Hemophagocytic lymphohistiocytosis is associated with deficiency and closed conformation of ADAMTS-13.

Background: A disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS-13) is the specific von Willebrand factor-cleaving protease and circulates in a closed and latent conformation due to a spacer/CUB1 domain interaction. ADAMTS-13 is allosterically activated after binding of its substrate or antibodies, inducing an open conformation. Recently, we suggested a potential role of plasmin (fibrinolysin) in hemostasis disorders reported in most patients with hemophagocytic lymphohistiocytosis (HLH), a rare and life-threatening condition related to a severe systemic inflammatory state. Most patients with HLH had a partial ADAMTS-13 deficiency, and plasmin could induce a truncation of the C-terminal part of ADAMTS-13 and thus an open conformation. Objectives: To understand the effect of plasmin on ADAMTS-13, our study aimed to investigate ADAMTS-13 conformation in patients with HLH. Methods: Forty-five critically ill patients with HLH were prospectively enrolled between April 2015 and December 2018. ADAMTS-13 activity was measured by fluorescent resonance energy transfer-VWF73 assay, ADAMTS-13 antigen, and conformation with our homemade 3H9-enzyme-linked immunosorbent assay and 1C4-enzyme-linked immunosorbent assay. Results: ADAMTS-13 activity ranged from <10 to 65 IU/dL, and 41 of the 45 patients had a quantitative deficiency in ADAMTS-13 (activity <50 IU/dL). Twenty patients had a severe ADAMTS-13 deficiency (activity <20 IU/dL). ADAMTS-13 conformation was folded in all patients under normal conditions. Surprisingly, the switch of ADAMTS-13 conformation expected with the monoclonal antibody 17G2 (anti-CUB1) was disturbed in 6 patients (activity <20 IU/dL). Conclusion: Our study reported that ADAMTS-13 conformation is closed in HLH and provides an indirect proof that plasmin is not able to massively degrade ADAMTS-13. Further studies on glycosylation and citrullination profiles of ADAMTS-13 are needed to understand their role in HLH.

A new approach to skin extravasation injury management during the neonatal period.

BACKGROUND: To identify a standard protocol for managing extravasation injuries in neonates. METHODS: We recruited all the neonates with extravasation wounds from the neonatal intensive care unit of Shariati hospital, Tehran, Iran, between October 2018 and October 2020. Sixteen patients with grade 3-4 extravasation were evaluated in this retrospective study. All grade 3 and 4 extravasation wounds were injected with hyaluronidase at 5 points of the wound circle; the procedure was repeated every 5 min at different points in a smaller circle to the core. The wound was then covered with a warm compress for 24 h. Twenty-four hours after injection, the cover was changed twice a day with normal saline irrigation. Fibrinolysin ointment was applied on top of the wound. The ulcer was then dressed with phenytoin ointment until healing. RESULTS: Out of 16 neonates who were followed up, 10 of them were male, with the average birth weight being 1.37 (range 1.05-3.75) kg. The mean (± SD) wound healing duration was 13.12 (± 6) (range: 7-29) days. Factors including the cannulation duration before the appearance of the lesion (R:0.2, P = 0.2), birth weight (R = -.37, P = 015), and extravasated substances (p = 0.2) were not associated with the duration of hospital stay. The only exception to this trend is the wound size factor of 7.31(± 7.45) (R = .83, P < 0.001). Continuous and categorical variables were summarized as mean (SD) and proportions, respectively, and the Kruskal-Wallis test and Spearman correlation coefficients were used. CONCLUSIONS: Limited evidence exists on the effects of different protocols on extravasation management in neonates in the NICU. We recommend our method as a standard protocol in NICU for high-stage extravasated lesions because of the shorter duration of healing, non-invasive nature of this procedure, and lack of side effects or surgical involvement.

A review of advances in intraocular fluid detection for high myopia and its relevant fundus diseases / 中华眼底病杂志

The fundus lesions caused by high myopia (HM) often lead to irreversible visual impairment or even blindness. However, the pathogenesis of HM and its fundus lesions is still unclear, the intraocular fluid detection technology of micro samples has brought new prospects for the early diagnosis, monitoring and intervention of the fundus lesions. The molecules associated with HM are various and functionally diverse, intermolecular interactions are staggered and the specific mechanism is complex. With the development of intraocular fluid detection technology, while gradually revealing the role of each molecule in the pathogenesis of HM, it is expected to successfully assist clinical work in the future, providing outpost markers for the progress of myopia and targets for early intervention, or providing a new therapy choice for HM fundus lesions at the molecular level targeting pathogenesis, which is expected to provide more accurate and effective treatment for HM patients in the future.

A review of advances in intraocular fluid detection for high myopia and its relevant fundus diseases / 中华眼底病杂志

The fundus lesions caused by high myopia (HM) often lead to irreversible visual impairment or even blindness. However, the pathogenesis of HM and its fundus lesions is still unclear, the intraocular fluid detection technology of micro samples has brought new prospects for the early diagnosis, monitoring and intervention of the fundus lesions. The molecules associated with HM are various and functionally diverse, intermolecular interactions are staggered and the specific mechanism is complex. With the development of intraocular fluid detection technology, while gradually revealing the role of each molecule in the pathogenesis of HM, it is expected to successfully assist clinical work in the future, providing outpost markers for the progress of myopia and targets for early intervention, or providing a new therapy choice for HM fundus lesions at the molecular level targeting pathogenesis, which is expected to provide more accurate and effective treatment for HM patients in the future.

Fibrinolysin production by Alcaligenes faecalis strain 26 isolated from environment.

BACKGROUND AND OBJECTIVES: Fibrinolytic drugs are commonly used for fibrin clot lysis but due to their inappropriate side effects, as well as their high costs, using fibrinolytic enzymes has been paid attention. Bacterial sources of this enzyme are a good alternative for this purpose. The aim was fibrinolysin production through screening of fibrinolysin producing bacteria from environmental samples. MATERIALS AND METHODS: Bacterial isolation was performed from different environmental samples and was screened based on sheep blood clot digestion and culture on plasma plate. The most potent isolate was optimized for different growth parameters including temperature, pH and fibrinolysin production at optimum growth conditions. The stability of produced enzyme at various temperatures and pH and treatment with MgSO4, NiSO4, SDS and EDTA was then investigated. Finally this isolate was identified based on the 16S rRNA sequencing. RESULTS: As a result, from 79 different isolates, the most potent fibrinolysin producer was identified as Alcaligenes faecalis strain 26. This isolate produced 12 mm halo zone on plasma plate. Its optimum growth temperature and pH was 43°C and 7, respectively. The produced enzyme had the best stability at pH 7 and was also active up to 60°C. The fibrinolytic activity of this isolate was reduced following treatment with MgSO4, NiSO4 and also with protease inhibitors, such as SDS and EDTA. CONCLUSION: Based on the obtained results it can be suggested that Alcaligenes faecalis strain 26 has appropriate efficiency for fibrinolysin production that can be used in food industry and medicine.

TAT and PIC better than D-dimer in monitoring hypercoagulability of cancer patients / 中华检验医学杂志

Objective@#The aim of this study is to investigate the variation tendency of coagulation and fibrinolysis biomarkers in cancer patients and to explore the effect of these biomarkers for the diagnosis of thrombosis in cancer patients.@*Methods@#171 cancer patients admitted to hospital from September 2017 to July 2019 were enrolled in the study, including 40 cancer patients undergoing surgery, 108 cancer patients without surgery in control group and 23 cancer patients with thrombus. New coagulation and fibrinolysis biomarkers, TM (Thrombomodulin), TAT (Thrombin -antithrombin complex), PIC (Plasmin alpha 2-plasmin inhibitor complex) and t-PAI·C (Tissue plasminogen activator-plasminogen activator inhibitor-1 complex), were tested in every patient. In addition, these new biomarkers are compared with D-dimer.@*Results@#A statistically difference was available on the value of TAT, TM, PIC, t-PAIC, between postoperative cancer patients group and control group (P<0.05, respectively). TAT, TM and PIC in thrombosis cancer group were higher than those in non-thrombosis cancer group (P<0.05; respectively). ROC was used to evaluate the performance of D-dimer, TAT and PIC on thrombosis in cancer patients. The results showed that the AUC of PIC and TAT were both higher than D-dimer (0.871 vs. 0.619; 0.788 vs. 0.619). The specificity of PIC alone was higher than that of D-dimer (91.9% vs. 82.4%), and the sensitivity of PIC and TAT alone was higher than that of D-dimer (73.9% vs. 47.8%, 73.9% vs. 47.8%, respectively).@*Conclusions@#The activity of coagulation and fibrinolysis in cancer patients was abnormally enhanced. TAT and PIC were better than D-dimer for the diagnosis of thrombosis in cancer patients.

TAT and PIC better than D-dimer in monitoring hypercoagulability of cancer patients / 中华检验医学杂志

Objective The aim of this study is to investigate the variation tendency of coagulation and fibrinolysis biomarkers in cancer patients and to explore the effect of these biomarkers for the diagnosis of thrombosis in cancer patients. Methods 171 cancer patients admitted to hospital from September 2017 to July 2019 were enrolled in the study, including 40 cancer patients undergoing surgery, 108 cancer patients without surgery in control group and 23 cancer patients with thrombus. New coagulation and fibrinolysis biomarkers, TM (Thrombomodulin), TAT (Thrombin-antithrombin complex), PIC (Plasmin alpha 2-plasmin inhibitor complex) and t-PAI · C (Tissue plasminogen activator-plasminogen activator inhibitor-1 complex), were tested in every patient. In addition, these new biomarkers are compared with D-dimer. Results A statistically difference was available on the value of TAT, TM, PIC, t-PAIC, between postoperative cancer patients group and control group (P<0.05, respectively). TAT, TM and PIC in thrombosis cancer group were higher than those in non-thrombosis cancer group (P<0.05;respectively). ROC was used to evaluate the performance of D-dimer, TAT and PIC on thrombosis in cancer patients. The results showed that the AUC of PIC and TAT were both higher than D-dimer (0.871 vs. 0.619;0.788 vs. 0.619). The specificity of PIC alone was higher than that of D-dimer(91.9％ vs. 82.4％), and the sensitivity of PIC and TAT alone was higher than that of D-dimer(73.9％ vs. 47.8％, 73.9％ vs. 47.8％, respectively). Conclusions The activity of coagulation and fibrinolysis in cancer patients was abnormally enhanced. TAT and PIC were better than D-dimer for the diagnosis of thrombosis in cancer patients.

Amplified endogenous plasmin activity resolves acute thrombotic thrombocytopenic purpura in mice.

Essentials Plasmin is able to proteolyse von Willebrand factor. It was unclear if plasmin influences acute thrombotic thrombocytopenic purpura (TTP). Plasmin levels are increased during acute TTP though suppressed via plasmin(ogen) inhibitors. Allowing amplified endogenous plasmin activity in mice results in resolution of TTP signs. SUMMARY: Background Thrombotic thrombocytopenic purpura (TTP) is an acute life-threatening pathology, caused by occlusive von Willebrand factor (VWF)-rich microthrombi that accumulate in the absence of ADAMTS-13. We previously demonstrated that plasmin can cleave VWF and that plasmin is generated in patients during acute TTP. However, the exact role of plasmin in TTP remains unclear. Objectives Investigate if endogenous plasmin-mediated proteolysis of VWF can influence acute TTP episodes. Results In mice with an acquired ADAMTS-13 deficiency, plasmin is generated during TTP as reflected by increased plasmin-α2-antiplasmin (PAP)-complex levels. However, mice still developed TTP, suggesting that this increase is not sufficient to control the pathology. As mice with TTP also had increased plasminogen activator inhibitor 1 (PAI-1) levels, we investigated whether blocking the plasmin(ogen) inhibitors would result in the generation of sufficient plasmin to influence TTP outcome in mice. Interestingly, when amplified plasmin activity was allowed (α2-antiplasmin-/- mice with inhibited PAI-1) in mice with an acquired ADAMTS-13 deficiency, a resolution of TTP signs was observed as a result of an increased proteolysis of VWF. In line with this, in patients with acute TTP, increased PAP-complex and PAI-1 levels were also observed. However, neither PAP-complex levels nor PAI-1 levels were related to TTP signs and outcome. Conclusions In conclusion, endogenous plasmin levels are increased during acute TTP, although limited via suppression through α2-antiplasmin and PAI-1. Only when amplified plasmin activity is allowed, plasmin can function as a back-up for ADAMTS-13 in mice and resolve TTP signs as a result of an increased proteolysis of VWF.

Effects of narrow-band ultraviolet B on levels of plasmin and CC chemokine ligand 20 in peripheral blood of patients with psoriasis vulgaris / 中华皮肤科杂志

Objective To investigate the effects of narrow-band ultraviolet B (NB-UVB) therapy on the levels of plasmin and CC chemokine ligand 20 (CCL20) in peripheral blood of patients with psoriasis vulgaris.Methods A total of 60 patients with psoriasis vulgaris in progressive stage were treated with NB-UVB radiation thrice a week for 8 weeks.Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of plasmin and CCL20 in the peripheral blood of the patients before and after the treatment,as well as in the peripheral blood of 50 healthy controls.Results After the treatment,psoriasis area and severity index (PASI) scores in patients were significantly decreased compared with those before the treatment (2.54 ± 1.64 vs.10.26 ± 3.14,t =17.40,P ＜ 0.05),and the response rate was up to 87％ (52/60).Before the treatment,levels of plasmin and CCL20 were both significantly higher in the patient group than in the control group (plasmin:180.07 ± 40.62 μg/L vs.76.30 ± 26.92 μg/L,t =15.45,P ＜ 0.05;CCL20:422.41 ± 129.87 pg/L vs.205.33 ± 49.89 pg/L,t =11.15,P ＜ 0.05).After the treatment,levels of plasmin (148.22 ± 40.05 μg/L) and CCL20 (329.67 ± 100.73 pg/L) in patients were significantly decreased compared with those before the treatment (t =4.97,6.44,P ＜ 0.05),but still significantly higher than those in controls (t =10.82,7.95,P ＜ 0.05).Before the treatment,the level of plasmin was positively correlated with the level of CCL20 in peripheral blood of the patients (r =0.57,P ＜ 0.05),and the levels of plasmin and CCL20 were both positively correlated with the PASI score (r =0.49,0.62,respectively,both P ＜ 0.05).Conclusion NB-UVB radiation may exert a therapeutic effect on psoriasis vulgaris by reducing levels of plasmin and CCL20 in peripheral blood of patients.

The current status and progress of ocriplasmin in treating vitreomacular interface diseases / 中华眼底病杂志

As a potent collagenase activator,ocriplasmin is a recombinant truncated form of serine protease that retains the protease activity of plasmin.Pre-clinical animal experiments,clinical trials and recent clinical studies all indicated a promising outcome of intravitreal injection of ocriplasmin to treat vitreomacular interface diseases,including vitreomacular adhesion (VMA),vitreomacular traction (VMT) and full-thickness macular hole.Ocriplasmin was approved by the Food and Drug Administration of USA in the management of symptomatic VMA,and by the European Medicines Agency in treating VMT-associated macular hole with less than or equal 400 pm.Further randomized controlled clinical trials are needed for further comprehensive observation and evaluation on its efficiency,safety and other noteworthy issues.

Initial experience with ocriplasmin in the treatment of vitreomacular traction / Experiência inicial com ocriplasmina no tratamento da tração vitreorretiniana

ABSTRACT This study aimed to report the clinical and structural outcomes of intravitreal ocriplasmin in the treatment of vitreomacular interface disorders in two tertiary centers in Brazil. A retrospective study was performed by reviewing medical records and spectral domain optical coherence tomography (SD-OCT) findings of seven patients who were treated with a single ocriplasmin injection. A total of 57.14% of patients achieved resolution of vitreomacular traction as evidenced by SD-OCT. Regarding our functional results, 87.71% maintained or improved visual acuity after follow-up. To the best of our knowledge, this is the first study reporting initial results of ocriplasmin therapy in Brazil.

RESUMO O objetivo desse estudo é relatar os resultados iniciais, tanto do ponto de vista funcional quanto anatômico, no tratamento das doenças da interface vítreo-macular com a ocriplasmina em 2 serviços terciários no Brasil. Um estudo retrospectivo foi realizado através de revisão de prontuários, além de análise de achados em tomografia de coerência óptica de domínio espectral (SD-OCT) em 7 pacientes tratados com uma única injeção intravítrea de ocriplasmina. Em nosso estudo 57,14% dos pacientes apresentaram resolução da tração vítreo-macular no SD-OCT. Em relação aos resultados funcionais, 87,71% dos pacientes mantiveram, ou melhoraram sua acuidade visual durante o acompanhamento. Para nosso conhecimento, trata-se do primeiro estudo em nosso país, mostrando resultados iniciais com ocriplasmina em pacientes tratados no Brasil.

Chronergy of Fibrinolysin in Treatment of Acute Cerebral Infarction / 医药导报

Objective To explore the chronergy of fibrinolysin and its influence on fibrinogen ( FIB ) and thrombus precursor protein (TpP) in treatment of acute cerebral infarction (ACI). Methods The clinical trial adopted the randomized single-blind placebo-controlled design.Totally, 150 patients with ACI (onset time≤12 h) were chosen and randomly divided into experimental group A ( group A receiving treatment of fibrinolysin after 12 h onset of ACI ) , experimental group B ( group B receiving treatment of fibrinolysin after 24 h onset of ACI) and control group ( group C without fibrinolysin treatment) , 50 cases in each group.The patients in experimental group A and B received basic treatment for ACI and fibrinolysin treatment.Patients in group C were given the basic treatment for ACI and placebo.The level of FIB and TpP before and after 7 days treatment, NIHSS scores before and after 14 days treatment, BI scores before and after 90 days treatment, incidence rate of progressive cerebral infarction ( PCI ) , stroke recurrence and mortality rate of the three groups were analyzed to evaluate the clinical effect of fibrinolysin.Hepatic and renal function before and after 7 days treatment, incidence rates of haemorrhage and hypersensitiveness were analyzed to evaluate the security of fibrinolysin. Results The NIHSS score of patients in group A, B and C (4.0±1.6, 6.5±2.2 and 8.0±4.7) was declined significantly after treatment (P0.05).The FIB in group A, B and C after treatment was (2.74±0.75) g?L-1,(2.82±0.83) and (3.67±1.35) g?L-1, respectively.The level of FIB in the three groups did not decrease significantly after treatment (P>0.05).However, the level of FIB in group A and B declined significantly as compared with that in group C.The TpP in group A, B and C after treatment was (3.56±1.26) mg?L-1, (3.43±1.22) and (13.21±6.54) mg?L-1, respectively.The level of TpP in group A and group B decreased significantly after treatment (P<0.05). The level of TpP in group A and B declined even more significantly than that in group C.Fibrinolysin did neither obviously injure liver and kidney nor increase the risk of bleeding, and had low hypersensitiveness incidence rate. Conclusion Treatment with fibrinolysin within 24 h after onset of cerebra infarction benefits the patients. However, dosing after 12 h onset of ACI benefits more than dosing after 24 h.Fibrinolysin plays a role of anti-thrombosis primarily by lowering the TpP level, and its influence on fibrinogen is limited.

Smad2-dependent protease nexin-1 overexpression differentiates chronic aneurysms from acute dissections of human ascending aorta.

OBJECTIVE: Tissue activation of proteolysis is involved in acute intramural rupture (dissections, acute ascending aortic dissection) and in progressive dilation (aneurysms, thoracic aneurysm of the ascending aorta) of human ascending aorta. The translational aim of this study was to characterize the regulation of antiproteolytic serpin expression in normal, aneurysmal, and dissecting aorta. APPROACH AND RESULTS: We explored expression of protease nexin-1 (PN-1) and plasminogen activator inhibitor-1 and their regulation by the Smad2 signaling pathway in human tissue and cultured vascular smooth muscle cells (VSMCs) of aneurysms (thoracic aneurysm of the ascending aorta; n=46) and acute dissections (acute ascending aortic dissection; n=10) of the ascending aorta compared with healthy aortas (n=10). Both PN-1 and plasminogen activator inhibitor-1 mRNA and proteins were overexpressed in medial tissue extracts and primary VSMC cultures from thoracic aneurysm of the ascending aorta compared with acute ascending aortic dissection and controls. Transforming growth factor-ß induced increased PN-1 expression in control but not in aneurysmal VSMCs. PN-1 and plasminogen activator inhibitor-1 overexpression by aneurysmal VSMCs was associated with increased Smad2 binding on their promoters and, functionally, resulted in VSMC self-protection from plasmin-induced detachment and death. This phenomenon was restricted to aneurysms and not observed in acute dissections. CONCLUSIONS: These results demonstrate that epigenetically regulated PN-1 overexpression promotes development of an antiproteolytic VSMC phenotype and might favor progressive aneurysmal dilation, whereas absence of this counter-regulation in dissections would lead to acute wall rupture.

Plasmin promotes foam cell formation by increasing macrophage catabolism of aggregated low-density lipoprotein.

OBJECTIVE: The plasmin/plasminogen system is involved in atherosclerosis. However, the mechanisms by which it stimulates disease are not fully defined. A key event in atherogenesis is the deposition of low-density lipoprotein (LDL) on arterial walls where it is modified, aggregated, and retained. Macrophages are recruited to clear the lipoproteins, and they become foam cells. The goal of this study was to assess the role of plasmin in macrophage uptake of aggregated LDL and foam cell formation. APPROACH AND RESULTS: Plasminogen treatment of macrophages catabolizing aggregated LDL significantly accelerated foam cell formation. Macrophage interaction with aggregated LDL increased the surface expression of urokinase-type plasminogen activator receptor and plasminogen activator activity, resulting in increased ability to generate plasmin at the cell surface. The high local level of plasmin cleaves cell-associated aggregated LDL, allowing a portion of the aggregate to become sequestered in a nearly sealed, yet extracellular, acidic compartment. The low pH in the plasmin-induced compartment allows lysosomal enzymes, delivered via lysosome exocytosis, greater activity, resulting in more efficient cholesteryl ester hydrolysis and delivery of a large cholesterol load to the macrophage, thereby promoting foam cell formation. CONCLUSIONS: These findings highlight a critical role for plasmin in the catabolism of aggregated LDL by macrophages and provide a new context for considering the atherogenic role of plasmin.

Consensus statement on the use of intravenous recombinant tissue plasminogen activator to treat acute ischemic stroke by the Chinese Stroke Therapy Expert Panel.

BACKGROUND: The last update of the consensus statement on intravenous recombinant tissue plasminogen activator (IV rt-PA) for acute ischemic stroke (AIS) by the Chinese Stroke Therapy Expert Panel was published in 2006. Great progress has been made since then. AIM: To provide another update on the new knowledge of IV rt-PA for AIS since 7 years ago. METHOD: In summer of 2012, the Chinese Stroke Therapy Expert Panel was reconvened. New publications on the use of IV rt-PA for AIS were reviewed. In addition, all newly published consensus and guidelines from other countries were reviewed. The 2006 version of Chinese Consensus was then updated. RESULTS: There is now clinical evidence to support the use of IV rt-PA between 3 and 4.5 h after the onset with several exclusion criteria. More studies are needed to provide the evidence for IV rt-PA use beyond 4.5 h. There is benefit giving IV rt-PA within 3 h to patients who are older than 80 and in patients with ongoing atrial fibrillation. Patients with INR<1.7 while on warfarin, minor strokes, rapid improving strokes and severe strokes should be treated and can all be benefited from IV rt-PA. DISCUSSION: Since IV rt-PA was initially recommended in 1996, there is now more evidence support its use, efficacy and safety. The treatment time window is also being expanded. More public education on stroke recognition are needed so many stroke patients may benefit from the treatment. CONCLUSION: The 2013 version of Chinese IV rt-PA consensus contains the most up-to-date information on the use of IV rt-PA for AIS. It will be a useful tool and guideline to provide appropriate thrombolytic therapy to stroke patients who meet the criteria.

Fibrinolysinoma after direct injection of fibrinolysin for treatment of nasal tip swelling: a case report.

Rhinoplasty is one of the most common aesthetic procedures in the world. It is the most common aesthetic surgery procedure in Iran. Achieving complete patient satisfaction is almost impossible but improving the aesthetics and function of the nose is the aim of surgery. This report describes a 34 years old woman with a large bump in the tip of the nose after three times cosmetic rhinoplasties. The first time was done 4 years before referral to our center as a reduction rhinoplasty operation. The next two subsequent surgeries were performed for revision and correcting the dorsal irregularities and supra tip bulge. Unfortunately the supratip bulge persisted and subsequent subcutaneous injections of corticosteroids and fibrinolysin were carried out. She developed a bulbous tip nose deformity. Therefore, after a few months; she was referred to our center. Surgical exploration showed a lesion in the supratip region and histopathologic examination showed a foreign body reaction and granuloma formation.

Antifibrinolítico em cirurgia cardíaca: como e quando usar? / Anfibrinolytic in cardiac surgery: how and when to use?

O sangramento pós-operatório continua sendo uma das principais complicações em cirurgia cardíaca. A etiologia desse sangramento é multifatorial, com hiperfibrinólise e disfunção plaquetária desempenhando papel fundamental Tendo em vista essas causas, as drogas antifibrinolíticas têm sido preconizadas. Desde a retirada da aprotinina do mercado, o ácido epsilon-aminocaproico e o ácido tranexâmico passaram a ser os únicos representantes disponíveis dessa classe de drogas. Essas medicações diminuem a perda de sangue e agem na resposta inflamatória associada ao procedimento cirúrgico. A eficácia variável dessas drogas ocorre devido aos vários esquemas terapêuticos e níveis séricos existentes. Recentemente têm surgido alguns questionamentos na literatura a respeito das complicações, doses, vias de administração e melhor momento para administração desses agentes...

The postoperative bleeding remains a major complication in cardiac surgery. The etiology of this bleeding is multifactorial, with hyperfibrinolysis and platelet dysfunction playing a key role. Given these causes antifibrinolytic drugs have been recommended Since the with drawal of aprotinin in the market, epsilon-aminocaproic acid and tranexamic acid became the sole representatives of this class of drugs available. These medications reduce blood loss and act on the inflammatory response associated with surgery. The variable efficacy of these drugs is due to multiple drug regimens and serum available. Recently some questions have arisen in the literature regarding the comptications, doses, routes of administration and timing for administration of these agents...

Construction of eukaryotic expression recombinant plasmid of human fibrinolysin / 吉林大学学报(医学版)

Objective To construct the eukaryotic expression vector of human fibrinolysin for further study on anti-thrombus and thrombolysis.Methods Human fibrinolysin gene was amplified from human fetal liver tissue with PCR,and was cloned into eukaryotic expression plasmid pCI-neo and then sequenced.After the correct identification by sequencing,the eukaryotic expression recombinant plasmid of human fibrinolysin was constructed and identified with PCR and enzyme digestion.Results The PCR amplification product of fibrinolysin gene was 1 740 bp.The result of sequencing was the same as that registered in GenBank.The results of PCR and enzyme digestion showed that the recombinant eukaryotic expression plasmid had correct codogenic gene fragment.Conclusion The eukaryotic expression recombinant plasmid of human fibrinolysin gene is successfully constructed and identified.

The Assay of Fibrinolytic Function in the Patients with SLE and its Significance / 中华皮肤科杂志

The fibrinolytic function of 98 patients with SLE were determined by spectrophotometric assay and immunodiffusion, 19 patients were observed before treatment, 1 month after treatment and 3 months after the disappearance of clinical symptoms. The results showed that the low level of fibrinolytic function correlated to the severity and the refractoriness of the disease, the activity of plasminogen activator inhibitor (PAI) was significantly increased in all patients. The activity ratio of tissue-type plasminogen activator (t-PA): PAI was significantly lower than normal level in the patients with lupus nephritis, not only the activity of PAI increased significantly, but also the activity of t-PA was significantly decreased, so the activity ratio of t-PA: PAI became much lower, the result suggested that it was related to the refractoriness of the disease. In patients in clinical remission, although the activity of PAI was still higher than normal level, the activity of t-PA was also significantly increased, therefore, the activity ratio of t-PA: PAI was nearly normal.