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      • KCI등재

        Diallyl Polysulfides from Allium sativum as Immunomodulators, Hepatoprotectors, and Antimycobacterial Agents

        Carel Oosthuizen,Miriam Arbach,Debra Meyer,Chris Hamilton,Namrita Lall 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.7

        Mycobacterium tuberculosis remains one of the world's deadliest killers, with an annual death rate of ∼1.5 million. The medicinal effects of garlic have been well documented, and natural products have been shown to have antimycobacterial activity. The current study evaluated the efficacy of six Allium sativum L. polysulfide mixtures as antimycobacterial agents together with their cytotoxic, immunomodulatory, and hepatoprotective activities. The microtitre PrestoBlue assay was used to determine the minimum inhibitory concentrations (MIC). Cytotoxicity was evaluated by using peripheral blood mononuclear cells (PBMC). Excreted cytokine levels were determined by utilizing an enzyme-linked immunosorbent assay (ELISA), by exposing isolated PBMCs to varying concentrations of polysulfide mixtures. Human C3A liver cells were utilized in the hepatoprotective study, to assess the protective effect against the toxicity induced by acetaminophen. Samples with higher amounts of diallyl trisulfide (Sample G4) showed the highest antimycobacterial activity, exhibiting an MIC of 2.5 μg/mL against M. tuberculosis H37Rv. Five samples showed moderate toxicity in PBMC, with G1 showing no toxicity. The selective index of G4 was the highest, with a selectivity index close to one. Two samples, G3 and G6 containing higher amounts of diallyl tetrasulfide and lower amounts of diallyl trisulfide, showed >50% hepatoprotection. This is comparable to a hepatoprotective agent, Silymarin, which showed a hepatoprotective effect of 30% at the tested concentration. Diallyl tetrasulfide showed significant antimycobacterial activity. A combination of higher diallyl tetrasulfide and lower diallyl trisulfide was indicative of hepatoprotective activity.

      • KCI등재

        Phenotypic and Cell Wall Proteomic Characterization of a DDR48 Mutant Candida albicans Strain

        ( Pamela El Khoury ),( Carell Salameh ),( Samer Younes ),( Andy Awad ),( Yana Said ),( Roy A. Khalaf ) 한국미생물 · 생명공학회 2019 Journal of microbiology and biotechnology Vol.29 No.11

        Candida albicans is an opportunistic fungus possessing multiple virulence factors controlling pathogenicity. Cell wall proteins are the most important among these factors, being the first elements contacting the host. Ddr48 is a cell wall protein consisting of 212 amino acids. A DDR48 haploinsufficient mutant strain was previously found necessary for proper oxidative stress response and drug resistance. In this study, we aimed to further elucidate the role of Ddr48 by performing additional phenotypic characterization assays. A combinatory proteomic and bioinformatics approach was also undertaken to determine differentially expressed cell wall proteins. Results showed that the mutant strain exhibited a 10% decrease in adhesion mirrored by a 20% decrease in biofilm formation, and slight sensitivity to menadione, diamide, and SDS. Both strains showed similar hyphae formation, virulence, temperature tolerance, and calcofluor white and Congo red sensitivities. Furthermore, a total of 8 and 10 proteins were identified exclusively in the wild-type strain grown under filamentous and nonfilamentous conditions respectively. Results included proteins responsible for superoxide stress resistance (Sod4 and Sod6), adhesion (Als3, Hyr4, Pmt1, and Utr2), biofilm formation (Hsp90, Ece1, Rim9, Ipp1, and Pra1) and cell wall integrity (Utr2 and Pga4). The lack of detection of these proteins in the mutant strain correlates with the observed phenotypes.

      • KCI등재

        The Effect of Bariatric Surgery on Diabetic Retinopathy: Good, Bad, or Both?

        Dora M. Gorman,Carel W. le Roux,Neil G. Docherty 대한당뇨병학회 2016 Diabetes and Metabolism Journal Vol.40 No.5

        Bariatric surgery, initially intended as a weight-loss procedure, is superior to standard lifestyle intervention and pharmacological therapy for type 2 diabetes in obese individuals. Intensive medical management of hyperglycemia is associated with improved microvascular outcomes. Whether or not the reduction in hyperglycemia observed after bariatric surgery translates to improved microvascular outcomes is yet to be determined. There is substantial heterogeneity in the data relating to the impact of bariatric surgery on diabetic retinopathy (DR), the most common microvascular complication of diabetes. This review aims to collate the recent data on retinal outcomes after bariatric surgery. This comprehensive evaluation revealed that the majority of DR cases remain stable after surgery. However, risk of progression of pre-existing DR and the development of new DR is not eliminated by surgery. Instances of regression of DR are also noted. Potential risk factors for deterioration include severity of DR at the time of surgery and the magnitude of glycated hemoglobin reduction. Concerns also exist over the detrimental effects of postprandial hypoglycemia after surgery. In vivo studies evaluating the chronology of DR development and the impact of bariatric surgery could provide clarity on the situation. For now, however, the effect of bariatric surgery on DR remains inconclusive.

      • KCI우수등재

        Amylin as a Future Obesity Treatment

        Babak Dehestani,Nicholas RS Stratford,Carel W. le Roux 대한비만학회 2021 The Korean journal of obesity Vol.30 No.4

        Obesity is defined as abnormal or excessive fat accumulation that contributes to detrimental health impacts. One-third of the population suffers from obesity, and it is important to consider obesity as a chronic disease requiring chronic treatment. Amylin is co-secreted with insulin from β pancreatic cells upon nutrient delivery to the small intestine as a satiety signal, acts upon sub-cortical homeostatic and hedonic brain regions, slows gastric emptying, and suppresses post-prandial glucagon responses to meals. Therefore, new pharmacological amylin analogues can be used as potential anti-obesity medications in individuals who are overweight or obese. In this narrative review, we analyse the efficacy, potency, and safety of amylin analogues. The synthetic amylin analogue pramlintide is an approved treatment for diabetes mellitus which promotes better glycaemic control and small but significant weight loss. AM833 (cagrilintide), an investigational novel long-acting acylated amylin analogue, acts as a non-selective amylin receptor. This calcitonin G protein-coupled receptor agonist can serve as an attractive novel treatment for obesity, resulting in reduction of food intake and significant weight loss in a dose-dependent manner.

      • Changes in one-carbon metabolism after duodenal-jejunal bypass surgery

        Jung, Jeeyoun,Ha, Tae Kyung,Lee, Jueun,Lho, Yunmee,Nam, Miso,Lee, Doohae,le Roux, Carel W.,Ryu, Do Hyun,Ha, Eunyoung,Hwang, Geum-Sook American Physiological Society 2016 AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND M Vol.310 No.8

        <P>Bariatric surgery alleviates obesity and ameliorates glucose tolerance. Using metabolomic and proteomic profiles, we evaluated metabolic changes in serum and liver tissue after duodenal-jejunal bypass (DJB) surgery in rats fed a normal chow diet. We found that the levels of vitamin B-12 in the sera of DJB rates were decreased. In the liver of DJB rats, betaine-homocysteine S-methyltransferase levels were decreased, whereas serine, cystathionine, cysteine, glutathione, cystathionine beta-synthase, glutathione S-transferase, and aldehyde dehydrogenase levels were increased. These results suggested that DJB surgery enhanced trans-sulfuration and its consecutive reactions such as detoxification and the scavenging activities of reactive oxygen species. In addition, DJB rats showed higher levels of purine metabolites such as ATP, ADP, AMP, and inosine monophosphate. Decreased guanine deaminase, as well as lower levels of hypoxanthine, indicated that DJB surgery limited the purine degradation process. In particular, the AMP/ATP ratio and phosphorylation of AMP-activated protein kinase increased after DJB surgery, which led to enhanced energy production and increased catabolic pathway activity, such as fatty acid oxidation and glucose transport. This study shows that bariatric surgery altered trans-sulfuration and purine metabolism in the liver. Characterization of these mechanisms increases our understanding of the benefits of bariatric surgery.</P>

      • KCI등재후보

        An Evidence-Based Multidisciplinary Practice Guideline to Reduce the Workload due to Lifting for Preventing Work-Related Low Back Pain

        P Paul FM Kuijer,Jos HAM Verbeek,Bart Visse,Leo AM Elders,Nico Van Roden,Marion ER Van den Wittenboer,Marian Lebbink,Alex Burdorf,Carel TJ Hulshof 대한직업환경의학회 2014 대한직업환경의학회지 Vol.26 No.-

        We developed an evidence-based practice guideline to support occupational safety and health (OSH) professionals in assessing the risk due to lifting and in selecting effective preventive measures for low back pain (LBP) in the Netherlands. The guideline was developed at the request of the Dutch government by a project team of experts and OSH professionals in lifting and work-related LBP. The recommendations for risk assessment were based on the quality of instruments to assess the risk on LBP due to lifting. Recommendations for interventions were based on a systematic review of the effects of worker- and work directed interventions to reduce back load due to lifting. The quality of the evidence was rated as strong (A), moderate (B), limited (C) or based on consensus (D). Finally, eight experts and twenty-four OSH professionals commented on and evaluated the content and the feasibility of the preliminary guideline. For risk assessment we recommend loads heavier than 25 kg always to be considered a risk for LBP while loads less than 3 kg do not pose a risk. For loads between 3?25 kg, risk assessment shall be performed using the Manual handling Assessment Charts (MAC)-Tool or National Institute for Occupational Safety and Health (NIOSH) lifting equation. Effective work oriented interventions are patient lifting devices (Level A) and lifting devices for goods (Level C), optimizing working height (Level A) and reducing load mass (Level C). Ineffective work oriented preventive measures are regulations to ban lifting without proper alternatives (Level D). We do not recommend worker-oriented interventions but consider personal lift assist devices as promising (Level C). Ineffective worker-oriented preventive measures are training in lifting technique (Level A), use of back-belts (Level A) and pre-employment medical examinations (Level A). This multidisciplinary evidence-based practice guideline gives clear criteria whether an employee is at risk for LBP while lifting and provides an easy-reference for (in)effective risk reduction measures based on scientific evidence, experience, and consensus among OSH experts and practitioners.

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