Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration.

Cancer, developmental biology and tissue injury present multiple examples where groups of cells residing in close proximity communicate via paracrine factors. It is nearly impossible to dissect such cellular interactions in vivo and is quite challenging in vitro. The goal of this study is to utilize a reconfigurable microfluidic device in order to study paracrine signal exchange between groups of primary hepatocytes in vitro. Previously, we demonstrated that hepatocytes residing on protein spots containing collagen and hepatocyte growth factor (HGF) spots expressed epithelial (hepatic) phenotypes and also rescued them in neighboring hepatocytes on collagen spots that did not receive direct HGF stimulus. Herein, we designed a microfluidic device with parallel fluidic channels separated by retractable (reconfigurable) walls and employed this device to investigate interactions between groups of HGF-stimulated and unstimulated hepatocytes. Using a novel reconfigurable microfluidic device, we demonstrate that cultivation of HGF-containing protein spots upregulates the production of endogenous HGF in hepatocytes and that these HGF molecules diffuse over, causing phenotype enhancement in the recipient cells. We also show that selective treatment of the recipient hepatocytes with a c-met inhibitor (SU11274) diminishes the rescue effect, as gauged by the down-regulation of albumin and HGF expression. Our study is one of the first to demonstrate paracrine signaling via HGF in primary hepatocytes. More broadly, tools and methods described here may be used to study paracrine signaling in other types of cells and will have relevance for various fields of biomedical research from cancer to immunology.

Thrombolytic therapy, also known as clot busting drug, is a breakthrough treatment which has saved untold lives. It has been used in the clinical area to treat venous and arterial thromboembolic complaints which are a foremost cause of death. In 1761, Morgagni lead the way of thrombolytic therapy. Now day's different types of thrombolytic drugs are currently available in market: alteplase, anistreplase, urokinase, streptokinase, tenecteplase, and so forth. Thrombolytic therapy should be given with maintaining proper care in order to minimize the risk of clinically important bleeding as well as enhance the chances of successfully thrombolysis of clot. These cares include preinfusion care, during the infusion care, and postinfusion care. Besides proper knowledge of contraindication, evolutionary factor, and combination of drug is essential for successful thrombolytic therapy. In these review we discussed about these aspect of thrombolytic therapy.

This chapter about fibrinolytic, antiplatelet, and antithrombin treatment for acute ST-segment elevation (STE) myocardial infarction (MI) is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the chapter by Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with ischemic symptoms characteristic of acute MI of < or = 12 h in duration and persistent STE, we recommend that all undergo rapid evaluation for reperfusion (primary percutaneous coronary intervention [PCI] or fibrinolytic) therapy and have a reperfusion strategy implemented promptly after contact with the health-care system (Grade 1A). For patients with ischemic symptoms characteristic of acute MI of < or = 12 h in duration and persistent STE, we recommend administration of streptokinase, anistreplase, alteplase, reteplase, or tenecteplase over no fibrinolytic therapy (all Grade 1A). For patients with symptom duration < or = 6 h, we recommend the administration of alteplase or tenecteplase over streptokinase (both Grade 1A). We recommend aspirin over no aspirin therapy followed by indefinite therapy (Grade 1A); we also recommend clopidogrel in addition to aspirin for up to 28 days (Grade 1A). In addition to aspirin and other antiplatelet therapies, we recommend the use of antithrombin therapy (eg, unfractionated heparin (UFH), enoxaparin, or fondaparinux) over no antithrombin therapy (Grade 1A), including for those patients receiving fibrinolysis (and regardless of which lytic agent is administered), primary PCI, or patients not receiving reperfusion therapy.

Crosstalk is the coupling of energy between the elements of an ultrasonic transducer array. This coupling degrades the performance of transducers in applications such as medical imaging and therapeutics. In this paper, we present an experimental demonstration of guided interface waves in capacitive micromachined ultrasonic transducers (CMUTs). We compare the experimental results to finite element calculations using a commercial package (LS-DYNA) for a 1-D CMUT array operating in the conventional and collapsed modes. An element in the middle of the array was excited with a unipolar voltage pulse, and the displacements were measured using a laser interferometer along the center line of the array elements immersed in soybean oil. We repeated the measurements for an identical CMUT array covered with a 4.5-microm polydimethylsiloxane (PDMS) layer. The main crosstalk mechanism is the dispersive guided modes propagating in the fluid-solid interface. Although the transmitter element had a center frequency of 5.8 MHz with a 130% fractional bandwidth in the conventional operation, the dispersive guided mode was observed with the maximum amplitude at a frequency of 2.1 MHz, and had a cut-off frequency of 4 MHz. In the collapsed operation, the dispersive guided mode was observed with the maximum amplitude at a frequency of 4.0 MHz, and had a cut-off frequency of 10 MHz. Crosstalk level was lower in the collapsed operation (-39 dB) than in the conventional operation (-24.4 dB). The coverage of the PDMS did not significantly affect the crosstalk level, but reduced the phase velocity for both operation modes. Lamb wave modes, A0 and S0, were also observed with crosstalk levels of -40 dB and -65 dB, respectively. We observed excellent agreement between the finite element and the experimental results.

Thrombolytic drugs play a crucial role in the management of patients with acute myocardial infarction, pulmonary embolism, deep vein thrombosis, arterial thrombosis, acute thrombosis of retinal vessel, extensive coronary emboli, and peripheral vascular thromboembolism. Recognition of the importance of fibrinolytic system in thrombus resolution has resulted in the development of different fibrinolytic agents. Now a days several newer plasminogen activators with different pharmacokinetic and pharmacodynamic properties have been developed to treat thrombotic disease, which are fibrin specific with prolonged half-life and can be administered as a single bolus.

This chapter about antithrombotic therapy for acute myocardial infarction (MI) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following: For patients with ischemic symptoms characteristic of acute MI of < 12 h in duration, and ST-segment elevation or left bundle-branch block (of unknown duration) on the ECG, we recommend administration of any approved fibrinolytic agent (Grade 1A). We recommend the use of streptokinase, anistreplase, alteplase, reteplase, or tenecteplase over placebo (all Grade 1A). For patients with symptom duration < 6 h, we recommend the administration of alteplase over streptokinase (Grade 1A). For patients with known allergy or sensitivity to streptokinase, we recommend alteplase, reteplase, or tenecteplase (Grade 1A). For patients with acute posterior MI of < 12 h duration, we suggest fibrinolytic therapy (Grade 2C). In patients with any history of intracranial hemorrhage, closed head trauma, or ischemic stroke within past 3 months, we recommend against administration of fibrinolytic therapy (Grade 1C+). For patients with acute ST-segment elevation MI whether or not they receive fibrinolytic therapy, we recommend aspirin, 160 to 325 mg p.o., at initial evaluation by health-care personnel followed by indefinite therapy, 75 to 162 mg/d p.o. (both Grade 1A). In patients allergic to aspirin, we suggest use of clopidogrel as an alternative therapy to aspirin (Grade 2C). For patients receiving streptokinase, we suggest administration of either i.v. unfractionated heparin (UFH) [Grade 2C] or subcutaneous UFH (Grade 2A). For all patients at high risk of systemic or venous thromboembolism (anterior MI, pump failure, previous embolus, atrial fibrillation, or left ventricular thrombus), we recommend administration of IV UFH while receiving streptokinase (Grade 1C+).