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  1. Sachithanandan A, Fahmi PA, Faisal I, Badmanaban B, Abdul Muis J, Mohd Arif MN
    Med J Malaysia, 2013 Jun;68(3):227-30.
    PMID: 23749011 MyJurnal
    Emergency lung resection for chest trauma is a rare event with a reported incidence of 0.08-1.3% but is associated with a high morbidity and mortality especially if a pneumonectomy is required, if due to blunt chest trauma or when concomitant injuries are present. We report three cases of young adult males with penetrating chest injuries that required emergency thoracotomy (ET) and anatomical lung resection to achieve definitive control of life threatening pulmonary haemorrhage. All patients survived to hospital discharge and remained well on follow-up. Indications for an ET and what constitutes the optimal operative management of such patients is discussed.
  2. Lee CC, Harun F, Jalaludin MY, Heh CH, Othman R, Mat Junit S
    Int J Endocrinol, 2013;2013:987186.
    PMID: 23737781 DOI: 10.1155/2013/987186
    Congenital hypothyroidism (CH) with multinodular goiter (MNG) is uncommonly seen in children. However, CH associated with goiter is often caused by defective Thyroid peroxidase (TPO) gene. In this study, we screened for mutation(s) in the TPO gene in two siblings with CH and MNG and their healthy family members. The two sisters, born to consanguineous parents, were diagnosed with CH during infancy and received treatment since then. They developed MNG during childhood despite adequate L-thyroxine replacement and negative thyroid antibody screening. PCR-amplification of all exons using flanking primers followed by DNA sequencing revealed that the two sisters were homozygous for a novel c.1502T>G mutation. The mutation is predicted to substitute valine for glycine at a highly conserved amino acid residue 501 (p.Val501Gly). Other healthy family members were either heterozygotes or mutation-free. The mutation was not detected in 50 healthy unrelated individuals. In silico analyses using PolyPhen-2 and SIFT predicted that the p.Val501Gly mutation is functionally "damaging." Tertiary modeling showed structural alterations in the active site of the mutant TPO. In conclusion, a novel mutation, p.Val501Gly, in the TPO gene was detected expanding the mutation spectrum of TPO associated with CH and MNG.
  3. Taha M, Ismail NH, Jaafar FM, Aziz AN, Yousuf S
    PMID: 23634042 DOI: 10.1107/S1600536813005692
    In the title compound, C16H16N2O3·H2O, the dihedral angle between the benzene rings is 30.27 (7)°. In the crystal, the components are linked by N-H⋯O, O-H⋯O and C-H⋯O inter-actions into a three-dimensional network.
  4. Ullah A, Ashraf M, Javeed A, Anjum AA, Attiq A, Ali S
    Environ Toxicol Pharmacol, 2016 Jul;45:227-34.
    PMID: 27327526 DOI: 10.1016/j.etap.2016.05.017
    Pathophysiological changes in diabetes like hyperglycemia, oxidative stress, insulin resistance and compensatory hyperinsulinemia predispose cells to malignant transformation and damage DNA repair mechanism. This study was designed to explore the potential synergistic toxic effects of anti-diabetic drug (Metformin), and an analgesic drug (Celecoxib) at cellular level. MTT assay run on Vero cell line revealed that the combinations of Metformin and Celecoxib augment the anti-proliferative effects, whereas Single cell gel electrophoresis spotlighted that Metformin produce non-significant DNA damage with the threshold concentration of 400μg/ml in peripheral blood mononuclear cells (lymphocytes and monocytes), while Celecoxib produced significant (P<0.05) DNA damage (class III comets) above the concentration of 75μg/ml, however the DNA damage or DNA tail protrusions by combinations of both drugs were less than what was observed with Celecoxib alone. Metformin or Celecoxib did not appear mutagenic against any mutant strains (TA 100 and TA 98) but their combination exhibited slight mutagenicity at much higher concentration. The results obtained at concentrations higher than the therapeutic level of drugs and reflect that Metformin in combination with Celecoxib synergistically inhibits the cell proliferation in a concentration dependent pattern. Since, this increase in cytotoxicity did not confer an increase in DNA damage; this combination could be adopted to inhibit the growth of malignant cell without producing any genotoxic or mutagenic effects at cellular level.
  5. Teh TL, Rahman NN, Shahadat M, Wong YS, Syakir MI, Omar AK
    Environ Monit Assess, 2016 Jul;188(7):404.
    PMID: 27295186 DOI: 10.1007/s10661-016-5394-0
    The present study deals with possible contamination of the soil by metal ions which have been affecting the environment. The concentrations of metal ions in 14 borehole samples were studied using the ICP-OES standard method. The degree of contamination was determined on the basis of single element pollution index (SEPI), combined pollution index (CPI), soil enrichment factor (SEF), and geo-accumulation index (Igeo). Geo-accumulation indices and contamination factors indicated moderate to strong contaminations for eight boreholes (BL-1, BL-2, BL-6, BL-8, BL-9, BL-10, BL-12, and BL-13) while the rest were extremely contaminated. Among all the boreholes, BL-3 and BL-11 demonstrated the highest level of Cd(II) and Pb(II) which were found the most polluted sites. The level of metal contamination was also compared with other countries. The development, variation, and limitations regarding the regulations of soil and groundwater contamination can be provided as a helpful guidance for the risk assessment of metal ions in developing countries.
  6. He L, Gong H, Zhang J, Zhong C, Huang Y, Zhang C, et al.
    Saudi J Biol Sci, 2016 Jul;23(4):531-41.
    PMID: 27298588 DOI: 10.1016/j.sjbs.2016.02.021
    The effects of differences in smoke concentration and exposure duration in Sprague Dawley rats to determine variation in type and severity of the testis apoptosis were evaluated. The daily dosages were 10, 20 and 30 non-filter cigarettes for a period of 2, 4, 6, 8 and 12 weeks. Mainstream smoke exposure suppressed body weight gain in all regimens. A dose-related increase in plasma nicotine concentration was observed in smoke-exposed groups for 4, 6, 8 and 12 week regimens. Histopathological examination of the exposed groups showed disturbances in the stages of spermatogenesis, tubules atrophying and these appeared to be dose-related. Cytoplasmic caspase-3 immunostaining was detected both in Sertoli cells and germ cells in smoke-exposure groups. An increase in TUNEL-positive cells of testicular cells was observed after 6 weeks of cigarette exposure. The results indicate that cigarette exposure concentration and duration have interaction effect to induce apoptosis in the rat testes.
  7. Taha M, Sultan S, Nuzar HA, Rahim F, Imran S, Ismail NH, et al.
    Bioorg Med Chem, 2016 08 15;24(16):3696-704.
    PMID: 27312423 DOI: 10.1016/j.bmc.2016.06.008
    Thirty N-arylidenequinoline-3-carbohydrazides (1-30) have been synthesized and evaluated against β-glucuronidase inhibitory potential. Twenty four analogs showed outstanding β-glucuronidase activity having IC50 values ranging between 2.11±0.05 and 46.14±0.95 than standard d-saccharic acid 1,4 lactone (IC50=48.4±1.25μM). Six analogs showed good β-glucuronidase activity having IC50 values ranging between 49.38±0.90 and 80.10±1.80. Structure activity relationship and the interaction of the active compounds and enzyme active site with the help of docking studies were established. Our study identifies novel series of potent β-glucuronidase inhibitors for further investigation.
  8. Gnanaraj C, Shah MD, Haque AT, Makki JS, Iqbal M
    PMID: 27279582 DOI: 10.1615/JEnvironPatholToxicolOncol.2016013802
    Synedrella nodiflora is a medicinal plant that is used by the natives of Sabah, Malaysia to treat rheumatism and several other ailments. This study aims to evaluate the ability of the crude aqueous extract of S. nodiflora leaves to protect against carbon tetrachloride (CCl4)-mediated hepatic injury in rats. S. nodiflora aqueous extract was orally administered to adult Sprague Dawley rats once daily for 14 days (150 and 300 mg/kg body weight [b.w.]) before CCl4 oral treatment (1.0 mL/kg b.w.) on the 13th and 14th days. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), hepatic antioxidant enzymes, and malondialdehyde (MDA) levels were estimated. Immunohistochemistry was performed for oxidative stress markers (4-hydroxynonenal [HNE], 8-hydroxy-deoxyguanosine [8-OHdG]) and proinflammatory markers (tumor necrosis factor-α, interleukin-6, prostaglandin E2). Biochemical, immunohistochemical, histological, and ultrastructural findings were in agreement to support the hepatoprotective effect of S. nodiflora against CCl4-mediated oxidative hepatic damage. Hepatoprotective effects of S. nodiflora might be attributable to the presence of phenolic antioxidants and their free radical scavenging property.
  9. Qin H, Tang G, Yi P, Pan X, Huang H, Chang R, et al.
    Saudi Pharm J, 2016 May;24(3):265-72.
    PMID: 27275113 DOI: 10.1016/j.jsps.2016.04.015
    The present study aimed to establish a genus-specific PCR-based assay to detect helicobacters using 16S rRNA gene as the target template. We designed the hemi-nested primers based on sequences of 16S rRNA gene of 34 types of Helicobacter species. The inclusivity, sensitivity, and specificity of the PCR assay using these primers were examined in three different models, comprising feces simulated samples, BLAB/c mice infection model and clinic patients samples. The detection sensitivity of Helicobacter pylori, Helicobacter hepaticus and Helicobacter bilis strains from feces simulated samples was all 102 CFU/ml. We successfully detected H. hepaticus and H. bilis in the liver, cecum and feces of experimentally infected mice. H. pylori was successfully detected in the feces samples from 3 patients infected with H. pylori while not in the feces samples from 3 healthy human. However, the C97/C05-C97/C98 PCR assay detected H. pylori in the 2 positive samples. Due to the PCR assay's excellent inclusivity, high sensitivity and specificity it may be used to detect the presence of Helicobacters.
  10. Wahab AH, Kadir MR, Harun MN, Kamarul T, Syahrom A
    Med Biol Eng Comput, 2017 Mar;55(3):439-447.
    PMID: 27255451 DOI: 10.1007/s11517-016-1525-6
    The present study was conducted to compare the stability of four commercially available implants by investigating the focal stress distributions and relative micromotion using finite element analysis. Variations in the numbers of pegs between the implant designs were tested. A load of 750 N was applied at three different glenoid positions (SA: superior-anterior; SP: superior-posterior; C: central) to mimic off-center and central loadings during activities of daily living. Focal stress distributions and relative micromotion were measured using Marc Mentat software. The results demonstrated that by increasing the number of pegs from two to five, the total focal stress volumes exceeding 5 MPa, reflecting the stress critical volume (SCV) as the threshold for occurrence of cement microfractures, decreased from 8.41 to 5.21 % in the SA position and from 9.59 to 6.69 % in the SP position. However, in the C position, this change in peg number increased the SCV from 1.37 to 5.86 %. Meanwhile, micromotion appeared to remain within 19-25 µm irrespective of the number of pegs used. In conclusion, four-peg glenoid implants provide the best configuration because they had lower SCV values compared with lesser-peg implants, preserved more bone stock, and reduced PMMA cement usage compared with five-peg implants.
  11. Al Musawi MS, Jaafar MS, Al-Gailani B, Ahmed NM, Suhaimi FM, Bakhsh M
    Lasers Med Sci, 2016 Jun 1.
    PMID: 27250712 DOI: 10.1007/s10103-016-1972-1
    This study is designed to investigate in vitro low-level laser (LLL) effects on rheological parameter, erythrocyte sedimentation rate (ESR), of human blood. The interaction mechanism between LLL radiation and blood is unclear. Therefore, research addresses the effects of LLL irradiation on human blood and this is essential to understanding how laser radiation interacts with biological cells and tissues. The blood samples were collected through venipuncture into EDTA-containing tubes as an anticoagulant. Each sample was divided into two equal aliquots to be used as a non-irradiated sample (control) and an irradiated sample. The aliquot was subjected to doses of 36, 54, 72 and 90 J/cm(2) with wavelengths of 405, 589 and 780 nm, with a radiation source at a fixed power density of 30 mW/cm(2). The ESR and red blood cell count and volume are measured after laser irradiation and compared with the non-irradiated samples. The maximum reduction in ESR is observed with radiation dose 72 J/cm(2) delivered with a 405-nm wavelength laser beam. Moreover, no hemolysis is observed under these irradiation conditions. In a separate protocol, ESR of separated RBCs re-suspended in irradiated plasma (7.6 ± 2.3 mm/h) is found to be significantly lower (by 51 %) than their counterpart re-suspended in non-irradiated plasma (15.0 ± 3.7 mm/h). These results indicate that ESR reduction is mainly due to the effects of LLL on the plasma composition that ultimately affect whole blood ESR.
  12. Batumalaie K, Amin MA, Murugan DD, Sattar MZ, Abdullah NA
    Sci Rep, 2016 06 02;6:27236.
    PMID: 27250532 DOI: 10.1038/srep27236
    Activation of inflammatory pathways via reactive oxygen species (ROS) by free fatty acids (FFA) in obesity gives rise to insulin resistance and endothelial dysfunction. Withaferin A (WA), possesses both antioxidant and anti-inflammatory properties and therefore would be a good strategy to suppress palmitic acid (PA)-induced oxidative stress and inflammation and hence, insulin resistance and dysfunction in the endothelium. Effect of WA on PA-induced insulin resistance in human umbilical vein endothelial cells (HUVECs) was determined by evaluating insulin signaling mechanisms whilst effect of this drug on PA-induced endothelial dysfunction was determined in acetylcholine-mediated relaxation in isolated rat aortic preparations. WA significantly inhibited ROS production and inflammation induced by PA. Furthermore, WA significantly decreased TNF-α and IL-6 production in endothelial cells by specifically suppressing IKKβ/NF-κβ phosphorylation. WA inhibited inflammation-stimulated IRS-1 serine phosphorylation and improved the impaired insulin PI3-K signaling, and restored the decreased nitric oxide (NO) production triggered by PA. WA also decreased endothelin-1 and plasminogen activator inhibitor type-1 levels, and restored the impaired endothelium-mediated vasodilation in isolated aortic preparations. These findings suggest that WA inhibited both ROS production and inflammation to restore impaired insulin resistance in cultured endothelial cells and improve endothelial dysfunction in rat aortic rings.
  13. Abdul Majid H, Ramli L, Ying SP, Su TT, Jalaludin MY, Abdul Mohsein NA
    PLoS One, 2016;11(5):e0155447.
    PMID: 27187889 DOI: 10.1371/journal.pone.0155447
    Optimal nutrition is essential for healthy growth during adolescence. This study aims to investigate the baseline nutritional intake of Malaysian adolescents by gender, body mass index, and places of residence, both urban and rural. A cohort study was conducted consisting of 794 adolescents (aged 13-years) attending 15 public secondary schools from the Central (Kuala Lumpur and Selangor) and Northern (Perak) Regions of Peninsular Malaysia. Qualified dietitians conducted a 7-day historical assessment of habitual food intakes. Facilitated by flipcharts and household measurement tools, detailed information on portion sizes and meal contents were recorded. Nutritionist Pro™ Diet Analysis software was also used to analyze the dietary records.The mean age of the adolescents was 12.86 ± 0.33 y; the mean energy intake was 1659.0 ± 329.6 kcal/d. Males had significantly (P < .001) higher energy intake than females (1774.0 ± 369.8 vs 1595.2 ± 320.6 kcal/d); adolescents in rural schools consumed more energy and cholesterol (P < .001) compared to adolescents in urban schools (1706.1 ± 377.7 kcal/d and 244.1 ± 100.2 mg/d, respectively). Obese adolescents in rural schools consumed more energy and sugar (1987.6 ± 374.0 kcal/d and 48.9 ± 23.0 g/d) (p-value <0.001).The dietary intake of normal weight versus obese adolescents differs by the location of their school. Thus, the implementation of a structured and tailored intervention is recommended to help minimize this nutritional inequality.
  14. Al-Garadi MA, Khan MS, Varathan KD, Mujtaba G, Al-Kabsi AM
    J Biomed Inform, 2016 08;62:1-11.
    PMID: 27224846 DOI: 10.1016/j.jbi.2016.05.005
    BACKGROUND: The popularity and proliferation of online social networks (OSNs) have created massive social interaction among users that generate an extensive amount of data. An OSN offers a unique opportunity for studying and understanding social interaction and communication among far larger populations now more than ever before. Recently, OSNs have received considerable attention as a possible tool to track a pandemic because they can provide an almost real-time surveillance system at a less costly rate than traditional surveillance systems.

    METHODS: A systematic literature search for studies with the primary aim of using OSN to detect and track a pandemic was conducted. We conducted an electronic literature search for eligible English articles published between 2004 and 2015 using PUBMED, IEEExplore, ACM Digital Library, Google Scholar, and Web of Science. First, the articles were screened on the basis of titles and abstracts. Second, the full texts were reviewed. All included studies were subjected to quality assessment.

    RESULT: OSNs have rich information that can be utilized to develop an almost real-time pandemic surveillance system. The outcomes of OSN surveillance systems have demonstrated high correlations with the findings of official surveillance systems. However, the limitation in using OSN to track pandemic is in collecting representative data with sufficient population coverage. This challenge is related to the characteristics of OSN data. The data are dynamic, large-sized, and unstructured, thus requiring advanced algorithms and computational linguistics.

    CONCLUSIONS: OSN data contain significant information that can be used to track a pandemic. Different from traditional surveys and clinical reports, in which the data collection process is time consuming at costly rates, OSN data can be collected almost in real time at a cheaper cost. Additionally, the geographical and temporal information can provide exploratory analysis of spatiotemporal dynamics of infectious disease spread. However, on one hand, an OSN-based surveillance system requires comprehensive adoption, enhanced geographical identification system, and advanced algorithms and computational linguistics to eliminate its limitations and challenges. On the other hand, OSN is probably to never replace traditional surveillance, but it can offer complementary data that can work best when integrated with traditional data.

  15. Santhanam RK, Ahmad S, Abas F, Safinar Ismail I, Rukayadi Y, Tayyab Akhtar M, et al.
    Molecules, 2016 May 24;21(6).
    PMID: 27231889 DOI: 10.3390/molecules21060652
    Zanthoxylum rhetsa is an aromatic tree, known vernacularly as "Indian Prickly Ash". It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in different solvent fractions of Z. rhetsa bark using GC-MS analysis and isolated two tetrahydrofuran lignans (yangambin and kobusin), a berberine alkaloid (columbamine) and a triterpenoid (lupeol) from the bioactive chloroform fraction. The solvent fractions and purified compounds were tested for their cytotoxic potential against human dermal fibroblasts (HDF) and mouse melanoma (B16-F10) cells, using the MTT assay. All the solvent fractions and purified compounds were found to be non-cytotoxic to HDF cells. However, the chloroform fraction and kobusin exhibited cytotoxic effect against B16-F10 melanoma cells. The presence of bioactive lignans and alkaloids were suggested to be responsible for the cytotoxic property of Z. rhetsa bark against B16-F10 cells.
  16. Jaafar SA, Latif MT, Razak IS, Shaharudin MZ, Khan MF, Wahid NBA, et al.
    Mar Pollut Bull, 2016 Aug 15;109(1):480-489.
    PMID: 27230987 DOI: 10.1016/j.marpolbul.2016.05.017
    This study determined the effect of monsoonal changes on the composition of atmospheric surfactants in coastal areas. The composition of anions (SO4(2-), NO3(-), Cl(-), F(-)) and the major elements (Ca, K, Mg, Na) in aerosols were used to determine the possible sources of surfactants. Surfactant compositions were determined using a colorimetric method as methylene blue active substances (MBAS) and disulphine blue active substances (DBAS). The anion and major element compositions of the aerosol samples were determined by ion chromatography (IC) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. The results indicated that the concentrations of surfactant in aerosols were dominated by MBAS (34-326pmolm(-3)). Monsoonal changes were found to significantly affect the concentration of surfactants. Using principal component analysis-multiple linear regressions (PCA-MLR), major possible sources for surfactants in the aerosols were motor vehicle emissions, secondary aerosol and the combustion of biomass along with marine aerosol.
  17. Azali MA, Yean Yean C, Harun A, Aminuddin Baki NN, Ismail N
    J Trop Med, 2016;2016:2060241.
    PMID: 27127522 DOI: 10.1155/2016/2060241
    The presence of pathogenic Leptospira spp. in the environment poses threats to human health. The aim of this study was to detect and characterize Leptospira spp. from environmental samples. A total of 144 samples comprised of 72 soil and 72 water samples were collected from markets and recreational areas in a north-eastern state in Malaysia. Samples were cultured on Ellinghausen and McCullough modified by Johnson and Harris media. Leptospires were positive in 22.9% (n = 33) of the isolates. Based on partial sequences of 16S rRNA, a pathogenic leptospire, Leptospira alstonii (n = 1/33), was identified in 3% of the isolates followed by intermediate leptospire (L. wolffii, n = 1/33, and L. licerasiae, n = 7/33) and nonpathogenic leptospire, L. meyeri (n = 22/33) in 24.2% and 66.7%, respectively. This study demonstrates the presence of a clinically significant pathogenic L. alstonii in the environments which could pose health risks to the occupants and visitors.
  18. Masum AK, Azad MA, Hoque KE, Beh LS, Wanke P, Arslan Ö
    PeerJ, 2016;4:e1896.
    PMID: 27168960 DOI: 10.7717/peerj.1896
    The aim of this study was to identify the facets influencing job satisfaction and intention to quit of nurses employed in Turkey. Using a non-probability sampling technique, 417 nurses from six large private hospitals were surveyed from March 2014 to June 2014. The nurses' demographic data, their job-related satisfaction and turnover intentions were recorded through a self-administered questionnaire. In this study, descriptive and bivariate analyses were used to explore data, and multivariate analysis was performed using logistic regression. Nurses' job satisfaction was found at a moderate level with 61% of the nurses intended to quit. Nevertheless, nurses reported a high satisfaction level with work environment, supervisor support, and co-workers among the selected nine facets of job satisfaction. They also reported a low satisfaction level with contingent reward, fringe benefits, and pay. The impact of demographic characteristics on job satisfaction and intention to quit was also examined. The study revealed a negative relationship between job satisfaction and intention to quit the existing employment. Moreover, satisfaction with supervisor support was the only facet that significantly explained turnover intent when controlling for gender, age, marital status, education, and experience. The implications for nurse management were also described for increasing nurses' job satisfaction and retention. This study is beneficial for hospital management to ensure proper nursing care that would lead to a better quality healthcare service.
  19. Ten Bosch QA, Singh BK, Hassan MR, Chadee DD, Michael E
    PLoS Negl Trop Dis, 2016 05;10(5):e0004680.
    PMID: 27159023 DOI: 10.1371/journal.pntd.0004680
    The epidemiology of dengue fever is characterized by highly seasonal, multi-annual fluctuations, and the irregular circulation of its four serotypes. It is believed that this behaviour arises from the interplay between environmental drivers and serotype interactions. The exact mechanism, however, is uncertain. Constraining mathematical models to patterns characteristic to dengue epidemiology offers a means for detecting such mechanisms. Here, we used a pattern-oriented modelling (POM) strategy to fit and assess a range of dengue models, driven by combinations of temporary cross protective-immunity, cross-enhancement, and seasonal forcing, on their ability to capture the main characteristics of dengue dynamics. We show that all proposed models reproduce the observed dengue patterns across some part of the parameter space. Which model best supports the dengue dynamics is determined by the level of seasonal forcing. Further, when tertiary and quaternary infections are allowed, the inclusion of temporary cross-immunity alone is strongly supported, but the addition of cross-enhancement markedly reduces the parameter range at which dengue dynamics are produced, irrespective of the strength of seasonal forcing. The implication of these structural uncertainties on predicted vulnerability to control is also discussed. With ever expanding spread of dengue, greater understanding of dengue dynamics and control efforts (e.g. a near-future vaccine introduction) has become critically important. This study highlights the capacity of multi-level pattern-matching modelling approaches to offer an analytic tool for deeper insights into dengue epidemiology and control.
  20. Siddique MI, Katas H, Amin MC, Ng SF, Zulfakar MH, Jamil A
    Int J Pharm, 2016 Jun 30;507(1-2):72-82.
    PMID: 27154252 DOI: 10.1016/j.ijpharm.2016.05.005
    The objective of this study was to investigate the in-vivo behavior of topically applied cationic polymeric chitosan nanoparticles (CSNPs) loaded with anti-inflammatory (hydrocortisone, HC) and antimicrobial (hydroxytyrosol, HT) drugs, to elucidate their skin targeting potential for the treatment of atopic dermatitis (AD). Compared to the commercial formulation, the HC-HT loaded CSNPs showed significantly improved drug penetration into the epidermal and dermal layers of albino Wistar rat skin without saturation. Dermal pharmacokinetic of CSNPs with a size of 228.5±7nm and +39±5mV charges revealed that they penetrated 2.46-fold deeper than the commercial formulation did, and had greater affinity at the skin target site without spreading to the surrounding tissues, thereby providing substantial safety benefits. In repeated dermal application toxicity studies, the HC-HT CSNPs showed no evidence of toxicity compared to the commercial formulation, which induced skin atrophy and higher liver enzyme levels. In conclusion, the positively charged HC-HT CSNP formulation exhibited promising local delivery and virtually no treatment-related toxicities, suggesting it may be an efficient and viable alternative for commercially available AD treatments.
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