Difficult airway due to cervical haemorrhage caused by spontaneous rupture of a parathyroid adenoma: A case report.

BACKGROUND: Cervical haemorrhage due to spontaneous rupture of a parathyroid adenoma is a rare complication that may cause life-threatening acute airway compromise. CASE SUMMARY: A 64-year-old woman was admitted to the hospital 1 day after the onset of right neck enlargement, local tenderness, head-turning difficulty, pharyngeal pain, and mild dyspnoea. Repeat routine blood testing showed a rapid decrease in the haemoglobin concentration, indicating active bleeding. Enhanced computed tomography images showed neck haemorrhage and a ruptured right parathyroid adenoma. The plan was to perform emergency neck exploration, haemorrhage removal, and right inferior parathyroidectomy under general anaesthesia. The patient was administered 50 mg of intravenous propofol, and the glottis was successfully visualised on video laryngoscopy. However, after the administration of a muscle relaxant, the glottis was no longer visible and the patient had a difficult airway that prevented mask ventilation and endotracheal intubation. Fortunately, an experienced anaesthesiologist successfully intubated the patient under video laryngoscopy after an emergency laryngeal mask placement. Postoperative pathology showed a parathyroid adenoma with marked bleeding and cystic changes. The patient recovered well without complications. CONCLUSION: Airway management is very important in patients with cervical haemorrhage. After the administration of muscle relaxants, the loss of oropharyngeal support can cause acute airway obstruction. Therefore, muscle relaxants should be administered with caution. Anaesthesiologists should pay careful attention to airway management and have alternative airway devices and tracheotomy equipment available.

Specific antagonist of receptor for advanced glycation end­products attenuates delirium­like behaviours induced by sevoflurane anaesthesia with surgery in aged mice partially by improving damage to the blood­brain barrier.

Postoperative delirium (POD), which occurs in hospital up to 1-week post-procedure or until discharge, is a common complication, especially in older adult patients. However, the pathogenesis of POD remains unclear. Although damage to blood-brain barrier (BBB) integrity is involved in the neuropathogenesis of POD, the specific role of the BBB in POD requires further elucidation. Anaesthesia using 2% isoflurane for 4 h results in the upregulation of hippocampal receptor for advanced glycation end-products (RAGE) expression and ß-amyloid accumulation in aged rats. The present study investigated the role of RAGE in BBB integrity and its mechanisms in POD-like behaviours. The buried food, open field and Y maze tests were used to evaluate neurobehavioural changes in aged mice following 2.5% sevoflurane anaesthesia administration with exploratory laparotomy. Levels of tight junction proteins were assessed by western blotting. Multiphoton in vivo microscopy was used to observe the ultrastructural changes in the BBB in the hippocampal CA1 region. Anaesthesia with surgery decreased the levels of tight junction proteins occludin and claudin 5, increased matrix metalloproteinases (MMPs) 2 and 9, damaged the ultrastructure of the BBB and induced POD-like behaviour. FPS-ZM1, a specific RAGE antagonist, ameliorated POD-like behaviour induced by anaesthesia and surgery in aged mice. Furthermore, FPS-ZM1 also restored decreased levels of occludin and claudin 5 as well as increased levels of MMP2 and MMP9. The present findings suggested that RAGE signalling was involved in BBB damage following anaesthesia with surgery. Thus, RAGE has potential as a novel therapeutic intervention for the prevention of POD.

Inhibition of visfatin alleviates sepsis-induced intestinal damage by inhibiting Hippo signaling pathway.

BACKGROUND: The aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism. METHODS: C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines. RESULTS: The expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866. CONCLUSION: In short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target.

Low Concentration of Antibiotics Modulates Gut Microbiota at Different Levels in Pre-Weaning Dairy Calves.

The aim of this study was to investigate the effect of feeding milk replacer (MR) with two different antibiotics treatments on the gut microbiota of pre-weaning calves. Twelve (12) Holstein male calves at 1-day-old were randomly assigned to: milk replacer without antibiotics (CON), milk replacer plus low cocktail of antibiotics (LCA) concentration (penicillin 0.024 mg/L, streptomycin 0.025 mg/L, tetracycline 0.1 mg/L, ceftiofur 0.33 mg/L), and milk replacer plus a low concentration of single antibiotic (LSA; ceftiofur 0.33 mg/L). All the calves were harvested at 35-day-old, and the digesta from the ileum and colon was collected in addition to fecal samples. Samples were analyzed by 16S rRNA gene using Illumina MiSeq platform. Results showed that there were significant differences among treatments in the ileum, where LCA significantly reduced the relative abundance of Enterobacteriaceae (P = 0.02) especially Escherichia-coli (P = 0.02), while LSA significantly reduced the relative abundance of Comamonas (P = 0.02). In the colon and rectum, LSA treatment was significantly enriched with the class Bacilli, whereas the control group was significantly enriched with Alloprevotlla (P = 0.03). However, at the family level in the rectum LCA and LSA significantly reduced the relative abundance of Acidaminococcaceae (P = 0.01). Moreover, at the genera level in the colon, LSA significantly increased Prevotellaceae_Ga6A1_ group (P = 0.02), whereas in the rectum both of treatments reduced the relative abundance of Phascolarctobacterium (P = 0.01). In conclusion, the overall low cocktail of antibiotics concentration induced changes at different taxonomic levels; specifically the decrease in Escherichia-coli which might subsequently reduce the incidences of diarrhea in calves.

Duration-dependent regulation of autophagy by isoflurane exposure in aged rats.

Current evidence suggests a central role for autophagy in many inflammatory brain disorders, including Alzheimer's disease (AD). Furthermore, it is also well accepted that some inhalation anesthetics, such as isoflurane, may cause AD-like neuropathogenesis and resultant postoperative cognitive dysfunction, especially in the elderly population. However, the impact of inhalation anesthetics on autophagic components in the brain remains to be documented. Hence, our objective was to investigate the effects of different durations of isoflurane exposure on hippocampus-dependent learning and hippocampal autophagy in aged rats. Aged Sprague-Dawley rats (20 months old) were randomly exposed to 1.5% isoflurane or 100% oxygen for 1 or 4 h. Animals were then trained in the Morris water maze (4 trials/day for 5 consecutive days). Hippocampal phagophore formation markers, beclin 1 and protein microtubule-associated protein 1 light chain-3B (LC3B), as well as p62, an indicator of autophagic flux, were quantified by western blotting. There was no significant difference in the escape latencies and time spent in the target quadrant, as well as hippocampal expression of beclin 1, LC3B-II, and p62 at 24 h post-anesthesia between the 1-h isoflurane-exposed rats and their controls (P >0.05). Four-hour exposure to isoflurane resulted in spatial learning and memory deficits, as evidenced by prolonged escape latencies on days 4 and 5 post-anesthesia and less time spent in the target quadrant than sham-exposed animals (P <0.05). These events were accompanied by a decline in hippocampal expression of LC3B-I, LC3B-II, and beclin 1 24 h after isoflurane (P <0.01 and P <0.05). Nevertheless, no significant change in p62 expression was found. Further kinetics study of autophagic changes induced by 4 h of isoflurane showed a transient upregulation of LC3B-I, LC3B-II, and beclin 1 at the end of exposure and a subsequent striking decrease within 12-24 h post-anesthesia (P <0.05). Hippocampal p62 peaked at 6 h but subsequently resolved. These results from our pilot in vivo study support a duration-dependent relationship between 1.5% isoflurane exposure, and spatial cognitive function as well as hippocampal phagophore formation.

Surgical stress induces brain-derived neurotrophic factor reduction and postoperative cognitive dysfunction via glucocorticoid receptor phosphorylation in aged mice.

AIMS: This study explored whether surgical stress-induced glucocorticoid receptor (GR) phosphorylation is related to postoperative cognitive dysfunction (POCD) in aged individuals. Inhibition of GR activation could be an effective treatment for POCD. METHODS: A laparotomy was given to C57/BL6 mice in POCD group both 20 and 6 months old. Animals in control group were treated in identical manners except for laparotomy. Cognitive function was evaluated by Morris water maze and elevated plus maze. Western blot and Elisa assay were used to detect related molecules. Mifepristone and roscovitine were treated as inhibitions of GR phosphorylation. RESULTS: The cognitive function was impaired, and brain-derived neurotrophic factor (BDNF) was found reduced in aged POCD group. GR translocation into nucleus and elevated GR phosphorylation were found in prefrontal cortex of aged POCD mice. Cyclin-dependent Kinase 5 (CDK5), kinase for GR phosphorylation also elevated in aged POCD mice. With GR antagonist and CDK5 inhibitor, reduction of BDNF and cognitive dysfunction in aged mice were both rescued. CONCLUSION: These results presented a mechanism that surgical stress-induced GR phosphorylation contributes to POCD in aged individuals. Inhibition of GR activation and phosphorylation might be a potential treatment target of POCD.

Activation of the canonical nuclear factor-κB pathway is involved in isoflurane-induced hippocampal interleukin-1ß elevation and the resultant cognitive deficits in aged rats.

Although much recent evidence has demonstrated that neuroinflammation contributes to volatile anesthetic-induced cognitive deficits, there are few existing mechanistic explanations for this inflammatory process. This study was conducted to investigate the effects of the volatile anesthetic isoflurane on canonical nuclear factor (NF)-κB signaling, and to explore its association with hippocampal interleukin (IL)-1ß levels and anesthetic-related cognitive changes in aged rats. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in IκB kinase and IκB phosphorylation, as well as a reduction in the NF-κB inhibitory protein (IκBα), were observed in the hippocampi of isoflurane-exposed rats compared with control rats. These events were accompanied by an increase in NF-κB p65 nuclear translocation at 6h after isoflurane exposure and hippocampal IL-1ß elevation from 1 to 6h after isoflurane exposure. Nevertheless, no significant neuroglia activation was observed. Pharmacological inhibition of NF-κB activation by pyrrolidine dithiocarbamate markedly suppressed the IL-1ß increase and NF-κB signaling, and also mitigated the severity of cognitive deficits in the Morris water maze task. Overall, our results demonstrate that isoflurane-induced cognitive deficits may stem from upregulation of hippocampal IL-1ß, partially via activation of the canonical NF-κB pathway, in aged rats.

Curcumin inhibits TGF-ß1-induced MMP-9 and invasion through ERK and Smad signaling in breast cancer MDA- MB-231 cells.

OBJECTIVE: To evaluate the effects of curcumin on matrixmetalloproteinase-9 (MMP-9) and invasion ability induced by transforming growth factor-ß1 (TGF-ß1) in MDA-MB-231 cells and potential mechanisms. METHODS: Human breast cancer MDA- MB-231 cells were used with the CCK-8 assay to measure the cytotoxicity of curcumin. After treatment with 10 ng/ml TGF-ß1, with or without curcumin (≤10 µM), cell invasion was checked by transwell chamber. The effects of curcumin on TGF-ß1-stimulated MMP-9 and phosphorylation of Smad2, extracellular-regulated kinase (ERK), and p38 mitogen activated protein kinases (p38MAPK) were examined by Western blotting. Supernatant liquid were collected to analyze the activity of MMP-9 via zymography. Following treatment with PD98059, a specific inhibitor of ERK, and SB203580, a specific inhibitor of p38MAPK, Western blotting and zymography were employed to examine MMP-9 expression and activity, respectively. RESULTS: Low dose curcumin (≤10 µM) did not show any obvious toxicity to the cells, while 0~10 µmol/L caused a concentration-dependent reduction in cell invasion provoked by TGF-ß1. Curcumin also markedly inhibited TGF-ß1-regulated MMP-9 and activation of Smad2, ERK1/2 and p38 in a dose- and time-dependent manner. Additionally, PD98059, but not SB203580, showed a similar pattern of inhibition of MMP-9 expression. CONCLUSION: Curcumin inhibited TGF-ß1-stimulated MMP-9 and the invasive phenotype in MDA-MB-231 cells, possibly associated with TGF-ß/Smad and TGF-ß/ERK signaling.