Time- and dose-dependent correlations between patient-controlled epidural analgesia and intrapartum maternal fever.

BACKGROUND: To investigate the relationship between intrapartum maternal fever and the duration and dosage of patient-controlled epidural analgesia (PCEA). METHODS: This observational study included 159 pregnant women who voluntarily accepted PCEA. During labor, patients with body temperature ≥ 38 °C were classified into the Fever group, (n = 42), and those with body temperature < 38 °C were classified into the No-fever group (n = 117). The outcome measures included the duration of PCEA, number of PCEA, and total PCEA amount. Body temperature and parturient variables, including interpartum fever status and the duration of any fever were monitored. RESULTS: The total PCEA duration and total PCEA amount in the Fever group were significantly higher than the corresponding values in the No-fever group (both, p < 0.05). The duration of fever was weakly correlated with the duration of PCEA (R2 = 0.08) and the total PCEA amount (R2 = 0.05) (both, p < 0.05). The total and effective PCEA were higher in the Fever group than in the No-fever group (both, p < 0.05). The total PCEA duration and total PCEA amount were positively correlated with the incidence of fever (both, p < 0.05). The diagnostic cutoff value for fever was 383 min, with a sensitivity of 78.6% and specificity of 57.3%. The mean temperature-time curves showed that parturients who developed fever had a steeper rise in temperature. CONCLUSIONS: This study showed that there were weak time- and dose-dependent correlations between PCEA and maternal fever during delivery. A total PCEA duration exceeding 6.3 h was associated with an increase in the duration of maternal intrapartum fever.

Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway.

Context: Cisplatin-based chemotherapy was widely used in treating human malignancies. However, side effects and chemoresistance remains the major obstacle.Objective: To verify whether natural borneol (NB) can enhance cisplatin-induced glioma cell apoptosis and explore the mechanism.Materials and methods: Cytotoxicity of cisplatin and/or NB towards U251 and U87 cells were determined with the MTT assay. Cells were treated with 0.25-80 µg/mL cisplatin and/or 5-80 µM NB for 48 h. The effects of NB and/or cisplatin on apoptosis and cell cycle distribution were quantified by flow cytometric analysis. Protein expression was detected by western blotting. ROS generation was conducted by measuring and visualising an oxidation-sensitive fluorescein DCFH-DA.Results: NB synergistically enhanced the anticancer efficacy of cisplatin in human glioma cells. Co-treatment of 40 µg/mL NB and 40 µg/mL cisplatin significantly inhibited U251 cell viability from 100% to 28.2% and increased the sub-G1 population from 1.4% to 59.3%. Further detection revealed that NB enhanced cisplatin-induced apoptosis by activating caspases and triggering reactive oxygen species (ROS) overproduction as evidenced by the enhancement of green fluorescence intensity from 265% to 645%. ROS-mediated DNA damage was observed as reflected by the activation of ATM/ATR, p53 and histone. Moreover, MAPKs and PI3K/AKT pathways also contributed to co-treatment-induced U251 cell growth inhibition. ROS inhibition by antioxidants effectively improved MAPKs and PI3K/AKT functions and cell viability, indicating that NB enhanced cisplatin-induced cell growth in a ROS-dependent manner.Discussion and conclusions: Natural borneol had the potential to sensitise human glioma cells to cisplatin-induced apoptosis with potential application in the clinic.

Enhanced anticancer efficiency of doxorubicin against human glioma by natural borneol through triggering ROS-mediated signal.

Doxorubicin (DOX) as a first-line chemotherapeutic drug has been widely used for therapy of human cancers. However, side effects and chemo-resistance severely blocked its clinic application. Herein, natural borneol (NB) as a novel monoterpenoid chemosensitizer was found to have the potential to increase the blood brain barrier (BBB) permeability and intracellular uptake of DOX in vitro, and synergistically enhanced DOX-induced cytotoxicity in human glioma cells. NB treatment significantly potentiated DOX-induced G2/M cell cycle arrest by triggering reactive oxygen species (ROS)-mediated DNA damage. NB also enhanced DOX-induced dysfunction of MAPKs and PI3 K/AKT pathways. Furthermore, U251 human glioma xenograft growth in vivo was also effectively inhibited by combined treatment of DOX with NB through induction of G2/M-phase arrest and antiangiogenesis. Taken together, our finding validated that NB could act as novel chemosensitizer to enhance DOX-induced anticancer efficacy, and strategy of using NB and DOX could be a high efficient way in therapy of human cancers.

Hyperbaric oxygen treatment at various stages following chronic constriction injury produces different antinociceptive effects via regulation of P2X4R expression and apoptosis.

PURPOSE: The aims of this study were to investigate the effect of hyperbaric oxygen (HBO) treatment at various stages following chronic constriction injury (CCI) and to explore the underlying mechanisms of HBO treatment. METHODS: Forty adult male Sprague-Dawley rats were randomly assigned to five groups (n = 8 for each group): the sham group, CCI group, HBO1 group, HBO2 group, and HBO3 group. Neuropathic pain was induced by CCI of the sciatic nerve. HBO treatment began on postoperative days 1, 6, and 11 and continued for 5 days. The mechanical withdrawal threshold and thermal withdrawal latency were tested on preoperative day 3 and postoperative days 1, 3, 5, 7, 10, 14, and 21. The expression of P2X4R was determined by immunohistochemistry and western blot analysis. Cell apoptosis was measured using TUNEL staining. The expression of caspase 3 was measured using reverse transcription polymerase chain reaction (RT-PCR). Electron microscopy was used to determine the ultrastructural changes. RESULTS: Early HBO treatment beginning on postoperative day 1 produced a persistent antinociceptive effect and inhibited the CCI-induced increase in the expression of P2X4R without changing CCI-induced apoptosis. In contrast, late HBO treatment beginning on postoperative day 11 produced a persistent antinociceptive effect and inhibited CCI-induced apoptosis and upregulation of caspase-3 without changing the expression of P2X4R. In addition, late HBO treatment reduced CCI-induced ultrastructural damage. However, HBO treatment beginning on postoperative day 6 produced a transient antinociceptive effect without changing the expression of P2X4R or CCI-induced apoptosis. CONCLUSION: HBO treatment at various stages following CCI can produce antinociceptive effects via different mechanisms. Early HBO treatment is associated with inhibition of P2X4R expression, and late HBO treatment is associated with inhibition of cell apoptosis.

Hyperbaric oxygen treatment produces an antinociceptive response phase and inhibits astrocyte activation and inflammatory response in a rat model of neuropathic pain.

Hyperbaric oxygen (HBO) treatment has been proven to be a promising candidate for protection of the nervous system after acute injury in animal models of neuropathic pain. The purposes of this study were to examine the antinociceptive response phase induced by HBO treatment in a model of neuropathic pain and to determine the dependence of the treatment's mechanism of alleviating neuropathic pain on the inhibition of spinal astrocyte activation. Neuropathic pain was induced in rats by chronic constriction injury of the sciatic nerve. Mechanical threshold and thermal latency were tested preoperatively and for 1 week postoperatively, four times daily at fixed time points. Methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD) parameters were used as indices of oxidative stress response and tested before and after the treatment. The inflammatory cytokines interleukin (IL)-1ß and IL-10 were assayed in the sciatic nerve were with enzyme-linked immunoassay. Glial fibrillary acidic protein activation in the spinal cord was evaluated immunohistochemically. The rats exhibited temporary allodynia immediately after HBO treatment completion. This transient allodynia was closely associated with changes in MDA and SOD levels. A single HBO treatment caused a short-acting antinociceptive response phase. Repetitive HBO treatment led to a long-acting antinociceptive response phase and inhibited astrocyte activation. These results indicated that HBO treatment played a dual role in the aggravation and alleviation of neuropathic pain, though the aggravated pain effect (transient allodynia) was far less pronounced than the antinociceptive phase. Astrocyte inhibition and anti-inflammation may contribute to the antinociceptive effect of HBO treatment after nerve injury.