scholarly journals Comparison of availability and plasma clearance rates of β-hydroxy-β-methylbutyrate delivery in the free acid and calcium salt forms

2015 ◽  
Vol 114 (9) ◽  
pp. 1403-1409 ◽  
Author(s):  
John C. Fuller ◽  
Rick L. Sharp ◽  
Hector F. Angus ◽  
Paul Y. Khoo ◽  
John A. Rathmacher
Keyword(s):  
Clearance Rate ◽  
Plasma Clearance ◽  
Free Acid ◽  
Peak Plasma ◽  
Human Subjects ◽  
Pharmacokinetic Parameters ◽  
Treatment Interaction ◽  
Free Acid Form ◽  
And Performance ◽  
Performance Gains

Abstractβ-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, has long been supplemented as a Ca salt (Ca-HMB) to increase strength and performance gains with exercise and to reduce recovery time. Recently, the free acid form of HMB (HMB-FA) has become commercially available in capsule form (gelcap). The current study was conducted to compare the bioavailability of HMB using the two commercially available capsule forms of HMB-FA and Ca-HMB. We also compared the pharmacokinetics of each form when administered mixed in water. Ten human subjects (five male and five female) were studied in a randomised crossover design. There was no significant sex by treatment interaction for any of the pharmacokinetic parameters measured. HMB-FA administered in capsules was more efficient than Ca-HMB capsule at HMB delivery with a 37 % increase in plasma clearance rate (74·8 (sem 4·0) v. 54·5 (sem 3·2) ml/min, P<0·0001) and a 76 % increase in peak plasma HMB concentration (270·2 (sem 17·8) v. 153·9 (sem 17·9) μmol/l, P<0·006), which was reached in one-third the time (P<0·009). When HMB-FA and Ca-HMB were administered in water, the differences still favoured HMB-FA, albeit to a lesser degree. Plasma HMB with HMB-FA administered in water was greater during the early phase of absorption (up to 45 min postadministration, P<0·05); this resulted in increased AUC during the first 60 min after administration, when compared with Ca-HMB mixed in water (P<0·03). In conclusion, HMB-FA in capsule form improves clearance rate and availability of HMB compared with Ca-HMB in capsule form.

Free acid gel form of β-hydroxy-β-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt

2010 ◽  
Vol 105 (3) ◽  
pp. 367-372 ◽  
Author(s):  
John C. Fuller ◽  
Rick L. Sharp ◽  
Hector F. Angus ◽  
Shawn M. Baier ◽  
John A. Rathmacher
Keyword(s):  
Free Acid ◽  
Peak Plasma ◽  
Human Subjects ◽  
Plasma Concentrations ◽  
Nutritional Supplement ◽  
Disease States ◽  
Health And Disease ◽  
Acid Gel ◽  
The Times ◽  
Leucine Metabolite

The leucine metabolite, β-hydroxy-β-methylbutyrate (HMB), is a nutritional supplement that increases lean muscle and strength with exercise and in disease states. HMB is presently available as the Ca salt (CaHMB). The present study was designed to examine whether HMB in free acid gel form will improve HMB availability to tissues. Two studies were conducted and in each study four males and four females were given three treatments in a randomised, cross-over design. Treatments were CaHMB (gelatin capsule, 1 g), equivalent HMB free acid gel swallowed (FASW) and free acid gel held sublingual for 15 s then swallowed (FASL). Plasma HMB was measured for 3 h following treatment in study 1 and 24 h with urine collection in study 2. In both the studies, the times to peak plasma HMB were 128 (sem 11), 38 (sem 4) and 38 (sem 1) min (P < 0·0001) for CaHMB, FASW and FASL, respectively. The peak concentrations were 131 (sem 6), 249 (sem 14) and 239 (sem 14) μmol/l (P < 0·0001) for CaHMB, FASW and FASL, respectively. The areas under the curve were almost double for FASW and FASL (P < 0·0001). Daily urinary HMB excretion was not significantly increased resulting in more HMB retained (P < 0·003) with FASW and FASL. Half-lives were 3·17 (sem 0·22), 2·50 (sem 0·13) and 2·51 (sem 0·14) h for CaHMB, FASW and FASL, respectively (P < 0·004). Free acid gel resulted in quicker and greater plasma concentrations (+185 %) and improved clearance (+25 %) of HMB from plasma. In conclusion, HMB free acid gel could improve HMB availability and efficacy to tissues in health and disease.

Calcium ion imaging in plant cells

1993 ◽  
Vol 51 ◽  
pp. 132-133
Author(s):  
Peter K. Hepler ◽  
Dale A. Callaham
Keyword(s):  
Plant Cell Wall ◽  
Cytoplasmic Membrane ◽  
Fluorescent Dyes ◽  
Free Acid ◽  
Methyl Esters ◽  
Free Calcium ◽  
Local Concentration ◽  
Ion Imaging ◽  
Membrane Compartments ◽  
Free Acid Form

Calcium ions (Ca) participate in many signal transduction processes, and for that reason it is important to determine where these ions are located within the living cell, and when and to what extent they change their local concentration. Of the different Ca-specific indicators, the fluorescent dyes, developed by Grynkiewicz et al. (1), have proved most efficacious, however, their use on plants has met with several problems (2). First, the dyes as acetoxy-methyl esters are often cleaved by extracellular esterases in the plant cell wall, and thus they do not enter the cell. Second, if the dye crosses the plasma membrane it may continue into non-cytoplasmic membrane compartments. Third, even if cleaved by esterases in the cytoplasm, or introduced as the free acid into the cytoplasmic compartment, the dyes often become quickly sequestered into vacuoles and organelles, or extruded from the cell. Finally, the free acid form of the dye readily complexes with proteins reducing its ability to detect free calcium. All these problems lead to an erroneous measurement of calcium (2).

Catabolism of Human Fibrinogen Fragment D in Normal Subjects and Patients with Liver Cirrhosis

1980 ◽  
Vol 44 (03) ◽  
pp. 146-149 ◽  
Author(s):  
Nicole Ardaillou ◽  
Jeannine Yvart ◽  
Philippe Le Bras ◽  
Marie-José Larrieu
Keyword(s):  
Liver Cirrhosis ◽  
Clearance Rate ◽  
Plasma Clearance ◽  
Normal Subjects ◽  
Fractional Catabolic Rate ◽  
Human Fibrinogen ◽  
Plasma Pool ◽  
Catabolic Rate ◽  
Chloramine T

SummaryThe catabolism of human fragment D, (FgD), obtained by plasmin digestion of fibrinogen has been investigated in normal subjects and patients with liver cirrhosis and the results compared with those obtained for fibrinogen (Fg). Fg was labelled with I-125 and Fg D with I-131 using the chloramine T method. The plasma disappearance curves of both labelled proteins fitted a two exponential curve. In controls the plasma clearance rate of Fg D was greater than that of Fg as shown by the marked difference between the half-lives of these two tracers: 8,9 and 83,5 hours for Fg D and Fg respectively. The fractional catabolic rate of Fg D was 3.38 times the plasma pool per day. In nine patients with liver cirrhosis, catabolism of Fg was not modified. In contrast, catabolism of Fg D was significantly reduced with a half life of 13.0 hours and a low fractional catabolic rate. These results suggest the role of the liver in the catabolism of Fg D in man.

Information Theoretic Analysis and Performance Gains of 3-Color Shift Keying

2021 ◽  
pp. 1-1
Author(s):  
Alexandros E. Tzikas ◽  
Panagiotis D. Diamantoulakis ◽  
George K. Karagiannidis
Keyword(s):  
Theoretic Analysis ◽  
Information Theoretic ◽  
Color Shift ◽  
Shift Keying ◽  
And Performance ◽  
Performance Gains

Recovery from memory failure when recalling a memorized performance: The role of musical structure and performance cues

2021 ◽  
pp. 102986492110254
Author(s):  
Roger Chaffin ◽  
Jane Ginsborg ◽  
James Dixon ◽  
Alexander P. Demos
Keyword(s):  
Vocal Music ◽  
Musical Structure ◽  
Public Performance ◽  
Memory Failure ◽  
And Performance ◽  
Written Recall ◽  
Performance Gains ◽  
Over Time

To perform reliably and confidently from memory, musicians must able to recover from mistakes and memory failures. We describe how an experienced singer (the second author) recovered from mistakes and gaps in recall as she periodically recalled the score of a piece of vocal music that she had memorized for public performance, writing out the music six times over a five-year period following the performance. Five years after the performance, the singer was still able to recall two-thirds of the piece. When she made mistakes, she recovered and went on, leaving gaps in her written recall that lengthened over time. We determined where in the piece gaps started ( losses) and ended ( gains), and compared them with the locations of structural beats (starts of sections and phrases) and performance cues ( PCs) that the singer reported using as mental landmarks to keep track of her progress through the piece during the sung, public performance. Gains occurred on structural beats where there was a PC; losses occurred on structural beats without a PC. As the singer’s memory faded over time, she increasingly forgot phrases that did not start with a PC and recovered at the starts of phrases that did. Our study shows how PCs enable musicians to recover from memory failures.

Chronopharmacology of β-Adrenoceptor-Blocking Drugs: Pharmacokinetic and Pharmacodynamic Studies in Rats

1983 ◽  
Vol 2 (6) ◽  
pp. 347-358 ◽  
Author(s):  
B. Lemmer ◽  
K. Bathe ◽  
P. H. Lang ◽  
G. Neumann ◽  
H. Winkler
Keyword(s):  
Treatment Time ◽  
Human Subjects ◽  
Temporal Variations ◽  
Male Rats ◽  
Pharmacokinetic Parameters ◽  
Nonspecific Effects ◽  
Elimination Half ◽  
Receptor Blockers ◽  
Β Receptor ◽  
Kinetics Of

Specific and nonspecific effects and the pharmacokinetic behavior of β-adrenoceptor-blocking drugs of different Iipophilicity (atenolol, bupranolol, carazolol, metoprolol, ox-prenolol, practolol, propranolol, sotalol) were investigated in L-D-synchronized male rats as a function of treatment time. The studies revealed that pharmacodynamic effects on heart rate, cardiac noradrenaline turnover, and motor activity as well as pharmacokinetic parameters of racemic mixtures of β-receptor blockers display temporal variations with more pronounced pharmacological effects and shorter elimination half-lives in the dark span. Studies with the isomers of bupranolol and practolol indicate no stereospecificity in the central depressant effect; the kinetic behavior of, for example, propranolol, however, exhibits stereospecificity. The results demonstrate the importance of circadian rhythms in modifying the effects and kinetics of drugs. These findings may have therapeutic implication in human subjects.

An ATP-sensitive conductance in cultured smooth muscle cells from pregnant rat myometrium

1989 ◽  
Vol 257 (2) ◽  
pp. C297-C305 ◽  
Author(s):  
E. Honore ◽  
C. Martin ◽  
C. Mironneau ◽  
J. Mironneau
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Voltage Clamp ◽  
Free Acid ◽  
Muscle Cells ◽  
Monovalent Cation ◽  
Acid Form ◽  
Pregnant Rat ◽  
Free Acid Form ◽  
Cultured Smooth Muscle Cells

The whole cell voltage-clamp technique was used to study the effects of extracellular ATP in cultured smooth muscle cells isolated from pregnant rat myometrium. An inward current was elicited by ATP (IATP) in cells held at -70 mV under voltage clamp. The amplitude of IATP was reduced by estrogen pretreatment and by the end of pregnancy. IATP not only did not undergo any desensitization but showed facilitation. The current-voltage relationship of IATP was linear and reversed close to 0 mV. Changing the sodium electrochemical gradient by decreasing extracellular or intracellular sodium resulted in a linear relationship between the reversal potential of IATP and Na equilibrium potential that, however, differed from the predicted curve for a purely sodium conductance. The conductance activated by ATP was monovalent cation selective with little discrimination between potassium, cesium, and sodium ions. IATP was depressed by divalent cations, and the rank order of potency was Co greater than Mg greater than Ca greater than Ba, suggesting that the free-acid form of ATP was the effective ligand. Adenosine, AMP, and ADP were ineffective in eliciting IATP, whereas ATP gamma S and alpha,beta-methylene ATP were capable of mimicking the effects of ATP, although they were less potent. These results are consistent with the free-acid form of ATP activating a monovalent cation-selective and estrogen-sensitive conductance in myometrium.

scholarly journals Emulsification by TPGS or Quillaja Extract Increased Absorption and Affected Metabolism of Berberine in Humans

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 381-381
Author(s):  
Yavuz Yagiz ◽  
Gary Wang ◽  
Liwei Gu
Keyword(s):  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Total Content ◽  
Compartment Model ◽  
Analysis Of Covariance ◽  
High Tech ◽  
Pharmacokinetic Parameters ◽  
Funding Sources ◽  
Human Volunteers

Abstract Objectives Berberine is a botanical alkaloid used widely for the prevention of several diseases. However, the absorption rate of berberine is less than 1% in human. The objectives of this study were to determine whether emulsification by TPGS or Quillaja extract affect the absorption and metabolism of orally ingested berberine in human volunteers. Methods Twelve healthy subjects (7 male and 5 females, 21–50-year-old) participated this study. Each subject received 800 mg berberine in a powder form or emulsified with TPGS or Quillaja extract using a randomized crossover design with one-week washout period. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after dose. Plasma was hydrolyzed with glucuronidase and sulfatase before total content of berberine and its metabolites were analyzed on LC/MS/MS. Free forms of metabolites were determined in plasma without hydrolysis. Pharmacokinetic parameters were calculated using a non-compartment model before they were compared by analysis of covariance. Results The area under the curve (AUC) and peak plasma concentration (Cmax) of berberine was 6.6 μM.hr and 0.9 μM in participants received berberine powder. They were increased to 18.3 μM.hr and 4.5 μM by TPGS emulsification and 28 μM.hr and 5.1 μM by Quillaja extract emulsification, respectively. Berberrubine and demethylberberine were major metabolites of berberine. The AUC of free Berberrubine and demethylberberine was increased by 1.9 fold and 1.6 fold by TPGS and 5.9 folds and 2.7 folds by Quillaja extract, respectively, compared to berberine powder. Participants received berberine powder had AUC of 254 μM.hr and Cmax of 33 μM for total berberrubine. TPGS emulsification increased these values to 425 μM.hr and 54 μM, while Quillaja extract increased them to 341 μM.hr and 44 μM, respectively. Significant increases of AUC and Cmax were also observed for total demethylberberine by TPGS or Quillaja extract emulsification. Conclusions Emulsification of berberine with TPGS or Quillaja extract significantly increased the absorption of berberine and its metabolites in human compared to berberine supplement without emulsifiers. Funding Sources Florida High Tech Corridor Council and Designs for Health.

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