scholarly journals Severity of Thrombocytopenia at the Time of Platelet Transfusion Influences Post-Transfusion Platelet Kinetics and the Effects of Platelets on Plasma Cytokines in a Model of Murine Neonatal Sepsis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 98-98
Author(s):  
Patricia Davenport ◽  
Jorge Canas ◽  
Viola Lorenz ◽  
Zhi-Jian Liu ◽  
Chiara Badur ◽  
...  
Keyword(s):  
Neonatal Sepsis ◽  
Platelet Transfusion ◽  
Bleeding Risk ◽  
Tnf Alpha ◽  
Preterm Neonates ◽  
Laboratory Equipment ◽  
Newborn Mice ◽  
Plasma Cytokines ◽  
Anti Inflammatory ◽  
Platelet Transfusions

Thrombocytopenia affects 20-30% of neonates admitted to the Neonatal Intensive Care Unit (NICU) and up to 70% of those born extremely prematurely, with sepsis being one of the most frequent causes. Since preterm neonates also have a high bleeding risk, it has been widely accepted that they should receive platelet transfusions at higher platelet count (PC) thresholds than older children or adults. However, there is no consensus regarding what the appropriate threshold should be, particularly in critically ill infants. Surveys and observational studies have revealed extraordinary world-wide variability in neonatal platelet transfusion thresholds, with North-American neonatologists typically using more liberal thresholds (i.e. PC<100x109/L) than European neonatologists. Here we hypothesized that the severity of thrombocytopenia at the time of platelet transfusion would influence the post-transfusion platelet kinetics and the effects of platelets on the inflammatory response of septic newborn mice. To test these hypotheses, we used a validated model of neonatal sepsis/peritonitis, consisting of injecting cecal slurry (CS) or 15% glycerol (control) IP into post-natal day 10 (P10) mice. The CS dose used in these studies induced severe sepsis with a high mortality. c-MPL KO pups (which lack the TPO receptor, pre-infection PC 92±38 x 103/µL) and WT B6 pups (pre-infection PC 748±169 x 103/µL) were used to model severe and mild thrombocytopenia at the time of transfusion, respectively. Two hours after infection, mice from both genotypes were transfused with washed platelets from adult GFP mice (5x107platelets/gram) or with Tyrode's buffer. PCs and GFP% were measured by flow cytometry 2 and 22 hrs post-transfusion. At 2 hours, as expected, transfused septic mice of both genotypes had higher PCs than non-transfused septic littermates (217±118 vs 24±9 x103/µL for c-MPLKO mice, p<0.0001, and 764±193 vs. 549±155 x103/µL for WT mice, p<0.01). By 22 hours post-transfusion, transfused septic c-MPL KO mice still had significantly higher PCs than their non-transfused septic littermates (127±71 vs. 21±12 x103/µL, p<0.01; n=7 per group), but there were no significant differences between transfused and non-transfused septic WT mice (415±139 vs. 310±113 x 103/µL, p=0.1;n=7 per group). Between 2 and 22 hrs post-transfusion, PCs dropped at a nearly three-fold higher rate in transfused septic WT mice than in transfused septic c-MPL KO mice (by 17±8 vs. 6±5 x103 platelets/µL/h). In that interval, adult transfused platelets (GFP+) decreased by a larger percentage than neonatal platelets (GFP-) in transfused septic mice of both genotypes (by 64±14% vs. 46±21% in WT mice, and by 53±27% vs. 28±28% in c-MPL KO mice, both p<0.01), although these observations don't account for ongoing neonatal platelet production. Examination of a panel of plasma cytokines 24h after infection revealed significantly increased levels of pro-inflammatory (IL-6, TNF-alpha, and MCP-1) and anti-inflammatory (IL-10) cytokines in non-transfused septic neonates of both genotypes, compared to controls. Interestingly, platelet transfusions significantly reduced the levels of these cytokines in septic WT mice compared to non-transfused littermates, but had no effect on the cytokine levels of septic c-MPLKO mice. Platelets have been recently shown to reduce TNF-alpha production by murine macrophages at high LPS concentrations (Xiang, 2013) and to sequester both pro- and anti-inflammatory cytokines released by monocytes in response to LPS (Carestia, 2019). Our findings suggest that, in neonatal sepsis, this might require PCs to be above a certain threshold. The consequences of these differences on the outcomes of neonatal sepsis are being investigated. Disclosures Stowell: Grifols: Honoraria. Sola-Visner:Sysmex America, Inc.: Other: Laboratory equipment on loan, Research Funding.

scholarly journals Pro-Inflammatory Effects of Platelet Transfusions in Newborn Mice with and without Underlying Inflammation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2146-2146
Author(s):  
Patricia E Davenport ◽  
Emily Nolton ◽  
Henry Feldman ◽  
Zhi-Jian Liu ◽  
Martha Sola-Visner
Keyword(s):  
Inflammatory Response ◽  
Conflicts Of Interest ◽  
Lethal Dose ◽  
Preterm Neonates ◽  
Genetic Syndromes ◽  
Newborn Mice ◽  
Inflammatory Conditions ◽  
Anti Inflammatory ◽  
Underlying Inflammation ◽  
Platelet Transfusions

Abstract Platelet transfusions (PTx) are frequently given to thrombocytopenic preterm neonates at higher platelet count (PC) thresholds than those used in adults, in an attempt to reduce their bleeding risk. However, in the largest randomized trial of neonatal PTx thresholds, infants transfused at a higher PC threshold had a significantly higher mortality and/or major bleeding compared to infants transfused at a lower threshold. Since platelets carry multiple cytokines and chemokines, and since activated adult platelets may have a higher ability to interact with immune cells than neonatal platelets (due to their higher P-selectin expression levels), we hypothesized that the deleterious effects of PTx in neonates would be related to pro-inflammatory effects. We further hypothesized that the effects of PTx on the systemic inflammatory response would be different in thrombocytopenic neonates with non-inflammatory conditions (e.g., intrauterine growth restriction, drugs, genetic syndromes) compared to neonates with underlying inflammation (e.g., sepsis, necrotizing enterocolitis). To test the effects of PTx in the absence of inflammation, we transfused healthy post-natal day 10 (P10) C57BL/6 pups with washed platelets (5x10 7/g, isolated from adult C57BL/6J mice or eGFP+ mice) or with Tyrode's buffer (TY control). Blood was collected via terminal bleed 2h, 4h, and 6h after transfusion, and plasma was separated for quantification of 31 pro- and anti-inflammatory cytokines by multiplex (n=5-10 mice per group/timepoint). Two hours after PTx, the transfused mice exhibited significantly higher levels of G-CSF, IL-1, IL-1, IL-6, IL-17, KC (CXCL1) and MCP-1 compared to controls, with the most striking increases observed in IL-6 (928±19 vs. 135±36 pg/dL, p<0.001) and KC (1201±239 vs 371±77 pg/dL, p=0.001). At 4h post-transfusion, the levels of most cytokines were decreasing, with the exception of G-CSF (1940±276 vs. 825±126 pg/dL, p=0.003), MCP-1 (185±39 vs. 58±14 pg/dL, p=0.003), and IL-17 (2.12±1 vs. 0.66±0.3 pg/dL, p=0.002), which peaked at four hours. All cytokines were decreasing by 6h. Next, to model neonates with inflammatory conditions, we injected P10 pups with lipopolysaccharide (LPS) IP at a sub-lethal dose (1µg/g), which induced mild weight loss, thrombocytopenia (~ 50% drop in PC), and leukopenia followed by leukocytosis. Two hours after LPS injection, pups were transfused with washed platelets from adult C57BL/6 mice or TY (as above). Blood was obtained by terminal phlebotomy 4h, 8h or 18h post LPS injection and plasma was separated and stored for cytokine quantification by multiplex. 4h after LPS, PTx pups had significantly higher levels of leukemia inhibitory factor (LIF, a member of the IL-6 family) compared to TY controls (35±6 pg/mL vs. 17±3.9 pg/mL, p<0.01). At both 4 and 8h, IL-6 and G-CSF levels were extremely high and at or above the upper limit of the standard curve in both groups. By 18h post-LPS, the majority of cytokines had decreased to near-normal levels in TY control pups, while IL-6, IL-5, KC (CXCL1) and IL-10 remained significantly elevated in PTx mice (IL-6: 601±114 vs. 187±38 pg/mL, p=0.0007; IL-5: 659±257 vs. 486±191 pg/mL, p=0.01; KC: 4569±1370 vs. 2686±827 pg/mL, p=0.04; IL-10: 729±283 vs. 330±131 pg/mL, p=0.009). Since IL-10 is an anti-inflammatory cytokine, we also evaluated the relation of IL-6 to IL-10 in PTx vs. TY control mice. This analysis showed that IL-6 levels were 2.3 times higher for any given IL-10 level in pups who received PTx compared to controls. In conclusion, our findings suggest that platelet transfusions induce an inflammatory response in newborn mice without underlying inflammation, characterized mostly by elevations in IL-6, G-CSF and KC. In newborn pups with underlying sub-lethal inflammation, platelet transfusions seem to prolong the inflammatory response. These observations may provide an explanation for the increased morbidity and mortality in human neonates receiving liberal PTx. Studies to identify the mechanisms through which platelets induce these responses are ongoing. Disclosures No relevant conflicts of interest to declare.

scholarly journals Platelet Transfusions Can Increase or Decrease the Inflammatory Response and Mortality in a Murine Model of Neonatal Polymicrobial Sepsis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2147-2147
Author(s):  
Patricia E Davenport ◽  
Hsuan-Hao Fan ◽  
Emily Nolton ◽  
Henry Feldman ◽  
Viola Lorenz ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Murine Model ◽  
Neonatal Sepsis ◽  
Statistical Significance ◽  
Bacterial Species ◽  
Polymicrobial Sepsis ◽  
Preterm Neonates ◽  
Significant Difference ◽  
Buffer Control ◽  
Platelet Transfusions

Abstract Thrombocytopenia affects 18-35% of all neonates in the Neonatal Intensive Care Unit and ~70% of those born extremely prematurely, with sepsis being a frequent cause. Platelet transfusions (PTx) are frequently given to septic preterm neonates at higher platelet count (PC) thresholds than those used in adults, in an attempt to reduce their bleeding risk. However, in the largest randomized trial of neonatal PTx thresholds, infants transfused at a higher PC threshold had a significantly higher mortality and/or major bleeding compared to infants transfused at a lower threshold. We hypothesized that the deleterious effects of PTx would be related to a potential "developmental mismatch" resulting from adult platelets being transfused into a neonate. Among other developmental differences, adult platelets (human and murine) exhibit significantly higher surface P-selectin expression following activation than neonatal platelets. P-selectin is essential for the interaction of platelets with immune cells. Thus, we hypothesized that adult platelets transfused into septic neonates would be consumed faster than endogenous neonatal platelets (due to higher potential for immune interaction), and would increase inflammation and mortality. To test these hypotheses, we used a published murine model of neonatal sepsis, consisting of injecting cecal slurry (CS) into C57BL/6 pups. CS batches were prepared by isolating the cecal content of adult C57BL/6 mice, which was weighted, aliquoted and frozen until use. Three different CS batches were prepared and injected IP into post-natal day 10 pups at a dose of 1.1 (CS1) or 1.0 mg/g (CS2 and 3). Two hours after infection, pups were transfused with washed platelets from adult GFP mice (5x10 7 platelets/g) or Tyrode's buffer (control). Weights, PCs and GFP platelet % were measured before, 4h and 24h post-infection. Blood was collected via terminal bleed at 24h, and plasma separated for quantification of 31 cytokines by multiplex. Despite identical preparation, CS batches varied greatly in their 24h mortality (11% vs 73% vs. 30% for CS1, 2 and 3, respectively). Moreover, PTx had different effects on the mortality of pups infected with different CS batches, increasing the 24h mortality of pups infected with CS1 (30% in transfused vs 11% in non-transfused, RR 2.70, 95% CI 1.02-7.15) but decreasing the mortality of pups infected with CS2 (46% vs. 73%) or CS3 (9% vs. 30%), with a combined RR of 0.52; 95% CI 0.30-0.91. Bacterial counts differed between CS batches, but did not correlate with mortality. Comparison of the microbiome composition using deep sequencing revealed an increased presence of pathogenic bacterial species (Legionella, Sutterella, and Helicobacter species) in CS2 and 3 compared to CS1, and a relative abundance of beneficial bacterial (Actinobacteria and Proteobacteria) in CS1. Different CS batches also elicited different cytokine responses, with significant differences noted in G-CSF, IL-1α, IL-1β, IL-3, IL-7, IL-12p70, and IL-15 levels (p<0.05). For all of these cytokines, except G-CSF, levels were lower in mice infected with CS1 compared to CS2 or 3. Next, we investigated the effects of PTx on the plasma cytokine profile of mice infected with CS1 or CS2/3 (combined), compared to their infected, non-transfused littermates. For nearly all cytokines, PTx increased the response after infection with CS1, but decreased it after infection with CS2/3, with a significant difference in mean global cytokine effect (p<0.0001). For individual cytokines, however, these differences only reached statistical significance for LIX (CXCL5, p=0.04) and approached significance for IL15 and IL17 (p=0.06). Finally, we developed a mathematical model to compare the consumption of endogenous neonatal platelets (GFP-) to that of transfused adult platelets (GFP+) in pups infected with CS1 vs. CS2. In both, the calculated percent consumption was higher for adult platelets than for neonatal platelets (54.8% vs. 32.6% for CS1 and 56.5% vs. 40.4% for CS2). In conclusion, our findings support the hypothesis that adult transfused platelets are consumed faster than endogenous platelets in early neonatal sepsis, and demonstrate that platelet transfusions can either enhance or attenuate the neonatal inflammatory response and the mortality in a model of murine polymicrobial sepsis, depending on the bacterial composition of the inoculum and/or the severity of the sepsis. Disclosures Stowell: Grifols: Speakers Bureau; Argenx: Speakers Bureau; Alexion: Consultancy.

scholarly journals Platelet Transfusions for Thrombocytopenic Preterm Neonates: The Monet Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 707-707
Author(s):  
Suzanne F Fustolo-Gunnink ◽  
K Fijnvandraat ◽  
I M Ree ◽  
C Caram-Deelder ◽  
P Andriessen ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Platelet Count ◽  
Platelet Transfusion ◽  
Bleeding Risk ◽  
Hazard Ratio ◽  
Sensitivity Analyses ◽  
P Value ◽  
Risk Of Bleeding ◽  
The Impact ◽  
Platelet Transfusions

Abstract Introduction Limited evidence supports the widely used practice of administering platelet transfusions to prevent major bleeding in preterm thrombocytopenic neonates. Only 1 randomized controlled trial addressed this issue, but used thresholds higher than those currently used in clinical practice. In order to assess the impact of platelet transfusions on bleeding risk, the primary objective of this study was to develop a prediction model for bleeding. Platelet transfusion was included as variable in this model. In these secondary analyses, we further explored the impact of platelet transfusions on bleeding risk. Materials and methods In this multicenter cohort study, neonates with a gestational age (GA) <34 weeks at birth, admitted to a neonatal intensive care unit (NICU) who developed a platelet count <50x109/L were included. The main study endpoint was major bleeding, defined as intraventricular hemorrhage (IVH) grade 3, IVH with parenchymal involvement, other types of intracranial hemorrhage visible on ultrasound scans, pulmonary hemorrhage or any other type of bleeding requiring immediate interventions. The prediction model was developed using landmarking, in which multiple cox models at regular time-points were combined into 1 supermodel. To further explore the impact of platelet transfusions on bleeding risk, we performed 3 sensitivity analyses by selecting specific transfusions (instead of all transfusions). Sensitivity analysis 1 : transfusions according to protocol, defined as transfusions for platelet counts >20x109/L only allowed in case of GA<32 weeks and <1500 grams and presence of NEC, sepsis, or treatment with mechanical ventilation, or in case of invasive procedures. Sensitivity analysis 2: transfusions with fair increments, defined as platelet count ≥50x109/L within 24 hours. Sensitivity analysis 3: transfusion dose 11 ml/kg or higher. Results A total of 640 neonates were included with a median gestational age of 28 weeks. 70 neonates developed a major bleed. IUGR, postnatal age, platelet count and mechanical ventilation were independent predictors of bleeding. The model allowed calculation of two bleeding risks for individual neonates: one in case of platelet transfusion and one in case of no platelet transfusion. 1361 platelet transfusions were administered to 449 of 640 (70%) neonates, of which 87 were hyperconcentrates. The hazard ratio for transfusion in the original model was 1.0, indicating no predictive power. Sensitivity analysis 1: 704 (52%) transfusions were given according to protocol. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.5, but the p-value remained > 0.05.Sensitivity analysis 2: 764 (56%) of transfusions resulted in a count >50x109/L within 24 hours. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.25, but the p-value remained >0.05. 115 (8%) transfusions did not have a follow up platelet count within 24 hours. Sensitivity analysis 3: of the non-hyperconcentrated platelet transfusions, 517 of 1274 (41%) transfusions were ≥ 11 ml/kg. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.1, with a p-value of 0.05. Conclusion With this tool, absolute risk of bleeding in individual preterm thrombocytopenic neonates can be calculated. Additionally, risk of bleeding can be assessed for 2 scenarios: with and without platelet transfusion. This can help clinicians in deciding whether or not to transfuse a patient. In the primary model, platelet transfusion was not a predictor for bleeding risk. However, the findings of the sensitivity analyses suggest that transfusions with a dose > 11ml/kg may have a more profound effect on bleeding risk. Disclosures No relevant conflicts of interest to declare.

PATHOPHYSIOLOGY OF THROMBOCYTOPENIA AND RESULTANT CLINICAL INDICATIONS FOR PLATELET TRANSFUSION

1987 ◽  
Author(s):  
Sherrill J Slichter
Keyword(s):  
Platelet Count ◽  
Survival Data ◽  
Platelet Transfusion ◽  
Disease Process ◽  
Bleeding Risk ◽  
Underlying Disease ◽  
Transfusion Therapy ◽  
Platelet Counts ◽  
Platelet Survival ◽  
Platelet Transfusions

Careful evaluation of platelet survival data in normal individuals and patients with thrombocytopeniasecondary to marrow aplasia has demonstrated that platelets are lost from circulation by two mechanisms a fixed fraction of platelets, amounting to approxi mately 7,100 platelets/ul/day, are lost randomly while the remaining platelets are removed by senescent mechanisms. At platelet counts of <100,000/ul, platelet survival becomes progressively shorter as the fixed platelet loss becomes a proportionately greater fraction of the circulating platelets. Thus, there is a direct relationship between platelet count and platelet survival in thrombocytopenic patients. Therefore, when judging the effectiveness of platelet therapy in thrombocytopenic patients, the influence of platelet count on platelet survival must be considered. As yet, there have been no studies to determine if there are ways to interrupt this fixed platelet loss? whether such therapy might improve platelet support in thrombocyotpenic patients by prolonging platelet survival? or, alternatively, whether such therapy might enhance the bleeding risk if random platelet removal is related to physiologic platelet-endothelial cell interactions.Besides taking into account the effect of thrombocytopenia on the expected response to platelet transfusions, the risk of alloimmunization with platelet transfusion therapy requires a careful assessment of the indications for platelet transfusions for each patient.Based on 51Cr-labeled stool blood loss measurements, we have determined that the bleeding risk is minimal at platelet counts above 10,000 platelets/ul.Only when the platelet count falls to a lower level of 5,000/ul is GI bleeding significantly increased. However, there are certain medications that may enhance the bleeding risk and require platelet transfusions to be given at higher platelet counts.In those patients who are thrombocytopenic, not because of failure of marrow platelet production, but rather because of accelerated platelet removal, indications for platelet transfusions must be adjusted to meet the particular problem. For example, for patients with autoimmune thrombocytopenic purpura, platelet transfusions are rarely indicated (one exception being intracerebral bleeding) because of the rapid rate of platelet removal and because the patients are usually releasing young hyperfunctional platelets from the bone marrow reducing the hemorrhagic risk at any given platelet count. In some patients with consumptive coagulopathies, even though platelet removal is rapid, platelets may have to be provided until specific therapy resolves the underlying disease process causing the platelet consumption. For these patients, increased levels of fibrinogen/fibrin degregation products, as well as various medications they maybe receiving, may produce platelet dysfunction necessitating platelet transfusions at higher platelet levels. Finally, massive transfusion patients may develop a dilution thrombocytopenia requiring platelet transfusions.

Physician Compliance With Platelet Usage Criteria

2008 ◽  
Vol 132 (8) ◽  
pp. 1321-1324
Author(s):  
Daphne Chua Ang ◽  
Luminita Marinescu ◽  
Mercy Kuriyan
Keyword(s):  
Platelet Transfusion ◽  
Tertiary Care ◽  
Bleeding Risk ◽  
Antiplatelet Drug ◽  
Transfusion Medicine ◽  
Strict Adherence ◽  
Platelet Counts ◽  
Physician Compliance ◽  
Medicine Physician ◽  
Platelet Transfusions

Abstract Context.—Platelet transfusions are used in clinical practice as prophylaxis or to treat bleeding thrombocytopenic patients. This procedure also carries risks and costs and must be allocated appropriately. Objective.—To evaluate physician compliance with the platelet transfusion criteria in our tertiary care academic institution. Design.—We evaluated platelet unit releases from the transfusion service for 4 months, and we retrieved pretransfusion platelet counts. Reasons for transfusion were obtained by reviewing patient charts and talking to clinicians. Compliance with hospital criteria for platelet use was determined. Results.—Platelets were given to 113 patients in 282 transfusion episodes. Criteria were not met for 32 (11%) of 282 platelet transfusions. Justifiable reasons for transfusion at platelet counts of greater than 10 × 103/μL included bleeding risk from oral ulcers, other risks of bleeding in patients who were transfused before discharge, and antiplatelet drug use in cardiac surgery patients. Reasons for transfusion at platelet counts greater than 10 × 103/ μL that were not justified include transfusion at a platelet count of 110 × 103/μL to a lung cancer patient with no platelet dysfunction and transfusion to 4 septic patients with platelet counts of 70 to 90 × 103/μL. Conclusions.—This study showed 89% physician compliance with hospital platelet transfusion criteria. Transfusion-medicine specialists concurred that strict adherence to hospital blood usage criteria was not applicable for 9.2% of these patients; however, 5 (1.8%) of 282 platelet transfusions were not indicated and could have been prevented by transfusion medicine physician intervention.

scholarly journals The Association Between Platelet Transfusion and Mortality Rate Among Preterm Neonates in the Eastern Province, Saudi Arabia

2021 ◽  
Author(s):  
Fatimah Abdullah Alhamad ◽  
Ahlam Mohammed Hussein ◽  
Friyal Mubarak Alqahtani
Keyword(s):  
Saudi Arabia ◽  
Mortality Rate ◽  
Significant Relationship ◽  
Platelet Transfusion ◽  
Survival Rates ◽  
Preterm Neonates ◽  
High Threshold ◽  
Main Mode ◽  
Transfusion Threshold ◽  
Platelet Transfusions

Platelet transfusion is the main mode of management of thrombocytopenia. However, some studies link frequent and high-threshold platelet transfusions with an incremental increase of mortality rate. Aim: This study aims to assess the association between the frequency and the threshold of platelet transfusions, with the mortality rate among preterm neonates. Methods: A retrospective cohort study design was used. This study was conducted at maternity and children's hospitals in Al-Ahasa, Saudi Arabia. The sample size includes 154 preterm neonates, included in the study by the use of the convenience sampling technique. Result: There is a significant relationship found between the gestational age and the birth weight of the preterm neonates with the survival rates among both groups. In contrast, there is no significant relationship found between transfusion frequency, transfusion threshold, and the survival rates of the group which received platelet transfusion. Implications for Practice and Research: The current study found that mortality is mainly associated with lower gestational ages, and not platelet transfusions. More studies are needed to fill the remaining gaps of knowledge, and to optimise platelet transfusion practices among preterm neonates. Key Words: platelet transfusion, preterm neonate, platelet transfusion threshold, mortality rate.

Frühgeborene unter maschineller Beatmung: Immunmodulatorischer Effekt der präventiven Gabe von Azithromycin

2020 ◽  
pp. 1-3
Author(s):  
Maximilian Jorczyk
Keyword(s):  
Very Low Birth Weight ◽  
Controlled Trial ◽  
Preterm Neonates ◽  
Double Blind ◽  
Mechanically Ventilated ◽  
Before And After ◽  
Anti Inflammatory ◽  
To Receive ◽  
Therapeutic Possibilities ◽  
Inflammatory Effect

<b>Introduction:</b> Macrolides have anti-inflammatory and immunomodulatory properties that give this class of antibiotics a role that differs from its classical use as an antibiotic, which opens new therapeutic possibilities. <b>Objective:</b> The aim of this study was to evaluate the anti-inflammatory effect of azithromycin in preventing mechanical ventilation (MV)-induced lung injury in very-low-birth-weight preterm neonates. <b>Methods:</b> This is a randomized, double-blind, placebo-controlled trial of preterm neonates who received invasive MV within 72 h of birth. Patients were randomized to receive intravenous azithromycin (at a dose of 10/mg/kg/day for 5 days) or placebo (0.9% saline) within 12 h of the start of MV. Two blood samples were collected (before and after intervention) for measurement of interleukins (ILs) and PCR for <i>Ureaplasma</i>. Patients were followed up throughout the hospital stay for the outcomes of death and bronchopulmonary dysplasia defined as need for oxygen for a period of ≥28 days of life (registered at ClinicalTrials.gov, No. NCT03485703). <b>Results:</b> Forty patients were analyzed in the azithromycin group and 40 in the placebo group. Five days after the last dose, serum IL-2 and IL-8 levels dropped significantly in the azithromycin group. There was a significant reduction in the incidence of death and O<sub>2</sub> dependency at 28 days/death in azithromycin-treated patients regardless of the detection of <i>Ureaplasma</i> in blood. <b>Conclusions:</b> Azithromycin has anti-inflammatory effects, with a decrease in cytokines after 5 days of use and a reduction in death and O<sub>2</sub> dependency at 28 days/death in mechanically ventilated preterm neonates.

scholarly journals Tibolone has anti-inflammatory effects in estrogen-deficient female rats on the natriuretic peptide system and TNF-alpha

2012 ◽  
Vol 179 (1-3) ◽  
pp. 55-60 ◽  
Author(s):  
Ana Raquel Santos de Medeiros ◽  
Aline Zandonadi Lamas ◽  
Izabela Facco Caliman ◽  
Polyana L. Meireles Dalpiaz ◽  
Luciana Barbosa Firmes ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Female Rats ◽  
Tnf Alpha ◽  
Peptide System ◽  
Anti Inflammatory ◽  
Natriuretic Peptide System

scholarly journals Phytochemical Analysis of Anti-Inflammatory and Antioxidant Effects of Mahonia aquifolium Flower and Fruit Extracts

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Andra-Diana Andreicut ◽  
Alina Elena Pârvu ◽  
Augustin Cătălin Mot ◽  
Marcel Pârvu ◽  
Eva Fischer Fodor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Stress Index ◽  
Tnf Alpha ◽  
Phytochemical Analysis ◽  
Anti Inflammatory ◽  
Mahonia Aquifolium ◽  
Antioxidant Effects

Oxidative stress and inflammation are interlinked processes. The aim of the study was to perform a phytochemical analysis and to evaluate the antioxidant and anti-inflammatory activities of ethanolic Mahonia aquifolium flower (MF), green fruit (MGF), and ripe fruit (MRF) extracts. Plant extract chemical composition was evaluated by HLPC. A DPPH test was used for the in vitro antioxidant activity. The in vivo antioxidant effects and the anti-inflammatory potential were tested on a rat turpentine oil-induced inflammation, by measuring serum nitric oxide (NOx) and TNF-alpha, total oxidative status (TOS), total antioxidant reactivity (TAR), oxidative stress index (OSI), 3-nitrothyrosine (3NT), malondialdehyde (MDA), and total thiols (SH). Extracts were administrated orally in three dilutions (100%, 50%, and 25%) for seven days prior to inflammation. The effects were compared to diclofenac. The HPLC polyphenol and alkaloid analysis revealed chlorogenic acid as the most abundant compound. All extracts had a good in vitro antioxidant activity, decreased NOx, TOS, and 3NT, and increased SH. TNF-alpha was reduced, and TAR increased only by MF and MGF. MDA was not influenced. Our findings suggest that M. aquifolium has anti-inflammatory and antioxidant effects that support the use in primary prevention of the inflammatory processes.

scholarly journals Gratophyllum Pictum (L.) Griff Extract as Anti-Inflammatory on Wistar Rat with Experimental Hemorrhoids. Study on serum IL-6, COX-2, TNF-alpha and total leucocytes in anal tissue.

2020 ◽  
Author(s):  
Sigit Adi Prasetyo ◽  
Ignatius Riwanto ◽  
Edi Dharmana ◽  
Neni Susilaningsih ◽  
Yan Wisnu Prajoko ◽  
...  
Keyword(s):  
Leucocyte Count ◽  
Wistar Rat ◽  
Tnf Alpha ◽  
Croton Oil ◽  
Post Test ◽  
Physiologic Saline ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Anti Inflammation ◽  
Better Than

The author would like to study the effects of ethanol Graptophyllum pictum (L.) Griff extract (EGPE) as anti-inflammation on wistar with experimental hemorrhoids. RCT post-test only design were done on 28 wistar, that were allocated into four groups. The 2nd , 3rd and 4th group were induced with 6% croton oil into anus for three days, the 1st group was not induced. On the 4th day, 1st and 2nd group were given physiologic saline, 3rd and 4th group was given EGPE 100 mg and 300 mg/ kg bw respectively. At the 9th day, before termination, blood was aspirated from retro-ocular region for examination of serum IL-6, COX-2 and TNF-alpha using ELISA method, and SGOT, SGPT, urea and creatinine level. Anus was removed and prepared for microscopic examination to count the leucocyte under 400 HPF. Induction of 6% croton oil was significantly increased TNF-alpha, IL-6, COX-2 and leucocyte count. Treatment with EGPE dose 100 mg and 300 mg/ kg bw significantly reduce TNF-alpha, IL-6, COX-2 and leucocyte count, dose 100 mg was even better than 300 mg except for leucocyte count. SGOT, SGPT, blood urea and creatinine were not significantly different among groups. In conclusion, the EGPE 100 mg and 300 mg have anti-inflammatory effects in hemorrhoids wistar, which can suppress IL-6, COX-2, TNF-alpha, and total leucocytes. The EGPE dose 100 mg is better than dose 300 mg. EGPE save for kidney and liver.

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