Defibrotide

Baker, Danial E.; Demaris, Kendra

doi:10.1310/hpj5110-847

Cited by 17 publications

(16 citation statements)

References 38 publications

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“…Various pharmacological agents are currently under investigation as potential treatments for SOS/VOD. Defibrotide, approved in many European and US, has been shown to suppress SOS/VOD by inducing TM and prostaglandin I2 in endothelial cells and by inhibiting the expression of PAI-1 (16)(17)(18). The present study focused on TM, which has recently been reported to have not only an anticoagulant effect but also a wide range of other effects, such as anti-inflammatory and angiogenic effects, and a protective effect on the vascular endothelium (29).…”

Section: Discussionmentioning

confidence: 98%

“…Although no method has yet been established for the prevention and treatment of SOS/VOD, defibrotide has been a focus of attention in other countries (16)(17)(18); however, in Japan, it cannot be used because the costs are not covered by insurance. Recently, recombinant human soluble thrombomodulin (rTM), which has been used as a therapeutic agent for the treatment of disseminated intravascular coagulation, has gained attention because of its anti-inflammatory properties and protective effect on the vascular endothelium (19).…”

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confidence: 99%

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Prophylactic Effect of Recombinant Human Soluble Thrombomodulin for Hepatic Sinusoidal Obstruction Syndrome Model Mice

Kanou

Miyashita

Yamamoto

et al. 2020

In Vivo

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Aim: The present study aimed to examine the effects of prophylactic administration of recombinant human soluble thrombomodulin (rTM) for the prevention of sinusoidal obstruction syndrome (SOS). Materials and Methods: Crl:CD1 mice were allocated to the rTM, placebo, and control groups. The rTM group received an intraperitoneal administration of rTM, with intraperitoneal administration of monocrotaline (MCT) 1 h later. The placebo group received PBS instead of rTM, and the control group received PBS instead of rTM and MCT. Mice were sacrificed 48 h after MCT administration, and blood and liver tissues were evaluated. Immunostaining was performed using anti-CD42b and anti-SE-1 antibodies, and AZAN staining. Levels of plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS) in whole liver tissues were estimated using RT-PCR. Results: Hematoxylineosin staining showed that SOS-related findings were markedly attenuated in the rTM group compared to the placebo group. CD42b immunostaining showed the presence of extravasated platelet activation (EPA) in the Disse space in the placebo group, but this was less noticeable in the rTM group. PAI-1 levels were significantly lower in the rTM group than in the placebo group in RT-PCR. However, eNOS levels were significantly higher in the rTM group than in the placebo group. Conclusion: Administration of rTM may prevent SOS by protecting sinusoidal endothelial cells.

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Prophylactic Effect of Recombinant Human Soluble Thrombomodulin for Hepatic Sinusoidal Obstruction Syndrome Model Mice

Kanou

Miyashita

Yamamoto

et al. 2020

In Vivo

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“…The agent aids to reduce cardiovascular disease risk by reducing low-density lipoprotein (LDL) cholesterol levels. Defibrotide is a polydisperse oligo-nucleotide purified from porcine intestinal mucosa that has been approved as a drug against severe hepatic veno-occlusive disease, where it acts in a complex sequenceindependent mechanism on fibrosis, angiogenesis, apoptosis, and aggregation of thrombocytes (15,16). Other nucleotide-based therapeutic approaches are currently being tested in clinical trials (17,18).…”

Section: Rnasmentioning

confidence: 99%

Unresolved Issues in RNA Therapeutics in Vascular Diseases With a Focus on Aneurysm Disease

Schellinger

Dannert

Mattern

et al. 2021

Front. Cardiovasc. Med.

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New technologies have greatly shaped the scientific and medical landscape within the last years. The unprecedented expansion of data and information on RNA biology has led to the discovery of new RNA classes with unique functions and unexpected modifications. Today, the biggest challenge is to transfer the large number of findings in basic RNA biology into corresponding clinical RNA-based therapeutics. Lately, this research begins to yield positive outcomes. RNA drugs advance to the final phases of clinical trials or even receive FDA approval. Furthermore, the introduction of the RNA-guided gene-editing technology CRISPR and advances in the delivery of messenger RNAs have triggered a major progression in the field of RNA-therapeutics. Especially short interfering RNAs and antisense oligonucleotides are promising examples for novel categories of therapeutics. However, several issues need to be addressed including intracellular delivery, toxicity, and immune responses before utilizing RNAs in a clinical setting. In this review, we provide an overview on opportunities and challenges for clinical translation of RNA-based therapeutics, with an emphasis on advances in novel delivery technologies and abdominal aortic aneurysm disease where non-coding RNAs have been shown to play a crucial regulatory role.

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“…Pre-existing thrombocytopenia, and Renal failure, Patients with impaired blood clotting. Should not be given along with anticoagulants, and platelet inhibitors Hemorrhage, hypotension, interstitial lung disease, cystitis hemorrhagic, renal failure, haematuria, gastrointestinal hemorrhage Should be avoided with systemic anticoagulant or fibrinolytic therapy [78].…”

Section: Pregnancymentioning

confidence: 99%

<sup></sup><strong>Repurposing of FDA Approved Drugs as COVID-19 Therapeutics: Safety Concerns and Contraindications of Drugs in Clinical Trials</strong>

Dharavath¹,

Dutt²,

Kumar³

et al. 2020

Preprint

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Coronavirus disease (COVID-19) is the current global public health threat with no specific, effective, and approved treatment available till date. The outbreak of COVID-19 has led the world into an unimagined and uncertain situation by disrupting the economies, claiming human lives, and leaving many into secondary mental health problems. As per the latest WHO report, approximately 8.2 million people are infected, and nearly 0.44 million lives are lost to COVID. The infection has spread to over 200 countries and territories around the world. The world is in search of efficient diagnostics and therapeutics, including vaccines, biologics and drugs. With the rapid increase in rates of infection and time constraints, drug repurposing seems to be a potential and viable option to find the promising anti-COVID therapeutics. In the wake of a rapid increase in the number of clinical trials involving drugs for repurposing, we aim to provide information on the safety concerns related to the drugs currently investigated in trials. This review also highlights the possible mechanisms of actions, adverse drug reactions, and contraindications of the drugs under repurposing evaluation.

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Defibrotide

Cited by 17 publications

References 38 publications

Prophylactic Effect of Recombinant Human Soluble Thrombomodulin for Hepatic Sinusoidal Obstruction Syndrome Model Mice

Prophylactic Effect of Recombinant Human Soluble Thrombomodulin for Hepatic Sinusoidal Obstruction Syndrome Model Mice

Unresolved Issues in RNA Therapeutics in Vascular Diseases With a Focus on Aneurysm Disease

<sup></sup><strong>Repurposing of FDA Approved Drugs as COVID-19 Therapeutics: Safety Concerns and Contraindications of Drugs in Clinical Trials</strong>

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