The Use of Antithrombotic Therapies in Reducing Synthetic Small-Diameter Vascular Graft Thrombosis

2012 ◽  
Vol 46 (3) ◽  
pp. 212-222 ◽  
Author(s):  
Mark Tatterton ◽  
Stacy-Paul Wilshaw ◽  
Eileen Ingham ◽  
Shervanthi Homer-Vanniasinkam

Background. Thrombosis of synthetic small-diameter bypass grafts remains a major problem. The aim of this article is to review the antithrombotic strategies that have been used in an attempt to reduce graft thrombogenicity. Methods. A PubMed/MEDLINE search was performed using the search terms “vascular graft thrombosis,” “small-diameter graft thrombosis,” “synthetic graft thrombosis” combined with “antithrombotic,” “antiplatelet,” “anticoagulant,” “Dacron,” “PTFE,” and “polyurethane.” Results. The majority of studies on antithrombotic therapies have used either in vitro models or in vivo animal experiments. Many of the therapies used in these settings do show antithrombotic efficacy against synthetic graft materials. There is however, a distinct lack of human in vivo studies to further delineate the performance and limitations of therapies displaying good antithrombotic characteristics. Conclusion. Very few antithrombotic therapies have translated into clinical use. More human in vivo studies are required to assess the efficacy and safety of such therapies.

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.


2020 ◽  
Vol 15 (3) ◽  
pp. 193-206
Author(s):  
Brognara Lorenzo ◽  
Salmaso Luca ◽  
Mazzotti Antonio ◽  
Di M. Alberto ◽  
Faldini Cesare ◽  
...  

Background: Chronic wounds are commonly associated with polymicrobial biofilm infections. In the last years, the extensive use of antibiotics has generated several antibiotic-resistant variants. To overcome this issue, alternative natural treatments have been proposed, including the use of microorganisms like probiotics. The aim of this manuscript was to review current literature concerning the application of probiotics for the treatment of infected chronic wounds. Methods: Relevant articles were searched in the Medline database using PubMed and Scholar, using the keywords “probiotics” and “wound” and “injuries”, “probiotics” and “wound” and “ulcer”, “biofilm” and “probiotics” and “wound”, “biofilm” and “ulcer” and “probiotics”, “biofilm” and “ulcer” and “probiotics”, “probiotics” and “wound”. Results: The research initially included 253 articles. After removal of duplicate studies, and selection according to specific inclusion and exclusion criteria, 19 research articles were included and reviewed, accounting for 12 in vitro, 8 in vivo studies and 2 human studies (three articles dealing with animal experiments included also in vitro testing). Most of the published studies about the effects of probiotics for the treatment of infected chronic wounds reported a partial inhibition of microbial growth, biofilm formation and quorum sensing. Discussion: The application of probiotics represents an intriguing option in the treatment of infected chronic wounds with multidrug-resistant bacteria; however, current results are difficult to compare due to the heterogeneity in methodology, laboratory techniques, and applied clinical protocols. Lactobacillus plantarum currently represents the most studied strain, showing a positive application in burns compared to guideline treatments, and an additional mean in chronic wound infections. Conclusions: Although preliminary evidence supports the use of specific strains of probiotics in certain clinical settings such as infected chronic wounds, large, long-term clinical trials are still lacking, and further research is needed.


2021 ◽  
Vol 22 (15) ◽  
pp. 7929
Author(s):  
Megan Chesnut ◽  
Thomas Hartung ◽  
Helena Hogberg ◽  
David Pamies

Neurodevelopment is uniquely sensitive to toxic insults and there are concerns that environmental chemicals are contributing to widespread subclinical developmental neurotoxicity (DNT). Increased DNT evaluation is needed due to the lack of such information for most chemicals in common use, but in vivo studies recommended in regulatory guidelines are not practical for the large-scale screening of potential DNT chemicals. It is widely acknowledged that developmental neurotoxicity is a consequence of disruptions to basic processes in neurodevelopment and that testing strategies using human cell-based in vitro systems that mimic these processes could aid in prioritizing chemicals with DNT potential. Myelination is a fundamental process in neurodevelopment that should be included in a DNT testing strategy, but there are very few in vitro models of myelination. Thus, there is a need to establish an in vitro myelination assay for DNT. Here, we summarize the routes of myelin toxicity and the known models to study this particular endpoint.


2009 ◽  
Vol 3 (4) ◽  
Author(s):  
Fangmin Xu ◽  
Kevin Hart ◽  
Claire E. Flanagan ◽  
John C. Nacker ◽  
Roham Moftakhar ◽  
...  

The treatment of cerebral aneurysms is frequently accomplished via endovascular delivery of metal coils in order to occlude the aneurysm and prevent rupture. This procedure involves imprecise packing of large lengths of wire into the aneurysm and often results in high rates of aneurysm recanalization. Over time, this incomplete aneurysm occlusion can lead to aneurysm enlargement, which may have fatal consequences. This report describes the fabrication and preliminary testing of a novel aneurysm occlusion device composed of a single metal coil surrounded by a biocompatible polymer shell. These coil-in-shell devices were tested under flow conditions in synthetic in vitro models of saccular aneurysms and deployed in vivo in a short-term porcine aneurysm model to study occlusion efficacy. A single nickel titanium shape memory wire was used to deploy a biocompatible, elastic polymeric shell, leading to aneurysmal sac filling in both in vitro and in vivo aneurysm models. The deployment of this coil-in-shell device in synthetic aneurysm models in vitro resulted in varying degrees of aneurysm occlusion, with less than 2% of trials resulting in significant leakage of fluid into the aneurysm. Meanwhile, in vivo coil-in-shell device implantation in a porcine aneurysm model provided proof-of-concept for successful occlusion, as both aneurysms were completely occluded by the devices. Both in vitro and in vivo studies demonstrated that this coil-in-shell device may be attractive as an alternative to traditional coil embolization methods in some cases, allowing for a more precise and controlled aneurysm occlusion.


Author(s):  
Aloisio Cunha de Carvalho ◽  
Leoni Villano Bonamin

Background: Several reviews about phytotherapy and homeopathy have been published in the last years, including Viscum album (VA.L). VA is a parasite plant whose extract has anti-cancer proprieties and is used alone or in combination with conventional chemotherapy. Methods: We performed a systematic review about the in vivo and in vitro models described in the literature, including veterinary clinical trials. The literature was consulted from Pubmed database. Results: There are several kinds of pharmaceutical preparations about VA and their active principles used in experimental studies, lectin being frequently studied (alone or as an extract compound). More than 50% of available literature about VA is related to the lectin effects. On the other hand, the effects of viscotoxins are less studied. Among the in vivo experimental studies about VA and its compounds, the B16 murine melanoma is the most used model, followed by Ehrlich, Walker and Dalton tumors. The results point to the apoptotic effects, metastasis control and tumor regression. Some veterinary clinical studies about the use of VA in the treatment of sarcoid, fibrosarcoma and neuroblastoma are quoted in literature too, with interesting results. Considering the in vitro models, our review revealed that NALM6 leukemia cells, B16 melanoma and NC1-H460 lung carcinoma were the most studied tumor models, apoptosis signals being the most important findings. Only one study verified immunoglobulin and interleukin production. All consulted papers were related to phytotherapy preparations only. Conclusions: Although the literature about the anti-cancer activity of VA extract and its lectins is enough, there is a marked lack of information about viscotoxin activities and about the effects of homeopathic preparations of this plant on animal tumors and on in vitro cultivated tumor cells.


2019 ◽  
Vol 30 (1) ◽  
pp. 16-21 ◽  
Author(s):  
T. Aghaloo ◽  
J.J. Kim ◽  
T. Gordon ◽  
H.P. Behrsing

Traditional tobacco products have well-known systemic and local oral effects, including inflammation, vasoconstriction, delayed wound healing, and increased severity of periodontal disease. Specifically in the oral cavity and the lung, cigarette smoking produces cancer, increased infectivity, acute and chronic inflammation, changes in gene expression in epithelial lining cells, and microbiome changes. In recent years, cigarette smoking has greatly decreased in the United States, but the use of new tobacco products has gained tremendous popularity. Without significant knowledge of the oral sequelae of products such as electronic cigarettes, researchers must evaluate current in vitro and in vivo methods to study these agents, as well as develop new tools to adequately study their effects. Some in vitro testing has been performed for electronic cigarettes, including toxicologic models and assays, but these mostly study the effect on the respiratory tract. Recently, direct exposure of the aerosol to in vitro 3-dimensional tissue constructs has been performed, demonstrating changes in cell viability and inflammatory cytokines. For in vivo studies, a universal e-cigarette testing machine or standard vaping regime is needed. A standard research electronic cigarette has recently been developed by the National Institute of Drug Abuse, and other devices delivering aerosols with different nicotine concentrations are becoming available. One of the biggest challenges in this research is keeping up with the new products and the rapidly changing technologies in the industry.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Therina Du Toit ◽  
Amanda C Swart

Abstract The metabolism of 11β-hydroxyandrostenedione (11OHA4), a major adrenal C19 steroid, was first characterised in our in vitro prostate models showing that 11OHA4, catalysed by 11βHSDs, 17βHSDs and 5α-reductases, yields potent androgens, 11keto-testosterone (11KT) and 11keto-dihydrotestosterone (11KDHT) in the 11OHA4-pathway [1]. Findings have since led to the analysis of C11-oxy steroids in PCOS, CAH and 21OHD. However, the only circulating C11-oxy steroids included to date have been 11OHA4, 11keto-androstenedione (11KA4), 11β-hydroxytestosterone (11OHT) and 11KT, with 11KT reported as the only potent androgen produced from 11OHA4. We have identified higher levels of 11KDHT compared to 11KT in prostate cancer tissue and benign prostatic hyperplasia tissue and serum, with data suggesting impeded glucuronidation of the C11-oxy androgens [2,3]. The assessment of 11KDHT and the inactivation/conjugation of the C11-oxy steroids in clinical conditions is therefore crucial. We investigated the metabolism of testosterone, 11KT, 11OHT, dihydrotestosterone, 11KDHT and 11OHDHT in JEG-3 placenta choriocarcinoma, MCF-7 BUS and T-47D breast cancer cells, focusing on glucuronidation and sulfation. Steroids were assayed at 1 µM and metabolites were quantified using UPC2-MS/MS. Conjugated steroids were not detected in JEG-3 cells with DHT (0.6 µM remaining) metabolised to 5α-androstane-3α,17β-diol and androsterone (AST), and 11KDHT (0.9 µM remaining) to 11OHAST and 11KAST. 11OHA4 was converted to 11KA4 (12%) and 11KT (2.5%); and 11KT to 11KDHT (14%). In MCF-7 BUS cells, DHT was significantly glucuronidated, whereas 11KDHT was not. 11KAST was the only steroid in the MCF-7 BUS and T-47D cells that was significantly sulfated (p<0.05). In parallel we investigated sulfation in the LNCaP prostate model. Comparing sulfated to glucuronidated levels, only DHT was sulfated, 26%. Analysis showed that C19 steroids were significantly conjugated (glucuronidated + sulfated) compared to the C11-oxy C19 steroids. As there exists an intricate interplay between steroid production and inactivation, impacting pre- and post-receptor activation, efficient conjugation would limit adverse downstream effects. Our data demonstrates the production and impeded conjugation of active C11-oxy C19 steroids, allowing the prolonged presence of androgenic steroids in the cellular microenvironment. Identified for the first time is the 11OHA4-pathway in placenta and breast cancer cells, and the sulfation of 11KAST. Characterising steroidogenic pathways in in vitro models paves the direction for in vivo studies associated with characterising clinical disorders and disease, which the C11-oxy C19 steroids and their intermediates, including inactivated and conjugated end-products, have highlighted. [1] Bloem, et al. JSBMB 2015, 153; [2] Du Toit & Swart. MCE 2018, 461; [3] Du Toit & Swart, JSBMB 2020, 105497.


Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1913 ◽  
Author(s):  
Bahare Salehi ◽  
Lorene Armstrong ◽  
Antonio Rescigno ◽  
Balakyz Yeskaliyeva ◽  
Gulnaz Seitimova ◽  
...  

This work is an updated snapshot of Lamium plants and their biological activities. The main features of the plant are described and the components of its essential oils are summarized. The traditional medicinal uses of Lamium plants has been reported. The presence of these chemicals i.e., hydroxycinnamic acids, iridoids, secoiridoids, flavonoids, anthocyanins, phenylpropanoids, phytoecdysteroids, benzoxazinoids, betaine can provide biological activities. After the discussion of antioxidant properties documented for Lamium plants, the biological activities, studied using in vitro models, antimicrobial, antiviral, anti-inflammatory, anti-nociceptive activity, and pain therapy and cytotoxicity and cytoprotective activity are here described and discussed. Finally, targeted examples of in vivo studies are reported.


2020 ◽  
Vol 20 (3) ◽  
pp. 1900234 ◽  
Author(s):  
Jean‐Marc Behr ◽  
Scott Alexander Irvine ◽  
Chaw‐Su Thwin ◽  
Ankur Harish Shah ◽  
Min‐Chul Kraun Bae ◽  
...  

Toxics ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 27
Author(s):  
Tania Charette ◽  
Danyel Bueno Dalto ◽  
Maikel Rosabal ◽  
J. Jacques Matte ◽  
Marc Amyot

Fish consumption is the main exposure pathway of the neurotoxicant methylmercury (MeHg) in humans. The risk associated with exposure to MeHg may be modified by its interactions with selenium (Se) and arsenic (As). In vitro bioaccessibility studies have demonstrated that cooking the fish muscle decreases MeHg solubility markedly and, as a consequence, its potential absorption by the consumer. However, this phenomenon has yet to be validated by in vivo models. Our study aimed to test whether MeHg bioaccessibility can be used as a surrogate to assess the effect of cooking on MeHg in vivo availability. We fed pigs raw and cooked tuna meals and collected blood samples from catheters in the portal vein and carotid artery at: 0, 30, 60, 90, 120, 180, 240, 300, 360, 420, 480 and 540 min post-meal. In contrast to in vitro models, pig oral bioavailability of MeHg was not affected by cooking, although the MeHg kinetics of absorption was faster for the cooked meal than for the raw meal. We conclude that bioaccessibility should not be readily used as a direct surrogate for in vivo studies and that, in contrast with the in vitro results, the cooking of fish muscle did not decrease the exposure of the consumer to MeHg.


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