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[Effects of pH and ionic strength on interaction of different histone fractions and protamine with immobilized histone H4].

The interaction of histone H4 immobilized on Sepharose 4B with protamine and individual and total histone fractions from calf thymus has been studied. In accordance with the strength of their interaction with histone H4, the individual histone fractions can be arranged in the following order: H4 greater than H2a greater than H2b greater than H1 and protamine. The structure of the complexes, which are formed in a solution of a total histone fraction and specifically interact with the immobilized histone H4, depends on the ionic composition and pH of the medium.

Animals↗

Monitoring of blood coagulation in open heart surgery. I. Effects of conventional dosages of heparin and protamine.

In twenty unselected patients coming for surgery with cardio-pulmonary by-pass coagulation studies were performed. Laboratory results before and after by-pass were compared with serial measurements of ACtivated Clotting Times (ACT) during and after operation using conventional dosages of heparin and protamine. Values of ACT's are presented and compared with a previously published protocol according to Bull (1). Monitoring of ACT during operation was found to be easily applicable and highly desirable. Overdosage of both heparin and protamine was suggested as a correctable cause of proven abnormal coagulation after cardio-pulmonary by-pass.

Adolescent↗

[Mechanism of the stimulating effect of protamines on the infectivity of DNA phages].

The interaction of styrin (protamine from sturgeon milt) with E. coli spheroplasts was investigated with the aid of the fluorescent probe--5-dimethylamino-1-naphthalenesulfonyl-chloride (DNS). Not less than 40% of the total (15 mug ml-1) DNA-protamine concentration was bound to spheroplasts. A part of the protein was found in the isolated membranes and inside the cell. There was a correlation between the binding of protein with spheroplasts and its biological action. The dansylation somehow decreased the protein stimulating activity in transfection.

Animals↗

Neonatal depression after a protamine sulfate injection. A case report.

The intravenous administration of protamine sulfate in adults has been associated with acute hypotension, bradycardia and anaphylactoid reactions. However, no reports of its use in pregnancy have been available before. We describe a case of severe neonatal depression following maternal protamine sulfate injection immediately prior to delivery.

Adolescent↗

Complete selective absence of protamine P2 in humans.

Male sterility due to abnormal sperm morphology or motion has been widely reported, although relatively little has been published on the sperm nuclear protein abnormalities. We report the first cases worldwide of infertile patients having a complete selective absence of protamine P2 in the sperm nucleus. This provides a selective phenotype that will aid understanding of the mechanisms of synthesis, processing, or function of the P2 protamines. In addition, it is of marked immediate relevance to medicine as it allows the diagnosis of this type of human male sterility and the opportunity to understand the basis of this defect.

Electrophoresis, Polyacrylamide Gel↗

[Protamine sulfate reference standard (Control 941) of the National Institute of Health Sciences].

Three kinds of the candidate raw material for protamine sulfate was tested for preparation of the "Protamine Sulfate Reference Standard (Control 941)". The candidates were evaluated by physicochemical tests and anti-heparin tests. Analytical data were summarized in Table 1. Based on the above results, the best one having the highest anti-heparin activity was selected and authorized as the Japanese Pharmacopoeia Reference Standard (Control 941).

Chemical Phenomena↗

Ketanserin in the treatment of protamine-induced pulmonary hypertension.

The reversal of heparin by protamine may cause severe hemodynamic deterioration, characterized by systemic hypotension, pulmonary hypertension, and bronchoconstriction. A case report is presented concerning the administration of ketanserin in the treatment of pulmonary vasoconstriction and right ventricular failure following the infusion of protamine in a patient undergoing coronary artery bypass surgery and mitral valve replacement. The potential role of serotonin in the development of this serious complication is discussed.

Aged↗

The use of a heparin removal device: a valid alternative to protamine.

PURPOSE: Experiments were carried out to test the efficacy and safety of the heparin removal device, a plasmapheresis filter that binds and eliminates heparin, in the context of extracorporeal circulation. PROCEDURES AND FINDINGS: Six dogs were put on cardiopulmonary bypass after heparinization. Upon weaning, additional heparin was administered to obtain an activated clotting time above 900s. The animals were connected to the heparin removal device and with flows of 500 ml/min, activated clotting time, activated partial thromboplastin time and plasma heparin concentrations were normalised to baseline after 30 min. Hemodynamic parameters remained unaffected. A slight decrease in red and white blood cell count and in platelets was observed which however recovered spontaneously two hours after the filter procedure. No damage to blood components could be observed. CONCLUSIONS: The use of a heparin removal device is as efficient as systemic administration of protamine to reverse the effects of heparinization. It may prevent the adverse reactions linked to protamine administration and therefore be indicated in certain subgroups of patients undergoing cardiopulmonary bypass.

Animals↗

Serum fibrinogen-fibrin related antigen and protamine sulfate test in patients with septic abortion and acute renal failure.

Decreased platelet count and platelet adhesiveness as well as increased values of the protamine sulfate test were found in 26 patients with septic abortion (9 of them anuric). Serum fibrinogen-fibrin related antigen (FR-antigen) values, detected in 13 patients (7 of them anuric) were greatly increased although euglobulin lysis time was rather prolonged (more than 400 min). Less increased FR-antigen values were noted in 15 cirrhotic patients with enhanced fibrinolytic activity in the circulating blood (euglobulin lysis time less than 120 min). These findings suggest that an important increase of FR-antigen in serum is likely to indicate a local fibrinolytic response to an initial coagulation event. Since platelet count and adhesiveness as well as FR-antigen and protamine sulfate test were similarly changed in patients with septic abortion who developed acute renal failure and in those who did not, it seems that the above mentioned parameters are not predictive for the evolution of thrombotic deposits and for possible renal complications following an episode of disseminated intravascular coagulation.

Abortion, Septic↗

[Objectivization of the protamine sulfate test through photometric measurements].

The demonstration of monomeric complexes of fibrin in the blood is regarded as a secure sign of an increased consumption of coagulation factors in the sense of a consumption coagulopathy. As a simple and sensitive method for the demonstration of these intermediate products of the coagulation the protamine sulphate test proved its worth in clinical practice. The subjective judgment of this test-tube test frequently becomes difficult in the borderline region between normal and pathologic. On the basis of own comparative investigations it could, however, be demonstrated that by means of photometric measurements an objective and exact evidence about the result of the protamine sulphate test can be made. It is referred to the advantages in the judgment of the course of a consumption coagulopathy during the treatment.

Adult↗

Comparison of injection techniques for soluble and protamine zinc insulins in diabetes mellitus.

Soluble and protamine zinc insulins were given to six insulin-dependent diabetic patients using three different techniques of administration to determine whether the recommended single injection of the insulins, from separate syringes with the needle redirected, compared more closely with separate injections or with a single injection from the same syringe. It was shown that the mixture of the two insulins in the same syringe resulted in both a significant loss of the initial rapid effect of soluble insulin and an increased protamine zinc action with the risk of late night-time hypoglycaemia. A single injection of the insulins, using separate syringes and redirecting needle, gave at least as satisfactory control of the 24-hour blood glucose profile as when they were given by separate injections.

Adolescent↗

Comparison of two ultralente insulin preparations with protamine zinc insulin in clinically normal cats.

The absorption kinetics and glycemic effects of 3 long-acting insulin preparations (protamine zinc beef-pork insulin, ultralente beef-pork insulin, and ultralente human insulin) were evaluated in 9 healthy, adult, domestic shorthair cats (6 males, 3 females). A triple crossover study was performed, in which the serial serum concentrations of insulin and glucose were determined over a 24-hour period after SC administration of the 3 insulin preparations (dosage, 1.0 U/kg of body weight) at 3-week intervals. A control study was also performed in 4 of the cats by serially collecting samples for insulin and glucose determinations after administration of insulin diluent. After administration of protamine zinc insulin (PZI), mean (+/- SEM) serum insulin concentration increased significantly (P < 0.05) above baseline, reached a peak value (484 +/- 287 pmol/L) at 1 hour, and remained significantly (P < 0.05) higher than baseline at 24 hours. After administration of ultralente human insulin, the serum insulin curve was similar to that obtained after PZI administration, but mean serum insulin concentration took longer to peak (538 +/- 177 pmol/L at 4 hours). After administration of ultralente beef-pork insulin, mean peak serum insulin concentration was lower (220 +/- 54 pmol/L, not statistically significant) than that obtained after administration of PZI and ultralente human insulins; it then decreased to values statistically indistinguishable from baseline by 16 hours. The area under the serum insulin concentration curve for PZI (5,063 +/- 681 pmol x h/L) and ultralente human insulin (4,138 +/- 439 pmol x h/L) was significantly (P < 0.05) larger than that for ultralente beef-pork insulin (2,378 +/- 561 pmol x h/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A demonstration of androgen and estrogen receptors in a human breast cancer using a new protamine sulfate assay.

Separate receptors for estrogen and androgen are demonstrated in cells from metastic human breast cancer. By criteria of binding affinity, number of binding sites, and specificity of the receptor for different steroids, the receptors are shown to be distinguishable. The protamine sulfate receptor assay technique employed allows both kinds of receptor to be quantified conveniently and reproducibly without interference by plasma steroid-binding components.

Binding Sites↗

Immediate protamine administration and sheath removal following percutaneous coronary intervention: a prospective study of 429 patients.

We tested the approach of reversing anticoagulation following PCI and immediate sheath removal in 429 consecutive patients. On completion of the PCI, protamine was administered, and the vascular sheath was immediately removed. Stents were used in 364 patients (85%) and GP IIb/IIIa inhibitors were used in 52 patients (12%). Time to achieve hemostasis was 30 +/- 17 min. Minor groin bleeding occurred in six patients. One patient required repair of femoral pseudoaneurysm. Mean creatine kinase at 8 and 16 hr post-PCI were 129 +/- 35 and 145 +/- 32 units, respectively. Creatine kinase rose to > 3 times normal in 12 out of 350 patients (3.4%). Prior to 48 hr, eight patients (1.9%) required emergency PCI or coronary bypass surgery. Follow-up at 30 days observed no deaths and only three target vessel revascularizations (0.7%). In conclusion, immediate reversal of anticoagulation and sheath removal after PCI is safe and feasible.

Aged↗

Basic polyaminoacids and protamine stimulate enzyme release from frog muscles.

Polylysines, polyornithine, and protamine increased the release of creatine kinase (CK) and lactate dehydrogenase (LDH) from frog muscles. With 5 micrograms/ml (50 nM) of a polylysine of molecular weight 100,000, enzyme release reached peak values (ten-fold above control) within 30 minutes; subsequent removal of the polylysine did not reduce significantly the release rates. The effectiveness of the polycations increased with the degree of polymerization. Their effects were prevented by pretreatment of the muscles with polyanions (heparin or polyglutamic acids) and were reversed when heparin was applied within 30 minutes of exposure to polylysine. The initial stimulation of enzyme release by polylysine was attenuated by Ca-free solutions and by low temperature (4 degrees C). It is suggested that, while fiber damage can explain the increased loss of sarcoplasmic enzymes after prolonged treatment of frog muscles with polycations, other mechanisms (perhaps exocytosis) are involved in the stimulation of CK and LDH release during brief exposures to nanomolar concentrations of polylysines or polyornithine.

Animals↗

Expression of transferrin receptor and ferritin following ferumoxides-protamine sulfate labeling of cells: implications for cellular magnetic resonance imaging.

Ferumoxides-protamine sulfate (FE-Pro) complexes are used for intracellular magnetic labeling of cells to non-invasively monitor cell trafficking by in vivo MRI. FE-Pro labeling is non-toxic to cells; however, the effects of FE-Pro labeling on cellular expression of transferrin receptor (TfR-1) and ferritin, proteins involved in iron transport and storage, has not been reported. FE-Pro-labeled human mesenchymal stem cells (MSCs), HeLa cells and primary macrophages were cultured from 1 week to 2 months and evaluated for TfR-1 and ferritin gene expression by RT-PCR and protein levels were determined using Western blots. MTT (proliferation assay) and reactive oxygen species (ROS) analysis were performed. FE-Pro labeling of HeLa and MSCs resulted in a transient decrease in TfR-1 mRNA and protein levels. In contrast, Fe-Pro labeling of primary macrophages resulted in an increase in TfR-1 mRNA but not in TfR-1 protein levels. Ferritin mRNA and protein levels increased transiently in labeled HeLa and macrophages but were sustained in MSCs. No changes in MTT and ROS analysis were noted. In conclusion, FE-Pro labeling elicited physiological changes of iron metabolism or storage, validating the safety of this procedure for cellular tracking by MRI.

Cell Differentiation↗

Establishment of a partially informative porcine somatic cell hybrid panel and assignment of the loci for transition protein 2 (TNP2) and protamine 1 (PRM1) to chromosome 3 and polyubiquitin (UBC) to chromosome 14.

Porcine lymphocytes and fibroblasts were fused with 3 different permanent rodent cell lines, and 21 stable somatic cell hybrid lines were established. These hybrid cell lines were characterized cytogenetically by sequential QFQ banding and chromosome painting using fluorescence in situ hybridization with porcine DNA. The lines were further characterized by PCR analysis with primer pairs derived from genes with confirmed mapping information. Using this panel, we assigned the locus encoding polyubiquitin (UBC) to chromosome 14, and the transition protein 2 locus (TNP2) and protamine loci (PRM1 and PRM2) to chromosome 3. Two chromosomal localizations have been further refined by radioactive in situ hybridization. UBC maps to chromosome 14q12-q15 and TNP2 to 3p11-p12.

Animals↗