Plasminogen Activators in Inflammation and Sepsis

Pechlaner, Christoph

doi:10.1046/j.1563-2571.2002.02011.x

Cited by 5 publications

(3 citation statements)

References 206 publications

(240 reference statements)

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“…People who have genetic polymorphisms that lead to excess expression of PAI-1 also have increased levels of TNF-alpha, and IL-1 (32). Some view the relationship between fibrin and inflammation so convincing that they advocate plasminogen activator inhibitors as therapy for sepsis (33).…”

Section: Respiratory Distress Syndrome (Rds) In Preterm Newbornsmentioning

confidence: 99%

Coagulation, Inflammation, and the Risk of Neonatal White Matter Damage

Leviton

Dammann

2004

Pediatr Res

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Indicators of coagulation activation are sometimes increased in the blood of newborns and adults who have a systemic inflammatory response. These coagulation factors have the ability to exacerbate inflammation, which in turn can promote coagulation. Therapies directed solely at coagulation factors and therapies directed solely at inflammation factors have not proved effective in reducing mortality in adults with a systemic inflammatory response syndrome and multiorgan dysfunction (SIRS/MOD). On the other hand, the only therapy that has reduced mortality in SIRS/MOD is activated protein C, which has both anti-coagulation and anti-inflammatory effects. This and other observations support the view that activated coagulation factors enhance inflammation. Since newborns at risk of cerebral white matter damage and cerebral palsy are more likely than their peers to have a systemic inflammatory response, which is sometimes accompanied by elevated blood levels of coagulation factors, we suggest that activated coagulation factors contribute to the occurrence of cerebral white matter damage by exacerbating inflammatory phenomena, rather than by occluding cerebral blood vessels. Preterm newborns with respiratory distress syndrome and term newborns who develop cerebral palsy tend to have elevated blood levels of coagulation factors. In this essay, we suggest that these coagulation factors, when activated, produce their effects not so much by promoting coagulation as by promoting inflammation, a view supported by studies of adults with a systemic inflammatory response syndrome with multiorgan dysfunction (SIRS/MOD). We also suggest that activated systemic coagulation factors in the preterm newborn contribute to cerebral white matter damage (WMD) and to its clinical sequelae, including cerebral palsy (CP). NEWBORNS Respiratory distress syndrome (RDS) in preterm newborns.Fibrin is a major part of hyaline membranes, which are viewed as locally produced clots in neonatal RDS (1, 2). Indeed, the severity of RDS has been linked to the systemic concentration of thrombin-antithrombin III complex (3). In addition, preterm babies with RDS are more likely than their peers to have systemic activation of inflammation (4, 5). We do not yet know if products of coagulation and inflammation co-occur in the blood of infants destined to develop bronchopulmonary dysplasia.In newborn immature sheep with RDS, inflammation and clotting are activated shortly after birth (6). "Because activation of clotting and platelet activation are found later than activation of inflammation," Jaarsma and colleagues recently wrote, "we consider activation of clotting is not causative in RDS, but is activated secondary to activation of inflammation" (6).We postulate that this scenario of inflammation promoting coagulation also applies to neonatal WMD. Moreover, we postulate that inflammation promotes coagulation, which in turn further promotes inflammation (Fig. 1).CP in term newborns. Support for the systemic activation of both inflammation and coagulation in newb...

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Section: Respiratory Distress Syndrome (Rds) In Preterm Newbornsmentioning

confidence: 99%

Coagulation, Inflammation, and the Risk of Neonatal White Matter Damage

Leviton

Dammann

2004

Pediatr Res

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“…10,11 Streptokinase and other fibrinolytic substances had the ability to destruct the fibrin threads, which subsequently leads to opening of the loculi, and eventually enhancing the fluid evacuation and healing. [12][13][14] However, this area of research is still growing, putting into consideration the safety and efficacy issues.…”

Section: Introductionmentioning

confidence: 99%

Intrapleural Instillation of Sodium Bicarbonate versus Urokinase in Management of Complicated Pleural Effusion: A Comparative Cohort Study

Zayed¹,

Fakharany²,

Abozaid³

2022

IJGM

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The main target is evacuation; however, with evidence about the value of intrapleural instillation of different fibrinolytic agents still under evaluation, our aim was comparing the effectiveness and safety of intrapleural instillation of sodium bicarbonate (NaHCO 3 ) in comparison with urokinase in patients with infected pleural effusion. Methods: Our prospective cohort study included 40 patients with complicated empyema; the diagnosis was based on analysis of aspirated fluid in association with radiological and bacteriological culture. The patients were subjected to instillation of two different fibrinolytic agents; the first one was NaHCO 3 , the second was urokinase. Results:The commonest underlying chest infection that was visualized by CT was pneumonia 70%. Nearly half of cases had community-acquired infection (45%), and more than half of them (55%) had anaerobic infection, and only five cases had TB pleural effusion based on ADA-positive, tuberculin skin test in addition to Abram's needles closed biopsy. The rate of repeated therapeutic thoracentesis success in each group was 85%; 80% in NaHCO 3 group, and 90% in urokinase group, both of them was significantly equal, P=0.37. Moreover, the frequency of complications in all patients was less than 13%, hence hemothorax and iatrogenic pneumothorax was 12.5%, and only 10% of cases were admitted in ICU after the maneuver, with insignificant difference in between the groups. However, looking at the smaller rate of RTT failure of NaHCO 3 or urokinase, the logistic regression model showed that RTT-NaHCO 3 was insignificantly related to failure in both unadjusted and adjusted models, P=0.37 and 0.32, respectively, and only smoking habits increase the likelihood of failure 9-fold (OR=8.9, P=0.04) with respect to age, sex, and treatment methods. Conclusion:The efficacy of repeated therapeutic thoracentesis (RTT) with intrapleural instillation of NaHCO 3 was effective and safe, the same as urokinase, with consideration that NaHCO 3 was much more available and affordable than urokinase.

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“…However, a fever that becomes too high can cause extensive and possibly irreversible damage to the host. At an excessively high body temperature, or chronic fever, enzymes along with other proteins can become denatured, an overabundance of cytokines can be stimulated resulting in tissue damage that may not be able to be repaired, multiple organ failure occurs as a result of tissue damage and septic shock or systemic inflammation response syndrome (SIRS) occurs (Kengatharanetal, 1998;Pechlaner, 2002) (Kluger et al, 1995). Over 210,000 people a year in the United States alone die from septic shock with 45% of cases of septicemia due to gram-positive bacterial infections (Morris, 2001).…”

Section: Innate Immunitymentioning

confidence: 99%

Effects of induced acute phase response in ewes on early embryo survival

Dow¹

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Early pregnant ewes, 5/6 day post coitus (dpc) were used as a model to study early embryonic loss via gram-positive bacterial infections, such as mastitis. Ewes 5/6 dpc were injected with a gram-positive bacteria cell wall component, peptidoglycanpolysaccharide (PG-PS), to induce an innate immune system acute phase response (APR). The induction of the APR and its reactant molecules, such as cytokines and acute phase proteins (APP), were initiated to study their effects on embryonic loss. Twenty Suffolk ewes were synchronized for estrus and bred by fertile rams. At 4 dpc ewes were anesthetized and catheters were surgically placed in the right rear leg in the caudal vena cava via saphenous vein, as well as in the jugular. Ewes were randomly assigned to treatment groups on 5 dpc, and received either a 60 µg/kg BW dose of PG-PS (n=10) or a sham injection of 0.9% NaCl (n=10) i.v. in the jugular vein contralateral of the catheter. Plasma was collected from jugular and caudal vena cava via the saphenous vein before challenge, followed by post challenge samples every 15 minutes until 2 hours, every hour until 12 hours, and once at 24, 36, and 48 hours. Assays were conducted for APR reactants tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), and haptoglobin (Hp), as well as the pregnancy maintenance hormone, progesterone (P 4). In addition, behavior changes and body temperature were also documented before PG-PS injection followed by every hour for 12 hours and then again at 24, 36, and 48 post challenge. Concentrations of TNF-α and P 4 were quantified using radioimmunoassay, whereas ELISA was used to measure SAA and HP concentrations. Intoxication of day 5/6 pregnant ewes with 60 µg/kg BW PG-PS induced significant differences in TNF-α concentration between sample sites (p<0.001) and treatment groups (p<0.02). SAA and Hp concentrations increased significantly (p<0.0001) in challenged ewes. Fever, loss of appetite, lethargy, and vaginal discharge were documented in all treated ewes, as well as 100 % embryonic loss by 21 dpc. Data from this experiment demonstrate that injection of PG-PS systemically leads to production of APP and behavioral changes characteristic of an APR.

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Plasminogen Activators in Inflammation and Sepsis

Cited by 5 publications

References 206 publications

Coagulation, Inflammation, and the Risk of Neonatal White Matter Damage

Coagulation, Inflammation, and the Risk of Neonatal White Matter Damage

Intrapleural Instillation of Sodium Bicarbonate versus Urokinase in Management of Complicated Pleural Effusion: A Comparative Cohort Study

Effects of induced acute phase response in ewes on early embryo survival

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