ABSTRACT
Nod-like receptor protein 3 (NLRP3), absent in melanoma 2 (AIM2), and interferon gamma inducible protein 16 (IFI16) are innate immune sensors for intracellular microbes, which can be activated by various dangerous signals and subsequently lead to caspase-1 (CASP1) activation and the maturation cleavage of effector molecules pro-IL-1ß and pro-IL-18. Their roles in immunopathology of acute and chronic hepatitis B virus (HBV) infection are still unclear. In this study, we first investigated the activation of NLRP3, AIM2, and IFI16 inflammasomes in peripheral blood mononuclear cells (PBMCs) from patients infected with acute hepatitis B (AHB) and chronic hepatitis B (CHB) by quantitative real-time PCR and enzyme-linked immunosorbent assay. We next analyzed the impact of hepatitis B e antigen (HBeAg) on activation of AIM2 and IFI16 inflammasomes in PBMCs of CHB patients stimulated in vitro with AIM2 and IFI16 agonist ligands, poly (dA:dT) and VACA-70mer, respectively. The results showed that the mRNA expression levels of AIM2, IFI16, and CASP1 in PBMCs from AHB and CHB patients were both upregulated. Furthermore, the mRNA levels of AIM2 and IFI16 in CHB patients were significantly positively correlated with serum HBV loads. However, only in patients with AHB there was elevation of serum IL-1ß and IL-18. There was no activation of NLRP3, AIM2, and IFI16 inflammasomes in CHB patients. Stimulation of PBMCs of CHB patients in vitro with poly (dA:dT) and VACA-70mer induced the activation of AIM2 and IFI16 inflammasomes, respectively. This ligand-induced activation was suppressed by HBeAg. Our results suggest that there exists activation of the AIM2 and IFI16 inflammasomes, but not the NLRP3 inflammasome, in AHB, and the activation of the AIM2 and IFI16 inflammasomes can be inhibited by HBeAg in CHB, which may contribute to HBV-induced immunotolerance.
Subject(s)
DNA-Binding Proteins/metabolism , Hepatitis B, Chronic/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Nuclear Proteins/metabolism , Phosphoproteins/metabolism , Acute Disease , Adult , DNA, Viral/blood , DNA-Binding Proteins/agonists , DNA-Binding Proteins/genetics , Female , Hepatitis B e Antigens/metabolism , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/immunology , Humans , Immunity, Innate/immunology , Interleukin-18/blood , Interleukin-1beta/blood , Leukocytes, Mononuclear/immunology , Male , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Nuclear Proteins/agonists , Nuclear Proteins/genetics , Phosphoproteins/agonists , Phosphoproteins/genetics , Polydeoxyribonucleotides/antagonists & inhibitors , Polydeoxyribonucleotides/pharmacologyABSTRACT
BACKGROUND: The association between body postural changes and temporomandibular disorders (TMD) has been widely discussed in the literature, however, there is little evidence to support this association. OBJECTIVES: The aim of the present study was to conduct a systematic review to assess the evidence concerning the association between static body postural misalignment and TMD. METHOD: A search was conducted in the PubMed/Medline, Embase, Lilacs, Scielo, Cochrane, and Scopus databases including studies published in English between 1950 and March 2012. Cross-sectional, cohort, case control, and survey studies that assessed body posture in TMD patients were selected. Two reviewers performed each step independently. A methodological checklist was used to evaluate the quality of the selected articles. RESULTS: Twenty studies were analyzed for their methodological quality. Only one study was classified as a moderate quality study and two were classified as strong quality studies. Among all studies considered, only 12 included craniocervical postural assessment, 2 included assessment of craniocervical and shoulder postures,, and 6 included global assessment of body posture. CONCLUSION: There is strong evidence of craniocervical postural changes in myogenous TMD, moderate evidence of cervical postural misalignment in arthrogenous TMD, and no evidence of absence of craniocervical postural misalignment in mixed TMD patients or of global body postural misalignment in patients with TMD. It is important to note the poor methodological quality of the studies, particularly those regarding global body postural misalignment in TMD patients. .
Subject(s)
Heparin/pharmacology , Poly dA-dT/antagonists & inhibitors , Polydeoxyribonucleotides/antagonists & inhibitors , RNA Polymerase II/antagonists & inhibitors , Sarcosine/analogs & derivatives , Transcription, Genetic , Catalysis , Detergents/pharmacology , Poly dA-dT/metabolism , RNA Polymerase II/metabolism , Sarcosine/pharmacology , TriticumABSTRACT
Defibrotide (D), a polydeoxyribonucleotide obtained from mammalian lungs, reduced the ischemic contracture due to low perfusion (0.2 ml/min) of the isovolumic left heart of the rabbit and abolished the irregularity of the rhythm of the heart, thereby restoring the cardiomechanical activity upon reperfusion (20 ml/min). D stimulated the release of PG-like material. Indomethacin infusion completely prevented both the antiischemic activity of D and its ability to increase the generation of prostaglandins in the rabbit heart. Measurement by atomic absorption spectroscopy of calcium content in ischemic heart tissue and its mitochondrial fraction indicated that the ischemic procedure significantly increased tissue calcium content in both. D, Prostacyclin (PGI2) and Nifedipine protected the heart from ischemic ventricular contracture and prevented accumulation of calcium in the heart. The effect of D on preventing Ca++ overload was completely abolished by indomethacin infusion. The results indicate that the beneficial effects of Defibrotide in experimental ischemia are primarily due to a release of Prostaglandin E2 (PGE2) and PGI2, which in turn may inhibit the detrimental effects of calcium overload in myocytes and mitochondria.
Subject(s)
Calcium/metabolism , Coronary Disease/drug therapy , Fibrinolytic Agents/pharmacology , Polydeoxyribonucleotides/pharmacology , Animals , Coronary Disease/metabolism , Dinoprostone/metabolism , Epoprostenol/metabolism , Indomethacin/pharmacology , Male , Perfusion , Polydeoxyribonucleotides/antagonists & inhibitors , RabbitsABSTRACT
Incubation of purified wheat-germ RNA polymerase II with poly[d(A-T)] template, Mn2+, U-A dinucleoside monophosphate primer and UTP substrate resulted in catalytic formation of the trinucleoside diphosphate U-A-U, in accordance with the results of previous studies. Both Sarkosyl and heparin inhibited completely and immediately (within less than 1 min) U-A-U synthesis, if either of these compounds was added to the assays during the progress of the reaction. This behaviour is in marked contrast to that reported for single-step addition reactions catalysed by Escherichia coli RNA polymerase on the same template [Sylvester & Cashel (1980) Biochemistry 19, 1069-1074]. However, treatment of the transcription complexes with Sarkosyl or heparin for periods sufficient to abolish U-A-U formation completely did not suppress completely the ability of such complexes to elongate RNA chains. Hence, the effect of Sarkosyl or heparin on the rate of U-A-U synthesis was predominantly due to change in the rate (or in the mechanism) of trinucleotide product release by the transcription complexes. Furthermore, once U-A-U synthesis has begun on the poly[d(A-T)] template, the transcription complexes became resistant to the action of a competitor DNA such as poly[d(G-C)]. The results are consistent with a model where at least a sizeable fraction of the enzyme molecules remains associated with the DNA template upon formation of a single phosphodiester bond.
Subject(s)
Heparin/pharmacology , Poly dA-dT/antagonists & inhibitors , Polydeoxyribonucleotides/antagonists & inhibitors , RNA Polymerase II/antagonists & inhibitors , Sarcosine/analogs & derivatives , Transcription, Genetic , Catalysis , Detergents/pharmacology , Poly dA-dT/metabolism , RNA Polymerase II/metabolism , Sarcosine/pharmacology , TriticumABSTRACT
Defibrotide is a partially depolymerized DNA fraction, having a molecular weight of about 20,000 and possessing antithrombotic and fibrinolytic activities. The present study was designed to investigate the action of defibrotide on PGI2 and thromboxane formation as well as left ventricular pressure and coronary vascular resistance in the platelet-perfused in vitro heart (Schrör et al. 1981). Defibrotide (0.1 mg/ml) administration resulted in a longlasting and significant elevation, seven-fold above control within 80 min, of PGI2 release from the platelet-perfused heart preparation while thromboxane and PGE2 release remained unaffected. This effect was only seen in presence of platelets but not in platelet-free perfused heart preparations. Urokinase, at an equieffective fibrinolytic concentration (10 IU/ml, euglobulin clot-lysis time) did not influence PGI2 generation. Treatment of the platelets with acetylsalicylic acid prevented the stimulatory action of defibrotide on vascular PGI2 as well as the transient decrease in coronary vascular resistance seen after administration of the agent. The data suggest that defibrotide is a selective stimulus for coronary vascular PGI2 formation. The mechanism of action is unknown, but appears to require platelets as an essential cofactor. The PGI2 stimulation by defibrotide appears not to be associated with its fibrinolytic action.
