Plasma Production Research Articles

Value of Prophylactic Plasma Treatment and Incidence of Acute Episodes in Patients Enrolled in the International Hereditary Thrombotic Thrombocytopenic Purpura Registry

Background: Hereditary thrombotic thrombocytopenic purpura (hTTP), or Upshaw-Schulman syndrome, is a rare thrombotic microangiopathy due to a severe congenital deficiency of ADAMTS13 resulting from bi-allelic ADAMTS13 mutations. As in other plasma factor deficiencies, treatment consists of replacement of the missing ADAMTS13, which can currently be attempted with fresh frozen plasma, solvent/detergent plasma or plasma-derived factor VIII/Von Willebrand factor concentrates. Although prophylactic plasma infusions prevent acute episodes in many but not all hTTP patients, current treatment guidelines state conditional recommendations for prophylaxis outside of pregnancy, because evidence supporting the burdensome plasma prophylaxis in hTTP patients is scarce. Aims: Prospective evaluation of the incidence of acute episodes occurring in hTTP patients during periods with and without prophylactic plasma treatment. Methods: All patients with a confirmed diagnosis of hTTP enrolled in the International hTTP Registry between January 01, 2006 and December 31, 2021 were eligible for study. Diagnosis of hTTP was based on persisting ADAMTS13 activity <10%, bi-allelic ADAMTS13 mutations, and/or an infusion trial with full recovery and a half-life of plasma ADAMTS13 of around 60 hours. We recorded the patients' detailed medical history at enrollment and then collected prospective data on the clinical course, treatment modalities and laboratory values through site-visits and case report forms completed by treating physicians during annual visits or at occurrence of acute TTP episodes. Patients were followed until December 31, 2022 (database lock), death, or loss to follow-up, whatever came first. This post-hoc analysis evaluated acute TTP episodes during follow-up, stratified by periods on prophylaxis and without prophylaxis. Patients could contribute follow-up time to both periods (strata), but never simultaneously and gestation periods were excluded. Minimum criterion for long-term prophylaxis was defined as at least one monthly plasma infusion over a period of ≥ 6 months. Results were reported using descriptive statistics without formal statistical comparison and incident rates of acute TTP events were calculated per 1000 person-years with corresponding 95% confidence intervals (CIs). Results: At the end of December 2021, the International hTTP Registry had 182 confirmed hTTP patients eligible for this analysis that were followed for a median period of 3.6 (range, 0-18.5) years. The gender distribution showed more female (n=98, 53.8%) than male (n= 84, 46.2%) patients enrolled, a disparity likely related to a surge of diagnosis in women due to pregnancy complications. During prospective follow-up, 47 (25.8%) hTTP patients never had prophylactic treatment, while 135 (74.2%) received any form of prophylactic treatment, including long-term prophylaxis in 117 (86.7%). Patients who received any prophylactic treatment during follow-up had an incidence rate (95% CI) of acute TTP episodes of 272.4 (230.8-319.3) per 1000 person-years while receiving prophylaxis and of 520.4 (401.6-663.3) per 1000 person-years during periods without prophylaxis (Table 1). In the patients on long-term prophylaxis, the incidence rate of acute TTP episodes was 267.1 (226.0-313.6) per 1000 person-years in periods with prophylaxis, and 879.6 (664.4-1142.2) per 1000 person-years without prophylaxis. Irrespective of treatment interval, about half of patients on prophylaxis had break-through events, with the highest incidence rate observed in the group of patients receiving plasma products weekly, possibly reflecting their more precarious or severe disease course. Conclusions: In this large hTTP patient cohort observed for five years on average, we confirm the incidence rate of acute events as reported by Tarasco et al. (Blood 2021;137;3563-75). Here, we demonstrate for the first time that hTTP patients with disease courses requiring prophylaxis benefit from this burdensome treatment, which was most evident in patients on long-term prophylaxis. Current treatment options are however insufficient to suppress residual disease activity leading to break-through events observed in half of the patients on prophylaxis. Novel therapies, such as recombinant ADAMTS13, with the potential of reaching higher plasma levels, will likely overcome limitations of current treatment options.

Damage Control Resuscitation in Traumatic Hemorrhage: It Is More Than Fixing the Holes and Filling the Tank.

Damage control resuscitation is the foundation of hemorrhagic shock management and includes early administration of plasma, tranexamic acid, and limited crystalloid-containing products.

Applicability of the Klein-Gordon equationfor pair production in vacuum and plasma.

In this paper, a phase-space description of electron-positron pair creation will be applied, based on a Wigner transformation of the Klein-Gordon equation. The resulting theory is similar in many respects to the equationsfrom the Dirac-Heisenberg-Wigner formalism. However, in the former case, all physics related to particle spin is neglected. In the present paper we compare the pair-production rate in vacuum and plasmas, with and without spin effects, in order to evaluate the accuracy and applicability of the spinless approximation. It is found that for modest frequencies of the electromagnetic field the pair production rate of the Klein-Gordon theory is a good approximation to the Dirac theory, provided the matter density is small enough for Pauli blocking to be neglected, and a factor of 2 related to the difference in the vacuum energy density is compensated for.

Hematological disorders as a complication of COVID-19

Background. Coronavirus disease (COVID-19) can affect the blood and hemostasis systems and lead to complications that require intensive care. The aim is to detect such common complications by studying literary sources and clinical experience. Materials and methods. The search for relevant literature was conducted in PubMed, and in the other databases such as Science Direct, Google Scholar, Scopus and Web of Science. The literature search was done using the keywords “COVID-19”, “SARS-CoV-2” in combination with “coagulation dysfunction”, “coagulopathy”, “hematological manifestations”, “hematological parameters”, “deep vein thrombosis”, “pulmonary embolism”, “arterial thrombosis”, “D-dimer”, “fibrinogen”, “lymphopenia”, “thrombocytopenia”. Results. COVID-19-associated coagulopathy is characterized by high levels of D-dimer and fibrin degradation products in blood plasma, changes in prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count. Endothelial dysfunction caused by coronavirus leads to an increased risk of thrombotic complications, both in venous and arterial systems, additionally to the existing higher risk of thrombosis in the intensive care unit. The venous thromboembolism frequency among unvaccinated hospitalized patients and during ultrasound screening is significantly higher. Coronavirus disease can lead to arterial thrombosis in areas such as the aorta, kidneys, cerebral and peripheral arteries. COVID-19 can cause enhanced-fibrinolytic-type disseminated intravascular coagulation or limited thrombotic microangiopathy. According to research, patients with severe COVID-19 usually had leukocytosis, lymphopenia, and an elevated neutrophil-to-lymphocyte ratio. Thrombocytopenia is observed not only during the acute coronavirus disease, but also in the post-COVID-19 period. Both thrombosis and bleeding can occur in patients undergoing extracorporeal membrane oxygenation. Conclusions. A high level of D-dimer, a prolongation of prothrombin time, an increase or a quick decrease in fibrinogen level, lymphopenia, neutrophilia, and an increase in the neutrophil-to-lymphocyte ratio are considered prognostic factors for the severity of coronavirus disease. Deep vein thrombosis and pulmonary embolism are the most common thrombotic events in patients with COVID-19. Arterial thrombosis occurs more often in the cerebral arteries and arteries of the extremities.

The Simulation of Dielectric Barrier Discharge for Breakdown Voltage in Starch Modification

This paper presents the simulation results for dielectric barrier discharge (DBD) at atmospheric pressure in argon gas for different relative permittivity, granule shape, thickness layer, and granule diameter measurements for starch on the breakdown voltage. DBD is commonly utilized to generate cold plasma for starch modification. The electric field was computed using COMSOL Multiphysics 5.3a software. The breakdown voltage was calculated employing Paschen’s law for this electric field. The voltage was found according to the breakdown criterion for gap distance 0.2–1.0 cm, and then the Paschen curve could be plotted. The results show that the top electrode of the plasma system may be replaced with the parallel plate electrode by a mesh electrode with a bigger mesh size to achieve a lower breakdown voltage. In addition, increasing the relative permittivity and decreasing the thickness layer can reduce the applied voltage for plasma formation. When compared to the sphere and ellipsoid shapes, starch with a polyhedral granule shape requires a significantly lower voltage for breakdown. The starch granule diameter does not affect the breakdown voltage. These findings can be utilized to determine the optimal breakdown voltage for each type of starch modification, contributing to the construction of a high-efficiency plasma production system for starch modification.

Recombinant Human Diamine Oxidase Against Histamine Induced Shock - Implications for Mast Cell Activation Syndrome

Background and Objective:Mastocytosis patients suffer from a clonal increase in mast cells which produce and release excessive amounts of histamine even under stable conditions (Keyzer et al. 1983). Unfortunately, symptom control with new kinase inhibitors is variable and modest at best. Mast cell activation syndrome may further enhance histamine release which can result in recurrent shocks (Böhm et al. 2019), or severe, protracted anaphylaxis refractory to epinephrine (Grafeneder et al. 2022). Previously we demonstrated that recombinant human diamine oxidase (rhDAO) fully degrades 100-fold elevated histamine concentrations in plasma samples from mastocytosis patients. In vivo rhDAO, with a mutated heparin binding motif (mHBM), was able to digest massively increased histamine levels, thereby improving indirect measures of shock such as a temperature drop in mice (Karer et al. 2022). As mice are insensitive to histamine (intravenous LD50 of 385mg/kg in mice compared with 0.18mg/kg in guinea pigs), this unfortunately limits their translational value. To assess the therapeutic potential of rhDAO_mHBM, we tested its efficacy for the prevention and treatment of histamine induced shock in guinea pigs, the only histamine sensitive rodent species. Methods:Guinea pigs received continuous intravenous infusions of 8 µg/kg/min histamine to model its release from activated circulating basophils or subcutaneous injections of 1mg/kg histamine to mimic peripheral histamine release by mast cells. We used intramuscular injections of 5µg/kg adrenaline as a benchmark, because it is recommended in guidelines for the treatment of anaphylaxis, although its efficacy had never been proven. Infusions of rhDAO_mHBM were given either prophylactically before- or therapeutically after - symptom onset. Mean arterial pressure was measured intra-arterially and rhDAO_mHBM levels were quantified by enzyme immunoassay and histamine concentrations by a liquid chromatography -tandem mass spectrometry (LC-MS/MS) method. The primary outcome variable was prevention of shock as defined by a >=30% drop in mean arterial blood pressure. Results:Guinea pigs pretreated with 4 mg/kg rhDAO_mHBM showed lower mean heart rate (p<0.01) and higher body core temperatures at the end of the intravenous histamine infusions compared to controls (p<0.05). Histamine infusions increased median urinary excretion of histamine and N-methyl-histamine 8.6- and 4.0-fold (p<0.05), respectively. Pretreatment with 4 mg/kg rhDAO_mHBM reduced urinary histamine (p<0.01) and N-methyl-histamine (p<0.01) concentrations compared with controls. Subcutaneous injections of 1 mg/kg histamine induced shock within 20 minutes in all control animals, and the experiments had to be terminated prematurely in several animals. Intramuscular injection of 5mcg/kg adrenaline (similar to human adrenaline auto-injector doses) after symptom onset was unable to prevent shock, confirming its lack of efficacy demonstrated previously in an anaphylaxis model in dogs (Mink et al. 2004). In contrast, prophylactic infusions of 4-8mg/kg rhDAO_mHBM prevented hypotensive shock in all treated animals (p<0.01). After an initial histamine induced drop in blood pressure, 8mg/kg rhDAO_mHBM restored blood pressure and prevented shock in all animals when injected at the time of symptom occurrence (p<0.01 Chi2 test). Figure 1 demonstrates the median drop in blood pressure and development of shock (indicated by the dashed line) by subcutaneous injection of 1mg/kg histamine (black squares), and the prevention of shock by rhDAO-mHBM given before (blue up triangles) or after (red circles) histamine injections. Conclusion: This is the first demonstration of the beneficial effects of rhDAO_mHBM in a histamine-sensitive species. rhDAO_mHBM is a novel therapeutic approach targeting histamine excess which effectively prevented shock, in contrast to intramuscular epinephrine. As the mechanism of action is not species specific, these findings can be translated from guinea pigs to humans: it will help to select optimal dosing of rhDAO_mHBM during clinical development for the prophylaxis in - and treatment of - mastocytosis patients suffering from histamine induced symptoms or mast cell activation syndrome, or patients with anaphylaxis induced by asparaginase, plasma products or other medications.

Nitrogen fixation as NOx using air plasma coupled with heterogeneous catalysis at atmospheric pressure

AbstractThis study presents insights into the use of activated catalysts to improve the energy efficiency of production in atmospheric pressure air plasma. The introduction of catalysts in the direct current glow discharge system reduces the energy cost of production by up to 45% at low gas flow rates. Notably, even when positioned away from the plasma zone, the catalyst enhanced production, suggesting a significant role for the catalytic activation of downstream neutral species. The study also introduced a novel approach involving an air plasma jet infused with floating catalyst powder. This method significantly increased energy efficiency at higher discharge currents, with an associated energy cost of 2.9 MJ/mol for production.

Stark broadening of the cesium 52D5/2 → 102F line shape

Pump modulated laser absorption spectroscopy was used to measure the cesium 52D5/2→102F5/2,7/2 line shape. Alkali density in an optically pumped low pressure cell was increased from 0.5 to 85×1012cm−3, resulting in a factor of 200 increase in Lorentzian width due to Stark broadening (2.76GHz/1012cm−3). The observed red shift is consistent with literature, and the shift-to-width ratio δ/γ=−0.356±0.015 informs an electron temperature of 1820±100K. A linear trend between alkali density and electron density is seen, suggesting that electron impact is the primary plasma production mechanism. A maximum ionized concentration of 28% was observed.

Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections

Group A streptococcus (GAS) is a major bacterial pathogen responsible for both local and systemic infections in humans. The molecular mechanisms that contribute to disease heterogeneity remain poorly understood. Here we show that the transition from a local to a systemic GAS infection is paralleled by pathogen-driven alterations in IgG homeostasis. Using animal models and a combination of sensitive proteomics and glycoproteomics readouts, we documented the progressive accumulation of IgG cleavage products in plasma, due to extensive enzymatic degradation triggered by GAS infection in vivo. The level of IgG degradation was modulated by the route of pathogen inoculation, and mechanistically linked to the combined activities of the bacterial protease IdeS and the endoglycosidase EndoS, upregulated during infection. Importantly, we show that these virulence factors can alter the structure and function of exogenous therapeutic IgG in vivo. These results shed light on the role of bacterial virulence factors in shaping GAS pathogenesis, and potentially blunting the efficacy of antimicrobial therapies.

Implementation of Indian National plasma policy at blood bank of a tertiary care hospital: A step towards strengthening of blood transfusion services

IntroductionThe World Health Organization has advocated that every country should make its own policy for ensuring safe and adequate supply of plasma derived medicinal products through mobilization and usage of locally collected plasma. The National Plasma Policy (NPP) of India was published in 2014 with a dual objective to achieve self sufficiency in the production of plasma derived medicinal products and at the same time to augment the component preparation facilities in India and overall upliftment of blood transfusion services in the country. Thus the present study was done to access the impact of implementation of NPP in our blood bank on the blood transfusion services in our hospital. Materials and methodsThe present study was a retrospective observational study conducted in the department of transfusion medicine of a tertiary care hospital in India involving analysis of data from 1st January 2019 till 31st December 2022. For the purpose of data analysis the time period was divided into 2 periods: (i) Pre-NPP implementation period from 1st January 2019 till 31st December 2020; (ii) Post-NPP period from 1st January 2021 till 31st December 2022. The following parameters were compared for the two periods: (i) component preparation rate; (ii) percentage of component therapy; (iii) total number of FFP transferred to plasma fractionation centers; (iv) total amount of exchange amount generated in lieu of transferred FFP to plasma fractionation centers. ResultsThe component preparation rate after NPP implementation was significantly higher as compared to the pre NPP implementation period (93.81% vs 56.70%; p = 0.007). The percentage of component therapy in the patients was also significantly higher as compared to the pre-NPP implementation period (97.9% vs 73.6%; p = 0.005). The total amount of exchange amount generation in Indian rupee (INR) after NPP implementation was INR 1419462 (15835€) while it was INR 636898 (7105€) in the pre NPP implementation period. This amount was utilized for procurement of various blood bank equipment, in addition 2 lab technicians were also hired for the blood bank. ConclusionsThe implementation of NPP resulted in upliftment of blood transfusion services in our hospital. Other low and middle income countries can benefit from implementation of similar plasma policy in their countries.

Histomorphology of the vesicular and prostate glands of newborn piglets

The economic efficiency of animal husbandry depends on the productivity of the herd, which is usually assessed by analyzing the reproductive performance of females. However, similar indicators of males should be equally taken into account. The accessory sex glands of males are involved in the production of seminal plasma, thereby playing an important role in the reproductive process. The aim of the study is to give a histomorphological characteristic of the accessory sex glands and to determine their functional state in newborn piglets. The object of the study was the accessory sex glands of newborn piglets at the age of 1 day. The vesicular and prostate glands were selected for histological examination. The material was fixed in a 10% solution of neutral formalin for 24 hours, after which it was poured into paraffin according to the generally accepted method. Then sections with a thickness of 3- 5 microns were made, which were stained with hematoxylin and eosin. Some of the sections were painted with Masson Trichrome, alcian blue. It was found that in newborn piglets, the vesicular gland is located on the dorsal surface of the bladder, at the beginning of the pelvic part of the urethra, the prostate gland is located caudally from the vesicular gland, dorsally from the genitourinary canal. The study established the main histomorphological features of the vesicular and prostate glands in newborn piglets. The parenchyma of the glands is in the stage of functional immaturity, most of the organ is occupied by the connective tissue stroma, among the elements of which there is a large number of fibroblastic cells. At the same time, secretory activity of some end sections of the vesicular gland is noted. The data obtained are the starting point for further studies of the functional activity of the cells of the accessory sex glands in boars.

Analysis of antibodies avidity for Tityus serrulatus scorpion venom in antivenom production and its potential for application as a potency test

Antivenoms are the only specific medication for neutralizing toxins present in venom of animals such scorpions and snakes through antigen-antibody binding. Several analyses are carried out throughout its production in order to ensure the quality and effectiveness of the antivenom that will be administered to the patient. One of these is the potency assay, which is performed to assess the ability of antivenoms to neutralize the toxic effects of the venom injected in mice. The substitution of in vivo for in vitro assays such as ELISA has been presented by other authors, bringing several advantages such as the reduction in the use of animals, in costs and in the duration of the assays. However, the avidity index of antivenom antibodies determined by ELISA has not yet been applied for this purpose. Therefore, the objective of this study was to evaluate the avidity of sera from hyperimmunized horses with crude Tityus serrulatus venom, a scorpion species associated with the most serious accidents in Brazil, and its potential for application as a potency test replacing the in vivo assay. The avidity ELISA proved to be interesting for monitoring the binding strength of antibodies produced by horses in hyperimmune plasma production programs. It was possible to verify oscillations in antibody avidity that occurred along the immunization cycles, differences between novice and veteran horses, maturation of antibody avidity, and correlation between avidity index and antibody titre. Similar results were obtained for crude venom and purified Ts1 toxin. In addition, the avidity ELISA apparently demonstrated potential for application as a potency test in the initial stage of antivenom production. However, more studies are necessary.

Вплив aктовегіну на механізми розвитку окисного стресу у хворих на цукровий діабет 2-го типу з кардіоваскулярною автономною нейропатією

The effects of actovegin on the mechanisms of oxidative stress (OS) developing in the blood of patients with type 2 diabetes mellitus (DM2) and cardiovascular autonomic neuropathy (CVAN) were investigated. The aim of the study was to establish the effectiveness of treatment with actovegin for the pro- and antioxidant balance impairment and changes in gene expression of HIF-1α and mTOR in the blood of patients with DM2 and CVAN. It was shown that intravenous injections of actovegin at a dose of 1000 mg per day for 10 days and further prolonged oral administration of this drug at a dose of 800 mg per day for 90 days led to a decrease in the content of secondary products of lipid peroxidation in blood plasma and H2O2 production in erythrocytes of patients with DM2 and CVAN. These changes were indicative of a weakening of OS intensity. It was also shown that treatment with actovegin promoted an increase in total plasma SOD activity as well as reduced glutathione and glutathione peroxidase activity in erythrocytes from patients. Treatment with actovegin also raised the gene expression of HIF-1α and reduced the gene expression of mTOR in leukocytes of patients with DM2 and CVAN. These genetic changes may serve as a protective mechanism against the development of OS, which acts through different metabolic pathways. So, actovegin administration counteracting OS development due to the impact on the different components of pro- and antioxidant system as well as on HIF-1α and mTOR genes expression may offer new clinical avenues for pharmacological treatment of patients with DM2 and CVAN.

A novel reagent for the screening of haptoglobin-deficient blood donors.

In Japan, the prevalence of haptoglobin deficiency is approximately 1 in 4000. Haptoglobin-deficient individuals may produce anti-haptoglobin from allo-immunization, leading to serious transfusion reactions. Therefore, implementation of a consistent supply of haptoglobin-deficient fresh frozen plasma is crucial. We developed a novel reagent to facilitate large-scale identification of haptoglobin-deficient individuals as potential donors of plasma products. We established mouse monoclonal anti-haptoglobin-producing cell lines (three clones) using the hybridoma method by immunizing mice with the haptoglobin protein. Purified antibodies were conjugated with carboxylate-modified polystyrene latex beads and used for haptoglobin measurements by the latex agglutination method using an automatic analyser (LABOSPECT008). Samples with low protein concentrations were re-examined by enzyme-linked immunosorbent assay to confirm the results. Additionally, the haptoglobin gene was amplified by polymerase chain reaction to confirm the haptoglobin deletion allele (Hpdel ). From February to October 2022, 7476 blood donor samples were screened. Two haptoglobin-deficient and 21 low-haptoglobin-expressing individuals were identified. Two haptoglobin-deficient donors were found homozygous for Hpdel , and 19 (90%) of the 21 low-haptoglobin-expressing individuals were heterozygous for Hpdel , which includes the first reported case of heterozygous Hpdel /HpJohnson . We developed a new reagent for the detection of haptoglobin deficiency, which is automatable and inexpensive and appears useful for large-scale screening of blood donors.

B-100 Hbsag Performance Improvement of Novel MASTM Infectious Controls for Serology Diagnostic Tests

Abstract Background Hepatitis B is a liver infection caused by the Hepatitis B virus. While preventable by vaccination, Hepatitis B remains prevalent across the globe. While prevalence is low in many areas of the world, there are still regions in which the prevalence is considered to be high. Hepatitis B surface antigen (HBsAg) can be one of the first indicators of Hepatitis B infection, and it is a commonly screened diagnostic test to determine if a patient is immune, susceptible, or has acute or chronic HBV infection. While HBsAg is a critical marker in diagnosing a patient, it presents unique challenges. The Thermo Scientific™ MAS™ Omni™ Infectious BSI Positive Control Panel* is a multi-constituent IVD control containing anti-HIV-1/2, anti-HBc, anti-HCV, and anti-HTLV I/II antibodies, as well as Hepatitis B surface antigen (HBsAg) in a human plasma-based matrix. Development and Stability Studies were conducted to evaluate and ensure optimal analyte performance throughout the shelf-life duration. As this is a multi-constituent control, the HBsAg challenges must be adequately addressed to ensure the integrity and reliability of the results of all analytes. Two specific areas of focus are HBsAg instability at increased temperature and HBsAg-Fibrinogen interaction in plasma products. We report here the continued development and assessment of HBsAg in the MAS™ Omni Infectious Controls family. Methods The BSI Positive Control Panel was evaluated with IVD assays to assess Shelf-Life and demonstrate the effect of elevated temperature and fibrinogen on HBsAg. Shelf life of the products was determined by real-time, accelerated, open vial, and in-use stability monitoring. Additionally, open-vial stability monitoring demonstrates the relationship between HBsAg and fibrinogen within the control products. Between Month 0 and 12, samples were run neat without processing. At Month 12, samples were centrifuged to verify the validity of the open-vial stability claim. Results The evaluation of the BSI Positive Control Panel demonstrates the effects of temperature and fibrinogen on HBsAg. The Real-Time and Accelerated stability studies combine to demonstrate the effect of elevated temperatures on HBsAg within the multi-analyte control. The Open-Vial stability studies completed at 0 and 12 months combine to demonstrate the effect of fibrinogen on HBsAg within the multi-analyte control. Conclusions The MAS™ Omni Infectious control products will perform optimally provided the proper sample processing and storage conditions are implemented. Improper storage at elevated temperatures will result in degradation at an increased rate for the HBsAg present in the sample. Additionally, it is imperative that the proper raw materials are chosen in the production of the multi-analyte controls. When using plasma products, it is best to use defibrinated plasma. For extra precaution, raw material should be centrifuged and filtered prior to production to avoid degradation due to fibrinogen. Reliable, high-quality controls are vital in ensuring that clinical diagnostic assays are functioning properly. *Availability of product in each country depends on local regulatory marketing authorization status

The effects of resuscitation with different plasma products on endothelial permeability and organ injury in a rat pneumosepsis model

BackgroundEndothelial injury and permeability are a hallmark of sepsis. Initial resuscitation of septic patients with crystalloids is associated with aggravation of endothelial permeability, which may be related either to low protein content or to volume. We investigated whether initial resuscitation with different types of plasma or albumin decreases endothelial dysfunction and organ injury in a pneumosepsis rat model compared to the same volume of crystalloids.Study design and methodsSprague–Dawley rats were intratracheally inoculated with Streptococcus pneumoniae. Twenty-four hours after inoculation, animals were randomized to 2 control groups and 5 intervention groups (n = 11 per group) to receive resuscitation with a fixed volume (8 mL/kg for 1 h) of either Ringer’s Lactate, 5% human albumin, fresh frozen plasma derived from syngeneic donor rats (rFFP), human-derived plasma (hFFP) or human-derived solvent detergent plasma (SDP). Controls were non-resuscitated (n = 11) and healthy animals. Animals were sacrificed 5 h after start of resuscitation (T = 5). Pulmonary FITC-dextran leakage as a reflection of endothelial permeability was used as the primary outcome.ResultsInoculation with S. Pneumoniae resulted in sepsis, increased median lactate levels (1.6–2.8 mM, p < 0.01), pulmonary FITC-dextran leakage (52–134 µg mL−1, p < 0.05) and lung injury scores (0.7–6.9, p < 0.001) compared to healthy controls. Compared to animals receiving no resuscitation, animals resuscitated with rFFP had reduced pulmonary FITC leakage (134 vs 58 µg/mL, p = 0.011). However, there were no differences in any other markers of organ or endothelial injury. Resuscitation using different human plasma products or 5% albumin showed no differences in any outcome.ConclusionsResuscitation with plasma did not reduce endothelial and organ injury when compared to an equal resuscitation volume of crystalloids. Rat-derived FFP may decrease pulmonary leakage induced by shock.

Efficacy Comparison of Three Atmospheric Pressure Plasma Sources for Soybean Seed Treatment: Plasma Characteristics, Seed Properties, Germination

Plasma seed treatment has proven to be a useful technique for improving germination, growth dynamics, as well as plant resistance. In this paper, we studied the efficacy of soybean seeds treatment using various sources of cold atmospheric pressure plasma generated in air. We compared three types of plasma treatments: direct treatment with plasma generated by a diffuse coplanar surface barrier discharge (DCSBD), direct treatment with plasma generated by a multi-hollow surface dielectric barrier discharge, and indirect treatment using the gaseous products of plasma generated by an air plasma jet. The composition of plasma generated by each of the sources was analysed using optical emission spectroscopy and Fourier Transform Infrared spectroscopy (FTIR). Parameters of the plasma treatments have been optimized to improve soybean germination. Plasma-treated seeds were examined by the means of water contact angle, surface free energy and imbibition measurements, attenuated total reflectance FTIR (ATR-FTIR), x-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM) analyses. Surface analysis by ATR-FTIR and XPS showed changes in the chemical bonds on the surface of the plasma-treated seeds, which led to an increase in wettability and imbibition. SEM analysis confirmed that the plasma treatment is non-invasive and does not cause changes in seed surface morphology. Among the studied sources, DCSBD proved to be the best suited for soybean seed treatment in terms of germination improvement as well as treatment time and energy efficiency.

Electric Field Promoted Click Surface-Enhanced Raman Spectroscopy for Rapid and Specific Detection of DNA 2-Deoxyribose 5'-Aldehyde Oxidation Products in Plasma.

Rapid identification of DNA oxidative damage sites is of great significance for disease diagnosis. In this work, electric field-regulated click reaction surface-enhanced Raman spectroscopy (e-Click-SERS) was developed aiming at the rapid and specific analysis of furfural, the biomarker of oxidative damage to the 5-carbon site of DNA deoxyribose. In e-Click-SERS, cysteamine-modified porous Ag filaments (cys@p-Ag) were prepared and used as electrodes, amine-aldehyde click reaction sites, and SERS substrates. Cysteamine was controlled as an "end-on" conformation by setting the voltage of cys@p-Ag at -0.1 V, which ensures its activity in participating in the amine-aldehyde click reaction during the detection of furfural. Benefiting from this, the proposed e-Click-SERS method was found to be sensitive, rapid-responding, and interference-resistant in analyzing furfural from plasma. The method detection limits of furfural were 5 ng mL-1 in plasma, and the whole "extraction and detection" procedure was completed within 30 min with satisfactory recovery. Interference from 13 kinds of common plasma metabolites was investigated and found to not interfere with the analysis, according to the exclusive adaptation of the amine-aldehyde click reaction. Notably, the e-Click-SERS technique allows in situ analysis of biological samples, which offers great potential to be a point-of-care testing tool for detecting DNA oxidative damage.

TRANSFUSION AND INFUSION THERAPY FOR MASSIVE BLOOD LOSS. PART 1, UNEXPECTED INTRAOPERATIVE HAEMORRHAGE

TRANSFUSION AND INFUSION THERAPY FOR MASSIVE BLOOD LOSS. PART 1, UNEXPECTED INTRAOPERATIVE HAEMORRHAGE

Effect of external magnetic field and dust grains on the properties of ion-acoustic waves

An experimental study to investigate the effect of an external magnetic field on the propagation of ion-acoustic waves (IAWs) has been carried out in hydrogen plasma containing two-temperature electrons and dust grains. It is a first step in understanding the propagation properties of IAWs in such an environment. A low-pressure hot cathode discharge method is chosen for plasma production. The desired two-electron groups with distinct temperatures are achieved by inserting two magnetic cages with a cusp-shaped magnetic field of different surface field strengths in the same chamber. The dust grains are dropped into the plasma with the help of a dust dropper, which gain negative charges by interacting with the plasma. The IAWs are excited with the help of a mesh grid inserted into the plasma. A planar Langmuir probe is used as a detector to detect the IAWs. The time-of-flight technique has been applied to measure the phase velocity of the IAWs. The results suggest that in the presence of a magnetic field, the phase velocity of IAWs increases, whereas introducing the dust particles leads to the lower phase velocity. The magnetic field is believed to have a significant effect on the wave damping. This study will aid in utilising IAWs as a diagnostic tool to estimate plasma parameters in the presence of an external magnetic field.