Displaying publications 281 - 296 of 296 in total

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  1. Lim CS, Shaharuddin MS, Sam WY
    Glob J Health Sci, 2013 Mar;5(2):1-12.
    PMID: 23445691 DOI: 10.5539/gjhs.v5n2p1
    A cross sectional study was conducted to estimate risk of exposure to lead via tap water ingestion pathway for the population of Seri Kembangan (SK).
    Matched MeSH terms: Lead/analysis*
  2. Lah ZMANH, Ahmad SAA, Zaini MS, Kamarudin MA
    J Pharm Biomed Anal, 2019 Sep 10;174:608-617.
    PMID: 31265987 DOI: 10.1016/j.jpba.2019.06.024
    A facile electrochemical sandwich immunosensor for the detection of a breast cancer biomarker, the human epidermal growth factor receptor 2 (HER2), was designed, using lead sulfide quantum dots-conjugated secondary HER2 antibody (Ab2-PbS QDs) as a label. Using Ab2-PbS QDs in the development of electrochemical immunoassays leads to many advantages such as straightforward synthesis and well-defined stripping signal of Pb(II) through acid dissolution, which in turn yields better sensing performance for the sandwiched immunosensor. In the bioconjugation of PbS QDs, the available amine and hydroxyl groups from secondary anti-HER2 and capped PbS QDs were bound covalently together via carbonyldiimidazole (CDI) acting as a linker. In order to quantify the biomarker, SWV signal was obtained, where the Pb2+ ions after acid dissolution in HCl was detected. The plated mercury film SPCE was also detected in situ. Under optimal conditions, HER2 was detected in a linear range from 1-100 ng/mL with a limit of detection of 0.28 ng/mL. The measures of satisfactory recoveries were 91.3% to 104.3% for the spiked samples, displaying high selectivity. Therefore, this method can be applied to determine HER2 in human serum.
    Matched MeSH terms: Lead/chemistry*
  3. Bhatti S, Ali Shah SA, Ahmed T, Zahid S
    Drug Chem Toxicol, 2018 Oct;41(4):399-407.
    PMID: 29742941 DOI: 10.1080/01480545.2018.1459669
    The present study investigates the neuroprotective effects of Foeniculum vulgare seeds in a lead (Pb)-induced brain neurotoxicity mice model. The dried seeds extract of Foeniculum vulgare was prepared with different concentrations of organic solvents (ethanol, methanol, n-hexane). The in vitro antioxidant activity of Foeniculum vulgare seed extracts was assessed through DPPH assay and the chemical composition of the extracts was determined by high-resolution 1H NMR spectroscopy. The age-matched male Balb/c mice (divided into 9 groups) were administered with 0.1% Pb and 75% and 100% ethanol extracts of Foeniculum vulgare seeds at a dose of 200 mg/kg/day and 20 mg/kg/day. The maximum antioxidant activity was found for 75% ethanol extract, followed by 100% ethanol extract. Gene expression levels of oxidative stress markers (SOD1 and Prdx6) and the three isoforms of APP (APP common, 770 and 695), in the cortex and hippocampus of the treated and the control groups were measured. Significant increase in APP 770 expression level while a substantial decrease was observed for SOD1, Prdx6 and APP 695 expression in Pb-treated groups. Interestingly, the deranged expression levels were significantly normalized by the treatment with ethanol extracts of Foeniculum vulgare seeds (specifically at dose of 200 mg/kg/day). Furthermore, the Pb-induced morphological deterioration of cortical neurons was significantly improved by the ethanol extracts of Foeniculum vulgare seeds. In conclusion, the present findings highlight the promising therapeutic potential of Foeniculum vulgare to minimize neuronal toxicity by normalizing the expression levels of APP isoforms and oxidative stress markers.
    Matched MeSH terms: Lead/toxicity*
  4. Daramola J, M Ekhwan T, Adepehin EJ, Mokhtar J, Lam KC, Er AC
    Heliyon, 2019 Jul;5(7):e02121.
    PMID: 31384682 DOI: 10.1016/j.heliyon.2019.e02121
    Water constitutes a major environmental and public health concerns worldwide. A large proportion of global water consumption is sourced from surface water. The dependency level on surface water is higher in developing countries, especially in rural-to-semi-urban areas, where subsurface water is not accessible. Presented in this paper is a spatiotemporal and hydrochemical quality assessment of the spring-originated Landzun Stream in Bida, Nigeria; which is usually consumed in its untreated state. Water samples were systematically collected in eighteen locations along the stream channel in both rainy and dry seasons at an equidistance interval of 500m. On-site and laboratory measurement of important physical and hydrochemical parameters were carried out using standard procedures. Water temperature in the rainy season (34-37 °C) slightly exceeds measured values in the dry season (29-33 °C). 72.22% (rainy) and 83.33% (dry) of collected samples did not meet the odourless requirement for drinking water. Similarly, estimated percentages of 66.67 and 94.44 of collected samples in rainy and dry seasons respectively have a taste. Contrary to data in the rainy season, 89%, 11%, 67% and 56% of the dry season's samples were enriched in magnesium (Mg), lead (Pb), potassium (K) and iron (Fe) respectively above the 2018 World Health Organisation guidelines for drinking water. This study further established that seasonal variation plays a major role in altering the aesthetic surface water quality. The intake of untreated surface water is a vehicle for potential water-borne diseases and allergies, hence alternative sources of drinking water for the populace dependent on the Landzun Stream is recommended to reduce risks and possible dangers of consuming the stream water.
    Matched MeSH terms: Lead
  5. Osman NA, Ujang FA, Roslan AM, Ibrahim MF, Hassan MA
    Sci Rep, 2020 04 20;10(1):6613.
    PMID: 32313095 DOI: 10.1038/s41598-020-62815-0
    Phytoremediation is one of the environmental-friendly and cost-effective systems for the treatment of wastewater, including industrial wastewater such as palm oil mill effluent final discharge (POME FD). However, the effects of the wastewater on the phytoremediator plants, in term of growth performance, lignocellulosic composition, and the presence of nutrients and heavy metals in the plants are not yet well studied. In the present work, we demonstrated that POME FD increased the growth of P. purpureum. The height increment of P. purpureum supplied with POME FD (treatment) was 61.72% as compared to those supplied with rain water (control) which was 14.42%. For lignocellulosic composition, the cellulose percentages were 38.77 ± 0.29% (treatment) and 34.16 ± 1.01% (control), and the difference was significant. These results indicated that POME FD could be a source of plant nutrients, which P. purpureum can absorb for growth. It was also found that the heavy metals (Al, As, Cd, Co, Cr, Ni and Pb) inside the plant were below the standard limit of the World Health Organization (WHO). Since POME FD was shown to have no adverse effects on P. purpureum, further research regarding the potential application of P. purpureum following phytoremediation of POME FD such as biofuel production is warranted to evaluate its potential use to fit into the waste-to-wealth agenda.
    Matched MeSH terms: Lead
  6. See I, Ee GCL, Jong VYM, Teh SS, Acuña CLC, Mah SH
    Nat Prod Res, 2020 Oct 23.
    PMID: 33094642 DOI: 10.1080/14786419.2020.1836629
    Four xanthones, α-mangostin (1), β-mangostin (2), mangostenol (3), mangaxanthone B (4), three benzophenones, mangaphenone (5), benthamianone (6), congestiflorone (7) and one sterol, stigmasterol (8) were isolated from the stem barks of Garcinia mangostana L. and G. benthamiana (Planch. & Triana) Pipoly. Compounds 1, 2, 4 and 5 exhibited significant cytotoxicity through MTT assay towards MCF-7 and MDA-MB-231 cells with the IC50 values range from 4.4 to 12.0 µM. Remarkably, mangaphenone (5) showed non-cytotoxicity against normal Vero cells, revealing its potential as lead compound for anti-breast cancer drug. Structure-activity relationship postulated that the prenyl and hydroxyl groups present in xanthones are important in promoting anti-proliferative effects. Molecular docking simulation study of 1, 2, 4 and 5 with 2OCF and 4PIV implied that the induction of apoptosis for both cancer cells involve ER and FAS signaling pathways. Future study on the lead optimization of 5 is highly recommended.
    Matched MeSH terms: Lead
  7. Normina Ahmad Bustami, Yu Bin Ho, Chung Keat Tan, Ahmad Zaharin Aris, Eugenie Sin Sing Tan
    MyJurnal
    Introduction: Consumption of Chinese Herbal Medicine (CHMs) have escalated globally. They are preferred treat- ment for minor diseases or disorders. In Malaysia, CHMs are common home remedies during pregnancy and postpar- tum. Angelica sinensis (Danggui) is a staple CHMs during postpartum for purpose of nourishing blood and resolving stasis. Concerns are raised over possible heavy metals toxicity. Objective: This study aims to (i) determine Danggui consumption among postpartum mothers, (ii) quantify its heavy metals level, namely Lead (Pb), Cadmium (Cd), Ar- senic (As) and Chromium (Cr) and (iii) determine health risks of Danggui consumption among mothers. Methods: A cross-sectional study involving 112 postpartum mothers was carried out in Kuala Lumpur. Danggui samples were collected from nine districts in Kuala Lumpur (Segambut, Seputeh, Cheras, Kepong, Bandar Tun Razak, Titiwangsa, Setiawangsa, Batu and Lembah Pantai). Heavy metals were extracted using microwave digester and analysed using Inductively coupled plasma mass spectrometry (ICPMS). Hazard Quotient (HQ) was used to determine non-carcino- genic health risks for herbal medicine consumption. Results: Danggui was consumed by 19.6% of mothers (n=22). Among them, incidence of jaundice was 63.6% and need for phototherapy was 40.9%. Heavy metals contamina- tions were found in the decreasing order of Cr > As > Pb > Cd with median (interquartile) of 3996.3 (2805.6) μg/ kg, 128.3 (56.7), 98.6 (99.1) and 37.0 (35.0) respectively. No non-carcinogenic health risks were found for all four metals. Conclusion: Alarming concentrations of heavy metals were quantified in Danggui warranting for further in- vestigation to safeguard health of postpartum mothers.
    Matched MeSH terms: Lead
  8. Balam SK, Soora Harinath J, Krishnammagari SK, Gajjala RR, Polireddy K, Baki VB, et al.
    ACS Omega, 2021 May 04;6(17):11375-11388.
    PMID: 34056293 DOI: 10.1021/acsomega.1c00360
    A series of 3-amino-2-hydroxybenzofused 2-phosphalactones (4a-l) has been synthesized from the Kabachnik-Fields reaction via a facile route from a one-pot three-component reaction of diphenylphosphite with various 2-hydroxybenzaldehyes and heterocyclic amines in a new way of expansion. The in vitro anti-cell proliferation studies by MTT assay have revealed them as potential Panc-1, Miapaca-2, and BxPC-3 pancreatic cell growth inhibitors, and the same is supported by molecular docking, QSAR, and ADMET studies. The MTT assay of their SAHA derivatives against the same cell lines evidenced them as potential HDAC inhibitors and identified 4a, 4b, and 4k substituted with 1,3-thiazol, 1,3,4-thiadiazol, and 5-sulfanyl-1,3,4-thiadiazol moieties on phenyl and diethylamino phenyl rings as potential ones. Additionally, the flow cytometric analyses of 4a, 4b, and 4k against BxPC-3 cells revealed compound 4k as a lead compound that arrests the S phase cell cycle growth at low micromolar concentrations. The ADMET properties have ascertained their inherent pharmacokinetic potentiality, and the wholesome results prompted us to report it as the first study on anti-pancreatic cancer activity of cyclic α-aminophosphonates. Ultimately, this study serves as a good contribution to update the existing knowledge on the anticancer organophosphorus heterocyclic compounds and elevates the scope for generation of new anticancer drugs. Further, the studies like QSAR, drug properties, toxicity risks, and bioactivity scores predicted for them have ascertained the synthesized compounds as newer and potential drug candidates. Hence, this study had augmented the array of α-aminophosphonates by adding a new collection of 3-amino-2-hydroxybenzofused 2-phosphalactones, a class of cyclic α-aminophosphonates, to it, which proved them as potential anti-pancreatic cancer agents.
    Matched MeSH terms: Lead
  9. LAURA DINES NGAU, BOON SIONG WEE, NAZARATUL ASHIFA ABD SALIM
    MyJurnal
    Trace elements play a significant role in giving nutritional benefits to the body because they act as essential cofactors for all physiological processes. However, there are some trace elements which may bring more harm than good when entering the human body. Due to its ability to incorporate trace elements in an amount that is proportional to an individual’s dietary intake and environmental exposure, human fingernails are suitable biomarkers in assessing the health status of an individual as they reflect on the trace element concentration present in the body. This study has analysed fingernail samples of 23 adult females residing in Kuching and Kota Samarahan, Sarawak, Malaysia for four elements, namely Cd, Cu, Pb and Zn. By using flame atomic absorption spectroscopy (FAAS), the mean elemental concentrations found in fingernail samples of research participants were 171.8 ± 33.8 μg/g for Zn, 27.8 ± 14.8 μg/g for Cu and 2.64 ± 0.94 μg/g for Pb. Cd concentrations were not able to be detected as they were below the detection limits. A standard reference material, NIST 1568b Rice Flour was used to verify the methods used in elemental analysis using FAAS. Independent t-test which was used to compare the means of Zn and Cu between vegetarians and non-vegetarians showed no significant differences for both elements. Moreover, correlation analysis showed negative correlations between Cu/Zn pair and Pb/Zn pair, whereas significant positive correlation was obtained for Cu/Pb pair. The overall data from this study showed good agreements with data obtained from studies in other countries. Therefore, the current data in this study represents the latest background elemental concentrations in fingernails of the residents in Kuching and Kota Samarahan, Sarawak.
    Matched MeSH terms: Lead
  10. Thang LY, Breadmore MC, See HH
    J Chromatogr A, 2016 Jul 27.
    PMID: 27485148 DOI: 10.1016/j.chroma.2016.07.067
    An online preconcentration method, namely electrokinetic supercharging (EKS), was evaluated for the determination of tamoxifen and its metabolites in human plasma in nonaqueous capillary electrophoresis with ultraviolet detection (NACE-UV). This method was comprehensively optimized in terms of the leading electrolyte (LE) and terminating electrolyte (TE) injection lengths, as well as electrokinetic sample injection time. The optimized EKS conditions employed were as follows: hydrodynamic injection (HI) of 10mM potassium chloride as LE at 150mbar for 36s (4% of total capillary volume). The sample was injected at 10kV for 300s, followed by HI of 10mM pimozide as TE at 150mbar for 36s (4% of total capillary volume). Separation was performed in 7.5mM deoxycholic acid sodium salt, 15mM acetic acid and 1mM 18-crown-6 in 100% methanol at +25kV with UV detection at 205nm. Under optimized conditions, the sensitivity was enhanced between 160- and 600-fold when compared with our previously developed method based on HI at 150mbar for 12s. The detection limit of the method for tamoxifen and its metabolites were 0.05-0.25ng/mL, with RSDs between 2.1% and 3.5%. Recoveries in spiked human plasma were 95.6%-99.7%. A comparison was also made between the proposed EKS approach and the standard field-amplified sample injection (FASI) technique. EKS proved to be 3-5 times more sensitive than the FASI. The new EKS method was applied to the analysis of tamoxifen and its metabolites in plasma samples from breast cancer patients after liquid-liquid extraction.
    Matched MeSH terms: Lead
  11. Dora Esphylin, Sharifah Norkhadijah Syed Ismail, Sarva Mangala Praveena, Zailina Hashim, Emilia Zainal Abidin
    MyJurnal
    Background: Prolonged exposure of heavy metals in the respirable particulate matter (PM10) from municipal solid waste (MSW) landfills may affect children health. Objective: To investigate the association of reported respiratory symptom with heavy metals in PM10, with heavy metals in fingernails among children residing close to MSW landfills. Methods: Two groups of children age 7 to 12 years old were involved in this cross-sectional study. Those residing within 3 km radius from a landfill were the exposed group and those residing more than 3 km radius as the unexposed group. Questionnaires adapted from American Thoracic Society were applied in the survey. Fingernails were used as biomarker. Ten heavy metals elements in PM and fingernail samples were analysed using inductively coupled plasma mass spectrometry (ICP-MS). Results: The cadmium, chromium, copper, manganese, nickel and lead concentrations in PM around the MSW landfills and residential areas exceeded the Canada and USEPA standard permissible limit. Heavy metals in fingernails (p
    Matched MeSH terms: Lead
  12. Shamsudin R, Abdul Azam F', Abdul Hamid MA, Ismail H
    Materials (Basel), 2017 Oct 17;10(10).
    PMID: 29039743 DOI: 10.3390/ma10101188
    The aim of this study was to prepare β-wollastonite using a green synthesis method (autoclaving technique) without organic solvents and to study its bioactivity. To prepare β-wollastonite, the precursor ratio of CaO:SiO₂ was set at 55:45. This mixture was autoclaved for 8 h and later sintered at 950 °C for 2 h. The chemical composition of the precursors was studied using X-ray fluorescence (XRF), in which rice husk ash consists of 89.5 wt % of SiO₂ in a cristobalite phase and calcined limestone contains 97.2 wt % of CaO. The X-ray diffraction (XRD) patterns after sintering showed that only β-wollastonite was detected as the single phase. To study its bioactivity and degradation properties, β-wollastonite samples were immersed in simulated body fluid (SBF) for various periods of time. Throughout the soaking period, the molar ratio of Ca/P obtained was in the range of 1.19 to 2.24, and the phase detected was amorphous calcium phosphate, which was confirmed by scanning electron microscope with energy dispersive X-ray analysis (SEM/EDX) and XRD. Fourier-transform infrared spectroscopy (FTIR) analysis indicated that the peaks of the calcium and phosphate ions increased when an amorphous calcium phosphate layer was formed on the surface of the β-wollastonite sample. A cell viability and proliferation assay test was performed on the rice husk ash, calcined limestone, and β-wollastonite samples by scanning electron microscope. For heavy metal element evaluation, a metal panel that included As, Cd, Pb, and Hg was selected, and both precursor and β-wollastonite fulfilled the requirement of an American Society for Testing and Materials (ASTM F1538-03) standard specification. Apart from that, a degradation test showed that the loss of mass increased incrementally as a function of soaking period. These results showed that the β-wollastonite materials produced from rice husk ash and limestone possessed good bioactivity, offering potential for biomedical applications.
    Matched MeSH terms: Lead
  13. Ahmad NF, Kamboh MA, Nodeh HR, Halim SNBA, Mohamad S
    Environ Sci Pollut Res Int, 2017 Sep;24(27):21846-21858.
    PMID: 28776296 DOI: 10.1007/s11356-017-9820-9
    The present work describes the successful functionalization/magnetization of bio-polymeric spores of Lycopodium clavatum (sporopollenin) with 1-(2-hydroxyethyl) piperazine. Analytical techniques, i.e., Fourier transform infrared (FT-IR), field emission scanning electron microscope (FESEM), energy-dispersive X-ray spectroscopy (EDS), and vibrating sample magnetometer (VSM), were used to confirm the formation of 1-(2-hydroxyethyl) piperazine-functionalized magnetic sporopollenin (MNPs-Sp-HEP). The proposed adsorbent (MNPs-Sp-HEP) was used for the removal of noxious Pb(II) and As(III) metal ions from aqueous media through a batch-wise method. Different experimental parameters were optimized for the effective removal of selected noxious metal ions. Maximum adsorption capacity (q m ) 13.36 and 69.85 mg g-1 for Pb(II) and As(III), respectively, were obtained. Thermodynamic parameters such as free energy (ΔG°), entropy (ΔS°), and enthalpy (ΔH°) were also studied from the adsorption results and were used to elaborate the mechanism of their confiscation. The obtained results indicated that newly adsorbent can be successfully applied for the decontamination of noxious Pb(II) and As(III) from the aqueous environment.
    Matched MeSH terms: Lead
  14. Hasan N, Sham NFR, Karim MKA, Fuad SBSA, Hasani NAH, Omar E, et al.
    Sci Rep, 2021 Jul 15;11(1):14559.
    PMID: 34267293 DOI: 10.1038/s41598-021-93964-5
    We presented a development of a custom lead shield and mouse strainer for targeted irradiation from the gamma-cell chamber. This study was divided into two parts i.e., to (i) fabricate the shield and strainer from a lead (Pb) and (ii) optimize the irradiation to the mice-bearing tumour model with 2 and 8 Gy absorbed doses. The lead shielding was fabricated into a cuboid shape with a canal on the top and a hole on the vertical side for the beam path. Respective deliveries doses of 28 and 75 Gy from gamma-cell were used to achieve 2 and 8 Gy absorbed doses at the tumour sites.
    Matched MeSH terms: Lead
  15. Ithnin A, Zubir A, Awang N, Mohamad Sulaiman NN
    Pak J Biol Sci, 2019 Jan;22(3):143-147.
    PMID: 30972984 DOI: 10.3923/pjbs.2019.143.147
    BACKGROUND AND OBJECTIVE: Welding fume exposure has led to the respiratory problems among welders including cough, phlegm, chest illnesses, nausea and fatigue. Inadequate ventilation during welding works causes the situation to worsen. Welding fumes can cause a decrease in lung function among welders. Chronic exposure will lead to other health effects especially COPD (Chronic Obstructive Pulmonary Disease). The objective of this study is to determine the exposure of welding fumes (Cd, Fe, Pb and Zn) towards respiratory health including lung function test (FEV1, FVC, FEV1/FVC, PEFR) of workers in Lumut shipyard, Perak.

    MATERIAL AND METHODS: This research study the relationship between exposures of welding fumes towards lung function test among workers in Lumut shipyard, Perak. Lung function test was measured by spirometry among 30 welders and 31 non-welders. The concentration welding fume exposure was measured using OSHA ID-121 method. Sociodemographic data, respiratory symptoms and smoking habit data was analyzed based on the ATS 1987 questionnaire.

    RESULTS: The mean concentration for Pb in welding fumes was 2.752 mg m-3 which is above 0.5 mg m-3 PEL-TWA. The FEV1 and FVC readings showed significant different between welders and non-welders (p = 0.001). Cough and phlegm symptoms showed significant different between welders and non-welders (p = 0.001). Welders had higher prevalence in smoking habit than the non-welders. Chest illnesses symptom showed an association with the smoking habit (p = 0.01).

    CONCLUSION: There is relationship between welding fumes exposure on lung function test of workers in Lumut shipyard. Pb in welding fumes has high concentration and exceeded PEL-TWA level. The FEV1 and FVC in welders are lower than non-welder due to the fumes exposure. Welders showed higher respiratory symptoms than non-welders. Smoking habit is a contributing factor towards respiratory problem.
    Matched MeSH terms: Lead
  16. Gunter NV, Teh SS, Lim YM, Mah SH
    Front Pharmacol, 2020;11:594202.
    PMID: 33424605 DOI: 10.3389/fphar.2020.594202
    The pathogenesis of skin inflammatory diseases such as atopic dermatitis, acne, psoriasis, and skin cancers generally involve the generation of oxidative stress and chronic inflammation. Exposure of the skin to external aggressors such as ultraviolet (UV) radiation and xenobiotics induces the generation of reactive oxygen species (ROS) which subsequently activates immune responses and causes immunological aberrations. Hence, antioxidant and anti-inflammatory agents were considered to be potential compounds to treat skin inflammatory diseases. A prime example of such compounds is xanthone (xanthene-9-one), a class of natural compounds that possess a wide range of biological activities including antioxidant, anti-inflammatory, antimicrobial, cytotoxic, and chemotherapeutic effects. Many studies reported various mechanisms of action by xanthones for the treatment of skin inflammatory diseases. These mechanisms of action commonly involve the modulation of various pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α (TNF-α), as well as anti-inflammatory cytokines such as IL-10. Other mechanisms of action include the regulation of NF-κB and MAPK signaling pathways, besides immune cell recruitment via modulation of chemokines, activation, and infiltration. Moreover, disease-specific activity contributed by xanthones, such as antibacterial action against Propionibacterium acnes and Staphylococcus epidermidis for acne treatment, and numerous cytotoxic mechanisms involving pro-apoptotic and anti-metastatic effects for skin cancer treatment have been extensively elucidated. Furthermore, xanthones have been reported to modulate pathways responsible for mediating oxidative stress and inflammation such as PPAR, nuclear factor erythroid 2-related factor and prostaglandin cascades. These pathways were also implicated in skin inflammatory diseases. Xanthones including the prenylated α-mangostin (2) and γ-mangostin (3), glucosylated mangiferin (4) and the caged xanthone gambogic acid (8) are potential lead compounds to be further developed into pharmaceutical agents for the treatment of skin inflammatory diseases. Future studies on the structure-activity relationships, molecular mechanisms, and applications of xanthones for the treatment of skin inflammatory diseases are thus highly recommended.
    Matched MeSH terms: Lead
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