Multi-Omics Analysis Reveals the Regulatory Mechanism of Probiotics on the Growth Performance of Fattening Sheep.

Probiotics have been proven to improve the growth performance of livestock and poultry. The aim of this experiment was to investigate the effects of probiotic supplementation on the growth performance; rumen and intestinal microbiota; rumen fluid, serum, and urine metabolism; and rumen epithelial cell transcriptomics of fattening meat sheep. Twelve Hu sheep were selected and randomly divided into two groups. They were fed a basal diet (CON) or a basal diet supplemented with 1.5 × 108 CFU/g probiotics (PRB). The results show that the average daily weight gain, and volatile fatty acid and serum antioxidant capacity concentrations of the PRB group were significantly higher than those of the CON group (p < 0.05). Compared to the CON group, the thickness of the rumen muscle layer in the PRB group was significantly decreased (p < 0.01); the thickness of the duodenal muscle layer in the fattening sheep was significantly reduced; and the length of the duodenal villi, the thickness of the cecal and rectal mucosal muscle layers, and the thickness of the cecal, colon, and rectal mucosal layers (p < 0.05) were significantly increased. At the genus level, the addition of probiotics altered the composition of the rumen and intestinal microbiota, significantly upregulating the relative abundance of Subdivision5_genera_incertae_sedis and Acinetobacter in the rumen microbiota, and significantly downregulating the relative abundance of Butyrivibrio, Saccharofermentans, and Fibrobacter. The relative abundance of faecalicoccus was significantly upregulated in the intestinal microbiota, while the relative abundance of Coprococcus, Porphyromonas, and Anaerobacterium were significantly downregulated (p < 0.05). There were significant differences in the rumen, serum, and urine metabolites between the PRB group and the CON group, with 188, 138, and 104 metabolites (p < 0.05), mainly affecting pathways such as vitamin B2, vitamin B3, vitamin B6, and a series of amino acid metabolisms. The differential genes in the transcriptome sequencing were mainly enriched in protein modification regulation (especially histone modification), immune function regulation, and energy metabolism. Therefore, adding probiotics improved the growth performance of fattening sheep by altering the rumen and intestinal microbiota; the rumen, serum, and urine metabolome; and the transcriptome.

Multi-omics analysis on the mechanism of the effect of Isatis leaf on the growth performance of fattening sheep.

Introduction: This study evaluated the effects of Isatis Leaf (ISL) on the growth performance, gastrointestinal tissue morphology, rumen and intestinal microbiota, rumen, serum and urine metabolites, and rumen epithelial tissue transcriptome of fattening sheep. Methods: Twelve 3.5-month-old healthy fattening sheep were randomly divided into two groups, each with 6 replicates, and fed with basal diet (CON) and basal diet supplemented with 80 g/kg ISL for 2.5 months. Gastrointestinal tract was collected for histological analysis, rumen fluid and feces were subjected to metagenomic analysis, rumen fluid, serum, and urine for metabolomics analysis, and rumen epithelial tissue for transcriptomics analysis. Results: The results showed that in the ISL group, the average daily gain and average daily feed intake of fattening sheep were significantly lower than those of the CON group (P < 0.05), and the rumen ammonia nitrogen level was significantly higher than that of the CON group (P < 0.01). The thickness of the reticulum and abomasum muscle layer was significantly increased (P < 0.05). At the genus level, the addition of ISL modified the composition of rumen and fecal microorganisms, and the relative abundance of Methanobrevibacter and Centipeda was significantly upregulated in rumen microorganisms, The relative abundance of Butyrivibrio, Saccharofermentans, Mogibacterium, and Pirellula was significantly downregulated (P < 0.05). In fecal microorganisms, the relative abundance of Papillibacter, Pseudoflavonifractor, Butyricicoccus, Anaerovorax, and Methanocorpusculum was significantly upregulated, while the relative abundance of Roseburia, Coprococcus, Clostridium XVIII, Butyrivibrio, Parasutterella, Macellibacteroides, and Porphyromonas was significantly downregulated (P < 0.05). There were 164, 107, and 77 different metabolites in the rumen, serum, and urine between the ISL and CON groups (P < 0.05). The differential metabolic pathways mainly included thiamine metabolism, niacin and nicotinamide metabolism, vitamin B6 metabolism, taurine and taurine metabolism, beta-Alanine metabolism and riboflavin metabolism. These metabolic pathways were mainly involved in the regulation of energy metabolism and immune function in fattening sheep. Transcriptome sequencing showed that differentially expressed genes were mainly enriched in cellular physiological processes, development, and immune regulation. Conclusion: In summary, the addition of ISL to the diet had the effect of increasing rumen ammonia nitrogen levels, regulating gastrointestinal microbiota, promoting body fat metabolism, and enhancing immunity in fattening sheep.

Electroacupuncture alleviates ventilator-induced lung injury in mice by inhibiting the TLR4/NF-κB signaling pathway.

OBJECTIVE: This study was aimed to explore the protective effect of electroacupuncture (EA) pretreatment at Zusanli point (ST36) on ventilation-induced lung injury (VILI) and its potential anti-inflammatory mechanism. METHODS: High tidal volume ventilation was used to induce the VILI in mice, and EA pretreatment at ST36 was given for 7 consecutive days. The wet/dry ratio and pathological injury score of lung tissue, and total protein content of pulmonary alveolar lavage fluid (BALF) were detected after 4 h of mechanical ventilation (MV). Meanwhile, the expressions of TLR4 and NF- κB in lung tissue were evaluated by Western Blot, and the inflammatory factors in lung tissue were detected by ELISA. RESULTS: After four hours of mechanical ventilation, mice with ventilator-induced lung injury showed significant increases in lung wet/dry ratio, tissue damage scores, and protein content in bronchoalveolar lavage fluid. Pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α) and TLR4/NF-κB expression levels in the lung were also markedly elevated (P < 0.05). Conversely, ST36 acupuncture point pre-treatment significantly reduced these parameters (P < 0.05). CONCLUSION: EA pretreatment at ST36 could alleviate the inflammatory response for VILI via inhibiting TLR4/NF- κB pathway.

Exosomal microRNAs: implications in the pathogenesis and clinical applications of subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a severe acute neurological disorder with a high fatality rate. Early brain injury (EBI) and cerebral vasospasm are two critical complications of SAH that significantly contribute to poor prognosis. Currently, surgical intervention and interventional therapy are the main treatment options for SAH, but their effectiveness is limited. Exosomes, which are a type of extracellular vesicles, play a crucial role in intercellular communication and have been extensively studied in the past decade due to their potential influence on disease progression, diagnosis, and treatment. As one of the most important components of exosomes, miRNA plays both direct and indirect roles in affecting disease progression. Previous research has found that exosomal miRNA is involved in the development of various diseases, such as tumors, chronic hepatitis, atherosclerosis, diabetes, and SAH. This review focuses on exploring the impact of exosomal miRNA on SAH, including its influence on neuronal apoptosis, inflammatory response, and immune activation following SAH. Furthermore, this review highlights the potential clinical applications of exosomal miRNA in the treatment of SAH. Although current research on this topic is limited and the clinical application of exosomal miRNA has inherent limitations, we aim to provide a concise summary of existing research progress and offer new insights for future research directions and trends in this field.

Multi-Omics Analysis of the Mechanism of Mentha Haplocalyx Briq on the Growth and Metabolic Regulation of Fattening Sheep.

Mentha haplocalyx Briq (MHB) and its components have been proven to improve the growth performance of livestock and poultry. The aim of this experiment was to investigate the effects of MHB addition on growth performance, rumen and fecal microbiota, rumen fluid, serum and urine metabolism, and transcriptomics of rumen epithelial cells in meat sheep. Twelve Hu sheep were selected for the experiment and fed with basic diet (CON) and a basal diet supplemented with 80 g/kg DM of Mentha haplocalyx Briq (MHB). The experimental period was 10 weeks with the first 2 weeks as the pre-trial period. The results showed that compared with the CON group, the average daily weight gain of meat sheep in the MHB group increased by 20.1%; the total volatile fatty acid (VFA) concentration significantly increased (p < 0.05); The thickness of the cecal mucosal layer was significantly reduced (p < 0.01), while the thickness of the colonic mucosal layer was significantly increased (p < 0.05), the length of ileal villi significantly increased (p < 0.01), the thickness of colonic mucosal layer and rectal mucosal muscle layer significantly increased (p < 0.05), and the thickness of cecal mucosal layer significantly decreased (p < 0.05); The serum antioxidant capacity has increased. At the genus level, the addition of MHB changed the composition of rumen and fecal microbiota, increased the relative abundance of Paraprevotella, Alloprevotella, Marinilabilia, Saccharibacteria_genera_incertae_sedis, Subdivision5_genera_incertae_sedis and Ornatilinea in rumen microbiota, and decreased the relative abundance of Blautia (p < 0.05). The relative abundance of Prevotella, Clostridium XlVb and Parasutterella increased in fecal microbiota, while the relative abundance of Blautia and Coprococcus decreased (p < 0.05). There were significant differences in the concentrations of 105, 163, and 54 metabolites in the rumen, serum, and urine between the MHB group and the CON group (p < 0.05). The main metabolic pathways of the differences were pyrimidine metabolism, taurine and taurine metabolism, glyceride metabolism, and pentose phosphate pathway (p < 0.05), which had a significant impact on protein synthesis and energy metabolism. The transcriptome sequencing results showed that differentially expressed genes were mainly enriched in immune regulation, energy metabolism, and protein modification. Therefore, adding MHB improved the growth performance of lambs by altering rumen and intestinal microbiota, rumen, serum and urine metabolomics, and transcriptome.

CRISPR-based m6A modification and its potential applications in telomerase regulation.

Telomerase determines cell lifespan by controlling chromosome stability and cell viability, m6A epigenetic modification plays an important role in the regulation of telomerase activity. Using CRISPR epigenome editing to analyze specific m6A modification sites in telomerase will provide an important tool for analyzing the molecular mechanism of m6A modification regulating telomerase activity. In this review, we clarified the relevant applications of CRISPR system, paid special attention to the regulation of m6A modification in stem cells and cancer cells based on CRISPR system, emphasized the regulation of m6A modification on telomerase activity, pointed out that m6A modification sites regulate telomerase activity, and discussed strategies based on telomerase activity and disease treatment, which are helpful to promote the research of anti-aging and tumor related diseases.

Hypertensive crisis merging with paroxysmal supraventricular tachycardia after dezocine injection during cesarean delivery: A case report.

Hypertensive crisis and paroxysmal supraventricular tachycardia are serious adverse reactions that can lead to fatal consequences. We reported a 28-year-old woman who underwent emergency cesarean section of her first fetus due to pelvic outlet stenosis and had a hypertensive crisis, merging with paroxysmal supraventricular tachycardia after dezocine was administrated during the procedure. Her symptoms returned to normal after esmolol and urapidil were administrated. In order to rule out hypertension crisis caused by other diseases, the anesthesiologist immediately accessed the thyroid function, myocardial enzymes, catecholamines, and arterial blood gas analysis of the patient. No obvious abnormality was found in all the test results. We infer the conclusion that the symptoms of this patient during the operation were most likely related to dezocine administration. This case highlights the need to pay attention to possible malignant adverse reactions while using dezocine during cesarean section, and we recommend the immediate use of α-receptor blockers and/or ß-receptor blockers in situations like to avoid serious complications caused by supraventricular tachycardia.

Anesthesia management of an aged patient with giant abdominal tumor and large hiatal hernia: A case report and literature review.

Introduction: A giant abdominal tumor with a large hiatal hernia remains a rare disease with few studies regarding its implications in anesthesia. A large hiatal hernia may compress the heart and cause arrhythmia and even cardiac arrest, which greatly increases the risks and challenges of anesthesia management. Case description: We present a case in which a patient with a giant abdominal desmoid tumor and large hiatal hernia experienced a critical situation during anesthesia and surgery. Conclusions: It is a great challenge for anesthesiologists to manage a patient's respiratory system and circulation. Careful perioperative management and optimized multidisciplinary teams are the key factors in the successful management of this rare condition. In addition, awake endotracheal intubation, ventilation preserving spontaneous breathing and target-directed fluid therapy play an essential role in anesthesia management.

Role of Iron-Related Oxidative Stress and Mitochondrial Dysfunction in Cardiovascular Diseases.

Iron is indispensable in numerous biologic processes, but abnormal iron regulation and accumulation is related to pathological processes in cardiovascular diseases. However, the underlying mechanisms still need to be further explored. Iron plays a key role in metal-catalyzed oxidative reactions that generate reactive oxygen species (ROS), which can cause oxidative stress. As the center for oxygen and iron utilization, mitochondria are vulnerable to damage from iron-induced oxidative stress and participate in processes involved in iron-related damage in cardiovascular disease, although the mechanism remains unclear. In this review, the pathological roles of iron-related oxidative stress in cardiovascular diseases are summarized, and the potential effects and mechanisms of mitochondrial iron homeostasis and dysfunction in these diseases are especially highlighted.

The efficacy of different alveolar recruitment maneuvers in holmium laser lithotripsy surgery under general anesthesia using a laryngeal mask.

BACKGROUND: Alveolar recruitment maneuvers (ARMs) is an important part of lung-protective ventilation strategies (LPVSs), but the optimal duration and interval Remain unclear. METHODS: Patients:252 patients who underwent holmium laser lithotripsy surgery and meet inclusion criteria were included and randomized into three groups based on the duration and frequency of ARMs (Regular, one 30 s ARM (RARMs); Improved and intermittent, three 10s ARMs (IARMs); and Control (C), no ARMs). INTERVENTIONS: Groups R and I received ARMs at 20 cmH2O pressures every 30 min. All patients received the same anesthesia and mechanical ventilation. MEASUREMENTS: Outcomes included heart rate and mean arterial pressure changes during ARMs and postoperative pulmonary complications (PPCs) within the first 7 postoperative days. MAIN RESULTS: Incidences of PPCs in groups R(7.1%) and I (5.0%)were slightly lower than those in group C (8.9%).This indicated the potential to reduce lung injury. Heart rate and mean arterial pressure fluctuations during ARMs were significantly higher in groups R and I than in group C (P < 0.01). The rate of blood pressure decrease was significantly higher in group R than in group I (P < 0.01). CONCLUSIONS: IARMs can reduce cycle fluctuations than RARMs in patients Undergoing holmium laser lithotripsy surgery with laryngeal mask general anesthesia. Low tidal volume ventilation and low PEEP combined with ARM did not significantly reduce the incidence of PPCs in healthy lung patients, but tended to reduce lung injury. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Registry. ( ChiCTR2000030815 ,15/03/2020). This study was approved by the ethics committee of Chengdu Fifth People's Hospital with approval number(2020-005(Study)-1).

Genetic Regulation of N6-Methyladenosine-RNA in Mammalian Gametogenesis and Embryonic Development.

Emerging evidence shows that m6A is the most abundant modification in eukaryotic RNA molecules. It has only recently been found that this epigenetic modification plays an important role in many physiological and pathological processes, such as cell fate commitment, immune response, obesity, tumorigenesis, and relevant for the present review, gametogenesis. Notably the RNA metabolism process mediated by m6A is controlled and regulated by a series of proteins termed writers, readers and erasers that are highly expressed in germ cells and somatic cells of gonads. Here, we review and discuss the expression and the functional emerging roles of m6A in gametogenesis and early embryogenesis of mammals. Besides updated references about such new topics, readers might find in the present work inspiration and clues to elucidate epigenetic molecular mechanisms of reproductive dysfunction and perspectives for future research.

Posttreatment With the Fatty Acid Amide Hydrolase Inhibitor URB937 Ameliorates One-Lung Ventilation-Induced Lung Injury in a Rabbit Model.

BACKGROUND: One-lung ventilation (OLV)-induced inflammation is a risk factor for acute lung injury that is responsible for 20% of postoperative pulmonary complications after lung resection. Inflammation is an important trigger for acute lung injury. Fatty acid amide hydrolase (FAAH) is the major enzyme that degrades the endocannabinoid arachidonoylethanolamine (AEA), an important regulator of inflammation, and its downstream metabolites such as arachidonic acid (AA) are also involved in inflammation. Importantly, AEA is also found in lung parenchyma. However, it remains unclear whether pharmacological inhibition of FAAH inhibitor using compounds such as URB937 can attenuate OLV-induced lung injury. MATERIALS AND METHODS: New Zealand white rabbits were anesthetized to establish a modified OLV-induced lung injury model. Twenty-four male rabbits were randomly divided into four groups (n = 6): TLV-S (2.5-h two-lung ventilation [TLV] + 1.5 mL/kg saline + 1-h TLV), OLV-S (2.5-h OLV + 1.5 mL/kg saline + 0.5-h OLV + 0.5-h TLV), U-OLV (1.5 mL/kg URB937 + 3.0-h OLV + 0.5-h TLV), and OLV-U (2.5-h OLV + 1.5 mL/kg URB937 + 0.5-h OLV + 0.5-h TLV). Arterial blood gases, lung wet/dry ratio, and lung injury score of the nonventilated lungs were measured. The levels of AEA, AA, prostaglandin I2 (PGI2), thromboxane A2 (TXA2), and leukotriene B4 (LTB4) in the nonventilated lung were also quantified. RESULTS: The arterial oxygenation index (PaO2/FiO2) decreased after 0.5-h OLV in the three OLV groups. The PaO2/FiO2 in the OLV-U group was better than that in the OLV-S and U-OLV groups and was accompanied with reductions in the wet/dry ratio and lung injury scores of the nonventilated lungs. The FAAH inhibitor URB937 administered not before but 2.5 h after OLV attenuated OLV-induced lung injury by increasing AEA levels and reducing the levels of downstream metabolites including AA, PGI2, TXA2, and LTB4. CONCLUSIONS: Posttreatment with the FAAH inhibitor URB937 attenuated OLV-induced lung injury in rabbits and was associated with increased AEA levels and decreased levels of AA and its downstream metabolites.

Dorsal Penile Nerve Block With Ropivacaine-Reduced Postoperative Catheter-Related Bladder Discomfort in Male Patients After Emergence of General Anesthesia: A Prospective, Randomized, Controlled Study.

Catheter-related bladder discomfort (CRBD) is a distressing symptom complex after surgery, especially in male patients who have had urinary catheterization under general anesthesia. In this prospective, randomized, controlled trial, we compared dorsal penile nerve block (DPNB) with 0.33% ropivacaine with intravenous tramadol 1.5 mg kg(-1) in prevention of CRBD, as well as the incidences of postoperative side effects. Fifty-eight male patients aged 18 to 50 years, undergoing elective liver surgery and limb surgery with urinary catheterization, were enrolled and divided randomly into 2 groups. In the DPNB group, patients were given dorsal penile nerve block with 15 mL of 0.33% ropivacaine, and in the tramadol intravenous administration (TRAM) group, patients were given 1.5 mg kg(-1) tramadol after the completion of surgery before extubation. The primary outcome was the incidence of CRBD, and the secondary outcomes included the severity of CRBD, postoperative side effects, postoperative pain, and the acceptance of urinary catheterization. Patients were evaluated upon arrival to postanesthetic care unit (PACU), at 0.5, 1, 2, 4, and 6 hours after patients' arrival in the PACU for outcomes. The incidence of CRBD was significantly lower in the DPNB group than in the TRAM group, either upon arrival to PACU (10.3% vs 37.9%, P = 0.015), or at 0.5 hours (3.4% vs 34.5%, P = 0.003), 1 hours (3.4% vs 37.9%, P = 0.001), 2 hours (6.9% vs 34.5%, P = 0.010), and 4 hours (6.9% vs 27.6%, P = 0.039) after patients' arrival in PACU. Compared with the TRAM group, the severity of postoperative CRBD upon arrival to PACU (P = 0.011) and at 0.5 hours (P = 0.005), 1 hours (P = 0.002), 2 hours (P = 0.005), 4 hours (P = 0.017), and 6 hours (P = 0.047) after patients' arrival in PACU were all significantly reduced in the DPNB group. The incidences of postoperative nausea, vomiting, dizziness, and sedation were decreased significantly in the DPNB group compared with the TRAM group (P < 0.05). The acceptance of urinary catheterization was 93.1% (27/29 patients) in the DPNB group and 58.6% (17/29 patients) in the TRAM group, respectively (P < 0.001).DPNB with ropivacaine has a better effect for CRBD reduction and less side effects than intravenous tramadol administration. The trial has been registered at www.clinicaltrials.gov (NCT01721031).

Emulsified halothane produces long-term epidural anesthetic effect: a study in rabbits.

Previous studies have demonstrated that volatile anesthetics could produce local anesthesia. Emulsified isoflurane at 8% has been reported to produce epidural anesthetic effect in rabbits. This study was designed to investigate the long-term epidural anesthetic effect of emulsified halothane in rabbits. In this study, 40 healthy adult rabbits (weighting 2.0-2.5 kg) with an epidural catheter were randomly divided into 4 groups (n=10/group), receiving epidural administration of 1% lidocaine (lido group), 8% emulsified isoflurane 1ml (8% E-iso group), 8% emulsified halothane (8% E-Halo group) and 12% emulsified halothane (12% E-Halo group). After administration, sensory and motor functions as well as consciousness state were assessed until 60 minutes after sensory and motor function returned to its baseline or at least for 180 min. After epidural anesthesia, all the rabbits were continuously observed for 7 days and sacrificed for pathological evaluations. As a result, all the four study solutions produced typical epidural anesthesia. Onset times of sensory and motor function blockade were similar among the four groups (P>0.05). Duration of sensory blockade in 12% E-Halo group (83±13 min) was significantly longer than other groups: 51±12 min in 8% E-Halo group (P<0.01), 57±8 min in 8% E-iso group (P<0.01) and 47±9 min in lido group (P<0.01). Duration of sensory blockade in 8% E-iso group is longer than lido group (P<0.05). Duration of motor blockade in 12% E-Halo group (81±12 min) was also significantly longer than other groups: 40±8 min in 8% E-Halo group (P<0.01), 37±3 min in 8% E-iso group (P<0.01), 37±6 min in lido group (P<0.01). Normal consciousness was found in the rabbits from 8% E-Halo, 8% E-iso and lido groups while there were four rabbits in 12% E-Halo group (4/10) showed a light sedation. For all the rabbits, no pathological injury was found. The present study demonstrates that emulsified halothane produces reversible concentration-dependent epidural anesthesia and at 12% (v/v), emulsified halothane could produce long-term anesthesia without pathological injury.

Airtraq(®) laryngoscope-assisted fiberoptic bronchoscope intubation in a child with Pierre-Robin sequence: a case report.

We present a new strategy method of combining use of Airtraq(®) and fiberoptic bronchoscope (FOB) for tracheal intubation in 3-year-old child with Pierre-Robin sequence.

Polymerized placenta hemoglobin attenuates ischemia/reperfusion injury and restores the nitroso-redox balance in isolated rat heart.

Ischemia/reperfusion (I/R) injury mainly caused by oxidative stress plays a major role in cardiac damage. The extent of the I/R injury is also an important factor that determines the function of a transplanted heart. This study first examined whether hemoglobin-based oxygen carriers (HBOCs) could protect isolated rat heart from I/R injury and then elucidated the underlying mechanism. Using the Langendorff model, isolated Sprague-Dawley rat hearts were arrested and stored at 4 degrees C for 8 h and then reperfused for 2 h. Compared with St. Thomas' solution (STS) and rat self blood in STS, polymerized placenta hemoglobin (PolyPHb) in STS greatly improved heart contraction and decreased infarction size. The extent of myocardial apoptosis was also significantly decreased, which was related to reduced iNOS-derived nitric oxide production, increased protein ratio of Bcl-2/Bax, and reduced caspase-3 activity and cleavage level. Furthermore, PolyPHb in STS did not increase malondialdehyde, peroxynitrite, or mitochondrial hydrogen peroxide formation, but greatly elevated superoxide dismutase activity and preserved mitochondrial ATP synthesis, which served to maintain redox homeostasis in I/R heart. In conclusion, our results demonstrate that HBOCs protected isolated heart from I/R injury and this protection was associated with attenuation of NO-mediated myocardial apoptosis and restoration of the nitroso-redox balance.

[Fentanyl hypnotic interaction with emulsified isoflurane].

OBJECTIVES: To explore the effect of fentanyl on 50% effective dose (ED50) of emulsified isoflurane for hypnosis and to define the type of interaction between fentanyl and emulsified isoflurane during rat hypnosis. METHODS: 125 male adult Sprague-Dawley rats (240-300 g) were divided into 5 groups depending on the drugs administered via the tail vein. The up-and-down sequential allocation technique was used to determine ED50 of fentanyl in the loss of righting reflex. According to above experiment results, the up-and-down sequential allocation technique was also used to determine ED50 of emulsified isoflurane combined with different fentanyl dose of 7.2 microg/kg (1/4 ED50), 14.3 microg/kg (1/2 ED50) or 21.5 microg/kg (3/4 ED50), respectively, and also without the fentanyl in the loss of righting reflex. Fentanyl was administered intravenously for 20 s followed by emulsified isoflurane for 10 s. The interval between the two was 1.5 min in groups administered with both. ED50 was calculated by using Dixon-Mood method. The isobolographic and algebraic analyses were used to define the type of interaction between fentanyl and emulsified isoflurane. RESULTS: The body weight and sex of rats was not significantly different between the 5 groups. ED50 was (28.7 +/- 2.1) microg/kg (26.5-30.8 microg/kg) in the fentanyl group, (0.525 +/- 0.032) mL/kg in the fentanyl 7.2 microg/kg +/- isoflurane group, (0.108 +/- 0.019) mL/kg in the fentanyl 14.3 microg/kg+isoflurane group, (0.075 +/- 0.011) mL/kg in the fentanyl 21.5 microg/kg+isoflurane group and (0.670 +/- 0.054) mL/kg in the isoflurane group. The isobolographic analysis indicated that ED50 of isoflurane decreased progressively in a non-linear fashion in the presence of increasing dose of fentanyl. The isobolographic and algebraic analyses demonstrated that the combination use of fentanyl and emulsified isoflurane could produce a synergistic effect on hypnosis. CONCLUSIONS: Fentanyl enhances the hypnotic effect induced by emulsified isoflurane. The administration of associating fentanyl with emulsified isoflurane produces a synergistic effect on rat hypnosis.