Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Protamines”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed1986

Protamine increases the affinity of 3'-phosphoadenosine 5'-phosphosulfate toward a sulfotransferase from chicken embryo epiphyseal cartilage.

A 3' -phosphoadenosine 5' -phosphosulfate (PAPS):chondroitin sulfate sulfotransferase from chicken embryo epiphyseal cartilage, which was partially purified, exhibited a molecular mass of 150 kDa. The enzymatic sulfation of totally desulfated chondroitin was activated up to 12-fold by protamine while the sulfation of partially sulfated chondroitin was activated only 3-fold. Protamine increased the affinity of the enzyme for PAPS about 4-fold when partially desulfated chondroitin was used as sulfate acceptor. The S 0.5 for the totally desulfated chondroitin was not affected by protamine, while high PAPS concentration slightly increased the affinity of the enzyme for the same sulfate acceptor. The possible role of these substances in the regulation of the sulfation of chondroitin sulfate is discussed.

Adenine Nucleotides↗
PubMed2005

Titrimetric method for determination of O-desulfated heparin in physiological samples using protamine-sensitive membrane electrode as endpoint detector.

O-Desulfated heparin (ODSH) is a promising new anti-inflammatory agent for the prevention of reperfusion injury following myocardial infarction or stroke. This partially desulfated heparin derivative has less anticoagulant activity than unfractionated heparin but retains the inherent anti-inflammatory properties of heparin. Thus, ODSH could be administered at the high doses needed to achieve desired anti-inflammatory function without risk of hemorrhage. However, given the very low anticoagulant activity of this species, traditional methods for heparin determination in clinical samples might not be well suited for ODSH measurements. In this article, a novel titrimetric method for detection of ODSH in buffer and plasma is described using a protamine-sensitive polymer membrane electrode as the detector. Titrations of ODSH with the heparin antagonist protamine yield sharp endpoints with sensitivity to ODSH in the micrograms per milliliter range for plasma samples. The stoichiometry for protamine interaction with ODSH is determined to average 1.39 microg protamine/microg ODSH in plasma. This technology is further applied to a toxicokinetic study of ODSH in an animal model, demonstrating the ability to detect the changes in ODSH concentrations in biological samples.

Animals↗
PubMed2005

Cyproterone acetate affects protamine gene expression in the testis of adult male rat.

The temporal effects of oral administration of cyproterone acetate (CPA), a progestational androgen receptor blocker, were studied on the fertility of adult male rat sires, at a dose of 20 mg kg-1 day-1 after 15 days of gavage. The treatment reduced the fertility and weights of accessory sex glands, without altering the serum levels of luteinizing hormone, follicle-stimulating hormone (FSH) and testosterone (T). Sperm counts were significantly reduced after treatment. Several changes were evident in caput epididymal sperm chromatin in treated rats. The in vitro decondensation rates of sperm chromatin and total fluorescent acridine orange (AO) dye uptake were enhanced. The fluorescent AO dye uptake by the double- and single-stranded sperm chromatin increased. The uptake of thiol-specific monobromobimane fluorescent dye by sperm chromatin was significantly reduced. Sperm of treated rats exhibited hypoprotamination. Protamine levels in the testis were significantly reduced after treatment. Androgen-binding protein (ABP) expression was significantly reduced in testis after treatment. A slight but significant increase was observed in cyclic AMP immunoexpression in testis after treatment. The expression and levels of transition proteins 1 (TP1) and 2 (TP2) as well as cyclic AMP response element modulator protein-tau were maintained at control levels in the testis of treated rats. The present study reports that androgen receptor occupation by CPA preferentially reduces the levels of spermatidal protamine in testis and spermatozoa involved in nuclear chromatin condensation. It is inferred that ABP could be mediating the effects of T in modulating the sequential expression of TPs and protamines during nuclear chromatin condensation. It is likely that indirect effects of T involve its aromatization in spermatids.

Androgen Antagonists↗
PubMed2005

Evaluation of nuclear transfer and transcription of plasmid DNA condensed with protamine by microinjection: the use of a nuclear transfer score.

In the present study, the nuclear delivery of a green fluorescence protein (GFP)-encoding pDNA condensed by protamine was investigated in terms of trans-gene expression after cytoplasmic (E(cyt)) and nuclear (E(nuc)) microinjection. To compare the nuclear transfer process, a novel parameter; the nuclear transfer (NT) score was introduced. The E(cyt) value for protamine/pDNA particles increased in a charge ratio-dependent manner. The calculated NT score showed that this increase results from an enhancement in nuclear transfer efficiency, which was also quantitatively confirmed by a recently developed confocal image-assisted three-dimensionally integrated quantification (CIDIQ) method. Moreover, E(nuc) for protamine/pDNA particles was significantly higher than that for poly-L-lysine/pDNA particles, suggesting that pDNA, when condensed with protamine, is more accessible to intra-nuclear transcription. Collectively, protamine is an excellent DNA condenser, with bi-functional advantages: improvement in nuclear delivery and efficient intra-nuclear transcription.

Cell Nucleus↗
PubMed2006

Global sperm deoxyribonucleic acid methylation is unaffected in protamine-deficient infertile males.

Sperm protamine-1 (P1) and protamine-2 (P2) concentrations were evaluated concomitantly with global DNA methylation patterns in a population of male infertility patients. Protamine quantification and immunofluorescence microscopy in conjunction with quantitative image analysis revealed no significant relationships between the P1/P2 ratio, P1 concentrations, or P2 concentrations and levels of global DNA methylation in mature spermatozoa.

Adult↗
PubMed2006

Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization pregnancy rates and predictive of fertilization ability.

OBJECTIVE: To evaluate whether aberrant sperm P1/P2 ratios are predictive of abnormal fertilizing ability and are related to in vitro fertilization (IVF) outcome. DESIGN: Prospective case-control study. SETTING: University-based infertility and IVF clinic. PATIENT(S): Forty-three male infertility patients with an abnormally reduced P1/P2 ratio, 251 patients with a normal P1/P2 ratio, and 121 patients with an abnormally elevated P1/P2 ratio. INTERVENTION(S): Human IVF, the sperm penetration assay (SPA), and sperm protamine quantification via nuclear protein extraction, gel electrophoresis, and densitometry analysis. MAIN OUTCOME MEASURE(S): Sperm P1/P2 ratios; P1 and P2 quantities; SPA scores; and IVF-fertilization, embryo-quality, pregnancy, delivery, and spontaneous-abortion rates. RESULT(S): Standard IVF fertilization rates and SPA scores were significantly reduced in patients with abnormally low and high P1/P2 ratios. In vitro fertilization embryo quality was comparable between these groups, but pregnancy rates were significantly reduced in patients with abnormally reduced P1/P2 ratios. CONCLUSION(S): The P1/P2 ratio has a significant relationship to sperm fertilization ability. The relationship between protamines and fertilization ability is not understood but may be either a reflection of generalized abnormalities during spermiogenesis or an indication of protamine deficiency acting as a regulator or checkpoint of spermatogenesis.

Biomarkers↗
PubMed2004

Determination of protamine peptides in insulin drug products using reversed phase high performance liquid chromatography.

This paper describes the establishment and validation of a reversed phase HPLC (RP-HPLC) method for determination of protamine peptides in protamine sulphate raw material and insulin drug products, discusses the analytical results obtained for a number of protracted insulin formulations and the potential of the method in connection with protamine sulphate raw material and final drug product quality control.

Chromatography, High Pressure Liquid↗
PubMed2006

A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: the EVOLUTION-ON study.

OBJECTIVES: Unfractionated heparin and its antidote, protamine sulfate, allow for rapid and reversible anticoagulation during cardiac surgery with cardiopulmonary bypass, yet limitations exist, including a variable dose-response, dependence on a cofactor for anticoagulant effect, and antigenic potential. This trial was performed to evaluate the safety and efficacy of bivalirudin as an alternative to heparin with protamine reversal in on-pump cardiac surgery. METHODS: We conducted a randomized, open-label, multicenter trial comparing heparin with protamine reversal to bivalirudin in patients undergoing cardiac surgery with cardiopulmonary bypass. The primary objective was to demonstrate comparable rates of in-hospital procedural success defined as freedom from death, Q-wave myocardial infarction, stroke, or repeat revascularization. Twenty-one institutions enrolled 101 patients randomized to bivalirudin and 49 patients to heparin treatment. RESULTS: The primary end point of procedural success was not significantly different between the bivalirudin arm and the heparin/protamine arms at 7 days, 30 days, or 12 weeks' follow-up. Adequate anticoagulation was achieved in all patients. Secondary end points including mortality, 24-hour blood loss, overall incidence of transfusions, and duration of surgery were similar between the two arms. CONCLUSIONS: Bivalirudin is a safe and effective anticoagulant for patients undergoing a wide range of cardiac surgical procedures with cardiopulmonary bypass. Procedural success rates with bivalirudin were similar to rates in patients receiving heparin anticoagulation, with no difference in mortality. Avoidance of blood stasis and attention to the intraoperative medical management of patients is critical for successful use of bivalirudin during cardiopulmonary bypass.

Aged↗
PubMed1997

In-laboratory removal of femoral sheath following protamine administration in patients having intracoronary stent implantation.

Two hundred twenty-eight patients with successful coronary stent implantation were randomized either to protamine administration and femoral sheath removal (group I, n = 117) or no heparin neutralization and delayed sheath removal (group II, n = 111). The hospital stay after treatment was shorter in patients receiving protamine; therefore, protamine use for neutralizing circulating heparin may be safely administered immediately after stent implantation.

Anticoagulants↗
PubMed1988

Hemodynamic and morphologic alterations after experimental administration of protamine sulfate.

The hemodynamic, hematologic, and morphologic effects induced by protamine sulfate have been studied in 28 dogs divided into 6 groups. All of the groups were given heparin (3 mg/kg body weight) and Groups I, II, III, and IV were given protamine (5 mg/kg body weight). Group I (control group) was not subjected to extracorporeal circulation. The other groups had the following interventions: Group II, cardiopulmonary bypass without aortic clamp, hypothermia, or cardioplegia; Groups III and V, hypothermia of 25 degrees C, aortic clamping for 25 minutes, administration of cardioplegic solution, and slow rewarming; and Groups IV and VI, the same as Groups III and V, but with rapid rewarming. After injection of protamine sulfate, there was a decrease in mean arterial pressure due to peripheral vasodilation and an increase in the mean pulmonary pressure due to increased pulmonary vascular resistance; marked diminution of the number of circulating platelets aside from the extracorporeal circulation; a decrease in the contractility of both ventricles with augmented right ventricular work and decreased cardiac output; and right ventricular edema in Groups I, II, III, and IV. These alterations were most evident in Groups III and IV.

Animals↗
PubMed1976

Histones instead of protamines in terminal germ cells of infertile, oligospermic men.

A study was carried out, by means of polyacrylamide gel electrophoresis, of the nucleoproteins of spermatozoa from infertile, oligospermic patients affected by partial idiopathic spermatidic arrest. Results in a normal group of men, in agreement with previous reports, showed the presence of protamines in mature spermatozoa. Data relative to nucleoproteins in "spermatozoa" from the infertile patients showed that, in these cells, no protamines were detectable, but histones exclusively. These findings suggest that in our patients a maturational defect of spermatogenesis exists both at the meiotic level (a DNA content double that of spermatozoa) and during spermatidic maturation (no substitution of histones by protamines). Therefore, the nuclear maturation of these terminal germ cells is that typical of that of primary spermatocytes.

Adult↗
PubMed1994

Protamine sulfate and vancomycin are synergistic against Staphylococcus epidermidis prosthesis infection in vivo.

We have previously demonstrated that the quaternary amine, protamine sulfate (PS), is bactericidal against Staphylococcus epidermidis. In an attempt to decrease genitourinary prosthesis infection rates, we examined the ability of PS as a wound irrigant to inhibit Staphylococcus epidermidis viability. Eighty-seven Sprague-Dawley rats were studied by implanting a sterile silicone pellet in their dorsum. The pellet was inoculated with Staphylococcus epidermidis and the rats were divided into four groups based on the wound irrigant employed after inoculation: (1) control (sterile water) (2) vancomycin; (3) PS; (4) vancomycin + PS. All rats received perioperative and daily intramuscular vancomycin, and the pellets were explanted on postoperative day 28 and cultured. The infection rates were: (1) control 77%, (2) vancomycin 50%, (3) protamine sulfate 67%, and (4) protamine sulfate and vancomycin 19%. The differences between (2) vancomycin versus (4) vancomycin + PS and (3) PS versus (4) vancomycin + PS were significant (p = 0.05 and p < 0.005). The data suggest that PS potentiates vancomycin as a wound irrigant in prosthesis implantation.

Animals↗
PubMed2001

Assessment of murine bladder permeability with fluorescein: validation with cyclophosphamide and protamine.

OBJECTIVES: Bladder hyperpermeability should result in elevated blood levels of intravesically administered agents. Reabsorption from a hyperpermeable bladder should result in prolonged urinary excretion of an agent after parenteral administration. To test these hypotheses, urinary clearance and plasma levels of sodium fluorescein (NaF) were measured in mice before and during cyclophosphamide (CYP) and protamine-induced hemorrhagic cystitis. METHODS: To measure the plasma uptake of NaF from the bladder, 10 mg/mL NaF was instilled, either by catheter or retrograde urethral infusion, 15 minutes before retro-orbital or ventricular sampling. The plasma levels were measured 24 hours and 14 days after exposure to CYP 300 mg/kg or 15 minutes after instillation of protamine 10 mg/mL. Hourly urine concentrations were measured immediately after intraperitoneal administration of 10 mg/kg NaF. Pretreatment samples were compared with those obtained 24 hours after intraperitoneal administration of 300 mg/kg CYP. RESULTS: Urinary NaF excretion was delayed in CYP-exposed mice. A bi-exponential model provided an appropriate fit of the data, both before and after CYP administration. The plasma levels of NaF were significantly elevated at 24 hours and 14 days after CYP exposure when sampled by ventricular nick or retro-orbitally. The median concentration of fluorescein in the protamine-treated mice was significantly higher than in the control mice. CONCLUSIONS: Fluorescein can be used to measure alterations in bladder permeability after bladder mucosal injury in mice. Urinary excretion of NaF is a bi-exponential process that is delayed after bladder mucosal injury, presumably because of increased mucosal permeability and resorption from the urine into the bloodstream.

Analysis of Variance↗
PubMed1999

Improved postprandial blood glucose control and reduced nocturnal hypoglycemia during treatment with two novel insulin lispro-protamine formulations, insulin lispro mix25 and insulin lispro mix50. Mix50 Study Group.

The objective of this 6-month, open-label, randomized, two-period crossover study was to compare glycemic control when patients were treated with (1) 2 manufactured premixed insulin formulations containing insulin lispro and a novel insulin lispro-protamine formulation, neutral protamine lispro (NPL), and (2) 2 manufactured premixed human insulin formulations, human insulin 50/50 and human insulin 30/70. One hundred individuals, 37 with type 1 diabetes mellitus (12 females, 25 males; mean age, 39.4 years; mean body mass index [BMI], 24.8; mean duration of diabetes, 12.9 years) and 63 with type 2 diabetes mellitus (33 females, 30 males; mean age, 59.0 years; mean BMI, 28.4; mean duration of diabetes, 12.6 years), were treated with insulin lispro mixtures. Insulin lispro Mix50 (50% insulin lispro/50% NPL) and human insulin 50/50 (50% regular insulin/50% neutral protamine Hagedorn [NPH] insulin) were administered before breakfast; insulin lispro Mix25 (25% insulin lispro/75% NPL) and human insulin 30/70 (30% regular insulin/70% NPH) were administered before dinner. Blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG <3.0 mmol/L), insulin dose and timing of dose before meals, and hemoglobin A1c were measured. Mean doses of insulin lispro and human insulin mixtures were similar overall and for both diabetes subgroups. However, compared with human insulin mixtures, twice-daily administration of insulin lispro mixtures resulted in improved postprandial glycemic control, similar overall glycemic control, and less nocturnal hypoglycemia, as well as offering the convenience of dosing closer to meals.

Adult↗
PubMed2003

Encapsulation of protamine sulphate compacted DNA in polylactide and polylactide-co-glycolide microparticles.

This paper details the development and characterisation of a DNA-loaded microsphere system for gene delivery purposes. Encapsulation of DNA in microspheres was carried out by precondensation of the DNA with protamine sulphate, followed by encapsulation in a polymeric microsphere using a water-oil-water (w/o/w) solvent evaporation-emulsion process. The polymers used were polylactide and polylactide-co-glycolide. The amount of DNA encapsulated in the microsphere formulation was dependent on the weight ratio of protamine sulphate: DNA, with higher ratios (0.87:1 or 2:1) giving better encapsulation efficiencies (> or =62%). Additionally, compared to non-compacted DNA, the encapsulation of a protamine sulphate:DNA complex increased protection of the DNA against nuclease and decreased shear effects during processing. The release profile of DNA was shown to be dependent on the polymer type and polymer molecular weight. DNA was released relatively quickly from the microspheres and the released DNA primarily existed in a relaxed state. However, in vitro transfection experiments indicated that the DNA was still active upon release from the microspheres.

DNA↗
PubMed1978

Radiation exposure and recognition of electron microscopic images of protamine at high resolution.

The effect of radiation exposure on visual recognition of individual macromolecules of the protein protamine was examined using high resolution electron microscopy in scanning transmission, fixed beam transmission, dark field and bright field, and recording of images on plates or via video imaging systems including image intensifiers and digital image storage. Loss of recognition of protamine, including its 5 A substructure, followed approximately three-hit kinetics with a Do on the exponential portion of the curve of about 470 e/A2. In spite of the inevitable chemical damage at high doses, virtually all molecules in orientations that exhibited the characteristic protamine structure could still be recognized in dark field scanning transmission or fixed beam bright field at 100-200 e/A2. Recognition fell from 30 to 6% when doses were increased from 1000 to 2000 e/A2 in fixed beam dark field. Exposure rates, varied over seven orders of magnitude from 0.15 e/A2-s to 3 X 10(6) e/A2-s, had no effect at all on the recognition of structures.

Animals↗
PubMed1998

Determination of protamine sulphate in drug formulations using high performance liquid chromatography.

Protamine sulphate, which has the property of neutralising heparin, is determined in pharmaceutical formulations using spectrophotometric (BP 1995) or biochemical methods (USP XXIII 1995). Accuracy of these methods is not very high. We applied the HPLC technique for the assay of protamine sulphate in a gel formulation. The assay was carried out on a diol-type column with a mobile phase containing 8% acetonitrile in 0.15% trifluoroacetic acid at pH 2.5. The flow rate was 1.0 ml min(-1). The results obtained show that HPLC can be used for the determination of protamine sulphate in pharmaceutical preparations. The method is rapid and more accurate than those described until now.

Chromatography, High Pressure Liquid↗
PubMed1992

The gene for human transition protein 2: nucleotide sequence, assignment to the protamine gene cluster, and evidence for its low expression.

We have isolated the gene for transition protein 2 (TNP2) from a human cosmid clone that contains the genes for protamines 1 and 2. A nucleotide sequence of 1776 bp that comprises 268 bp of the 5'-noncoding region, 400 bp of exon 1, 849 bp of an intron, 17 bp of exon 2, and 242 bp of the 3'-noncoding region was determined. A modified CAT box, a TATAA box, and two possible polyadenylation sites were identified. Transcripts in testicular RNA could be detected only by RT-PCR and RNase protection assays. By direct sequencing of the PCR products, a cDNA sequence was established. It can be deduced from these results that, in contrast to other mammalian genes, the human TNP2 gene is expressed at a very low level. The human gene differs from that of other mammalian species by the absence of a conserved GCCATCAC nucleotide sequence in the 3'-untranslated region. Since both protamine genes are known to be localized on chromosome 16p13.3, this chromosomal localization holds true for the human TNP2 gene as well. The genes for both protamines and TNP2 are arranged in a DNA stretch of 13 kb.

Amino Acid Sequence↗