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.

scholarly journals Complementary Methodologies To Investigate Human Gut Microbiota in Host Health, Working towards Integrative Systems Biology

2017 ◽  
Vol 200 (3) ◽  
Author(s):  
Celia Méndez-García ◽  
Coral Barbas ◽  
Manuel Ferrer ◽  
David Rojo
Keyword(s):  
Human Subjects ◽  
Human Microbiome ◽  
Fecal Microbiota ◽  
Microbiome Composition ◽  
Disease States ◽  
Microbial Product ◽  
Host Health ◽  
Health And Disease ◽  
The Cost ◽  
Biological State

ABSTRACT In 1680, Antonie van Leeuwenhoek noted compositional differences in his oral and fecal microbiota, pioneering the study of the diversity of the human microbiome. From Leeuwenhoek's time to successful modern attempts at changing the gut microbial landscape to cure disease, there has been an exponential increase in the recognition of our resident microbes as part of ourselves. Thus, the human host and microbiome have evolved in parallel to configure a balanced system in which microbes survive in homeostasis with our innate and acquired immune systems, unless disease occurs. A growing number of studies have demonstrated a correlation between the presence/absence of microbial taxa and some of their functional molecules (i.e., genes, proteins, and metabolites) with health and disease states. Nevertheless, misleading experimental design on human subjects and the cost and lack of standardized animal models pose challenges to answering the question of whether changes in microbiome composition are cause or consequence of a certain biological state. In this review, we evaluate the state of the art of methodologies that enable the study of the gut microbiome, encouraging a change in broadly used analytic strategies by choosing effector molecules (proteins and metabolites) in combination with coding nucleic acids. We further explore microbial and effector microbial product imbalances that relate to disease and health.

scholarly journals Simulation-based optimisation to quantify heterogeneity of specific ventilation and perfusion in the lung by the Inspired Sinewave Test

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. C. Tran ◽  
V. Nguyen ◽  
R. Bruce ◽  
D. C. Crockett ◽  
F. Formenti ◽  
...  
Keyword(s):  
Human Subjects ◽  
Characteristic Curve ◽  
Mechanically Ventilated ◽  
Disease States ◽  
Simulation Based ◽  
Gold Classification ◽  
Health And Disease ◽  
Respiratory Test ◽  
Distribution Type ◽  
Ventilation And Perfusion

AbstractThe degree of specific ventilatory heterogeneity (spatial unevenness of ventilation) of the lung is a useful marker of early structural lung changes which has the potential to detect early-onset disease. The Inspired Sinewave Test (IST) is an established noninvasive ‘gas-distribution’ type of respiratory test capable of measuring the cardiopulmonary parameters. We developed a simulation-based optimisation for the IST, with a simulation of a realistic heterogeneous lung, namely a lognormal distribution of spatial ventilation and perfusion. We tested this method in datasets from 13 anaesthetised pigs (pre and post-lung injury) and 104 human subjects (32 healthy and 72 COPD subjects). The 72 COPD subjects were classified into four COPD phenotypes based on ‘GOLD’ classification. This method allowed IST to identify and quantify heterogeneity of both ventilation and perfusion, permitting diagnostic distinction between health and disease states. In healthy volunteers, we show a linear relationship between the ventilatory heterogeneity versus age ($${R}^{2}=0.42$$ R 2 = 0.42 ). In a mechanically ventilated pig, IST ventilatory heterogeneity in noninjured and injured lungs was significantly different (p < 0.0001). Additionally, measured indices could accurately identify patients with COPD (area under the receiver operating characteristic curve is 0.76, p < 0.0001). The IST also could distinguish different phenotypes of COPD with 73% agreement with spirometry.

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.

OBSERVATIONS ON GROWTH OF FINGERNAILS IN HEALTH AND DISEASE

PEDIATRICS ◽  
1959 ◽  
Vol 24 (2) ◽  
pp. 225-233
Author(s):  
Maarten S. Sibinga
Keyword(s):  
Dietary Restriction ◽  
Human Subjects ◽  
Severe Attack ◽  
Marked Individual ◽  
Photographic Technique ◽  
Rate Of Growth ◽  
Disease States ◽  
Individual Variations ◽  
Health And Disease

Using a modification of the Babcock photographic technique, it has been possible to make measurements of the day to day growth of the fingernail in human subjects. There are marked individual variations in the rate of growth at all ages, but for the same individual and the same nail the rate of growth is relatively constant and can be used to study the effect of various physiologic and pathologic disturbances. Preliminary observations indicate that nail growth is unfavorably affected in certain disease states, notably measles and nephrosis. Malnutrition and certain dietary restriction were not found to affect this parameter appreciably. Growth of the nails was followed for 10 days after death and was found to be measurable, the rate exceeding that noted during a severe attack of measles.

scholarly journals Significantly Elevated Levels of Plasma Nicotinamide, Pyridoxal, and Pyridoxamine Phosphate Levels in Obese Emirati Population: A Cross-Sectional Study

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3932
Author(s):  
Ghada Rashad Ibrahim ◽  
Iltaf Shah ◽  
Salah Gariballa ◽  
Javed Yasin ◽  
James Barker ◽  
...  
Keyword(s):  
Pyridoxal Phosphate ◽  
Plasma Concentrations ◽  
Initial Study ◽  
Cross Sectional Study ◽  
Water Soluble ◽  
Vitamin B3 ◽  
Cross Sectional ◽  
Disease States ◽  
Health And Disease ◽  
Ethnically Isolated

Water-soluble vitamins like B3 (nicotinamide), B6 (pyridoxine), and B9 (folic acid) are of utmost importance in human health and disease, as they are involved in numerous critical metabolic reactions. Not surprisingly, deficiencies of these vitamins have been linked to various disease states. Unfortunately, not much is known about the physiological levels of B6 vitamers and vitamin B3 in an ethnically isolated group (such as an Emirati population), as well as their relationship with obesity. The aim of the present study was to quantify various B6 vitamers, as well as B3, in the plasma of obese and healthy Emirati populations and to examine their correlation with obesity. A sensitive and robust HPLC-MS/MS-based method was developed for the simultaneous quantitation of five physiologically relevant forms of vitamin B6, namely pyridoxal, pyridoxine, pyridoxamine, pyridoxamine phosphate, and pyridoxal phosphate, as well as nicotinamide, in human plasma. This method was used to quantify the concentrations of these vitamers in the plasma of 57 healthy and 57 obese Emirati volunteers. Our analysis showed that the plasma concentrations of nicotinamide, pyridoxal, and pyridoxamine phosphate in the obese Emirati population were significantly higher than those in healthy volunteers (p < 0.0001, p = 0.0006, and p = 0.002, respectively). No significant differences were observed for the plasma concentrations of pyridoxine and pyridoxal phosphate. Furthermore, the concentrations of some of these vitamers in healthy Emirati volunteers were significantly different than those published in the literature for Western populations, such as American and European volunteers. This initial study underscores the need to quantify micronutrients in distinct ethnic groups, as well as people suffering from chronic metabolic disorders.

scholarly journals Absorption and metabolism of bioactive molecules after oral consumption of cooked edible heads ofCynara scolymusL. (cultivar Violetto di Provenza) in human subjects: a pilot study

2007 ◽  
Vol 97 (5) ◽  
pp. 963-969 ◽  
Author(s):  
E. Azzini ◽  
R. Bugianesi ◽  
F. Romano ◽  
D. Di Venere ◽  
S. Miccadei ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Chlorogenic Acid ◽  
Caffeic Acid ◽  
Peak Plasma ◽  
Human Subjects ◽  
Cholesterol Biosynthesis ◽  
Plasma Concentrations ◽  
Antioxidant Properties ◽  
Hydroxycinnamic Acids ◽  
Bioactive Molecules

The current growing interest for natural antioxidants has led to a renewed scientific attention for artichoke, due not only to its nutritional value, but, overall, to its polyphenolic content, showing strong antioxidant properties. The major constituents of artichoke extracts are hydroxycinnamic acids such as chlorogenic acid, dicaffeoylquinic acids caffeic acid and ferulic acid, and flavonoids such as luteolin and apigenin glycosides.Invitrostudies, using cultured rat hepatocytes, have shown its hepatoprotective functions andin vivostudies have shown the inhibition of cholesterol biosynthesis in human subjects. Several studies have shown the effect on animal models of artichoke extracts, while information on human bioavailability and metabolism of hydroxycinnamates derivatives is still lacking. Results showed a plasma maximum concentration of 6·4 (sd 1.8) ng/ml for chlorogenic acid after 1 h and its disappearance within 2 h (P < 0·05). Peak plasma concentrations of 19·5 (sd6·9) ng/ml for total caffeic acid were reached within 1 h, while ferulic acid plasma concentrations showed a biphasic profile with 6·4 (sd1·5) ng/ml and 8·4 (sd4·6) ng/ml within 1 h and after 8 h respectively. We observed a significant increase of dihydrocaffeic acid and dihydroferulic acid total levels after 8 h (P < 0·05). No circulating plasma levels of luteolin and apigenin were present. Our study confirms the bioavailability of metabolites of hydroxycinnamic acids after ingestion of cooked edibleCynara scolymusL. (cultivar Violetto di Provenza).

Comparative Plasma Heparin Levels after Subcutaneous Sodium and Calcium Heparin

1978 ◽  
Vol 40 (02) ◽  
pp. 397-406 ◽  
Author(s):  
Joyce Low ◽  
J C Biggs
Keyword(s):  
Peak Plasma ◽  
Plasma Concentrations ◽  
Factor Xa ◽  
Normal Subjects ◽  
Sodium Salts ◽  
Sodium Heparin ◽  
Significant Difference ◽  
Heparin Plasma ◽  
Calcium Heparin ◽  
Plasma Heparin

SummaryComparative plasma heparin levels were measured in normal subjects injected subcutaneously with 5,000 units of the sodium and calcium salts of heparin. Plasma heparin levels were measured up to 7 hr post-injection by an anti-factor Xa assay (Denson and Bonnar 1973). Preliminary studies indicated that heparin levels were reproducible in subjects who received two injections of the same heparin. Peak plasma concentrations (Cmax) and the time at which peak concentration was reached (Tmax) varied greatly from subject to subject. In one group of subjects (15) two commonly used heparins, a sodium heparin (Evans) and a calcium heparin (Choay) were compared. Peak heparin concentrations were not significantly different. However the Tmax for the sodium heparin (1.5 hr) was significantly earlier than the Tmax for the calcium heparin (3 hr) and this was not due to a difference in the volume of the two heparin injections. No significant difference could be detected in the plasma clearance rate and the molecular weight distribution of the two heparins.In two other groups of subjects, sodium and calcium preparations from two manufacturers were compared. In general, the sodium salts gave rise to significantly higher plasma concentrations, which could be interpreted as a greater bioavailability of sodium salts. These results indicate that the salt of the heparin can influence the plasma concentration achieved after subcutaneous injection.

Bioavailability in Rats of Human Recombinant Tissue Plasminogen Activator After Subcutaneous and Intramuscular Injection

1986 ◽  
Vol 56 (03) ◽  
pp. 299-301 ◽  
Author(s):  
L J Garcia Frade ◽  
S Poole ◽  
S Hanley ◽  
L J Creighton ◽  
A D Curtis ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Inferior Vena ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Vena Cava ◽  
Recombinant Tissue Plasminogen Activator ◽  
Fibrin Plate ◽  
Tissue Plasminogen

SummaryThe bioavailability of human recombinant tissue plasminogen activator (rt-PA) in rats was measured after subcutaneous (s.c.) and intramuscular (i.m.) injection. Rt-PA was absorbed after both i.m. and s.c. injection, giving peak plasma concentrations within 30 min and 1 h, respectively, with detectable concentrations up to 6 h. These peak values of bioavailable t-PA were obtained in a functional fibrin plate assay of euglobulin precipitates and expressed as +88% and +243% (for s.c. and i.m. routes respectively) above basal rat fibrinolytic activity. Prior injection of rt-PA, s.c. or i.m., significantly reduced the weights of thrombi induced in the inferior vena cava after injection.

Hypoxic Pulmonary Vasoconstriction and Chronic Lung Disease

2013 ◽  
Vol 12 (3) ◽  
pp. 135-144 ◽  
Author(s):  
Erik R. Swenson
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Disease ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
World Health ◽  
Disease States ◽  
Pulmonary Vasoconstriction ◽  
Local Ventilation ◽  
Pulmonary Vascular Endothelium ◽  
Health And Disease ◽  
Health Organization

Hypoxic vasoconstriction in the lung is a unique and fundamental characteristic of the pulmonary circulation. It functions in health and disease states to better preserve ventilation-perfusion matching by diverting blood flow to better ventilated regions when local ventilation is compromised. As more areas of lung become hypoxic either with high altitude or global lung disease, then hypoxic pulmonary vasoconstriction (HPV) becomes less effective in ventilation-perfusion matching and can lead to pulmonary hypertension. HPV is intrinsic to the vascular smooth muscle and its mechanisms remain poorly understood. In addition, the pulmonary vascular endothelium, red cells, lung innervation, and numerous circulating vasoactive agents also affect the strength of HPV. This review will discuss the pathophysiology of HPV and address its role in pulmonary hypertension associated with World Health Organization Group 3 diseases. When sustained beyond many hours, HPV may initiate pulmonary vascular remodeling and lead to more fixed and less oxygen-responsive pulmonary hypertension if the hypoxic stimulus is maintained.

In Vitro Immunodetection of Prothymosin Alpha in Normal and Pathological Conditions

2020 ◽  
Vol 27 (29) ◽  
pp. 4840-4854 ◽  
Author(s):  
Chrysoula-Evangelia Karachaliou ◽  
Hubert Kalbacher ◽  
Wolfgang Voelter ◽  
Ourania E. Tsitsilonis ◽  
Evangelia Livaniou
Keyword(s):  
Mammalian Cells ◽  
Therapeutic Potential ◽  
Prothymosin Alpha ◽  
Disease States ◽  
Leading Role ◽  
Tissue Extracts ◽  
Biologic Response ◽  
Health And Disease ◽  
Almost All

Prothymosin alpha (ProT&#945;) is a highly acidic polypeptide, ubiquitously expressed in almost all mammalian cells and tissues and consisting of 109 amino acids in humans. ProT&#945; is known to act both, intracellularly, as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response modifier mediating immune responses similar to molecules termed as “alarmins”. Antibodies and immunochemical techniques for ProT&#945; have played a leading role in the investigation of the biological role of ProT&#945;, several aspects of which still remain unknown and contributed to unraveling the diagnostic and therapeutic potential of the polypeptide. This review deals with the so far reported antibodies along with the related immunodetection methodology for ProT&#945; (immunoassays as well as immunohistochemical, immunocytological, immunoblotting, and immunoprecipitation techniques) and its application to biological samples of interest (tissue extracts and sections, cells, cell lysates and cell culture supernatants, body fluids), in health and disease states. In this context, literature information is critically discussed, and some concluding remarks are presented.

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