due to flare of RA. She developed worsening cough 4 months later and HRCT scan revealed consolidation in the left upper lobe with biopsy proven OP. She responded within 6 months of corticosteroid therapy with clinical and radiological resolution. This case series highlights that OP may developed with low-dose MTX (as early as 3 weeks) and leflunomide and the diagnosis requires a high index of suspicion.
    Matched MeSH terms: Methotrexate/adverse effects*
  17. Fulltext Role of nitric oxide-scavenging activity of Karanjin and Pongapin in the treatment of Psoriasis
    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
  18. Fulltext The identification of novel Mycobacterium tuberculosis DHFR inhibitors and the investigation of their binding preferences by using molecular modelling
    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
  19. Fulltext Hyaluronic Acid-Mediated Drug Delivery System Targeting for Inflammatory Skin Diseases: A Mini Review
    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
  20. Fulltext Pemphigus vulgaris in a pregnant woman and her neonate
    Ibrahim SB, Yashodhara BM, Umakanth S, Kanagasabai S
    BMJ Case Rep, 2012;2012.
    PMID: 22744241 DOI: 10.1136/bcr.02.2012.5850
    A 23-year-old pregnant woman in her second trimester of pregnancy presented with blisters on the face, abdomen and the leg. Based on the clinical presentation and skin biopsy (histopathology and direct immunofluorescence) the diagnosis of pemphigus vulgaris was established. The child born to this patient also had similar skin lesions. The lesions in the mother and the child improved after treatment. The authors report a rare case of pemphigus vulgaris in a pregnant lady and neonatal pemphigus in her child, both of whom were treated successfully.
    Matched MeSH terms: Methotrexate/therapeutic use
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