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Clinical Research in Cardiology :... Dec 2023Despite continued efforts to improve the safety of catheter ablation, pericardial tamponade remains one of its more frequent, potentially life-threatening complications....
BACKGROUND
Despite continued efforts to improve the safety of catheter ablation, pericardial tamponade remains one of its more frequent, potentially life-threatening complications. Management of cardiac tamponade is not standardized and uncertainties regarding acute treatment remain.
METHODS
This survey sought to evaluate the management of cardiac tamponade in German EP centers via a standardized postal questionnaire. All 341 identified German EP centers were invited to return a questionnaire on their standards for the management of cardiac tamponade.
RESULTS
A total of 189 German EP centers completed the questionnaire. Several precautions are followed to avoid pericardial tamponade: A minority of centers preclude very old patients (19%) or those with a high body mass index (30%) from ablation. Non-vitamin K antagonist oral anticoagulants are briefly paused in most centers (88%) before procedures, while vitamin K antagonists are continued. Pericardial tamponade is usually treated using reversal of heparin by applying protamine (86%) and pericardiocentesis under both, fluoroscopic and echocardiographic guidance (62%). A pigtail catheter is mostly inserted (97%) and autotransfusion of aspirated blood is performed in 47% of centers. The decision for surgical repair depends on different clinical and infrastructural aspects. The timing of reinitiation of anticoagulation widely differs between the centers. Approximately 1/3 of centers prescribe nonsteroidal anti-inflammatory agents, colchicine or steroids after pericardiocentesis.
CONCLUSION
The present survey shows that the management of cardiac tamponade is still inhomogeneous in German ablation centers. However, multiple findings of this survey can be generalized and might guide especially less experienced operators and centers in their treatment and decision strategies.
Topics: Humans; Cardiac Tamponade; Pericardiocentesis; Anticoagulants; Heparin; Cardiac Electrophysiology
PubMed: 35713695
DOI: 10.1007/s00392-022-02042-x -
Thrombosis and Haemostasis Dec 2023The presence of dextran sulfate (DS) in reagents and the type of blood collection tube (citrate/citrated-theophylline-adenosine-dipyridamole [CTAD]) can lead to...
BACKGROUND
The presence of dextran sulfate (DS) in reagents and the type of blood collection tube (citrate/citrated-theophylline-adenosine-dipyridamole [CTAD]) can lead to discrepancies between unfractionated heparin (UFH) anti-Xa levels.
OBJECTIVES
To evaluate the extent of the effect (1) of different reagents containing or not containing DS and (2) of the blood collection tubes, on UFH anti-Xa levels, in various clinical situations (NCT04700670).
METHODS
We prospectively included patients from eight centers: group (G)1, cardiopulmonary bypass (CPB) after heparin neutralization ( = 39); G2, cardiothoracic intensive care unit (ICU) after CPB ( = 35); G3, medical ICU ( = 53); G4, other medical inpatients ( = 38). Blood was collected into citrated and CTAD tubes. Chromogenic anti-Xa assays were centrally performed, using seven reagent/analyzer combinations including two without DS. The association between anti-Xa levels and covariates was tested using a linear mixed-effects model.
RESULTS
We analyzed 4,546 anti-Xa values from 165 patients. Median anti-Xa levels were systematically higher with reagents containing DS, whatever the patient group, with the greatest effect observed in G1 (0.32 vs 0.05 IU/mL). Anti-Xa levels were slightly higher in CTAD than in citrate samples, irrespective of the assay. The model showed: (1) a significant dextran-patient group interaction ( < 0.0001), the effect of DS on anti-Xa levels varying from 30.9% in G4 to 296% in G1, and (2) a significant effect of CTAD, varying between patient groups ( = 0.0302).
CONCLUSION
The variability of anti-Xa levels with a great overestimation of the values, using a reagent containing DS, can lead to different treatment decisions, especially after heparin neutralization by protamine. Clinical consequences of these differences remain to be demonstrated.
Topics: Humans; Heparin; Anticoagulants; Prospective Studies; Critical Illness; Heparin, Low-Molecular-Weight; Citric Acid; Citrates; Factor Xa Inhibitors; Partial Thromboplastin Time
PubMed: 37321244
DOI: 10.1055/s-0043-1770096 -
Molecular Pain 2024Pruritis, the sensation of itch, is produced by multiple substances, exogenous and endogenous, that sensitizes specialized sensory neurons (pruriceptors and...
Pruritis, the sensation of itch, is produced by multiple substances, exogenous and endogenous, that sensitizes specialized sensory neurons (pruriceptors and pruri-nociceptors). Unfortunately, many patients with acute and chronic pruritis obtain only partial relief when treated with currently available treatment modalities. We recently demonstrated that the topical application of high molecular weight hyaluronan (HMWH), when combined with vehicles containing transdermal transport enhancers, produce potent long-lasting reversal of nociceptor sensitization associated with inflammatory and neuropathic pain. In the present experiments we tested the hypothesis that the topical formulation of HMWH with protamine, a transdermal transport enhancer, can also attenuate pruritis. We report that this topical formulation of HMWH markedly attenuates scratching behavior at the nape of the neck induced by serotonin (5-hydroxytryptamine, 5-HT), in male and female rats. Our results support the hypothesis that topical HMWH in a transdermal transport enhancer vehicle is a strong anti-pruritic.
Topics: Animals; Hyaluronic Acid; Male; Female; Rats; Rats, Sprague-Dawley; Administration, Cutaneous; Protamines; Molecular Weight; Serotonin; Administration, Topical
PubMed: 38728068
DOI: 10.1177/17448069241254455 -
Europace : European Pacing,... Dec 2023Pericardial tamponade (PT) is the most frequent severe complication during electrophysiology (EP) procedures and requires immediate, co-ordinated, and effective...
AIMS
Pericardial tamponade (PT) is the most frequent severe complication during electrophysiology (EP) procedures and requires immediate, co-ordinated, and effective treatment. However, multiple aspects of PT treatment are either not standardized or are under ongoing debate.
METHODS AND RESULTS
An online questionnaire consisting of 26 multiple-choice questions was sent out to the European Heart Rhythm (EHRA) Research Network and also distributed via social media outputs. The EHRA survey was conducted between May and June 2023. A total of 213 replies were received from European (87%) and non-European countries. Ninety per cent of all participants perform interventions in dedicated EP labs equipped with different ablation platforms. In case of PT, most participants use X-ray as the main imaging modality guiding pericardial puncture, predominantly aiming for an anterior puncture site. Sheaths of different sizes are introduced into the pericardial space (84.3%), followed by a pigtail catheter. Application of protamine is an established but variable step in the majority (84.6%). Novel oral anticoagulants (NOAC) antidotes are not used by 73.3% of participants, while 15.2% routinely apply them. Re-transfusion of aspirated blood is performed by 72.1% [before protamine administration (18.2%), after protamine administration (13.5%), if pericardial effusion cannot be controlled (40.4%)]. A total of 72.4% re-transfuse without blood filter systems. A decision for surgical intervention is mostly taken if bleeding continues despite all interventional measures.
CONCLUSION
The current survey demonstrates that the management of PT is heterogeneous among centres. The findings of this survey may help to guide operators in their treatment and decisions in the setting of PT.
Topics: Humans; Anticoagulants; Cardiac Tamponade; Surveys and Questionnaires; Protamines; Electrophysiology
PubMed: 38163951
DOI: 10.1093/europace/euad378 -
Scientific Reports Aug 2023Interstitial cystitis (IC) has severe clinical symptoms with unclear mechanism. The continuous inflammatory response of the bladder is the basis of its pathogenesis....
Interstitial cystitis (IC) has severe clinical symptoms with unclear mechanism. The continuous inflammatory response of the bladder is the basis of its pathogenesis. Endoplasmic reticulum stress (ERS) is involved in the regulation and development of various inflammatory diseases. And autophagy plays an important role in IC. In this study, we mainly focus on the therapeutic effect of endoplasmic reticulum stress and autophagy on protamine/lipopolysaccharide-induced interstitial cystitis. Female Sprague-Dawley rats were randomized into three experimental groups as follows: sham controls(N), IC alone, and IC+4-PBA.Rats in group IC received 10 mg/ml PS in the urinary bladder, followed by 2 mg/ml LPS instillation after 30 min, IC+4-PBA group SD rats received 4-PBA solution administered intragastrically once a day for 5 days. ERS biomarker (GRP78), autophagy-related proteins (LC3I/II, and Beclin1), autophagic flux biomarker (P62), inflammatory biomarkers (IL-6, TNF-a, NF-κB), apoptotic biomarkers (Caspase 3, Bax) were highest in the IC group compared to IC+4-PBA group and N group and the biomarkers expression in IC+4-PBA group were lower than in the IC group, anti-apoptotic biomarker (Bcl-2) was highest in the N group compared to the IC group and IC+4-PBA group and lower in the IC group than in the IC+4-PBA group, oxidative stress biomarkers (HO-1, NQO-1) were remarkably lower in the control group than in the IC and IC+4-PBA groups and notably lower in the IC group than in the IC+4-PBA group. The histological score and mast cell count demonstrated most severe in the IC group than those in the IC+4-PBA group. TUNEL assay examined the level of apoptosis in IC group was higher than in the IC+4-PBA group. The bladder micturition function was significantly improved with 4-PBA treatment. 4-PBA inhibits ERS to recover autophagic flux, and then to suppress the bladder oxidative stress, the inflammatory reaction and apoptosis, finally improve the bladder urinary function in Protamine/Lipopolysaccharide (PS/LPS) induced IC.
Topics: Female; Rats; Animals; Cystitis, Interstitial; Lipopolysaccharides; Rats, Sprague-Dawley; Autophagy; Endoplasmic Reticulum Stress
PubMed: 37640742
DOI: 10.1038/s41598-023-38584-x -
Pharmaceutics Jul 2023Substrate reduction therapy (SRT) has been proposed as a new gene therapy for Fabry disease (FD) to prevent the formation of globotriaosylceramide (Gb3). Nanomedicines...
Substrate reduction therapy (SRT) has been proposed as a new gene therapy for Fabry disease (FD) to prevent the formation of globotriaosylceramide (Gb3). Nanomedicines containing different siRNA targeted to Gb3 synthase (Gb3S) were designed. Formulation factors, such as the composition, solid lipid nanoparticles (SLNs) preparation method and the incorporation of different ligands, such as gold nanoparticles (GNs), protamine (P) and polysaccharides, were evaluated. The new siRNA-golden LNPs were efficiently internalized in an FD cell model (IMFE-1), with GNs detected in the cytoplasm and in the nucleus. Silencing efficacy (measured by RT-qPCR) depended on the final composition and method of preparation, with silencing rates up to 90% (expressed as the reduction in Gb3S-mRNA). GNs conferred a higher system efficacy and stability without compromising cell viability and hemocompatibility. Immunocytochemistry assays confirmed Gb3S silencing for at least 15 days with the most effective formulations. Overall, these results highlight the potential of the new siRNA-golden LNP system as a promising nanomedicine to address FD by specific SRT.
PubMed: 37514122
DOI: 10.3390/pharmaceutics15071936 -
NMR in Biomedicine Nov 2023Chemical exchange saturation transfer (CEST) MRI has been identified as a novel alternative to classical diagnostic imaging. Over the last several decades, many studies...
Chemical exchange saturation transfer (CEST) MRI has been identified as a novel alternative to classical diagnostic imaging. Over the last several decades, many studies have been conducted to determine possible CEST agents, such as endogenously expressed compounds or proteins, that can be utilized to produce contrast with minimally invasive procedures and reduced or non-existent levels of toxicity. In recent years there has been an increased interest in the generation of genetically engineered CEST contrast agents, typically based on existing proteins with CEST contrast or modified to produce CEST contrast. We have developed an in silico method for the evolution of peptide sequences to optimize CEST contrast and showed that these peptides could be combined to create de novo biosensors for CEST MRI. A single protein, superCESTide, was designed to be 198 amino acids. SuperCESTide was expressed in E. coli and purified with size exclusion chromatography. The magnetic transfer ratio asymmetry generated by superCESTide was comparable to levels seen in previous CEST reporters, such as protamine sulfate (salmon protamine) and human protamine. These data show that novel peptides with sequences optimized in silico for CEST contrast that utilize a more comprehensive range of amino acids can still produce contrast when assembled into protein units expressed in complex living environments.
Topics: Humans; Escherichia coli; Magnetic Resonance Imaging; Peptides; Protamines; Amino Acids; Biosensing Techniques; Contrast Media
PubMed: 37469121
DOI: 10.1002/nbm.5007 -
International Journal of Molecular... Jan 2024Infertility affects millions of couples worldwide and has a profound impact not only on their families, but also on communities. Telomere attrition has been associated...
Infertility affects millions of couples worldwide and has a profound impact not only on their families, but also on communities. Telomere attrition has been associated with infertility, DNA damage and fragmentation. Oxidative stress has been shown to affect sperm DNA integrity and telomere length. Sirtuins such as SIRT1 and SIRT3 are involved in aging and oxidative stress response. The aim of the present study is to determine the role of SIRT1 and SIRT3 in regulating oxidative stress, telomere shortening, and their association with oligospermia. Therefore, we assessed the protein levels of SIRT1 and SIRT3, total antioxidant capacity (TAC), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase activity (CAT) in the seminal plasma of 272 patients with oligospermia and 251 fertile men. We also measured sperm telomere length (STL) and leukocyte telomere length (LTL) using a standard real-time quantitative PCR assay. Sperm chromatin and protamine deficiency were also measured as per standard methods. Our results for oligospermic patients demonstrate significant reductions in semen parameters, shorter STL and LTL, lower levels of SOD, TAC, CAT, SIRT1 and SIRT3 levels, and also significant protamine deficiency and higher levels of MDA and DNA fragmentation. We conclude that a shorter TL in sperms and leukocytes is associated with increased oxidative stress that also accounts for high levels of DNA fragmentation in sperms. Our results support the hypothesis that various sperm parameters in the state of oligospermia are associated with or caused by reduced levels of SIRT1 and SIRT3 proteins.
Topics: Humans; Male; Semen; Oligospermia; Antioxidants; Sirtuin 3; Sirtuin 1; Spermatozoa; Protamines; Superoxide Dismutase
PubMed: 38255792
DOI: 10.3390/ijms25020718 -
Biochemistry and Cell Biology =... Jun 2024Insects are the largest group of animals when it comes to the number and diversity of species. Yet, with the exception of , no information is currently available on the...
Insects are the largest group of animals when it comes to the number and diversity of species. Yet, with the exception of , no information is currently available on the primary structure of their sperm nuclear basic proteins (SNBPs). This paper represents the first attempt in this regard and provides information about six species of Neoptera: , and . The SNBPs of these species were characterized by acetic acid urea gel electrophoresis (AU-PAGE) and high-performance liquid chromatography fractionated. Protein sequencing was obtained using a combination of mass spectrometry sequencing, Edman N-terminal degradation sequencing and genome mining. While the SNBPs of several of these species exhibit a canonical arginine-rich protamine nature, a few of them exhibit a protamine-like composition. They appear to be the products of extensive cleavage processing from a precursor protein which are sometimes further processed by other post-translational modifications that are likely involved in the chromatin transitions observed during spermiogenesis in these organisms.
Topics: Animals; Male; Amino Acid Sequence; Protamines; Nuclear Proteins; Insect Proteins; Insecta; Molecular Sequence Data; Spermatozoa
PubMed: 38408323
DOI: 10.1139/bcb-2023-0363 -
Cureus Sep 2023Infective endocarditis can be acute or subacute. It can be caused by viral, bacterial, fungal, and sometimes nonbacterial etiologies. It is an important cause of...
Infective endocarditis can be acute or subacute. It can be caused by viral, bacterial, fungal, and sometimes nonbacterial etiologies. It is an important cause of mortality and morbidity in children as well as adolescents, despite advances in management. A 59-year-old male with a past medical history of aortic valve (AV) replacement on warfarin presented to the Emergency Department with dull right flank pain and poor dentition on examination. Computerized tomography (CT) scans of the abdomen revealed the presence of splenic and renal infarcts. Warfarin was held after the international normalized ratio (INR) was noted to be elevated at 11. Following the activation of the sepsis bundle in the ER, he received intravenous fluids (30 cc/kg) and was started on vancomycin and ceftriaxone. On further evaluation, the transesophageal echocardiogram revealed mobile densities on the aortic surface concerning vegetation. Antibiotics were transitioned to cefazolin, gentamycin, and rifampin for the management of prosthetic valve endocarditis. The patient's INR improved to 3.5 on the third day of hospitalization, and heparin was initiated to maintain anticoagulation for the prosthetic valve. However, on the eighth day of hospitalization, the patient developed left-sided weakness and slurred speech. The CT head showed acute frontoparietal intracranial hemorrhage (ICH), with an INR noted to be 5. Heparin was reversed with protamine sulfate, and vitamin K was administered, following which the INR improved to 2.3. The patient was transferred to intensive care, but on the second day of the ICU stay, the INR again shot up to 6 with normal LFTS. The patient received vitamin K, but the INR only improved to 5. Subsequently, antibiotics were changed from cefazolin to nafcillin. INR thus fell to 1.6 in two days after changing the antibiotics. The patient was soon transferred to a higher center for aortic valve replacement. While few case reports have described severe coagulopathy induced by cefazolin, it is particularly seen with impaired renal function; however, our patient's renal function was completely normal. Coagulopathy is due to the drug's effect on intestinal flora and its structural methyl-thiadiazole side chain, which has similar effects as epoxide reductase inhibitors and results in INR elevation. Patients on cefazolin need to be closely monitored for INR levels every day, as there is a high likelihood of developing complications like ICH, as noted in this patient. While the monitoring of cefazolin levels is not necessarily indicated, it is necessary to place patients on fall precautions and monitor INR levels every day, as mentioned above.
PubMed: 37814735
DOI: 10.7759/cureus.44875