GB001, a selective prostaglandin D2 receptor 2 antagonist, blocks signaling in the peripheral blood of healthy subjects

Author(s):  
Gregory Opiteck ◽  
Kristen Taylor Meadows ◽  
Eric Butz ◽  
Scott Sugden ◽  
Richard Aranda ◽  
...  
2021 ◽  
pp. 1-5
Author(s):  
Mahdi Ramezani ◽  
Alireza Komaki ◽  
Mohammad Mahdi Eftekharian ◽  
Mehrdokht Mazdeh ◽  
Soudeh Ghafouri-Fard

Migraine is a common disorder which is placed among the top ten reasons of years lived with disability. Cytokines are among the molecules that contribute in the pathophysiology of migraine. In the current study, we evaluated expression levels of IL-6 coding gene in the peripheral blood of 120 migraine patients (54 migraine without aura and 66 migraine with aura patients) and 40 healthy subjects. No significant difference was detected in expression of IL-6 between total migraine patients and healthy controls (Posterior beta = 0.253, P value = 0.199). The interaction effect between gender and group was significant (Posterior beta =-1.274, P value = 0.011), therefore, we conducted subgroup analysis within gender group. Such analysis revealed that while expression of this gene is not different between male patients and male controls (Posterior beta =-0.371, P value > 0.999), it was significantly over-expressed in female patients compared with female controls (Posterior beta = 0.86, P= 0.002). Expression of IL-6 was significantly higher in patients with aura compared with controls (Posterior beta = 0.63, adjusted P value = 0.019). However, expression of this cytokine coding gene was not different between patients without aura and healthy subjects (Posterior beta = 0.193, adjusted P value = 0.281). Therefore, IL-6 might be involved in the pathophysiology of migraine among females and migraine with aura among both sexes.


2004 ◽  
Vol 37 (2) ◽  
pp. 165-168 ◽  
Author(s):  
Fátima Regina Vilani-Moreno ◽  
Luciana Moreira Silva ◽  
Diltor Vladimir Araújo Opromolla

Studies on host-parasite interaction in Jorge Lobo's disease are scarce, with no report in the literature on the phagocytosis of Lacazia loboi by phagocytic mononuclear cells. Thus, the objective of the present study was to assess the phagocytic activity of blood monocytes in the presence of L. loboi in patients with the disease and in healthy subjects (controls) over 3 and 24 hours of incubation. Statistical analyses of the results showed no significant difference in percent phagocytosis of the fungus between patient and control monocytes. With respect to incubation time, however, there was a significant difference, in that percent phagocytosis was higher at 3 hours than at 24 hours (p <0.01). These results suggest that monocytes from patients with the mycosis are able to phagocyte the fungus, as also observed in control individuals.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Amin Safa ◽  
Elham Badrlou ◽  
Shahram Arsang-Jang ◽  
Arezou Sayad ◽  
Mohammad Taheri ◽  
...  

Abstract NF-κB signaling pathway has important roles in the regulation of growth and development of nervous system. This pathway has also been shown to participate in the pathogenesis of schizophrenia. Meanwhile, activity of NF-κB signaling pathway is regulated by several factors including non-coding RNAs (lncRNAs). In the current study, we evaluated expression of nine NF-κB-related lncRNAs namely DILC, ANRIL, PACER, CHAST, ADINR, DICER1-AS1, HNF1A-AS1, H19 and NKILA as well as two mRNA coding genes namely ATG5 and CEBPA in the peripheral blood of patients with schizophrenia compared with matched healthy subjects. Expressions of these genes were assessed by real time PCR technique. Expression of PACER was lower in patients with schizophrenia compared with controls (Posterior beta = − 0.684, P value = 0.049). On the other hand, expressions of CHAST, CEBPA, H19, HNF1A-AS1 and DICER1-AS1 were higher in patients compared with controls (Posterior beta = 0.39, P value = 0.005; Posterior beta = 0.844, P value < 0.0001; Posterior beta = 0.467, P value < 0.0001; Posterior beta = 1.107, P value = 0.005; Posterior beta = 0.176, P value = 0.044, respectively). We also appraised the diagnostic power of transcript quantities of CHAST, CEBPA, DICER1-AS1, H19 and HNF1A-AS1 in distinguishing between patients with schizophrenia and controls through depicting ROC curves. Based on the area under curve (AUC) values, CEBPA had the best diagnostic power (AUC = 0.948, P < 0.0001), followed by H19 (AUC = 0.815, P < 0.0001). Taken together, our study demonstrated dysregulation of NF-κB-related lncRNAs and genes in the peripheral blood of patients with schizophrenia and their potential as peripheral markers for this psychiatric condition.


2000 ◽  
Vol 9 (3-4) ◽  
pp. 189-191
Author(s):  
Neville A. Punchard ◽  
John Cason ◽  
Jonathan Mullins ◽  
Chaman Chander ◽  
Richard P. H. Thompson

Basal, lipopolysaccharide (LPS) and silica-stimulated prostaglandin (PG) production were compared between peripheral blood mononuclear cells (PBMNC) from UC patients and healthy subjects (HS). Basal and LPS-stimulated PBMNC PGI2, but not PGE2, production was greater in UC. LPS stimulated both PGE2and PGI2by PBMNC from HS and UC patients. Silica stimulated production of both PGs by cells from HS but only PGE2by cells from UC patients. The differences in responses to silica and LPS may result from differences in activation of NFκB or, alternatively, prior sensitisation to one of these agents. That PBMNC PGE2production is not increased in UC, as it is in Crohn’s disease, suggests that there are differences in PBMNC behaviour between these two diseases.


2021 ◽  
Author(s):  
Martin L. Ogletree ◽  
Kate Chander Chiang ◽  
Rashmi Kulshreshta ◽  
Aditya Agarwal ◽  
Ashutosh Agarwal ◽  
...  

Abstract COVID-19 associated pneumonia and acute respiratory distress syndrome are characterized by a lipid mediator storm with massive increases in lung and systemic thromboxane A2 >> prostaglandin D2. Thromboxane A2 is a potent vasoconstrictor of pulmonary veins >> arteries, and thereby promotes an increase in pulmonary capillary pressures, transudation of fluid into the alveolar space, pulmonary edema and ARDS. Thromboxane A2 also increases vascular permeability, contracts bronchial smooth muscle, triggers and amplifies platelet activation, and promotes a prothrombotic state. PGD2 promotes a Th2 immune response that is atypical for viral infections and inhibits antiviral defense by suppressing interferon λ expression. D-dimers, urinary 11-dehydro-TxB2, and IL-13, a Th2 cytokine, have emerged as key biomarkers of severity and organ failure in COVID-19. Ramatroban is an orally bioavailable, potent, dual antagonist of the thromboxane A2 (TPr) and PGD2 (DPr2) receptors. We report use of ramatroban in 4 COVID-19 outpatients, 22 to 87 years of age, with acute onset / worsening of respiratory distress and hypoxemia. All four patients experienced decrease in respiratory distress and increase in SpO2, within hours of the first dose and thereby avoided hospitalization. By the 5th day all 4 patients had complete resolution of respiratory distress and hypoxemia. Ramatroban (Baynas®, Bayer Yakuhin Ltd., Japan) has an established safety profile, having been indicated in Japan for the treatment of allergic rhinitis for over 20 years. As a broncho-relaxant, anti-vasospastic, anti-thrombotic and immunomodulator, ramatroban addresses the fundamental pathophysiologic mechanisms underlying respiratory and critical organ failure in COVID-19, and therefore merits urgent clinical trials that might impact the ongoing pandemic.


2002 ◽  
Vol 119 (3) ◽  
pp. 609-616 ◽  
Author(s):  
Masahiro Iwasaki ◽  
Kinya Nagata ◽  
Shoichi Takano ◽  
Kazuo Takahashi ◽  
Norihisa Ishii ◽  
...  

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