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1.
J Surg Case Rep ; 2024(5): rjae308, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38764740

RESUMEN

Postoperative pneumothorax is a well-known but relatively rare complication after laparoscopic surgery. Herein, we report a case of persistent pneumothorax after laparoscopic appendectomy. A 57-year-old male, with a history of minimally invasive esophagectomy and intrathoracic gastric tube reconstruction 5 years before, underwent a laparoscopic appendectomy. A chest X-ray taken on postoperative Day 1 revealed the development of the right pneumothorax, which took more than 3 days to resolve spontaneously. Although the mechanism of postoperative pneumothorax was unclear, it seemed likely that the air that had replaced carbon dioxide in the peritoneal cavity migrated into the thoracic cavity through the esophageal hiatus, which was not covered by the peritoneum or pleura after surgical resection. The present case, together with our previous similar case, suggests that a history of esophageal cancer surgery per se increases the risk of pneumothorax after laparoscopic surgery, probably regardless of when this was performed.

2.
AME Case Rep ; 8: 16, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38234342

RESUMEN

Background: Patients who have had laryngectomy require a thorough preoperative assessment for potential stomal stenosis, and an action plan for possible inadvertent displacement of the voice prosthesis (VP) must be considered. We report the anesthetic management of a post-laryngectomy patient undergoing lung resection surgery. The patient had both a laryngectomy and a VP in situ. Case Description: A 66-year-old man with Parkinson's disease, who had previously undergone total laryngectomy for supraglottic laryngeal cancer, had a cuffed tracheostomy tube and a VP inserted into the tracheoesophageal fistula below it. He was scheduled for segmentectomy combined with lymph node dissection under combined epidural-general anesthesia due to lung cancer in the apical segment of the right lung. Following induction of general anesthesia, instead of using a double-lumen endotracheal tube, we inserted a long spiral single-lumen tube (SLT) (6 mm inner diameter, 8.7 mm outer diameter) through the tracheostoma under the guidance of a 4 mm bronchoscope because of concerns about airway injury due to the narrowed diameter of the stoma and potential dislodgement of the VP. The tube was carefully advanced and smoothly placed into the left main bronchus, and the surgery was completed using one-lung ventilation (OLV). Conclusions: For post-total laryngectomy patients, it is important to assess the size and condition of the tracheostoma and the usage of a VP, and choose an appropriate endotracheal tube. A long spiral SLT might be an option for OLV in patients after laryngectomy with a tracheoesophageal VP.

3.
Clin Nutr ESPEN ; 58: 208-212, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38057007

RESUMEN

BACKGROUND & AIMS: The optimal nutrition intake during surgery is unknown. This study aimed to investigate the prognosis of low-dose nutrition during laparoscopic colorectal cancer surgery. METHODS: In the glucose and amino acids (GA) group, 20 patients were infused with glucose (75 g/L) and amino acids (30 g/L) at 60 mL/h and bicarbonate Ringer's solution. However, 20 patients in the control (C) group were infused with bicarbonate Ringer's solution without GA. The length of hospital stay was determined, and measurements were taken before (TI) and after (T2) the surgery under general anesthesia. RESULTS: The lengths of hospital stay were comparable between the GA (13 days) and C (16 days) groups. Ketone body levels were 294 (C group) and 33 (GA group) µmol/L at T2. Nitrogen balance was 0.32 g (GA group) and -1.60 g (C group) at T2. CONCLUSIONS: Although the lengths of hospital stay were comparable, ketone body levels, and nitrogen balance were significantly different (P < 0.01) between the two groups after surgery.


Asunto(s)
Bicarbonatos , Glucosa , Humanos , Solución de Ringer , Aminoácidos , Pronóstico , Nitrógeno , Cetonas
4.
Int J Mol Sci ; 24(24)2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38139455

RESUMEN

Patients with chronic pain are affected psychologically and socially. There are also individual differences in treatment efficacy. Insufficient research has been conducted on genetic polymorphisms that are related to individual differences in the susceptibility to chronic pain. Autoimmune disorders can lead to inflammation and chronic pain; therefore, we focused on the autoimmune-related protease-activated receptor 2 (PAR2/F2RL1) and interleukin 17A (IL-17A/IL17A) genes. PAR2 and IL-17A are associated with autoimmune diseases that lead to chronic pain, and PAR2 regulates T-helper (Th) cell activation and differentiation. We hypothesized that the PAR2 and IL-17A genes are associated with chronic pain. The present study used a case-control design to statistically examine associations between genetic polymorphisms and the vulnerability to chronic pain. The rs2243057 polymorphism of the PAR2 gene and rs3819025 polymorphism of the IL-17A gene were previously reported to be associated with pain- or autoimmune-related phenotypes. Thus, these polymorphisms were investigated in the present study. We found that both rs2243057 and rs3819025 were significantly associated with a susceptibility to chronic pain. The present findings revealed autoimmune-related genetic factors that are involved in individual differences in chronic pain, further aiding understanding of the pathomechanism that underlies chronic pain and possibly contributing to future personalized medicine.


Asunto(s)
Enfermedades Autoinmunes , Dolor Crónico , Interleucina-17 , Receptor PAR-2 , Humanos , Estudios de Casos y Controles , Dolor Crónico/genética , Predisposición Genética a la Enfermedad , Interleucina-17/genética , Polimorfismo de Nucleótido Simple , Receptor PAR-2/genética
5.
JA Clin Rep ; 9(1): 65, 2023 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-37803183

RESUMEN

BACKGROUND: We report a case in which veno-venous extracorporeal membrane oxygenation (V-V ECMO) saved the life of a patient who developed severe hypoxemia due to unusual unilateral pulmonary edema (UPE) after cardiopulmonary bypass (CPB). CASE PRESENTATION: A 69-year-old man underwent aortic valve replacement and coronary artery bypass grafting. Following uneventful weaning off CPB, he developed severe hypoxemia. The ratio of arterial oxygen tension to inspired oxygen fraction (PaO2/FiO2) decreased from 301 mmHg 5 min after CPB to 42 mmHg 90 min after CPB. A chest X-ray revealed right-sided UPE. Immediately established V-V ECMO increased PaO2/FiO2 to 170 mmHg. Re-expansion pulmonary edema (REPE) was likely, as the right lung remained collapsed during CPB following the accidental opening of the right chest cavity during graft harvesting. CONCLUSIONS: V-V ECMO was effective in improving oxygenation and saving the life of a patient who had fallen into unilateral REPE unusually developing after conventional CPB.

6.
Cancers (Basel) ; 15(19)2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37835423

RESUMEN

Considerable individual differences are widely observed in the incidence of postoperative nausea and vomiting (PONV). We conducted a genome-wide association study (GWAS) to identify potential candidate single-nucleotide polymorphisms (SNPs) that contribute to PONV by utilizing whole-genome genotyping arrays with more than 950,000 markers. The subjects were 806 patients who provided written informed consent and underwent elective surgery under general anesthesia with propofol or desflurane. The GWAS showed that two SNPs, rs2776262 and rs140703637, in the LOC100506403 and CNTN5 gene regions, respectively, were significantly associated with the frequency of nausea. In another GWAS conducted only on patients who received propofol, rs7212072 and rs12444143 SNPs in the SHISA6 and RBFOX1 gene regions, respectively, were significantly associated with the frequency of nausea as well as the rs2776262 SNP, and the rs45574836 and rs1752136 SNPs in the ATP8B3 and LOC105370198 gene regions, respectively, were significantly associated with vomiting. Among these SNPs, clinical and SNP data were available for the rs45574836 SNP in independent subjects who underwent laparoscopic gynecological surgery, and the association was replicated in these subjects. These results indicate that these SNPs could serve as markers that predict the vulnerability to PONV. Our findings may provide valuable information for achieving satisfactory prophylactic treatment for PONV.

7.
JA Clin Rep ; 9(1): 37, 2023 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-37347313

RESUMEN

BACKGROUND: Postoperative pneumothorax is a well-known but relatively rare complication after laparoscopic surgery. There has been no report describing pneumothorax that persisted for a week or more after laparoscopic surgery. Herein, we report a case of bilateral pneumothorax after laparoscopic surgery, which appears to have occurred by a different mechanism than previously described. CASE PRESENTATION: A 65-year-old male, with a past history of esophagectomy and retrosternal gastric tube reconstruction 4 months earlier, underwent a robotic-assisted inguinal hernia repair. Postoperative chest x-rays revealed the development of bilateral pneumothorax, which became worse on postoperative day (POD) 1 and took more than 9 days to resolve spontaneously. We assumed that intra-abdominal gas replaced by the air after pneumoperitoneum might have migrated into thoracic cavities through an opened esophageal hiatus or along the retrosternal route. CONCLUSIONS: Laparoscopic surgery after radical esophagectomy may be associated with an increased risk of postoperative pneumothorax.

8.
Clin Case Rep ; 11(6): e7444, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37266349

RESUMEN

In a patient with Parkinson's disease (PD) who underwent spine surgery 13 h after the last anti-Parkinson medications, negative pressure pulmonary edema from upper airway obstruction developed immediately after extubation. Although oxygenation improved with high-flow nasal cannula therapy, such complications might develop due to abrupt discontinuation of medication for PD.

9.
Int J Mol Sci ; 24(9)2023 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-37176075

RESUMEN

Remifentanil (REM) and fentanyl (FEN) are commonly used analgesics that act by activating a µ-opioid receptor (MOR). Although optimal concentrations of REM can be easily maintained during surgery, it is sometimes switched to FEN for optimal pain regulation. However, standards for this switching protocol remain unclear. Opioid anesthetic efficacy is decided in part by MOR desensitization; thus, in this study, we investigated the desensitization profiles of REM and FEN to MOR. The efficacy and potency during the 1st administration of REM or FEN in activating the MOR were almost equal. Similarly, in ß arrestin recruitment, which determines desensitization processes, they showed no significant differences. In contrast, the 2nd administration of FEN resulted in a stronger MOR desensitization potency than that of REM, whereas REM showed a higher internalization potency than FEN. These results suggest that different ß arrestin-mediated signaling caused by FEN or REM led to their distinct desensitization and internalization processes. Our three-dimensional analysis, with in silico binding of REM and FEN to MOR models, highlighted that REM and FEN bound to similar but distinct sites of MOR and led to distinct ß arrestin-mediated profiles, suggesting that distinct binding profiles to MOR may alter ß arrestin activity, which accounts for MOR desensitization and internalization.


Asunto(s)
Fentanilo , Receptores Opioides , Receptores Opioides/metabolismo , Fentanilo/farmacología , Remifentanilo/farmacología , Receptores Opioides mu/metabolismo , Analgésicos Opioides/farmacología , beta-Arrestinas/metabolismo , Morfina
10.
Int J Mol Sci ; 24(9)2023 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-37176129

RESUMEN

Sensitivity to opioids varies widely among individuals. To identify potential candidate single-nucleotide polymorphisms (SNPs) that may significantly contribute to individual differences in the minimum effective concentration (MEC) of an opioid, fentanyl, we conducted a three-stage genome-wide association study (GWAS) using whole-genome genotyping arrays in 350 patients who underwent laparoscopic-assisted colectomy. To estimate the MEC of fentanyl, plasma and effect-site concentrations of fentanyl over the 24 h postoperative period were estimated with a pharmacokinetic simulation model based on initial bolus doses and subsequent patient-controlled analgesia doses of fentanyl. Plasma and effect-site MECs of fentanyl were indicated by fentanyl concentrations, estimated immediately before each patient-controlled analgesia dose. The GWAS revealed that an intergenic SNP, rs966775, that mapped to 5p13 had significant associations with the plasma MEC averaged over the 6 h postoperative period and the effect-site MEC averaged over the 12 h postoperative period. The minor G allele of rs966775 was associated with increases in these MECs of fentanyl. The nearest protein-coding gene around this SNP was DRD1, encoding the dopamine D1 receptor. In the gene-based analysis, the association was significant for the SERP2 gene in the dominant model. Our findings provide valuable information for personalized pain treatment after laparoscopic-assisted colectomy.


Asunto(s)
Fentanilo , Laparoscopía , Humanos , Estudio de Asociación del Genoma Completo , Dolor Postoperatorio/etiología , Dolor Postoperatorio/genética , Analgésicos Opioides/uso terapéutico , Polimorfismo de Nucleótido Simple , Colectomía
11.
Neuroradiol J ; 36(5): 601-609, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37106524

RESUMEN

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) can develop after intravascular administration of iodinated contrast media. Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker for AKI that helps to detect subclinical CA-AKI. We investigated the incidence of and risk factors for clinical and subclinical CA-AKI in patients who underwent neuroendovascular surgery. METHODS: We retrospectively investigated 228 patients who underwent neuroendovascular surgery in 2020. Changes in serum creatinine and urine output were used to detect clinical CA-AKI. Urine NGAL concentration was used to detect subclinical CA-AKI in 67 out of 228 patients. RESULTS: In 228 patients, serum creatinine, hemoglobin, hematocrit, total protein, and blood urea nitrogen (BUN) decreased significantly (p < 0.001) after surgery. However, serum creatinine decreased less significantly (p < 0.05) than hemoglobin, hematocrit, total protein, and BUN on postoperative Day 3. Two patients out of 228 developed clinical CA-AKI, and seven patients out of 67 with urine NGAL measurements developed subclinical CA-AKI. Multivariate regression analysis revealed that diabetes mellitus and carotid artery stenosis were significantly (p < 0.05) associated with the development of clinical and/or subclinical CA-AKI. CONCLUSION: There was a large difference between the incidences of clinical CA-AKI (0.88%) and subclinical CA-AKI (10.4%). The difference might have primarily resulted from the different sensitivities between serum creatinine and urine NGAL and possibly from underestimation of the incidence of clinical AKI due to a postoperative decrease in serum creatinine caused by hemodilution. In addition to diabetes mellitus, carotid artery stenosis could also be a risk factor for CA-AKI.

12.
Ann Transl Med ; 11(5): 206, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-37007544

RESUMEN

Background: Recently, robot-assisted thoracic surgery has been increasingly performed for mediastinal disease. However, appropriate postoperative analgesic methods have not been evaluated. Methods: We retrospectively studied patients who underwent robot-assisted thoracic surgery for mediastinal disease at a single university hospital between January 2019 and December 2021. Patients were performed either general anesthesia alone, general anesthesia combined with thoracic epidural anesthesia, or general anesthesia combined with ultrasound-guided thoracic block. Patients were divided into three groups [non-block (NB), thoracic epidural analgesia (TEA), and thoracic paraspinal block (TB)] according to postoperative analgesic methods, and they compared with terms of postoperative pain scores by using numerical rating scale (NRS) at 0, 3, 6, 12, 18, 24, and 48 h. Additionally, rescue supplemental analgesic within 24 h, side effects of anesthesia such as respiratory depression, hypotension, postoperative nausea and vomiting, pruritus and urinary retention, time to ambulation after surgery, and hospital stay after surgery were also compared among the three groups. Results: Data from 169 patients (Group NB: 25, Group TEA: 102, and Group TB: 42) were progressed to the analysis. Postoperative pain scale at 6 and 12 h was significantly lower in Group TEA than NB (1.2±1.6 vs. 2.4±1.8, P<0.01; and 1.2±1.5 vs. 2.2±1.7, P=0.018, respectively). There were no differences in pain scores between Groups TB and TEA at any point. The incidence of patients using rescue analgesics within 24 h was significantly different between groups [Group NB: 15/25 (60%), Group TEA: 30/102 (29.4%), Group TB: 25/42 (59.5%), P=0.01]. For postoperative side effects, only the number of patients complaining of postoperative nausea and vomiting for 24 h after surgery differed significantly between groups [Group NB: 7/25 (28%), Group TEA: 19/102 (18.6%), Group TB: 1/42 (2.4%), P=0.01]. Conclusions: TEA provided better analgesia after robot-assisted thoracic surgery for mediastinal disease than NB as indicated by lower pain scores and fewer rescue analgesic requirements. However, the frequency of postoperative nausea and vomiting was lowest in Group TB of all the groups. Thus, TBs might also provide adequate postoperative analgesia following robot-assisted thoracic surgery for mediastinal disease.

13.
Heart Vessels ; 38(6): 839-848, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36692544

RESUMEN

Cerebral tissue oximetry with near-infrared spectroscopy (NIRS) is used to monitor cerebral oxygenation during cardiac surgery. To date, reduced baseline cerebral NIRS values have been attributed to reduced cerebral blood flow primarily based on a significant positive correlation between left ventricular ejection fraction (LVEF) and baseline rSO2 measured with the INVOS 5100C oximeter. Reportedly, however, rSO2, but not StO2 measured with the FORESIGHT Elite oximeter, correlated with LVEF. We, thus, investigated associations among baseline NIRS values measured with three different oximeters before anesthesia for cardiac surgery and preoperative transthoracic echocardiography (TTE) variables, including LVEF, to examine whether there are inter-device differences in associations among baseline NIRS values and TTE variables. Using Spearman's correlation coefficient, we retrospectively investigated associations among 15 preoperative TTE variables, including LVEF, and baseline NIRS values, including rSO2, StO2, and TOI with the NIRO-200NX oximeter in 1346, 515, and 301 patients, respectively. Only rSO2 (p < 0.00001), but not TOI or StO2 (p > 0.05), positively correlated with LVEF. On the other hand, baseline rSO2, TOI, and StO2 consistently, negatively correlated with the left atrial diameter index (LADI), early diastolic transmitral flow velocity (E), E-to-early diastolic mitral annular velocity ratio (E/e'), estimated right ventricular systolic pressure (eRVP), and inferior vena cava diameter index (IVCDI) (p < 0.0005 to p < 0.00001). Because all of these five TTE variables could be positively associated with right as well as left ventricular filling pressure, our results indicated that reduced baseline NIRS values were consistently associated not with reduced LVEF but with TTE findings indicative of elevated biventricular filling pressure. Our data suggest that regional venous congestion greatly contributes to reduced baseline NIRS values in patients undergoing cardiac surgery.


Asunto(s)
Anestesia , Procedimientos Quirúrgicos Cardíacos , Humanos , Espectroscopía Infrarroja Corta/métodos , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular Izquierda , Oximetría/métodos , Oxígeno , Ecocardiografía
14.
Int J Mol Sci ; 24(2)2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36674543

RESUMEN

Chronic pain is reportedly associated with the transient receptor potential canonical 3 (TRPC3) gene. The present study examined the genetic associations between the single-nucleotide polymorphisms (SNPs) of the TRPC3 gene and chronic pain. The genomic samples from 194 patients underwent linkage disequilibrium (LD) analyses of 29 SNPs within and around the vicinity of the TRPC3 gene. We examined the associations between the SNPs and the susceptibility to chronic pain by comparing the genotype distribution of 194 patients with 282 control subjects. All SNP genotype data were extracted from our previous whole-genome genotyping results. Twenty-nine SNPs were extracted, and a total of four LD blocks with 15 tag SNPs were observed within and around the TRPC3 gene. We further analyzed the associations between these tag SNPs and chronic pain. The rs11726196 SNP genotype distribution of patients was significantly different from the control subjects even after multiple-testing correction with the number of SNPs. The TT + TG genotype of rs11726196 is often carried by chronic pain patients, suggesting a causal role for the T allele. These results contribute to our understanding of the genetic risk factors for chronic pain.


Asunto(s)
Dolor Crónico , Polimorfismo de Nucleótido Simple , Canales Catiónicos TRPC , Humanos , Dolor Crónico/genética , Ligamiento Genético , Predisposición Genética a la Enfermedad , Genotipo , Desequilibrio de Ligamiento , Canales Catiónicos TRPC/genética
15.
Juntendo Iji Zasshi ; 69(5): 378-387, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38845727

RESUMEN

Objectives: To investigate the effects of interventions provided by a multidisciplinary team consisting of anesthesiologists, dentists, pharmacists, and nurses at a Preoperative Clinic (POC) on postoperative outcomes. Methods: We retrospectively investigated patients who underwent preoperative evaluation at the POC at Juntendo University Hospital between May and July, 2019. Patients were divided into intervention and non-intervention groups according to whether they received intervention(s) at the POC or not. Postoperative outcomes were compared between the groups, before and after propensity score (PS) matching. Results: We investigated 909 patients who completed POC evaluation and underwent surgery. Patients in the intervention group (n = 455 [50.1%]) received at least one intervention delivered, in the order of higher delivery frequencies, by dentists, pharmacists, nurses, and anesthesiologists. Before PS matching, the intervention group was associated with older age, more frequent cardiovascular comorbidities, and higher ASA-PS grades than the non-intervention group, while neither frequencies nor severities of postoperative complications differed between the groups. These outcomes did not differ between 382 PS-matched pairs with comparable risk factors either. Conclusions: Before PS matching, postoperative outcomes did not differ between the groups, although the intervention group was associated with higher risks. These suggested that POC interventions could have improved postoperative outcomes in the higher-risk intervention group to the same level as in the non-intervention group. However, such potential beneficial effects of interventions could not be proven after PS matching. Further studies are required to elucidate effects of POC interventions on postoperative outcomes.

16.
J Med Syst ; 46(12): 95, 2022 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-36374361

RESUMEN

To evaluate effects of the multidisciplinary preoperative clinic (POC) consisting of anesthesiologists, dentists, pharmacists, and nurses on elective surgery cancellation, we retrospectively investigated patients who underwent elective non-cardiac, non-obstetric surgeries between October, 2018 and March, 2019 (before the POC establishment: Group 1) and between October, 2019 and March, 2020 (after the POC establishment: Group 2). Among reasons for surgery cancellation allocated into eight categories, three reasons for cancellation (related to consent authorization, medication, and significant comorbidities) were considered preventable. We compared incidences of overall and preventable cancellations of surgeries between 4,198 patients in Group 1 and 4,664 patients in Group 2, who had significantly different clinical backgrounds, including the ASA-PS class. There was no significant difference in the incidence of overall cancellation between Group 1 and Group 2 (4.1% vs. 4.1%, p = 0.96). However, the incidence of preventable cancellation was significantly lower in Group 2 than in Group 1 (0.4% vs. 0.7%, p = 0.045). In addition, the incidence of overall cancellation was significantly lower in 3,741 Group 2 patients visiting the POC than in 5,121 patients not visiting the POC in both Groups (3.2% vs. 4.7%, p < 0.001). Further, in 3,423 pairs of patients with comparable clinical backgrounds created from both Groups using propensity score matching, incidences of overall cancellation (2.2% vs. 3.1%) and preventable cancellation (0.1% vs. 0.6%) were significantly lower in Group 2 than in Group 1 (p = 0.036 and 0.008, respectively). In conclusion, the multidisciplinary POC was effective in reducing elective surgery cancellation.


Asunto(s)
Citas y Horarios , Quirófanos , Humanos , Incidencia , Estudios Retrospectivos , Procedimientos Quirúrgicos Electivos
17.
Molecules ; 27(20)2022 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-36296658

RESUMEN

Opioid receptors (ORs) are classified into three types (µ, δ, and κ), and opioid analgesics are mainly mediated by µOR activation; however, their use is sometimes restricted by unfavorable effects. The selective κOR agonist nalfurafine was initially developed as an analgesic, but its indication was changed because of the narrow safety margin. The activation of ORs mainly induces two intracellular signaling pathways: a G-protein-mediated pathway and a ß-arrestin-mediated pathway. Recently, the expectations for κOR analgesics that selectively activate these pathways have increased; however, the structural properties required for the selectivity of nalfurafine are still unknown. Therefore, we evaluated the partial structures of nalfurafine that are necessary for the selectivity of these two pathways. We assayed the properties of nalfurafine and six nalfurafine analogs (SYKs) using cells stably expressing κORs. The SYKs activated κORs in a concentration-dependent manner with higher EC50 values than nalfurafine. Upon bias factor assessment, only SYK-309 (possessing the 3S-hydroxy group) showed higher selectivity of G-protein-mediated signaling activities than nalfurafine, suggesting the direction of the 3S-hydroxy group may affect the ß-arrestin-mediated pathway. In conclusion, nalfurafine analogs having a 3S-hydroxy group, such as SYK-309, could be considered G-protein-biased κOR agonists.


Asunto(s)
Analgésicos Opioides , Receptores Opioides kappa , Analgésicos , Analgésicos Opioides/farmacología , beta-Arrestinas/metabolismo , Proteínas de Unión al GTP/metabolismo , Receptores Opioides kappa/agonistas , Receptores Opioides mu/metabolismo
18.
Int J Mol Sci ; 23(17)2022 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-36077505

RESUMEN

Neuroinflammation, where inflammatory cytokines are produced in excess, contributes to the pathogenesis of delirium. Microglial cells play a central role in neuroinflammation by producing and releasing inflammatory cytokines in response to infection, tissue damage and neurodegeneration. Dexmedetomidine (DEX) is a sedative, which reduces the incidence of delirium. Thus, we hypothesized that DEX may alleviate delirium by exhibiting anti-inflammatory action on microglia. In the present study, we investigated the anti-inflammatory action of DEX on human microglial HMC3 cells. The results indicated that DEX partially suppressed the IL-6 and IL-8 production by lipopolysaccharide (LPS)-stimulated HMC3 cells as well as the phosphorylation of p38 MAPK and IκB and the translocation of NF-κB. Furthermore, DEX substantially suppressed IL-6 and IL-8 production by unstimulated HMC3 cells as wells as the phosphorylation of p38 MAPK and IκB and the translocation of NF-κB. These observations suggest that DEX exhibits anti-inflammatory action on not only LPS-stimulated but also unstimulated microglial cells via the suppression of inflammatory signaling and cytokine production.


Asunto(s)
Delirio , Dexmedetomidina , Antiinflamatorios/farmacología , Citocinas , Dexmedetomidina/farmacología , Humanos , Proteínas I-kappa B , Interleucina-6 , Interleucina-8 , Lipopolisacáridos/farmacología , Microglía , FN-kappa B , Proteínas Quinasas p38 Activadas por Mitógenos
19.
J Laparoendosc Adv Surg Tech A ; 32(12): 1260-1264, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35904967

RESUMEN

Introduction: Cerebral and renal regional oxygen saturation (C-rSO2 and R-rSO2, respectively) were monitored using near-infrared spectroscopy in pediatric patients (range: 0.3-14.3 years) during minimally invasive surgery (MIS) taking at least 3 hours performed by laparoscopy (Lap), thoracoscopy (Tho), or retroperitoneoscopy (Ret) from January 2019 to December 2021. Materials and Methods: Criteria compared were operative time, preoperative/intraoperative hemoglobin, blood loss, mean arterial pressure, arterial partial pressure of carbon dioxide (PaCO2), peripheral oxygen saturation (SpO2), C-rSO2, and R-rSO2. Pathological desaturation (PD) was defined as >20% decrease from baseline, and statistical significance as P < .05. Results: Subjects (n = 79) were similar for gender, age, and body mass index. MIS procedures were: Lap = 45, Tho = 20, Ret = 14; one Lap case required conversion for severe adhesions, not PD. Intraoperative PaCO2 (mmHg) was significantly higher in Tho (maximum: 59.5 ± 17.0, minimum: 39.9 ± 7.5) versus Lap (maximum: 39.9 ± 5.1, minimum: 34.6 ± 3.9) and Ret (maximum: 37.8 ± 4.2, minimum: 35.0 ± 3.3); P < .0001 (maximum), P = .0013 (minimum). Minimum intraoperative SpO2 was significantly lower in Tho (P < .0001). Mean operative times were significantly shorter in Tho (259 ± 114 minutes) versus Lap (433 ± 154 minutes) and Ret (342 ± 100 minutes); P < .0001, respectively. PD was absent during Ret (C-rSO2: 0/14 = 0% and R-rSO2: 0/14 = 0%). Differences in PD for Lap (C-rSO2: 7/45 = 15.6% and R-rSO2: 10/45 = 22.2%) and Tho (C-rSO2: 9/20 = 45.0%, and R-rSO2: 7/20 = 35.0%) were significant; P = .0028 for C-rSO2 and P = .0497 for R-rSO2. Hemoglobin and blood loss were similar. Conclusions: PD was absent during Ret, despite longer operative times. If Ret is indicated for a procedure, neurodevelopmental sequelae of MIS could be minimized.


Asunto(s)
Laparoscopía , Espectroscopía Infrarroja Corta , Humanos , Niño , Espectroscopía Infrarroja Corta/métodos , Oxígeno , Procedimientos Quirúrgicos Mínimamente Invasivos , Toracoscopía , Encéfalo
20.
Transl Cancer Res ; 11(4): 736-744, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35571644

RESUMEN

Background: Anesthesia with desflurane or propofol enables rapid emergence. In patients undergoing lung cancer surgery, however, the speed of emergence from desflurane, but not from propofol, may be affected by the deteriorated postoperative respiratory function. We prospectively compared the speed and quality of emergence between desflurane and propofol. Methods: We conducted a parallel study. Eighty patients scheduled for lung cancer surgery were randomly allocated to Desflurane group (Group D) and Propofol group (Group P). Combined general and epidural anesthesia was performed in the identical way except for the anesthetic. Results: There was no significant difference between the groups in the time to awakening, extubation, or orientation. However, emergence agitation (EA) occurred more frequently in Group D than in Group P (20/40 vs. 4/40, P<0.001). Numbers of patients not achieving full scores in respiration and circulation components of the modified Aldrete score 5 min after extubation were more in Group D (4/40 vs. 0/40, P=0.040; and 8/40 vs. 2/40, P=0.043, respectively). More patients required antiemetics during postoperative 24 hours in Group D (15/40 vs. 7/40, P=0.045). Conclusions: Desflurane was not inferior to propofol in the speed of emergence from anesthesia after lung cancer surgery, but it was slightly inferior to propofol in the quality of emergence. Trial Registration: UMIN-CTR identifier: UMIN000009221.

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