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Unexpected link between iron and drug resistance of Candida spp.: iron depletion enhances membrane fluidity and drug diffusion, leading to drug-susceptible cells 下载免费PDF全文
Prasad T Chandra A Mukhopadhyay CK Prasad R 《Antimicrobial agents and chemotherapy》2006,50(11):3597-3606
Inthis study, we show that iron depletion in Candida albicans with bathophenanthrolene disulfonic acid and ferrozine as chelators enhanced its sensitivity to several drugs, including the most common antifungal, fluconazole (FLC). Several other species of Candida also displayed increased sensitivity to FLC because of iron restriction. Iron uptake mutations, namely, Deltaftr1 and Deltaftr2, as well as the copper transporter mutation Deltaccc2, which affects high-affinity iron uptake in Candida, produced increased sensitivity to FLC compared to that of the wild type. The effect of iron depletion on drug sensitivity appeared to be independent of the efflux pump proteins Cdr1p and Cdr2p. We found that iron deprivation led to lowering of membrane ergosterol by 15 to 30%. Subsequently, fluorescence polarization measurements also revealed that iron-restricted Candida cells displayed a 29 to 40% increase in membrane fluidity, resulting in enhanced passive diffusion of the drugs. Northern blot assays revealed that the ERG11 gene was considerably down regulated in iron-deprived cells, which might account for the lowered ergosterol content. Our results show a close relationship between cellular iron and drug susceptibilities of C. albicans. Considering that multidrug resistance is a manifestation of multifactorial phenomena, the influence of cellular iron on the drug susceptibilities of Candida suggests iron as yet another novel determinant of multidrug resistance. 相似文献
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Arora T Anastasovska J Gibson G Tuohy K Sharma RK Bell J Frost G 《The British journal of nutrition》2012,108(8):1382-1389
There is an increased interest in investigating the relationship between the gut microbiota and energy homeostasis. Probiotics are health beneficial microbes mainly categorised under the genus Lactobacillus and Bifidobacterium, which when administered in adequate amounts confer health benefits to the host, and have been implicated in various physiological functions. The potential role of probiotics in energy homeostasis is a current and an emerging area of research. In the present study, Lactobacillus acidophilus NCDC 13 was used to evaluate its anti-obesity potential in diet-induced obese (C57BL/6) mice. The probiotic bacterial culture was administered in Indian yogurt preparation called 'dahi', prepared using native starter cultures, and compared with control dahi containing only dahi starter cultures. The dietary intervention was followed for 8 weeks, and whole-body fat composition, and liver and muscle adiposity were measured using MRI. Changes in gut microbiota were assessed by fluorescent in situ hybridisation in faeces and caecal contents. The feeding of the probiotic brought no changes in body-weight gain, food and dahi intake when compared with the control dahi-fed animals. No significant changes in body fat composition, liver and muscle adiposity were also observed. At the end of the dietary intervention, a significant increase (P?0·05) in the number of total Bifidobacterium was observed in both faeces and caecal contents of mice as a result of probiotic dahi administration. Thus, L. acidophilus NCDC 13 supplementation could be beneficial in shifting the gut microbiota balance positively. However, its anti-obesity potential could not be established in the present study and warrants further exploration. 相似文献
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Pigment dispersion syndrome predominantly affects young myopes. It is not uncommon for such patients to seek refractive surgery. It may also be encountered after an uneventful refractive surgery. We report a case of a young myopic male who presented with bilateral pigment dispersion syndrome 9 months after an uneventful photorefractive keratectomy. A meticulous ocular examination is the cornerstone of a successful refractive surgery. Through this report, we highlight the need for gonioscopy to be included as a routine examination in screening for refractive surgery. 相似文献
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Abedin M Omland T Ueland T Khera A Aukrust P Murphy SA Jain T Gruntmanis U McGuire DK de Lemos JA 《The American journal of cardiology》2007,99(4):513-518
Circulating osteoprotegerin (OPG) has been shown to be elevated in patients with vascular disease. The role of OPG as a biomarker for atherosclerosis in a large, unselected population is not well known. Plasma OPG levels were measured in 3,386 subjects in the Dallas Heart Study, a multiethnic, population-based probability sample of adults aged 30 to 65 years. Coronary artery calcium (CAC) was measured by electron beam computed tomography. Aortic plaque was assessed by magnetic resonance imaging. Multivariable logistic regression was used to assess associations among OPG, cardiovascular risk factors, CAC, and aortic plaque. Age, female gender, black race, smoking, personal and family history of coronary artery disease (CAD), diabetes mellitus, hyperlipidemia, CAC, and aortic plaque were significantly associated with higher plasma OPG levels (p <0.01) in univariable analyses. The prevalence of CAC and aortic plaque increased across OPG quartiles (p <0.001 for each). An OPG level in the fourth quartile was independently associated with CAC (RR 1.39, 95% confidence interval 1.01 to 1.93) and aortic plaque (RR 1.42, 95% confidence interval 1.09 to 1.86) after adjustment for age, gender, smoking, diabetes, hyperlipidemia, and family history of premature CAD. In conclusion, plasma OPG is independently associated with CAC and aortic plaque in an unselected population, suggesting it may be a novel biomarker for atherosclerosis in humans. 相似文献
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Kunal Chawla Richa Gupta Harsimran Jit Singh Tulika Gupta Anjali Aggarwal Daisy Sahni 《Surgical and radiologic anatomy : SRA》2014,36(4):393-396
During routine dissection of 82-year-old female cadaver with no known unfavorable medical history, we observed bilateral bifid ureter and variation in arterial supply of left kidney only. Careful examination revealed that there were bifid ureters on both sides enclosed in single facial sheath. It was also observed that both the ureter have different pattern of origin. On the right side, both the ureters were seen to be emerging from the hilum, one below another and joined together at the brim of the lesser pelvis just before crossing the right external iliac artery. Right kidney was supplied by single renal artery lying anterior to both the ureters. On the left side one ureter emerged from the hilum while the second one exited the kidney from a prominent lobule present below the inferior pole. 相似文献
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Tulika Tripathi Prateek Gupta Jitender Sharma Priyank Rai Vinod Kumar Gupta Navneet Singh 《Journal of orthodontics》2018,45(1):4-10
Objective: The present study was aimed to assess levels of serum Bone-specific alkaline phosphatase (BALP) and serum Insulin-like growth factor-1 (IGF-1) and comparing with cervical vertebral maturation index (CVMI) stages.Design: Cross-sectional study.Setting: Maulana Azad Institute of Dental Sciences, New Delhi, India.Participants: 150 subjects (75 males and 75 females) in the age group of 8–20 years.Methods: Subjects were divided into six CVMI stages. Enzyme-linked immunosorbant assay was performed for the estimation of serum BALP and serum IGF-1 levels. Mann–Whitney U test was performed to compare mean ranks of serum BALP and serum IGF-1 with different CVMI stages. Spearman correlation between serum BALP and serum IGF-1 was done across 6 CVMI stages.Results: Peak serum IGF-1 levels were found at CVMI stages 4 and 3 for males and females respectively. Peak levels for serum BALP were found at stage 3 for both genders with significant differences from other stages. A statistically significant correlation was seen between serum IGF-1 and serum BALP from CVMI stages 1 to 3 and 4 to 6 (p?.01).Conclusions: BALP showed promising results and can be employed as a potential biomarker for the estimation of growth status. 相似文献
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Chang AY Ayers C Minhajuddin A Jain T Nurenberg P de Lemos JA Wild RA Auchus RJ 《Clinical endocrinology》2011,74(1):89-96
Objective Polycystic ovarian syndrome (PCOS), the most common endocrinopathy of young women, is characterized by androgen excess and is frequently associated with cardiovascular risk factors. However, it is unclear whether PCOS is a risk factor for atherosclerosis. We sought to determine in a multiethnic population‐based sample whether women with PCOS have greater measures of subclinical atherosclerosis than women without PCOS. Design Cross‐sectional study of a nested cohort from the Dallas Heart Study (2000–2002). Participants Women between the ages of 35 and 49 (n = 827). PCOS was defined by Rotterdam criteria. The normal control group had regular menses, total testosterone <2·78 nmol/l, no signs of hirsutism and no polycystic ovarian morphology by magnetic resonance imaging (MRI). Measurements Subclinical atherosclerosis defined as coronary artery calcium (CAC) by computed tomography and abdominal aortic plaque by MRI. Results The prevalence of PCOS in Dallas County was 19·6% (n = 144), and 8·0% (n = 56) had both oligomenorrhea and hyperandrogenism. Women with PCOS had higher body mass index, blood pressure, insulin and leptin than regularly cycling controls. Despite a greater prevalence of cardiovascular risk factors, women with PCOS did not have a greater prevalence of CAC > 10 Agatston units (PCOS 5%, controls 6·3%, P = 0·74) or abdominal aortic plaque (PCOS 25·8%, controls 34·4%, P = 0·13) than controls. Conclusions In a large, multiethnic, population‐based sample of premenopausal women, PCOS, defined by Rotterdam criteria, was not associated with a higher prevalence of coronary artery calcium or abdominal aortic plaque. 相似文献