Cyclo-oxygenase (COX) inhibitors for preventing preterm labour

Khanprakob, Thirawut; Laopaiboon, Malinee; Lumbiganon, Pisake; Sangkomkamhang, Ussanee S

doi:10.1002/14651858.cd007748.pub2

Cited by 15 publications

(6 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of PTGS2 but not PTGS1 is increased at term labor in human gestational tissues such as amnion, choriodecidua and myometrium [ 68 , 69 ]. The administration of PTGS2 (COX-2) inhibitor can effectively suppress LPS-induced PTL [ 70 , 71 ], implying the crucial roles of COX-2-mediated PGs. We proved that the lack of CX3CR1 decreased the intrauterine gene expression of Ptgs2 after LPS treatment.…”

Section: Discussionmentioning

confidence: 99%

Prevention of lipopolysaccharide-induced preterm labor by the lack of CX3CL1-CX3CR1 interaction in mice

et al. 2018

View full text Add to dashboard Cite

Preterm labor (PTL) is the most common cause of neonatal death and long-term adverse outcome. The pharmacological agents for PTL prevention are palliative and frequently fail to prevent PTL and improve neonatal outcome. It is essential to fully understand the molecular mechanisms of PTL in order to develop novel therapeutic methods against PTL. Several lines of evidence indicate some chemokines are expressed in gestational tissues during labor or PTL. To reveal the pathophysiological roles of the CX3CL1-CX3CR1 axis in PTL, we performed present study using LPS-induced PTL mice model in CX3CR1-deficient (Cx3cr1-/-) mice. We indicated that PTL was suppressed in Cx3cr1-/- mice and immunoneutralization of CX3CL1 in WT mice. From immunohistochemical and the gene expression analyses, the CX3CL1-CX3CR1 axis has detrimental roles in PTL through intrauterine recruitment of macrophages and the enhancement of macrophage-derived inflammatory mediators. Thus, the CX3CL1-CX3CR1 axis may be a good molecular target for preventing PTL.

show abstract

Section: Discussionmentioning

confidence: 99%

Prevention of lipopolysaccharide-induced preterm labor by the lack of CX3CL1-CX3CR1 interaction in mice

et al. 2018

View full text Add to dashboard Cite

show abstract

“…There is little evidence to suggest COX-inhibitors should be prioritized as effective tocolytics when compared with other available therapeutics; however, some studies have indicated a potential use for NSAIDs in preventing PTB [100]. In 2015, a Cochrane review and meta-analysis evaluated the use of indomethacin for the prevention of PTB [101].…”

Section: Nonsteroidal Anti-inflammatory Drugs As Tocolytic Agents: a Short-term Prostaglandin Blockadementioning

confidence: 99%

Landscape of Preterm Birth Therapeutics and a Path Forward

Coler

Shynlova

Boros-Rausch

et al. 2021

JCM

View full text Add to dashboard Cite

Preterm birth (PTB) remains the leading cause of infant morbidity and mortality. Despite 50 years of research, therapeutic options are limited and many lack clear efficacy. Tocolytic agents are drugs that briefly delay PTB, typically to allow antenatal corticosteroid administration for accelerating fetal lung maturity or to transfer patients to high-level care facilities. Globally, there is an unmet need for better tocolytic agents, particularly in low- and middle-income countries. Although most tocolytics, such as betamimetics and indomethacin, suppress downstream mediators of the parturition pathway, newer therapeutics are being designed to selectively target inflammatory checkpoints with the goal of providing broader and more effective tocolysis. However, the relatively small market for new PTB therapeutics and formidable regulatory hurdles have led to minimal pharmaceutical interest and a stagnant drug pipeline. In this review, we present the current landscape of PTB therapeutics, assessing the history of drug development, mechanisms of action, adverse effects, and the updated literature on drug efficacy. We also review the regulatory hurdles and other obstacles impairing novel tocolytic development. Ultimately, we present possible steps to expedite drug development and meet the growing need for effective preterm birth therapeutics.

show abstract

“…52,73,75 Despite promising animal models, the single randomized controlled trial of COX inhibitors to reduce the risk of preterm labor is disappointing; COX inhibitors were associated with an increase in preterm birth and PPROM. 78,79 A recent study suggested a novel mechanism for infectionassociated PPROM that involves downregulation of genes critical for tensile strength within the chorioamnion. 80 In a nonhuman primate model of an early GBS choriodecidual infection, there was a significant downregulation of multiple cytokeratin and other genes critical for maintenance of chorioamnion tensile strength including cytokeratins (CK3, CK6A, CK7, CK8, CK14, CK15, CK16, CK19, and CK24), collagens and collagen-binding proteins (COL1A2, COL7A1, COL5A1, and LUM), and components of the intracellular matrix (laminins 6 Reproductive Sciences and desmoplakin).…”

Section: Infection and Inflammationmentioning

confidence: 99%

Synergy and Interactions Among Biological Pathways Leading to Preterm Premature Rupture of Membranes

et al. 2014

View full text Add to dashboard Cite

Preterm premature rupture of membranes (PPROM) occurs in 1% to 2% of births. Impact of PPROM is greatest in low- and middle-income countries where prematurity-related deaths are most common. Recent investigations identify cytokine and matrix metalloproteinase activation, oxidative stress, and apoptosis as primary pathways to PPROM. These biological processes are initiated by heterogeneous etiologies including infection/inflammation, placental bleeding, uterine overdistention, and genetic polymorphisms. We hypothesize that pathways to PPROM overlap and act synergistically to weaken membranes. We focus our discussion on membrane composition and strength, pathways linking risk factors to membrane weakening, and future research directions to reduce the global burden of PPROM.

show abstract

Cyclo-oxygenase (COX) inhibitors for preventing preterm labour

Cited by 15 publications

References 35 publications

Prevention of lipopolysaccharide-induced preterm labor by the lack of CX3CL1-CX3CR1 interaction in mice

Prevention of lipopolysaccharide-induced preterm labor by the lack of CX3CL1-CX3CR1 interaction in mice

Landscape of Preterm Birth Therapeutics and a Path Forward

Synergy and Interactions Among Biological Pathways Leading to Preterm Premature Rupture of Membranes

Contact Info

Product

Resources

About