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1.
Acta cir. bras ; Acta cir. bras;37(1): e370108, 2022. graf, ilus
Article de Anglais | LILACS, VETINDEX | ID: biblio-1374064

RÉSUMÉ

Purpose: Traumatic brain injury (TBI) remains a major public health problem and cause of death. Ulinastatin (UTI), a serine protease inhibitor, has been reported to have an anti-inflammatory effect and play a role in immunoregulation and organ protection by reducing reactive oxygen species (ROS) production, oxidative stress and inflammation. However, the neuroprotective of UTI in TBI has not been confirmed. Therefore, this study aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in TBI-induced EBI in a C57BL/6 mouse model. Methods: The neurological score and brain water content were evaluated. Enzyme-linked immunosorbent assay was used to detect neuroinflammatory cytokine levels, ROS and malondialdehyde detection to evaluate oxidative stress levels, and TUNEL staining and western blotting to examine neuronal damages and their related mechanisms. Results: Treatment with UTI markedly increased the neurological score; alleviated brain oedema; decreased the inflammatory cytokine tumour necrosis factor a, interleukin-1ß (IL-1ß), IL-6 and nuclear factor kappa B (NF-kB) levels; inhibited oxidative stress; decreased caspase-3 and Bax protein expressions; and increased the Bcl-2 levels, indicating that UTI-mediated inhibition of neuroinflammation, oxidative stress and apoptosis ameliorated neuronal death after TBI. The neuroprotective capacity of UTI is partly dependent on the TLR4/NF-kB/p65 signalling pathway. Conclusions: Therefore, this study reveals that UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation, oxidative stress and apoptosis.


Sujet(s)
Animaux , Souris , Lésions encéphaliques/thérapie , Inhibiteurs de la sérine protéinase/administration et posologie , Inhibiteurs de la sérine protéinase/usage thérapeutique , Apoptose , Stress oxydatif
3.
Indian J Biochem Biophys ; 2015 Feb; 52 (1): 14-22
Article de Anglais | IMSEAR | ID: sea-157950

RÉSUMÉ

Proteases have been considered as an important group of targets for development of antiprotozoal drugs due to their essential roles in host-parasite interactions, parasite immune evasion, life cycle transition and pathogenesis of parasitic diseases. The development of potent and selective serine protease inhibitors targeting L. donovani secretory serine protease (pSP) could pave the way to the discovery of potential antileishmanial drugs. Here, we employed different classical serine protease inhibitors (SPIs), such as aprotinin, N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), N-tosyl-lysine chloromethyl ketone (TLCK), benzamidine (Bza) and pSP-antibody to determine the role of the protease in parasitic survival, growth and infectivity. Among the different classical SPIs, aprotinin appeared to be more potent in arresting L. donovani promastigotes growth with significant morphological alterations. Furthermore, aprotinin and anti-pSP treated parasites significantly decreased the intracellular parasites and percentage of infected macrophages. These results suggest that SPIs may reduce the infectivity by targeting the serine protease activity and may prove useful to elucidate defined molecular mechanisms of pSP, as well as for the development of novel antileishmanial drugs in future.


Sujet(s)
Antiprotozoaires/usage thérapeutique , Leishmania donovani/effets des médicaments et des substances chimiques , Leishmania donovani/génétique , Leishmaniose/traitement médicamenteux , Vaccins antileishmaniose/immunologie , Protéines de protozoaire/génétique , Protéases à sérine/usage thérapeutique , Inhibiteurs de la sérine protéinase/usage thérapeutique
4.
Biol. Res ; 47: 1-9, 2014. ilus, tab
Article de Anglais | LILACS | ID: biblio-950754

RÉSUMÉ

Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM) leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF) to induce the angiogenesis process. Alpha-1 antitrypsin (AAT) is the most important circulating inhibitor of serine proteases (SERPIN). Its targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, proteinase 3 (PR-3) and plasminogen activator (PAI). AAT modulates the effect of protease-activated receptors (PARs) during inflammatory responses. Plasma levels of AAT can increase 4-fold during acute inflammation then is so-called acute phase protein (APPs). Individuals with low serum levels of AAT could develop disease in lung, liver and pancreas. AAT is involved in extracellular matrix remodeling and inflammation, particularly migration and chemotaxis of neutrophils. It can also suppress nitric oxide (NO) by nitric oxide sintase (NOS) inhibition. AAT binds their targets in an irreversible way resulting in product degradation. The aim of this review is to focus on the points of contact between multiple factors involved in diabetic retinopathy and AAT resembling pleiotropic effects that might be beneficial.


Sujet(s)
Humains , Animaux , Inhibiteurs de la sérine protéinase/usage thérapeutique , alpha-1-Antitrypsine/usage thérapeutique , Rétinopathie diabétique/traitement médicamenteux , Hypoxie cellulaire , Inhibiteurs de la sérine protéinase/métabolisme , Mouvement cellulaire/physiologie , Chimiotaxie/physiologie , alpha-1-Antitrypsine/métabolisme , Facteur de transcription NF-kappa B/métabolisme , Facteur de nécrose tumorale alpha/métabolisme , Médiateurs de l'inflammation/antagonistes et inhibiteurs , Nitric oxide synthase/antagonistes et inhibiteurs , Agents protecteurs/métabolisme , Récepteurs activés par la protéinase/métabolisme , Rétinopathie diabétique/physiopathologie , Radicaux libres , Inflammation/métabolisme , Anti-inflammatoires/métabolisme , Anti-inflammatoires/usage thérapeutique , Granulocytes neutrophiles/physiologie
5.
Article de Coréen | WPRIM | ID: wpr-147874

RÉSUMÉ

BACKGROUND/AIMS: ERCP is the most common procedure for the diagnosis and treatment of bile duct and pancreatic disease, but Post-ERCP pancreatitis makes poor outcome in some cases. The protease inhibitors, nafamostat and gabexate, have been used to prevent pancreatitis related to ERCP, but there is some debate. We tried to evaluate the efficacy of gabexate and nafamostat for the prevention of post-ERCP pancreatitis. METHODS: Two hundred forty two patients (73 patients in the gabexate group, 88 patients in the nafamostat group and 81 patients in the placebo group) were included in the study after selective exclusion. The incidence of pancreatitis after ERCP was compared among groups. RESULTS: The incidence of pancreatitis were 6.8% in the gabexate group, 5.7% in the nafamostat group and 6.2% in the placebo group (p=0.954). CONCLUSIONS: There was no meaningful difference among the gabexate, nafamostat and placebo group.


Sujet(s)
Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Cholangiopancréatographie rétrograde endoscopique/effets indésirables , Gabexate/usage thérapeutique , Guanidines/usage thérapeutique , Pancréatite/étiologie , Effet placebo , Enquêtes et questionnaires , Inhibiteurs de la sérine protéinase/usage thérapeutique
6.
Rev. Assoc. Med. Bras. (1992, Impr.) ; Rev. Assoc. Med. Bras. (1992, Impr.);43(3): 189-94, jul.-set. 1997. tab
Article de Portugais | LILACS | ID: lil-201482

RÉSUMÉ

A deficiência de antitrombina III (ATIII) é observada na hepatopatia grave e pode ser decorrente da reduçäo de síntese ou de consumo aumentado, o que poderia ser compensado com o uso de concentrado de ATIII. OBJETIVO. Avaliar a eficiência da administraçäo de uma dose fixa de concentrado de ATIII, em pacientes com hepatopatia descompensada com distúrbio de hemostasia. CASUISTICA E MÉTODO. Foram avaliados seis pacientes, com idade média de 44 anos, variando de 14 a 63 anos, portadores de cirrose (quatro de etiologia alcoólica, um viral e um doença de Wilson), com alteraçäo de pelo menos dois dos parâmetros da hemostasia (TP> 1,40, TTPA> 1,25, fibrinogênio < 1,5g/L, plaquetas < 80.000/mm3). A média do nível de albumina foi de 2,6g/dL (1,9 a 3,8g/dL). O concentrado de ATIII (Kybernin) foi administrado na dose de 50U/kg, em dias alternados. Foi colhido sangue antes da primeira infusäo, 4 horas após e, depois, diariamente, antes da infusäo do dia, para medida da ATIII plasmática (amidolítico). Nenhum paciente recebeu hemoderivados. RESULTADOS. As médias da dosagem de ATIII foram: inicial = 35,8 por cento, 4 horas = 56,2 por cento*, 2 dias = 48,7 por cento*, 4 dias = 45,7 por cento* e 8 dias = 42,3 por cento*. Após a infusäo houve elevaçäo significante dos níveis de ATIII (* = p < 0,02, teste de Friedman), que se manteve até o 4§ dia. Näo houve alteraçäo dos demais parâmetros de coagulaçäo. CONCLUSÕES. O uso de concentrado de ATIII na dose utilizada é suficiente para elevar os níveis desse inibidor na hepatopatia; entretanto, com essa dose näo se obteve normalizaçäo de seus níveis. Esses dados sugerem que doses mais elevadas devem ser usadas em pacientes com hepatopatias graves, que apresentam näo apenas reduçäo de síntese, mas aumento de consumo dos fatores da coagulaçäo e de seus inibidores.


Sujet(s)
Humains , Mâle , Femelle , Adolescent , Adulte , Adulte d'âge moyen , Troubles de l'hémostase et de la coagulation/thérapie , Inhibiteurs de la sérine protéinase/usage thérapeutique , Antithrombine-III/usage thérapeutique , Cirrhose du foie , Temps partiel de thromboplastine , Numération des plaquettes , Temps de prothrombine , Fibrinogène , Antithrombine-III , Hépatites virales humaines/complications , Dégénérescence hépatolenticulaire/complications , Cirrhose du foie/étiologie , Maladies alcooliques du foie/complications
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