Agricultural and Biological Sciences › Animal Science and Zoology

Pharmacological Effects and Assays

Works Count: 32142

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Description

This cluster of papers focuses on the effects, detection, and adverse consequences of beta-adrenergic agonists, such as clenbuterol, ractopamine, and zilpaterol, in livestock. The research covers topics such as their impact on meat quality, performance, and the development of detection methods including immunoassays and electrochemical sensors.

Keywords

Clenbuterol; Ractopamine; Zilpaterol; Meat Quality; Livestock; Performance; Detection; Immunoassay; Electrochemical Sensor; Adverse Effects

Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action.

1998-01-01

H. J. Mersmann

The beta-adrenergic receptors (beta-AR) are present on the surface of almost every type of mammalian cell. These receptors are stimulated physiologically by the neurotransmitter, norepinephrine and the adrenal medullary hormone, … The beta-adrenergic receptors (beta-AR) are present on the surface of almost every type of mammalian cell. These receptors are stimulated physiologically by the neurotransmitter, norepinephrine and the adrenal medullary hormone, epinephrine. There are three subtypes of beta-AR, namely, beta1-AR, beta2-AR, and beta3-AR; the pharmacological and physiological responses of an individual cell result from the particular mixture of the three beta-AR subtypes present on that cell. Species-specific structure (amino acid sequence) also causes modification of the function of a given beta-AR subtype. Knowledge of the beta-AR subtypes present in various cell types, coupled with knowledge of receptor structure (sequence), will allow an understanding of the complexity of physiological function regulated by beta-AR. Oral administration of some beta-AR agonists increases muscle and decreases fat accretion in cattle, pigs, poultry, and sheep. The large number of physiological functions controlled by beta-AR suggests that the mechanism(s) for the observed changes in carcass composition may be extremely complex. Any proposed mechanism must begin with the possibility of direct effects of the agonist on skeletal muscle and adipocyte beta-AR. However, many other mechanisms, such as modification of blood flow, release of hormones, or central nervous system control of feed intake may contribute to the overall effects observed with a given beta-AR agonist in a given species. Furthermore, the pharmacodynamic properties of a particular agonist are complex and expected to vary among species as well as within the same species at different ages or when fed different diets.

Somatomedin-C stimulates the phosphorylation of the beta-subunit of its own receptor.

1983-08-01

Steven Jacobs , Frederick C. Kull , H. Shelton Earp +3 more

Phosphorylation of the somatomedin-C receptor was investigated both in intact IM-9 cells and in IM-9 cells that had been solubilized with Triton X-100. Intact IM-9 cells were incubated with [32P]H3PO4 … Phosphorylation of the somatomedin-C receptor was investigated both in intact IM-9 cells and in IM-9 cells that had been solubilized with Triton X-100. Intact IM-9 cells were incubated with [32P]H3PO4 for 1 h and for an additional 5 min in the absence or presence of insulin or somatomedin-C. The cells were then solubilized and subjected to wheat germ agglutinin Sepharose chromatography. The extent of phosphorylation of insulin and somatomedin-C receptors was assessed by immunoprecipitating the wheat germ agglutinin Sepharose eluates with monoclonal antibodies specific for each receptor and analyzing the immunoprecipitates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The beta-subunits of both receptors were phosphorylated in the absence of hormone, and the extent of phosphorylation of each receptor was enhanced by both hormones. However, each hormone was more potent than the other in enhancing phosphorylation of its own receptor. The beta-subunit of the somatomedin-C receptor was also phosphorylated when solubilized IM-9 cells that had been purified on wheat germ agglutinin Sepharose were incubated with [gamma-32P]ATP. In this soluble preparation, phosphorylation occurred on tyrosyl residues and was enhanced by concentrations of somatomedin-C in the range of 2.5 to 250 ng/ml, which is consistent with its receptor affinity. Tyrosyl phosphorylation of the somatomedin-C receptor also occurred when highly purified receptor, prepared by wheat germ agglutinin Sepharose affinity chromatography followed by immunoprecipitation, was incubated with [gamma-32P]ATP. This indicates that the responsible tyrosyl kinase activity is intrinsic to the receptor or tightly associated with it.

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Differential expression of the beta2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help.

1997-05-01

V M Sanders , Ross A. Baker , D S Ramer-Quinn +3 more

An important function of the sympathetic nervous system is to maintain homeostasis by modulating the level of cellular activity in many diverse organ systems. The sympathetic neurotransmitter norepinephrine modulates the … An important function of the sympathetic nervous system is to maintain homeostasis by modulating the level of cellular activity in many diverse organ systems. The sympathetic neurotransmitter norepinephrine modulates the level of T and B lymphocyte activity by binding to the beta2-adrenergic receptor (beta2AR). The present study was designed to elucidate the mechanism by which stimulation of the beta2AR affects both Th1/Th2 cell cytokine production and Th1/Th2 cell-dependent Ab production. Clones of murine Th1/Th2 cells were exposed to the beta2AR agonist terbutaline before activation by Ag-presenting B cells. Terbutaline exposure of Th1 cells before activation inhibited IFN-gamma production by Th1 cells and subsequent IgG2a production by B cells. IgG2a inhibition was prevented by addition of the betaAR antagonist nadolol or exogenous IFN-gamma. In contrast to Th1 cells, terbutaline did not affect either IL-4 production by Th2 cells or subsequent IgG1 production by B cells. Although baseline levels of intracellular cAMP were similar in both subsets, terbutaline induced an increase in cAMP levels in Th1 cells only. Radioligand binding studies showed that a detectable number of beta2AR binding sites were present on Th1 cells, but not on Th2 cells. Immunofluorescence analyses showed that Th1 cells expressed a higher level of the beta2AR cytoplasmic carboxyl terminus than did Th2 cells. These results show that expression of the beta2AR binding site by Th1 cells, but not by Th2 cells, establishes a physiologic mechanism for selective modulation of Th1 cell IFN-gamma production and IFN-gamma-dependent IgG2a production, provided that beta2AR stimulation occurs before cell activation by a B cell.

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Adrenergic Receptors in Man

1982-07-01

Harvey Motulsky , Paul A. Insel

THE catecholamines norepinephrine and epinephrine are key regulators of many physiologic events in human beings; norepinephrine acts primarily as a neurotransmitter released from sympathetic-nerve terminals, and epinephrine functions as a … THE catecholamines norepinephrine and epinephrine are key regulators of many physiologic events in human beings; norepinephrine acts primarily as a neurotransmitter released from sympathetic-nerve terminals, and epinephrine functions as a circulating hormone released from the adrenal medulla. These catecholamines initiate target-cell responses by binding to specific recognition sites, the adrenergic receptors. That receptors are the initial decoders of extracellular messages is a concept that has guided research on hormone and neurotransmitter action for many years. Studies of adrenergic receptors focused first on physiologic responses that are promoted by adrenergic stimulation and demonstrated the existence of two primary types of adrenergic . . .

Mechanism of action, metabolism, and toxicity of buthionine sulfoximine and its higher homologs, potent inhibitors of glutathione synthesis.

1982-11-01

Owen W. Griffith

The abbreviations used are: GSH, glutathione (reduced); GSSG, glutathione disulfide.Total glutathione refers to GSH equivalents determined as described under "Experimental Procedures."It is essentially GSH + 2 X GSSG; intracellular GSSG … The abbreviations used are: GSH, glutathione (reduced); GSSG, glutathione disulfide.Total glutathione refers to GSH equivalents determined as described under "Experimental Procedures."It is essentially GSH + 2 X GSSG; intracellular GSSG << GSH.a-Ethylmethionine sulfoximine is a specific inhibitor of glutamine synthetase (7).

Structural basis of β‐adrenergic receptor function

1989-05-01

Catherine D. Strader , Irving S. Sigal , Richard A. F. Dixon

Receptors that mediate their actions by stimulating guanine nucleotide binding regulatory proteins (G proteins) share structural as well as functional similarities. The structural motif characteristic of receptors of this class … Receptors that mediate their actions by stimulating guanine nucleotide binding regulatory proteins (G proteins) share structural as well as functional similarities. The structural motif characteristic of receptors of this class includes seven hydrophobic putative transmembrane domains linked by hydrophilic loops. Genetic analysis of the β-adrenergic receptor (βAR) revealed that the ligand binding domain of this receptor, like that of rhodopsin, involves residues within the hydrophobic core of the protein. On the basis of these studies, a model for ligand binding to the receptor has been developed in which the amino group of an agonist or antagonist is anchored to the receptor through the carboxylate side chain of Asp113 in the third transmembrane helix. Other interactions between specific residues of the receptor and functional groups on the ligand have also been proposed. The interaction between the βAR and the G protein Gs has been shown to involve an intracellular region that is postulated to form an amphi-philic α helix. This region of the βAR is also critical for sequestration, which accompanies agonist-mediated desensitization, to occur. Structural similarities among G protein-linked receptors suggest that the information gained from the genetic analysis of the βAR should help define functionally important regions of other receptors of this class.— Strader, C. D.; Sigal, I. S.; Dixon, R. A. F. Structural basis of β-adrenergic receptor function. FASEB J. 3: 1825-1832; 1989.

Log-normal distribution of equiefective doses of norepinephrine and acetylcholine in several tissues.

1972-05-01

William W. Fleming , D P Westfall , I.S. de la Lande +1 more

Frequency distributions of equieffective doses of norepinephrine in the rat vas deferens, the perfused artery of the rabbit ear, the aortic strip of the rabbit, the nietitating membrane of the … Frequency distributions of equieffective doses of norepinephrine in the rat vas deferens, the perfused artery of the rabbit ear, the aortic strip of the rabbit, the nietitating membrane of the spinat cat and the guinea-pig atrium and of acetylcholine in the rat vas deferens are presented. In all six, the distributions on an arthmetic scale tended to deviate from normal but the distributions on a log scale did not. In the three groups of data with the larger N 's, this deviation from normal of the arithmetic frequency distribution was significant by the Kolmogorov-Smirnov test. It is concluded that the distribution of equieffective doses of agonists is generally normal on a log scale but not on an arithmetic scale. Therefore, the means of equieffective doses and the statistical tests of their significance should be based on mean logs or their antilogs, the geometric means, not on arithmetic means.

Glucagon and plasma catecholamine responses to graded and prolonged exercise in man

1975-01-01

H. Galbo , Jens J. Holst , Niels Juel Christensen

Eight men were studied during graded (47, 77, and 100% of maximal oxygen uptake) and prolonged (76%) exhaustive treadmill running. During graded exercise the glucagon concentration increased 35% from 81 … Eight men were studied during graded (47, 77, and 100% of maximal oxygen uptake) and prolonged (76%) exhaustive treadmill running. During graded exercise the glucagon concentration increased 35% from 81 plus or minus 7 pg/ml (mean and SE) at rest to 109 plus or minus 17 after the heaviest load. During prolonged exercise glucagon increased progressively to three times (226 plus or minus 40) the resting value. Norepinephrine increased from 0.40 plus or minus 0.06 ng/ml to 2.22 plus or minus 0.39, epinephrine from 0.07 plus or minus 0.01 to 0.42 plus or minus 0.13 during graded, and to 1.51 plus or minus 0.08 and 0.33 plus or minus 0.04, respectively, during prolonged exercise. Insulin concentrations were depressed during work except for the heaviest load. Fatty acids rose throughout prolonged exercise, whereas blood glucose significantly diminished 30 min afterward. Glucagon concentrations correlated significantly with norepinephrine and epinephrine concentrations during prolonged and with epinephrine during graded exercise. Although increments in catecholamines were similar, the glucagon secretion was larger during prolonged than during graded exercise. While increments in catecholamines might explain increased glucagon secretion during graded exercise, they cannot account completely for the rise of glucagon during prolonged exercise.

THE FATE OF H3-NOREPINEPHRINE IN ANIMALS

1961-05-01

L. G. Whitby , J Axelrod , H. Weil‐Malherbe

The fate of H3-norepinephrine has been investigated after intravenous injection into animals. In cats, it distributes unequally in the various tissues examined; it is selectively taken up and retained by … The fate of H3-norepinephrine has been investigated after intravenous injection into animals. In cats, it distributes unequally in the various tissues examined; it is selectively taken up and retained by heart, spleen and adrenal gland. After H3-norepinephrine administration H3-normetanephrine is found in all tissues analyzed, but the individual concentrations vary considerably; it is retained by tissues to a lesser extent than H3-norepinephrine, except in skeletal muscle where more H3-normetanephrine is found after 2 hours than after 2 minutes. In the whole mouse H3-norepinephrine disappears rapidly at first, but then relatively slowly. H3-normetanephrine accounts for most of the H3-norepinephrine that disappears early in these experiments. The importance of binding as a mechanism for the inactivation of circulating catecholamines is emphasized, and it is shown to be quantitatively more important for norepinephrine than for epinephrine. Differences in the degree of binding explain why H3-norepinephrine disappears more slowly than H3-epinephrine from blood and from tissues.

A Radioimmunoassay for Plasma Aldosterone1

1970-05-01

Darrel M. Mayes , Shozo Furuyama , David C. Kem +1 more

The properties of antibodies to steroid-protein conjugates were investigated many years ago by Lieberman and his coworkers (1). Recently antibodies to an estradiol-protein conjugate have been used for assay of … The properties of antibodies to steroid-protein conjugates were investigated many years ago by Lieberman and his coworkers (1). Recently antibodies to an estradiol-protein conjugate have been used for assay of estradiol in human plasma (2). This report describes a method, using antibodies to an aldosterone-protein conjugate, to measure aldosterone in extracts of plasma purified by one column and one paper chromatography. 1,2-3H-aldosterone (New England Nuclear Corp., 29.5 c/mM) was purified every two weeks by paper chromatography in the system benzene:methanol:water 100:50:25. The purity of the labelled steroid was also examined once by acetylation and chromatography of the diacetate. Aldosterone was used as obtained from Mann Research Laboratories. The source and purification of solvents and the preparation of columns were as previously described (3). Silica gel (Merck, no. 7734) purified as previously described for Al2O3 (3). The source and method for washing chromatography paper and precoated thin layer chromatography plates and the composition of the scintillation fluid were as described earlier (4).

Central cardiovascular effects of alpha adrenergic drugs: differences between catecholamines and imidazolines.

1984-07-01

Pascal Bousquet , James A. Feldman , J. Schwartz

To check whether the central hypotensive effect of alpha adrenergic agonists is linked with the stimulation of alpha-2 receptors, such drugs were administered directly to the nucleus reticularis lateralis, which … To check whether the central hypotensive effect of alpha adrenergic agonists is linked with the stimulation of alpha-2 receptors, such drugs were administered directly to the nucleus reticularis lateralis, which is an important site for the hypotensive action of clonidine. These experiments were carried out by microinjections (0.5 microliter on each side) in normotensive cats anesthetized with pentobarbital. alpha-Methylnorepinephrine, a selective alpha-2 agonist (0.1-10 micrograms/kg) had no hypotensive effect in this region, whereas potent alpha-1 agonists such as cirazoline (0.01-1 micrograms/kg) and ST 587 (1-10 micrograms/kg), like clonidine, produced dose-dependent hypotensive effects. Our results suggest that alpha-2 selective catecholamines are not active in the nucleus reticularis lateralis region, whereas imidazolines induce a hypotensive effect whatever their affinity for one subtype of alpha adrenoceptors. Therefore, there may be some form of structure-activity relationship which would indicate the existence, in this particular region of the medulla oblongata, of sites preferring the imidazoline structure.

The physiological action of β‐iminazolylethylamine

1910-12-31

H. H. Dale , P. P. Laidlaw

8-IMINAZOLYLETHYLAMINE is the amine which is produced when carbon dioxide is split off from histidine.It was first prepared synthetically by Windaus and Vogt'.Recently Ackermann2 obtained a large yield of the … 8-IMINAZOLYLETHYLAMINE is the amine which is produced when carbon dioxide is split off from histidine.It was first prepared synthetically by Windaus and Vogt'.Recently Ackermann2 obtained a large yield of the base by submitting histidine to the action of putrefactive organisms.It has been shown that several of the amines thus related to amino-acids possess marked physiological activity.The activity of j8-iminazolylethylamine was discovered in the course of the investigation of ergot and its extracts by G. Barger and one of us3, who attributed this structure to a base which they obtained, and which in minute doses produced tonic contraction of the uterus.The synthetic substance, and the base produced by splitting off carbon dioxide from histidine by bacterial action or by chemical means, were found to have an identical action.Meanwhile Kutscher4 had simultaneously and independently described the isolation from ergot of a base having this action and presumably identical with that obtained by Barger and Dale.By its chemical properties this first ergot base of Kutscher was not distinguishable from 8-iminazolylethylamine; but certain apparent differences in the physiological action of the two bases, observed by Ackermann and Kutscber-5, led them to the conclusion that the ergot base, though closely related to 8-iminazolylethylamine, is not identical with it.The alleged difference in action, on the existence and cause of which our experiments throw light, was as follows: the 1 Ber.

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FATTY-ACID RATIOS IN FREE-LIVING AND DOMESTIC ANIMALS

1968-06-01

Michael A. Crawford

Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response.

1986-12-01

Michael B. Fowler , J Laser , G L Hopkins +2 more

We developed methods for identifying beta-adrenergic receptors in human right ventricular endomyocardial biopsy tissue with the radioligand (-)[125I]iodocyanopindolol (ICYP). Specific ICYP binding in a crude, high-yield membrane preparation derived from … We developed methods for identifying beta-adrenergic receptors in human right ventricular endomyocardial biopsy tissue with the radioligand (-)[125I]iodocyanopindolol (ICYP). Specific ICYP binding in a crude, high-yield membrane preparation derived from endomyocardial biopsy tissue was high (specificity greater than 90%), of high affinity (KD around 20 pM), saturable and stereospecific for the (-) vs the (+) isomer of isoproterenol. Subjects with mild-moderate and severe biventricular dysfunction had respective decreases in beta-adrenergic receptor density of 38.2% and 57.7% when normalization methods were averaged, with no significant differences in ICYP dissociation constant. A subgroup of subjects was subdivided by left ventricular ejection fraction (LVEF) into those with mild cardiac dysfunction (LVEF less than 0.50 greater than 0.40) and severe heart failure (LVEF less than 0.20) and given graded sequential infusions of dobutamine and calcium gluconate. Those with severe cardiac dysfunction had marked impairment of the dobutamine dP/dt and stroke work index response, whereas these responses to calcium did not differ in the two groups. These data indicate that in the intact human heart endomyocardial biopsy may be used for direct analysis of beta-adrenergic receptors, heart failure-associated myocardial beta-adrenergic down-regulation begins with mild-moderate ventricular dysfunction, reduction in myocardial beta-receptor density is related to degree of heart failure, and beta-receptor down-regulation is associated with pharmacologically specific impairment of the beta-agonist-mediated contractile response.

An Improved Method for Fluorimetric Determination of Small Amounts of Adrenaline and Noradrenaline in Plasma and Tissues

1963-11-01

Jan Häggendal

Abstract H äggendal , J. An improved method for fluorimetric determination of small amounts of adrenaline and noradrenaline in plasma and tissues . Acta physiol. scand. 1963. 59 . 242–254. … Abstract H äggendal , J. An improved method for fluorimetric determination of small amounts of adrenaline and noradrenaline in plasma and tissues . Acta physiol. scand. 1963. 59 . 242–254. — By the introduction of several modifications of the trihydroxyindole method for the determination of adrenaline and noradrenaline appreciable improvement of the sensitivity has been obtained. The blank values have been considerably reduced and stabilized by substituting dimercaptopropanol (BAL) in sodium sulfite solution for ascorbic acid. The eluate volume has been reduced and the degree of purification has been increased by a modified ion‐exchange procedure (Dowex 50 W‐X8). Deproteinization of plasma before the column procedure could be omitted. When this procedure was applied to 10 ml plasma obtained from normal persons at rest, noradrenaline spectra, with two activation peaks, were usually obtained. The average concentration of the noradrenaline was 0.3 ± 0.11 μ g per litre of plasma. Normally no adrenaline was found. Noradrenaline occurred in plasma in both free and conjugated form.

Analytical strategies for residue analysis of veterinary drugs and growth-promoting agents in food-producing animals—a review

2005-03-01

A.A.M. Stolker , U.A.Th. Brinkman

ADENYL CYCLASE AS AN ADRENERGIC RECEPTOR*

1967-02-01

G. Alan Robison , R.W. Butcher , Earl W. Sutherland

Monensin interrupts the recycling of low density lipoprotein receptors in human fibroblasts

1981-05-01

Sandip K. Basu , Joseph L. Goldstein , Richard G.W. Anderson +1 more

The action of sympathomimetic amines in animals treated with reserpine

1958-12-04

J. H. Burn , M. J. Rand

Simplified 2,4-dinitrophenylhydrazine spectrophotometric assay for quantification of carbonyls in oxidized proteins

2014-05-06

Cristina Sousa Mesquita , Raquel Oliveira , M. Fátima Bento +3 more

A simple and rapid HPLC–MS method for the simultaneous determination of epinephrine, norepinephrine, dopamine and 5-hydroxytryptamine: Application to the secretion of bovine chromaffin cell cultures

2006-10-19

Victoria Carrera , Esther Sabater , Eugenio Vilanova +1 more

Cross-Linking in Adhesive Quinoproteins: Studies with Model Decapeptides

2000-08-17

Luis A. Burzio , J. Herbert Waite

Mytilus edulis foot protein-1 (mefp1) is a major component of the byssus, an adhesive holdfast in mussels. The recent report of 5,5'-di(dihydroxyphenyl-l-alanine) (diDOPA) cross-links in byssus [McDowell et al. (1999) … Mytilus edulis foot protein-1 (mefp1) is a major component of the byssus, an adhesive holdfast in mussels. The recent report of 5,5'-di(dihydroxyphenyl-l-alanine) (diDOPA) cross-links in byssus [McDowell et al. (1999) J. Biol. Chem. 274, 20293] has raised questions about the relationship of these to mefp1. About 80% of the primary structure of mefp1 consists of a tandemly repeated consensus sequence Ala1-Lys2-Pro3-Ser4-Tyr5-Pro6-Pro7-Thr8-Tyr9-Lys10 with varying degrees of posttranslational hydroxylation to hydroxyprolines in positions 3, 6, and 7 and to DOPA in positions 5 and 9. Six natural or synthetic variants of this decapeptide were subjected to oxidation by tyrosinase or periodate. DOPA is the only residue to suffer losses in all oxidized peptides. Moreover, using MALDI TOF mass spectrometry, oxidized decapeptides all showed evidence of multimer formation and a mass loss of 6 Da per coupled pair of peptides. Multimer formation was inhibited by addition of DOPA-like o-diphenols, but addition of simple amines such as free Lys had no effect. The results are consistent with aryloxy coupling to diDOPA followed by reoxidation to diDOPA quinone. There are subtle but noteworthy variations, however, in multimer formation among the peptide congeners. Decapeptides with Pro3 modified to trans-4-hydroxyproline do not form multimers beyond dimers; they also exhibit significant Lys losses following oxidation of DOPA. Moreover, in Ala-Lys-Hyp-Ser-Tyr-DiHyp-Hyp-Thr-DOPA-Lys, Tyr appears to be protected from oxidation by tyrosinase.

A sensitive method for the determination of plasma catecholamines using liquid chromatography with electrochemical detection

1978-09-01

H. Hällman , Lars‐Ove Farnebo , Bertil Hamberger +1 more

Influence of the site of conjugation on the specificity of antibodies to progesterone

1973-09-01

G. D. Niswender

EFFECT OF MORPHINE ON ADRENERGIC TRANSMISSION IN THE MOUSE VAS DEFERENS. ASSESSMENT OF AGONIST AND ANTAGONIST POTENCIES OF NARCOTIC ANALGESICS

1975-03-01

Joel W. Hughes , H. W. Kosterlitz , Frances M. Leslie

Morphine inhibits the electrically evoked (0.1‐0.15 Hz, 1 ms) contractions of the longitudinal muscle of the mouse vas deferens but not of the rabbit, guinea‐pig, rat, cat, hamster or gerbil. … Morphine inhibits the electrically evoked (0.1‐0.15 Hz, 1 ms) contractions of the longitudinal muscle of the mouse vas deferens but not of the rabbit, guinea‐pig, rat, cat, hamster or gerbil. This effect is stereospecific and is antagonized by naloxone or naltrexone. Normorphine is equiactive with morphine but its effects are more rapid in onset and decline. In the mouse vas deferens, the resting outflow of tritium‐labelled catecholamines is unaffected by morphine. The electrically evoked outflow is depressed by morphine or normorphine in a dose‐dependent manner. The ID 50 for inhibition of contraction and for depression of outflow is 0.5 μM. The relative agonist potencies of compounds without antagonist component (codeine, pethidine, morphine, normorphine, heroin, levorphanol, Ba‐20227, etorphine) show good correlation with the relative agonist potencies determined in the guinea‐pig ileum and for analgesia in man. For compounds with dual agonist and antagonist properties, the dose‐response curves for agonist activity are shallow. When the lowest concentrations giving a depression of the contraction of the mouse vas deferens are used, a good correlation is obtained with the guinea‐pig ileum. The relative antagonist potencies of naloxone, nalorphine, levallorphan and cyclazocine agree well with those obtained in the guinea‐pig ileum; these, in turn, correlate well with the values obtained in the morphine‐dependent monkey. The fact that the agonist effects of drugs with dual agonist and antagonist action show little or no dependence on concentration, makes the mouse vas deferens particularly suitable for the assay of antagonist activity. As an assay preparation, the mouse vas deferens is less robust and consistent in its responses than the guinea‐pig ileum.

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Role of β-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease

2008-04-01

Gordon S. Lynch , James G. Ryall

The importance of β-adrenergic signaling in the heart has been well documented, but it is only more recently that we have begun to understand the importance of this signaling pathway … The importance of β-adrenergic signaling in the heart has been well documented, but it is only more recently that we have begun to understand the importance of this signaling pathway in skeletal muscle. There is considerable evidence regarding the stimulation of the β-adrenergic system with β-adrenoceptor agonists (β-agonists). Although traditionally used for treating bronchospasm, it became apparent that some β-agonists could increase skeletal muscle mass and decrease body fat. These so-called “repartitioning effects” proved desirable for the livestock industry trying to improve feed efficiency and meat quality. Studying β-agonist effects on skeletal muscle has identified potential therapeutic applications for muscle wasting conditions such as sarcopenia, cancer cachexia, denervation, and neuromuscular diseases, aiming to attenuate (or potentially reverse) the muscle wasting and associated muscle weakness, and to enhance muscle growth and repair after injury. Some undesirable cardiovascular side effects of β-agonists have so far limited their therapeutic potential. This review describes the physiological significance of β-adrenergic signaling in skeletal muscle and examines the effects of β-agonists on skeletal muscle structure and function. In addition, we examine the proposed beneficial effects of β-agonist administration on skeletal muscle along with some of the less desirable cardiovascular effects. Understanding β-adrenergic signaling in skeletal muscle is important for identifying new therapeutic targets and identifying novel approaches to attenuate the muscle wasting concomitant with many diseases.

A Method for the Fluorimetric Determination of Adrenaline and Noradrenaline in Tissues.1

1958-08-01

Åke Bertler , Arvid Carlsson , Evald Rosengren

Summary. A method for chemical assay of small amounts of adrenaline and noradrenaline in tissues is described. The catechol amines are extracted with perchloric acid. The extracts are passed through … Summary. A method for chemical assay of small amounts of adrenaline and noradrenaline in tissues is described. The catechol amines are extracted with perchloric acid. The extracts are passed through a cation exchange column (Dowex 50) which takes up the catechol amines. Elution of the amines from the column is performed by hydrochloric acid. Estimation of the two amines in the eluates is made fluorimetrically after oxidation and rearrangement in alkali. Differentiation between adrenaline and noradrenaline is performed by utilizing the difference in the activation spectra of the fluoro‐phores.

8-Hydroxy-2-(dipropylamino)tetralin, a new centrally acting 5-hydroxytryptamine receptor agonist

1981-08-01

L.‐E. ARVIDSSON , Uli Hacksell , Jonas Nilsson +5 more

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT8-Hydroxy-2-(dipropylamino)tetralin, a new centrally acting 5-hydroxytryptamine receptor agonistLars Erik Arvidsson, Uli Hacksell, J. Lars G. Nilsson, Stephan Hjorth, Arvid Carlsson, Per Lindberg, Domingo Sanchez, and Haakan WikstroemCite … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT8-Hydroxy-2-(dipropylamino)tetralin, a new centrally acting 5-hydroxytryptamine receptor agonistLars Erik Arvidsson, Uli Hacksell, J. Lars G. Nilsson, Stephan Hjorth, Arvid Carlsson, Per Lindberg, Domingo Sanchez, and Haakan WikstroemCite this: J. Med. Chem. 1981, 24, 8, 921–923Publication Date (Print):August 1, 1981Publication History Published online1 May 2002Published inissue 1 August 1981https://pubs.acs.org/doi/10.1021/jm00140a002https://doi.org/10.1021/jm00140a002research-articleACS PublicationsRequest reuse permissionsArticle Views381Altmetric-Citations320LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Mode of coupling between the β-adrenergic receptor and adenylate cyclase in turkey erythrocytes

1978-09-05

Aviva M. Tolkovsky , Alexander Levitzki

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMode of coupling between the β-adrenergic receptor and adenylate cyclase in turkey erythrocytesAviva M. Tolkovsky and Alexander LevitzkiCite this: Biochemistry 1978, 17, 18, 3795–3810Publication Date (Print):September 5, … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMode of coupling between the β-adrenergic receptor and adenylate cyclase in turkey erythrocytesAviva M. Tolkovsky and Alexander LevitzkiCite this: Biochemistry 1978, 17, 18, 3795–3810Publication Date (Print):September 5, 1978Publication History Published online1 May 2002Published inissue 5 September 1978https://pubs.acs.org/doi/10.1021/bi00611a020https://doi.org/10.1021/bi00611a020research-articleACS PublicationsRequest reuse permissionsArticle Views237Altmetric-Citations274LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Differentiation of receptors responsive to isoproterenol

1967-11-01

A.M. Lands , F.P. Ludueña , H.J. Buzzo

A radioimmunoassay for plasma testosterone

1970-07-01

Shunsuke Furuyama , Darrel M. Mayes , Charles A. Nugent

Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure.

1986-09-01

Michael R. Bristow , Robert Ginsburg , Victor A. Umans +7 more

We used radioligand binding techniques and measurement of beta-agonist-mediated positive inotropic responses in isolated cardiac tissue to examine beta-adrenergic-receptor subpopulations in nonfailing and failing human left and right ventricular myocardium. … We used radioligand binding techniques and measurement of beta-agonist-mediated positive inotropic responses in isolated cardiac tissue to examine beta-adrenergic-receptor subpopulations in nonfailing and failing human left and right ventricular myocardium. In tissue derived from 48 human hearts the receptor subtypes identified in nonfailing ventricle by radioligand binding were beta 1 (77%) and beta 2 (23%), with no evidence of an "atypical" beta-adrenergic receptor. In failing left ventricle the beta 1:beta 2 ratio was markedly different, i.e., 60:38. This decrease in the beta 1 proportion and increase in the beta 2 proportion in the failing ventricles were due to a 62%, "selective" down-regulation of the beta 1 subpopulation, with little or no change in beta 2 receptors. In muscle bath experiments in isolated trabeculae derived from nonfailing and failing right ventricles, both beta 1- and beta 2-adrenergic receptors were coupled to a positive inotropic response. In nonfailing myocardium, beta 1 responses predominated, as the selective beta 1 agonist denopamine produced a response that was 66% of the total contractile response of isoproterenol. In heart failure the beta 1 component was markedly decreased, while the beta 2 component was not significantly diminished. Moreover, in heart failure the beta 2 component increased in prominence, as the contractile response to the selective beta 2 agonist zinterol increased from a minority (39%) to a majority (60%) of the total response generated by isoproterenol. We conclude that failing human ventricular myocardium contains a relatively high proportion of beta 2 receptors, due to selective down-regulation of beta 1 receptors. As a result, in the failing human heart the beta 2-receptor subpopulation is a relatively important mediator of inotropic support in response to nonselective beta-agonist stimulation and is available for inotropic stimulation by selective beta 2 agonists.

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An investigation of the ionic mechanism of intracellular pH regulation in mouse soleus muscle fibres

1977-12-01

C C Aickin , R C Thomas

1. Intracellular pH (pH(i)) of surface fibres of the mouse soleus muscle was measured in vitro by recessed-tip pH-sensitive micro-electrodes. pH(i) was displaced in an acid direction by removal of … 1. Intracellular pH (pH(i)) of surface fibres of the mouse soleus muscle was measured in vitro by recessed-tip pH-sensitive micro-electrodes. pH(i) was displaced in an acid direction by removal of external (NH(4))(2)SO(4) after a short exposure, and the mechanism of recovery from this acidification was investigated.2. Removal of external K caused a very slow acidification (probably due to the decreasing Na gradient) but had no effect on the rate of pH(i) recovery following acidification. This indicates that K(+)-H(+) exchange is not involved in the pH(i) regulating system.3. Short applications of 10(-4)M ouabain had no obvious effect on pH(i) and did not alter the rate of pH(i) recovery following acidification. This suggests that there is no direct connexion between the regulation of pH(i) and the Na pump.4. Reduction of external Ca from 10 to 1 mM caused a transient fall in pH(i), but the rate of pH(i) recovery following acidification was unaffected. This suggests that Ca(2+)-H(+) exchange is not involved in the pH(i) regulating system.5. An 11% reduction in external Na caused a significant slowing of pH(i) recovery following acidification. 90% or complete removal of external Na almost stopped pH(i) recovery. This suggests that Na(+)-H(+) exchange is involved in pH(i) regulation.6. Amiloride (10(-4)M) reversibly reduced the rate of pH(i) recovery to much the same extent as removal of external Na. Its effect was not additive to that of removal of external Na.7. Internal Na ion concentration ([Na(+)](i)), measured using Na(+)-sensitive micro-electrodes, fell on application of (NH(4))(2)SO(4) and increased on its removal. The increase transiently raised [Na(+)](i) above the level recorded before (NH(4))(2)SO(4) application. This overshoot of [Na(+)](i) was almost completely inhibited by amiloride. This is consistent with the involvement of Na(+)-H(+) exchange in the pH(i) regulating system.8. Removal of external CO(2) or application of SITS (10(-4)M) caused some slowing of the rate of pH(i) recovery following acidification by removal of (NH(4))(2)SO(4). The effect of SITS was additive to that of Na-free Ringer or amiloride. These results suggest that Cl(-)-HCO(3) (-) exchange is also involved in the pH(i) regulating system and that it is a separate mechanism. Under the conditions used, Cl(-)-HCO(3) (-) exchange formed about 20% of the pH(i) regulating system.9. Decreasing the temperature from 37 to 28 degrees C not only caused an increase in pH(i), but also considerably slowed the rate of pH(i) recovery following acidification. We have calculated a Q(10) for Na(+)-H(+) exchange of 1.4 and for Cl(-)-HCO(3) (-) exchange, 6.9.10. We conclude that the pH(i) regulating system is comprised of two separate ionic exchange mechanisms. The major mechanism is Na(+)-H(+) exchange, which is probably driven by the transmembrane Na gradient. The other mechanism is Cl(-)-HCO(3) (-) exchange, which probably requires metabolic energy.

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The Estimation of Catechol Amines in Urine

1959-04-01

U. S. von Euler , F. Lishajko

Abstract. Some modifications in the fluorimetric method of E uler and F loding are described. The urine sample, usually 25 ml, is adjusted to pH 8.2–8.3 and passed through a … Abstract. Some modifications in the fluorimetric method of E uler and F loding are described. The urine sample, usually 25 ml, is adjusted to pH 8.2–8.3 and passed through a column of aluminium oxide. The catechols are eluted with acetic acid, neutralized with ammonia to pH 6.2–6.3, oxidized with potassium ferricyanide and transformed to stable lutines with alkali and ascorbic acid. The fluorescence of the lutines is read with two filter sets and the amounts of adrenaline and noradrenaline computed.

Nanoparticle‐induced platelet aggregation and vascular thrombosis

2005-09-12

Anna Radomski , Paul Jurasz , David Alonso‐Escolano +4 more

Ever increasing use of engineered carbon nanoparticles in nanopharmacology for selective imaging, sensor or drug delivery systems has increased the potential for blood platelet-nanoparticle interactions. We studied the effects of … Ever increasing use of engineered carbon nanoparticles in nanopharmacology for selective imaging, sensor or drug delivery systems has increased the potential for blood platelet-nanoparticle interactions. We studied the effects of engineered and combustion-derived carbon nanoparticles on human platelet aggregation in vitro and rat vascular thrombosis in vivo. Multiplewall (MWNT), singlewall (SWNT) nanotubes, C60 fullerenes (C60CS) and mixed carbon nanoparticles (MCN) (0.2-300 microg ml(-1)) were investigated. Nanoparticles were compared with standard urban particulate matter (SRM1648, average size 1.4 microm). Platelet function was studied using lumi aggregometry, phase-contrast, immunofluorescence and transmission electron microscopy, flow cytometry, zymography and pharmacological inhibitors of platelet aggregation. Vascular thrombosis was induced by ferric chloride and the rate of thrombosis was measured, in the presence of carbon particles, with an ultrasonic flow probe. Carbon particles, except C60CS, stimulated platelet aggregation (MCN>or=SWNT>MWNT>SRM1648) and accelerated the rate of vascular thrombosis in rat carotid arteries with a similar rank order of efficacy. All particles resulted in upregulation of GPIIb/IIIa in platelets. In contrast, particles differentially affected the release of platelet granules, as well as the activity of thromboxane-, ADP, matrix metalloproteinase- and protein kinase C-dependent pathways of aggregation. Furthermore, particle-induced aggregation was inhibited by prostacyclin and S-nitroso-glutathione, but not by aspirin. Thus, some carbon nanoparticles and microparticles have the ability to activate platelets and enhance vascular thrombosis. These observations are of importance for the pharmacological use of carbon nanoparticles and pathology of urban particulate matter.

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Chemical energetics of slow- and fast-twitch muscles of the mouse.

1982-01-01

Michael T. Crow , Martin J. Kushmerick

The energy utilization associated with contraction was measured in isolated slow- and fast-twitch muscles of the mouse at 20 degrees C. The extent of this utilization was estimated from either … The energy utilization associated with contraction was measured in isolated slow- and fast-twitch muscles of the mouse at 20 degrees C. The extent of this utilization was estimated from either the extent of high-energy phosphate splitting occurring during contraction (the initial chemical change, delta approximately P init) or from the extent of recovery resynthesis calculated from the observed oxygen consumption and lactate production occurring during the recovery period (recovery chemical resynthesis, delta approximately P rec). For short tetani, the cost to maintain isometric tension in the fast-twitch extensor digitorum longus (EDL) was approximately threefold greater than that in the slow-twitch soleus. With prolonged stimulation, however, the energy cost in the EDL diminished so that after 12 s of stimulation, the energy cost in the EDL was only 50% greater than that of the soleus. For both the slow-twitch soleus and the fast-twitch EDL and for all tetanus durations (up to 15 s), the extent of the initial chemical change was identical with the amount of recovery chemical resynthesis, showing that a biochemical energy balance existed in these muscles.

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Inverse agonist activity of beta-adrenergic antagonists.

1994-03-01

Peter Chidiac , Terence E. Hébert , Manon Valiquette +2 more

Agonist-independent properties of the human beta 2-adrenergic receptor (beta 2AR) were studied using the baculovirus expression system in Sf9 cells. In the absence of agonist but in the presence of … Agonist-independent properties of the human beta 2-adrenergic receptor (beta 2AR) were studied using the baculovirus expression system in Sf9 cells. In the absence of agonist but in the presence of GTP, membranes from cells expressing the beta 2AR exhibited higher levels of cAMP production than did membranes from uninfected cells or from cells infected with wild-type baculovirus. The increase in cAMP production was proportional to the number of beta 2AR expressed, up to 40 pmol/mg of membrane protein, and it could be inhibited in a dose-dependent manner by beta AR antagonists. The increase and its reversal both were independent of the possible presence of contaminating catecholamines in the culture medium and thus appear to reflect spontaneous beta 2AR activity and direct antagonist-receptor interactions, respectively. The maximal level of inhibition varied among the beta AR ligands tested, to yield the following rank order of "inverse efficacy"; timolol > or = propranolol > alprenolol > or = pindolol > labetalol > dichloroisoproterenol. The same rank order was observed using membranes prepared from Chinese hamster fibroblasts expressing beta 2AR. The effect of timolol was partly blocked by labetalol and dichloroisoproterenol, in an apparently competitive manner. The intracellular cAMP content of Sf9 cells cultured in serum-free medium was also increased by the expression of beta 2AR, and that increase was reversed by timolol and propranolol, consistent with observations in membrane preparations. The properties revealed by the expression of the beta 2AR in Sf9 cells suggest two agonist-independent traits of G protein-linked receptors, i.e., 1) that unliganded receptors are able to activate G proteins both in membrane preparations and in whole cells and 2) that antagonists may mediate their effects not only by preventing the binding of agonists but also by decreasing the propensity of the receptor to assume an active state.

Identification of platelet activating factor isolated from rabbit basophils as acetyl glyceryl ether phosphorylcholine.

1980-06-01

D J Hanahan , Constantinos A. Demopoulos , Joachim G. Liehr +1 more

Platelet activating factor obtained from antigen-stimulated rabbit buffy coat leukocytes containing 10% IgE-sensitized basophils was shown by gas-liquid chromatographic and mass spectrometric analysis of products after acetolysis and by base … Platelet activating factor obtained from antigen-stimulated rabbit buffy coat leukocytes containing 10% IgE-sensitized basophils was shown by gas-liquid chromatographic and mass spectrometric analysis of products after acetolysis and by base and acid hydrolysis to be acetyl-alkylglyceryl phosphorylcholine. The alkyl side chains were composed of octadecyl (greater than 90%) and hexadecyl (less than 10%) residues.

A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines.

1962-12-01

Aaron H. Anton , David F. Sayre

A reliable, quantitative, highly sensitive, adaptable method for the estimation of catecholamines in diverse biological material from various vertebrate species is presented in detail. This method, which differs in several … A reliable, quantitative, highly sensitive, adaptable method for the estimation of catecholamines in diverse biological material from various vertebrate species is presented in detail. This method, which differs in several significant aspects from other procedures, involves the selective adsorption of the catecholamines onto a constant amount of aluminum oxide, elution with constant volume of perchlonic acid (0.05 N) and their measurement by the formation of a fluorescent trihydroxyindole derivative in the presence of potassium ferricyanide and alkaline (10 N alkali) ascorbate. In the light of our findings several other procedures have been critically evaluated. In a comparative study on the distribution of norepinephrine and epinephnine in several species, their presence was detected in the poison gland of a snake. From a study of a large number of analogs of norepinephrine the specificity of the method has been more clearly delineated.

STUDIES ON BEHAVIOR. IV. STIMULANT ACTIONS OF METHAMPHETAMINE

1958-01-01

Peter Dews

The number of responses made by pigeons in a fixed period of time is greatly increased by methamphetamine, when the birds are working under certain schedules (159 Fl and FR … The number of responses made by pigeons in a fixed period of time is greatly increased by methamphetamine, when the birds are working under certain schedules (159 Fl and FR 900); but is only slightly increased when they are working under other schedules (19 VI and FR 50). It is suggested that, in appropriate doses, methamphetamine tends to reduce the number and length of inter-response times in excess of 5 seconds but that rather larger doses also tend to prolong inter-response times shorter than 1 second. Some similar effects were obtained with d-amphetamine and pipradrol.

Nitric oxide release is present from incubated skeletal muscle preparations

1994-12-01

T. W. Balon , Jerry L. Nadler

To determine whether nitric oxide (NO) synthase activity exists in rat skeletal muscle, media from incubated rat extensor digitorum longus muscle preparations were assayed for NO with a chemiluminescent detection … To determine whether nitric oxide (NO) synthase activity exists in rat skeletal muscle, media from incubated rat extensor digitorum longus muscle preparations were assayed for NO with a chemiluminescent detection system. Although small amounts of NO were detected in media alone, the addition of muscle increased NO concentration in the media by 30-fold. The release of NO into the media diminished over time. Either arginine (10(-6) M), sodium nitroprusside (10(-6) M), or prior electrical stimulation in vivo caused 50–200% increases (P < 0.05) in NO concentration. NG-monomethyl-L-arginine monoacetate (10(-6) M), an NO synthase inhibitor, decreased both basal 2-deoxyglucose transport and NO efflux, indicating that NO may play a role in modulating skeletal muscle carbohydrate metabolism. These data indicate that NO is released from an incubated skeletal muscle preparation and presents the possibility that muscle-derived NO may play an important metabolic role.

Biochemistry, Physiology and Pathology of Zinc

1959-07-01

Bert L. Vallée

Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells

1990-08-01

Kenneth M. Baker , Joseph F. Aceto

The octapeptide [Ile5]angiotensin II (ANG II), which is the principal circulating hormone of the renin-angiotensin system, could modulate or mediate cardiac hypertrophy via indirect effects, through increases in total peripheral … The octapeptide [Ile5]angiotensin II (ANG II), which is the principal circulating hormone of the renin-angiotensin system, could modulate or mediate cardiac hypertrophy via indirect effects, through increases in total peripheral vascular resistance, or by direct effects on cardiac cells, which result in increased protein synthesis and cell growth. In this study we determined whether ANG II stimulated protein synthesis and cell growth in cultures of embryonic chick myocytes. After 3 h of exposure to ANG II, there were significant increases in total cellular protein at 120, 144, and 168 h and in the relative rate of protein synthesis at 120 and 144 h. There was a significant increase in the fractional rate of protein synthesis of 32.2% (0.0119 +/- 0.0008 h-1 for ANG II stimulated and 0.0090 +/- 0.0003 h-1 for control). The stimulatory effects of ANG II on protein synthesis and cell growth were inhibited by the ANG II antagonist [Sar1,Ile8]ANG II and the hexapeptide ANG II-(3-8). ANG II significantly increased total RNA levels in myocytes, at 12 h after exposure to the peptide. The stimulatory effect of ANG II (32%) on total cellular protein was slightly greater than that seen with norepinephrine (20%) in contrast to the greater stimulatory effect seen with phorbol 12,13-dibutyrate (47%). ANG II and [Sar1,Ile8]ANG II each stimulated increases in cytosolic-free Ca2+, whereas ANG II-(3-8) did not. Growth-related effects of changes in the chronotropic state of the myocytes were excluded, in that, ANG II-stimulated increases in protein synthesis and cellular protein were not inhibited by potassium chloride depolarization of the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

REACTIONS OF STRIPS OF RABBIT AORTA TO EPINEPHRINE, ISOPROPYLARTERENOL, SODIUM NITRITE AND OTHER DRUGS

1953-06-01

Robert F. Furchgott , Suchin Bhadrakom

1. The general properties of spirally cut strips of rabbit aorta as pharma-cological test objects have been described. Such strips possess only a very small amount of spontaneous tone and … 1. The general properties of spirally cut strips of rabbit aorta as pharma-cological test objects have been described. Such strips possess only a very small amount of spontaneous tone and never exhibit rhythmic contractions. When freshly mounted in muscle chambers they undergo a gradual elongation and gradual increase in sensitivity to stimulating drugs over a period of about two to three hours. If a fully sensitized strip is caused to contract maximally by temporary exposure to a high concentration of epinephrine, it reverts to a state of low sensitivity. 2. Drugs which were found to give only contraction of aortic strips fall in the following order as to potency: norepinephrine and epinephrine > histamine > acetyicholine. 3. Sodium nitrite causes complete relaxation of strips initially placed in a state of low to moderate tone by the previous addition of a stimulating drug. It also appears to be able to completely suppress spontaneous tone of aortic strips. However, in the face of maximal tone due to high concentrations of epinephrine, it causes only slight relaxation. 4. Isopropylarterenol causes relaxation at low concentrations. However, at high concentrations it causes contraction. 5. The time-characteristics of contraction on addition, and of relaxation after washout, of epinephrine and certain other drugs have been described. 6. Concentration-activity curves for epinephrine have been presented. The relation of the observed curves to theoretical curves predicted by Clark9s equation has been discussed.

Simultaneous Determination of Beta-1 and Beta-2-Adrenergic Receptors in Tissues Containing Both Receptor Subtypes

1979-07-01

Kenneth P. Minneman , Linda R. Hegstrand , Perry B. Molinoff

A method for determining the relative concentrations and properties of β-1 and β-2-adrenergic receptors in tissues containing both receptor subtypes has been developed. Since (125I)-iodohydroxybenzylpindolol has similar affinities for β-1 … A method for determining the relative concentrations and properties of β-1 and β-2-adrenergic receptors in tissues containing both receptor subtypes has been developed. Since (125I)-iodohydroxybenzylpindolol has similar affinities for β-1 and β-2-adrenergic receptors, it is possible to determine the total concentration of β-adrenergic receptors in a tissue by Scatchard analysis of specific (125I)-iodohydroxybenzylpindolol binding. In the presence of GTP, inhibition of specific (125I)-iodohydroxybenzylpindolol binding in rat heart, lung and five regions of rat brain by agonists and antagonists that are not specific for β-1 or β-2-adrenergic receptors yields linear Hofstee plots with Hill coefficients of approximately 1.0. On the other hand, the inhibition of specific (125I)-iodohydroxybenzylpindolol binding by drugs which have been shown to have different affinities for heart (β-1) and lung (β-2) receptors in vitro results in nonlinear Hofstee plots in each of these tissues. Two of these drugs (practolol and metoprolol) are more potent on β-1 than β-2 receptors and two of these drugs (zinterol and salmefamol) are more potent on β-2 than on β-1 receptors. The nonlinear Hofstee plots are consistent with there being two types of binding sites in each of the tissues with different affinities for the drugs. The relative number of each type of binding site and the affinity of each drug for each of the two types of site has been calculated using a computer based iterative procedure. Using this method, the relative percentages of the two receptor subtypes in rat heart, lung, cerebral cortex, caudate, cerebellum, hippocampus and diencephalon were determined. In each tissue, the use of four different drugs with different in vitro selectivity (two β-1 selective and two β-2 selective) resulted in approximately the same calculated β-1/β-2 ratio. This suggests that the assumption that the nonlinear Hofstee plots are composed of only two components is correct. In addition, the calculated affinity of each drug for β-1 and β-2 receptors was quantitatively similar in each of the seven tissues examined. The calculated ratios of β-l:β-2-adrenergic receptors are: heart 83:17; lung 15:85; cortex 81:19; caudate 76:24; cerebellum 15:85; hippocampus 81:19; and diencephalon 71:29. The absolute concentrations of β-1-adrenergic receptors in the brain regions examined varied by almost 20-fold. However, the absolute concentration of β-2-adrenergic receptors varied less than 3-fold. This suggests that β-2-adrenergic receptors in rat brain are associated with a more homogeneously distributed cellular element than are β-1-adrenergic receptors.

ACTIVE PHASE OF FROG'S END-PLATE POTENTIAL

1959-07-01

A. Takeuchi , Noriko Takeuchi

Mammalian Muscle Receptors and Their Central Actions

1973-08-01

Muriel McGlamery

Journal Article Mammalian Muscle Receptors and Their Central Actions Get access Mammalian Muscle Receptors and Their Central Actions. By Matthews PBC. Baltimore, The Williams & Wilkins Company, 1972, cloth, 630 … Journal Article Mammalian Muscle Receptors and Their Central Actions Get access Mammalian Muscle Receptors and Their Central Actions. By Matthews PBC. Baltimore, The Williams & Wilkins Company, 1972, cloth, 630 pp, illus, $32.25 Muriel E. McGlamery, M.D. Muriel E. McGlamery, M.D. Search for other works by this author on: Oxford Academic Google Scholar Physical Therapy, Volume 53, Issue 8, August 1973, Pages 927–928, https://doi.org/10.1093/ptj/53.8.927b Published: 01 August 1973

Journal of Sports Science and Medicine

2014-08-22

Matthew Stewart

The Classification of Adrenoceptors (Adrenergic Receptors). An Evaluation from the Standpoint of Receptor Theory

1972-01-01

Robert F. Furchgott

Maternal exposure to difenoconazole-induced developmental defects and its mechanisms in F1 zebrafish (Danio rerio)

2025-06-23

Ying Zhang , Fuqi Yang , Qian Zhang +4 more | Ecotoxicology and Environmental Safety

Advanced Au/SnS2 photoelectrochemical sensor for epinephrine detection in athletes' biological samples

2025-06-21

Jinliang Zhang , Enyu Guo , Ying Xin | Alexandria Engineering Journal

Disposable Printed Sensors Based on Carbon Black/Carbon Dots Conductive Ink for Sensitive Voltammetric Determination of Kopexil (Aminexil) in Lotion Samples

2025-06-18

Abdulkarim Albishri , Mashael M. Alharbi , Razan M. Snari +5 more | Journal of The Electrochemical Society

Abstract Herein, a disposable screen-printed sensor enriched with a blend of carbon black (CB)/carbon dots (CDs) was fabricated for a novel precise differential pulse voltammetric determination of kopexil (KOP) in … Abstract Herein, a disposable screen-printed sensor enriched with a blend of carbon black (CB)/carbon dots (CDs) was fabricated for a novel precise differential pulse voltammetric determination of kopexil (KOP) in topical lotion samples and spiked plasma. The fabricated sensors were fully characterized, and the formulation of the homemade printing ink matrix was optimized. Modification of the electrode matrix with the carbonaceous nanoparticles improved their voltammetric response against oxidation of the KOP molecule at 1.17V in BR buffer, pH 5 following diffusion-controlled reaction mechanism. Based on the theoretical molecular orbital calculations and electroanalytical studies, oxidation of KOP molecule may undergoes through oxidation of the terminal nitrogen atom (N8) with the transfer of two protons/electrons in the electrode reaction. At the optimized measuring conditions, the reported calibration graphs showed linear dynamic range within the KOP concentration ranged from 0.080 to 2.633µgmL-1, and a limit of detection of 26.0ngmL-1. Prolonged operational lifetime with high measurement reproducibility was reported for the fabricated sensors. With improved sensitivity and selectivity toward KOP, the CB/CDs based sensor were validated as a green analytical method for KOP assaying in lotion and spiked plasma samples with enhanced sensitivity compared with the chromatographic and spectrophotometric techniques.

A portable electrochemical detection system for rapid quantitative carbendazim analysis in agricultural food

2025-06-17

Phuritat Kaewarsa , Vitsarut Primpray , Hossein Khosropour +2 more | Innovative Food Science & Emerging Technologies

Magnetic Particle-Based Automated Chemiluminescence Immunoassay for the Determination of Hydrocortisone Residues in Milk

2025-06-16

Yuanyuan Yang , Bao-Zhu Jia , Zhenlin Xu +2 more | Foods

Hydrocortisone is a typical glucocorticoid commonly used in livestock production; however, its overuse can result in hormone residues in milk. Long-term consumption of such milk may lead to a series … Hydrocortisone is a typical glucocorticoid commonly used in livestock production; however, its overuse can result in hormone residues in milk. Long-term consumption of such milk may lead to a series of health issues. Therefore, the timely and rapid detection of hydrocortisone in milk is crucial for protecting human health. In this study, a magnetic particle-based direct chemiluminescence immunoassay (MP-DCLIA) incorporating a streptavidin-biotin signal amplification system was developed for the rapid and high-throughput detection of hydrocortisone in milk. Automated operations reduce human error and enhance the accuracy and repeatability of tests. The assay can be completed in 12 min with a linear detection range of 13.09-261.71 μg/L, a limit of detection (LOD) of 4.94 μg/L, a limit of quantification (LOQ) of 14.84 μg/L, and intra- and inter-batch variations of less than 5%. The method demonstrated stability and exhibited no cross-reactivity with structural analogues. Spiked recoveries of milk samples ranged from 85.85% to 100.30%, with results strongly correlating with those obtained from LC-MS/MS. The MP-DCLIA offers rapidity, high efficiency, stability, and precision, making it a promising tool for practical testing applications.

Rapid Detection of Clenbuterol and Ractopamine in Pork: Sulfonate Functionalized Ion Exchange Magnetic Solid Phase Extraction Combined with Visual Protein Microarray Chip

2025-06-14

Kaihan Yang , Xiaobing Yan , Minmin Tang +2 more | Talanta

Acute toxicity via oral administration of naproxen in body mass gain and organs mass of female albino rats (Rattus rattus)

2025-06-13

Wurood Hasan Hadi | Scientific Modelling and Research

Naproxen, 4,2-(6′-methoxy-2′-naphthyl)-propionic acid is a nonsteroidal anti-inflammatory drug (NSAID); as in recent toxicity research, the determination of danger has been demonstrated in rats with a curative dose compared to the … Naproxen, 4,2-(6′-methoxy-2′-naphthyl)-propionic acid is a nonsteroidal anti-inflammatory drug (NSAID); as in recent toxicity research, the determination of danger has been demonstrated in rats with a curative dose compared to the human dose. Actually, it is used in both rheumatic and non-rheumatic inflammatory pain. In this study, repeated oral doses of naproxen were administered once daily. The research model consisted of 20 white rats. The four groups, each consisting of five individuals, received the drug for 28 days at the following doses: 500, 750, and 1000 mg/kg/day. Group 1 was the control group, receiving saline as a daily dose. Group 2 received 500 mg/kg each day, Group 3 received 750 mg/kg each day, and Group 4 received 1000 mg/kg each day. The rats were slaughtered after 28 days of treatment. After receiving treatment for 28 days, the rats were slaughtered, and the animals were weighed before and after the end of the period, as well as the vital organs (liver, kidney, and testicle), followed by statistical studies of the recorded weights. As a result of the drug's effect, weight was affected in a decreasing manner from the lowest dose to the highest according to the study program, and statistically significant differences were observed. Cases of hematuria were recorded, which led to damage and a sharp drop in weight. The harmful effects of naproxen are notable in the short term. Thus, this assay was conducted to certify the effect of naproxen on body weight gain as a primary criterion for harm in female rats.

A Simple, Sensitive and Wide Range Electrochemical Sensor for Tinidazole Detection in Water, Food and Pharmaceutical Samples

2025-06-01

Arun Warrier , Pooja Das M , Dhanya Gangadharan +1 more | Electrochimica Acta

Comparative study of extraction and spectrophotometric determination of salbutamol sulphate by Fe 3 O 4 /SiO 2 /CPC and Fe 3 O 4 /Al 2 O 3 /CPC adsorbents: analytical greenness profile

2025-05-30

Tabarak Mohammed , Hind Hadi , Khanda F.M. Amin | International Journal of Environmental & Analytical Chemistry

How Do Individually Ventilated Cages Affect the Welfare of Male BALB/c Mice? Comprehensive Assessment of Behavior, Metabolism, and Responses to Acute Painful Stimuli

2025-05-30

Aslı Çelik , Cemre Ural , Efsun Kolatan +5 more | Brain and Behavior

ABSTRACT Introduction Housing conditions, which have a major impact on the welfare of laboratory animals, are an important issue in experimental research. Individually ventilated cage (IVC) and open‐top cage (OTC) … ABSTRACT Introduction Housing conditions, which have a major impact on the welfare of laboratory animals, are an important issue in experimental research. Individually ventilated cage (IVC) and open‐top cage (OTC) systems are widely used for housing laboratory mice. Purpose This study aimed to comprehensively investigate the effects of OTC and IVC housing conditions on the behavior, metabolism, and pain responses of laboratory mice from an animal welfare perspective. Method We measured body temperature, body weight, anxiety levels (using the elevated plus maze and open field test), and thermal nociceptive responses (using the hot‐plate and tail‐flick tests) in male albino BALB/c mice. At the end of these procedures, the mice were sacrificed, and the serum levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), ghrelin, and leptin were determined by ELISA, and the weight of the adrenal glands was measured. Findings The results showed that there were significant differences in body weight, body temperature, anxiety‐related behaviors, pain latency, and hormonal parameters between the OTC group and the IVC group. Compared to OTC, IVC had lower levels of leptin, especially under stress conditions, where a significant interaction between housing and stress was observed, and higher levels of ghrelin, ACTH, and CORT. IVC group also had increased body weight, adrenal gland weight, and body temperature. In the hot‐plate test, the IVC group showed increased latency of hind limb responses compared to the OTC group, but not in the tail‐flick test. IVC group exhibited more anxiety‐related behaviors in the OFT, while no differences were observed in the EPM. Conclusion According to the results of this study, housing mice in IVCs appears to compromise welfare, altering behavioral, hormonal, and pain responses. This suggests that the IVC system can induce physiological and behavioral stress, potentially acting as a systemic confounding factor in mouse research.

Comparative Energy Analysis of Bio-Receptive and Conventional Façades in Different Climates

2025-05-29

Niharika Mishra | INTERANTIONAL JOURNAL OF SCIENTIFIC RESEARCH IN ENGINEERING AND MANAGEMENT

Abstract - This review paper presents a comparative analysis of the energy performance of bio-receptive façades and conventional façade systems across diverse climatic contexts. With the increasing emphasis on sustainable … Abstract - This review paper presents a comparative analysis of the energy performance of bio-receptive façades and conventional façade systems across diverse climatic contexts. With the increasing emphasis on sustainable architecture and environmentally responsive design, bio-receptive façades have emerged as an innovative solution that integrates biological elements—such as mosses, algae, or microorganisms—into building envelopes. These systems offer potential benefits including enhanced thermal insulation, passive cooling, and carbon sequestration, thereby contributing to the overall energy efficiency and ecological performance of buildings. The study employs a combination of case studies and simulation-based methodologies to evaluate the thermal behavior, heating and cooling load implications, and overall energy efficiency of bio-receptive façades in comparison to conventional alternatives. Given the evolving nature of this technology, the analysis is grounded in a comprehensive review of current literature, industry data, and relevant sustainability standards. The findings are critically examined in relation to established environmental performance benchmarks to identify alignments, discrepancies, and areas requiring further development. Preliminary results suggest that bio-receptive façades demonstrate considerable potential in enhancing building energy performance, particularly in temperate and humid climates. However, several challenges persist, including maintenance complexity, variability in biological growth, and integration with existing construction practices. This study concludes that while the adoption of bio-receptive façade systems is promising, successful implementation will require coordinated efforts among architects, engineers, and policymakers to address technical barriers and refine performance assessment frameworks. Key Words: Bio-receptive facade, Energy efficiency, Sustainable architecture, Climate-responsive design, Thermal performance.

One-step SPE-UHPLC-MS/MS for simultaneous detection of fipronil and metabolites in animal-derived foods

2025-05-28

Mengying Wang , Meng Sun , Wangang Zhang +4 more

Clenbuterol Abuse in Bodybuilding and Athletics: Unsupervised Use, Psychological Motivations, and Health Consequences

2025-05-27

Suhas Kataveni , Raga Priya Gourishetty , Shruti M Mundada +3 more

Assessment of a non-invasive approach for pressure volume loop prediction in mice

2025-05-25

Luis A. Reyes , Michael E. Alfaro , Janet Akoth Kireta +5 more

Left ventricular pressure-volume (PV) loop measurement provides insights into cardiac function by mapping the relationship between left ventricular pressure and volume throughout the cardiac cycle. PV loops are used extensively … Left ventricular pressure-volume (PV) loop measurement provides insights into cardiac function by mapping the relationship between left ventricular pressure and volume throughout the cardiac cycle. PV loops are used extensively in pre-clinical studies, but they are obtained through invasive and often terminal procedures. In prior studies utilizing data from large mammals (e.g., pigs and humans), quantitative models have been utilized to estimate PV loops utilizing non-invasive measurements. These studies rely on three key assumptions: constant normalized elastance (ratio of pressure over volume) across individuals, accurate non-invasive estimation of left ventricular systolic and diastolic pressure, and non-invasive estimation of left ventricular volume data. Here we assessed the application and suitability of these approaches to mice, a smaller pre-clinical animal. We found limitations of this approach due to variability in elastance among mice, suggesting that the constancy observed in larger animals might not generally extend to rodents. Additionally, while non-invasive estimates of end systolic pressures were close to invasively obtained measurements, they were not reliable for determining maximum elastance. Moreover, although individual correlations between invasive and non-invasive volume measurements were strong, creating a generalized predictive model of pressure-volume loop proved challenging due to variability across sample data set.

Salbutamol

2025-05-24

Longitudinal Metabolic Profiling of Women Using Selective Serotonin Reuptake Inhibitors During Pregnancy

2025-05-23

Anna Itkonen , Olli Kärkkäinen , Heidi Sahlman +2 more

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressants for pregnant women. While SSRIs are known to alter the circulating metabolic profile in non-pregnant individuals, the association between … Introduction: Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressants for pregnant women. While SSRIs are known to alter the circulating metabolic profile in non-pregnant individuals, the association between SSRIs and the changes in circulating metabolome during pregnancy remains unstudied. Pregnancy itself induces significant metabolic adjustments to meet the increased nutritional demands, and these maternal metabolic changes are crucial for the normal development and growth of the fetus. Objectives: To study the impact of SSRI usage on circulating maternal metabolome during pregnancy. Methods: A targeted nuclear magnetic resonance (NMR) spectroscopy method was used to analyze maternal serum samples obtained from the 1st trimester of pregnancy and at the time of the delivery from both SSRI users (n =122) and non-depressive controls without antidepressants (n =117) for concentrations of metabolites and lipoproteins. Results: During the 1st trimester of pregnancy, SSRI usage was associated with increased lipid content in sixteen very low-density lipoprotein (VLDL) and chylomicron subtypes. At delivery, SSRI users exhibited alterations in lipoprotein lipid and fatty acid ratios. Similarly, while investigating the influence of SSRI usage on the pregnancy-driven changes in the metabolome, the interplay between pregnancy progression and SSRI usage lowered the lipoprotein lipid ratios. Conclusion: Our analysis revealed a significant association between SSRIs and lipid metabolism. However, the observed changes were minor, suggesting a limited clinical impact. The findings enhance our understanding of the safe usage of SSRI medication during pregnancy.

Chemical Immobilization of Red Serows (Capricornis rubidus) with Ketamine and Medetomidine.

2025-05-21

Sanath Krishna Muliya , Lallianpuii Kawlni , John Lalhnuna +3 more

The red serow (Capricornis rubidus) is a solitary, cryptic, forest-dwelling goat-antelope species from Asia, with very limited veterinary and health information. We report on the chemical immobilization of three red … The red serow (Capricornis rubidus) is a solitary, cryptic, forest-dwelling goat-antelope species from Asia, with very limited veterinary and health information. We report on the chemical immobilization of three red serows by using medetomidine (0.03 mg/kg) and ketamine (3 mg/kg). This combination may be useful for chemical capture and field anaesthesia of these animals.

Opioid quantification via microsampling techniques to assess opioid use in human laboratory studies

2025-05-21

Ramisa Fariha , Emma Rothkopf , Carolina L. Haass‐Koffler +1 more

Despite progress in neurobiological studies with human subjects, sample availability remains a challenge. Urine samples, widely used for screening, suffer from false-positive results due to immunoassay cross-reactivity. Serum, used for … Despite progress in neurobiological studies with human subjects, sample availability remains a challenge. Urine samples, widely used for screening, suffer from false-positive results due to immunoassay cross-reactivity. Serum, used for confirmatory testing, offers advantages but faces limitations due to blood collection. Microsamples, with a working volume less than 50 μL, present an ideal strategy for robust quantitative data collection in investigations and human laboratory studies. We developed, validated, and automated a serum-based LC-MS/MS assay for accurate quantification of six opioids using only 20 μL of patient samples. Our method, applied in a clinical trial with patients with opioid use disorder (N = 20) receiving intranasal oxytocin, or placebo, for one week in addition to opioid agonist therapy (buprenorphine or methadone). We quantified six different opioids, undetected by urine strip tests, that were used by patients during the treatment phase. Our high-throughput, automated approach surpasses existing methods in literature, enhancing efficiency in multi-matrix studies.

Efficient inference of rankings from multi-body comparisons

2025-05-20

NULL AUTHOR_ID

Green and sustainable LC-APCI-MS/MS method for simultaneous quantification of genotoxic nitrosamines in antidiabetic medication: sitagliptin

2025-05-20

Sriram Pepakayala , Venkata Nadh Ratnakaram , Yuvaraj Zunjarrao +1 more

The International Agency for Research on Cancer categorized nitrosamines as potential or probable human carcinogens. Hence, nitrosamine impurities should be controlled to minimize the cancer risk. Sustainable Development Goal 9 … The International Agency for Research on Cancer categorized nitrosamines as potential or probable human carcinogens. Hence, nitrosamine impurities should be controlled to minimize the cancer risk. Sustainable Development Goal 9 (SDG9: Industry, Innovation, and Infrastructure), Target 9.4 was realized by developing a simple and straightforward LC-APCI-MS/MS method for simultaneous determination of potential nitrosamines: N-nitroso dimethylamine, N-nitroso di isopropyl amine, N-nitroso isopropyl ethylamine and N-nitroso methyl aminopyridine (NDMA, NDIPA, NIPEA and NMAP) in Sitagliptin Phosphate Monohydrate API (STG-API), an antidiabetic medication for type-2 diabetes and validated as per ICH (Q2 R2) guidelines. As a part of SDG9 (Industry, Innovation, and Infrastructure), Target 9.4, greater adoption of clean and environmentally sound technologies is possible by using the current analytical method in view of (a) less consumption of solvents as it has a lower run time of 18 min (b) at-line sample collection (c) simple sample preparation (d) sample preparation process that does not require derivatization or sample extraction. The optimized LC method conditions are an Agilent Poroshell EC C18 column, a flow rate of 0.6 mL/min, an injection volume of 40 µL, a column oven temperature set at 50 °C, and a sample cooler temperature set at 6 °C. A gradient method was adopted using a mixture of mobile phases (Solvent A: 0.1% formic acid in water and Solvent B: a mixture of 50% Methanol and 50% Acetonitrile). The response was obtained with Multiple Reaction Monitoring (MRM) in APCI mode. The current method can quantify NDMA, NIPEA, NDIPA, and NMAP to a lower level of 74.19 ng/g, 19.62 ng/g, 20.36 ng/g, and 13.65 ng/g, respectively, which is less than 10% of the specified limits. Good linearity in the range of Limit of Quantitation (LOQ) to 150% of the specification limit was observed, with correlation coefficients higher than 0.996. The recoveries were over the range between 90.23 and 103.36%. Assessed the method's eco-friendliness by greenness tools like the Modified Green Analytical Procedure Index (MoGAPI), ComplexMoGAPI, Analytical GREEnness (AGREE), and Analytical Eco-Scale, and found it to be eco-friendly.

Evaluation of changes in the characteristics of beta2-adrenergic receptors in healthy volunteers under the influence of cholinergics using a modified radioligand analysis technique

2025-05-17

Anna V. Eremenko , E. V. Smolyakova , Yuri S. Skoblov +2 more

Background. Reseaching of the properties of β-adrenergic receptors (β-AR) is an urgent area in both fundamental and applied medicine. One of the most exact ways to determine the characteristics of … Background. Reseaching of the properties of β-adrenergic receptors (β-AR) is an urgent area in both fundamental and applied medicine. One of the most exact ways to determine the characteristics of β-AR is the radioligand method using [125I]cyanopindolol. This method сan determine the binding activity of β-AR on human blood cells. It is especially important to study the receptor link under the influence of various external factors and drugs. Aims — to evaluate the binding activity of β2-AR on T-lymphocytes of peripheral blood cells using radioligand analysis in healthy volunteers and in professional athletes under the influence of cholinergics. Methods. Healthy volunteers and athletes were given methacholine inhalation. Blood sampling was carried out initially on a clean background and after the methacholine test. To level out the differences in the conditions of formulation and to bring the results to the same coordinate system, the evaluation of the characteristics of β-AR in the framework of the study was carried out according to the specific binding index (ISS) — value reflecting the proportion of specific binding of receptors from the total specific. Results. During the study, when dividing volunteers into smokers and non-smokers, a tendency to decrease binding activity was noted. As a result of the study, in the general group of volunteers was registerd a significant decrease in the binding activity of beta2 receptors under the influence of methacholine. In the group of athletes, no significant changes were kept. Conclusions. The reason for these results may be both intense training, which changes the number of receptors, and the presence or absence of eosinophilic inflammation. The smoking factor does not play a significant role.

Hypogonadotropic hypogonadism diagnosis in boys under one year of age based on gonadotrophins, testosterone, antimullerian hormone (AMH) and inhibin B (INHB) measurements

2025-05-09

Tifenn Gueguen , Martinerie Laetitia , Sarah Castets +7 more

Voltammetric Determination of Salbutamol, Sulfamethoxazole, and Trimethoprim as Anthropogenic Impact Indicators Using Commercial Screen-Printed Electrodes

2025-05-09

Jing Huang , Julio Bastos‐Arrieta , Núria Serrano +1 more

A voltammetric method based on the use of screen-printed carbon electrodes (SPCEs) is presented for the simultaneous determination of salbutamol (SAL), sulfamethoxazole (SMX), and trimethoprim (TMP), with high sensitivity, fast … A voltammetric method based on the use of screen-printed carbon electrodes (SPCEs) is presented for the simultaneous determination of salbutamol (SAL), sulfamethoxazole (SMX), and trimethoprim (TMP), with high sensitivity, fast response, and excellent repeatability and reproducibility. Under the optimal voltammetric conditions, the simultaneous analysis showed linear ranges of 0.3-2.5 mg L-1, 0.3-11.1 mg L-1, and 0.5-9.0 mg L-1 for SAL, SMX, and TMP, respectively, and detection limits of 83.8 μg L-1, 88.7 μg L-1, and 139.2 μg L-1, respectively. Additionally, the developed method was successfully validated by the analysis of a spiked river water sample with satisfactory recovery values in the range of 97.0-98.8%. The added value of the presented method relays in combining cost-effective disposable SPCEs with rapid analysis (<30 s), providing portable electrochemical tools for the on-site monitoring of pharmaceutical residues, which is critical for addressing contamination linked to anthropogenic activity.

EXPRESS: Expression of Tacr1 and Gpr83 by spinal projection neurons

2025-05-07

Wenhui Ma , Allen C. Dickie , Erika Polgár +5 more

Anterolateral system (ALS) projection neurons underlie perception of pain, itch and skin temperature. These cells are heterogeneous, and there have therefore been many attempts to define functional populations. A recent … Anterolateral system (ALS) projection neurons underlie perception of pain, itch and skin temperature. These cells are heterogeneous, and there have therefore been many attempts to define functional populations. A recent study identified two classes of ALS neuron in mouse superficial dorsal horn (SDH) based on expression of the G protein-coupled receptors Tacr1 or Gpr83. It was reported that cells expressing these receptors formed largely non-overlapping populations, and that ~60% of ALS cells in SDH expressed Tacr1. An additional finding was that while Tacr1- and Gpr83-expressing ALS cells projected to several brain nuclei, their axons did not reach the ventral posterolateral (VPL) thalamic nucleus, which is reciprocally connected to the primary somatosensory cortex. These results were surprising, because we had reported that ~90% of SDH ALS neurons in the mouse possess the neurokinin 1 receptor (NK1r), which is encoded by Tacr1, and in addition the VPL is thought to receive input from lamina I ALS cells. Here we use retrograde and anterograde labelling in Tacr1CreERT2 and Gpr83CreERT2 mice to reinvestigate the expression of the receptors by ALS neurons and to reassess their projection patterns. We find that ~90% of ALS neurons in SDH express Tacr1, with 40-50% expressing Gpr83. We also show that axons of both Tacr1- and Gpr83-expressing ALS neurons reach the VPL. These results suggest that ALS neurons in the SDH that express these GPCRs show considerable overlap, and that they are likely to contribute to the sensory-discriminative dimension of pain through their projections to VPL.

DEVELOPMENT AND VALIDATION OF A STABILITY-INDICATING RP-HPLC METHOD FOR QUANTITATIVE DETERMINATION OF NITROXYNIL AND ITS IMPURITIES AS PER ICH GUIDELINES

2025-05-07

Tata Santosh , Prafulla Kumar Sahu

Objective: An isocratic elution method for the determination of Nitroxynil (NTX), its related substances was developed and validated as per ICH guidelines. Methods: The process impurity4-Hydroxy-3-nitrobenzonitrile (NTX impurity-1) and key … Objective: An isocratic elution method for the determination of Nitroxynil (NTX), its related substances was developed and validated as per ICH guidelines. Methods: The process impurity4-Hydroxy-3-nitrobenzonitrile (NTX impurity-1) and key starting material 4-cyanophenol (4-CP) along with NTX were separated using a 50: 50%v/v composition of acetonitrile and 1% Orthophosphoric acid solution as mobile phase at a flow rate of 1 ml/min under isocratic mode. Separation was achieved on a Kromasil Eternity XT C18,4.6×250 mm, 5µ within a 30 min run time. The detection was made using a photo diode array detector and quantification was carried out at 244 nm. Forced degradation study was also conducted to confirm the specificity of the method. The method was found to be robust and rugged and complied with ICH guidelines. Results: The calibration curve ranged from 0.5 – 7.5 ppm for NTX and its impurities. The Limit of Detection (LOD) for NTX is 0.09 ppm and Limit Of Quantification (LOQ) was 0.28 ppm. The LOD for NTX impurity-1 and 4-CP were 0.02 and 0.04 ppm, respectively, while the corresponding LOQ values were 0.06 and 0.13 ppm. In samples spiked with NTX and its impurities, the mean recovery was approximately 102.5±2%. Conclusion: The method confirms its stability indicating nature was successfully applied for quality evaluation of NTX in bulk API. The method was validated as per guidelines of the International Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH).

[Determination of 27 perfluoroalkyl substances in pork by ultra-high performance liquid chromatography-tandem mass spectrometry].

2025-05-01

Yushen Jin , Yang Xing , Kaixin Xu +2 more | PubMed

A method based on QuEChERS and ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was established for the detection of 27 perfluoroalkyl substances(PFASs) in pork. Pork samples were extracted with acetonitrile-water(8∶2, V/V), and … A method based on QuEChERS and ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was established for the detection of 27 perfluoroalkyl substances(PFASs) in pork. Pork samples were extracted with acetonitrile-water(8∶2, V/V), and the supernatant was purified with 100 mg primary secondary amine(PSA) and 40 mg octadecylsilyl(C18). Separation was performed using an Ascentis~(TM) Express F5(2.1 mm × 150 mm, 2 μm) chromatographic column, and detection was carried out using UPLC-MS/MS with internal standard quantification. The 27 PFASs exhibited good linearity in the range of 0.01-50 μg/L, with limit of detection(LOD) ranging from 0.004 to 0.044 μg/L and limit of quantification(LOQ) ranging from 0.015 to 0.145 μg/L. The intra-day and inter-day precision were determined at a spiking level of 2LOQ, with a recovery rate of 72.4%-109.7% and 78.6%-110.7%, an intra-day relative standard deviation(RSD) of 1.2%-9.6%(n=6), and an inter-day RSD of 1.0%-13.8%(n=5), respectively. Using this method, 52 pork samples from Beijing markets were tested, and the result showed that all 26 PFASs compounds, except perfluorooctanesulfonamide(PFOSA), were ubiquitous and accumulated to varying degrees in pork. This method is simple, time-saving, and has high accuracy, sensitivity, and reliability, making it suitable for simultaneous determination of 27 PFASs in pork samples and applicable to routine monitoring and quality control of PFASs in pork samples.

Reference intervals for electrocardiograms and arrhythmia incidence in healthy, sedated cynomolgus macaques

2025-05-01

Nakkawee Saengklub , Taratorn Kemthong , Pakit Boonpala +4 more

Aptamer‐Functionalized Screen‐Printed Carbon Electrodes Coated with Polymerized Catecholamine Film for Capacitive Sensing of Acetamiprid

2025-05-01

Abdulhadi H. Almarri

The detection of acetamiprid (ACE) residues remains a critical challenge in environmental and food safety monitoring. Herein, a novel biosensing platform is presented, based on screen‐printed carbon electrodes (SPCEs) modified … The detection of acetamiprid (ACE) residues remains a critical challenge in environmental and food safety monitoring. Herein, a novel biosensing platform is presented, based on screen‐printed carbon electrodes (SPCEs) modified with an electrodeposited catecholamine film and a specific anti‐ACE aptamer as the biorecognition element. The electroactive polymeric film was electrochemically deposited onto the SPCE surface, providing enhanced electron transfer properties and increased electroactive surface area. The subsequent immobilization of an anti‐ACE aptamer created a selective biosensing interface. Using redox capacitance spectroscopy, it is demonstrated that the interaction between ACE and the biomodified electrode surface induced measurable changes in interfacial charge distribution and capacitance. The biosensor exhibited a linear response across a wide dynamic range of ACE concentrations (1 fg·mL −1 to 10 pg·mL −1 ), with a detection limit of 0.57 fg·mL −1 (∼2.56 aM) (S/N = 3). The practical utility of the sensor was validated through recovery studies on lettuce and tomatoes, demonstrating its potential for routine ACE monitoring in vegetables. This label‐free electrochemical approach offers a promising platform for the rapid and sensitive detection of pesticides in complex matrices.

88 Effects of perfluorooctanoic acid exposure and heat stress on performance and liver health biomarkers in post-pubertal gilts

2025-05-01

Bridget M Buol , Collins Antwi-Boasiako , E.J. Mayorga +3 more

Abstract Objectives were to evaluate how dietary perfluorooctanoic acid (PFOA) exposure and heat stress (HS) affects growth performance and the hepatic profile in pigs. Crossbred post-pubertal gilts (n = 48; … Abstract Objectives were to evaluate how dietary perfluorooctanoic acid (PFOA) exposure and heat stress (HS) affects growth performance and the hepatic profile in pigs. Crossbred post-pubertal gilts (n = 48; 157.0 ± 29.5 kg BW) were blocked by BW and randomly assigned to 1 of 4 treatments: 1) thermoneutral (TN) control (n = 12; TN-CON), 2) TN and PFOA (n = 12; TN-PFOA), 3) HS control (n = 12; HS-CON), or 4) HS and PFOA (n = 12; HS-PFOA). Pigs were enrolled in 3 experimental periods (P). During P1 (3 d), pigs were housed in TN conditions (20.3 ± 0.1ºC) and baseline data were collected. During P2 (15 d), HS-CON and HS-PFOA pigs were exposed to cyclical HS (29.3 ± 0.1 ºC to 31.9 ± 0.8 ºC), while TN-CON and TN-PFOA remained in TN conditions. Altrenogest was administered once daily (0800 h) during P2 to synchronize estrus. In P3 (4 d), Altrenogest was withdrawn to induce estrus, while experimental treatments remained the same. PFOA (70 ng/kg BW) was orally administered once daily (0800 h) during P2 and P3. Pigs were sacrificed at the end of P3. HS increased rectal temperature, skin temperature, and respiration rate compared to TN counterparts in P2 (0.34 ºC, 5.67 ºC, and 22 bpm, respectively; P &lt; 0.01) and P3 (0.26 ºC, 6.96 ºC, and 22 bpm, respectively; P &lt; 0.01) and these were slightly influenced by PFOA. During P2 and P3, HS markedly decreased feed intake (FI) and ADG as expected, and this was not affected by PFOA. PFOA tended to decrease FI and ADG and it was most pronounced during TN conditions (410 g/d; P ≤ 0.08 and 320 g/d; P ≤ 0.09, respectively) during P2 and P3. HS decreased circulating alkaline phosphatase and alanine aminotransferase in P2 and P3 (P ≤ 0.01) and gamma-glutamyl transferase increased by HS in P2 (P &lt; 0.01) but were unaffected by PFOA. Other liver health biomarkers observed little to no other treatment or environmental effects. HS decreased absolute and relative liver, lung, and kidney weights, and PFOA decreased absolute lung weight (11%; P &lt; 0.05) and relative lung weight (0.06%; P = 0.09). In summary, PFOA and HS independently compromise appetite and growth, but the effects of PFOA are not additive during HS.

130 Effect of dietary additives on nursery pig performance

2025-05-01

S.R. Craig , M. Mayer , Caitlyn Wileman +3 more

Abstract A total of 450 newly weaned pigs (PIC 337 x 1050, Genus, Hendersonville, TN) were used to evaluate the use of dietary ingredients to improve nursery pig gut health … Abstract A total of 450 newly weaned pigs (PIC 337 x 1050, Genus, Hendersonville, TN) were used to evaluate the use of dietary ingredients to improve nursery pig gut health and growth performance. Pigs were sorted into pens (5 barrows and 5 gilts each (10 pigs/pen) and randomly assigned to one of five dietary treatments. The dietary treatments included: control (CN, standard diet with ZnO (3500 ppm); negative control (NC, control with no ZnO); sodium gluconate (SG, 0.25 % inclusion in NC, Sumitomo, Tokyo, Japan); butyrate (BP, 0.09% inclusion in NC, Kemin, Des Moines, IA) or monoglycerides (MG, 0.3% inclusion stepdown to 0.25% in NC, BASF, Florham Park, NJ). Diets were fed in three phases: 0-7 days, 7-21 days, and 21-42 days. Diets were formulated to meet or exceed all other NRC (2012) dietary recommendations. Pen and feeder weights were recorded on days 0, 7, 21, and 42 to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain to feed (G:F). Data were analyzed using a linear model in R (v4.4.1) with significance set at P ≤ 0.05 and tendencies at 0.05 &lt; P ≤ 0.10. Pen was the experimental unit. The pigs developed hemolytic Escherichia coli at approximately d10. The average starting pig body weight (BW) was 5.52 ± 0.123 kg. By day 21, the CN had significantly heavier BW compared to the other diets (10.58, 9.31, 9.55, 9.81, 9.24 kg, respectively; P &lt; 0.01). Phase 1 ADG showed a significant difference with CN being higher than other diets (0.033, -0.017, -0.011, -0.008, -0.036; P &lt; 0.01). ADG during phase 2 was significantly higher for the CN compared to other diets (0.332, 0.261, 0.274, 0.295, 0.237 kg/d; P &lt; 0.01). Overall ADG (0.373, 0.329, 0.328, 0.345, 0.321 kg/d; P = 0.09) did show a tendency towards difference between diets. Overall G:F was 0.714, 0.756, 0.755, 0.759, and 0.746 kg, respectively, and showed no significant difference between diets (P = 0.66). ADFI during phase 2 showed a significant difference with the CN being higher than the other treatments (0.321, 0.246, 0.234, 0.248, 0.198; P &lt; 0.01). Overall ADFI did show a significant difference for the CN diet (0.513, 0.438, 0.426, 0.463, 0.423; P &lt; 0.01). Sodium gluconate, zinc oxide, and butyrate supplementation had limited effects on growth performance in nursery pigs, with zinc oxide showing the most notable differences. ADFI was improved overall when pigs were fed CN (zinc oxide) and some significant effects in early phases of ADG when feeding CN (zinc oxide), but these effects on ADG did span across the whole period.

A traffic light-fluorescent lateral flow immunoassay with dual-color quantum dot nanobeads for the simultaneous detection of ractopamine and clenbuterol

2025-05-01

Runxian Li , Decheng Suo , Zhinong Yu +5 more

MASS SPECTROMETRY-BASED QUANTIFICATION OF ACTIVE ANGIOTENSINOGEN IN DIFFERENT VERTEBRATE SPECIES

2025-05-01

Dunja van Oyen , Melanie Zillinger , Marko Poglitsch +2 more

Surveillance of Anabolic Agent Residues in US Meat Supply by Liquid Chromatography With High‐Resolution Tandem Mass Spectrometry

2025-05-01

Cade M. Snethen , Matthew Fedoruk , Elizabeth D. Ahrens +3 more

ABSTRACT This study provides data on the prevalence of animal growth promoter residues through a comprehensive US surveillance approach targeting multiple species via retail purchases. Over a year, residue levels … ABSTRACT This study provides data on the prevalence of animal growth promoter residues through a comprehensive US surveillance approach targeting multiple species via retail purchases. Over a year, residue levels were analyzed in beef, pork, and poultry samples from eight US cities, screening for a panel of anabolic steroids, other anabolic agents, selective androgen receptor modulators (SARMs), and non‐prohibited controls using sensitive high‐resolution tandem mass spectrometry. Thirteen of the 53 beef samples tested positive for ractopamine, with a peak concentration of 14 ng/g in liver—well below CODEX and FDA maximum residue limits (MRLs). Trenbolone‐17β and estradiol were also found in beef but remained within MRLs, indicating no health risk. In addition, pork samples showed minimal contamination, with just one pork kidney testing positive for nandrolone (0.08 ng/g) under the limit of detection and estradiol (0.5 ng/g), likely from endogenous hormone production in intact male pigs. Pork muscle and liver samples were residue‐free. Chicken samples showed limited residues, with estradiol detected in three out of 35 muscle samples at 0.01 ng/g. These findings highlight the effectiveness of regulatory practices in limiting growth promoter residues in commercial meat, affirming that residue levels in meat products remain within regulatory limits and reinforces consumer safety and confidence.