Self-sacrificing templated-derived chitosan microcapsules for targeted drug delivery in thrombolytic therapy.

ABSTRACTReduced graphene oxide (rGO) sheets were first modified with 2‐hydroxypropyltrimethyl ammonium chloride chitosan (HACC), and these modified rGO sheets (named HACC–rGO) were used as reinforcement materials and introduced to the walls of chitosan (CS) microcapsules. All of the monodisperse microcapsules were conveniently generated by a gas–liquid microfluidic technique. The results of scanning electron microscopy, X‐ray diffraction, and thermogravimetric analysis all demonstrate that the HACC–rGO sheets existed and were dispersed in the capsular shell. The HACC–rGO‐reinforced CS microcapsules showed better mechanical strength and better chemical stability with an α‐cyclodextrin solution than the CS microcapsules without HACC–rGO. Importantly, the HACC–rGO‐reinforced CS microcapsules exhibited a slower drug‐release behavior and provide a method for the control of the release rate of drug‐loaded microcapsules. In an in vitro cytotoxicity evaluation by a 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide assay, the Schwann cells still showed good cell viability after they were treated by extracts of the CS/HACC–rGO microcapsules with concentrations ranging from 0.02 to 2000 μg/mL. Therefore, the HACC–rGO‐reinforced CS microcapsules are promising for applications in the fields of drug delivery and controlled release. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44549.

Pseudomonas aeruginosa is considered a public threat, with antibiotics increasing their resistance. Essential oils (EOs) have demonstrated significant effects against microorganisms. However, due to their volatile nature, they cannot be used in their free-state. Here, hydrogel-like films were produced from a combination of sodium alginate (SA) and gelatin (GN) to serve as delivery platforms for the controlled release of cinnamon leaf oil (CLO) entrapped within chitosan (CS) microcapsules. The minimum inhibitory concentration (MIC) of CLO was established at 39.3 mg/mL against P. aeruginosa. CS microcapsules were prepared via ionotropic gelation with tripolyphosphate (TPP), encapsulating CLO at MIC. Successful production was confirmed by fluorescent microscopy using Nile red as a detection agent. Microcapsules were embedded within a biodegradable SA/GN polymeric matrix processed by solvent casting/phase inversion with SA/GN used at 70/30 polymer ratio at 2 wt.% SA concentration. A concentration of 2 wt.% CaCl2 was used as a coagulation bath. The CLO-containing CS microcapsules’ homogeneous distribution was guaranteed by successive vortex and blending processes applied prior to casting. CLO controlled release from the films was monitored in physiological pH for 24 h. Hydrated films were obtained, with the presence of loaded CS capsules being confirmed by FTIR. Qualitative/quantitative antimicrobial examinations validated the loaded film potential to fight P. aeruginosa.

Facile method for forming ionically cross-linked chitosan microcapsules from Pickering emulsion templates

Phlegmasia cerulea dolens (PCD) is a rare complication of acute deep vein thrombosis (DVT) characterized by fulminant venous thrombosis that compromises arterial blood flow, resulting in tissue ischemia, venous gangrene, and possible loss of limb. A high rate of morbidity and mortality associated with PCD requires prompt recognition and treatment. An accepted therapeutic algorithm for the management of PCD does not currently exist. Acute reduction in clot burden can be achieved through catheter-directed thrombolysis (CDT) with lower rates of post-thrombotic symptoms, and there has been a recent trend toward use of CDT. We report the case of a 26-year-old female who presented with PCD of her left leg and underwent successful CDT, highlighting the benefits of rapid recognition of a rare complication of acute DVT, and the role for a multidisciplinary endovascular approach to managing fulminant limb-threatening venous thrombosis. La phlegmatia caerulea dolens (PCD) est une complication rare de la thrombose veineuse profonde (TVP) aiguë caractérisée par une thrombose veineuse foudroyante qui compromet le débit sanguin et résulte en une ischémie tissulaire, une évolution vers la gangrène et le risque de perte de membre. La PCD est associée à un taux élevé de morbidité et de mortalité et requiert une reconnaissance et un traitement rapides. Il n’existe actuellement pas de modèle défini d’intervention pour la prise en charge de la PCD. Une réduction rapide du caillot peut être obtenue par thrombolyse guidée par cathéter (TGC), intervention associée à un taux plus faible de symptômes post-thrombotiques. Le recours à la TGC est d’ailleurs plus fréquent depuis peu. Nous décrivons ici le cas d’une patiente âgée de 26 ans qui présentait une PCD à la jambe gauche et qui a été traitée avec succès par TGC. Ce cas fait ressortir l’importance de savoir reconnaître rapidement une complication rare de la TVP aiguë, ainsi que d’appliquer une approche endovasculaire multidisciplinaire dans la prise en charge d’une thrombose veineuse fulminante susceptible de causer la perte d’un membre.

Thrombolytic therapy for prosthetic valve thrombosis in children: two case reports and review of the literature

Objective To evaluate the effectiveness and safety of ultrasound-enhanced thrombolysis for acute ischemic stroke. Methods Fifty stroke patients with acute middle cerebral artery occlusion were randomly divided into either a ultrasound-enhanced thrombolysis group (recombinant tissue-plasminogen activator [rtPA]+ 2 MHz ultrasound monitoring for 2 h) or a standard thrombolysis group (rtPA alone). The demographic characteristics, vascular risk factors, blood pressure before treatment, thrombolysis in brain ischemia (TIBI) grade before thrombosis, and vascular occlusion site of the patients were collected. The primary outcome endpoint was the good outcome rate (defined as the modified Rankin Scale score 0-1) at 3 months. The secondary outcome endpoints were complete recanalization at 2 h after thrombolysis, sustained complete recanalization, symptomatic intracerebral hemorrhage, and mortality. Results The good outcome rate of the ultrasound-enhanced thrombolysis group at 3 months after treatment was significantly higher than that of the standard thrombolysis group (64% vs. 36%; P=0.011). The sustained complete recanalization rate (40%vs. 8%; P=0.018) and complete recanalization rate (48% vs. 12%; P=0.012) of the ultrasound-enhanced thrombolysis group were significantly higher than those of the standard thrombolysis group, but there were no significant differences in the reocclusion rate (8% vs. 12%; P=0.637), incidence of symptomatic intracerebral hemorrhage (4% vs. 4%; P=1.000), and mortality (4% vs. 4%; P=1.000) compared with the standard thrombolysis group. Conclusions Ultrasound-enhanced thrombolysis can improve the sustained complete recanalization rate, complete recanalization rate, and good outcome rate after using rtPA within 2 h, and it does not increase the risks of symptomatic cerebral hemorrhage and death. It is a safe and effective adjunctive thrombolytic therapy. Key words: Stroke; Brain Ischemia; Thrombolytic Therapy; Tissue Plasminogen Activator; Ultrasonic Therapy; Ultrasonography, Doppler, Transcranial; Treatment Outcome

Tissue plasminogen activator for the treatment of adults with critical COVID-19: A pilot randomized clinical trial

Objective To compare the efficacy and safety of intravenous and intra-arterial thrombolysis with tissue plasminogen activator in Chinese patients with acute ischemic stroke.Methods Patients with acute ischemic stroke,consecutively registered in our database from 2005 to 2010,were included.Admission demographics,time window,procedure delay in hospital,route of thrombolysis,dose of tissue plasminogen activator,stroke severity,laboratory tests and vital signs of these patients were collected.CT manifestations and TOAST subtypes were obsevred.Outcome variables included hemorrhagic transformation,re-canalization of responsible vessels,favorable functional outcome 90 d after thrombolysis and mortality were evaluated.Univariate and multivariate logistic regression were used to select the potential variables and compare the differences between the two kinds of route in thrombolysis.Results A total of 96 patients were included with one loss of follow-up.Forty-three were male (44.8％) and 53 female.Median age was 72 years,median body weight 58.5 kilograms,and median time window 4.3 hours.Sixty-four patients received intravenous thrombolysis and 32 patients intra-arterial thrombolysis.Favorable outcome was achieved in 43.8％ patients 90 d after thrombolysis with a mortality reaching 17.9％.Univariate analysis showed intra-arterial thrombolysis had a much higher cost (47623.6 vs 25699.8 RMB),longer procedure delay (3.17 h vs 1.73 hours) and time window (5.54 vs 3.58 hours),and lower dose (20 vs 50 mg) as compared with intravenous thrombolysis (P＜0.05);however,no significant differences were found between the 2 groups in re-canalization of responsible vessels (64.9％ vs 53.8％),hemorrhagic transformation (25％ vs 31.3％),favorable outcome (45.3％ vs 40.6％) and mortality (14.7％ vs 3.2％).Multivariate logistic regression indicated that route of thrombolysis did not predict unfavorable outcome (OR=0.54,P=0.824,95％ CI:0.00-131.46);re-canalization could independently predict the functional outcome (OR=0.11,P=0.027,95％ CI:0.02-0.78),while the route of thrombolysis itself did not influence the re-canalization.Conclusion In patients with acute ischemic stroke,the treatment efficacy and safety of intravenous and intra-arterial thrombolysis with tissue plasminogen activator are similar,not enjoying significant difference in hemorrhagic transformation and mortality. Key words: Acute ischemic stroke; Intra-arterial thrombolysis; Thrombolytic therapy; Tissue plasminogen activator; Comparative study

Objective To observe the curative effect of thrombolysis and anticoagulant therapy on submassive pulmonary emblism (PE) patients.Methods Fifty six submassive PE patients were randomly divided thrombolysis group and anticoagulant group.The thrombolysis group were given thrombolysis therapy with Recombinant tissue plasminogen activator (rt-PA) and given anticoagulant therapy (Low molecular heparin and Warfarin) sequentially.The anticoagulant group were given anticoagulant therapy merely.The total effective rate and bleeding rate were observed.Results The total effective rate were 96.4％ in thrombolysis group and higher than that in anticoagulant group (65.4％,P ＜ 0.05).There were no intracranial hemorrhages and severe hemorrhages of other body parts.There was no significant difference in bleeding incidence rate between the two groups (P ＞ 0.05).Conclusions If there is no contraindication of thrombolysis we should choice thrombolysis to treat submassive PE patients that can improve the symptoms of right ventricle dysfunction quickly and increase the effective treatment rate. Key words: Submassive pulmonary embolism; Thrombolysis; Recombinant tissue plasminogen activator

Preparation of strawberry chitosan composite microcapsules and their application in textiles

Objective To investigate the clinical efficacy of transcranial Doppler(TCD)-assisted interventional intra-arterial thrombosis in patients with acute ischemic stroke.Methods This clinical trial enrolled 22 patients with acute ischemic stroke(13 with occlusion of the middle cerebral artery within 6 h of symptom onset; 9 with occlusion of the base artery within 12 h of symptom onset); occlusive arterial cannula was performed and recombinant tissue plasminogen activator(rt-PA,20 mg)was injected to perform interventional intra-arterial thrombosis; and TCD ultrasonography of low frequency(2 MHz)and low intensity(0.25 W/cm2)was performed to assist the thrombosis.Cranial CT was performed again right after the operation and 24 h after the operation to observe the recanalization rate and intracranial hemorrhage; NIHSS scores and Barthel index scores were compared before and after the operation.Results The percentage ofrecanalization was 77.27％(17/22),including 22.73％(5/22)complete recanalization and 54.55％(12/22)partial recanalization; non-symptomatic intracerebral hemorrhage occurred in 3 patients and no symptomatic intracerebral hemorrhage was noted.NIHSS and Barthel index scores after the operation were obviously higher than those before the operation,indicating that favorable outcomes were achieved after thrombosis.Conclusion TCD-assited interventional intra-arterial thrombosis with rt-PA,significantly improving the recanalization rate of occlusive artery and remarkably reducing the happening ofintracerebral hemorrhage,can improve the prognosis and enjoy good clinical efficacy and safety in treatment of acute ischemic stroke. Key words: Cerebral infarction; Thrombolysis; Recombinant tissue plasminogen activator; Transcranial Doppler

Thrombolytic therapy

Objective To compare the effect of arterial thombolysis with urokinase and intravenous thrombolysis with recombinant tissue plasminogen activator(rt-PA) in treatment of ischemic stroke.Methods One hundred patients with ischemic stroke were divided into intravenous thrombolysis (with rt-PA) group and arterial thrombolysis (with urokinase) group with 50 cases each by random digits table method.The thrombolytic recanalization rate,mortality rate and complications after treatment were observed and compared between two groups.Results The thrombolytic recanalization rate in intravenous thrombolysis (with rt-PA) group was higher than that in arterial thrombolysis (with urokinase) group [88.0％ (44/50) vs.66.0％ (33/50)],the complication rate in intravenous thrombolysis (with rt-PA) group was lower than that in arterial thrombolysis (with urokinase) group [6.0％ (3/50) vs.28.0％ (14/50)],and there was significant difference (P ＜ 0.05).There was no significant difference in mortality between two groups (P ＞ 0.05).There was no significant difference in the National Institutes of Health Stroke Scale (NIHSS) scores before treatment between two groups (P ＞ 0.05).The NIHSS scores 1,3,10,30 d after treatment were lower than those before treatment in two groups,and there were significant differences (P ＜ 0.05).There was no significant difference in NIHSS scores at different times and modified Rankin Scale 30 d after treatment between two groups (P＞ 0.05).Conclusions The efficacy of rt-PA in ischemic stroke patients is significantly better than that of the arterial thrombolysis with urokinase,with higher recanalization rate and fewer complications.It is safe and effective,and can be as the first choice for the treatment of ischemic stroke thrombolysis. Key words: Thrombolytic therapy; Urokinase-type plasminogen activator; Tissue plasminogen activator; Stroke

Deep venous thrombosis is a possible complication of indwelling central venous catheters (CVC), with an incidence as high as 61%. We report a case of successful thrombolysis of a CVC-related right atrial thrombus in a pediatric cancer patient with recombinant human tissue plasminogen activator (0.1 mg/kg per h for 12 h) and heparin (10 IU/kg per h for 24 h) administered for 6 days. Daily echocardiographic examination showed progressive lysis of the thrombus. The thrombolytic treatment was associated with mild oozing from the venipuncture sites, but no major bleeding was noted; moreover, thrombin, thromboplastin time and fibrinogen were normal or only minimally altered. Anticoagulant therapy, with or without CVC removal, is the treatment of choice for uncomplicated CVC-related thrombosis. Fibrinolytic therapy may be indicated in some cases at risk of pulmonary embolism or to avoid open heart surgery. Recombinant human tissue plasminogen activator is increasingly used for thrombolytic treatment of organ and limb thrombosis, but experience with it in the pediatric hematology-oncology setting is still limited. This report showed that administering recombinant human tissue plasminogen activator in a pediatric cancer patient prior to hematopoietic stem cell transplantation was effective and safe under strict biochemical and instrumental monitoring. Further studies are needed to determine the best antithrombotic treatment for CVC-related thrombosis, and also the dosage of the medication selected and the duration of treatment.

Objectives Acute thrombotic ischemia is a very dangerous limb-threatening and life-threatening disease. It is better treated by catheter-directed thrombolysis. Now, tissue plasminogen activator like alteplase is safer than streptokinase or urokinase. The current study is designed to show its efficacy and safety and to investigate variables that correlate with outcome. Patients and methods This is a prospective cohort study. It included patients with acute thrombotic limb ischemia. Excluded ones were acute ischemia due to embolism, trauma, arterial dissection, complicated aneurysm, bleeding risk, history of recent intracranial bleeding, massive gangrene, or uncontrolled hypertension. The study is approved by ethical committee of Beni-Suef University. Primary end points were technical success, clinical success, and limb salvage. Secondary end points were procedural complications. Results A total of 36 patients were enrolled in the study from March 2019 to February 2020 in Beni-Suef University Hospital. It included 21 (58.33%) male patients. The patients’ mean age was 58.42 years and mean BMI was 31.56 kg/m2. Risk factors were smoking in 15 (41.67%) patients, diabetes mellitus in 16 (44.44%) patients, hypertension in 15 (41.67%) patients, ischemic heart disease in nine (25%) patients, and hyperlipidemia in 14 (38.89%) patients. Clinical presentation showed that 16 (44.44%) patients were in Rutherford IIa category and 20 (55.56%) patients were in Rutherford IIb category. Limb salvage was achieved in 14/16 (87.5%) of patients in Rutherford IIa category and 12/20 (60%) of patients in Rutherford IIb category. Statistical analysis showed a correlation of BMI and severity of ischemia with outcome. Moreover, the frequency of risk factors was correlated with outcome. Conclusion Catheter-directed thrombolysis using alteplase is effective and safe to treat acute thrombotic limb ischemia. Its outcome is better with lower BMI, less severe ischemia, and less or no comorbid disease.