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At least 721 records · Page 40Linked to original sources
PubMed1992

[Changes in glomerular polyanions and ultrastructure induced by protamine in rats].

Perfusion of rat kidneys with polycation protamine, resulted in pathologic alterations of glomeruli very similar to those observed in minimal change nephrotic syndrome in human. In the experimental model, colloidal iron stained kidney tissue sections were analyzed quantitatively by image analyzer and stereology in combination with the observation of other glomerular ultrastructure. The mean thickness of foot processes and the foot processes making up the volume fraction of glomerular capillary were determined. The studies showed that there was a significant decrease in glomerular polyanions of kidneys perfused with protamine as compared with that of the control group (P < 0.01). The glomerular alterations included swelling and fusion of foot processes and narrowing or loss of filtration slits. Electron-dense particles formed by binding of protamine to polyanions were seen primarily in the lamina rara externa of glomerular basement membrane and also along the lamina rara interna and on the foot process surface, which showed the distribution feature of glomerular filter. These results suggest that the ultrastructure alterations of glomeruli may result from the neutralization of polyanions by perfusion with protamine.

Animals↗
PubMed2005

Can lean body mass be used to reduce the dose of heparin and protamine for obese patients undergoing cardiopulmonary bypass?

Increasing numbers of obese patients are presenting for cardiac surgery. The convention for heparin dose dictates that a bolus of 300 IU heparin per kilogram of total body weight (TBW) is administered before CPB. During CPB, the activated clotting time (ACT) is maintained for longer than 480 seconds. At the end of the procedure, protamine is administered to neutralize heparin and achieve hemostasis. Both of these drugs can have serious side effects: heparin can induce thrombocytopenia, and protamine has been known to cause reactions in patients allergic to fish, vasectomized men, and some patients with insulin-dependent diabetes. The calculation of lean body mass (LBM) may be a more accurate method of determining drug doses as opposed to TBW and may avoid giving obese patients a relative overdose of heparin, which must subsequently be neutralized with protamine. LBM can be determined by different methods. This study used bio-electrical impedance analysis as a simple, quick, and accurate method of calculating LBM. A comparison was made between two groups of patients whose body mass index (BMI) was >27 kg/m2: Group 1, n = 13, mean BMI = 32, mean body fat = 36% received the conventional dose of 300 IU/kg heparin for their TBW. Group 2, n = 14, mean BMI = 31, mean body fat = 35% received a dose of 300 IU/kg heparin for their calculated LBM. ACT was conducted before and after heparin administration. Additional heparin was administered as required to achieve target ACT > 400 s. Mean ACT results and total heparin doses were analyzed using unpaired two tailed t tests. Our results indicate that with care, a reduction of as much as 25% in the doses of heparin (p = 0.0001) and protamine can be achieved for a substantial number of patients classified as overweight or obese.

Aged↗
PubMed1990

Reduction in rat mesentery mast cell staining after degranulation by protamine. A competitive antagonism.

Degranulation of rat mesentery mast cells by increasing concentrations of protamine causes a parallel decrease in the numbers of mast cells stained with toluidine blue or with berberine sulfate. No decrease in mast cell numbers occurs when degranulation is inhibited. Since protamine does not enter into non stimulated mast cells, these results suggest that this reduction in mast cell numbers is caused by the binding of protamine to the anionic sites of heparin of exocytosed granules thereby preventing their staining. There seems to be a competitive antagonism between protamine and toluidine blue at the anionic sites of heparin for increasing concentrations of toluidine blue progressively reverse the reduction in mast cell numbers.

Animals↗
PubMed2006

[Clinical analysis of yuziwan in the treatment of 30 sterile men with abnormal protamine].

OBJECTIVE: To study the clinical application and effects of Yuziwan in the treatment of male sterility patient with abnormal protamine. METHODS: The changes of protamine, semen and sex hormones of 30 male sterility patients treated by Yuziwan were observed before and after the treatment. RESULTS: After a 3-month course of treatment, 9 cases were cured, 15 obviously improved and 6 failed to respond. The ratio of histone to protamine was decreased from (1.34 +/- 0.52) before the treatment to (0.72 +/- 0.32) after it, with significant difference (P < 0.01), the semen quality obviously improved (P < 0.05), and the LH and T levels markedly raised (P < 0.01). Yuziwan evidently improved the abnormal protamine, sperm quality and endocrine function of the sterility patients. CONCLUSION: Yuziwan has good curative effect on male sterility.

Adult↗
PubMedDate not supplied

[Effect of protamine on the composition of blood lipoproteins at various periods of hypercholesterolemia in rabbits].

Protamine has been studied for its effect on changes in the protein-lipid composition of main fractions of blood lipoproteins in different periods (1- and 7-months) of hypercholesterolemia in rabbits. Daily introduction of protamine to intact animals for 30 days did not change the studied parameters. Results of analysis of the protamine action against the background of the 1-month hypercholesterolemia testify to an increase of the protein and cholesterin concentration in apoB-containing lipoproteins. A moderate increase of the cholesterin concentration in the HDL composition has been observed, the protein concentration remaining at high level. The atherogenic diet for 7 month has induced in animals subjected to its dyslipoproteinemia and atherosclerosis of vessels. Under these conditions protamine has inhibited "proatherogenic" alterations in the composition of lipoproteins. The concentration of protein, cholesterin and triglycerides in the apoB-containing fractions decreased and the concentration of total cholesterin and triglycerides in the blood serum fell considerably.

Animals↗
PubMed1990

[Cellular mechanisms of pulmonary vasoconstriction in an experimental model of protamine reversal of heparin].

The neutralisation of heparin by protamine can cause life-threatening pulmonary hypertension. We studied this reaction in animal experimental models (sheep and rat) to determine the cellular mechanisms of the pulmonary vasoconstriction. The heparin-protamine reaction (H-P) with pulmonary hypertension (peak of mean pulmonary artery pressure = 57.3 +/- 2.2 mmHg), decreased cardiac output (-20%), leukopenia (-30%) and plasma release of high concentrations of thromboxane B2 (6.03 +/- 0.03 ng/ml) was constantly observed in sheep. The reaction was identical in sheep with induced thrombocytopenia by administration of antiplatelet antibodies. On the other hand, the neutralisation of heparin by protamine in rats did not cause thromboxane release or pulmonary vasoconstriction although the leukopenia was identical to that observed in sheep. Therefore, the platelets and white blood cells did not seem to cause the pulmonary vasoconstriction induced by the H-P complexes. The inter-species difference observed suggests that pulmonary intravascular macrophages may be responsible for the liberation of eicosanoids and acute pulmonary vasoconstriction occurring during the neutralisation of heparin by protamine.

Animals↗
PubMed1990

[Effects of protamine on blood lipoproteins in the early period of hypercholesterolemia in rabbits].

The content of protein, cholesterol and triglycerides in chylomicrons and different classes of blood serum lipoproteins was studied under protamine action in early (1 month) hypercholesterolemia. Except the low density lipoproteins the amount of triglycerides in the particles studied was practically unchanged. The content of proteins in all classes of lipoproteins was greatly increased and this may indicate that protamine activates the blood lipoprotein system. The enrichment of lipoproteins with cholesterol may be taken as being a result of protamine action in early hypercholesterolemia. The peculiar feature in the effect of protamine on mentioned lipoprotein components was that the protein/cholesterol ratio didn't change in chylomicrons, decreased in very low density lipoproteins and low density lipoproteins and increased in high density lipoproteins as compared with controls.

Animals↗
PubMed1990

Zinc-induced secondary structure transitions in human sperm protamines.

Using CD we show that human group II protamines undergo novel zinc-dependent secondary structure transitions. The CD spectra of protamine is characteristic of random coil proteins with a large minima at 197 nm. Upon the addition of 1 mM zinc, the magnitude of this minima is decreased by 44%. This spectral change is not induced by 1 mM calcium or magnesium. Cadmium, which has chemical properties similar to zinc, can also induce the structural transition although not as effectively as zinc. The spectral changes that accompany zinc binding are indicative of an increase in beta-turn and anti-parallel beta-sheet structures. This is consistent with the predicted secondary structure for protamines which is dominated by beta-turns. Our data support a model in which protamine adopts a folded structure in the presence of zinc. We propose that a zinc-modulated structure is physiologically significant considering the relatively high levels of zinc in human sperm.

Amino Acid Sequence↗
PubMed1989

Chicken protamine genes are intronless. The complete genomic sequence and organization of the two loci.

A positive cosmid clone obtained from a pwe15-rooster DNA library using a chicken protamine cDNA probe reveals the complete sequence of the two loci for the rooster protamine genes. The organization of these two loci within the cosmid clone matches that of genomic DNA. The copy number per haploid genome is two. The sequence for the rooster protamine predicted from the coding region shows differences from that previously determined at the protein level (Nakano, M., Tobita, T., and Ando, T. (1976) Int. J. Peptide Protein Res. 8, 565-578). A recent re-determination of the rooster protamine amino acid sequence (28 residues from the N terminus) matches that predicted from the genome rather than the sequence of Nakano et al. (1976). Both loci are intronless and the gene is extremely GC-rich (88% in the coding region). The 5' region of the gene contains a typical TATAAA box, several CG boxes, as well as other characteristic motifs. The 3' region of the gene contains the polyadenylation signal and several GT repeats of known Z-DNA forming potential. A correlation between the functional map of the gene and the tendency of the DNA to bend or to adopt the Z-conformation is presented and possible roles for these conformations in the transcription of this gene are discussed.

Amino Acid Sequence↗
PubMed1987

[Immunocytological distribution of HP1 group protamines in human testes and ejaculated spermatozoa].

Specific antisera have been obtained against the purified human sperm protamine HP1b. The specificity of antibodies was assessed in dot-blot and western-blot assays. Antibodies showed high binding to protamine HP1 group. Nevertheless cross-reactivity between HP1 and the other protamines (HP2 - HP3 - HP4) could not be excluded. Immunohistochemical studies revealed that protamines HP1 were detected in nuclei of ejaculated sperm after chromatin decondensation. In testis, they appeared in nuclei of elongating spermatids.

Ejaculation↗
PubMed1987

Hemodynamics of protamine administration. Comparison of right atrial, left atrial, and aortic injections.

Protamine administration for heparin reversal after cardiopulmonary bypass on occasion is associated with mild to severe hemodynamic deterioration. The route of administration may modify these reactions. A prospective randomized study was done in 68 patients undergoing isolated coronary artery bypass grafting. The route of protamine administration was randomized in a balanced fashion between right atrium, left atrium, and aorta. The preoperative and operative characteristics of the three groups were similar. Hemodynamic measurements were recorded before cannulation, after removal of the venous drainage catheter, and 1 minute, 5 minutes, and 10 minutes after protamine administration. Hypotension occurred in 11 patients with no significant difference among the three groups. The hypotension was immediate in three patients in whom route of administration was the aorta. The overall hemodynamic changes observed for the three treatment groups were not significantly different. An analysis for type II error indicated that it was unlikely that an important difference had been missed. We conclude that the route of administration does not affect the hemodynamic changes associated with protamine administration. We did not observe a case of severe hemodynamic deterioration, so that we cannot assess the effect of route of administration on the severity of an anaphylactic reaction.

Aorta↗
PubMedDate not supplied

Protamine sulphate and heparin rebound following open-heart surgery.

The efficacy of heparin reversal was investigated in 35 patients undergoing open-heart surgery. A total protamine sulphate dose of 3.0 mgs/kg was administered in divided doses and given as a continuous infusion. On this regime complete heparin neutralisation was observed 10 min after decannulation, but heparin levels were again detectable in 29% of cases 2 hours later. This phenomenon was found to correlate with the total circulating load of heparin to be neutralised. All cases with detectable postoperative heparin levels had in-vivo protamine sulphate: heparin ratios of less than 1.6. These data suggest that in-vitro assays of protamine sulphate neutralisation of heparin may seriously underestimate the required dose of protamine sulphate following open-heart surgery.

Adult↗
PubMed1985

Adverse reactions to protamine.

Adverse responses to protamine are most likely multifactorial in nature. Mechanisms include immune-mediated anaphylaxis, complement-mediated and non-complement-mediated anaphylactoid reactions, and catastrophic pulmonary vasoconstriction. Some patients may be at higher risk for an adverse reaction to protamine. Whereas patient historical data may influence the decision to administer protamine, once administration is decided on all patients should receive protamine in a cautious manner. Rechallenge may be hazardous, but has occurred without problem in some patients.

Anaphylaxis↗
PubMed1979

Measurement of the heparin neutralizing capacity of protamine.

Several methods of estimating the heparin neutralizing capacity of protamine were investigated for their reliability and practicability. The results from two chemical methods were compared with those from two in vitro biological assays, one of which was the method of the British Pharmacopoeia (1973). An in vivo method using mice was used to assess the accuracy of the in vitro test methods. Three standard heparin preparations were tested against the W.H.O. 1st International Reference Preparation for Protamine. Two of the heparin preparations were of mucosal origin, one of which was the 3rd International Standard, and the third heparin preparation was of lung origin (the 2nd International Standard for Heparin). The mean neutralization values (all methods) of heparin by protamine for a House Reference Preparation and the 3rd and 2nd International Standards for Heparin were 95.8, 109.8 and 89.9 units per mg of Protamine, respectively. All methods read the House Reference Preparation to have a lower value than the 3rd International Standard, which had a higher value than the 2nd International Standard for Heparin. There was a constant relationship between the results of any one method and those of another. The chemical and in vitro biological methods gave results of comparable precision although the latter required a greater degree of technical skill and time to perform.

Animals↗
PubMedDate not supplied

[Quantitative determination of proteins in the cytosol fractions of human and rat sex steroids after precipitation with protamine sulfate].

A simple procedure is developed for estimation of proteins after precipitation with protamine sulfate in cytosol fraction of human tissues-target dor sex steroids (prostate adenoma, cancer of prostate, mammalian gland cancer) and in similar target tissues of rats (ventral prostate and uterus). Human blood serum did not interfere with the protein estimation after the protamine sulfate precipitation. This method for estimation of protein using protamine sulfate might be critically important in calculation of the binding capacity of target-tissues with sex steroids (quantitative estimation of receptors), especially in human tissues because the interference of blood proteins is eliminated. The efficiency of the procedure developed was confirmed by comparative study of binding capacity of the tissues of prostate adenoma, cancer of prostate and mammalian gland cancer towards 3H-17 beta-estradiol and 3H-dihydrotestosterone, calculated per total protein and the protein precipitated by protamine sulfate.

Animals↗
PubMed1984

Protamine sulfate inhibition of serum-induced mitogenic responses: differential effects on normal and neoplastic cells.

Protamine sulfate reversibly inhibits serum-induced mitogenic stimulation of several nontransformed and neoplastic cell types in vitro. Fifty percent inhibition was induced by approximately 120-150 micrograms protamine sulfate/ml. Cells were affected directly, and inhibition depended on the duration of cell exposure. Heparin, chondroitin sulfate, heparan sulfate, and dextran sulfate neutralized protamine sulfate effects during the early stages of treatment. Nontransformed cells [bovine aortic endothelial cells, adult human gingival fibroblasts (strains 423 and 1101), fetal rat skin (strain 921-K) and muscle fibroblasts] required longer exposure to induce inhibition than did neoplastic cells [rat 3-methylcholanthrene-induced fibrosarcoma cell lines (MCA-6 and MCA-9), a macrophage-like cell line (NCTC-3749), Walker 256 rat carcinoma cells (ATCC-CCL-38), rat Morris hepatoma cells (ATCC-CCL-144), murine melanoma cells (B16), and rat bladder squamous cell carcinoma cells (804-G)]. Other polycationic compounds, including histone type VIII-S, poly-L-lysine, poly-L-arginine, and protamine (free base), were also effective inhibitors, whereas the basic proteins cytochrome c and lysozyme had no effect. Poly-L-histidine, poly-L-glutamic acid, poly-L-aspartic acid, and dextran blue also had no inhibitory effect.

Animals↗
PubMed1980

[The influence of artificial infrared radiation and microwaves upon mucopolysaccharides, protamine sulphate, and mucin in virus-infected organ cultures (author's transl)].

Infrared radiation and 1-2 micron microwaves influenced the infectivity of Newcastle Disease Virus (NDV) upon chick embryo tracheal tissue in such a way that the expected destruction of ciliated epithelium turned out to be incomplete or did not take place at all, respectively. Due to the fact that direct damaging of viruses following such radiation was not shown and that it was our intention to arrange the experimental set-up as if natural rhinolaryngeal conditions had induced the infection of the mucous membrane of the respiratory tract a study was performed in order to establish the radiation influence on mediator substances involved in the virus infection of mucous membranes. The mucopolysaccharides, chondroitine sulphate and hyaluronic acid, as well as mucin served as models; in addition protamine sulphate was used for reasons of comparison. The influence of the above substances upon NDV-infection in organ cultures and the effect of electromagnetic waves upon such influence were studied. By choosing a virus concentration of 10(-8)/ml on chick embryo tracheal tissue it was established that the application of infrared radiation (Osram Siccatherm Infrared Radiator,- 1-2 micron) and cm-waves (Klystron Raytheon Comp. Mass. USA, - 1.35 cm) for a length of 10 min. inhibited Newcastle Disease Virus (NDV) infectivity. The suspension fluid was treated with infrared and the tissue with cm-waves. Previous experiments revealed that direct radiation influence upon viruses cannot be taken for granted which is why the agents, chondroitine sulphate (polyanion) 5-10 microgram/ml, and hyaluronic acid (polyanion) 10-50 microgram/ml, were used in order to study such influence upon NDV-infected tracheal mucous membrane. In addition, protamine sulphate (polycation), 5-10 microgram/ml, and mucin were used. All the above mentioned substances influenced viral infectivity in organ cultures-expressed in terms of quotients: quotient 1 means no influence on the motility of the ciliated mucous membrane cells and quotient 0.01 means the complete destruction of the cells. Chondroitine sulphate inhibited strong but promoted weak virus infectivity, hyaluronic acid inhibited strong virus infectivity, protamine sulphate inhibited strong but promoted weak virus infectivity and mucin promoted weak virus infectivity in accordance with the used virus concentrations (Table 2). Under the influence of infrared radiation the mediator substances exercised a different influence upon viral infectivity: 25 times out of 32 experiments chondroitine sulphate was inhibited and hyaluronic acid increased in 8 out of 12 experiments (Table 2). The influence of protamine sulphate on viral infectivity was found to be increased 39 times and inhibited 14 times out of 54 experiments, mucin was inhibited 6 times. Furthermore, it is to be added that additional radiation with cm-waves increased the influence of infrared radiation (Table 1)...

Adsorption↗
PubMed1983

Influence of protamine on heparin-induced increases of lidocaine free fraction.

It has been suggested that heparin-induced increases in drug free fraction are largely artifactual as a result of continued in vitro activity of lipoprotein lipases after blood samples collection. The influence of different concentrations of protamine (1.0, 2.5, 5.0 and 10.0 mg/ml), an inhibitor of lipoprotein lipases, on lidocaine free fraction was studied before (control) and 10 min after heparinization (3000 IU) in 7 cardiac catheterized patients. Heparin increased the mean free fraction of lidocaine by 85% (p less than 0.001) and was associated with more than 2-fold increases in free fatty acids (FFAs). The presence of protamine at 2.5, 5.0 and 10.0 mg/ml diminished both the heparin-induced elevation of lidocaine free fraction (p less than 0.001) and FFAs (p less than 0.001). At a protamine concentration of 10.0 mg/ml, the FFAs remained higher than control value (p less than 0.05) while the free fraction was not different from control preheparin value. There were significant relationships (p less than 0.01) between log protamine concentration and the changes in both free fraction (r2 = 0.906) and FFAs (r2 = 0.931). The inhibitor also reduced (p less than 0.01) the lidocaine free fraction in control samples but these changes were not correlated with changes of FFAs. These results indicate that it is impossible, at this point, to abolish the artifactual effect of heparin without altering protein binding of lidocaine.

Adult↗