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Abstract Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.

Abstract Airway clearance is crucial for successful fiberoptic intubation. We hypothesized that tongue retraction using a McIvor blade could facilitate fiberoptic intubation. This randomized clinical trial aimed to compare intubation time and airway condition between the jaw thrust maneuver and tongue retraction with the McIvor blade during fiberoptic intubation. Ninety-four adult patients scheduled for elective surgery were randomly assigned to one of two groups. During fiberoptic intubation, airway clearance was secured by applying the jaw-thrust maneuver (J group) or by tongue retraction using the McIvor blade (M group). We assessed the total intubation time, number of attempts for tube advancement, and airway clearance at the soft palate and epiglottis levels. The total intubation time was significantly shorter in the M group than in the J group (p = 0.035). The number of attempts to advance the tube was significantly lower in the M group (p = 0.033). Airway clearance at the soft palate level was significantly better in the M group than in the J group (p = 0.027). Retracting the tongue with the McIvor blade demonstrated a better condition for fiberoptic intubation and shortened total intubation time compared with the jaw-thrust maneuver. Clinicalregistiration: CRIS; http://cris.nih.go.kr (KCT0002392) registered 28/07/2017.

Abstract Various techniques have been formulated to reduce pain and ensure early recovery after surgery, as these are major concerns among surgeons, anesthesiologists, and patients. Erector spinae plane block (ESPB), the injection of local anesthetic into the fascial plane, is a simple and novel analgesia technique widely used due to its minimal risk of complications. ESPB has been tried in various surgeries; however, no study has reported its use in colorectal surgery. This study investigated whether ESPB could promote early recovery following laparoscopic colorectal surgery (LCS) by reducing opioid consumption and pain intensity. After randomization into the ESPB or control groups, an ultrasound-guided ESPB was performed at the thoracic 10th–11th level with 40 mL of 0.25% bupivacaine or normal saline. The ESPB group used less fentanyl during the initial 24 h after surgery (P = 0.004) and experienced less pain (P

Abstract Regulatory T (Treg) cells maintain immune homeostasis by preventing abnormal or excessive immune responses. Histone deacetylase 6 (HDAC6) regulates expression of Foxp3, and thus, Treg cell differentiation; however, its role in Treg cell differentiation is unclear and somewhat controversial. Here, we investigated the role of HDAC6 in TGF-β-induced murine Treg cells. HDAC6 expression was higher in Treg cells than in other T helper cell subsets. Pharmacological inhibitors of HDAC6 selectively inhibited Treg cell differentiation and suppressive function. A specific HDAC6 inhibitor induced changes in global gene expression by Treg cells. Of these changes, genes related to cell division were prominently affected. In summary, HDAC6 plays an important role in TGF-β-induced murine Treg cell differentiation by regulating cell proliferation.

Adoptive transfer of γδ T cells is a novel immunotherapeutic approach to glioblastoma. Few recent studies have shown the efficacy of γδ T cells against glioblastoma, but no previous studies have identified the ligand–receptor interactions between γδ T cells and glioblastoma cells. Here, we identify those ligand–receptor interactions and provide a basis for using γδ T cells to treat glioblastoma. Vγ9Vδ2 T cells were generated from peripheral blood mononuclear cells of healthy donors using artificial antigen presenting cells. MICA, ULBP, PVR and Nectin-2 expression in 10 patient-derived glioblastoma (PDG) cells were analyzed. The in vitro cytokine secretion from the γδ T cells and their cytotoxicity toward the PDG cells were also analyzed. The in vivo anti-tumor effects were evaluated using a U87 orthotopic xenograft glioblastoma model. Expression of ligands and cytotoxicity of the γδ T cells varied among the PDG cells. IFN-γ and Granzyme B secretion levels were significantly higher when γδ Tcells were co-cultured with high-susceptible PDG cells than when they were co-cultured with low-susceptible PDG cells. Cytotoxicity correlated significantly with the expression levels of DNAM-1 ligands of the PDG cells. Blocking DNAM-1 resulted in a decrease in γδ T cell–mediated cytotoxicity and cytokine secretion. Intratumoral injection of γδ T cells showed anti-tumor effects in an orthotopic mouse model. Allogenic γδ T cells showed potent anti-tumor effects on glioblastoma in a DNAM-1 axis dependent manner. Our findings will facilitate the development of clinical strategies using γδ T cells for glioblastoma treatment.

Background and Objectives: Developing effective treatment outcomes for multidrug-resistant Acinetobacter baumannii (MRAB) infections, with colistin and tigecycline the current frontline therapies, is challenging, because of the risk of renal toxicity and low blood concentrations of active ingredients when administered intravenously. This study aimed to identify the effect of combination therapy using conventional antimicrobial agents that are used for treating drug-resistant bacteria and the additional synergistic effect of four probiotic culture extracts isolated from the human body and Lactobacillus preparations. Materials and Methods: The antimicrobial combination and synergistic effect of adding Lactobacillus extract against 33 strains of A. baumannii isolated from pus, urine, and other specimens submitted to the Department of Laboratory Medicine of a university hospital, located in Gyeonggi-do, Korea, was investigated over a 3-year period between January 2017 and December 2019. Results: Antimicrobial susceptibility tests on bacteria isolated in clinical practice demonstrated that 26 strains (79%) were MRAB, while multi-locus sequence typing indicated that ST191 was the predominant type (45%; n = 15). Checkerboard test results demonstrated that combination therapy using meropenem and colistin had the highest synergistic effect (fractional inhibitory concentration index = 0.5), while the time–kill assay test using Lactobacillus spp. culture extract exhibited an inhibitory effect within 1 h and complete inhibition of MRAB within 3 h. Lactobacillus paracasei exhibited the fastest antimicrobial reactivity and longest sustained antimicrobial activity. Conclusion: These findings provide useful foundational data for an appropriate combination of colistin with other antimicrobial agents for treating MRAB infection in clinical settings, and the use of various probiotic culture extracts to reduce the required dosage, and therefore toxicity of colistin.

In view of this pandemic, as of February 2020, South Korea has the second highest number of confirmed cases in the world. Herein, we report four confirmed coronavirus disease 2019 (COVID-19) cases in the early stage of the pandemic in South Korea and describe the identification, diagnosis, clinical course, and management, including one patient’s initial mild symptoms at presentation and their progression to pneumonia on day 21 of illness. Within 48 hours of hospitalization, all four patients underwent evaluation for initial laboratory parameters, COVID-19 polymerase chain reaction (PCR), and chest computed tomography (CT) findings. All four mild COVID-19 patients were discharged, and they were re-examined 14 days after discharge. Despite all four of them being asymptomatic, one patient was re-admitted after confirmation of COVID-19 through PCR viral nucleic acid detection. She could be discharged after 7 days with two subsequent negative COVID-19 PCR at 24-hour intervals. Patients with mild COVID-19 generally have normal follow-up chest CT scans after discharge, even if the early chest CT definitely indicates pneumonia. Re-hospitalized patients with COVID-19 PCR positive results after discharge were not related to her initial chest CT, lab, symptoms compared other three patients.

Background/Aims: Recent advances in understanding the genetics of pancreatic ductal adenocarcinoma (PDAC) have led to the potential for a personalized approach. Several studies have described the feasibility of generating genetic profiles of PDAC with next-generation sequencing (NGS) of samples obtained through endoscopic ultrasound-guided tissue acquisition (EUS-TA). The aim of this study was to find the best EUS-TA approach for successful NGS of PDAC. Methods: We attempted to perform NGS with tissues from 190 patients with histologically proven PDAC by endoscopic ultrasound-guided fine-needle aspiration and endoscopic ultrasound-guided fine-needle biopsy at Samsung Medical Center between November 2011 and February 2015. The medical records of these patients were retrospectively reviewed for parameters including tumor factors (size, location, and T stage), EUS-TA factors (needle gauge [G], needle type, and number of needle passes) and histologic factors (cellularity and blood contamination). The sample used for NGS was part of the EUS-TA specimen that underwent cytological and histological analysis. Results: NGS could be successfully performed in 109 patients (57.4%). In the univariate analysis, a large needle G (p=0.003) and tumor located in the body/tail (p=0.005) were associated with successful NGS. The multivariate logistic regression analysis revealed that the needle G was an independent factor of successful NGS (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; p=0.031). Conclusions: The needle G is an independent factor associated with successful NGS. This finding may suggest that the quantity of cells obtained from EUS-TA specimens is important for successful NGS.

There is an urgent need for new biomarkers that address the shortcomings of current screening methods which fail to detect a large proportion of cases with hepatocellular carcinoma (HCC) at early stage. To develop a robust, multiple‐biomarker panel based on multiple reaction monitoring–mass spectrometry with high performance in detecting early‐stage HCC within at‐risk populations. In the discovery set, 150 samples were analyzed to identify candidate biomarkers. The resulting list of candidates was tested in the training set (713 samples) to establish a multimarker panel, which was evaluated in the validation set (305 samples). We identified 385 serum HCC biomarker candidates in the discovery set and developed a multimarker panel consisting of 28 peptides that best differentiated HCC from controls. The area under the receiver operating characteristic curve of multimarker panel was significantly higher than alpha‐fetoprotein (AFP) in the training (0.976 vs. 0.804; P

Matrine is a natural compound extracted from the herb Sophora flavescens Ait which is widely used in traditional Chinese medicine for treating various diseases. Recently, matrine was reported to have antitumor effects against a variety of cancers without any obvious side effects; however, the molecular mechanisms of its antiproliferative effects on cancer are unclear. Here, we report that matrine inhibits autophagy‐mediated energy metabolism, which is necessary for pancreatic cancer growth. We found that matrine significantly reduces pancreatic cancer growth in vitro and in vivo by insufficiently maintaining mitochondrial metabolic function and energy level. We also found that either pyruvate or α‐ketoglutarate supplementation markedly rescues pancreatic cancer cell growth following matrine treatment. Inhibition of mitochondrial energy production results from matrine‐mediated autophagy inhibition by impairing the function of lysosomal protease. Matrine‐mediated autophagy inhibition requires stat3 downregulation. Furthermore, we found that the antitumor effect of matrine on pancreatic cancer growth depends on the mutation of the KRAS oncogene. Together, our data suggest that matrine can suppress the growth of KRAS‐mutant pancreatic cancer by inhibiting autophagy‐mediated energy metabolism.

All-inorganic perovskites consisting of only inorganic elements have been recently considered as highly stable semiconductors for photoactive layer of optoelectronics applications. However, the formation of high-quality thin film and trap-reduced interface has still remains an important task, which should be solved for improving the performances of all-inorganic perovskite-based photovoltaics. Here, we adopted facile method that could reduce charge-carrier recombination by depositing a passivation agent on the top surface of the CsPbBr3 all-inorganic perovskite layer. We also found that the CsPbBr3 perovskite photovoltaic prepared from surface treatment method using n-octylammonium bromide provides an improved stability in ambient environment and 1-sun illuminating condition. Therefore, the perovskite photovoltaics fabricated from our approach offered an improved power conversion efficiency of 5.44% over that of the control device without surface treatment (4.12%).

In this study, carbon nanotubes (CNTs) were used as cathodes for lithium–oxygen (Li–O2) batteries to confirm the effect of oxygen functional groups present on the CNT surface on Li–O2 battery performance. A coating technology using atomic layer deposition was introduced to remove the oxygen functional groups present on the CNT surface, and ZnO without catalytic properties was adopted as a coating material to exclude the effect of catalytic reaction. An acid treatment process (H2SO4:HNO3 = 3:1) was conducted to increase the oxygen functional groups of the existing CNTs. Therefore, it was confirmed that ZnO@CNT with reduced oxygen functional groups lowered the charging overpotential by approximately 230 mV and increased the yield of Li2O2, a discharge product, by approximately 13%. Hence, we can conclude that the ZnO@CNT is suitable as a cathode material for Li–O2 batteries.

In Korea, herbal remedies have been widely used to treat polycystic ovarian syndrome (PCOS). We report the case of a woman with obese-type PCOS who was successfully treated with Korean herbal medicine (KHM) and lifestyle management. A 23-year-old female patient was first examined at our clinic in April 2015. She had amenorrhea for the previous 9 months and presented with obesity and abnormal reproductive hormone levels. She was treated using KHM and lifestyle management. We observed her menstrual cycles and re-evaluated her hormonal levels during the treatment. After KHM therapy, her body weight decreased from 88.2 kg to 66.7 kg. Her menstrual cycles resumed regularly, and the serum levels of the hormones had normalized. No adverse effects on liver and renal functions were observed. This study indicates that KHM might be considered an option for treating women with obese-type PCOS. Further large-scale trials are needed.

Background/AimsHepatocellular carcinoma (HCC) can develop in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels. Therefore, methods that can stratify an individual’s HCC risk are needed.Methods : A simple HCC risk score was developed from 971 patients with CHB who had elevated hepatitis B virus DNA levels (>2,000 IU/mL) with normal or mildly elevated ALT levels (

Laryngospasm, an occlusion of the glottis, can occur at any time during anesthesia, and is associated with serious perioperative complications such as hypoxia, hypercabia, aspiration, bronchospasm, arrhythmia, prolonged recovery, cardiac collapse, and eventually catastrophic death. Importantly, postoperative negative pressure pulmonary edema (NPPE) is a rare, but well described life-threatening complication related to acute and chronic upper airway obstruction. Sugammadex well known for affirmatively reducing the postoperative pulmonary complications associated with residual neuromuscular blockade may have an indirect role in triggering the negative intrathoracic pressure by raising a rapid and efficacious respiratory muscle strength in acute upper airway obstruction. Herein, we report a case of postoperative NPPE following repetitive laryngospasm even after reversal of rocuronium-induced neuromuscular blockade using sugammadex.

BackgroundSore throat and hoarseness are common complications after general anesthesia with tracheal intubation. The position for patients can affect the incidence of postoperative sore throat (POST) by causing displacement of the endotracheal tube. This study investigated the prophylactic effect of dexamethasone in prone position surgeries.MethodsOne hundred-fifty patients undergoing lumbar spine surgery (18-75 yr) were randomly allocated into the normal saline group (group P, n = 50), dexamethasone 0.1 mg/kg group (group D1, n = 50) or dexamethasone 0.2 mg/kg group (group D2, n = 50). The incidence and severity of POST, hoarseness, and cough were measured using direct interview at 1, 6, and 24 h after tracheal extubation. The severity of POST, hoarseness, and cough were graded using a 4-point scale.ResultsAt 1, 6, and 24 h after extubation, the incidence of sore throat was significantly lower in group D1 (1 h; P = 0.015, 6 h; P < 0.001, 24 h; P = 0.038) and group D2 (1 h; P < 0.001, 6 h; P < 0.001, 24 h; P = 0.017) compared to group P. There were less number of patients in the groups D1 and D2 than group P suffering from moderate grade of POST at 1, 24 h after extubation. The incidence of hoarseness at 1, 6, and 24 h after extubation was significantly lower in groups D2 than group P (P < 0.001). There were no significant differences in the incidence of cough among the three groups.ConclusionsThe prophylactic use of dexamethasone 0.1 mg/kg and 0.2 mg/kg in prone surgery reduces the incidence of postoperative sore throat and dexamethasone 0.2 mg/kg decreases the incidence of hoarseness.

Inulae Flos, the flower of Inula britannica L., is used as a dietary supplement, beverage, and medicine in East Asia. In this study, we evaluated the gastroprotective effects of Inulae Flos extract (IFE) against gastric mucosal lesions induced by hydrochloric acid (HCl)/ethanol in rats and explored its potential mechanisms by measuring antioxidant enzyme activity, mucus secretion, and prostaglandin E2 (PGE2) levels. Pretreatment with IFE at doses of 100 and 300 mg/kg significantly inhibited gastric lesions in HCl/ethanol-treated rats. IFE increased the activities of superoxide dismutase and catalase and the levels of glutathione and PGE2 in gastric tissues. The administration of IFE also significantly increased the gastric wall mucus contents in HCl/ethanol-induced gastric lesions. These findings suggest that IFE has gastroprotective effects against HCl/ethanol-induced gastric lesions and exerts these effects through increased antioxidant levels and gastric mucus secretion. Inulae Flos may be a promising agent for the prevention and treatment of gastritis and gastric ulcers.

BackgroundIn laparoscopic surgical procedures, many clinicians recommend supraglottic airway devices as good alternatives to intubation. We compared the i-gel® (i-gel) and LMA Supreme® (Supreme Laryngeal Mask Airway, SLMA) airway devices during laparoscopic cholecystectomy regarding sealing pressure and respiratory parameters before, during, and after pneumoperitoneum.MethodsFollowing Institutional Review Board approval and written informed consent, 93 patients were randomly allocated into the i-gel (n = 47) or SLMA group (n = 46). Insertion time, number of insertion attempts, and fiberoptic view of glottis were recorded. Oropharyngeal leak pressure (OLP), the use of airway manipulation, peak inspiratory pressure, lung compliance, and hemodynamic parameters were measured before, during, and after pneumoperitoneum.ResultsThere were no significant differences between the two groups regarding demographic data, insertion time, fiberoptic view of glottis, and the use of airway manipulation. The gastric tube insertion time was longer in the i-gel group (20.4 ± 3.9 s) than in the SLMA group (16.7 ± 1.6 s) (P < 0.001). All devices were inserted on the first attempt, excluding one case in each group. Peak inspiratory pressure, lung compliance, and OLP changed following carbon dioxide pneumoperitoneum in each group, but there were no significant differences between the groups.ConclusionsBoth the i-gel and SLMA airway devices can be comparably used in patients who undergo laparoscopic cholecystectomy, and they offer similar performance including OLP.

BackgroundMagnesium, ropivacaine, gentamicin, and rocuronium block neuromuscular (NM) transmission by different mechanisms. Therefore, concurrent administration of these agents may induce prolonged muscle paralysis via synergistic interaction. This study investigated the efficacy and safety of NM block caused by the administration of high concentrations of magnesium in combination with ropivacaine, gentamicin, and rocuronium.MethodsEighty-three left phrenic nerve-hemidiaphragms from male SD rats (150-250 g) were hung in Krebs solution. Three consecutive single twitch tension (ST, 0.1 Hz) and one tetanic tension (TT, 50 Hz for 1.9 s) were obtained before drug application and at each new drug concentration. The concentration of MgCl2 and MgSO4 in Krebs solution was increased until an 80 to 90% reduction in ST was reached. To test the effects of combinations of NM agents, a Krebs solution was premixed with MgCl2 alone, MgCl2 and ropivacaine, or MgCl2, ropivacaine, and gentamicin. The concentration of ropivacaine, gentamicin, or rocuronium was then progressively increased until an 80 to 90% reduction in ST was reached. The effective concentrations were estimated with a probit model.ResultsThe potency of MgCl2 was greater than that of MgSO4, and pretreatment with MgCl2 increased the potency of gentamicin and rocuronium. Unexpectedly, MgCl2 did not potentiate ropivacaine, and the potency of gentamicin and rocuronium failed to show an increase when premixed with 0.5 µM ropivacaine.ConclusionsThe concomitant administration of high concentrations of magnesium and ropivacaine together with clinically relevant concentrations of gentamicin or rocuronium potentiated NM blockade but not with clinically relevant concentrations of ropivacaine.

The association between the 6-thioguanine nucleotide (6-TGN) level and clinical remission in Crohn's disease (CD) remains controversial. Thiopurine-induced leukopenia is a life-threatening complication of CD in Asians that was recently shown to strongly correlate with NUDT15 genetic variants. This study aimed to determine the relationship between thiopurine metabolite levels and therapeutic response, and to investigate the association of NUDT15, TPMT, and thiopurine metabolites with leukopenia in patients with CD. We enrolled 165 adult patients with CD undergoing thiopurine treatment. Clinical evaluation and laboratory examinations were carried out every 2-3 months. We measured thiopurine metabolites levels and genotyped NUDT15 and TPMT. During the median 12-month observational period, 95 (67.9%) patients exhibited clinical response and 45 (32.1%) did not respond to the treatment. The median 6-TGN level was significantly higher in responders than in non-responders (P < 0.001). The odds ratio of patients with a 6-TGN level ≥230 pmol/8 × 108 red blood cells for showing a clinical response was 4.63 (95% CI 1.62-11.9). NUDT15 variant types were strongly associated with developing leukopenia. Patients with NUDT15 homozygous variant genotype developed severe early leukopenia with an average reduction of 88.2% (range, 84-94%) from the baseline white blood cell count at 4 weeks. Our findings support the role of therapeutic drug monitoring in thiopurine maintenance treatment to optimize thiopurine therapy, especially, for non-responding CD patients. Thiopurine treatment should not be recommended to patients with NUDT15 homozygous variant genotype due to severe early leukopenia.

Natural orifice transluminal endoscopic surgery (NOTES) is an evolving field of minimally invasive surgery. NOTES reaches the target organ by inserting the endoscope through a natural orifice (e.g. mouth, anus, urethra, vagina) and offers advantages of less postoperative pain and lower complication rate. Since its first description in 2004, NOTES has progressed from use on animal models to humans. We experienced anesthetic care of two patients who underwent transoral NOTES under general anesthesia.

Fanconi syndrome (FS) is a rare condition that is characterized by defects in the proximal tubular function. A 48-year-old woman was admitted for evaluation of proteinuria. The patient showed normal anion gap acidosis, normoglycemic glycosuria, hypophosphatemia, and hypouricemia. Thus, her condition was compatible with FS. The M peak was found behind the beta globulin region in urine protein electrophoresis. Upon bone marrow examination, we found that 24% of cells were CD138+ plasma cells with kappa restriction. From a kidney biopsy, we found crystalline inclusions within proximal tubular epithelial cells. Thereafter, she was diagnosed with FS accompanied by multiple myeloma. The patient received chemotherapy and autologous stem cell transplantation, and obtained very good partial hematologic response. However, proximal tubular dysfunction was persistent until 1 year after autologous stem cell transplantation. In short, we report a case of FS accompanied by multiple myeloma, demonstrating crystalline inclusion in proximal tubular cells on kidney biopsy.

BackgroundThe oculocardiac reflex (OCR) can be elicited during manipulation of the orbital structures in the strabismus correction surgery. A sinus bradycardia is the most common manifestation of OCR; and cardiac dysrhythmia and asystole may also occur. Various efforts to reduce OCR have been attempted, but without coherent outcome results.MethodsSixty one children, undergoing elective strabismus surgery, were randomly allocated into 2 groups: Group K received ketamine 1.0 mg/kg; and Group M received midazolam 0.15 mg/kg for induction of anesthesia. Anesthesia was maintained with 1-1.3 MAC of sevoflurane with 50% N2O in O2. Heart rate and blood pressure were measured 30 seconds before extraocular muscle (EOM) traction and immediately after traction. The OCR was defined as a decrease in heart rate more than 20% of the baseline heart rate, following manipulating EOM. Postoperative nausea and vomiting (PONV) and emergence agitation (EA) were assessed in postanesthetic care unit (PACU).ResultsBlood pressure before tightening EOM in Group K was higher than that in Group M (P < 0.05). However Δ HR (2.7 ± 15% vs. - 0.9 ± 16%) and incidence of OCR (10.0% vs. 19.4%) after traction an EOM were not different between the two groups. The occurrence of PONV (6.7 vs. 9.7%) and EA (30.0% vs. 22.6%) were similar.ConclusionsKetamine does not reduce the incidence of OCR compared with midazolam in pediatric strabismus surgery. In addition, ketamine does not increase the incidence of PONV and EA. In conclusion, it is reliable to use ketamine in pediatric strabismus surgery.

BackgroundBupivacaine, clindamycin, and gentamicin inhibit neuromuscular (NM) conduction. When they are combined, they may synergistically reduce the effective concentration of each to the therapeutic concentration in augmenting rocuronium-induced NM block. Thus, the aim of this study was to investigate whether combinations of the three drugs, at around their therapeutic concentrations, potentiate rocuronium-induced NM block.MethodsFifty-seven left-phrenic nerve hemidiaphragms (Male S-D rats, 150-250 g) were hung in a 20-ml organ bath filled with Krebs solution. Three consecutive single-twitch tensions (0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained. A Krebs solution was premixed with concentration sets of bupivacaine and clindamycin, bupivacaine and gentamicin, or bupivacaine, clindamycin and gentamicin. Then, the concentration of rocuronium was cumulatively increased in the Krebs solution (1, 3, 5, 7, 9, 12, 14, 16, 18, and 20 µM) until an 80% to 90% reduction in single twitch was attained. The effective concentrations for each experiment were determined with the probit model.ResultsThe combinations of bupivacaine, clindamycin, and gentamicin enhanced rocuronium-induced NM block. When the three drugs were applied simultaneously, their concentrations were reduced to near-therapeutic levels in potentiating the action of rocuronium.ConclusionsBupivacaine, clindamycin, and gentamicin blocked NM conduction, and when all three drugs were applied together, they augmented rocuronium-induced NM block at their near-therapeutic concentrations. Clinicians should be aware of the cooperability in NM block between drugs that interrupt NM conduction.

BackgroundGentamicin reduces acetylcholine release and clindamycin causes end-plate ion channel blockade. Because of these reasons, two drugs show muscular relaxant effect and potentiate the action of nondepolarizing neuromuscular agents. This study was intended to evaluate the effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade and the interaction between these drugs.MethodsMale Sprague-Dawley rats' phrenic nerves and diaphragms were installed in a bath containing Krebs solution. They were divided into three study groups. The first group was pre-treated with 0.1 (n = 3), 0.2 (n = 4) or 0.5 (n = 3) mM gentamicin and the tension was measured as the concentration of rocuronium was increased. The second group was experimented by increasing gentamicin on 0.25 (n = 5), 0.5 (n = 6) or 1.0 (n = 6) mM clindamycin. The final group was pre-treated with various combinations of gentamicin and clindamycin. The drug concentration was gradually increased until single twitch tension decreased by around 80%. Effective concentration was calculated using a probit model and interaction indices derived the Loewe additivity.ResultsThe administration of gentamicin and the combination of gentamicin and clindamycin enhanced rocuronium-induced neuromuscular blockade. At 0.2 and 0.5 mM gentamicin, synergistic interactions with rocuronium were observed. Likewise, at 0.5 and 1.0 mM clindamycin, synergistic interactions with gentamicin appeared. When all three drugs were combined, in the tetanic fade, all the groups except for those administered with 0.01 mM gentamicin and 0.25 mM clindamycin showed synergistic interactions.ConclusionsThis study demonstrate that gentamicin and clindamycin potentiated rocuronium induced neuromuscular blockade. Moreover, it was found that these drugs interacted synergistically.

BackgroundPartially paralyzed patients may be placed in the risk of pharyngeal dysfunction. Bupivacaine acts as acetylcholine receptor ion channel blocker and may synergistically interact with rocuronium to augment NM blockade. Thus, this study aims to elucidate whether or not, at a therapeutic concentration, bupivacaine by itself may cause NM blockade and reduce an effective concentration of rocuronium.MethodsTwenty-two left phrenic nerve-hemidiaphragms (Male SD rats, 150-250 g) were hung in Krebs solution. Three consecutive ST, 0.1 Hz and one TT, 50 Hz for 1.9 s were obtained before drug application and at each new drug concentration. A concentration of bupivacaine in Krebs solution (n = 5) was cumulatively increased by way of 0.01, 0.1, 1, (1, 2, 3, 4, 5, 6, 7) × 10 µM. In a Krebs solution, pre-treated with bupivacaine 0 (n = 5), 0.1 (n = 5), 1.0 (n = 5), 10 (n = 2) µM, and then concentrations of rocuronium were cumulatively increased by way of 1, 3, 5, 7, 9, 12, 14, 16, 18, 20 µM. EC for each experiment were determined by a probit. The EC50's of rocuronium were compared using a Student's t-test with Bonferroni's correction. Differences were considered significant when P < 0.05.ResultsThe potency of bupivacaine for normalized TF was 11.4 (± 1.1) µM. Below 30 µM of bupivacaine, the single twitch potentiation sustained despite the development of tetanic fade and partial inhibition of PTT. Bupivacaine significantly facilitated the NM blockade induced by rocuronium.ConclusionsClinicians should be aware that bupivacaine by itself at its therapeutic concentration inhibit NM conduction and enhances rocuronium-induced muscle relaxation.