Displaying publications 61 - 80 of 2763 in total

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  1. Koh HP, Shamsudin NS, Tan MMY, Mohd Pauzi Z
    J Clin Pharm Ther, 2021 Aug;46(4):1129-1138.
    PMID: 33768601 DOI: 10.1111/jcpt.13410
    WHAT IS KNOWN AND OBJECTIVE: Nebulizer use has been suspended in Malaysian public health facilities due to the potential to aggravate COVID-19 nosocomial transmission. Currently, our facility uses the pressurized metered-dose inhaler (pMDI) bronchodilator with Venturi mask modified spacer (VMMS) in patients visiting the Emergency Department (ED) for mild to moderate exacerbation of asthma and chronic obstructive pulmonary disease (COPD). We sought to assess the outcomes and acceptance of pMDI-VMMS in the outpatient ED of a tertiary hospital in Malaysia.

    METHODS: We analysed the total visits and discharge rates during periods of using the nebulizer and current pMDI-VMMS methods. The acceptance of pMDI-VMMS by patients and assistant medical officers (AMOs) were assessed by questionnaire.

    RESULTS AND DISCUSSION: We analysed 3184 ED visits and responses from 103 patients and 32 AMOs. The direct discharge rate was similar for both nebulizer (n = 2162, 92.5%) and pMDI-VMMS method (n = 768, 90.7%) (p-value = 0.120). Twenty-eight patients (27.2%) favoured the pMDI-VMMS over the nebulizer, whereas 36 patients (35.0%) had no preference for either method. Sixty-four patients (62.1%) felt that the current pMDI-VMMS method was better or at least as effective in relieving their symptoms as a nebulizer. The current method was favoured over the nebulizer by twenty-seven AMOs (84.4%). Twenty-eight (87.5%) AMOs suggested that the current method was more effective than the nebulizer.

    WHAT IS NEW AND CONCLUSION: The bronchodilator delivered via pMDI-VMMS appeared to be comparable to nebulizer in treating mild to moderate asthma and COPD exacerbations in the outpatient ED. Most patients and AMOs accepted the use of pMDI-VMMS in the outpatient ED during the current COVID-19 pandemic. The Venturi mask modified spacer can be a cheap and effective alternative to the commercial spacer in a resource-limited situation.

    Matched MeSH terms: Bronchodilator Agents/administration & dosage*
  2. Al-Ziftawi NH, Shafie AA, Mohamed Ibrahim MI
    Expert Rev Pharmacoecon Outcomes Res, 2021 Aug;21(4):655-666.
    PMID: 32657174 DOI: 10.1080/14737167.2020.1794826
    BACKGROUND: Pharmacoeconomic evaluation is important for breast-cancer medications due to their high costs. To our knowledge, no systematic literature reviews of pharmacoeconomic studies for breast-cancer medication use are present in developing-countries.

    OBJECTIVES: To systematically review the existing cost-effectiveness evaluations of breast-cancer medication in developing-countries.

    METHODOLOGY: A systematic literature search was performed in PubMed, EMBASE, SCOPUS, and EconLit. Two researchers determined the final articles, extracted data, and evaluated their quality using the Quality of Health-Economic Studies (QHES) tool. The interclass-correlation-coefficient (ICC) was calculated to assess interrater-reliability. Data were summarized descriptively.

    RESULTS: Fourteen pharmacoeconomic studies published from 2009 to 2019 were included. Thirteen used patient-life-years as their effectiveness unit, of which 10 used quality-adjusted life-years. Most of the evaluations focused on trastuzumab as a single agent or on regimens containing trastuzumab (n = 10). The conclusion of cost-effectiveness analysis varied among the studies. All the studies were of high quality (QHES score >75). Interrater reliability between the two reviewers was high (ICC = 0.76).

    CONCLUSION: In many studies included in the review, the use of breast-cancer drugs in developing countries was not cost-effective. Yet, more pharmacoeconomic evaluations for the use of recently approved agents in different disease stages are needed in developing countries.

    Matched MeSH terms: Trastuzumab/administration & dosage; Antineoplastic Agents/administration & dosage*
  3. Sukarna N, Tan PC, Hong JGS, Sulaiman S, Omar SZ
    Arch Gynecol Obstet, 2021 08;304(2):345-353.
    PMID: 33452923 DOI: 10.1007/s00404-020-05950-3
    PURPOSE: To compare 3 consecutive days of hyperglycemic response following antenatal dexamethasone regimens of 12-mg or 6-mg doses 12 hourly in diet-controlled gestational diabetes.

    METHODS: A randomized controlled trial was carried out in a university hospital in Malaysia. Women with lifestyle-controlled gestational diabetes scheduled to receive clinically indicated antenatal corticosteroids (dexamethasone) were randomized to 12-mg 12 hourly for one day (2 × 12-mg) or 6-mg 12-hourly for two days (4 × 6-mg). 6-point (pre and 2-h postprandial) daily self-monitoring of capillary blood sugar profile for up to 3 consecutive days was started after the first dexamethasone injection. Hyperglycemia is defined as blood glucose pre-meal ≥ 5.3 or 2 h postprandial ≥ 6.7 mmol/L. The primary outcome was a number of hyperglycemic episodes in Day-1 (first 6 BSP points). A sample size of 30 per group (N = 60) was planned.

    RESULTS: Median [interquartile range] hyperglycemic episodes 4 [2.5-5] vs. 4 [3-5] p = 0.3 in the first day, 3 [2-4] vs. 1 [0-3] p = 0.01 on the second day, 0 [0-1] vs. 0 [0-1] p = 0.6 on the third day and over the entire 3 trial days 7 [6-9] vs. 6 [4-8] p = 0.17 for 6-mg vs. 12-mg arms, respectively. 2/30 (7%) in each arm received an anti-glycemic agent during the 3-day trial period (capillary glucose exceeded 11 mmol/L). Mean birth weight (2.89 vs. 2.49 kg p 

    Matched MeSH terms: Adrenal Cortex Hormones/administration & dosage; Dexamethasone/administration & dosage*
  4. Chong NS, Smith SR, Werkman M, Anderson RM
    PLoS Negl Trop Dis, 2021 08;15(8):e0009625.
    PMID: 34339450 DOI: 10.1371/journal.pntd.0009625
    The World Health Organization has recommended the application of mass drug administration (MDA) in treating high prevalence neglected tropical diseases such as soil-transmitted helminths (STHs), schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. MDA-which is safe, effective and inexpensive-has been widely applied to eliminate or interrupt the transmission of STHs in particular and has been offered to people in endemic regions without requiring individual diagnosis. We propose two mathematical models to investigate the impact of MDA on the mean number of worms in both treated and untreated human subpopulations. By varying the efficay of drugs, initial conditions of the models, coverage and frequency of MDA (both annual and biannual), we examine the dynamic behaviour of both models and the possibility of interruption of transmission. Both models predict that the interruption of transmission is possible if the drug efficacy is sufficiently high, but STH infection remains endemic if the drug efficacy is sufficiently low. In between these two critical values, the two models produce different predictions. By applying an additional round of biannual and annual MDA, we find that interruption of transmission is likely to happen in both cases with lower drug efficacy. In order to interrupt the transmission of STH or eliminate the infection efficiently and effectively, it is crucial to identify the appropriate efficacy of drug, coverage, frequency, timing and number of rounds of MDA.
    Matched MeSH terms: Anthelmintics/administration & dosage*
  5. Liew KB, Peh KK
    Arch Pharm Res, 2021 Aug;44(8):1-10.
    PMID: 25579848 DOI: 10.1007/s12272-014-0542-y
    Orally disintegrating tablet (ODT) is a user friendly and convenient dosage form. The study aimed to investigate the effect of polymers and wheat starch on the tablet properties of lyophilized ODT, with dapoxetine as model drug. Three polymers (hydroxypropylmethyl cellulose, carbopol 934P and Eudragit® EPO) and wheat starch were used as matrix forming materials in preparation of lyophilized ODT. The polymeric dispersion was casted into a mould and kept in a freezer at -20 °C for 4 h before freeze dried for 12 h. It was found that increasing in HPMC and Carbopol 934P concentrations produced tablets with higher hardness and longer disintegration time. In contrast, Eudragit® EPO was unable to form tablet with sufficient hardness at various concentrations. Moreover, HPMC seems to have a stronger effect on tablet hardness compared to Carbopol 934P at the same concentration level. ODT of less friable was obtained. Wheat starch acted as binder which strengthen the hardness of ODTs and prolonged the disintegration time. ODT comprising of HPMC and wheat starch at ratio of 2:1 was found to be optimum based upon the tablet properties. The optimum formulation was palatable and 80 % of the drug was released within 30 min in the dissolution study.
    Matched MeSH terms: Benzylamines/administration & dosage*; Naphthalenes/administration & dosage*
  6. Bosch J, Lonn EM, Dagenais GR, Gao P, Lopez-Jaramillo P, Zhu J, et al.
    Stroke, 2021 08;52(8):2494-2501.
    PMID: 33985364 DOI: 10.1161/STROKEAHA.120.030790
    Background and Purpose: The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups.

    Methods: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed.

    Results: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59–1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55–1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34–1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41–2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52–0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37–0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36–0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23–0.72]).

    Conclusions: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.

    Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00468923.

    Matched MeSH terms: Antihypertensive Agents/administration & dosage*; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage*
  7. Hassan J, Toh TH, Sivapunniam SK, Hasim R, Ghazali NF, Sulaiman S, et al.
    Pediatr Infect Dis J, 2021 08 01;40(8):774-781.
    PMID: 34250977 DOI: 10.1097/INF.0000000000003164
    BACKGROUND: Incorporating dengue vaccination within existing vaccination programs could help improve dengue vaccine coverage. We assessed the immunogenicity and safety of a quadrivalent human papillomavirus (HPV) vaccine administered concomitantly or sequentially with a tetravalent dengue vaccine (CYD-TDV) in healthy children 9-13 years of age in Malaysia.

    METHODS: In this phase IIIb, open-label, multicenter study (NCT02993757), participants were randomized 1:1 to receive 3 CYD-TDV doses 6 months apart and 2 doses of quadrivalent HPV vaccine concomitantly with, or 1 month before (sequentially), the first 2 CYD-TDV doses. Only baseline dengue-seropositive participants received the 3 doses. Antibody levels were measured at baseline and 28 days after each injection using an enzyme-linked immunosorbent assay for HPV-6, -9, -16 and -18, and the 50% plaque reduction neutralization test for the 4 dengue serotypes; immunogenicity results are presented for baseline dengue-seropositive participants. Safety was assessed throughout the study for all participants.

    RESULTS: At baseline, 197 of 528 (37.3%) randomized participants were dengue-seropositive [n = 109 (concomitant group) and n = 88 (sequential group)]. After the last HPV vaccine dose, antibody titers for HPV among baseline dengue-seropositive participants were similar between treatment groups, with between-group titer ratios close to 1 for HPV-6 and 0.8 for HPV-11, -16, and -18. After CYD-TDV dose 3, dengue antibody titers were similar between treatment groups for all serotypes [between-group ratios ranged from 0.783 (serotype 2) to 1.07 (serotype 4)]. No safety concerns were identified.

    CONCLUSIONS: The immunogenicity and safety profiles of CYD-TDV and quadrivalent HPV vaccines were unaffected when administered concomitantly or sequentially in dengue-seropositive children.

    Matched MeSH terms: Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/administration & dosage*; Vaccines, Combined/administration & dosage*; Dengue Vaccines/administration & dosage*
  8. Das S, Tripathy S, Pramanik P, Saha B, Roy S
    Cytokine, 2021 08;144:155555.
    PMID: 33992538 DOI: 10.1016/j.cyto.2021.155555
    Emergence and spread of resistant parasites to the newest chemotherapeutic anti-malarial agents are the biggest challenges against malaria control programs. Therefore, developing a novel effective treatment to reduce the overgrowing burden of multidrug resistant malaria is a pressing need. Herein, we have developed a biocompatible and biodegradable, non-toxic chitosan-tripolyphosphate-chloroquine (CS-TPP CQ) nanoparticle. CS-TPP CQ nanoparticles effectively kill the parasite through redox generation and induction of the pro- and anti-inflammatory cytokines in both sensitive and resistant parasite in vitro. The in vitro observations showed a strong inhibitory effect (p 
    Matched MeSH terms: Chitosan/administration & dosage; Nanoparticles/administration & dosage*
  9. Almoustafa HA, Alshawsh MA, Chik Z
    Anticancer Drugs, 2021 Aug 01;32(7):745-754.
    PMID: 33675612 DOI: 10.1097/CAD.0000000000001065
    Poly lactic-co-glycolic acid (PLGA) nanoparticles are intensively studied nanocarriers in drug delivery because of their biodegradability and biochemical characteristics. Polyethylene glycol (PEG) coating for nanocarriers gives them long circulation time in blood and makes them invisible to the reticuloendothelial system. Breast cancer cells have greater uptake of hyaluronic acid compared to normal cells as it binds to their overexpressed CD44 receptors. Since hypoxia plays an important role in cancer metastasis; we formulated PEG-PLGA nanoparticles coated with hyaluronic acid as targeted delivery system for doxorubicin (DOX) using nanoprecipitation method, and characterized them for chemical composition, size, surface charge, shape, and encapsulation efficiency. Then we tested them in vitro on hypoxia-optimized metastatic breast cancer cells. The nanoparticles were spherical with an average size of about 106 ± 53 nm, a negative surface charge (-15 ± 3 mV), and high encapsulation efficiency (73.3 ± 4.1%). In vitro investigation with hypoxia-elevated CD44 MDA-MB-231 cells showed that hyaluronic acid-targeted nanoparticles maintained their efficacy despite hypoxia-induced drug resistance unlike free DOX and nontargeted nanoparticles. In conclusion, this study revealed a simple third generation nanoparticle formulation for targeted treatment of hypoxia-induced drug resistance in breast cancer metastatic cells. Further, optimization is needed including In vivo efficacy and nanoparticle-specific pharmacokinetic studies.
    Matched MeSH terms: Antibiotics, Antineoplastic/administration & dosage; Doxorubicin/administration & dosage; Anthracyclines/administration & dosage
  10. Al-Mohammed HI, Sulieman A, Mayhoub FH, Salah H, Lagarde C, Alkhorayef M, et al.
    Sci Rep, 2021 Jul 15;11(1):14557.
    PMID: 34267237 DOI: 10.1038/s41598-021-93342-1
    Worldwide, thyroid cancer accounts for some 10% of total cancer incidence, most markedly for females. Thyroid cancer radiotherapy, typically using 131I (T1/2 8.02 days; β- max energy 606 keV, branching ratio 89.9%), is widely adopted as an adjunct to surgery or to treat inoperable cancer and hyperthyroidism. With staff potentially receiving significant doses during source preparation and administration, radiation protection and safety assessment are required in ensuring practice complies with international guidelines. The present study, concerning a total of 206 patient radioiodine therapies carried out at King Faisal Specialist Hospital and Research Center over a 6-month period, seeks to evaluate patient and occupational exposures during hospitalization, measuring ambient doses and estimating radiation risk. Using calibrated survey meters, patient exposure dose-rate estimates were obtained at a distance of 30-, 100- and 300 cm from the neck region of each patient. Occupational and ambient doses were measured using calibrated thermoluminescent dosimeters. The mean and range of administered activity (AA, in MBq) for the thyroid cancer and hyperthyroidism treatment groups were 4244 ± 2021 (1669-8066), 1507.9 ± 324.1 (977.9-1836.9), respectively. The mean annual occupational doses were 1.2 mSv, that for ambient doses outside of the isolation room corridors were found to be 0.2 mSv, while ambient doses at the nursing station were below the lower limit of detection. Exposures to staff from patients being treated for thyroid cancer were less compared to hyperthyroidism patients. With a well-defined protocol, also complying with international safety requirements, occupational exposures were found to be relatively high, greater than most reported in previous studies.
    Matched MeSH terms: Iodine Radioisotopes/administration & dosage
  11. Nandini C, Madhunapantula SV, Bovilla VR, Ali M, Mruthunjaya K, Santhepete MN, et al.
    J Ethnopharmacol, 2021 Jul 15;275:114074.
    PMID: 33831466 DOI: 10.1016/j.jep.2021.114074
    ETHNOPHARMACOLOGICAL RELEVANCE: Carica papaya leaf juice/decoction has been in use in folk medicine in Srilanka, Malaysia and in few parts of India for enhancing the platelet counts in dengue. In Siddha medicine, a traditional form of medicine in India, papaya leaf juice has been used for increasing the platelet counts. Papaya leaf has been reported to enhance blood volume in ancient Ayurveda books in India. Carica papaya leaf is well known for its platelet enhancement activity. Although many preclinical and clinical studies have demonstrated the ability of papaya leaf juice for platelet enhancement, but the underlying mechanisms are still unclear.

    AIM OF THE STUDY: The study is aimed at identifying the key ingredients of papaya leaf extract and elucidate the mechanism (s) of action of the identified potent component in mitigating thrombocytopenia (Thp).

    MATERIALS AND METHODS: C. papaya leaf juice was subjected for sequential fractionation to identify the anti-thrombocytopenic phytochemicals. In vivo, stable thrombocytopenia was induced by subcutaneous injection of 70 mg/kg cyclophosphamide (Cyp). After induction, rats were treated with 200 and 400 mg/kg body weight papaya leaf juice and with identified fractions for 14 days. Serum thrombopoietin level was estimated using ELISA. CD110/cMpl, a receptor for thrombopoietin on platelets was measured by western blotting.

    RESULTS: Administration of cyclophosphamide for 6 days induced thrombocytopenia (210.4 ± 14.2 × 103 cells/μL) in rats. Treating thrombocytopenic rats with papaya leaf juice and butanol fraction for 14 days significantly increased the platelet count to 1073.50 ± 29.6 and 1189.80 ± 36.5 × 103 cells/μL, respectively. C.papaya extracts normalized the elevated bleeding and clotting time and decreased oxidative markers by increasing endogenous antioxidants. A marginal increase in the serum thrombopoietin (TPO) level was observed in Cyp treated group compared to normal and treatment groups. Low expression of CD110/cMpl receptor found in Cyp treated group was enhanced by C. papaya extracts (CPJ) and CPJ-BT. Furthermore, examination of the morphology of bone marrow megakaryocytes, histopathology of liver and kidneys revealed the ability of CPJ and fractions in mitigating Cyp-induced thrombocytopenia in rats.

    CONCLUSION: C. papaya leaf juice enhances the platelet count in chemotherapy-induced thrombocytopenia by increasing the expression of CD110 receptor on the megakaryocytes. Hence, activating CD110 receptor might be a viable strategy to increase the platelet production in individuals suffering from thrombocytopenia.

    Matched MeSH terms: Plant Extracts/administration & dosage
  12. Ezeasor CK, Emikpe BO, Shoyinka SV, Sabri MY
    J Immunoassay Immunochem, 2021 Jul 04;42(4):424-443.
    PMID: 33724901 DOI: 10.1080/15321819.2021.1895216
    This study reports the influence of peste des petits ruminants (PPR) vaccination on the clinico-pathological outcomes of PPR in the face of an outbreak. Twenty-two West African dwarf goats procured for a different study started showing early signs of PPR during acclimatization. In response, PPR vaccine was administered either intranasally with phytogenic mucoadhesive gum (Group A; n = 6) or without gum (Group B; n = 6); subcutaneously (Group C; n = 6) or not vaccinated (Group D; n = 4) and studied for 21 days. The clinical scores, hematology, serology and pathology scores were evaluated. Clinical signs of PPR were present in all groups, presenting a percentage mortality of 33%; 33%; 64% and 100% for Groups A, B, C, and D, respectively. Polycythemia and mild leukopenia were observed in all groups, and all animals were seropositive by day 7 post-vaccination. The lung consolidation scores were low in Groups A and B, compared to Group C. Histopathological lesions consistent with PPR was observed in the lymphoid organs, gastrointestinal tract, and lungs with the presence of PPR antigen as detected by immunohistochemistry. The findings suggest that intranasal vaccination with or without mucoadhesive gum may influence the outcome of PPR infection more than the subcutaneous route in the face of an outbreak.
    Matched MeSH terms: Polymers/administration & dosage; Viral Vaccines/administration & dosage
  13. Se Thoe E, Fauzi A, Tang YQ, Chamyuang S, Chia AYY
    Life Sci, 2021 Jul 01;276:119129.
    PMID: 33515559 DOI: 10.1016/j.lfs.2021.119129
    Alzheimer's disease (AD) is a multifactorial neurodegenerative disease which is mainly characterized by progressive impairment in cognition, emotion, language and memory in older population. Considering the impact of AD, formulations of pharmaceutical drugs and cholinesterase inhibitors have been widely propagated, receiving endorsement by FDA as a form of AD treatment. However, these medications were gradually discovered to be ineffective in removing the root of AD pathogenesis but merely targeting the symptoms so as to improve a patient's cognitive outcome. Hence, a search for better disease-modifying alternatives is put into motion. Having a clear understanding of the neuroprotective mechanisms and diverse properties undertaken by specific genes, antibodies and nanoparticles is central towards designing novel therapeutic agents. In this review, we provide a brief introduction on the background of Alzheimer's disease, the biology of blood-brain barrier, along with the potentials and drawbacks associated with current therapeutic treatment avenues pertaining to gene therapy, immunotherapy and nanotherapy for better diagnosis and management of Alzheimer's disease.
    Matched MeSH terms: Pharmaceutical Preparations/administration & dosage*
  14. Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al.
    Life Sci, 2021 Jul 01;276:119436.
    PMID: 33789146 DOI: 10.1016/j.lfs.2021.119436
    Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.
    Matched MeSH terms: Rutin/administration & dosage; Nanoparticles/administration & dosage*
  15. Cromwell EA, Osborne JCP, Unnasch TR, Basáñez MG, Gass KM, Barbre KA, et al.
    PLoS Negl Trop Dis, 2021 07;15(7):e0008824.
    PMID: 34319976 DOI: 10.1371/journal.pntd.0008824
    Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.
    Matched MeSH terms: Ivermectin/administration & dosage
  16. Dinh TN, Parat MO, Ong YS, Khaw KY
    Pharmacol Res, 2021 07;169:105666.
    PMID: 33989764 DOI: 10.1016/j.phrs.2021.105666
    Benzyl isothiocyanate (BITC) is one of the common isothiocyanates found in cruciferous vegetables such as broccoli, cabbage or watercress. Preclinical studies report of its effectiveness in the prevention and treatment against several cancers. This review aims to report and discuss findings on anticancer activities of BITC and its modes of action against 14 types of cancer. A literature search was conducted using the keywords "BITC" and "anticancer" from PubMed, Google Scholar and CINAHL Plus to obtain relevant research articles. This review highlights the anticancer efficacy of BITC through modulation of various signaling pathways involved in apoptosis, cell proliferation, cell cycle arrest, metastasis, angiogenesis, autophagy and the effects of BITC in combination with other drugs. With the available pharmacology evidence, we conclude that further studies are needed to validate its effectiveness in humans for further development and translation into prophylaxis or therapy by promoting optimal therapeutic effects and minimizing toxicity in cancer treatment.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage; Isothiocyanates/administration & dosage
  17. Dear JW, Ng ML, Bateman DN, Leroy Sivappiragasam P, Choi H, Khoo BBJ, et al.
    Clin Transl Sci, 2021 Jul;14(4):1476-1489.
    PMID: 33742775 DOI: 10.1111/cts.13009
    N-acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol-APAP)-induced acute liver injury (ALI). The 3-bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose. This study evaluated the redox thiol response and APAP metabolites, in patients with a single APAP overdose treated with either the 20.25 h standard or 12 h modified regimen. We used liquid chromatography tandem mass spectrometry to quantify clinically important oxidative stress biomarkers and APAP metabolites in plasma samples from 45 patients who participated in a randomized controlled trial (SNAP trial). We investigated the time course response of plasma metabolites at predose, 12 h, and 20.25 h post-start of NAC infusion. The results showed that the 12 h modified regimen resulted in a significant elevation of plasma NAC and cysteine concentrations at 12 h post-infusion. We found no significant alteration in the metabolism of APAP, mitochondrial, amino acids, and other thiol biomarkers with the two regimens. We examined APAP and purine metabolism in overdose patients who developed ALI. We showed the major APAP-metabolites and xanthine were significantly higher in patients with ALI. These biomarkers correlated well with alanine aminotransferase activity at admission. Receiver operating characteristic analysis showed that at admission, plasma APAP-metabolites and xanthine concentrations were predictive for ALI. In conclusion, a significantly higher redox thiol response with the modified NAC regimen at 12 h postdose suggests this regimen may produce greater antioxidant efficacy. At baseline, plasma APAP and purine metabolites may be useful biomarkers for early prediction of APAP-induced ALI.
    Matched MeSH terms: Acetylcysteine/administration & dosage*; Antidotes/administration & dosage*
  18. Angelopoulou E, Paudel YN, Piperi C
    Mol Neurobiol, 2021 Jul;58(7):3031-3042.
    PMID: 33608826 DOI: 10.1007/s12035-021-02326-9
    Parkinson's disease is the most common neurodegenerative movement disorder with unclear etiology and only symptomatic treatment to date. Toward the development of novel disease-modifying agents, neurotrophic factors represent a reasonable and promising therapeutic approach. However, despite the robust preclinical evidence, clinical trials using glial-derived neurotrophic factor (GDNF) and neurturin have been unsuccessful. In this direction, the therapeutic potential of other trophic factors in PD and the elucidation of the underlying molecular mechanisms are of paramount importance. The liver growth factor (LGF) is an albumin-bilirubin complex acting as a hepatic mitogen, which also exerts regenerative effects on several extrahepatic tissues including the brain. Accumulating evidence suggests that intracerebral and peripheral administration of LGF can enhance the outgrowth of nigrostriatal dopaminergic axonal terminals; promote the survival, migration, and differentiation of neuronal stem cells; and partially protect against dopaminergic neuronal loss in the substantia nigra of PD animal models. In most studies, these effects are accompanied by improved motor behavior of the animals. Potential underlying mechanisms involve transient microglial activation, TNF-α upregulation, and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) and of the transcription factor cyclic AMP response-element binding protein (CREB), along with anti-inflammatory and antioxidant pathways. Herein, we summarize recent preclinical evidence on the potential role of LGF in PD pathogenesis, aiming to shed more light on the underlying molecular mechanisms and reveal novel therapeutic opportunities for this debilitating disease.
    Matched MeSH terms: Bilirubin/administration & dosage
  19. Subramaniam T, Fauzi MB, Lokanathan Y, Law JX
    Int J Mol Sci, 2021 Jun 17;22(12).
    PMID: 34204292 DOI: 10.3390/ijms22126486
    Skin injury is quite common, and the wound healing is a complex process involving many types of cells, the extracellular matrix, and soluble mediators. Cell differentiation, migration, and proliferation are essential in restoring the integrity of the injured tissue. Despite the advances in science and technology, we have yet to find the ideal dressing that can support the healing of cutaneous wounds effectively, particularly for difficult-to-heal chronic wounds such as diabetic foot ulcers, bed sores, and venous ulcers. Hence, there is a need to identify and incorporate new ideas and methods to design a more effective dressing that not only can expedite wound healing but also can reduce scarring. Calcium has been identified to influence the wound healing process. This review explores the functions and roles of calcium in skin regeneration and reconstruction during would healing. Furthermore, this review also investigates the possibility of incorporating calcium into scaffolds and examines how it modulates cutaneous wound healing. In summary, the preliminary findings are promising. However, some challenges remain to be addressed before calcium can be used for cutaneous wound healing in clinical settings.
    Matched MeSH terms: Calcium, Dietary/administration & dosage
  20. Alnuqaydan AM, Almutary AG, Sukamaran A, Yang BTW, Lee XT, Lim WX, et al.
    AAPS PharmSciTech, 2021 Jun 08;22(5):173.
    PMID: 34105037 DOI: 10.1208/s12249-021-02062-2
    Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.
    Matched MeSH terms: Antiviral Agents/administration & dosage
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