Effect of synthetic peptide thrombin receptor agonist encapsulated in microparticles based on lactic and glycolic acid copolymer on healing of experimental skin wounds in mice

Dugina, T. N.; Ev, Kiseleva; Lange, M; Васильева, Т. В.; Grandfils, Christian; Марквичева, Елена; ZhD, Bespalova; Palkeeva, M. E.; Strukova, S. M.

doi:10.1007/s10517-005-0071-2

Cited by 12 publications

(6 citation statements)

References 7 publications

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“…Other anti-inflammatory agents previously utilized to modulate macrophage behavior and reduce levels of pro-inflammatory cytokines upon implantation of biodegradable implants include prednisolone, 142 α-melanocyte stimulating hormone (α-MSH), 143 PAR1 peptide thrombin receptor agonist (PAR1-AP), 144 and tetracycline. 145 Scientists have also coated non-degradable implants with heparin and synthetic thrombin receptor agonist to shorten the inflammatory FBR, since they functions to bind to regulators of coagulation and complement activation.…”

Section: Efforts To Mitigate Fbrmentioning

confidence: 99%

Short-Term and Long-Term Effects of Orthopedic Biodegradable Implants

Amini

Wallace

Nukavarapu

2011

J Long Term Eff Med Implants

140

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Presently, orthopedic and oral/maxillofacial implants represent a combined $2.8 billion market, a figure expected to experience significant and continued growth. Although traditional permanent implants have been proved clinically efficacious, they are also associated with several drawbacks, including secondary revision and removal surgeries. Non-permanent, biodegradable implants offer a promising alternative for patients, as they provide temporary support and degrade at a rate matching tissue formation, and thus, eliminate the need for secondary surgeries. These implants have been in clinical use for nearly 25 years, competing directly with, or maybe even exceeding, the performance of permanent implants. The initial implantation of biodegradable materials, as with permanent materials, mounts an acute host inflammatory response. Over time, the implant degradation profile and possible degradation product toxicity mediate long-term biodegradable implant-induced inflammation. However, unlike permanent implants, this inflammation is likely to cease once the material disappears. Implant-mediated inflammation is a critical determinant for implant success. Thus, for the development of a proactive biodegradable implant that has the ability to promote optimal bone regeneration and minimal detrimental inflammation, a thorough understanding of short- and long-term inflammatory events is required. Here, we discuss an array of biodegradable orthopedic implants, their associated short- and long- term inflammatory effects, and methods to mediate these inflammatory events.

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Section: Efforts To Mitigate Fbrmentioning

confidence: 99%

Short-Term and Long-Term Effects of Orthopedic Biodegradable Implants

Amini

Wallace

Nukavarapu

2011

J Long Term Eff Med Implants

140

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“…Thrombin is key coagulation factor and is known to participate in other cellular processes including inflammation [4], and neuronal degeneration [5]. Thrombin pathway is activated by a number of G-protein coupled protease activated receptors (PARs), including PAR1, which is present on glia and neurons [6].…”

Section: Introductionmentioning

confidence: 99%

The role of thrombin in the pathogenesis of diabetic neuropathy

et al. 2019

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Diabetic neuropathy is common and disabling despite glycemic control. Novel neuroprotective approaches are needed. Thrombin and hypercoagulability are associated with diabetes and nerve conduction dysfunction. Our aim was to study the role of thrombin in diabetic neuropathy. We measured thrombin activity by a biochemical assay in streptozotocin (STZ)-induced diabetic neuropathy in male Sprague-Dawley rats. Neuropathy severity was assessed by thermal latency and nerve conduction measures. Thermal latencies were longer in diabetic rats, and improved with the non-specific serine-protease inhibitor Tosyl-L-lysine-chloromethyl ketone (TLCK) treatment (p<0.01). The tail nerve of diabetic rats showed slow conduction velocity (p˂0.01), and interestingly, increased thrombin activity was noted in the sciatic nerve (p˂0.001). Sciatic nodes of Ranvier and the thrombin receptor, protease activated receptor 1 (PAR1) reactivity showed abnormal morphology in diabetic animals by immunofluorescence staining (p<0.0001). Treatment of diabetic animals with either the specific thrombin inhibitor, N-alpha 2 naphtalenesulfonylglycyl alpha-4 amidino-phenylalaninepiperidide (NAPAP) or TLCK preserved normal conduction velocity, (p˂0.01 and p = 0.01 respectively), and prevented disruption of morphology (p˂0.05 and p˂0.03). The results establish for the first time an association between diabetic neuropathy and excessive activation of the thrombin pathway. Treatment of diabetic animals with thrombin inhibitors ameliorates both biochemical, structural and electrophysiological deficits. The thrombin pathway inhibition may be a novel neuroprotective therapeutic target in the diabetic neuropathy pathology.

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“…Thrombin is a key factor in the coagulation cascade and is known to participate in a wide variety of cellular and physiological processes including inflammation (21, 22), neurotrauma (23, 24), neuronal plasticity after vascular damage (25) and neuronal degeneration (26). Thrombin has a known role in central nervous system inflammatory diseases as shown in the EAE model (18, 19).…”

Section: Introductionmentioning

confidence: 99%

Blocking Thrombin Significantly Ameliorates Experimental Autoimmune Neuritis

et al. 2019

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Thrombin and its protease-activated receptor 1 (PAR1) are potentially important in peripheral nerve inflammatory diseases. We studied the role of thrombin and PAR1 in rat experimental autoimmune neuritis (EAN), a model of the human Guillain-Barré syndrome (GBS). EAN was induced by bovine peripheral myelin with complete Freund's adjuvant (CFA). Thrombin activity in the sciatic nerves, clinical scores and rotarod performance were measured. Thrombin activity in the sciatic nerve was elevated in EAN compared to CFA control rats (sham rats) (p ≤ 0.004). The effect of blocking the thrombin-PAR1 pathway was studied using the non-selective thrombin inhibitor N-Tosyl-Lys-chloromethylketone (TLCK), and the highly specific thrombin inhibitor N-alpha 2 naphtalenesulfonylglycyl 4 amidino-phenylalaninepiperidide (NAPAP). In-vitro TLCK and NAPAP significantly inhibited specific thrombin activity in EAN rats sciatics (p<0.0001 for both inhibitors). Treatment with TLCK 4.4 mg/kg and NAPAP 69.8 mg/kg significantly improved clinical and rotarod scores starting at day 12 and 13 post immunization (DPI12, DPI13) respectively (p < 0.0001) compared to the untreated EAN rats. In nerve conduction studies, distal amplitude was significantly lower in EAN compared to sham rats (0.76 ± 0.34 vs. 9.8 ± 1.2, mV, p < 0.0001). Nerve conduction velocity was impaired in EAN rats (23.6 ± 2.6 vs. sham 43 ± 4.5, m/s p = 0.01) and was normalized by TLCK (41.2 ± 7.6 m/s, p < 0.05). PAR1 histology of the sciatic node of Ranvier indicated significant structural damage in the EAN rats which was prevented by TLCK treatment. These results suggest the thrombin-PAR1 pathway as a possible target for future intervention in GBS.

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Effect of synthetic peptide thrombin receptor agonist encapsulated in microparticles based on lactic and glycolic acid copolymer on healing of experimental skin wounds in mice

Cited by 12 publications

References 7 publications

Short-Term and Long-Term Effects of Orthopedic Biodegradable Implants

Short-Term and Long-Term Effects of Orthopedic Biodegradable Implants

The role of thrombin in the pathogenesis of diabetic neuropathy

Blocking Thrombin Significantly Ameliorates Experimental Autoimmune Neuritis

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