Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial

Background: The use of L-carnitine has been proposed in haemodialysis (HD) when deficiency is present to improve anaemia resistant to erythropoietin stimulating agent, intradialytic hypotension or cardiac failure. We tested the effects of L-carnitine supplementation on parameters of chronic kidney disease-mineral bone disorder. Methods: CARNIDIAL was a randomized, double-blinded trial having included 92 incident HD subjects for a 1-year period to receive L-carnitine versus placebo. Determinant factors of C-terminal fibroblast growth factor 23 (cFGF23) and intact FGF23 were studied including Klotho level. The L-carnitine effect on mineral metabolism was analyzed between groups by mixed linear models for repeated measurements. Results: Klotho was below the lower limit of quantification (LLOQ) in 55% of the 163 samples. In multivariate analysis, cFGF23 was positively correlated with calcium and phosphate and was higher in subjects having Klotho > LLOQ. No correlation existed between Klotho and phosphate and phosphate was even higher in subjects having Klotho > LLOQ (p < 0.001). Both forms of FGF23 were not related to iron markers nor to IV iron dose. No L-carnitine effect was detected on parathyroid hormone (PTH) or FGF23 during the study period where PTH slightly decreased over time, whereas FGF23 increased. But calcium and phosphate increased more in the L-carnitine group. Conclusion: L-carnitine supplementation increased calcium and phosphate plasma concentrations with no detected downregulation effect on PTH and FGF23. (Clinical Trial 00322322, May 5, 2006).

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Acute Effects of an Inorganic Phosphorus Additive on Mineral Metabolism and Cardiometabolic Risk Factors in Healthy Subjects

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab635 ◽

2021 ◽

Author(s):

Christin Volk ◽

Benjamin Schmidt ◽

Corinna Brandsch ◽

Tabea Kurze ◽

Ulf Schlegelmilch ◽

...

Keyword(s):

Risk Factors ◽

Healthy Subjects ◽

Kidney Diseases ◽

Mineral Metabolism ◽

Fibroblast Growth Factor 23 ◽

Inorganic Phosphorus ◽

Dihydrogen Phosphate ◽

Double Blind ◽

Dietary Phosphorus ◽

The Impact

Abstract Context Hyperphosphatemia and high levels of fibroblast growth factor 23 (FGF23) are risk factors for cardiovascular events in patients with chronic kidney diseases. However, the impact of an inorganic phosphorus additive in healthy people is largely unknown. Objective We aimed to investigate the acute effect of excessive dietary phosphorus administered as sodium dihydrogen phosphate on the postprandial levels of Pi and FGF23 and the response to food. Methods This study was a double-blind placebo-controlled crossover study with 29 healthy male and female participants from the general community who were administered a single dose of either 700 mg phosphorus (NaH2PO4) or a sodium-adjusted placebo in combination with a test meal. Postprandial plasma levels of Pi and FGF23 were measured. Results Compared with placebo, oral phosphorus increased the plasma Pi level, which remained elevated during the ensuing 8 hours (at 480 minutes: 1.31 vs 1.16 mmol/l; P < 0.001), increased urinary Pi (iAUC0-480 789 vs 95 mmol/mmol; P < 0.001), reduced tubular Pi reabsorption (iAUC0-480 −31.5 vs −6.2; P < 0.001), decreased urinary calcium (iAUC0-240 30.6 vs 53.0 mmol/mmol; P = 0.009), and stimulated the release of parathyroid hormone (iAUC0-480 2212 vs 768 ng/l; P < 0.001). However, the FGF23 levels did not change. Postprandial levels of glucose, insulin, and lipids were not substantially affected by phosphorus vs placebo. Conclusion An oral phosphorus load can induce elevated postprandial levels of circulating Pi for hours in healthy subjects, despite rapid homeostatic counterreactions. FGF23 levels and the postprandial response to food were not affected.

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The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.05440517 ◽

2017 ◽

Vol 13 (1) ◽

pp. 36-44 ◽

Cited By ~ 14

Author(s):

Rakesh Malhotra ◽

Ronit Katz ◽

Andrew Hoofnagle ◽

Andrew Bostom ◽

Dena E. Rifkin ◽

...

Keyword(s):

Extended Release ◽

Mineral Metabolism ◽

Controlled Trial ◽

Fibroblast Growth Factor 23 ◽

Phosphate Transport ◽

Serum Phosphate ◽

Vitamin D Metabolites ◽

Long Term Effects ◽

Double Blind ◽

Low Hdl

Background and objectivesNiacin downregulates intestinal sodium-dependent phosphate transporter 2b expression and reduces intestinal phosphate transport. Short-term studies have suggested that niacin lowers serum phosphate concentrations in patients with CKD and ESRD. However, the long-term effects of niacin on serum phosphate and other mineral markers are unknown.Design, setting, participants, & measurementsThe Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Trial was a randomized, double-blind, placebo-controlled trial testing extended release niacin in persons with prevalent cardiovascular disease. We examined the effect of randomized treatment with niacin (1500 or 2000 mg) or placebo on temporal changes in markers of mineral metabolism in 352 participants with eGFR<60 ml/min per 1.73 m2 over 3 years. Changes in each marker were compared over time between the niacin and placebo arms using linear mixed effects models.ResultsRandomization to niacin led to 0.08 mg/dl lower plasma phosphate concentrations per year of treatment compared with placebo (P<0.01) and 0.25 mg/dl lower mean phosphate 3 years after baseline (3.32 versus 3.57 mg/dl; P=0.03). In contrast, randomization to niacin was not associated with statistically significant changes in plasma intact fibroblast growth factor 23, parathyroid hormone, calcium, or vitamin D metabolites over 3 years.ConclusionsThe use of niacin over 3 years lowered serum phosphorous concentrations but did not affect other markers of mineral metabolism in participants with CKD.

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Effects of blood-feeding on olfactory sensitivity of the malaria mosquito Anopheles gambiae: Application of mixed linear models to account for repeated measurements

Journal of Insect Physiology ◽

10.1016/j.jinsphys.2013.09.001 ◽

2013 ◽

Vol 59 (11) ◽

pp. 1111-1118 ◽

Cited By ~ 14

Author(s):

Yu-Tong Qiu ◽

Gerrit Gort ◽

Roberta Torricelli ◽

Willem Takken ◽

Joop J.A. van Loon

Keyword(s):

Anopheles Gambiae ◽

Linear Models ◽

Blood Feeding ◽

Repeated Measurements ◽

Olfactory Sensitivity ◽

Malaria Mosquito ◽

Mixed Linear Models ◽

Mosquito Anopheles Gambiae

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Caloric Intake in Renal Patients: Repercussions on Mineral Metabolism

Nutrients ◽

10.3390/nu13010018 ◽

2020 ◽

Vol 13 (1) ◽

pp. 18

Author(s):

Angela Vidal ◽

Rafael Ríos ◽

Carmen Pineda ◽

Ignacio López ◽

Ana I. Raya ◽

...

Keyword(s):

Bone Mass ◽

Current Knowledge ◽

Mineral Metabolism ◽

Fibroblast Growth Factor 23 ◽

Plasma Concentrations ◽

Caloric Intake ◽

Calorie Intake ◽

Caloric Content ◽

Major Interest ◽

Renal Patient

The aim of this paper is to review current knowledge about how calorie intake influences mineral metabolism focussing on four aspects of major interest for the renal patient: (a) phosphate (P) handling, (b) fibroblast growth factor 23 (FGF23) and calcitriol synthesis and secretion, (c) metabolic bone disease, and (d) vascular calcification (VC). Caloric intake has been shown to modulate P balance in experimental models: high caloric intake promotes P retention, while caloric restriction decreases plasma P concentrations. Synthesis and secretion of the phosphaturic hormone FGF23 is directly influenced by energy intake; a direct correlation between caloric intake and FGF23 plasma concentrations has been shown in animals and humans. Moreover, in vitro, energy availability has been demonstrated to regulate FGF23 synthesis through mechanisms in which the molecular target of rapamycin (mTOR) signalling pathway is involved. Plasma calcitriol concentrations are inversely proportional to caloric intake due to modulation by FGF23 of the enzymes implicated in vitamin D metabolism. The effect of caloric intake on bone is controversial. High caloric intake has been reported to increase bone mass, but the associated changes in adipokines and cytokines may as well be deleterious for bone. Low caloric intake tends to reduce bone mass but also may provide indirect (through modulation of inflammation and insulin regulation) beneficial effects on bone. Finally, while VC has been shown to be exacerbated by diets with high caloric content, the opposite has not been demonstrated with low calorie intake. In conclusion, although prospective studies in humans are needed, when planning caloric intake for a renal patient, it is important to take into consideration the associated changes in mineral metabolism.

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Evaluation of the Efficacy of Lacer HaliTM Treatment on the Management of Halitosis: A Randomized Double-Blind Clinical Trial

Journal of Clinical Medicine ◽

10.3390/jcm10112256 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2256

Author(s):

Laiqi Xiang ◽

Rosa Rojo ◽

Juan Carlos Prados-Frutos

Keyword(s):

Clinical Trial ◽

Hydrogen Sulfide ◽

Linear Models ◽

Antimicrobial Properties ◽

Placebo Treatment ◽

Positive Control ◽

Control Group ◽

Mixed Linear Models ◽

Double Blind ◽

Double Blinded

Background: Halitosis of oral origin is very common in the general population. Due to their antimicrobial properties, chlorhexidine-based products are widely used in the management of this condition, but these are associated with reversible side effects. In this study we evaluated the efficacy of Lacer HaliTM mouthrinse and toothpaste in subjects with intraoral halitosis after several applications under normal conditions of use. Methods: In this randomized clinical trial with mouth rinse and toothpaste, single-center, double-blinded, parallel participants were assigned to an experimental group (Lacer HaliTM,, n = 20), a positive control group (HalitaTM, n = 20), and a placebo group (n = 20). The active duration of the study was 18 days. The clinical follow-up evaluations were performed at five time points (T0, T1, T2, T3, and T4). The intensity of halitosis was evaluated by organoleptic measurement and the portable gas chromatograph OralChromaTM. The data were analyzed using generalized mixed linear models. Results: Sixty patients completed the study. Lacer HaliTM, in comparison with HalitaTM, did not show statistically significant differences at any time during the study except for the levels of hydrogen sulfide and total volatile sulfur compounds at 15 days, where HalitaTM was better. Compared to the placebo treatment, Lacer HaliTM, was significantly more efficient, in terms of both the organoleptic evaluations at 8 days and the levels of hydrogen sulfide. Conclusions: Lacer HaliTM is an alternative to chlorhexidine-based toothpaste and mouthwashes in the management of halitosis.

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Effect of recombinant bovine somatotropin on pregnancy rates of Nellore cows resynchronized with the use of new DIB and third use, and inseminated at fixed-time

JOURNAL OF ADVANCES IN AGRICULTURE ◽

10.24297/jaa.v4i1.4304 ◽

2015 ◽

Vol 4 (1) ◽

pp. 356-362

Author(s):

Josemara Silva Santos ◽

Tania Cavalcante ◽

Francisca Elda Ferreira Dias ◽

Domenica Palomaris Mariano de Souza ◽

Alencariano J.S. Falcão ◽

...

Keyword(s):

Artificial Insemination ◽

Linear Models ◽

Plasma Concentrations ◽

Fixed Time ◽

Estradiol Benzoate ◽

Pregnancy Rates ◽

Recombinant Bovine Somatotropin ◽

Equine Chorionic Gonadotropin ◽

Rectal Palpation ◽

Intravaginal Device

The objective of the experiment was to evaluate the effects of recombinant bovine somatropin (rbST), and the reuse of the progesterone (P4) releasing devices in resynchronization, on the pregnancy rates of Nellore cows submitted to fixed-time artificial insemination. A group of 123 multiparae Nellore cows, was submitted to a resynchronization protocol: on day 0 a Bovine Intravaginal Device (DIB® ) with 1,0g of P4 was implanted, associated with intramuscular administration of 2,0mg of estradiol benzoate (IM); on day 8 DIB was removed; and 1,0mg of estradiol cypionate, 0,15mg of prostaglandin F2? and 300 UI of equine chorionic gonadotropin were administered; on day 10, fixed-time artificial insemination was conducted (FTAI). The cows were randomized into G1 (n=12) – without rbST / with used Bovine Intravaginal Device, G2 (n=50) – without rbST / with new DIB, G3 (n=11) - with rbST / with used DIB and G4 (n=50) – with rbST/ with new DIB. rbST was introduced on the eighth day of the protocol. Sixty days after TAI, pregnancy diagnoses were conducted, via rectal palpation. Blood samples were taken on day 0, 8 and 10 of the protocol, in order to assess P4 plasma concentrations. Pregnancy rates were statistically evaluated through Generalized Linear Models Theory and their significance was tested with Analysis of Deviance. Pregnancy rates were 58%, 40%, 81% and 48% for G1, G2, G3 and G4, respectively, with significant statistical difference for G3. Plasma concentrations of P4 were not statistically different among groups, or collections. In view of the results obtained, we concluded that the administration of rbST in association with P4 DIB, used for the third time, improves pregnancy rates. Estrus resynchronization and re-insemination positively impacted pregnancy rates.

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Pharmacokinetics and Safety Assessment of Anti-HIV Dapivirine Vaginal Microbicide Rings with Multiple Dosing

10.31234/osf.io/su2kw ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Ex Vivo ◽

Oral Treatment ◽

Plasma Concentrations ◽

Vaginal Ring ◽

Vaginal Fluid ◽

Cervical Tissue ◽

Double Blind ◽

Group A ◽

Group B ◽

Anti Hiv

Objectives: Self-administered vaginal rings are a promising method for delivery of topical anti-HIV microbicidesand might offer an adherence advantage over daily or coitally-dependent dosage forms such as gels. This trialassessed the safety and pharmacokinetic aspects of the Dapivirine Vaginal Ring-004 when worn as multiple rings oversequential periods of ring use by healthy, sexually-active, HIV-negative women.Methods: This double-blind trial was conducted among 48 women (18-40 years). Participants were randomlyassigned to two groups (A or B) and received (3:1) either the dapivirine or a placebo vaginal ring. Group A used tworings over a 56-day period and Group B used three rings over a 57-day period. Safety evaluations were conductedthroughout the trial. Dapivirine concentrations were measured in plasma, vaginal fluid and cervical tissue samplescollected during and after the 56 days (Group A) or 57 days (Group B) of vaginal ring use.Results: Ring-004 was safe and well tolerated in all participants. The pharmacokinetic profile demonstrated arapid increase in plasma and vaginal fluid concentrations and achieved concentrations in vaginal fluids and cervicaltissue well above the in vitro IC99 in cervical tissue (3.3 ng/mL) that were sustained for a 28 to 35-day ring use period(approximately 3000 times higher in vaginal fluids and 14 -1000 times higher in cervical tissue). Drug levels wereassociated with significant inhibitory activity of genital secretions against HIV ex vivo, a biomarker of pharmacodynamics.Individual plasma dapivirine concentrations did not exceed 553 pg/mL and were well below plasma concentrations atthe maximum tolerated dose for oral treatment (mean Cmax 2286 ng/mL).Conclusions: The consecutive use of several rings over a period of up to 57 days was safe and well tolerated, andPK data indicate that a single Ring-004 is likely to be protective for at least 35 days.

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