Inflammatory Proteins in the Amniotic Fluid, Plasma, and Cervicovaginal Fluid for the Prediction of Intra-Amniotic Infection/Inflammation and Imminent Preterm Birth in Preterm Labor.

OBJECTIVE: This study was aimed to develop models using multiple cytokine/chemokine levels in cervicovaginal fluid (CVF) and plasma and widely used noninvasive parameters that have better accuracy for predicting intra-amniotic infection and/or inflammation (IAI) and imminent spontaneous preterm delivery (SPTD, ≤48 hours) in women with preterm labor (PTL). STUDY DESIGN: This was a retrospective cohort study of 95 singleton pregnant women with PTL (23-34 weeks) who underwent amniocentesis. Both CVF and plasma samples were obtained at the time of amniocentesis, and serum C-reactive protein (CRP) levels were measured. The amniotic fluid (AF), CVF, and plasma samples were assayed for interleukin (IL)-6, IL-8, IL-10, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1ß (MIP-1ß) levels using a multiplex immunoassay kit. RESULTS: The levels of most cytokines/chemokines measured in the AF and CVF were significantly higher in the women with than in those without IAI and imminent SPTD, whereas only high-plasma IL-10 level showed a significant association with imminent SPTD. In predicting IAI, proteins in AF had significantly higher areas under the curves (AUCs) than those in CVF and plasma. However, for predicting imminent SPTD, no significant differences in the AUCs of the outcome-associated proteins were observed among the measurements in AF, CVF, and maternal plasma. By using stepwise regression analyses, noninvasive models (using protein levels in CVF and baseline clinical parameters) were developed for the prediction of IAI and imminent SPTD. The AUC of these noninvasive models were similar to those of the invasive models (using AF protein levels and baseline clinical parameters). CONCLUSION: Noninvasive models based on CVF cytokine/chemokine levels and widely used noninvasive parameters (especially CRP) act as good indicators for predicting the risk of IAI and imminent SPTD in women with PTL. Evaluation of cytokine/chemokine levels in plasma samples did not add valuable information regarding the two outcome measures in the PTL setting. KEY POINTS: · Markers in either CVF or plasma alone did not have sufficient accuracy for predicting IAI and SPTD.. · Noninvasive models using CVF cytokine and CRP act as effective tools for predicting two outcomes.. · Evaluation of cytokine level in plasma did not add valuable information regarding two outcomes..

Cellular Mechanisms Mediating the Antinociceptive Effect of Botulinum Toxin A in a Rodent Model of Trigeminal Irritation by a Foreign Body.

Although numerous studies have described botulinum toxin type A (BTX-A) efficacy against trigeminal neuralgia (TN), the underlying cellular mechanisms remain unclear. We have investigated cellular mechanisms that mediate the antinociceptive effect of BTX-A in a rodent model of TN produced by compression of the trigeminal nerve root (TNR). Anesthetized male Sprague-Dawley rats were fixed in a stereotaxic instrument and compression of the TNR was then achieved with a 4% agar solution. This model produced a significant mechanical allodynia and increased the expression of hypoxia-inducible factor (HIF)-1α and cytokines levels including interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the trigeminal ganglion (TG) by postoperative day (POD) 7. Single or double treatments with a high BTX-A dose (3 U/kg) led to significantly prolonged antinociceptive effects. Furthermore, a single treatment with BTX-A (3 U/kg) significantly suppressed the upregulation of HIF-1α expression and IL-1ß, IL-6, and TNF-α concentrations in the TG. Intraganglionic injection of PX-12, a HIF-1α inhibitor, led to significant anti-allodynic effects and lowered the IL-1ß, IL-6, and TNF-α levels in the TG. These findings indicate that the antinociceptive effect of BTX-A is mediated via HIF-1α associated cytokines modulation in the TG and is therefore a potentially relevant treatment strategy for TN. PERSPECTIVE: The antinociceptive properties of BTX-A in a rat model of trigeminal neuralgia are mediated through the regulation of the HIF-1α associated cytokine pathway in the trigeminal ganglion. BTX-A is therefore a potentially effective treatment strategy for trigeminal neuralgia.