scholarly journals The use of HEPES-buffer in the production of gallium-68 radiopharmaceuticals – time to reconsider strict pharmacopoeial limits?

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jannie le Roux ◽  
Janke Kleynhans ◽  
Sietske Rubow
Keyword(s):  
Intravenous Infusion ◽  
Short Communication ◽  
Drug Formulation ◽  
Hepes Buffer ◽  
Beneficial Effects ◽  
Molar Activity ◽  
Ethanesulfonic Acid ◽  
Gallium 68 ◽  
Review Current ◽  
Hydroxyethyl Piperazine

AbstractHEPES (4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid) is a buffer that is used in the radiolabelling of gallium-68 compounds. The beneficial effects of HEPES on molar activity in bioconjugates have been well described. Current strict regulations on the HEPES content in radiopharmaceuticals limit its use when intended for parenteral administration.This short communication summarizes data from the literature on the toxicity of HEPES in dogs after intravenous infusion and the subsequent use in humans. We also highlight the use of HEPES in an FDA labelled intravenous drug formulation. Regulatory institutions may consider this data to review current strict limits.

scholarly journals Clinically Applicable Cyclotron-Produced Gallium-68 Gives High-Yield Radiolabeling of DOTA-Based Tracers

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1118
Author(s):  
Emma Jussing ◽  
Stefan Milton ◽  
Erik Samén ◽  
Mohammad Mahdi Moein ◽  
Lovisa Bylund ◽  
...  
Keyword(s):  
Metal Ion ◽  
Metal Content ◽  
Gamma Spectroscopy ◽  
Radiochemical Yield ◽  
High Yield ◽  
Automated Synthesis ◽  
Molar Activity ◽  
Icp Ms ◽  
Gallium 68 ◽  
Fe Impurities

By using solid targets in medical cyclotrons, it is possible to produce large amounts of 68GaCl3. Purification of Ga3+ from metal ion impurities is a critical step, as these metals compete with Ga3+ in the complexation with different chelators, which negatively affects the radiolabeling yields. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting 68GaCl3could be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. 68GaCl3 was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The 68Ga eluate was analyzed for radionuclidic purity (RNP) by gamma spectroscopy, metal content by ICP-MS, and by titrations with the chelators DOTA, NOTA, and HBED. The 68GaCl3eluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. GMP-compliant syntheses yielded up to 7 GBq/batch [68Ga]Ga-DOTATOC and [68Ga]Ga-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of 68Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis.

scholarly journals An Exploration of the Effects of an Early Postpartum Intravenous Infusion with Carnosic Acid on Physiological Responses of Transition Dairy Cows

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1478
Author(s):  
Tainara Cristina Michelotti ◽  
Erminio Trevisi ◽  
Johan S. Osorio
Keyword(s):  
Oxidative Stress ◽  
Dairy Cows ◽  
Intravenous Infusion ◽  
Transition Period ◽  
Carnosic Acid ◽  
Lactation Performance ◽  
Oxidative Stress Biomarkers ◽  
Blood Concentrations ◽  
Beneficial Effects ◽  
And Oxidative Stress

The objective of the present study was to evaluate the effects of an antioxidant and anti-inflammatory compound found in rosemary plants (Salvia rosmarinus) named carnosic acid during the transition period of dairy cows. From day 1 to 3 after calving, 16 multiparous Holstein cows received a daily intravenous infusion of either 500 mL of saline (NaCl 0.9%; Saline; n = 8) or carnosic acid at a rate of 0.3 mg/kg of BW supplied in 500 mL of saline (CA; n = 8). Blood samples were taken at –7, 2, 5, 7, 14, and 21 d relative to parturition, then analyzed for metabolites related to energy metabolism, muscle mass catabolism, liver function, inflammation, and oxidative stress. CA infusion tended to improve milk performance; however, DMI was unaffected by treatment. At 2 d relative to parturition, CA cows had lower blood concentrations of haptoglobin, paraoxonase, FRAP, and NO2– than saline cows. After treatment infusions, haptoglobin remained lower in CA cows than saline at 5 d relative to parturition. Our results demonstrate that carnosic acid promoted positive responses on inflammation and oxidative stress biomarkers and may promote beneficial effects on lactation performance in peripartal dairy cows.

scholarly journals A Review on the Extraction and Processing of Natural Source-Derived Proteins through Eco-Innovative Approaches

Processes ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1626
Author(s):  
Giselle Franca-Oliveira ◽  
Tiziana Fornari ◽  
Blanca Hernández-Ledesma
Keyword(s):  
Bioactive Peptides ◽  
Physiological Role ◽  
Food Products ◽  
Current Data ◽  
Beneficial Effects ◽  
Advantages And Disadvantages ◽  
High Concentrations ◽  
And Storage ◽  
Hydrolysis Of ◽  
Review Current

In addition to their nutritional and physiological role, proteins are recognized as the major compounds responsible for the rheological properties of food products and their stability during manufacture and storage. Furthermore, proteins have been shown to be source of bioactive peptides able to exert beneficial effects on human health. In recent years, scholarly interest has focused on the incorporation of high-quality proteins into the diet. This fact, together with the new trends of consumers directed to avoid the intake of animal proteins, has boosted the search for novel and sustainable protein sources and the development of suitable, cost-affordable, and environmentally friendly technologies to extract high concentrations of valuable proteins incorporated into food products and supplements. In this review, current data on emergent and promising methodologies applied for the extraction of proteins from natural sources are summarized. Moreover, the advantages and disadvantages of these novel methods, compared with conventional methods, are detailed. Additionally, this work describes the combination of these technologies with the enzymatic hydrolysis of extracted proteins as a powerful strategy for releasing bioactive peptides.

The Effects of Hepes Buffer on Clotting Tests, Assay of Factors V and VIII and on the Hydrolysis of Esters by Thrombin and Thrombokinase

1976 ◽  
Vol 35 (01) ◽  
pp. 202-210 ◽  
Author(s):  
Phyllis S. Roberts ◽  
Haywood N. Hughes ◽  
Patricia B. Fleming
Keyword(s):  
Ionic Strength ◽  
Human Plasma ◽  
Inhibitory Effect ◽  
Clotting Factors ◽  
Bovine Thrombin ◽  
Hepes Buffer ◽  
Human Thrombin ◽  
Ethanesulfonic Acid ◽  
Hydrolysis Of Esters ◽  
Hydrolysis Of

SummaryShorter clotting times were found in the presence of 50 mM Hepes (N-2-hydroxyethylpiper-azine-N1-2-ethanesulfonic acid) buffer than of 50 mM Imidazole buffer in one-stage assays of factors V and VIII, in modified APTT and PT tests and in tests of the clotting of human plasma by purified human thrombin. All tests were performed at ionic strength 0.155 in the presence of either Hepes. NaOH or Imidazole. HC1 buffer, pH 7.4 at 37°. The faster clotting in the presence of Hepes buffer, therefore, is probably due, at least in part, to acceleration by Hepes of thrombin’s enzymatic action on fibrinogen and/or of the polymerization of the fibrin monomers.Hepes may also have effects on other blood clotting reactions. Rates of hydrolysis of TAME or BAME (p-toluenesulfonyl-or benzoyl-L-arginine methyl ester) at pH 7.4, 37° by purified human or bovine thrombin were essentially the same in 200 mM Hepes as in 250 mM Tris. HQ buffer (rates in Hepes. NaOH or Hepes. KOH buffers were compared with those in Tris. HQ plus NaCl for KC1). However, with purified bovine thrombokinase, rates of TAME hydrolysis in Hepes buffer were accelerated and rates of BAME hydrolysis slightly inhibited. Hepes, therefore, reacts with thrombokinase but whether this accelerates (or inhibits) the rate of converting prothrombin to thrombin remains to be determined. In addition, Hepes has an inhibitory effect on clotting since increasing the concentration of Hepes from 50 mM to 200 mM inhibits clotting in the PT, APTT and bovine thrombin-human plasma tests.Hepes buffer is being added to some plasmas and to some reagents used in clotting tests. It is, therefore, important to realize that its concentration must be monitored closely or erroneous results may be obtained in clotting tests and assays of clotting factors.The clotting times were the same in the presence of 50 mM Tris. HC1 as in Imidazole. HC1 buffers in APTT tests at three ionic strengths but they differed slightly in plasma-thrombin tests. Depending upon the ionic strength, 17 mM Barbital Sodium. HC1 buffer inhibited APTT tests but accelerated plasma-thrombin tests. All the buffers tested, therefore, have individual effects on the clotting tests.

Dissociation between positive inotropic and alkalinizing effects of angiotensin II in feline myocardium

1997 ◽  
Vol 272 (3) ◽  
pp. H1131-H1136 ◽  
Author(s):  
A. Mattiazzi ◽  
N. G. Perez ◽  
M. G. Vila-Petroff ◽  
B. Alvarez ◽  
M. C. Camilion de Hurtado ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Simultaneous Measurement ◽  
Myocardial Contractility ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Papillary Muscles ◽  
Ang Ii ◽  
Acetoxymethyl Ester ◽  
Hepes Buffer ◽  
Ethanesulfonic Acid

The present study examines the intracellular pH (pHi) dependence of angiotensin (ANG) II-induced positive inotropic effect in cat papillary muscles contracting isometrically (0.2 Hz, 30 degrees C). Muscles were loaded with the fluorescent dye 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester for simultaneous measurement of pHi and contractility. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer (n = 4), there was a temporal dissociation between the positive inotropic and the alkalinizing effects of ANG II (0.5 microM). The positive inotropic effect of ANG II peaked at 9.7 +/- 0.8 min (240 +/- 57% above control) without significant changes in pHi. The increase in pHi became significant (0.05 +/- 0.01 pH units) only after 16 min of exposure to the drug, when the positive inotropic effect of ANG II was already fading. In HCO3- buffer (n = 7), the ANG II-induced positive inotropic effect occurred without significant pHi changes. In the presence of 5 microM ethyl isopropyl amiloride (EIPA, to specifically inhibit the Na+/H+ exchanger), the alkalinizing effect of ANG II was changed to a significant decrease in pHi, despite which ANG II still increased contractility by 87 +/- 16% (n = 6). The results indicate that in HEPES buffer only a fraction of the ANG II-induced positive inotropic effect can be attributed to a pHi change, whereas in a physiological CO2-HCO3- medium the positive inotropic effect of ANG II is independent of pHi changes. Furthermore, an ANG II-induced increase in myocardial contractility was observed even when ANG II administration elicited a decrease in pHi, as occurred after Na+/H+ exchanger blockade. The results show that in feline myocardium, the increase in contractility evoked by ANG II in a physiological CO2-HCO3- medium is not due to an increase in Ca2+ myofilament sensitivity secondary to an increase in myocardial pHi.

Negative Cardiac Inotropic Effects of Calcium Ion and of N-2-Hydroxyethylpiperazine-N′-2-ethanesulfonic Acid (HEPES) Buffer at Normal and Low Sodium Concentration

1974 ◽  
Vol 52 (5) ◽  
pp. 1025-1029 ◽  
Author(s):  
Peter E. Dresel
Keyword(s):  
Calcium Ions ◽  
Calcium Ion ◽  
Negative Inotropic Effect ◽  
Sodium Concentration ◽  
Contractile Force ◽  
Inotropic Effects ◽  
Hepes Buffer ◽  
Low Sodium ◽  
Ethanesulfonic Acid ◽  
Krebs Buffer

Isolated electrically driven left atria from rabbits were suspended in N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES) buffer and exposed to increasing concentration of calcium ions in the presence of different concentrations of sodium. Maximal contractile force occurred at 10 mM Ca and 145 mM Na. Higher concentrations of Ca had a negative inotropic effect. Lowering the Na concentration decreases the concentration of Ca required to observe the negative inotropy, until at 60–70 mM Na, it occurred at 5 mM Ca. This last result was confirmed in Krebs–Henseleit solution. Contractility at low Na and/or Ca media was less in HEPES than in Krebs buffer.

scholarly journals Buffer Standards for pH Measurement of N-(2-Hydroxyethyl)piperazine-N′-2-ethanesulfonic Acid (HEPES) for I=0.16 mol⋅kg−1 from 5 to 55 °C

2009 ◽  
Vol 38 (4) ◽  
pp. 449-458 ◽  
Author(s):  
Rabindra N. Roy ◽  
Lakshmi N. Roy ◽  
Shahaf Ashkenazi ◽  
Joshua T. Wollen ◽  
Craig D. Dunseth ◽  
...  
Keyword(s):  
Ph Measurement ◽  
Ethanesulfonic Acid ◽  
Hydroxyethyl Piperazine
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