Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study.

INTRODUCTION: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. METHODS: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. RESULTS: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. CONCLUSIONS: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

MBD1 Contributes to the Genesis of Acute Pain and Neuropathic Pain by Epigenetic Silencing of Oprm1 and Kcna2 Genes in Primary Sensory Neurons.

The transmission of normal sensory and/or acute noxious information requires intact expression of pain-associated genes within the pain pathways of nervous system. Expressional changes of these genes after peripheral nerve injury are also critical for neuropathic pain induction and maintenance. Methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, regulates gene transcriptional activity. We report here that MBD1 in the primary sensory neurons of DRG is critical for the genesis of acute pain and neuropathic pain as DRG MBD1-deficient mice exhibit the reduced responses to acute mechanical, heat, cold, and capsaicin stimuli and the blunted nerve injury-induced pain hypersensitivities. Furthermore, DRG overexpression of MBD1 leads to spontaneous pain and evoked pain hypersensitivities in the WT mice and restores acute pain sensitivities in the MBD1-deficient mice. Mechanistically, MDB1 represses Oprm1 and Kcna2 gene expression by recruiting DNA methyltransferase DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 is likely a key player under the conditions of acute pain and neuropathic pain.SIGNIFICANCE STATEMENT In the present study, we revealed that the mice with deficiency of methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, in the DRG displayed the reduced responses to acute noxious stimuli and the blunted neuropathic pain. We also showed that DRG overexpression of MBD1 produced the hypersensitivities to noxious stimuli in the WT mice and rescued acute pain sensitivities in the MBD1-deficient mice. We have also provided the evidence that MDB1 represses Oprm1 and Kcna2 gene expression by recruiting DNA methyltransferase DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 may participate in the genesis of acute pain and neuropathic pain likely through regulating DNMT3a-controlled Oprm1 and Kcna2 gene expression in the DRG neurons.

Cuff-leak test combined with interventional bronchoscopy benefits early extubation for patients who received tarp surgery.

PURPOSE: This study explored the performance characteristics of a cuff-leak test (CLT) combined with interventional fiberoptic bronchoscopy (FBS) for evaluating whether early nasoendotracheal extubation was possible for patients who had received transoral atlantoaxial reduction plate (TARP) internal fixation surgery. METHODS: 318 patients who underwent surgery were retrospectively analyzed (between January 2006 and December 2012). Extubation was performed by conventional approach (CA group, until December 2008) and improved approach (IA group, from January 2009) including CLT and an interventional FBS procedure. The extubation success within 1-3 days after surgery, incidence of postextubation stridor and tracheal reintubation were examined. RESULTS: More IA-treated patients experienced extubation during the first 2 days than those CA-treated, median extubation time was 3 (2, 3) days in the CA group and 2 (1, 2) days in the IA group (all P < 0.01). The incidence of stridor and reintubation was 5.69 and 0.57 % in IA and 11.98 and 4.93 % in CA, respectively (both P < 0.05). For the CLT-positive patients in the IA group that remained intubated until day 3-4, interventional FBS was applied for safe extubation and achieved 100 % success. CONCLUSION: Early extubation through IA is safe and interventional FBS assists successful extubation for CLT-positive patients who underwent TARP surgery.

Effect of preemptive local injection of ropivocaine with dexmedetomidine on mirror pain in rats and its mechanism.

OBJECTIVE: To observe the effect of preemptive local injection of ropivocaine with dexmedetomidine on activation of glial cells and on the mirror pain in rats and its mechanism. METHODS: A total of 48 adult male Sprague-Dawley rats (weighing 180 g-220 g) were included in the study and randomized into 3 groups, Group S, Group R, and Group RD1. A rat model of persistent postoperative pain evoked by skin/muscle incision and retraction was established in the three groups. Before procedures and nerve extraction, Group S (n = 16) was injected 0.9% saline locally; Group R (n = 16) was injected 0.5% ropivocaine locally, and Group RD1 (n = 16) was injected 0.5% ropivocaine in combined with 1 µg dexmedetomidine locally. After the model being established in the three groups, 8 rats were used for behavior test until 28 d, and dorsal root ganglions (DRGs) of the other 8 rats were harvested on the 3rd day after surgery. Immunofluorescent and transmission electron microscopy were used to observe the activation of glial cells in DRG, and the behavior test results in the three groups were compared. RESULTS: The results showed that mechanical pain threshold in ipsilateral hind-paws of the Group S, Group R, Group RD1 animals dropped to (3.640 ± 1.963) g, (5.827 ± 1.204) g, (7.482) ± 1.412 g at 3 d respectively; while in contralateral paws dropped to (7.100 ± 1.789) g, (17.687 ± 1.112) g, (16.213 ± 1.345) g on the 3 d respectively. Immunofluorescent showed that the glial cells were activated in bilateral side DRG after surgery in 3 groups, but ipsilateral paws expressed more active glial cells than contralateral paws. Transmission electron microscopy showed that mitochondria swelling/vacuolization and lysosomes were more obvious in ipsilateral paws than contralateral paws, but Group RD1 formula could reduce glial cells activity, mitochondria swelling/vacuolization and the amount of lysosomes. CONCLUSIONS: Local injection of ropivocaine and/or dexmedetomidine can effectively inhibit the activation of glial cells in DRG, mitigate the pathological changes of neuron in DRG and reduce mirror image pain.

Assessment of the relationship between ACE I/D gene polymorphism and renal allograft survival.

BACKGROUND AND OBJECTIVE: The relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and renal allograft survival after renal transplantation from the published reports are still debatable. This study was performed to evaluate the relationship between the ACE I/D gene polymorphism and renal allograft survival after renal transplantation using meta-analysis. METHOD: Eligible studies were identified from PubMed and Cochrane Library on 1 November 2014, and eligible studies were recruited and synthesized using a meta-analysis methodology. RESULTS: Twelve investigations were included in this meta-analysis for the assessment of the relationship between the ACE I/D gene polymorphism and renal allograft survival. In this meta-analysis, the ACE I/D gene polymorphism was not associated with renal allograft survival after renal transplantation for overall populations, Caucasians, Brazilians and Africans. Interestingly, the ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. CONCLUSIONS: ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. However, more studies should be performed to confirm this association.

Effect of aquaporin-4 deficiency on intravenous anaesthetic induced hypnotic effects in mice.

The deficiency of aquaporin-4 (AQP4) has been reported to alter release of neurotransmitters in the mouse brain. However, the functional relevance of AQP4 in mediating essential components of the general anaesthetic state is unknown. The aim of the present study was to investigate the role of AQP4 in general anaesthesia in mice lacking AQP4. The hypnotic effects of propofol, ketamine, and pentobarbital in AQP4 knockout (KO) and CD1 control mice were evaluated using the behavioural endpoint of loss of righting reflex (LORR). The effects of propofol on extracellular levels of amino acids in prefrontal cortex of freely moving mice were investigated using microdialysis coupled to high performance liquid chromatography with fluorescent detection. The result showed that, after receiving ketamine or pentobarbital, LORR occurred at earlier time in KO mice than that in control animals. Intraperitoneal injection of ketamine or pentobarbital increased the duration of LORR. After the administration of propofol, the duration of LORR was significantly reduced in KO mice compared with that in controls. Propofol increased the extracellular levels of aspartate, glutamate, and GABA, but not taurine, in prefrontal cortex. There were significant differences of increase patterns of the three kinds of neurotransmitters between KO and WT mice. Notably, the duration of GABA level increase correlated with the duration of LORR in two genotypes of mice. These results provide in vivo evidence of different responses in time-dependent release of excitatory and inhibitory neurotransmitters in prefrontal cortex of the two genotypes of mice. It is suggested that changes in anaesthetic reactions in mice with AQP4 loss may be related to neurotransmitter regulation, and that normal functioning of AQP4 plays an important role in the maintenance of anaesthetic hypnosis.

[Measurement of the minimum alveolar concentration of sevoflurane during combined anesthesia with sevoflurane, small-dose dexmedetomidine and fentanyl].

OBJECTIVE: To determine the minimum alveolar concentration (EC(50) and EC(95)) of sevoflurane in body movement response to surgical incision during combined anesthesia with dexmedetomidine, sevoflurane and fentanyl. METHODS: Twenty-six ASA class I or II patients (aged 18-60 years) underwent selective surgery for lumbar disc herniation under general anesthesia with the combination of with dexmedetomidine, sevoflurane and fentanyl. All the patients received infusion with 0.5 mg/kg dexmedetomidine for 10 min before anesthesia induction with intravenous injection of 3 µg/kg fentanyl 8% sevoflurane inhalation. Upon loss of consciousness, sevoflurane concentration was reduced to 5% with intravenous injection of 1-2 mg/kg succinylcholine, and intubation was started after muscles relaxation. Anesthesia was maintained by sevoflurane and dexmedetomidine (0.2 µg·kg(-1)·h(-1)). Before the surgery, a steady state end-tidal sevoflurane concentration was maintained for at least 10 min. The first patient of the series was tested with 1.5% sevoflurane, and the concentration was adjusted according to modified Dixons up-and-down method (with a step size of 0.2%). Probit analysis was used for calculating EC(50), EC(95) and the 95% confidence interval (CI). RESULTS: The EC(50) of sevoflurane was 0.94% (95%CI of 0.76%-1.07% ) and EC(95) was 1.23% (95%CI 1.09%-2.05% ). CONCLUSION: The EC(50) and EC(95) of sevoflurane are 0.94% and 1.23%, respectively, for suppressing body movement in response to surgical incision during combined anesthesia with sevoflurane, dexmedetomidine and fentanyl.

[Protective effects of sufentanil pretreatment against acute gastric mucosal lesion in rats and its relationship with acid-sensing ion channels].

OBJECTIVE: To investigate the effects of sufentanil pretreatment on acute gastric mucosal lesion and its impact on the expression of acid-sensing ion channel 3 (ASIC3) in thoracic dorsal root ganglia (DRG) neurons in rats with water immersion-restraint stress (WIRS). METHODS: Twenty-four Wistar rats were randomly assigned into 3 groups, namely the normal control group (n=6), WIRS group (n=12) and sufentanil pretreatment group (n=6). Gastric mucosal lesion was induced by WIRS, and after 6 h of WIRS, the gastric tissues were excised and observed under microscope, with the ulcer index (UI) calculated. The expression of ASIC3 in the DRG neurons was detected by immunofluorescence assay, and the ASIC3 mRNA expression by quantitative real-time RT-PCR. RESULTS: Compared with the normal control group, the rats in the WIRS group showed obvious gastric injury with increased UI and extensive expression of ASIC3 in the DRG neurons. Sufentanil pretreatment of the rats subjected to WIRS significantly alleviated the gastric mucosal injury, lowered the UI, and reduced ASIC3 mRNA expression in thoracic DRG neurons. CONCLUSION: ASIC3 is involved in the development of acute gastric mucosal lesion, and sufentanil pretreatment offers protection of gastric mucosa by inhibiting the expression of ASIC3.

Changes in erythrocyte membrane ATPases and plasma lipid peroxides in upper abdominal surgery under intravenous procaine-balanced anesthesia.

AIM:To observe the changes in erythrocyte membrane ATPases and plasma lipid peroxides (LPO) patients with in abdominal surgery under intravenous procainebalanced anesthesia.METHODS:By determining the ATPase activities of erythrocyte membrane, effects of upper abdominal surgery under intravenous procaine-balanced anesthesia on the function of erythrocytes were observed in 15 patients undergoing cholecystectomy and gastrectomy (5 males and 10 females, aged 45.9 ± 10.20 years and weighed 60.60kg ± 11.93kg). All patients were free from severe renal,hepatic, pulmonary, cardiac, metabolic and endocrinological diseases and acute infection for at least 2 weeks before surgery. Patients receiving any drug known to affect carbohydrate metabolism prior to anesthesia were excluded from the study.RESULTS:Erythrocyte membrane Na(+), K(+)-ATPase, Mg(2+)-ATPase, Ca(2+), Mg(2+)-ATPase activities were not significantly changed 60min-90min after incision as compared with 30min before anesthesia, but were decreased markedly 10min and 24 hours after completion of operation (P < 0.01). Plasma lipid peroxides (LPO) were increased significantly 24 hours after surgery (P < 0.01) following an initially marked but transient reduction. Plasma LPO changes were not correlated with erythrocyte membrane ATPase activities, r =-0.0396, -0.0097 and 0.4383, respectively (P > 0.05).CONCLUSION:Abdominal surgical trauma under intravenous procaine-balanced anesthesia may be associated with the decreased ATPase activities of erythrocyte membrane and increased LPO in plasma.