Effects of sevoflurane exposure during different stages of pregnancy on the brain development of rat offspring.

OBJECTIVE: This study explored the effects of sevoflurane exposure during different stages of pregnancy on the brain development of offspring. METHODS: Thirty-six pregnant SD rats were randomly divided into 4 groups: control, sevoflurane exposure in early (S1) pregnancy, sevoflurane exposure in middle (S2) pregnancy, and sevoflurane exposure in late (S3) pregnancy. After natural birth, the learning and memory capacity of offspring rats was analyzed using the Morris water maze experiment. The hippocampi of offspring rats were collected. The levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus were measured by ELISA. Additionally, the Nissl bodies in the hippocampus were analyzed using Nissl staining. Immunohistochemistry was used to examine the expression of BDNF and CPEB2 in the hippocampus of offspring. Proteins related to the NR4A1/NF-κB pathway were analyzed using western blotting. RESULTS: The memory and learning capacity of offspring rats was significantly reduced in the S1 and S2 groups compared to the control group (p < 0.05), while there was no obvious difference between the control and S3 groups (p > 0.05). The level of IL-1ß was significantly increased (p < 0.05) in the S1 group compared with the control group. Sevoflurane anesthesia received in early and middle pregnancy could significantly affect the formation of Nissl bodies in the hippocampi of offspring rats. In addition, the expression of BDNF and CPEB2 in the hippocampi of offspring rats was greatly decreased in the S1 group compared with the control group (p < 0.05). The expression of NR4A1 in the hippocampi of rat offspring was significantly decreased in the S1 and S2 groups compared with the control group (p < 0.05). The expression of proteins related to the NF-κB pathway was increased in the S1 group compared to the control group (p < 0.05). CONCLUSIONS: The neurotoxic effect of maternal sevoflurane anesthesia on the brain development of offspring is higher when the exposure occurs in early pregnancy than in late pregnancy, and its mechanism might involve the NR4A1/NF-κB pathway to increase the secretion of inflammatory cytokines.

The risk of shoulder pain after laparoscopic surgery for infertility is higher in thin patients.

Postlaparoscopic shoulder pain (PLSP) is a common clinical problem that needs to be addressed by medical professionals who are currently perform laparoscopic surgeries. The purpose of this study was to determine the perioperative clinical factors and demographic characteristics associated with PLSP. A prospective observational study was performed with 442 inpatients undergoing laparoscopic surgery for infertility. The pain visual analogue scale was used as the measuring instrument. To identify the predictors of PLSP, we performed multivariate conditional logistic regression. PLSP was correlated with body mass index (BMI, odds ratio = 0.815). The incidence of shoulder pain and more severe shoulder pain in patients with a lower BMI was significantly higher than it was in patients with a higher BMI, and BMI was significantly negatively correlated with PLSP. Most of the patients (95%) began to experience shoulder pain on the first postoperative day, and it rarely occurred on the day of surgery. Patients with lower BMI presented a higher risk of reporting shoulder pain on the first postoperative day. We should identify high-risk patients in advance and make specific treatment plans according to the characteristics of their symptoms.

Sevoflurane attenuates brain damage through inhibiting autophagy and apoptosis in cerebral ischemia­reperfusion rats.

The present study aimed to investigate the effects of sevoflurane post­conditioning in a rat brain cerebral ischemia­reperfusion (I/R) model and examine its possible mechanism. Rats were randomly divided into six groups: Sham control group (Sham), I/R group, sevoflurane group (Se), Toll­like receptor­4 (TLR4) inhibitor group (Tak­242), nuclear factor (NF)­κB inhibitor group (QNZ) and Sevoflurane post­conditioning combined with TLR4­NF­κB signaling pathway inhibitor group (Se + Tak­242). Morris water maze test and tetrazolium chloride staining were used to investigate the I/R injury. The nerve cell apoptosis and autophagy in cortical tissue were detected by TUNEL and transmission electron microscopy, respectively. The expression of TLR4 protein in cortical tissue was observed by immunohistochemical staining. The expression of autophagy and apoptotic associated proteins in cortical tissues and the activity of TLR4­NF­κB signaling pathway were assayed by western blot analysis. Sevoflurane post­conditioning improved the learning and memory dysfunction caused by cerebral I/R injury. The cerebral infarction area, nerve cell apoptosis and formation of autophagic vacuoles were reduced after sevoflurane administration. The expression of light chain 3II/I, Beclin­1, Bad and Cleaved­Caspase­3 proteins were inhibited and the expression of Bcl­2 protein was upregulated after sevoflurane administration. Sevoflurane post­conditioning also inhibited the TLR4 protein and NF­κB phosphorylation, and increased inhibitor of kBα phosphorylation. The treatment effect of Tak­242 and QNZ groups were not significantly different compared with the Se group (P>0.05), and the Se + Tak­242 group had the best results. The present study demonstrated that sevoflurane post­conditioning could protect middle cerebral artery occlusion­induced brain injury rats by inhibiting autophagy and apoptosis, and that its mechanism is related to the TLR4­NF­κB signaling pathway.

[Distribution characteristics of soil nematodes in reclaimed land of copper-mine-tailings in different plant associations].

A survey was carried out to investigate soil nematode communities in the plant associations of gramineae (Arthraxon lanceolatus, AL; Imperata cylindrica, IC) and leguminosae (Glycine soja, GS) in reclaimed land of copper-mine-tailings and in the plant associations of gramineae (Digitaria chrysoblephara, DC-CK) of peripheral control in Fenghuang Mountain, Tongling City. A total of 1277 nematodes were extracted and sorted into 51 genera. The average individual density of the nematodes was 590 individuals · 100 g(-1) dry soil. In order to analyze the distribution character- istics of soil nematode communities in reclaimed land of copper-mine-tailings, Shannon community diversity index and soil food web structure indices were applied in the research. The results showed that the total number of nematode genus and the Shannon community diversity index of soil nematode in the three plant associations of AL, IC and GS were less than that in the plant associations of DC-CK. Compared with the ecological indices of soil nematode communities among the different plant associations in reclaimed land of copper-mine-tailings and peripheral natural habitat, we found that the structure of soil food web in the plant associations of GS was more mature, with bacterial decomposition being dominant in the soil organic matter decomposition, and that the soil ecosystem in the plant associations of GS was not stable with low interference. This indicated that the soil food web in the plant associations of leguminosae had a greater development potential to improve the ecological stability of the reclaimed land of copper-mine-tailings. On the other hand, the structure of soil food web in the plant associations of AL and IC were relatively stable in a structured state with fungal decomposition being dominant in the decomposition of soil organic matter. This indicated that the soil food web in the plant associations of gramineae was at a poor development level.

Impact of epidural analgesia on quality of life and pain in advanced cancer patients.

Patients with advanced cancer often experience chronic postoperative pain and poor quality of life. The objective of this study was to determine if epidural self-controlled analgesia reduced the incidence of chronic pain and improved the quality of life when compared with intravenous self-controlled analgesia. A total of 50 patients diagnosed with advanced cancer who received analgesia treatment were randomly divided into two groups, epidural self-controlled analgesia group (EA group, n = 26) and intravenous self-controlled analgesia group (IA group, n = 24). Visual analog scale (VAS) and Karnofsky score were used to assess the pain and the quality of life, respectively. A multifunction monitor was used to continuously record the physical signs of patients after treatment. The physical signs, such as heart failure, respiration, pulse, blood pressure, and oxygen saturation, in the two groups were better after analgesia treatment. Meanwhile, the respiration and oxygen saturation in the EA group were significantly improved compared with that of the IA group (p < .05). The VAS in the EA group was significantly lower than that in the IA group (p < .05), and the Karnofsky score in the EA group was significantly higher than that in the IA group (p < .05). Moreover, patients treated with EA felt more satisfied and experienced fewer complications than those with IA (p < .05). The epidural self-controlled analgesia may greatly improve the quality of life and relieve the pain in patients with advanced cancer.

Different effects of isoflurane and sevoflurane on cytotoxicity.

BACKGROUND: Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in primary rat cortical neurons of rat in a concentration- and time-dependent manner by an unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum (ER) via activation of inositol 1, 4, 5-trisphosphate (IP(3)) receptors. Sevoflurane has a reduced ability to disrupt intracellular calcium homeostasis and is a less potent cytotoxic agent. This study examined and compared the cytotoxic effects of isoflurane and sevoflurane on rat primary cortical neurons and their relationship with disruption of intracellular calcium homeostasis and production of reactive oxygen species (ROS). METHODS: Primary rat cortical neurons were treated with the equivalent of 1 minimal alveolar concentration (MAC) of isoflurane and sevoflurane for 12 hours. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in the cytosolic space, [Ca(2+)](c), and production of ROS were determined after exposing primary rat cortical neurons to isoflurane and sevoflurane. We also determined the effects of IP(3) receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in primary rat cortical neurons. RESULTS: Isoflurane at 1 MAC for 12 hours induced cytotoxicity in primary rat cortical neurons, which was also associated with a high and fast elevation of peak [Ca(2+)](c). Xestospongin C significantly ameliorated isoflurane cytotoxicity in primary cortical neurons, as well as inhibited the calcium release from the ER in primary cortical neurons. Isoflurane did not induce significant changes of ROS production in primary rat cortical neurons. Sevoflurane, at equivalent exposure to isoflurane, did not induce similar cytotoxicity or elevation of peak [Ca(2+)](c) in primary rat cortical neurons. CONCLUSION: These results suggested that isoflurane induced elevation in [Ca(2+)](c), partially via elevated activity of IP(3) receptors, which rendered cells vulnerable to isoflurane neurotoxicity. ROS production was not involved in isoflurane-induced neurotoxicity. Sevoflurane, at an equivalent exposure to isoflurane, did not induce similar elevations of [Ca(2+)](c) or neurotoxicity in primary cortical neurons of rat.

[Effects of mechanical ventilation on the expression of Toll like receptor 4 in rat's alveolar macrophages].

OBJECTIVE: To investigate the effects of mechanical ventilation on Toll like receptor 4 (TLR4) in rat's alveolar macrophages (AM). METHODS: Eighteen clean grade adult male SD rats weighting 230-240 g were randomly divided into three groups (n=6): autonomous breathing group(R group), small tidal volume (V(T)) mechanical ventilation group (M group, V(T)=6 ml/kg) and large V(T) mechanical ventilation group (N group, V(T)=40 ml/kg). The animals were anesthetized with intraperitoneal 20% urethane 8 ml/kg, tracheostomized and mechanically ventilated [inhalation: exhalation (I:E)=1:1, with positive end-expiratory pressure (PEEP)=0, fraction of inspired oxygen (FiO(2))=0.21]. The respiratory rate was adjusted, and end-tidal carbon dioxide partial pressure (P(ET)CO(2)) was maintained at 35-45 mm Hg (1 mm Hg=0.133 kPa). Arterial blood samples were taken for blood gas analysis at the beginning of the experiment and 1, 2 and 3 hours after the experiment. The experiment was terminated, and pathomorphology score, pulmonary tissue wet/dry (W/D) weight ratio, white blood cells count (WBC) in bronchoalveolar lavage fluid (BALF) were determined at 3 hours. The rats were sacrificed by bloodletting after experiment. Then the rats' BALF and pulmonary albumin permeability (PAP) were determined. The expression of AM TLR4 mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). AM TLR4 protein expression was determined by immunohistochemistry. RESULTS: Over ventilation, elevated pH and lower partial pressure of carbon dioxide in arterial blood (PaCO(2)) were observed in N group at 1 hour, and other indexes were normal. The pulmonary pathomorphology score, pulmonary W/D weight ratio, WBC in BALF, PAP, and the mRNA expression of TLR4 and the protein of TLR4 in AM in the N group were greatly increased as compared with the R group (all P<0.01), while they were not significantly changed in the M group (all P>0.05). CONCLUSION: Large V(T) mechanical ventilation induced injury of lungs and up-regulated TLR4 expression in rat's AM. Small V(T) mechanical ventilation avoided above-mentioned changes.

[Influence of various ventilation manier on rat's lung and the expression of lung endotoxin receptor CD14 mRNA].

OBJECTIVE: To observe the influence of mechanical ventilation (MV) on rat's lung and the expression changes of lung endotoxin receptor CD14 mRNA. METHODS: Forty-eight male SD rats weighing 330-360 g were randomly divided into 4 groups (n = 12 each): group R received no mechanical ventilation, group P received small MV (VT = 6 ml/kg, PEEP = 8 mm Hg), group M received conventional MV (VT = 12 ml/kg, PEEP = 0 mm Hg), and group N received large tidal volume mechanical ventilation (VT = 40 ml/kg, PEEP = 0 mm Hg). The animals were anesthetized with intraperitoneal pentobarbital 100 mg x kg(-1), tracheotomized and mechanically ventilated (I:E = 1:1, FiO2 = 21%). The respiratory rate (RR) of MV was adjusted to maintain the end-tidal carbon dioxide in the rang of 35-45 mm Hg throughout the procedure. Right carotid artery and left femoral vein were cannulated for BP monitoring and fluid and drug administration. 6 rats in each group were injected 50 mg/kg Evans Blue (EB). The experiment was culminated in 3 hours, then the rats were killed by exsanguination via arteria carotis interna. Morphologic change scores of the rats' lungs, wet/dry weight ratio of lung tissue (W/D), bronchial lavage fluid (BALF) inflammatory cell population, and permeability of vessel wall were evaluated. The concentration of TNF-alpha and MIP-2 in the plasma were determined by enzyme immunoassay method (ELISA). The expressions of lung tissue endotoxin receptor CD14 were detected by RT-PCR, macrophage CD14 in BALF was also detected by immunohistochemistry. RESULTS: pulmonary pathomorphology scores: there were no alteration in R group and P group, but it were slightly increased in M group, there was significantly elevated in N group as compare to M group (F = 8.0, P = 0.000). Pulmonary tissue wet/dry weight ratio (W/D): Compare with R group, There was no statistically significant difference in P group and M group; the elevation in N group (t = 4.103, P = 0.02), EB: Compare with R group, There was no statistically significant difference in P group and M group; the obviously elevation in N group (t = 36.634, P = 0.000). WBC in BALF: Compare with R group, there was no change in P group, the elevation in M group (t = 4.272, P = 0.02), there was significantly elevated in N group (F = 26.68, P = 0.000). TNF-alpha had no manifest variation in 4 groups. MIP-2: compare with R group (31.5 +/- 2.4), There was no statistically significant difference in P group (35.4 +/- 5.3), the elevation in M group (44.7 +/- 6.9, t = 7.85, P = 0.04), there was significantly elevated in N group (167.7 +/- 11.8, t = 27.779, P = 0.000). The expressions of macrophage CD14 protein in BALF and lung tissue CD14 mRNA were fundamentally coincident in R group and P group; the expressions of CD14 mRNA were elevated, but the expressions of CD14 protein were no change in M group; the expressions of CD14 in N group manifestly elevated (P = 0.000). CONCLUSIONS: Conventional MV induces minor injury in rat's lung and can up regulate the expression of CD14 mRNA in the lung, but not up regulate the expression of CD14 protein; large tidal volume MV induces injury of rat's lung and evidently up regulates CD14 expression in the lung. Protective MV can avoid the above mentioned variations in rat's lung.