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1.
Sci Rep ; 14(1): 110, 2024 01 02.
Article in English | MEDLINE | ID: mdl-38167633

ABSTRACT

Non-alcoholic fatty liver disease is a common liver disease worldwide, and is associated with dysregulation of lipid metabolism, leading to inflammation and fibrosis. Acanthopanax senticosus Harms (ASH) is widely used in traditional medicine as an adaptogen food. We examined the effect of ASH on steatohepatitis using a high-fat diet mouse model. Mice were fed a choline-deficient, L-amino acid-defined, high-fat diet with ASH extract (ASHE). After 6 weeks, liver RNA transcriptome sequencing (RNA-Seq) was performed, followed by Ingenuity Pathway Analysis (IPA). Our findings revealed that mice fed a high-fat diet with 5% ASHE exhibited significantly reduced liver steatosis. These mice also demonstrated alleviated inflammation and reduced fibrosis in the liver. IPA of RNA-Seq indicated that hepatocyte nuclear factor 4 alpha (HNF4 alpha), a transcription factor, was the activated upstream regulator (P-value 0.00155, z score = 2.413) in the liver of ASHE-fed mice. Adenosine triphosphate binding cassette transporter 8 and carboxylesterase 2, downstream targets of HNF4 alpha pathway, were upregulated. Finally, ASHE-treated HepG2 cells exposed to palmitate exhibited significantly decreased lipid droplet contents. Our study provides that ASHE can activate HNF4 alpha pathway and promote fat secretion from hepatocytes, thereby serving as a prophylactic treatment for steatohepatitis in mice.


Subject(s)
Eleutherococcus , Non-alcoholic Fatty Liver Disease , Animals , Mice , Hepatocyte Nuclear Factor 4/genetics , Hepatocyte Nuclear Factor 4/metabolism , Eleutherococcus/chemistry , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Inflammation/pathology , Disease Models, Animal , Fibrosis , Mice, Inbred C57BL , Diet, High-Fat/adverse effects
2.
BMC Anesthesiol ; 23(1): 388, 2023 11 29.
Article in English | MEDLINE | ID: mdl-38031018

ABSTRACT

OBJECTIVES: The quantitative assessment of muscle stiffness or weakness is essential for medical care. Shear wave elastography is non-invasive ultrasound method and provides quantitative information on the elasticity of soft tissue. However, the universal velocity scale for quantification has not been developed. The aim of the study is to determine the shear wave velocities of abdominal muscle during anesthetic induction and to identify methods to cancel the effects of confounders for future development in the quantitative assessment of muscle tone using the universal scale. METHODS: We enrolled 75 adult patients undergoing elective surgery with ASA-PS I - III in the period between December 2018 and March 2021. We measured and calculated the shear wave velocity (SWV) before and after opioid administration (i.e., the baseline at rest and opioid-induced rigidity condition), and after muscle relaxant administration (i.e., zero reference condition). The SWV value was adjusted for the subcutaneous fat thickness by our proposed corrections. The SWVs after the adjustment were compared among the values in baseline, rigidity, and relaxation using one-way repeated-measures ANOVA and post hoc Tukey-Kramer test. A p-value of < 0.05 was considered to be statistically significant. UMIN Clinical Trials Registry identifier UMIN000034692, registered on October 30, 2018. RESULTS: The SWVs in the baseline, opioid-induced rigidity, and muscle relaxation conditions after the adjustment were 2.08 ± 0.48, 2.41 ± 0.60, and 1.79 ± 0.30 m/s, respectively (p < 0.001 at all comparisons). CONCLUSION: The present study suggested that the SWV as reference was 1.79 m/s and that the SWVs at rest and opioid-induced rigidity were ~ 10% and ~ 30% increase from the reference, respectively. The SWV adjusted for the subcutaneous fat thickness may be scale points for the assessment of muscle tone.


Subject(s)
Anesthetics , Elasticity Imaging Techniques , Adult , Humans , Muscle, Skeletal/physiology , Muscle Tonus , Analgesics, Opioid , Elasticity Imaging Techniques/methods
3.
J Clin Med ; 12(10)2023 May 14.
Article in English | MEDLINE | ID: mdl-37240566

ABSTRACT

Coronavirus disease 2019 (COVID-19) is associated with coagulopathy. However, the underlying mechanisms are not completely understood. We evaluated the association between COVID-19 coagulopathy and extracellular vesicle (EV) levels. We hypothesized that several EV levels would be higher in COVID-19 coagulopathy patients than in non-coagulopathy patients. This prospective observational study was conducted in four tertiary care faculties in Japan. We enrolled 99 COVID-19 patients (48 with coagulopathy and 51 without coagulopathy) aged ≥20 years who required hospitalization, and 10 healthy volunteers; we divided the patients into coagulopathy and non-coagulopathy groups according to the D-dimer levels (≥1 µg/mL and <1 µg/mL, respectively). We used flow cytometry to measure the tissue-factor-bearing, endothelium-derived, platelet-derived, monocyte-derived, and neutrophil-derived EV levels in platelet-free plasma. The EV levels were compared between the two COVID-19 groups as well as among the coagulopathy patients, non-coagulopathy patients, and healthy volunteers. No significant difference was found in EV levels between the two groups. Meanwhile, the cluster of differentiation (CD) 41 + EV levels were significantly higher in COVID-19 coagulopathy patients than in healthy volunteers (549.90 [255.05-984.65] vs. 184.3 [150.1-254.1] counts/µL, p = 0.011). Therefore, CD41+ EVs might play an essential role in COVID-19 coagulopathy development.

4.
JA Clin Rep ; 8(1): 66, 2022 Aug 22.
Article in English | MEDLINE | ID: mdl-35989409

ABSTRACT

BACKGROUND: Intraoperative motor-evoked potential (MEP) monitoring reduces postoperative motor deficits. Propofol-based total intravenous anesthesia is the gold standard for intraoperative myogenic MEPs. Although there is no contraindication to administering propofol in adults with peanut, soy, or egg allergies, its safety in children with these allergies remains unclear. CASE PRESENTATION: A 12-year-old girl required general anesthesia under intraoperative direct cortical MEP (dc-MEP) monitoring due to supratentorial glioma. Remimazolam-based anesthesia was selected, instead of propofol, due to the patient's egg hypersensitivity. Stable myogenic MEPs were recorded throughout the surgery with remimazolam at 0.9 mg/kg/h and remifentanil at 0.35 µg/kg/min, following adjustments of stimulation intensity and titration of remimazolam infusion. Neither intraoperative memory nor motor deficits were present after surgery. CONCLUSIONS: We present a pediatric case whose dc-MEP was recorded under remimazolam anesthesia. The cardiovascular stability and avoidance of propofol infusion syndrome with remimazolam were superior to propofol.

5.
J Anesth ; 36(3): 405-412, 2022 06.
Article in English | MEDLINE | ID: mdl-35471253

ABSTRACT

PURPOSE: Clear visualization of ultrasound (US) images is crucial for successful US-guided nerve block. However, accurate determination of local anesthetic (LA) distribution from US images remains difficult. Sonazoid®, which comprises perflubutane microbubbles, is used to diagnose hepatic and breast tumors. This study aimed to investigate the visibility of Sonazoid® in perioperative US-guided nerve block. METHODS: We performed rectus sheath block (RSB) in patients scheduled for laparoscopic abdominal surgery (n = 10). 10 mL of a mixture containing equal amounts of 0.75% ropivacaine and iohexol with the addition of Sonazoid® diluted 100-fold was administered. We investigated the correlation and agreement between Sonazoid® and iohexol distributions. The brightness of the solution and tissues was calculated: a grayscale value between 0 (dark) and 255 (bright) was measured in all pixels of the region of interest. Adverse events were also investigated. RESULTS: Sonazoid® was clearly visualized and distinguished from the surrounding tissues both during and after RSB. The spread of Sonazoid® and iohexol was significantly correlated (spearman's ρ = 0.53, p = 0.0004). Bland-Altman analyses revealed significant mean difference between two methods (15.6 mm; 95% confidence interval [CI]: 10.6, 20.6; standard deviation (SD) 15.65; p < 0.0001). Limits of agreement were - 14.94 to 46.24 mm. Sonazoid® significantly increased the mean grayscale values at the posterior rectus sheath (93.7 vs. 201.9, p < 0.0001). There were no complications. CONCLUSION: Sonazoid diluted 100-fold® was clearly visualized real-time, and the enhancement was sustained and measurable after RSB. Sonazoid® could potentially be used for the contrast agent of US-guided nerve block.


Subject(s)
Anesthetics, Local , Iohexol , Ferric Compounds , Humans , Iron , Oxides , Prospective Studies , Ultrasonography , Ultrasonography, Interventional/methods
6.
CNS Neurosci Ther ; 28(6): 922-931, 2022 06.
Article in English | MEDLINE | ID: mdl-35238164

ABSTRACT

AIMS: The molecular genetic mechanisms underlying postoperative nausea and vomiting (PONV) in the brain have not been fully elucidated. This study aimed to determine the changes in whole transcriptome in the nucleus of the solitary tract (NTS) in an animal model of PONV, to screen a drug candidate and to elucidate the molecular genetic mechanisms of PONV development. METHODS: Twenty-one female musk shrews were assigned into three groups: the Surgery group (shrew PONV model, n = 9), the Sham group (n = 6), and the Naïve group (n = 6). In behavioral studies, the main outcome was the number of emetic episodes. In genetic experiments, changes in the transcriptome in the NTS were measured. In a separate study, 12 shrews were used to verify the candidate mechanism underlying PONV. RESULTS: A median of six emetic episodes occurred in both the Sham and Surgery groups. Whole-transcriptome analysis indicated the inhibition of the GABAB receptor-mediated signaling pathway in the PONV model. Baclofen (GABAB receptor agonist) administration eliminated emetic behaviors in the shrew PONV model. CONCLUSIONS: Our findings suggest that the GABAB receptor-mediated signaling pathway is involved in emesis and that baclofen may be a novel therapeutic or prophylactic agent for PONV.


Subject(s)
Antiemetics , Animals , Antiemetics/therapeutic use , Baclofen/pharmacology , Baclofen/therapeutic use , Emetics , Female , Gene Expression Profiling , Postoperative Nausea and Vomiting/drug therapy , Shrews/physiology , Solitary Nucleus , Vomiting/drug therapy , Vomiting/prevention & control
7.
Biochem Biophys Res Commun ; 574: 8-13, 2021 10 15.
Article in English | MEDLINE | ID: mdl-34419875

ABSTRACT

Oxytocin is known as a social bonding hormone, but it also functions as an anxiolytic or analgesic neurotransmitter. When oxytocin regulates pain or anxiousness centrally as a neurotransmitter, it is secreted by neurons and directly projected to targeted regions. Although the function of oxytocin at the spinal level is well studied, its effects at the supraspinal level are poorly understood. We aimed to investigate the effect of oxytocin at the supraspinal level in vivo using C57BL/6J (wild-type [WT]), oxytocin-deficient (Oxt-/-), oxytocin receptor-deficient (Oxtr-/-), and oxytocin receptor-Venus (OxtrVenus/+) mice lines. Response thresholds in Oxtr-/- mice in Hargreaves and von-Frey tests were significantly lower than those in WT mice, whereas open field and light/dark tests showed no significant differences. Moreover, response thresholds in Oxt-/- mice were raised to those in WT mice after oxytocin administration. Following the Hargreaves test, we observed the co-localisation of c-fos with Venus or the oxytocin receptor in the periaqueductal gray (PAG), medial amygdala (MeA), and nucleus accumbens (NAc) regions in OxtrVenus/+ mice. Furthermore, in the PAG, MeA, and NAc regions, the co-localisation of oxytocin with c-fos and gamma-aminobutyric acid was much stronger in Oxtr-/- mice than in WT mice. However, following von-Frey test, the same findings were observed only in the MeA and NAc regions. Our results suggest that oxytocin exerts its analgesic effect on painful stimulation via the PAG region and a self-protective effect on unpleasant stimulation via the MeA and NAc regions.


Subject(s)
Central Nervous System/drug effects , Nociception/drug effects , Oxytocin/pharmacology , Animals , Central Nervous System/metabolism , Male , Mice , Mice, Inbred C57BL
8.
Genes Brain Behav ; : e12759, 2021 Jun 10.
Article in English | MEDLINE | ID: mdl-34114352

ABSTRACT

The genetic mechanisms of postoperative nausea and vomiting (PONV) and the involvement of the catecholamine system in the brain have not been elucidated. Eating kaolin clay as a type of pica has been examined as an alternative behavior to emesis. Here, we evaluated changes in whole-transcriptome analysis in the nucleus of the solitary tract (NTS) in a rat pica model as a surrogate behavior of PONV to elucidate the molecular genetic mechanisms of the development of PONV and the involvement of the catecholamine system in the NTS. First, kaolin pica behaviors were investigated in 71 female Wistar rats following isoflurane anesthesia, surgical insult or morphine administration. Multiple linear regression analysis showed that 3 mg/kg morphine increased kaolin intake by 2.8 g (P = 0.0002). Next, total RNA and protein were extracted from the dissected NTS, and whole-transcriptome sequencing (RNA-seq) was performed to identify PONV-associated genes and to verify the involvement of the catecholamine system. The gene expression levels of tyrosine hydroxylase and dopamine beta-hydroxylase in the catecholamine biosynthesis pathway decreased significantly in the PONV model. Release of noradrenaline, a catecholamine pathway end product, may have increased at the synaptic terminal of the NTS neuron after pica behavior. Systematic administration of α2 adrenergic receptor agonists after surgery reduced kaolin intake from 3.2 g (control) to 1.0 g (P = 0.0014). These results indicated that catecholamine neurotransmission was involved in the development of PONV in the NTS.

9.
Brain Sci ; 11(2)2021 Jan 22.
Article in English | MEDLINE | ID: mdl-33499207

ABSTRACT

Postoperative pain and consequent inflammatory responses after tissue incision adversely affects many surgical patients due to complicated mechanisms. In this study, we examined whether activation of protease-activated receptor 2 (PAR-2), which is stimulated by tryptase from mast cells, elicits nociception and whether the PAR-2 antagonist could reduce incisional nociceptive responses in vivo and in vitro. The effects of a selective PAR-2 antagonist, N3-methylbutyryl-N-6-aminohexanoyl-piperazine (ENMD-1068), pretreatment on pain behaviors were assessed after plantar incision in rats. The effects of a PAR-2 agonist, SLIGRL-NH2, on nociception was assessed after the injection into the hind paw. Furthermore, the responses of C-mechanosensitive nociceptors to the PAR-2 agonist were observed using an in vitro skin-nerve preparation as well. Intraplantar injection of SLIGRL-NH2 elicited spontaneous nociceptive behavior and hyperalgesia. Local administration of ENMD-1068 suppressed guarding behaviors, mechanical and heat hyperalgesia only within the first few hours after incision. SLIGRL-NH2 caused ongoing activity in 47% of C-mechanonociceptors in vitro. This study suggests that PAR-2 may support early nociception after incision by direct or indirect sensitization of C-fibers in rats. Moreover, PAR-2 may play a regulatory role in the early period of postoperative pain together with other co-factors to that contribute to postoperative pain.

10.
Biochem Biophys Res Commun ; 534: 395-400, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33246558

ABSTRACT

Chronic postsurgical pain (CPSP) is a serious issue for many postoperative patients. Though there are numerous treatment options for the prevention of CPSP, none of them is optimal as the mechanisms of the transition from acute to chronic postoperative pain have not been elucidated. Ketamine and opioids have been administered for chronic postoperative pain treatment but induce severe adverse reactions and/or physical dependency. Here, we examined whether pre-administration of the nonselective N-methyl-d-aspartate (NMDA) receptor antagonist magnesium sulfate attenuates CPSP behavior and alters the expression of glutamate ionotropic receptor NMDA type subunit 1a (Grin1 mRNA) in a rat skin/muscle incision and retraction (SMIR) model. We assessed the effects of a single subcutaneous magnesium sulfate injection on nociceptive behaviors including guarding pain, mechanical hyperalgesia, and heat hypersensitivity in rats after SMIR surgery. We used reverse transcription-quantitative PCR (RT-qPCR) to evaluate Grin1 mRNA expression in the dorsal horn of the spinal cord on postoperative day 14. Compared with the vehicle, magnesium sulfate administration before SMIR surgery reduced mechanical hyperalgesia for 17 d Grin1 gene expression was significantly higher on the ipsilateral side than the contralateral side (P = 0.001) on postoperative day 14. The magnesium sulfate injection prevented Grin1 mRNA upregulation in the spinal cord dorsal horn. A single magnesium sulfate injection mitigated SMIR-induced mechanical hyperalgesia possibly by modulating Grin1 expression. Preoperative magnesium sulfate administration could prove to be a simple and safe CPSP treatment.


Subject(s)
Analgesics/administration & dosage , Magnesium Sulfate/administration & dosage , Pain, Postoperative/prevention & control , Animals , Disease Models, Animal , Drug Administration Schedule , Gene Expression/drug effects , Hyperalgesia/genetics , Hyperalgesia/physiopathology , Hyperalgesia/prevention & control , Injections, Subcutaneous , Male , Pain, Postoperative/genetics , Pain, Postoperative/physiopathology , Preoperative Period , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/genetics , Spinal Cord/drug effects , Spinal Cord/metabolism , Up-Regulation/drug effects
11.
Anesth Prog ; 67(3): 158-163, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32992337

ABSTRACT

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders of the gastrointestinal tract including ulcerative colitis (UC) and Crohn's disease. Pain management can be challenging in patients with IBD because there are limitations on the use of analgesics. Use of nonsteroidal anti-inflammatory drugs is not recommended in patients with IBD because there is risk of relapse of IBD and an overall increase in disease activity. Opioids, although frequently used for treating severe acute pain, can have additional risks and complications in patients with IBD such as ileus, toxic megacolon, and narcotic bowel syndrome. Furthermore, little information is available in the literature on pain management in these patients undergoing noncolorectal surgery. This report describes 2 patients with UC in whom postoperative pain following oral and maxillofacial surgery was managed by intravenous patient-controlled analgesia with pentazocine. Apart from the development of acute dystonia in 1 case that was likely due to the use of droperidol for prevention of postoperative nausea and vomiting, postoperative pain was well controlled by pentazocine in both patients without any complications or UC exacerbations.


Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Humans , Pain, Postoperative , Patients
12.
Hum Genomics ; 14(1): 31, 2020 09 14.
Article in English | MEDLINE | ID: mdl-32928300

ABSTRACT

BACKGROUND: Genetic factors such as single-nucleotide polymorphisms (SNPs) play a key role in the development of postoperative nausea and vomiting (PONV). However, previous findings are not widely applicable to different populations because of population-specific genetic variation. We developed a Japanese-specific DNA microarray for high-throughput genotyping. The aim of the current study was to identify SNPs associated with PONV on a genome-wide scale using this microarray in a sample of Japanese surgical patients. METHODS: Associations between 659,636 SNPs and the incidence of PONV 24 h after surgery in a limited sample of 24 female patients were assessed using the microarray. After imputation of genotypes at 24,330,529 SNPs, 78 SNPs were found to be associated with the incidence of PONV. We chose 4 of the 78 SNPs to focus on by in silico functional annotation. Finally, we genotyped these 4 candidate SNPs in 255 patients using real-time PCR to verify association with the incidence of PONV. RESULTS: The T > C variant of rs11232965 in the long non-coding RNA MIR4300HG was significantly associated with reduced incidence of PONV among genotypes and between alleles (p = 0.01 and 0.007). CONCLUSIONS: We identified a novel SNP (rs11232965) in the long non-coding RNA MIR4300HG that is associated with PONV. The rs11232965-SNP variant (T > C) is protective against the incidence of PONV. TRIAL REGISTRATION: This study was registered at the UMIN Clinical Trials Registry (Identifier: UMIN000022903 , date of registration: June 27, 2016, retrospectively registered.


Subject(s)
Genetic Predisposition to Disease/genetics , Genome-Wide Association Study/methods , Polymorphism, Single Nucleotide , Postoperative Nausea and Vomiting/genetics , RNA, Long Noncoding/genetics , Aged , Aged, 80 and over , Alleles , Asian People/genetics , Cohort Studies , Female , Gene Frequency , Genetic Predisposition to Disease/ethnology , Genotype , Humans , Incidence , Japan/epidemiology , Male , Middle Aged , Postoperative Nausea and Vomiting/epidemiology , Postoperative Nausea and Vomiting/ethnology
13.
JA Clin Rep ; 6(1): 12, 2020 Feb 13.
Article in English | MEDLINE | ID: mdl-32056027

ABSTRACT

BACKGROUND: Wilms' tumor with hyperreninemia may result in critical cardiovascular decompensation. We report a case of severe hypertensive heart failure followed by tumor resection in a 3-month-old infant with Wilms' tumor. CASE PRESENTATION: A 3-month-old girl was admitted to the intensive care unit for Wilms' tumor with hypertension and hypoxia. Her systolic blood pressure was 110 mmHg, and her SpO2 was 92%. She presented with severe hypertensive heart failure and received mechanical ventilation and antihypertensive therapy for hypertension and heart failure. An alpha 2-adrenergic receptor agonist was used for sedation as part of her antihypertensive therapy. On hospital day 16, nephrectomy with tumor resection was performed under general anesthesia. Her systolic blood pressure did not vary more than 20 mmHg during surgery due to appropriate preoperative management. Hemodynamic collapse did not occur. CONCLUSIONS: The highlight of this case report is the successful management of an infant with Wilms' tumor, particularly with respect to preoperative hemodynamic control and sedation.

14.
BMC Anesthesiol ; 19(1): 50, 2019 04 09.
Article in English | MEDLINE | ID: mdl-30967133

ABSTRACT

BACKGROUND: Underbody blankets have recently been launched and are used by anesthesiologists for surgical patients. However, the forced-air warming effect of underbody blankets is still controversial. The aim of this study was to determine the effect of forced-air warming by an underbody blanket on body temperature in anesthetized patients. METHODS: We retrospectively analyzed 5063 surgical patients. We used propensity score matching to reduce the bias caused by a lack of randomization. After propensity score matching, the change in body temperature from before to after surgery was compared between patients who used underbody blankets (Under group) and those who used other types of warming blankets (Control group). The incidence of hypothermia (i.e., body temperature < 36.0 °C at the end of surgery) was compared between the two groups. A p value < 0.05 was considered to indicate statistical significance. RESULTS: We obtained 489 propensity score-matched pairs of patients from the two groups, of whom 33 and 63 had hypothermia in the Under and Control groups, respectively (odds ratio: 0.49, 95% confidence interval: 0.31-0.76, p = 0.0013). CONCLUSIONS: The present study suggests that the underbody blanket may help reduce the incidence of intraoperative hypothermia and may be more efficient in warming anesthetized patients compared with other types of warming blankets. TRIAL REGISTRATION: UMIN Clinical Trials Registry (Identifier: UMIN000022909 ; retrospectively registered on June 27, 2016).


Subject(s)
Bedding and Linens , Hot Temperature/therapeutic use , Hypothermia/prevention & control , Intraoperative Complications/prevention & control , Propensity Score , Adult , Aged , Anesthesia, General/adverse effects , Female , Humans , Hypothermia/etiology , Intraoperative Complications/etiology , Male , Middle Aged , Retrospective Studies
15.
Mol Med Rep ; 19(4): 3263-3272, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30816480

ABSTRACT

The impact of rare and damaging variants in genes associated with platelet function in large­vessel ischemic stroke (LVIS) remains unknown. The aim of this study was to investigate the contribution of some of these variants to the genetic susceptibility to LVIS in Polish patients using a deep re­sequencing of 54 selected genes, coding for proteins associated with altered platelet function. Targeted pooled re­sequencing (Illumina HiSeq 2500) was performed on genomic DNA of 500 cases (patients with history of clinically proven diagnosis of LVIS) and 500 age­, smoking status­, and sex­matched controls (no history of any type of stroke), and from the same population as patients with LVIS. After quality control and prioritization based on allele frequency and damaging probability, individual genotyping of all deleterious rare variants was performed in patients from the original cohort, and stratified to concomitant cardiac conditions differing between the study and stroke groups. We demonstrated a statistically significant increase in the number of rare and potentially damaging variants in some of the investigated genes in the LVIS pool (an increase in the genomic variants burden). Furthermore, we identified an association between LVIS and 6 rare functional and damaging variants in the Kv7.1 potassium channel gene (KCNQ1). The predicted functional properties (partial loss­of function) for the three most damaging variants in KCNQ1 coding locus were further confirmed in vitro by analyzing the membrane potential changes in cell lines co­transfected heterogeneously with human muscarinic type 1 receptor and wild­type or mutated KCNQ1 cDNA constructs using fluorescence imaging plate reader. The study demonstrated an increased rare variants burden for 54 genes associated with platelet function, and identified a putative role for rare damaging variants in the KCNQ1 gene on LVIS susceptibility in the Polish population.


Subject(s)
Genetic Association Studies , Genetic Predisposition to Disease , Genetic Variation , KCNQ1 Potassium Channel/genetics , Stroke/etiology , Alleles , Blood Platelets/metabolism , Case-Control Studies , Female , Gene Frequency , Genotype , Humans , Male , Open Reading Frames , Poland , Stroke/diagnosis
16.
J Pain Res ; 12: 377-385, 2019.
Article in English | MEDLINE | ID: mdl-30705603

ABSTRACT

PURPOSE: Remifentanil is associated with acute opioid tolerance that can lead to increased postoperative consumption of opioid analgesics. The purpose of this study was to determine whether a low dose of ketamine prevents remifentanil-induced acute opioid tolerance and affects the neutrophil-lymphocyte ratio (NLR), a newly recognized biomarker of inflammation. MATERIALS AND METHODS: Forty patients undergoing orthognathic surgery were enrolled in this prospective, randomized, double-blind study and randomly assigned to intraoperative administration of one of the following anesthetic regimens: high-dose remifentanil (0.6 µg/kg/minute); low-dose remifentanil (0.2 µg/kg/minute); or high-dose remifentanil with ketamine (remifentanil 0.6 µg/kg/minute with 0.5 mg/kg ketamine just after induction followed by an intraoperative infusion of ketamine 5 µg/kg/minute until wound closure). Fentanyl by intravenous patient-controlled analgesia was used for postoperative pain control. Visual Analog Scale pain scores and fentanyl consumption were recorded in the first 24 hours postoperatively. Perioperative serum C-reactive protein level and NLR were also determined. RESULTS: Baseline characteristics were similar in the three study groups. There were no between-group differences in Visual Analog Scale pain scores during the study period. The high-dose remifentanil group had a significantly higher requirement for fentanyl than the other two groups. Addition of ketamine did not affect the C-reactive protein level but increased the NLR; this increase was associated with decreased fentanyl consumption. CONCLUSION: High-dose intraoperative remifentanil induced postoperative acute opioid tolerance that was prevented by infusion of low-dose ketamine. Ketamine increased the postoperative NLR associated with decreased fentanyl requirement for postoperative pain control.

17.
Anesth Prog ; 66(4): 211-217, 2019.
Article in English | MEDLINE | ID: mdl-31891291

ABSTRACT

Epistaxis is one of the most common complications of nasotracheal intubation and can be life-threatening. However, there is little discussion in the current literature on the acute management of massive epistaxis after nasotracheal extubation. This is a report of 2 patients who experienced severe unanticipated nasal bleeding immediately after extubation, 1 after a surgical procedure for oral cancer and another after restorative dental treatment. In both cases the significant epistaxis was managed successfully with a Foley balloon catheter used to pack the posterior nasal cavity. The Foley catheter technique may be useful for managing and arresting sudden postextubation epistaxis.


Subject(s)
Airway Extubation , Epistaxis , Laryngoscopes , Adult , Aged , Airway Extubation/adverse effects , Dental Restoration Repair , Epistaxis/etiology , Epistaxis/therapy , Female , Humans , Intubation, Intratracheal , Male , Mouth Neoplasms/surgery , Nasal Cavity
18.
Int J Mol Sci ; 18(12)2017 Dec 11.
Article in English | MEDLINE | ID: mdl-29232918

ABSTRACT

The contribution of low-frequency and damaging genetic variants associated with platelet function to ischemic stroke (IS) susceptibility remains unknown. We employed a deep re-sequencing approach in Polish patients in order to investigate the contribution of rare variants (minor allele frequency, MAF < 1%) to the IS genetic susceptibility in this population. The genes selected for re-sequencing consisted of 26 genes coding for proteins associated with the surface membrane of platelets. Targeted pooled re-sequencing (Illumina HiSeq 2500) was performed on genomic DNA of 500 cases (patients with history of clinically proven diagnosis of large-vessel IS) and 500 controls. After quality control and prioritization based on allele frequency and damaging probability, follow-up individual genotyping of deleterious rare variants was performed in patients from the original cohort. Gene-based analyses identified an association between IS and 6 rare functional and damaging variants in the purinergic genes (P2RY1 and P2RY12 locus). The predicted properties of the most damaging rare variants in P2RY1 and P2RY12 were confirmed by using mouse fibroblast cell cultures transfected with plasmid constructs containing cDNA of mutated variants (FLIPR on FlexStation3). This study identified a putative role for rare variants in P2RY1 and P2RY12 genes involved in platelet reactivity on large-vessel IS susceptibility in a Polish population.


Subject(s)
Brain Ischemia/complications , Genetic Association Studies/methods , Polymorphism, Single Nucleotide , Receptors, Purinergic P2Y12/genetics , Receptors, Purinergic P2Y1/genetics , Stroke/genetics , Animals , Brain Ischemia/genetics , Cell Line , Female , Gene Frequency , Genetic Predisposition to Disease , High-Throughput Nucleotide Sequencing , Humans , Male , Mice , Poland , Sequence Analysis, DNA , Sequence Deletion
19.
J Clin Monit Comput ; 31(1): 117-122, 2017 Feb.
Article in English | MEDLINE | ID: mdl-26661716

ABSTRACT

Bispectral index (BIS) and auditory evoked potential (AEP) monitoring require the attachment of forehead sensors, posing difficulties when the surgical field involves the forehead. This study analyzed the relationship between BIS values and AEP indices from different sites on the head to establish alternative sensor locations for AEP recording. Thirty patients scheduled for elective surgery under sevoflurane anesthesia were randomly assigned to the forehead, nose or mandible groups (n = 10 patients per group). AEP sensors were placed at the assigned position for each group and BIS sensors were placed on the forehead. BIS value and AEP index were simultaneously recorded from induction until emergence from general anesthesia. Relationships between BIS values and AEP indices were analyzed using a regression method and compared between groups using Pearson's correlation coefficients. Square regression models better expressed the relationships than linear models in all groups. The z-transformed coefficient in the forehead group was the same as the nose group (p = 0.24) and significantly different in the mandible group (p = 0.0046). These findings suggest that AEPs can be accurately recorded from sensors placed on the nose. Nasal AEP might be useful for monitoring electrical activity in the brain during surgeries involving the forehead.


Subject(s)
Electroencephalography/methods , Evoked Potentials, Auditory , Monitoring, Intraoperative/methods , Monitoring, Physiologic/methods , Adult , Aged , Anesthesia/methods , Female , Forehead , Humans , Linear Models , Male , Mandible , Methyl Ethers/administration & dosage , Middle Aged , Nose , Regression Analysis , Sevoflurane
20.
Platelets ; 28(1): 66-73, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27533483

ABSTRACT

Platelets are critically involved in the development of cerebral ischemia. Our study aimed to establish an association between frequent (minor allele frequency (MAF) > 5%) genetic polymorphisms in 84 candidate genetic loci previously linked to platelet reactivity by the use of next-generation sequencing of exons from pooled DNA samples in Polish patients with a history of large-vessel ischemic stroke. Genetic analysis was performed on blood samples obtained from 500 patients (diagnosed with acute non-cardioembolic ischemic stroke with coexisting large-artery atherosclerosis) and age/sex/history of smoking matching 500 controls of Polish origin with high risk of cardiovascular disease. Sequencing of 10 pools (five for each ischemic and control groups) was performed on the Ilumina HiSeq2500 sequencer which generated an average of 36.1 (22.7-45.9 range) million pair-end 101 bp reads and 5.3 (3-7 range) Gbp per pooled sample consisting of 100 subjects. In total, we observed 789 frequent polymorphisms in the sequenced 84 genes (703 of single-nucleotide polymorphism (SNP) type and 86 indels). When the MAF between control and stroke groups was compared, only two intronic polymorphisms (1 SNP and 1 indel) in RGS7 (rs127445 36) and ANKS1B (rs398098426) genes, respectively, show statistically significant differences, which persisted after individual genotyping of the variants and adjustment for potential confounding factors. From the remaining variants, 35 polymorphisms displayed various degrees of nominal significance (from 0.6.3 × 10-5 to 5 × 10-2) and 754 polymorphisms did not show any statistical significance when comparison was evaluated for differences in MAF between the study groups. In conclusion, the results of the study demonstrate statistically significant differences in two frequent intronic genetic variants (in RGS7 and ANKS1B) that could be associated with the platelet function between ischemic stroke patients with coexisting large-vessel atherosclerosis and control patients having high vascular risk.


Subject(s)
Brain Ischemia/complications , Brain Ischemia/genetics , Gene Frequency , Genetic Predisposition to Disease , Genetic Variation , Platelet Activation/genetics , Stroke/etiology , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Female , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Odds Ratio , Poland/epidemiology , Polymorphism, Single Nucleotide , Risk Factors , Stroke/epidemiology
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