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At least 1,009 records · Page 56Linked to original sources
PubMed1976

An in vitro-formed protamine-heparin complex as a model for a two-compartment store for biogenic amines.

The capacity of an in vitro-formed protamine-heparin complex (PHC) to store inorganic cations and biogenic amines was investigated. The PHC behaves like a two-compartment storage system. One compartment corresponds to the terminal free carboxyl groups of the protamine moiety and has the characteristics of a cation exchanger, with the ability to bind inorganic cations and biogenic amines in a reversible and rather unslective manner. The cations and biogenic amines therefore compete for and displace each other from the common ionic binding sites. The binding sites in the other compartment, corresponding mainly to the carboxyl groups of the heparin moiety, are only unmasked at high ionic concentrations and show a specific affinity for biogenic amines. The storage of amines in this compartment of the PHC is reversible but is dependent not only on simple ionic binding but evidently also on other attractive forces, such as dipole and hydrogen bonding.

Binding Sites↗
PubMed1976

The effects of neuraminidase and protamine chloride on potential clamp parameters of the node of Ranvier (Xenopus laevis).

The effects of neuraminidase and protamine chloride on the ionic currents associated with step changes in membrane potential were studied. Neuraminidase (a hydrolase which cleaves glycosidically bound sialic acid) had negligible effects on the permeability properties. The polycation protamine chloride decreased the sodium as well as the potassium currents. The sodium equilibrium potential decreased during the experiments which indicates a gain in internal sodium concentration. The analysis showed that the effects on the currents were caused by a decrease of the specific permeability changes. No shift along the potential axis of the potential dependent parameters was observed.

Action Potentials↗
PubMed1989

Expression of mouse protamine 1 genes in transgenic mice.

Mouse protamine genes are expressed exclusively in spermatids. Mouse protamine 1 (mP1) transcriptional regulatory elements can target the expression of either marked mP1 transgenes or mP1 chimeric genes to spermatids in transgenic mice. Sequences between -40 and -465 bp relative to the transcription start site are required for expression in spermatids, whereas sequences 3' of the point of translation initiation are dispensable. mP1 transcriptional regulatory sequences were used to direct the expression of a toxic gene product to spermatids. The phenotypic consequences of toxin expression in spermatids are described.

Animals↗
PubMed1988

Reversible inactivation of bladder surface glycosaminoglycan antibacterial activity by protamine sulfate.

Prior studies in our laboratory have shown that the bladder surface is lined with glycosaminoglycans which appear to be an important antibacterial defense mechanism that operates by resisting bacterial adherence and infection. The present study further implicates bladder surface glycosaminoglycans as the key antiadherent factor and also suggests a potential model for diseases (such as urinary tract infections) whereby the antiadherent surface of the bladder is inactivated biochemically. Protamine sulfate treatment of bladder tissue was found to significantly increase bacterial adherence to the urinary bladder by approximately 2.3-fold. This effect was reversed by a second treatment of the bladder with pentosanpolysulfate (a polysaccharide known to duplicate the surface antiadherent effect). Protamine sulfate had no effect on bacterial viability or bacterial adherence when bacteria were pretreated with it.

Animals↗
PubMed1989

A recombinant hepatitis B core antigen polypeptide with the protamine-like domain deleted self-assembles into capsid particles but fails to bind nucleic acids.

We have cloned in Escherichia coli both the complete core gene of hepatitis B virus and a truncated version of it, leading to the synthesis of high levels of a core-antigen-equivalent polypeptide (r-p22) and of an e-antigen-equivalent polypeptide (r-p16), respectively. We then compared the structural and antigenic properties of the two polypeptides, as well as their ability to bind viral nucleic acids. r-p16 was found to self-assemble into capsid-like particles that appeared similar, when observed under the electron microscope, to those formed by r-p22. In r-p16 particles, disulfide bonds linked the truncated polypeptides in dimers, assembled in the particle by noncovalent interactions. In r-p22 capsids, further disulfide bonds, conceivably involving the carboxy-terminal cysteines of r-p22 polypeptides, joined the dimers together, converting the structure into a covalently closed lattice. The protamine-like domain was at least partly exposed on the surface of r-p22 particles, since it was accessible to selective proteolysis. Finally, r-p22, but not r-p16, was shown to bind native and denatured DNA as well as RNA. Taken together, these results suggest that the protamine-like domain in core polypeptides is a nucleic acid-binding domain and is dispensable for the correct folding and assembly of amino-terminal and central regions.

Capsid↗
PubMed1976

Cardiovascular depressant effect of protamine sulphate: experimental study and clinical implications.

The mechanisms underlying protamine-induced hypotension and bradycardia were the subject of this investigation. Six groups of dogs with intact circulation were tested in controlled circumstances with various drugs. The following parameters were observed: femoral arterial pressure, central venous pressure, left ventricular pressure and its rate of rise, left ventricular contractile element velocity of shortening, maximal Vce, and cardiac output. The six groups were studied under these pharmacological conditions: ganglionic and adrenal medullary block with hexamethonium chlroide, postganglionic parasympathetic blockade by atropine sulphate, alpha and beta adrenergic receptor block by phenoxybenzamine and propranolol respectively, and depletion of endogenous histamine by compound 48/80 (a condensation product of p-methoxyphenethyl methylamine with formaldehyde). The last group was put on extracorporeal circulation to isolate the vascular tree from the heart. The effect of the drug on this isolated vasculature was observed by recording the femoral arterial pressure. Our findings show that the hypotension and bradycardia are produced by a direct effect of protamine on the myocardium and peripheral vascular system.

Animals↗
PubMed2005

Filter run time in CVVH: pre- versus post-dilution and nadroparin versus regional heparin-protamine anticoagulation.

BACKGROUND/AIMS: To study the effect of different modes of continuous veno-venous haemofiltration (CVVH) on filter run time (FRT). METHODS: We studied, in two consecutive prospective, randomised and crossover studies, 16 and 15 patients with acute renal failure during critical illness. Study A compared pre- versus post-dilution, and study B compared regional anticoagulation with heparin (pre-filter) and protamine (post-filter) (HP) versus nadroparin (NP) pre-filter. All CVVH sessions were standardised. Analyses were by Wilcoxon rank sum tests. RESULTS: Study A: During pre-dilution the median FRT was 45.7 vs. 16.1 h in post-dilution CVVH (p = 0.005). The median creatinine clearance during pre-dilution was 33 vs. 45 ml/min in post-dilution (p = 0.001). Study B: During NP, median FRT was 39.5 vs. 12.3 h during HP CVVH (p = 0.045). CONCLUSIONS: Pre-dilution CVVH results in the greatest FRT but a lower plasma creatinine clearance compared to post-dilution. Regional anticoagulation with heparin-protamine resulted in a significantly shorter FRT compared to systemic NP anticoagulation.

Aged↗
PubMed1991

Chromosomal assignment of four rat genes coding for the spermatid-specific proteins proacrosin (ACR), transition proteins 1 (TNP1) and 2 (TNP2), and protamine 1 (PRM1).

The genes for proacrosin, protamines, and transition proteins are exclusively expressed in haploid spermatogenic cells. From the analysis of mouse x rat cell hybrids which segregate rat chromosomes, the rat gene for proacrosin (ACR) was assigned to chromosome 7, that for transition protein 1 (TNP1) to chromosome 9, and the genes for transition protein 2 (TNP2) and protamine 1 (PRM1) to chromosome 10.

Acrosin↗
PubMed1995

The rat Prm3 gene is an intronless member of the protamine gene cluster and is expressed in haploid male germ cells.

We have cloned and sequenced the cDNA of a novel gene from the rat protamine gene cluster. This gene, preliminarily referred to as Prm3, is intronless and resides between the genes for protamine 2 and transition protein 2. Prm3 is transcribed from the same strand as these genes and is expressed in haploid stages of spermatogenesis. The 410-bp-long cDNA possesses an ORF, coding for a putative 104-amino acid polypeptide with a high content of glutamic acid.

Amino Acid Sequence↗
PubMedDate not supplied

The influence of heparin and protamine sulfate on platelet ADP and platelet factor 4 release and the expression of glycoprotein IIb/IIIa.

We present results concerning the pathogenic mechanism of heparin-induced thrombocytopenia type I. An ELISA was developed for directly measuring the expression of glycoprotein IIb/IIIa (GPIIb/IIIa) on platelets in the presence and absence of ADP and under the influence of various heparins. In addition, the release of ADP and platelet factor 4 (PF4) was measured in platelet-rich plasma. Heparin also induced the expression of GPIIb/IIIa without prior stimulation with ADP. On the other hand we could demonstrate that the addition of heparins and protamine sulfate to platelets resulted in a significant release of intracellularly stored ADP and PF4. These results suggested that heparin(oid)s modulate the expression of GPIIb/IIIa with ADP as a mediator, and that protamine sulfate is contraindicated as an antidote in heparin-induced thrombocytopenia.

Adenosine Diphosphate↗
PubMed1992

Platelet factor 4 efficiently reverses heparin anticoagulation in the rat without adverse effects of heparin-protamine complexes.

BACKGROUND: It has been observed that the reversal of heparin anticoagulation in humans by protamine sulfate (PS) results in various adverse reactions including leukopenia, thrombocytopenia, activation of complement, increased vascular permeability, systemic hypotension, pulmonary vasoconstriction, and pulmonary edema. The purpose of this study was to compare the efficacy and effects of native platelet factor 4 (PF4) and recombinant platelet factor 4 (rPF4) with those of PS in heparin neutralization in vivo, using a rat model. METHODS AND RESULTS: Sprague-Dawley rats were anesthetized with sodium pentobarbital, and the right femoral vein and carotid artery were cannulated. For determination of activated partial thromboplastin time, platelet count, white blood cell count, and complement titer, arterial blood samples were taken before and immediately after heparin (10 units/100 g) infusion and at several time points after the infusion of the neutralizing agent (PS, 0.1 mg/100 g; PF4, 0.5 mg/100 g). In separate groups of animals, mean arterial blood pressure was monitored throughout identical protocols and the lungs were prepared for histological examination. The anticoagulant activity of heparin was effectively reversed by all of the neutralizing agents (PS, PF4, and rPF4). Platelet count (48% of initial), white blood cell count (52% of initial), complement titer (60% of initial), and mean arterial pressure (20% decrease) decreased significantly in heparinized animals receiving PS but not in those receiving PF4 or rPF4. Lung interstitium appeared normal when heparin was followed by PF4; however, interstitial edema and hemorrhage were observed with heparin-PS. CONCLUSIONS: These results suggest that PF4 efficiently reverses heparin anticoagulation in the rat without the adverse effects of heparin-protamine complexes. Therefore, rPF4 may be an appropriate substitute for PS in patients undergoing cardiovascular surgery and other procedures that require heparin anticoagulation.

Animals↗
PubMed1988

Acute pulmonary vasoconstriction and thromboxane release during protamine reversal of heparin anticoagulation in awake sheep. Evidence for the role of reactive oxygen metabolites following nonimmunological complement activation.

When protamine (2 mg/kg) was injected intravenously into awake sheep 5 minutes after infusing heparin (200 units/kg), there was transient diffuse pulmonary vasoconstriction with mean pulmonary arterial pressure increasing from 18.0 +/- 0.7 to 43.8 +/- 2.7 mm Hg at 1 minute (x +/- SEM; n = 10). In addition, there was profound leukopenia (36.9 +/- 7.7% of baseline values at 2 minutes) with transpulmonary leukocyte sequestration and transiently elevated plasma concentrations of C3a (from 420 +/- 146 to 1,599 +/- 249 ng/ml; n = 3, p less than 0.01) and thromboxane B2 (from 0.30 +/- 0.05 to 6.3 +/- 2.8 ng/ml; n = 10, p less than 0.0001), without significant increases of plasma 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, leukotrienes, or histamine. Intravenous injection of protamine alone produced no hemodynamic effects and did not increase plasma levels of vasoconstrictor eicosanoids. Intravenous pretreatment with either a cyclooxygenase inhibitor or a hydrogen peroxide scavenger (dimethylthiourea) blocked both the increases of thromboxane levels and the pulmonary vasoconstriction.

Animals↗
PubMed1988

Protamine sulfate and fatal anaphylactoid shock.

A 73-year-old male underwent uneventful three-vessel coronary artery bypass grafting after which he received iv protamine sulfate for reversal of systemic heparinization. Shortly thereafter, the patient developed and succumbed to an anaphylactoid reaction attributed to protamine. The patient had none of the previously reported risk factors for hypersensitivity to the drug and was therefore not considered at high risk for such a severe adverse reaction. Although uncommon, the fatal outcome of this low-risk patient seriously addresses the need for alternative measures for heparin reversal.

Aged↗
PubMed2004

Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI.

Recently, there have been several reports using various superparamagnetic iron oxide (SPIO) nanoparticles to label mammalian cells for monitoring their temporal and spatial migration in vivo by magnetic resonance imaging (MRI). The purpose of this study was to evaluate the efficiency and toxicity of labeling cells using 2 commercially available Food and Drug Administration (FDA)-approved agents, ferumoxides, a suspension of dextran-coated SPIO used as an MRI contrast agent, and protamine sulfate, conventionally used to reverse heparin anticoagulation but also used ex vivo as a cationic transfection agent. After labeling of human mesenchymal stem cells (MSCs) and hematopoietic (CD34+) stem cells and other mammalian cells with ferumoxides-protamine sulfate complexes (FE-Pro), cellular toxicity, functional capacity, and quantitative cellular iron incorporation were determined. FE-Pro-labeled cells demonstrated no short- or long-term toxicity, changes in differentiation capacity of the stem cells, or changes in phenotype when compared with unlabeled cells. Efficient labeling with FE-Pro was observed with iron content per cell varying between 2.01 +/- 0.1 pg for CD34+ cells and 10.94 +/- 1.86 pg for MSCs with 100% of cells labeled. Cell labeling using these agents should facilitate the translation of this method to clinical trials for evaluation of trafficking of infused or transplanted cells by MRI.

Animals↗
PubMed2004

Incomplete reversal of enoxaparin toxicity by protamine: implications of renal insufficiency, obesity, and low molecular weight heparin sulfate content.

The use of low molecular weight heparin (LMWH) is increasing throughout North America and Europe for a number of reasons: 1). ease of use; 2). predictable dose response; 3). less heparin associated thrombocytopenia. However, aside from increased costs, LMWH has significant potential drawbacks: 1). poor reversibility; 2). tendency to accumulate in renal insufficiency; 3). less experience in subset patient groups such as morbid obesity. We report a case of a postoperative morbidly obese patient who developed enoxaparin toxicity secondary to acute renal failure that did not reverse with protamine sulfate infusion. In addition, we review the use of LMWH in renal insufficiency, dosing in obese patients,and the importance of sulfate content in the efficacy of protamine sulfate as a reversing agent for LMWH.

Acute Kidney Injury↗
PubMed1979

Protamine and polyarginine bacteriolysis. Similarities in its mechanism with chromatin DNA picnosis.

Protamine and polyarginine had bacteriolytic effects indicating their primary sites of action as being wall components and showing bacterial diversity genetically determined. Shake-incubation was required in producing cell-lysis. Studies on Bacillus subtilis revealed a high polycation multiplicity per cell in lytic event displaying multihit lysing kinetics; bacteriolysis was inhibited by trypsin, pronase, purified polyanionic wall polysaccharide, and by dissociative actions of salt hypermolarities used in isolation of nucleic acids. The inactivation of polycation lytic abilities during bacteriolysis was accompanied by modifications in electrophoretic running of protamine and polyarginine. It is suggested as mechanism of cell-lysis, the multiple zonal surface condensations of polyanionic wall components by basic polypeptides, likely similar with chromatin DNA picnosis. This analogy is discussed.

Anti-Bacterial Agents↗
PubMed1982

The effect of protamine on proteinuria and glomerular sclerosis in aminonucleoside nephropathy.

An administration of protamine sulfate combined with aminonucleoside of puromycin (AN) could produce in rats severe nephrotic syndrome and histological changes similar to focal glomerular sclerosis more distinctly than AN alone. This may be attributed to the action of protamine which seemed to enhance the effect of AN, causing polyanion loss at the glomerular basement membrane.

Animals↗