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S Saputo, R C Faustoferri, R G Quivey
Vitamin D analogs were identified as compounds that induced lysis of planktonic cultures of Streptococcus mutans in a high-throughput screen of FDA-approved drugs. Previous studies have demonstrated that certain derivatives of vitamin D possess lytic activity against other bacteria, though the mechanism has not yet been established. Through the use of a combinatorial approach, the vitamin D derivative doxercalciferol was shown to act synergistically with bacitracin, a polypeptide-type drug that is known to interfere with cell wall synthesis, suggesting that doxercalciferol may act in a bacitracin-related pathway...
January 2018: Antimicrobial Agents and Chemotherapy
Xuening Wang, William K Beute, Jonathan S Harrison, George P Studzinski
Numerous clinical studies of vitamin D, its derivatives or analogs, have failed to clearly demonstrate sustained benefits when used for the treatment of human malignant diseases. However, given the strong preclinical evidence of anti-neoplastic activity and the epidemiological associations suggesting that vitamin D compounds may have a place in cancer therapy, attempts are continuing to devise new approaches to their therapeutic use. This laboratory has developed a strategy to enhance the effectiveness of the currently standard therapy of Acute Myeloid Leukemia (AML) by the immediate addition of the vitamin D2 analog Doxercalciferol combined with the plant polyphenol-derived Carnosic acid to AML cells previously treated with Cytarabine (AraC)...
July 29, 2017: Journal of Steroid Biochemistry and Molecular Biology
Yang Liu, Dong-Yeop Shin, Somi Oh, Sujong Kim, Youngil Koh, Inho Kim
KML001 (NaAsO2, sodium metaarsenite, KOMINOX), a kind of arsenic compound, that has shown promising efficacy in non-Hodgkin's lymphoma (NHL) both in vitro and in vivo. In our study, the antileukemic effect of KML001 on acute lymphoid leukemia (ALL) and its mechanism of action were investigated. The results showed that KML001 inhibited cell proliferation in two types of ALL cell lines, CCRF-CEM and Molt-4. Exposure of ALL cells to KML001 induced apoptosis in a time-dependent manner. KML001 caused cell cycle arrest at G2/M phase instead of G0/G1 phase shown in other leukemia cells...
June 1, 2017: Oncology Reports
Stephanie L Merrigan, Breandán N Kennedy
BACKGROUND AND PURPOSE: Pathological growth of ocular vasculature networks can underpin visual impairment in neovascular age-related macular degeneration, proliferative diabetic retinopathy and retinopathy of prematurity. Our aim was to uncover novel pharmacological regulators of ocular angiogenesis by phenotype-based screening in zebrafish. EXPERIMENTAL APPROACH: A bioactive chemical library of 465 drugs was screened to identify small molecule inhibitors of ocular hyaloid vasculature (HV) angiogenesis in zebrafish larvae...
August 2017: British Journal of Pharmacology
Xuening Wang, Jonathan S Harrison, George P Studzinski
Vitamin D has so far not fulfilled its early promise as an antineoplastic agent, in spite of compelling in vitro data. With the aim of bringing vitamin D or its derivatives (VDDs) effectively to the clinic, we developed a two-pronged approach. First, by adding the plant-derived Carnosic Acid (CA) to a vitamin D2 derivative Doxercalciferol we increased its differentiation potency without increasing it hypercalcemic properties. Second, we added these two agents together to AML cells already treated with Cytarabine (AraC), the standard drug for the treatment of patients with AML...
October 2017: Journal of Steroid Biochemistry and Molecular Biology
Jonathan S Harrison, Xuening Wang, George P Studzinski
Acute Myeloid Leukemia (AML) has grave prognosis due to aggressive nature of the disease, the toxicity of standard treatment, and overall low cure rates. We recently showed that AML cells in established culture treated with Cytarabine (AraC) and a differentiation agent combination show enhancement of AraC cytotoxicity. Here we elucidate molecular changes which underlie this observation with focus on AML blasts in primary culture. The cells were treated with AraC at concentrations achievable in clinical settings, and followed by the addition of Doxercalciferol, a vitamin D2 derivative (D2), together with Carnosic acid (CA), a plant-derived antioxidant...
June 14, 2016: Oncotarget
Qian Zhang, Ming Li, Tiansong Zhang, Jing Chen
BACKGROUND: Vitamin D receptor activators (VDRAs) can protect against mineral bone disease, but they are reported to elevate serum creatinine (SCr) and may also reduce glomerular filtration rate (GFR). METHODS: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate the effect of VDRAs on kidney function and adverse events. MEDLINE, EMBASE, the Cochrane Controlled Trials Register were searched for RCTs that evaluate vitamin D receptor activators (alfacalcidol, calcitriol, doxercalciferol, falecalcitriol, maxacalcitol and paricalcitol) up to March 2015...
2016: PloS One
Deirdre Hahn, Elisabeth M Hodson, Jonathan C Craig
BACKGROUND: Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates. This is an update of a review first published in 2010. OBJECTIVES: This review aimed to examine the benefits (improved growth rates, reduced risk of bone fractures and deformities, reduction in PTH levels) and harms (hypercalcaemia, blood vessel calcification, deterioration in kidney function) of interventions (including vitamin D preparations and phosphate binders) for the prevention and treatment of metabolic bone disease in children with CKD...
November 12, 2015: Cochrane Database of Systematic Reviews
Mario Cozzolino, Adrian Covic, Blanca Martinez-Placencia, Konstantinos Xynos
BACKGROUND: In patients with chronic kidney disease (CKD), impaired renal function leads to decreased vitamin D levels, which causes an increase in parathyroid hormone (PTH) production and contributes to the development of secondary hyperparathyroidism (SHPT). This may result in adverse clinical effects such as bone disorders, vascular calcification, cardiovascular disease, and increased mortality. Current treatment practices and associated outcomes with active vitamin D treatment in patients with CKD were reviewed with the objective to assess parameters (such as PTH and serum calcium levels) that may be used to define the failure of vitamin D treatment...
2015: American Journal of Nephrology
Renata C Pereira, Harald Jüppner, Barbara Gales, Isidro B Salusky, Katherine Wesseling-Perry
BACKGROUND: Osteocytic protein expression is dysregulated in CKD and is affected by changes in mineral metabolism; however the effects of active vitamin D sterol therapy on osteocyte protein expression in advanced CKD is unknown. METHODS: Eleven pediatric patients with end stage kidney disease underwent bone biopsy, were treated for 8 months with doxercalciferol, and then underwent a second bone biopsy. Bone expression of fibroblast growth factor 23 (FGF23), dentin matrix protein 1 (DMP1), and sclerostin were determined by immunohistochemistry and quantified by Ariol Scanning...
2015: PloS One
Jyoti Duggal, Jonathan S Harrison, George P Studzinski, Xuening Wang
1,25-dihydroxyvitamin D3 (1,25D) has been shown to influence differentiation, cell proliferation and cell death in cultured leukemia cells. However, its clinical use is limited by its hypercalcemic effects. An analog of 1,25D, doxercalciferol (1-D2), has anti-tumor activity, with markedly reduced calcemic effects, which makes it a potential agent for clinical treatment of AML. Previous studies suggested that the combination of 1,25D with other agents, such as plant-derived antioxidants, can have additive or synergistic anti-cancer activities in leukemia cells...
2012: MicroRNA
T Christopher Bond, Steve Wilson, John Moran, Mahesh Krishnan
BACKGROUND: Limited well-controlled research exists examining the impact of different formulations of oral vitamin D on clinical outcomes in dialysis patients, specifically those on peritoneal dialysis. For this retrospective mortality analysis, we compared mortality rates of patients on 3 of the most commonly prescribed vitamin D agents. METHODS: We examined 2 years (7/1/2008 to 6/30/2010) of oral medication records of peritoneal dialysis patients from a large US dialysis organization...
January 2015: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
Amit Sharma, Thomas S Marshall, Samina S Khan, Beverly Johns
BACKGROUND: The IMPACT SHPT [Improved Management of Intact Parathyroid Hormone (iPTH) with Paricalcitol-Centered Therapy Versus Cinacalcet Therapy with Low-Dose Vitamin D in Hemodialysis Patients with Secondary Hyperparathyroidism] study compared the effectiveness of paricalcitol and cinacalcet in the management of secondary hyperparathyroidism in haemodialysis patients but did not report the costs or cost effectiveness of these treatments. AIM: The aim of this study was to compare the cost effectiveness of a paricalcitol-based regimen versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients from a US payer perspective, using a 1-year time horizon...
February 2014: Clinical Drug Investigation
Valentin David, Bing Dai, Aline Martin, Jinsong Huang, Xiaobin Han, L Darryl Quarles
Calcium has recently been shown to regulate fibroblast growth factor 23 (FGF-23), a bone-derived phosphate and vitamin D-regulating hormone. To better understand the regulation of FGF-23 by calcium, phosphorus, 1,25 dihydroxyvitamin D3 [1,25(OH)2D], and PTH, we examined FGF-23 expression under basal conditions and in response to PTH, doxercalciferol, or high-calcium diet treatment in Gcm2(-/-) and Cyp27b1(-/-) mutant mice. Gcm2(-/-) mice exhibited low serum PTH and 1,25(OH)2D concentrations, hypocalcemia, and hyperphosphatemia, whereas Cyp27b1(-/-) mice had high PTH, undetectable 1,25(OH)2D, hypocalcemia, and hypophosphatemia...
December 2013: Endocrinology
Walter G Douthat, Mauro Castellano, Leandro Berenguer, M Alejandra Guzmán, Javier de Arteaga, Carlos R Chiurchiu, Pablo U Massari, Gabriela Garay, Raúl Capra, Jorge L de La Fuente
BACKGROUND: There are few data in Argentina on the prevalence and management of bone and mineral metabolism (BMM) in patients with chronic kidney disease (CKD). OBJECTIVES AND METHODS: A survey was carried out in dialysis units in 2010 to measure the prevalence of and types of treatments for BMM disorders in Argentina. The data obtained was then compared to the published results from other large population studies. We recorded characteristics of dialysis centres and participating patients, the frequency of measurements and individual results for BMM biochemical markers, as well as the type of management used to control hyperphosphataemia and secondary hyperparathyroidism...
2013: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
P C Dheerendra, V Sakhuja, H S Kohli, V Jha
This study was carried out to evaluate the efficacy and safety of doxercalciferol as therapy for secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stage 4 in a prospective clinical trial. A total of 35 CKD-4 patients who had a baseline parathyroid hormone (iPTH) >150 pg/mL and had not received any vitamin D analog in the preceding 8 weeks were followed up at intervals of 6 weeks for 18 weeks on oral therapy with doxercalciferol. The starting dose was 1.5 μg/day, and the dose was increased in steps of 1 μg/day if iPTH did not decrease by at least 30% on the subsequent visit...
July 2013: Indian Journal of Nephrology
Amal Kebede, Corey Ephrussi, Meredith Lamanna, Jorge Scheirer, Richard Alweis, Thomas Wasser
INTRODUCTION: Vitamin D has become an area of intensive scrutiny, both in medical and lay literature. However, there are limited data to suggest proper repletion regimens for those patients who have hypovitaminosis D. Consequently, various methods are used in clinical practice. The aim of this study was to assess the efficacy of various treatment strategies for hypovitaminosis D in an ambulatory internal medicine practice. METHODS: A retrospective chart review between October 2005 and June 2010 of a suburban internal medicine practice was performed via query of the electronic medical record (Centricity, General Electric Healthcare, UK)...
2012: Journal of Community Hospital Internal Medicine Perspectives
Amit Sharma, Markus Ketteler, Thomas S Marshall, Samina S Khan, Glen T Schumock
OBJECTIVE: The objective of this analysis was to compare costs of paricalcitol or cinacalcet plus low dose vitamin D, and of phosphate binders, in patients in the IMPACT SHPT study; and to extrapolate those to estimate expected annual maintenance costs. METHODS: IMPACT SHPT was a 28-week, randomized, open-label trial. Subjects from 12 countries received intravenous (IV) or oral paricalcitol, or oral cinacalcet plus fixed IV doxercalciferol or oral alfacalcidol. The primary end-point was the proportion of subjects who achieved a mean intact parathyroid hormone (iPTH) value of 150-300 pg/mL during weeks 21-28 (evaluation period)...
September 2013: Journal of Medical Economics
Ninus Simonzadeh, Bruce Ronsen, Subhash Upadhyaya, Erik Wilkinson, Kiran Kanesvaran, Vijay Patel, Pravin Bendale
In the current study, injectable formulations containing Doxercalciferol as the active pharmaceutical ingredient are analyzed by using gradient-elution high-performance liquid chromatography with ultraviolet detection. Various related impurities and degradants are quantified by using solid-phase extraction (SPE) for enhanced sensitivity. The assay of possible related impurities and Doxercalciferol analogues present at trace quantities is performed by using Trans-1-α-hydroxy vitamin D2 (Doxercalciferol related degradation product/Impurity B) as standard and 1-β-hydroxy vitamin D2 (Doxercalciferol related degradation product/Impurity C) as internal standards for the SPE study...
July 2014: Journal of Chromatographic Science
Jongha Park, Connie M Rhee, Wei Ling Lau, Kamyar Kalantar-Zadeh
Compared to such native vitamin D agents as cholecalciferol (D3), egocalciferol (D2), and calcifediol (25- hydroxy vitamin D3, which need 1-alpha hydroxylase to be activated, 1-alpha-ergocalciferol, also known as doxercalciferol, is a synthetically manufactured vitamin D analog used for treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). Doxercalciferol exhibits more structural similarities to plant-based vitamin D2, ergocalciferol, than with animal-based vitamin D3, cholecalciferol...
March 2014: Current Vascular Pharmacology
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