Cholecalciferol and Cancer: Is It a Big D3-eal?
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ABSTRACT:
SUBMITTER: Wickham R
PROVIDER: S-EPMC4093346 | biostudies-literature | 2012 Jul
REPOSITORIES: biostudies-literature
Publications
Cholecalciferol and Cancer: Is It a Big D3-eal?
Journal of the advanced practitioner in oncology 20120701 4
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Project description:Background and objectivesElevated concentrations of fibroblast growth factor 23 (FGF23) are postulated to promote 25-hydroxyvitamin D (25[OH]D) insufficiency in CKD by stimulating 24-hydroxylation of this metabolite, leading to its subsequent degradation; however, prospective human studies testing this relationship are lacking.Design, setting, participants, & measurementsAn open-label prospective study was conducted from October 2010 through July 2012 to compare the effect of 8 weeks of oral cholecalciferol therapy (50,000 IU twice weekly) on the production of 24,25(OH)2D3 in vitamin D-insufficient patients with CKD (n=15) and controls with normal kidney function (n=15). Vitamin D metabolites were comprehensively profiled at baseline and after treatment, along with FGF23 and other mineral metabolism parameters.ResultsVitamin D3 and 25(OH)D3 concentrations increased equivalently in the CKD and control groups following cholecalciferol treatment (median D3 change, 8.6 ng/ml [interquartile range, 3.9-25.6 ng/ml] for controls versus 12.6 ng/ml [6.9-41.2 ng/ml] for CKD [P=0.15]; 25(OH)D3 change, 39.2 ng/ml [30.9-47.2 ng/ml] for controls versus 39.9 ng/ml [31.5-44.1 ng/ml] for CKD [P=0.58]). Likewise, the absolute increase in 1α,25(OH)2D3 was similar between CKD participants and controls (change, 111.2 pg/ml [64.3-141.6 pg/ml] for controls versus 101.1 pg/ml [74.2-123.1 pg/ml] for CKD; P=0.38). Baseline and post-treatment 24,25(OH)2D3 concentrations were lower in the CKD group; moreover, the absolute increase in 24,25(OH)2D3 after therapy was markedly smaller in patients with CKD (change, 2.8 ng/ml [2.3-3.5 ng/ml] for controls versus 1.2 ng/ml [0.6-1.9 ng/ml] for patients with CKD; P<0.001). Furthermore, higher baseline FGF23 concentrations were associated with smaller increments in 24,25(OH)2D3 for individuals with CKD; this association was negated after adjustment for eGFR by multivariate analysis.ConclusionsPatients with CKD exhibit an altered ability to increase serum 24,25(OH)2D3 after cholecalciferol therapy, suggesting decreased 24-hydroxylase activity in CKD. The observed relationship between baseline FGF23 and increments in 24,25(OH)2D3 further refutes the idea that FGF23 directly contributes to 25(OH)D insufficiency in CKD through stimulation of 24-hydroxylase activity.
| S-EPMC4220759 | biostudies-literature
Project description:The introduced Australian brushtail possum is a major vertebrate pest in New Zealand, with impacts on conservation and agriculture being managed largely through poisoning operations. Cholecalciferol (vitamin D3) is registered for use in controlling possums and despite its many advantages it is expensive and relatively inhumane. Combination of a high proportion of aspirin with a low proportion of cholecalciferol was effective in killing high proportions of groups of acclimatised, caged possums: this is attributed to both an unexpectedly high toxicity of the type of cholecalciferol used, and a proposed synergistic mechanism between the two compounds. Death was caused by localised damage to heart ventricles by aspirin, and inhibition of tissue repair by both aspirin and cholecalciferol. The observed toxicosis had lower impact on the welfare of possums than either compound administered alone, particularly aspirin alone. Residue analyses of bait remains in the GI tract suggested a low risk of secondary poisoning by either compound. The combination of cholecalciferol and aspirin has the potential to meet key requirements of cost-effectiveness and humaneness in controlling possum populations, but the effect of the combination in non-target species has yet to be tested.
| S-EPMC3739777 | biostudies-literature
Project description:ObjectiveTo assess whether supplementation with calcium and cholecaliferol (vitamin D3) reduces the risk of fracture in women with one or more risk factors for fracture of the hip.DesignPragmatic open randomised controlled trial.SettingPractice nurse led clinics in primary care.Participants3314 women aged 70 and over with one or more risk factors for hip fracture: any previous fracture, low body weight (< 58 kg), smoker, family history of hip fracture, or fair or poor self reported health.InterventionDaily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls, or leaflet only (control group).Main outcome measuresPrimary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment, falls, and quality of life (measured with the SF-12).Results69% of the women who completed the follow-up questionnaire at 24 months were still taking supplements (55% with inclusion of randomised participants known to be alive). After a median follow-up of 25 months (range 18 to 42 months), clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures (odds ratio for fracture in supplemented group 1.01, 95% confidence interval 0.71 to 1.43). The odds ratio for hip fracture was 0.75 (0.31 to 1.78). The odds of a woman having a fall at six and 12 months was 0.99 and 0.98, respectively. Quality of life did not significantly differ between the groups.ConclusionWe found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture. Registration ISRCTN26118436, controlled trials registry.
| S-EPMC557150 | biostudies-literature
Project description:Cholecalciferol (vitamin D3) toxicity caused by defective pet food formulations is a rare occurrence described in cats. Nevertheless, it poses a health risk, even though the affected pet food is not fed as the sole diet. Excessive vitamin D3 intake might cause hypercalcemia and soft tissue mineralization, which are findings that prompt clinicians to further investigate the feasible etiology. This case series describes the effects of an extremely high vitamin D3 intake in five young cats caused by the consumption of a fish-based complementary kitten pet food (KPF) that was fed to all of the cats as part of their diet (cases 1, 2, and 3) or eaten exclusively (cases 4 and 5). Due to the different amounts of vitamin D3 consumed, diagnostic examinations showed different degrees of severity of hypercalcemia and azotemia as well as different radiographic findings in cases where diagnostic imaging was performed (cases 2, 4, and 5). All of the cats were treated by withdrawing the affected food and providing medical management of the hypercalcemia. All of the cats recovered, except for two persistent azotemic cats, which developed chronic kidney disease. The goal of this case series is, therefore, to describe the occurrence and resolution of an acute vitamin D3 toxicity due to the highest amount of dietary vitamin D3 intake that has ever been described in domestic cats.
| S-EPMC8416511 | biostudies-literature
Project description:Regulation of Dot-Icm effectors translocation by T4SS GGDEF-EAL proteins in Legionella pneumophila
| PRJEB33700 | ENA
Project description:Identification of genes involved in ecological preference in European white oaks
| PRJEB19536 | ENA
Project description:Introduction: Migraine is a common and debilitating pain disorder associated with dysfunction of the central nervous system. Advanced magnetic resonance imaging (MRI) studies have reported relevant pathophysiologic states in migraine. However, its molecular mechanistic processes are still poorly understood in vivo. This study examined migraine patients with a novel machine learning (ML) method based on their central μ-opioid and dopamine D2/D3 profiles, the most critical neurotransmitters in the brain for pain perception and its cognitive-motivational interface. Methods: We employed compressive Big Data Analytics (CBDA) to identify migraineurs and healthy controls (HC) in a large positron emission tomography (PET) dataset. 198 PET volumes were obtained from 38 migraineurs and 23 HC during rest and thermal pain challenge. 61 subjects were scanned with the selective μ-opioid receptor (μOR) radiotracer [11C]Carfentanil, and 22 with the selective dopamine D2/D3 receptor (DOR) radiotracer [11C]Raclopride. PET scans were recast into a 1D array of 510,340 voxels with spatial and intensity filtering of non-displaceable binding potential (BPND), representing the receptor availability level. We then performed data reduction and CBDA to power rank the predictive brain voxels. Results: CBDA classified migraineurs from HC with accuracy, sensitivity, and specificity above 90% for whole-brain and region-of-interest (ROI) analyses. The most predictive ROIs for μOR were the insula (anterior), thalamus (pulvinar, medial-dorsal, and ventral lateral/posterior nuclei), and the putamen. The latter, putamen (anterior), was also the most predictive for migraine regarding DOR D2/D3 BPND levels. Discussion: CBDA of endogenous μ-opioid and D2/D3 dopamine dysfunctions in the brain can accurately identify a migraine patient based on their receptor availability across key sensory, motor, and motivational processing regions. Our ML-based findings in the migraineur's brain neurotransmission partly explain the severe impact of migraine suffering and associated neuropsychiatric comorbidities.
| S-EPMC10294712 | biostudies-literature
Project description: Not available
| S-EPMC8276914 | biostudies-literature
Project description:The second messenger cyclic dimeric GMP (c-di-GMP) is almost ubiquitous among bacteria as are the c-di-GMP turnover proteins, which mediate the transition between motility and sessility. EAL domain proteins have been characterized as c-di-GMP-specific phosphodiesterases. While most EAL domain proteins contain additional, usually N-terminal, domains, there is a distinct family of proteins with stand-alone EAL domains, exemplified by Salmonella enterica serovar Typhimurium proteins STM3611 (YhjH/PdeH), a c-di-GMP-specific phosphodiesterase, and the enzymatically inactive STM1344 (YdiV/CdgR) and STM1697, which regulate bacterial motility through interaction with the flagellar master regulator, FlhDC. We have analyzed the phylogenetic distribution of EAL-only proteins and their potential functions. Genes encoding EAL-only proteins were found in various bacterial phyla, although most of them were seen in proteobacteria, particularly enterobacteria. Based on the conservation of the active site residues, nearly all stand-alone EAL domains encoded by genomes from phyla other than proteobacteria appear to represent functional phosphodiesterases. Within enterobacteria, EAL-only proteins were found to cluster either with YhjH or with one of the subfamilies of YdiV-related proteins. EAL-only proteins from Shigella flexneri, Klebsiella pneumoniae, and Yersinia enterocolitica were tested for their ability to regulate swimming and swarming motility and formation of the red, dry, and rough (rdar) biofilm morphotype. In these tests, YhjH-related proteins S4210, KPN_01159, KPN_03274, and YE4063 displayed properties typical of enzymatically active phosphodiesterases, whereas S1641 and YE1324 behaved like members of the YdiV/STM1697 subfamily, with Yersinia enterocolitica protein YE1324 shown to downregulate motility in its native host. Of two closely related EAL-only proteins, YE2225 is an active phosphodiesterase, while YE1324 appears to interact with FlhD. These results suggest that in FlhDC-harboring beta- and gammaproteobacteria, some EAL-only proteins evolved to become catalytically inactive and regulate motility and biofilm formation by interacting with FlhDC.IMPORTANCE The EAL domain superfamily consists mainly of proteins with cyclic dimeric GMP-specific phosphodiesterase activity, but individual domains have been classified in three classes according to their functions and conserved amino acid signatures. Proteins that consist solely of stand-alone EAL domains cannot rely on other domains to form catalytically active dimers, and most of them fall into one of two distinct classes: catalytically active phosphodiesterases with well-conserved residues of the active site and the dimerization loop, and catalytically inactive YdiV/CdgR-like proteins that regulate bacterial motility by binding to the flagellar master regulator, FlhDC, and are found primarily in enterobacteria. The presence of apparently inactive EAL-only proteins in the bacteria that do not express FlhD suggests the existence of additional EAL interaction partners.
| S-EPMC5573086 | biostudies-literature
Project description:IntroductionHip fractures have a huge impact in reducing the quality of life and increasing mortality. This review aims to assess the impact of daily oral supplementation of vitamin D3 plus calcium on the incidence of hip fracture in people over 65 years.MethodsPRISMA guidelines were followed and RCTs that evaluated the effectiveness of daily oral supplementation of vitamin D3 plus calcium in preventing hip fracture in adults over 65 years were included in the study. The databases such as Cochrane Library, Embase, Medline, PubMed, CINAHL, Web of Science and Scopus were searched from October 2019- January 2020.The Cochrane risk of bias tool was used to check the quality of the included studies. A meta-analysis with fixed effect model using Review Manager (Revman 5.3) was used to analyse the data.ResultsThe meta-analysis of seven RCTs on vitamin D3 plus calcium supplementation and hip fracture (n = 12,620) identified odds ratio (OR) of 0.75; 95% Confidence interval (CI): 0.64, 0.87; p = .0003. Daily oral supplementation of 800 IU of Vitamin D3 plus 1200 mg of calcium was found more effective (n = 5676 participants; OR = 0.69; 95% CI: 0.58, 0.82; p < .0001) than daily oral supplementation of 800 IU of Vitamin D3 plus 1000 mg of calcium (n = 6555,OR = 1.08; 95% CI: 0.74, 1.56; p = .70) in reducing hip fracture. A meta-analysis of the seven RCTs to identify the incidence of non-vertebral fracture gave the OR of 0.80; 95% CI: 0.72, 0.89; p < .0001. A meta-analysis of three RCTs on femoral neck bone mineral density (BMD) (n = 483) gave a mean difference of 1.21; 95% CI: -0.79, 3.20; p = .24.ConclusionDaily oral supplementation 800 IU of vitamin D3 plus 1200 mg of calcium reduces hip fracture and non-vertebral fracture in older people. Administering vitamin D3 and calcium supplements had no effect in increasing the femoral neck BMD.Implications for practiceEven though it is evident from the review that optimal daily intake of vitamin D3 plus calcium supplementation help in the prevention of fracture, it is only one essential element in fracture prevention. Also, people who are on dietary supplements should be compliant with same for better result. Efforts to prevent bone loss and osteoporosis should begin from an early age. It includes maintaining a healthy lifestyle, optimal intake of calcium and vitamin D3, proper nutrition, adequate exposure to sunlight, exercise etc. Proper education on healthy lifestyle, avoiding risk factors like smoking, caffeine, alcohol and awareness of bone health should continue throughout life with emphasis during menopause when increased bone loss is expected.
| S-EPMC10078370 | biostudies-literature