Search

Introduction: Individualized heparin and protamine management is increasingly used as a strategy to reduce coagulation activation and bleeding complications. While it is associated with increased heparin requirements during Cardiopulmonary Bypass (CPB), the impact on protamine administration remains controversial. We aim to investigate the effect of heparin level-guided monitoring on protamine dosing during cardiac surgery where low-anticoagulation protocols are implemented. Methods: This is a prospective, randomized, controlled trial. A total of 132 patients undergoing elective full-spectrum cardiac surgery with Minimal Invasive Extracorporeal Circulation (MiECC) were recruited. All patients were managed by the same anaesthetic, surgical and perfusion team. Patients were randomly allocated in two groups; the individualized heparin-protamine titration (IHPT) group and the conventional heparinization and reversal group by using ACT (cACT) with a 0.75:1, protamine: heparin ratio. Titration was accomplished with the Hepcon HMS Plus (Medtronic, Minneapolis, MN) system. The primary outcome of the study was the total protamine dose used. Secondary outcomes comprised of the total heparin dose, the percentage of patients achieving target ACT, 24-h transfusion requirements, postoperative bleeding, duration of mechanical ventilation, major morbidity and length of hospital stay. Patients in each group were divided in two subgroups according to the target ACT; those operated for coronary artery bypass grafting (CABG) using a target ACT >300 s and the rest (non-CABG) patients operated with a target ACT >400 s, respectively. Results: Protamine requirements were significantly reduced when IHPT was implemented; CABG (118 ± 24 mg vs 163 ± 61 mg; p < 0.001) and non-CABG cases (151 ± 46 mg vs 197 ± 45 mg; p < 0.001). Moreover, heparin requirements were significantly higher in the non-CABG subgroup managed with IHPT (34,539 ± 7658 IU vs 29,893 ± 9037 IU; p = 0.02). In overall, no significant differences were detected with respect to postoperative bleeding, transfusion of RBC or other blood products. Conclusions: Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery with MiECC implementing reduced anticoagulation strategy. Trial registration: clinicaltrials.gov; NCT04215588. [ABSTRACT FROM AUTHOR]

Aim: Paclitaxel and imatinib mesylate are drugs used in the treatment of breast cancer. Conventional drug-delivery systems have limitations in the effective treatment of breast cancer using the drugs. Materials & methods: Combination index studies were used to identify the optimum ratio of both drugs showing maximum synergistic effect. Using a systematic quality-by-design approach, protamine-coated PLGA nanoparticles co-loaded with paclitaxel and imatinib mesylate were formulated. Further characterization and cell line evaluations were performed. Results: Encapsulation efficiency obtained was 92.54% for paclitaxel and 75.12% for imatinib mesylate. A sustained (24 h) and controlled zero-order drug release was obtained. Conclusion: Formulated nanoparticles had a low IC50 value and enhanced cellular uptake. Graphical Abstract Article highlights Paclitaxel and imatinib (PXL and IMA) show synergistic efficacy against the MCF-7 cell line of breast cancer. PXL and IMA in the ratio of 4:1 show maximum effect and lowest combination index (CI). Quality-by-design methodology led to optimization and systematic formulation of coloaded protamine-coated PLGA nanoparticles. Protamine decreased the initial burst release of the formulations. A sustained zero-order drug release was obtained for both the formulations. Protamine coating was clearly visible on images using transmission electron microscopy analysis. Significant reduction in IC50 values showing increased cytotoxicity was observed. Roughly 30-fold increase in cellular uptake was obtained as compared with free drugs. [ABSTRACT FROM AUTHOR]

Protamines play a critical role in DNA compaction and stabilization in sperm cells, significantly influencing male fertility and various biotechnological applications. Traditionally, identifying these proteins is a challenging and time-consuming process due to their species-specific variability and complexity. Leveraging advancements in computational biology, we present PROTA, a novel tool that combines machine learning (ML) and deep learning (DL) techniques to predict protamines with high accuracy. For the first time, we integrate Generative Adversarial Networks (GANs) with supervised learning methods to enhance the accuracy and generalizability of protamine prediction. Our methodology evaluated multiple ML models, including Light Gradient-Boosting Machine (LIGHTGBM), Multilayer Perceptron (MLP), Random Forest (RF), eXtreme Gradient Boosting (XGBOOST), k-Nearest Neighbors (KNN), Logistic Regression (LR), Naive Bayes (NB), and Radial Basis Function-Support Vector Machine (RBF-SVM). During ten-fold cross-validation on our training dataset, the MLP model with GAN-augmented data demonstrated superior performance metrics: 0.997 accuracy, 0.997 F1 score, 0.998 precision, 0.997 sensitivity, and 1.0 AUC. In the independent testing phase, this model achieved 0.999 accuracy, 0.999 F1 score, 1.0 precision, 0.999 sensitivity, and 1.0 AUC. These results establish PROTA, accessible via a user-friendly web application. We anticipate that PROTA will be a crucial resource for researchers, enabling the rapid and reliable prediction of protamines, thereby advancing our understanding of their roles in reproductive biology, biotechnology, and medicine. [ABSTRACT FROM AUTHOR]

Background: A multidisciplinary Quality Assurance/Performance Improvement study to identify the incidence of "heparin rebound" in our adult cardiac surgical population instead detected a thromboelastometry pattern suggestive of initial protamine overdose in 34% despite Hepcon-guided anticoagulation management. Analysis of our practice led to an intervention that made an additional lower-range Hepcon cartridge available to the perfusionists. Methods: One year later, an IRB-approved retrospective study was conducted in >500 patients to analyze the effects of the intervention, specifically focusing on the impact of the initial protamine dose accuracy and 18-h mediastinal chest tube drainage (MCTd). Results: No differences were observed between group demographics, surgical procedures, duration of CPB or perioperative blood product transfusion. Both groups were managed using the same perfusion and anesthesia equipment, strategies, and protocols. The median initial protamine dose decreased by 19% (p <.001) in the intervention group (170 [IQR 140–220] mg; n = 295) versus the control group (210 [180–250] mg; n = 257). Mean 18-h MCTd decreased by 13% (p <.001) in the intervention group (405.15 ± 231.54 mL; n = 295) versus the control group (466.13 ± 286.73 mL; n = 257). Covariate-adjusted mixed effects model showed a significant reduction of MCTd in the intervention group, starting from hour 11 after surgery (group by time interaction p =.002). Conclusion: Though previous investigators have associated lower protamine doses with less MCTd, this study demonstrates that more accurately matching the initial protamine dose to the remaining circulating heparin concentration reduces postoperative bleeding. [ABSTRACT FROM AUTHOR]

A novel ratiometric fluorescent assay was proposed for protamine and heparin based on blue‐emitting N,P‐doped carbon dots (N,P‐CDs) and green‐emitting Eosin Y. The N,P‐CDs were prepared using arginine as carbon and nitrogen sources according to hydrothermal method with favorable luminescence intensity, photostability, and good reproducibility. And the N,P‐CDs were used as internal reference fluorescence molecules. The anionic Eosin Y was used as fluorescence signal molecule. Protamine with positive group could interact with Eosin Y through electrostatic effect, leading to the fluorescence quenching of Eosin Y. Upon the addition of heparin, heparin was combined with protamine with stronger affinity through electrostatic interactions and hydrogen bonds, which preventing the bonding of protamine with Eosin Y and obvious fluorescence emissions of Eosin Y at 538 nm could be observed. Meanwhile, the fluorescence signal of N,P‐CDs at 420 nm remained stable during the whole process. A good linear range between the fluorescence emission intensity ratio of I538/I420 was obtained for protamine from 0.01 to 40 μg/mL with a low detection limit of 5.6 ng/mL, and heparin from 0 to 35 μg/mL with a low detection limit of 2.5 ng/mL. Moreover, the method was further applied to detection of heparin with satisfactory results in fetal bovine serum samples. [ABSTRACT FROM AUTHOR]

Objectives: To optimize protamine titration for heparin antagonization after weaning from cardiopulmonary bypass (CPB). Design: A prospective, observational trial. Setting: Single-center, non-university teaching hospital. Participants: Forty patients presenting for elective on-pump coronary artery bypass grafting with or without single valve surgery. Interventions: At the end of CPB, the residual amount of heparin in the patient was estimated using a Bull-curve. The total protamine dose was calculated as 1 unit of protamine for 1 unit of heparin. Protamine was administered as 5 aliquots containing 20% of the total protamine dose each, with 2-min intervals. Measurements and main results: Activated Clotting Time (ACT) values were measured 2 min after administration of each aliquot. ROTEM(®)-analysis was performed after the full dose of protamine had been administered. After 60% of the total protamine dose had been administered, ACT values were normalized in 86.5% of patients. After the complete dose of protamine had been administered, 61.1% of patients displayed signs of protamine overdose on ROTEM(®)-analysis. Conclusions: In patients who present for on-pump coronary artery bypass grafting with or without single valve surgery, a 0.6-to-1 ratio of protamine-to-heparin to antagonize heparin may be sufficient and beneficial for patients. [ABSTRACT FROM AUTHOR]

Severe pulmonary vasoconstriction induced by protamine is a rare complication. We report a case of a 77-year-old male patient with a history of mitral valve plasty (MVP). He underwent redo MVP via right thoracotomy under the totally endoscopic procedure (MICS redo-MVP). Immediately after weaning cardiopulmonary bypass (CPB), protamine was administrated. 10 min later peak systolic pulmonary arterial pressure (sys PAP) rose to 62 mmHg, and 30 min later to 80 mmHg. Due to the negative impact of protamine administration, nitric oxide inhalation (iNO) therapy was started with a concentration of 20 ppm. 10 min after iNO therapy started, sys PAP decreased to 63 mmHg. After entering the intensive care unit (ICU), sys PAP decreased to 35 mmHg. Here, we present an effective iNO therapy case for pulmonary hypertension due to protamine and the patient had a good postoperative recovery. This study was approved by the Institutional Review Board at Kitaharima Medical Center (IRB-0602) with the waiver of informed consent. [ABSTRACT FROM AUTHOR]

Severe pulmonary vasoconstriction induced by protamine is a rare complication. We report a case of a 77-year-old male patient with a history of mitral valve plasty (MVP). He underwent redo MVP via right thoracotomy under the totally endoscopic procedure (MICS redo-MVP). Immediately after weaning cardiopulmonary bypass (CPB), protamine was administrated. 10 min later peak systolic pulmonary arterial pressure (sys PAP) rose to 62 mmHg, and 30 min later to 80 mmHg. Due to the negative impact of protamine administration, nitric oxide inhalation (iNO) therapy was started with a concentration of 20 ppm. 10 min after iNO therapy started, sys PAP decreased to 63 mmHg. After entering the intensive care unit (ICU), sys PAP decreased to 35 mmHg. Here, we present an effective iNO therapy case for pulmonary hypertension due to protamine and the patient had a good postoperative recovery. This study was approved by the Institutional Review Board at Kitaharima Medical Center (IRB-0602) with the waiver of informed consent.

Transfemoral Trans-catheter Aortic Valve Replacement (TF-TAVR) is a safe alternative to surgical aortic valve replacement (SAVR). Protamine is used to reverse heparin and reduce post-TAVR bleeding, but concerns about risks like valve thrombosis and stroke remain. This systematic review and meta-analysis, following PRISMA guidelines, found no statistically significant difference in major bleeding complications between the protamine and control groups [(3.0 % vs. 14.4 %); RR: 0.56; P = 0.16]. No differences were noted in life-threatening bleeding, blood transfusions, 30-day mortality, or stroke. Protamine appears safe post-TAVR without increasing stroke risk, but its effectiveness in reducing bleeding needs further investigation through a multicentric randomized study.

Protamine, first isolated from salmon fish sperm and now produced through recombinant biotechnology, is an antidote that neutralizes the anticoagulant properties of heparin. Protamine function is based on the capacity to dissociate the heparin–antithrombin III (AT III) complex (an important link that promotes blood fluidification by inhibiting coagulation), forming the inactive heparin–protamine complex. Protamine has itself dose-dependent anticoagulant properties: It interferes with coagulation factors and platelet function; it stimulates fibrinolysis; it can lead to thrombocytopenia and reduction in thrombin-related platelet aggregation; it decreases platelet response to thrombin receptor agonist in a dose-dependent manner. In this review, we will focus on protamine and its interaction with heparin. Notably, protamine is able to antagonize not only unfractionated heparin (UFH) but also low molecular weight heparins to various degrees. Protamine-allergic and anaphylactoid systemic reactions may affect up to 1 in 10 people and should be prevented and treated early.

Objective(s): Gene therapy is a hopeful approach for treatment of a wide range of life threatening disease from infectious and inherited diseases to cancer. Multifunctional Envelope-type Nano Device (MEND) is a new carrier as non-viral genetic vector. Moreover, associating peptide structures with the nuclear localization signals (NLSs), which contains various functional groups enables them to condense DNA and specifically transfer genetic material to the nucleus.Materials and Methods: In this study, two forms of low molecular weight protamine (LMWP) were used for preparation of MEND carrier. The MEND carriers were then targeted with GE11 ligand to obtain T-MEND structure. The size distribution of the resulting nanoparticles, as well as their transfection efficiency and cytotoxicity, were investigated on the A549 cell line.Results: Results demonstrated that the size of polyplex carrier’s formulation by both peptides (VV45 and VV32) was below 200 nm and MEND formulations were between 200-300 nm. T-MEND formulations contained VV32 and VV45 peptides showed slightly higher transfection than similar MEND formulations. Also, MEND formulation showed increased transfection efficiency compared to similar PD complexes. The result of metabolic activity test showed that MEND lipopolyplex did not represent any remarkable cytotoxicity.Conclusion: It can be concluded that multifunctional carriers designed based on LMWP are considered as the safe carrier for gene delivery. Presence of protamine and targeted ligand in the nanoparticulate structure did not increase the risk of cytotoxicity of carriers. So, MEND and T-MEND lipoplexes showed low cytotoxicity and acceptable transfection efficiency at the level of PEI 25 kDa.

Objective(s): Gene therapy is a hopeful approach for treatment of a wide range of life threatening disease from infectious and inherited diseases to cancer. Multifunctional Envelope-type Nano Device (MEND) is a new carrier as non-viral genetic vector. Moreover, associating peptide structures with the nuclear localization signals (NLSs), which contains various functional groups enables them to condense DNA and specifically transfer genetic material to the nucleus. Materials and Methods: In this study, two forms of low molecular weight protamine (LMWP) were used for preparation of MEND carrier. The MEND carriers were then targeted with GE11 ligand to obtain T-MEND structure. The size distribution of the resulting nanoparticles, as well as their transfection efficiency and cytotoxicity, were investigated on the A549 cell line. Results: Results demonstrated that the size of polyplex carrier's formulation by both peptides (VV45 and VV32) was below 200 nm and MEND formulations were between 200-300 nm. T-MEND formulations contained VV32 and VV45 peptides showed slightly higher transfection than similar MEND formulations. Also, MEND formulation showed increased transfection efficiency compared to similar PD complexes. The result of metabolic activity test showed that MEND lipopolyplex did not represent any remarkable cytotoxicity. Conclusion: It can be concluded that multifunctional carriers designed based on LMWP are considered as the safe carrier for gene delivery. Presence of protamine and targeted ligand in the nanoparticulate structure did not increase the risk of cytotoxicity of carriers. So, MEND and T-MEND lipoplexes showed low cytotoxicity and acceptable transfection efficiency at the level of PEI 25 kDa. [ABSTRACT FROM AUTHOR]

Protamine, first isolated from salmon fish sperm and now produced through recombinant biotechnology, is an antidote that neutralizes the anticoagulant properties of heparin. Protamine function is based on the capacity to dissociate the heparin--antithrombin III (AT III) complex (an important link that promotes blood fluidification by inhibiting coagulation), forming the inactive heparin--protamine complex. Protamine has itself dose-dependent anticoagulant properties: It interferes with coagulation factors and platelet function; it stimulates fibrinolysis; it can lead to thrombocytopenia and reduction in thrombin-related platelet aggregation; it decreases platelet response to thrombin receptor agonist in a dose-dependent manner. In this review, we will focus on protamine and its interaction with heparin. Notably, protamine is able to antagonize not only unfractionated heparin (UFH) but also low molecular weight heparins to various degrees. Protamine-allergic and anaphylactoid systemic reactions may affect up to 1 in 10 people and should be prevented and treated early. [ABSTRACT FROM AUTHOR]

Bleeding events are common in patients prescribed anticoagulants and can have devastating consequences. Several specific and nonspecific agents have been developed to reverse the effects of anticoagulant drugs or toxins. Vitamin K, as the oldest of these antidotes, specifically counteracts the effects of pharmaceuticals and rodenticides designed to deplete stores of vitamin K‐dependent factors. In cases of life‐threatening bleeding, the addition of prothrombin complex concentrates (PCCs) allows for the immediate replacement of coagulation factors. While the use of PCCs has been extended to the non‐specific reversal of the effects of newer direct oral anticoagulants, the specific agents idarucizumab, targeting dabigatran and andexanet‐α, binding factor Xa inhibitors, have recently been developed and are being preferentially recommended by most guidelines. However, despite having rapid effects on correcting coagulopathy, there is to date a lack of robust evidence establishing the clear superiority of direct oral anticoagulant‐specific reversal agents over PCCs in terms of haemostatic efficacy, safety or mortality. For andexanet‐α, a potential signal of increased thromboembolic risks, comparatively high costs and low availability might also limit its use, even though emerging evidence appears to bolster its role in intracranial haemorrhage. Protamine is the specific agent for the reversal of unfractionated heparin anticoagulation used mainly in cardiovascular surgery. It is much less effective for low molecular weight heparin fragments and is usually reserved for cases with life‐threatening bleeding. [ABSTRACT FROM AUTHOR]

Objectives: In our center, an unusual rate of patients had abnormalities of hemostasis in immediate postoperative period of cardiac surgery. Our objectives were to identify the cause of these sudden hemostasis abnormalities and to evaluate the performances of point of care coagulation testing. Methods: In this prospective and descriptive study, we included 33 consecutive patients undergoing elective cardiac surgery for 1 month. Heparin-induced anticoagulation and calculation of the protamine dose were tested by the Hemostasis Management System Plus device (Medtronic, Minneapolis, MN, USA). Fifteen minutes after the end of the protamine infusion, activated clotting time (ACT), activated partial thromboplastin time and anti Xa activity were measured. In case of unusual clinical bleeding, a Quantra analysis (Stago, HemoSonics LLC, Charlottesville, VA) was added. Results: Residual antiXa activity >0.2 IU/mL after neutralization was present in 44% of patients. Our investigation concluded incomplete heparin reversal. There was no association between cellular reinfusate and the presence of heparin. The unusual rate of hemostasis abnormalities was explained by a less efficient protamine reversal of heparin. ACT and Clot Time Ratio (CTR, Quantra system) correlated with AntiXa with Spearman's coefficients of 0.85 (p <.0001) and 0.95 (p =.0012), respectively. About ACT, a threshold of 150 seconds had a sensitivity of 85% [58–97] and a specificity of 85% [58–97%] for detection of AntiXa>0.2. For CTR, a threshold of 1.4 had a sensitivity of 67% [30–94] and a specificity of 100% [18–100]. Conclusion: The use of point of care coagulation testing is effective in detecting incomplete reversal of heparin. [ABSTRACT FROM AUTHOR]

Therapeutic proteins often require needle-based injections, which compromise medication adherence especially for those with chronic diseases. Sublingual administration provides a simple and non-invasive alternative. Herein, two novel peptides (lipid-conjugated protamine and a protamine dimer) were synthesized to enable sublingual delivery of proteins through simple physical mixing with the payloads. It was found that the novel peptides promoted intracellular delivery of proteins via increased pore formation on the cell surface. Results from in vitro models of cell spheroids and human sublingual tissue substitute indicated that the novel peptides enhanced protein penetration through multiple cell layers compared to protamine. The novel peptides were mixed with insulin or semaglutide and sublingually delivered to mice for blood glucose (BG) control. The effects of these sublingual formulations were comparable to the subcutaneous preparations and superior to protamine. In addition to peptide drugs, the novel peptides were shown to enable sublingual absorption of larger proteins with molecular weights from 22 to 150 kDa in mice, including human recombinant growth hormone (rhGH), bovine serum albumin (BSA) and Immunoglobulin G (IgG). The novel peptides given sublingually did not induce any measurable toxicities in mice. [Display omitted] • Two novel derivatives of protamine were synthesized to facilitate sublingual delivery of proteins. • These protamine derivatives enable delivery of proteins up to 150 KDa by simple mixing. • The protamine derivatives promoted transcellular delivery by forming nanopores on cell surface. • These protamine derivatives were safe in mice. [ABSTRACT FROM AUTHOR]

As effective methods to accurately and rapidly detect protamine remains a major challenge, here we present a fluorescent protein chromophore‐based probe (IDL‐FP) utilizing twisted‐intramolecular charge transfer (TICT) to detect protamine. The introduction of an electron‐donor group 4‐dimethylaminobenzaldehyde extends the emission wavelength of IDL‐FP to the red region. The deprotection of t‐butyloxy carbonyl groups can then generate an electronegative carboxyl group, which promotes the binding to protamine via electrostatic attraction. Thus, IDL‐FP is sensitive and specific towards protamine and can serve as a highly selective detector for protamine with a detection limit as low as 8.87 ng/mL. As IDL‐FP exhibited good stability in physiological pH environment, we successfully apply IDL‐FP to detect spiked‐in protamine in human serum. In summary, probe IDL‐FP is a promising tool for the quantitative determination of protamine. [ABSTRACT FROM AUTHOR]

Background: Bleeding after cardiac surgery is common and continues to require 10–20% of the national blood supply. Transfusion of allogeneic blood is associated with increased morbidity and mortality. Excessive protamine in the absence of circulating heparin after weaning off CPB can cause anticoagulation and precipitate bleeding. Hence, adequate dose calculation of protamine is crucial yet under evaluated. Study Design: Retrospective cohort study. Methods: We conducted a retrospective bi‐institutional analysis of cardiac surgical patients who underwent cardiopulmonary bypass (CPB)‐assisted cardiac surgery to assess the impact of protamine dosing in transfusion practice. Total 762 patients were identified from two institutions using electronic medical records and the Society of Thoracic Surgery (STS) database who underwent cardiac surgery using CPB. Patients were similar in demographics and other baseline characteristics. We divided patients into two groups based on mg of protamine administered to neutralize each 100 U of unfractionated heparin (UFH)—low‐ratio group (Protamine: UFH ≤ 0.8) and high‐ratio group (Protamine: UFH > 0.8). Results: We observed a higher rate of blood transfusion required in high‐ratio group (ratio >0.8) compared with low‐ratio group (ratio ≤0.8) (p <.001). The increased requirement was consistently demonstrated for intraoperative transfusions of red blood cells, plasma, platelets, and cryoprecipitate. Conclusion: High protamine to heparin ratio may cause increased bleeding and transfusion in cardiac surgical patients. Protamine to heparin ratio of 0.8 or lower is sufficient to neutralize circulating heparin after weaning off cardiopulmonary bypass. [ABSTRACT FROM AUTHOR]

Coenzyme Q10 (CoQ10) is an endogenous, lipophilic quinone compound that functions as an electron carrier in the mitochondrial respiratory chain and plays a pivotal role in cell metabolism. Despite its numerous important physiological functions, the practical application of CoQ10 is limited due to its high molecular weight, poor water solubility, photolability, chemical instability, and low bioavailability. To overcome these challenges, we developed a solid dispersion formulation of protamine loaded CoQ10 (CoQ10/Pr) using an efficient mechanochemical technology without solvents. Protamine was used as carrier and poloxamer 188 as solubilizer, while butylated hydroxytoluene (BHT) and micro powder silica gel were utilized as stabilizers and lubricants. The optimal ball milling condition to prepare CoQ10/Pr was at 100 r/min for 4 hours. The treated CoQ10/Pr has exhibited rapid-release properties, with significantly enhanced water solubility by 392,000 times, and bioavailability by 0.68 times. Furthermore, the treated CoQ10/Pr became resistant to moisture, high temperature and strong light, which makes it suitable for long-term storage. The molecular docking suggested that the solubilization mechanism of CoQ10 was closely associated with the encapsulation and complexation of protamine, as well as the formation of an intermolecular complex through hydrogen bond between CoQ10 and arginine residues on protamine. In summary, the CoQ10 solid dispersion formulation enjoys advantages such as excellent water solubility, stability, bioavailability, and low cost. This formulation also meets the stringent quality requirements of products in the food, cosmetic, and health industries. It offers dual benefits in both theoretical research and industrial development.

Protamines play a critical role in DNA compaction and stabilization in sperm cells, significantly influencing male fertility and various biotechnological applications. Traditionally, identifying these proteins is a challenging and time-consuming process due to their species-specific variability and complexity. Leveraging advancements in computational biology, we present PROTA, a novel tool that combines machine learning (ML) and deep learning (DL) techniques to predict protamines with high accuracy. For the first time, we integrate Generative Adversarial Networks (GANs) with supervised learning methods to enhance the accuracy and generalizability of protamine prediction. Our methodology evaluated multiple ML models, including Light Gradient-Boosting Machine (LIGHTGBM), Multilayer Perceptron (MLP), Random Forest (RF), eXtreme Gradient Boosting (XGBOOST), k-Nearest Neighbors (KNN), Logistic Regression (LR), Naive Bayes (NB), and Radial Basis Function-Support Vector Machine (RBF-SVM). During ten-fold cross-validation on our training dataset, the MLP model with GAN-augmented data demonstrated superior performance metrics: 0.997 accuracy, 0.997 F1 score, 0.998 precision, 0.997 sensitivity, and 1.0 AUC. In the independent testing phase, this model achieved 0.999 accuracy, 0.999 F1 score, 1.0 precision, 0.999 sensitivity, and 1.0 AUC. These results establish PROTA, accessible via a user-friendly web application. We anticipate that PROTA will be a crucial resource for researchers, enabling the rapid and reliable prediction of protamines, thereby advancing our understanding of their roles in reproductive biology, biotechnology, and medicine.

Protamine is a cationic peptide derived from fish sperm and has several important functional properties: antibacterial properties, acting as a carrier for injectable insulin and as a heparin antagonist, combatting fatigue, etc. Thus, it has been widely used in medicinal applications and food products. Cultured Takifugu flavidus is a type of pufferfish with a delicious taste that is popular in China, and its production is increasing significantly. Therefore, protamine was extracted via acid extraction from the sperm of Takifugu flavidus and further isolated and purified via sephadex gel chromatography, ion exchange chromatography, and desalination chromatography. Furthermore, the physicochemical properties of protamine were investigated. The results showed that the sperm of the cultured T. flavidus were non-toxic, and the extracted and purified protamine had high contents of arginine (36.90%) and lysine (27.02%), respectively. The secondary structure of protamine was mainly β-folded and irregularly curled. Additionally, protamine exhibited high thermal stability with a denaturation temperature of 176 °C. This study would provide a theoretical basis for the structural analysis, bioactivity, and resource development of pufferfish protamine and help to promote the development of the pufferfish industry. [ABSTRACT FROM AUTHOR]

This study developed an adsorption‐based determination system for protamine. A multi‐walled carbon nanotube (MWCNT), which is a strong adsorbent, was used. The competitive adsorption process between dyes and protamine formed the basis of the sensor system. The adsorption process was followed over the dyes by UV–Vis. absorption spectroscopy. This sensor system was developed using the thermodynamic parameters. Transmission electron microscopy and Fourier‐transform infrared spectroscopy techniques were used for the characterization of the sensor system. It was determined that the sensor system remained stable at physiological temperature and pH range. Limit of detection values of PyB‐COO‐MWCNT and PyY‐COO‐MWCNT systems were found to be 1.32 and 1.12 ng mL−1, respectively. The applicability of the sensor systems was demonstrated using bovine serum solutions. [ABSTRACT FROM AUTHOR]

Objective: To determine the dose of Protamine required for reversal of Heparin effect in Coronary Artery Bypass Grafting (CABG). Study Design: Quasi-experimental study. Place and Duration of Study: Adult Cardiac Surgery Unit, Armed Forces Institute of Cardiology/National Institute of Heart Diseases, Rawalpindi Pakistan, from May to Dec 2022. Methodology: Total 382 patients were included in this study through consecutive sampling and were divided into two groups (n=191 participants in each group). After induction of anesthesia, baseline Activated Clotting Time (ACT) was measured. About 300units/kg of unfractionated Heparin was given non-randomly before establishing Cardiopulmonary Bypass (CPB). After termination of CPB, Protamine was administered in doses of 1 mg/kg and 1.5 mg/kg to Group-A and Group-B respectively. Protamine was diluted in 20ml of saline, and administered at a rate of 100ml/hr. Once Protamine was administered, blood sample was taken after 5min for ACT measurement. If this ACT was within 10% of baseline, it was taken as sign for reversal of Heparin effect. Student t-test and Chi-square test were applied to compare the groups and level of significance taken was p

This article discusses the negative effects of protamine on the myocardium in pediatric patients undergoing cardiac surgery with a cardiopulmonary bypass machine. Protamine is commonly used to reverse the anticoagulant effects of heparin, but it has been associated with adverse events, including myocardial impairment. The research highlights the need for further investigation into the impact of protamine on the myocardium in pediatric patients, as well as the importance of proper dosage adjustment during administration. The article also mentions potential complications and side effects of protamine, such as immunological reactions, inflammatory changes, and cardiovascular complications. [Extracted from the article]

Introduction: Our study aim was to explore how different protamine-heparin ratios impacted enzymatic coagulation and acellular fibrin clot growth in plasma using an in vitro model. We hypothesized that a low protamine-heparin ratio would be associated with superior fibrin clot growth dynamics. Methods: We performed an in vitro study using 15 plasma samples from a commercial supplier. Different protamine-heparin ratios were added to each donor plasma sample: low ratio (0.7–1), traditional ratio (1–1), and high ratio (1.3–1) and clot formation dynamics were evaluated using a Thrombodynamics analyzer. Study outcomes were initial clot growth velocity and clot size at 30 min. Results: Plasma samples treated with a one-to-one protamine-heparin ratio had significantly lower mean initial clot growth velocity compared to samples treated with a low protamine-heparin ratio; mean difference −2.3 μm/min (95% CI = −4.0 to −0.7, p =.004). Plasma samples treated with a one-to-one protamine-heparin ratio also had significantly smaller mean clot size at 30 min compared to samples treated with a low protamine-heparin ratio; mean difference −54.0 μm (95% CI = −107.6 to −0.4, p =.048). There were no significant differences in mean initial clot growth velocity or clot size at 30 min between plasma samples treated with a high protamine-heparin ratio and those treated with a one-to-one or low protamine-heparin ratio (all p >.05). Conclusions: Plasma samples treated with a low protamine-heparin ratio had superior clot growth velocity and larger clot size at 30 min compared to a one-to-one ratio, supporting the notion that a low protamine-heparin ratio may optimize enzymatic coagulation after cardiopulmonary bypass. [ABSTRACT FROM AUTHOR]

Coenzyme Q10 (CoQ10) is an endogenous, lipophilic quinone compound that functions as an electron carrier in the mitochondrial respiratory chain and plays a pivotal role in cell metabolism. Despite its numerous important physiological functions, the practical application of CoQ10 is limited due to its high molecular weight, poor water solubility, photolability, chemical instability, and low bioavailability. To overcome these challenges, we developed a solid dispersion formulation of protamine loaded CoQ10 (CoQ10/Pr) using an efficient mechanochemical technology without solvents. Protamine was used as a carrier and poloxamer 188 as a solubilizer, while butylated hydroxytoluene (BHT) and micro powder silica gel were utilized as stabilizers and lubricants. The optimal ball milling condition to prepare CoQ10/Pr was at 100 r/min for four hours. The treated CoQ10/Pr exhibited rapid-release properties with significantly enhanced water solubility by 392,000 times and bioavailability by 0.68 times. Furthermore, the treated CoQ10/Pr became resistant to moisture, high temperature and strong light, which makes it suitable for long-term storage. Molecular docking suggested that the solubilization mechanism of CoQ10 was closely associated with the encapsulation and complexation of protamine, as well as the formation of an intermolecular complex through a hydrogen bond between CoQ10 and arginine residues on protamine. In summary, the CoQ10 solid dispersion formulation has advantages such as excellent water solubility, stability, bioavailability, and low cost. This formulation also meets the stringent quality requirements of products in the food, cosmetic, and health industries. It offers dual benefits in both theoretical research and industrial development. [ABSTRACT FROM AUTHOR]

Protamines (PRM1 and PRM2) are small, arginine-rich, nuclear proteins that replace histones in the final stages of spermiogenesis, ensuring chromatin compaction and nuclear remodeling. Defects in protamination lead to increased DNA fragmentation and reduced male fertility. Since efficient sperm production requires the translocation of protamines from the cytoplasm to the nucleus, we investigated whether SPAG17, a protein crucial for intracellular protein trafficking during spermiogenesis, participates in protamine transport. Initially, we assessed the protein-protein interaction between SPAG17 and protamines using proximity ligation assays, revealing a significant interaction originating in the cytoplasm and persisting within the nucleus. Subsequently, immunoprecipitation and mass spectrometry (IP/MS) assays validated this initial observation. Sperm and spermatids from Spag17 knockout mice exhibited abnormal protamination, as revealed by chromomycin A3 staining, suggesting defects in protamine content. However, no differences were observed in the expression of Prm1 and Prm2 mRNA or in protein levels between testes of wild-type and Spag17 knockout mice. Conversely, immunofluorescence studies conducted on isolated mouse spermatids unveiled reduced nuclear/cytoplasm ratios of protamines in Spag17 knockout spermatids compared to wild-type controls, implying transport defects of protamines into the spermatid nucleus. In alignment with these findings, in vitro experiments involving somatic cells, including mouse embryonic fibroblasts, exhibited compromised nuclear translocation of PRM1 and PRM2 in the absence of SPAG17. Collectively, our results present compelling evidence that SPAG17 facilitates the transport of protamines from the cytoplasm to the nucleus.

Simple Summary: Percutaneous hepatic melphalan perfusion (chemosaturation) is a treatment option in patients with inoperable liver metastases which is associated with considerable procedural challenges, especially hemodynamic depression, due to a reduced preload and impaired coagulation caused by the use of heparin. Studies on factors that contribute to bleeding complications and a prolonged intensive care unit length of stay are not available. In this retrospective analysis, we found that high perioperative infusion volumes and the omission of heparin reversal with protamine were associated with postoperative bleeding complications, while high infusion volumes also contributed to a length of stay in the intensive care unit of more than one day, which usually is not required. Furthermore, protamine use was not significantly associated with anaphylactic or thromboembolic complications. Our findings suggest a restrictive perioperative infusion regime and support the use of postoperative protamine for heparin reversal in chemosaturation procedures. Percutaneous hepatic melphalan perfusion (chemosaturation) in patients with liver metastases is known to be associated with procedure-related hemodynamic depression and coagulation impairment, which may cause bleeding complications and/or a prolonged intensive care unit length of stay (ICU LOS). We retrospectively analyzed possible predictive factors for bleeding complications and an ICU LOS > 1 d in a cohort of 31 patients undergoing 90 chemosaturation procedures. Using a multivariable mixed-model approach, we identified the amount of perioperative fluid volume (OR 12.0, 95% CI 2.3–60.0, p = 0.003) and protamine (OR 0.065, 95% CI 0.007–0.55, p = 0.012) to be associated with bleeding complications. Furthermore, the amount of perioperative fluid volume was associated with an ICU LOS > 1 d (OR 5.2, 95% CI 1.4–19.0, p = 0.011). Heparin dosage, melphalan dosage, extracorporeal circulation time, and noradrenaline dosage had no significant effects on outcomes. Protamine use was not associated with anaphylactic or thromboembolic complications. Despite the limited sample size, these results suggest a restrictive perioperative fluid regime to be beneficial, and support the use of protamine for heparin reversal after chemosaturation procedures. Further prospective randomized trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the efficacy and safety of low-dose protamine in reducing access site-related complications during Transcatheter Aortic Valve Implantation (TAVI) as compared to full-dose protamine. Background: Access site-related complications represent an independent predictor of poor outcomes of TAVI. Data regarding heparin reversal with protamine and the dosage needed to prevent bleeding complications are scarce among patients undergoing TAVI. Methods: A total of 897 patients were retrospectively included in the study. Patients who underwent percutaneous coronary intervention within 4 weeks before or concomitantly with TAVI (n = 191) were given 0.5 mg protamine for each 100 units of unfractionated heparin. All other patients (n = 706) were considered as a control group and 1 mg protamine for each 100 units of heparin was administered. Results: The combined intra-hospital endpoint of death, life-threatening major bleeding, and major vascular complications were significantly more frequent in patients receiving low-dose protamine [29 (15.2%) vs. 50 (7.1%), p < 0.001]. After propensity matching (n = 130 for each group) for relevant clinical characteristics including anti-platelet therapy [19 (14.6%) vs. 6 (4.6%), p = 0.006], low-dose protamine predicted the combined endpoint (OR 3.54, 95%-CI 1.36–9.17, p = 0.009), and even in multivariable analysis, low-dose protamine continued to be a predictor of the combined endpoint in the matched model (OR 3.07, 95%-CI 1.17–8.08, p = 0.023) alongside baseline hemoglobin. Conclusions: In this propensity-matched retrospective analysis, a low-dose protamine regime is associated with a higher rate of major adverse events compared to a full-dose protamine regime following transfemoral TAVI. [ABSTRACT FROM AUTHOR]

Previous studies have described impaired platelet function after cardiopulmonary bypass (CPB). Whether this is still valid in contemporary cardiac surgery is unclear. This study aimed to quantify changes in function and number of platelets during CPB in a present-day cardiac surgery cohort. Prospective, controlled clinical study. A single-center university hospital. Thirty-nine patients scheduled for coronary artery bypass graft surgery with CPB. Platelet function and numbers were measured at 6 timepoints in 39 patients during and after coronary artery bypass graft surgery; at baseline before anesthesia, at the end of CPB, after protamine administration, at intensive care unit (ICU) arrival, 3 hours after ICU arrival, and on the morning after surgery. Platelet function was assessed with impedance aggregometry and flow cytometry. Platelet numbers are expressed as actual concentration and as numbers corrected for dilution using hemoglobin as a reference marker. There was no consistent impairment of platelet function during CPB with either impedance aggregometry or flow cytometry. After protamine administration, a decrease in platelet function was seen with impedance aggregometry and for some markers of activation with flow cytometry. Platelet function was restored 3 hours after arrival in the ICU. During CPB (85.0 ± 21 min), the number of circulating platelets corrected for dilution increased from 1.73 ± 0.42 × 109/g to 1.91 ± 0.51 × 109/g (p < 0.001). During cardiac surgery with moderate CPB times, platelet function was not impaired, and no consumption of circulating platelets could be detected. Administration of protamine transiently affected platelet function. [ABSTRACT FROM AUTHOR]

Enterococcus faecalis (E. faecalis), a gram-positive facultative anaerobic bacterium, is likely to survive root canal treatment because of its extremely high alkaline tolerance, which may contribute to the refractory nature of apical periodontitis (AP). In this study, protamine was combined with calcium hydroxide to evaluate its efficacy in killing E. faecalis. First, the antibacterial activity of protamine against E. faecalis was investigated. Protamine reduced the E. faecalis growth rate at concentrations above the MIC (250 μg/mL), but was not bactericidal at any of the concentrations tested. Next, we investigated the calcium hydroxide tolerance of E. faecalis, using a 10% 310 medium, adjusted for pH by adding a calcium hydroxide solution. The results showed that E. faecalis could survive and proliferate in alkaline environments up to pH 10. However, the complete killing of E. faecalis was observed when protamine (250 μg/mL) was added. In addition, compared with treatment with protamine and calcium hydroxide alone, membrane damage and internalization of protamine into the cytoplasm of E. faecalis were enhanced. Therefore, the synergistic increase in antibacterial activity may be related to the action of both antimicrobial agents on the cell membrane. In conclusion, co-treatment with protamine and calcium hydroxide seems to be very effective in sterilizing E. faecalis, and has the potential to provide a novel control method against E. faecalis for root canal treatment. [ABSTRACT FROM AUTHOR]

In pulp and paper mills, effective biosludge dewatering is essential in wastewater treatment to reduce the large volume of biosludge that needs to be treated and disposed. The dewatering process normally requires the use of polymers from petroleum‐based sources. This study explores the potential of using cationic proteins such as protamine for biosludge dewatering through dual conditioning with a small amount of a synthetic anionic polymer such as anionic polyacrylamide (APAM). The results show that dual conditioning provides substantial synergistic enhancements in dewatering. The maximum cake solids content of biosludge achieved by adding protamine (7.5%) alone was 12%. By dual conditioning with a small amount of APAM (0.1%), not only the cake solids content was increased to 16%, but also the amount of protamine addition was substantially lowered to 2%. These results, coupled with the change in zeta potential of the particles in the biosludge samples, suggest that the cationic protamine reduced the negative charge of the particles, allowing smaller particles to agglomerate and providing a positively charged framework for the subsequent addition of the negatively charged APAM. After adding APAM, substantial floc‐bridging occurred, allowing smaller flocs to aggregate into larger flocs. These synergistic effects can lower the wastewater treatment cost by reducing the amount of synthetic polymer and by applying low‐value proteins from natural sources. [ABSTRACT FROM AUTHOR]

The paternal genome undergoes a massive exchange of histone with protamine for compaction into sperm during spermiogenesis. Upon fertilization, this process is potently reversed, which is essential for parental genome reprogramming and subsequent activation; however, it remains poorly understood how this fundamental process is initiated and regulated. Here, we report that the previously characterized splicing kinase SRPK1 initiates this life-beginning event by catalyzing site-specific phosphorylation of protamine, thereby triggering protamine-to-histone exchange in the fertilized oocyte. Interestingly, protamine undergoes a DNA-dependent phase transition to gel-like condensates and SRPK1-mediated phosphorylation likely helps open up such structures to enhance protamine dismissal by nucleoplasmin (NPM2) and enable the recruitment of HIRA for H3.3 deposition. Remarkably, genome-wide assay for transposase-accessible chromatin sequencing (ATAC-seq) analysis reveals that selective chromatin accessibility in both sperm and MII oocytes is largely erased in early pronuclei in a protamine phosphorylation-dependent manner, suggesting that SRPK1-catalyzed phosphorylation initiates a highly synchronized reorganization program in both parental genomes.

Introduction: E. coli is one of the failure factors in the pulpectomy of primary and permanent teeth. It is also responsible for many infectious diseases in Humans. This study aimed to determine antibacterial effect of arginine, protamine, aqueous extract of green tea, and Aloe vera against Escherichia coli (E. coli). Material & Methods: Aqueous extract of green tea, Aloe vera, and protamine with a concentration of 400 mg/ml, and arginine at a concentration of 160 mg/ml were used in this experimental study. E. coli was cultured on Mueller-Hinton broth and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the test materials against this microorganism was determined using micro-dilution test. Sodium hypochlorite 2.5% was used as a positive control. (Ethic code: 9643822) Findings: It was found that protamine had the highest antibacterial activity (with MIC and MBC 0.62 mg/mL) and aqueous extract of green tea showed the lowest antibacterial activity against E. coli (with MIC100 mg/ml and MBC 200 mg/ml). Positive control (sodium hypochlorite 2.5%) showed better antibacterial activity against E. coli compared to other test materials. Discussion & Conclusion: Apart from sodium hypochlorite, among the tested materials, protamine had the maximum effect and aqueous extract of aloe vera, arginine, and aqueous extract of green tea showed the lowest antibacterial effect against E. coli., respectively.

Unique chromatin remodeling factors orchestrate dramatic changes in nuclear morphology during differentiation of the mature sperm head. A crucial step in this process is histone-to-protamine exchange, which must be executed correctly to avoid sperm DNA damage, embryonic lethality and male sterility. Here, we define an essential role for the histone methyltransferase DOT1L in the histone-to-protamine transition. We show that DOT1L is abundantly expressed in mouse meiotic and postmeiotic germ cells, and that methylation of histone H3 lysine 79 (H3K79), the modification catalyzed by DOT1L, is enriched in developing spermatids in the initial stages of histone replacement. Elongating spermatids lacking DOT1L fail to fully replace histones and exhibit aberrant protamine recruitment, resulting in deformed sperm heads and male sterility. Loss of DOT1L results in transcriptional dysregulation coinciding with the onset of histone replacement and affecting genes required for histone-to-protamine exchange. DOT1L also deposits H3K79me2 and promotes accumulation of elongating RNA Polymerase II at the testis-specific bromodomain gene Brdt. Together, our results indicate that DOT1L is an important mediator of transcription during spermatid differentiation and an indispensable regulator of male fertility. [ABSTRACT FROM AUTHOR]

Purpose The case of a patient with a massive acute enoxaparin overdose managed with observation and minimal doses of protamine sulfate is reported. Summary Acute enoxaparin overdoses are uncommonly reported and management is widely variable. A 25-year-old man presented to the emergency department (ED) shortly after reporting that he had attempted suicide by injecting himself with 31 syringes of 80 mg of enoxaparin (a total of 2,480 mg) in the abdomen and other areas of his body. The patient also had self-inflicted superficial lacerations of the forearm. Due to concern over suspected compartment syndrome in the forearm, 25 mg of protamine was administered. Approximately 11 hours after reported enoxaparin self-injection, the patient's activated partial thromboplastin time (aPTT) was 206 seconds, prompting administration of an additional 50 mg of protamine. Three hours later, the aPTT had decreased to 79 seconds, then rose over several hours to 127 seconds before gradually declining to normal values. Protamine administration had no appreciable impact on anti–factor Xa activity. The patient did not require any blood products during the hospital admission. There were no further complications, and the patient was discharged to the inpatient psychiatry service on hospital day 8. Conclusion The case highlights the role of protamine as a reversal agent in the management of low-molecular-weight heparin overdoses. The optimal dosing and efficacy of protamine for this indication needs further investigation. [ABSTRACT FROM AUTHOR]

Across species, sperm maturation involves the dramatic reconfiguration of chromatin into highly compact nuclei that enhance hydrodynamic ability and ensure paternal genomic integrity. This process is mediated by the replacement of histones by sperm nuclear basic proteins, also referred to as protamines. In humans, a carefully balanced dosage between two known protamine genes is required for optimal fertility. However, it remains unknown how their proper balance is regulated and how defects in balance may lead to compromised fertility. Here, we show that a nucleolar protein, modulo, a homolog of nucleolin, mediates the histone-to-protamine transition during Drosophila spermatogenesis. We find that modulo mutants display nuclear compaction defects during late spermatogenesis due to decreased expression of autosomal protamine genes (including Mst77F) and derepression of Y-linked multicopy Mst77F homologs (Mst77Y), leading to the mutant’s known sterility. Overexpression of Mst77Y in a wild-type background is sufficient to cause nuclear compaction defects, similar to modulo mutant, indicating that Mst77Y is a dominant-negative variant interfering with the process of histone-to-protamine transition. Interestingly, ectopic overexpression of Mst77Y caused decompaction of X-bearing spermatids nuclei more frequently than Y-bearing spermatid nuclei, although this did not greatly affect the sex ratio of offspring. We further show that modulo regulates these protamine genes at the step of transcript polyadenylation. We conclude that the regulation of protamines mediated by modulo, ensuring the expression of functional ones while repressing dominant-negative ones, is critical for male fertility. [ABSTRACT FROM AUTHOR]

Proteins and peptides often require frequent needle-based administrations. Here, we report a non-parenteral delivery method for proteins through physical mixing with protamine, an FDA-approved peptide. Protamine was shown to promote tubulation and rearrangement of cellular actin, leading to enhanced intracellular delivery of proteins compared to poly(arginine) 8 (R8). While the R8-mediated delivery resulted in significant lysosomal accumulation of the cargo, protamine directed the proteins to the nuclei with little lysosomal uptake. Intranasal delivery of insulin mixed with protamine effectively reduced blood glucose levels in diabetic mice 0.5 h after administration and the effect lasted for ∼6 h, comparable to subcutaneously injected insulin at the same dose. In mice, protamine was shown to overcome mucosal and epithelial barriers and modulate adherens junctions, promoting insulin penetration to the lamina propria layer for systemic absorption. [Display omitted] • Protamine increased intracellular delivery of proteins compared to R8 in 2D and 3D cell models. • Proteins delivered by protamine displayed cytosolic delivery and little accumulation in lysosomes. • Protamine enhanced intracellular delivery of proteins by promoting actin rearrangement of tubulation. • Protamine increased systemic absorption of proteins via intranasal delivery compared to R8. [ABSTRACT FROM AUTHOR]

The common conception of "heparin rebound" invokes heparin returning to circulation in the postoperative period after apparently adequate intraoperative reversal with protamine. This is believed to portend increased postoperative bleeding and provides the rationale for administering additional empiric doses of protamine in response to prolonged coagulation tests and/or bleeding. However, the relevant literature of the last 60+ years provides only a weak level of evidence that "rebounded" heparin itself is a significant etiology of postoperative bleeding after cardiac surgery with cardiopulmonary bypass. Notably, many of the most frequently cited heparin rebound investigators ultimately concluded that although exceedingly low levels of heparin activity could be detected by anti-Xa assay in some (but not all) patients postoperatively, there was no correlation with actual bleeding. An understanding of the literature requires a careful reading of the details because the investigators lacked standardized definitions for "heparin rebound" and "adequate reversal" while studying the phenomenon with significantly different experimental methodologies and laboratory tests. This review was undertaken to provide a modern understanding of the "heparin rebound" phenomenon to encourage an evidence-based approach to postoperative bleeding. Literature searches were conducted via PubMed using the following MeSH terms: heparin rebound, heparin reversal, protamine, platelet factor 4, and polybrene. Relevant English language articles were reviewed, with subsequent references obtained from the internal citations. Perspective is provided for both those who use HepCon-guided management and those who do not, as are practical recommendations for the modern era based on the published data and conclusions of the various investigators. [ABSTRACT FROM AUTHOR]

Objective: The literature suggests that heparin reversal with protamine in transcarotid arterial revascularization (TCAR) decreases postoperative bleeding complications without an increase in stroke or death. However, the dosing of protamine in TCAR has not yet been evaluated. We aimed to evaluate our experience with intraoperative heparin reversal with protamine. Methods: This was a single-center, retrospective, observational study that evaluated the heparin and protamine doses used during TCAR. All adult patients who underwent TCAR between 9/1/2019 and 4/2/2021 were included. Demographic data was obtained from the Vascular Quality Initiative and protamine/heparin doses were obtained from a chart review. Multivariate logistic regression models were used to assess the association between the protamine/heparin dose ratio and other variables. Results: Sixty-two patients were included. The average protamine/heparin dose ratio used was 0.96 ± 0.12 mg/U; seven had a ratio less than 0.8 mg/U, and one was greater than 1.2 mg/U. Two patients experienced bleeding complications, which were managed non-operatively. No patient with a protamine/heparin ratio greater than 0.8 mg/U had postoperative bleeding. Postoperative bradycardia was observed in 32.3% of patients and hypotension in 35%, with 19% requiring vasopressors. No relationship was identified between the protamine/heparin ratio and bleeding, bradycardia, or hypotension. No 30-day myocardial infarction, stroke or death occurred. Conclusions: We identified a near 1:1 ratio of a protamine/heparin dosing regimen for the reversal of heparin during TCAR, with postoperative bleeding complications similar to those reported in the literature. However, patients who received a lower protamine/heparin ratio did not experience bleeding complications. In the era of protamine shortages, a future larger-scale study is needed to evaluate the impact of a lower protamine dose on postoperative complications. [ABSTRACT FROM AUTHOR]

Protamine is a cationic peptide derived from fish sperm and has several important functional properties: antibacterial properties, acting as a carrier for injectable insulin and as a heparin antagonist, combatting fatigue, etc. Thus, it has been widely used in medicinal applications and food products. Cultured Takifugu flavidus is a type of pufferfish with a delicious taste that is popular in China, and its production is increasing significantly. Therefore, protamine was extracted via acid extraction from the sperm of Takifugu flavidus and further isolated and purified via sephadex gel chromatography, ion exchange chromatography, and desalination chromatography. Furthermore, the physicochemical properties of protamine were investigated. The results showed that the sperm of the cultured T. flavidus were non-toxic, and the extracted and purified protamine had high contents of arginine (36.90%) and lysine (27.02%), respectively. The secondary structure of protamine was mainly β-folded and irregularly curled. Additionally, protamine exhibited high thermal stability with a denaturation temperature of 176 °C. This study would provide a theoretical basis for the structural analysis, bioactivity, and resource development of pufferfish protamine and help to promote the development of the pufferfish industry.

Changes in hemodynamics and coagulation hemostasis during the use of protamine sulfate to neutralize heparin in a ratio of 0.5:1 in coronary artery bypass graft surgery have been studied. A comparative analysis of hemodynamic abnormalities, postoperative blood loss, and the need for blood transfusion in patients receiving protamine sulfate at the above dose has been carried out. The study included 70 patients who were successively operated on at the Shalimov National Institute of Surgery and Transplantation due to coronary heart disease, in whom coronary artery bypass grafting was performed on a working heart. The study group included 30 patients in whom heparin was neutralized with protamine in a ratio of 1:0.5. The comparison group included patients in whom heparin was neutralized with protamine in a ratio of 1:1. Statistical processing of the material was performed using the software StatPlus professional 2007. Both parametric and non-parametric methods of statistical analysis were used. The parametric method (Student’s t-test) was used to test the hypothesis of the equality of the mean values of two samples from different general sets. Pearson’s criterion was used to compare the two sets by qualitative features. Statistically significant differences in the obtained results were considered at p

The development of antibacterial cotton fabrics with an overall performance is critical but remains challenging. In this study, we propose a facile method to prepare durable antibacterial cotton fabric without significant sacrifices of wearing comfortability. Cotton fabric is firstly oxidated to obtain dialdehyde groups, then treated with PM molecules to establish a PM coating on the fiber surfaces via Schiff base linkages. The resultant cotton fabrics show durably antibacterial activity, realizing high bacterial reduction rates against both E. coli and S. aureus higher than 99.99 %, and offering remarkable durabilities tolerable 50 washing cycles and 500 rubbing times. These fabrics also show reliable safety for human skin that proofed by a series of cytotoxicity tests with positive results. This work demonstrates an example of versatile strategy to impart effective antibacterial function with durable activity to cotton textiles, showing great potential for practical applications in functional textile fields. • The first demonstration of preparing antibacterial fabric with protamine. • Facile method to covalently link protamine on cotton fiber surfaces. • The grafted protamine offers remarkable antibacterial effect. • The acquired antibacterial function is durable against washing and abrading. • Low cytotoxicity of the modified fabric was confirmed. [ABSTRACT FROM AUTHOR]

(1) Background: Systemic mastocytosis is a rare, non-curable disease with potential life-threatening complications in patients receiving cardiac surgery. (2) Methods: This systematic review of the literature was prompted by the case of a life-threatening anaphylactic reaction during cardiac surgery related to systemic mastocytosis. The search of all types of studies, using several databases (Pubmed, Scopus and Web of Science), was conducted through September 2022 to identify the relevant studies. (3) Results: Twelve studies were included describing cases of patients undergoing cardiac surgery who were diagnosed with systemic mastocytosis. An adverse effect, namely anaphylaxis, has happened in three cases. Different strategies of premedication, intraoperative and postoperative management were used. In our case, the patient was admitted for elective biological aortic valve replacement due to severe aortic stenosis. Intraoperatively, the patient developed an anaphylactic shock during the administration of protamine after separation from the cardiopulmonary bypass. This anaphylaxis reaction was a complication of the pre-existing systemic mastocytosis and could be successfully managed by the administration of epinephrine, antihistamines and corticosteroids. (4) Conclusions: This systematic literature search and case report highlight the importance of careful preoperative planning, as well as coordination between cardiac surgeons, anesthesiologists and hemato-oncological specialists, in patients with rare but complication-prone diseases such as systemic mastocytosis. [ABSTRACT FROM AUTHOR]