Determination of Acetylamantadine by γ-Cyclodextrin-Assisted α-HL Nanopore for Potential Cancer Prediagnosis.

The high expression of Spermidine/spermine N1-acetyltransferase (SSAT-1) is an important indicator in early cancer diagnosis. Here, we developed a nanopore-based methodology with γ-cyclodextrin as an adaptor to detect and quantify acetylamantadine, the specific SSAT-1-catalyzed product from amantadine, to accordingly reflect the activity of SSAT-1. We employ γ-cyclodextrin and report that amantadine cannot cause any secondary signals in γ-cyclodextrin-assisted α-HL nanopore, while its acetylation product, acetylamantadine, does. This allows γ-cyclodextrin to practically detect acetylamantadine in the interference of excessive amantadine, superior to the previously reported ß-cyclodextrin. The quantification of acetylamantadine was not interfered with even a 50-fold amantadine and displayed no interference in artificial urine sample analysis, which indicates the good feasibility of this nanopore-based methodology in painless cancer prediagnosis. In addition, the discrimination mechanism is also explored by 2-D nuclear magnetic resonance (NMR) and nanopore experiments with a series of adamantane derivatives with different hydrophilic and hydrophobic groups. We found that both the hydrophobic region matching effect and hydrophilic interactions play a synergistic effect in forming a host-guest complex to further generate the characteristic signals, which may provide insights for the subsequent design and study of drug-cyclodextrin complexes.

Synthesis of Nanosized γ-Cyclodextrin Metal-Organic Frameworks as Carriers of Limonene for Fresh-Cut Fruit Preservation Based on Polycaprolactone Nanofibers.

To address the issue of bacterial growth on fresh-cut fruits, this paper reports the synthesis of nanosized γ-cyclodextrin metal-organic frameworks (CD-MOFs) using an ultrasound-assisted method and their application as carriers of limonene for antibacterial active packaging. The effects of the processing parameters on the morphology and crystallinity of the CD-MOFs are investigated, and the results prove that the addition of methanol is the key to producing nanosized CD-MOFs. The limonene loading content of the nanosized CD-MOFs can reach approximately 170 mg g-1. The sustained-release behaviors of limonene in the CD-MOFs are evaluated. Molecular docking simulations reveal the distribution and binding sites of limonene in the CD-MOFs. CD-MOFs are deposited on the surfaces of polycaprolactone (PCL) nanofibers via an immersion method, and limonene-loaded CD-MOF@PCL nanofibers are prepared. The morphology, crystallinity, thermal stability, mechanical properties, and antibacterial activity of the nanofibers are also studied. The nanofiber film effectively inhibits bacterial growth and prolongs the shelf life of fresh-cut apples. This study provides a novel strategy for developing antibacterial active packaging materials based on CD-MOFs and PCL nanofibers.

CD-MOF-1 Growth on Polysaccharide Gels through Only C2-OH/C3-OH or C5-O/C6-OH Group Formed Four-Coordinated K+ Ions for Developing Porous Biogels.

The γ-cyclodextrin (γ-CD) metal-organic frameworks (CD-MOF-1) consist of γ-CD and potassium (K+) ions through coordinating an eight-coordinated K+ ion with two C5-linked oxygen and C6-linked hydroxyl (C5-O/C6-OH) groups in the primary faces of adjacent γ-CD units and two C2- and C3-linked hydroxyl (C2-OH/C3-OH) groups in the secondary faces. Herein, we found polysaccharide gels with only C2-OH/C3-OH or C5-O/C6-OH groups in pyranoid rings can form four-coordinated K+ ions and then coordinate γ-CD in a KOH solution for CD-MOF-1 growth. Exposure of C2-OH/C3-OH or C5-O/C6-OH groups in polysaccharide gels is important to form active four-coordinated K+ ions. Mechanism supporting this work is that four-coordinated K+ ion sites are first formed after coordinating C2-OH/C3-OH groups in pectin and then coordinating C5-O/C6-OH groups in the primary faces of γ-CD units. Alternatively, four-coordinated K+ ions with C5-O/C6-OH groups in chitosan can coordinate the C2-OH/C3-OH groups in the secondary faces of γ-CD units. Mechanism of CD-MOF-1 growing on pectin and chitosan gels through the proposed four-coordinated K+ ions is also universally applicable to other polysaccharide gels with similar C2-OH/C3-OH or C5-O/C6-OH groups such as alginate gel. Based on this mechanism, we developed pectin and chitosan gel-based CD-MOF-1 composites and exemplified applications of them in antibacterial and organic dye removal. To help future research and applications of this mechanism, we share our theoretical assumption for further investigations that any matrices with an ortho-hydroxyl carbon chain or ortho-hydroxyl ether structures may form four-coordinated K+ ions for CD-MOF-1 growth. The proposed mechanism will broaden the development of novel CD-MOF-1 composites in various fields.

Phase III clinical trial comparing the efficacy and safety of adamgammadex with sugammadex for reversal of rocuronium-induced neuromuscular block.

BACKGROUND: Preliminary clinical trials of adamgammadex, a new cyclodextrin-based selective reversal agent, have demonstrated its efficacy in reversing neuromuscular block by rocuronium. METHODS: This multicentre, randomised, double-blind, positive-controlled, non-inferiority phase III clinical trial compared the efficacy and safety of adamgammadex and sugammadex. We randomised 310 subjects to receive adamgammadex (4 mg kg-1) or sugammadex (2 mg kg-1) at reappearance of the second twitch of the train-of-four (TOF), and standard safety data were collected. RESULTS: For the primary outcome, the proportion of patients with TOF ratio ≥0.9 within 5 min was 98.7% in the adamgammadex group vs 100% in the sugammadex group, with a point estimate and 95% confidence interval (CI) of 1.3% (-4.6%, +1.3%); the lower limit was greater than the non-inferiority margin of -10%. For the key secondary outcome, the median (inter quartile range) time from the start of administration of adamgammadex or sugammadex to recovery of TOF ratio to 0.9 was 2.25 (1.75, 2.75) min and 1.75 (1.50, 2.00) min, respectively. The difference was 0.50 (95% CI: 0.25, 0.50); the upper limit was lower than the non-inferiority margin of 5 min. In addition, there were no inferior results observed in secondary outcomes. Adamgammadex had a lower incidence of adverse drug reactions compared with sugammadex (anaphylactic reaction, recurarisation, decreased heart rate, and laryngospasm; P=0.047). CONCLUSIONS: Adamgammadex was non-inferior to sugammadex with a possible lower incidence of adverse drug reactions compared with sugammadex. Adamgammadex may have a potential advantage in terms of its overall risk-benefit profile. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000039525. Registered October 30, 2020. https://www.chictr.org.cn/showproj.html?proj=56825.

Analysis of the factors contributing to residual weakness after sugammadex administration in pediatric patients under 2 years of age.

BACKGROUND: Sugammadex reverses the neuromuscular blockade induced by rocuronium and vecuronium and is approved by the U.S. Food and Drug Administration for use in patients aged over 2 years. There is, however, a paucity of data regarding its dosing profile in infants and children younger than 2 years. AIMS: The aim of this study was to assess the risk of recurarization, or re-paralysis, in children under 2 years of age to increase awareness on the importance of appropriate neuromuscular blocked monitoring and reversal. METHODS: All patients aged ≤24 months who underwent an operative procedure at a tertiary medical center between January 1, 2018, and December 31, 2021, and received both rocuronium for neuromuscular blockade and sugammadex for neuromuscular blockade reversal, were identified in the electronic medical record. Patients were excluded from analysis if they (1) received vecuronium, cisatracurium, atracurium, or succinylcholine for neuromuscular blockade, (2) received neostigmine for reversal, or (3) underwent more than one operation within 24 h. We performed a survival analysis of sugammadex redose using a Cox proportional hazards model. RESULTS: We reviewed 2923 records. Sugammadex was redosed in 123 (4.2%) cases. The median [IQR] time to redose was 7 [4-17] min, and the median [IQR] amount of redose administered was 2.74 [1.96-3.99] mg/kg. Increasing patient age (p < .01) and weight (p < .01) were associated with reduced hazard rate of sugammadex redose. For a patient of median weight, increasing age from 3 to 13 months was associated with a 53% risk reduction (HR: 0.47; 95% CI: 0.24-0.91). For a patient of median age, increasing weight from 4.7 to 9.2 kg was associated with 41% risk reduction (HR: 0.59; 95% CI: 0.32-1.07). We failed to detect any other associations. CONCLUSIONS: In this single-center, retrospective cohort study of pediatric surgery patients, there was an association between the hazard of sugammadex redose with both increased age and weight.

Synthesis of γ-Cyclodextrin-Reduced Fe(III) Nanoparticles with Peroxidase-like Catalytic Activity for Bacteriostasis of Food.

Foodborne pathogens are a primary cause of human foodborne illness, making it imperative to explore novel antibacterial strategies for their control. In this study, Fe-γ-CD was successfully synthesized as a food antibacterial agent for use in milk and orange juice. The Fe-γ-CD consists of 6/11 Fe(II) and 5/11 Fe(III), which catalyze a Fenton-like catalytic reaction with H2O2 to generate •OH. Consequently, Fe-γ-CD exhibits exceptional peroxidase-like activity and broad-spectrum antibacterial efficacy. Fe-γ-CD not only disrupts the wall structure of ESBL-E. coli but also induces protein leakage and genetic destruction, ultimately leading to its death. Furthermore, Fe-γ-CD inhibits biofilm formation by MRSA and eradicates mature biofilms, resulting in MRSA's demise. Importantly, Fe-γ-CD demonstrates negligible cytotoxicity toward normal mammalian cells, making it an ideal candidate for application as an antibacterial agent in foodstuffs. These findings highlight that Fe-γ-CD is an effective tool for combating the spread of foodborne pathogens and food safety.

Chiral Selectivities of Permethylated α-, ß-, and γ-Cyclodextrins Containing Gas Chromatographic Stationary Phases towards Ibuprofen and Its Derivatives.

Ibuprofen is a well-known and broadly used, nonsteroidal anti-inflammatory and painkiller medicine. Ibuprofen is a chiral compound, and its two isomers have different biological effects, therefore, their chiral separation is necessary. Ibuprofen and its derivatives were used as model compounds to establish transportable structure chiral selectivity relationships. Chiral selectors were permethylated α-, ß-, and γ-cyclodextrins containing gas chromatographic stationary phases. The chiral selectivity of ibuprofen as a free acid and its various alkyl esters (methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and isoamyl esters) derivatives were tested at different temperatures. Every tested stationary phase was capable of the chiral separations of ibuprofen in its free acid form. The less strong included S optical isomers eluted before R optical isomers in every separate case. The results offer to draw transportable guidelines for the chiral selectivity vs. analyte structures. It was recognized that the S isomers of free ibuprofen acid showed an overloading phenomenon, but the R isomer did not. The results were supported by molecular modeling studies.

In Vitro Superparamagnetic Hyperthermia Employing Magnetite Gamma-Cyclodextrin Nanobioconjugates for Human Squamous Skin Carcinoma Therapy.

In vitro alternative therapy of human epidermoid squamous carcinoma (A431) by superparamagnetic hyperthermia (SPMHT) using Fe3O4 (magnetite) superparamagnetic nanoparticles (SPIONs) with an average diameter of 15.8 nm, bioconjugated with hydroxypropyl gamma-cyclodextrins (HP-γ-CDs) by means of polyacrylic acid (PAA) biopolymer, is presented in this paper. The therapy was carried out at a temperature of 43 °C for 30 min using the concentrations of Fe3O4 ferrimagnetic nanoparticles from nanobioconjugates of 1, 5, and 10 mg/mL nanoparticles in cell suspension, which were previously found by us to be non-toxic for healthy cells (cell viabilities close to 100%), according to ISO standards (cell viability must be greater than 70%). The temperature for the in vitro therapy was obtained by the safe application (without exceeding the biological limit and cellular damage) of an alternating magnetic field with a frequency of 312.4 kHz and amplitudes of 168, 208, and 370 G, depending on the concentration of the magnetic nanoparticles. The optimal concentration of magnetic nanoparticles in suspension was found experimentally. The results obtained after the treatment show its high effectiveness in destroying the A431 tumor cells, up to 83%, with the possibility of increasing even more, which demonstrates the viability of the SPMHT method with Fe3O4-PAA-(HP-γ-CDs) nanobioconjugates for human squamous cancer therapy.

Sugammadex for reversal of moderate-to-deep rocuronium block in a clinical setting: A retrospective report of 10 dogs.

OBJECTIVE: To compare recovery times of sugammadex with spontaneous recovery from rocuronium-induced neuromuscular block (NMB) in dogs. STUDY DESIGN: Retrospective, unmatchedcase-control study. ANIMALS: A total of 10 dogs administered sugammadex and 10 dogs recovering spontaneously from rocuronium-induced NMB. METHODS: Files of dogs administered rocuronium between March and August 2023 were inspected. The train-of-four (TOF) count at the time of sugammadex administration and the time between administration and TOF ratio >90% (recovery time) were recorded. The recovery time for those not administered reversal agents was considered from the first TOF value >0 until TOF ratio >90%. The dose of sugammadex and the cumulative dose of rocuronium were recorded. Rocuronium doses and recovery times were compared using Mann-Whitney tests. The coefficient of determination (R2) between the cumulative rocuronium dose and sugammadex dose and the recovery time were calculated. RESULTS: Dogs in the sugammadex and spontaneous recovery groups were administered intravenously (IV) 0.76 (0.4-2.6) and 0.61 (0.3-2.9) mg kg-1 of rocuronium, respectively (p = 0.325). Recovery time after 3.9 (2.9-5.5) mg kg-1 of sugammadex IV was 1 (1-3) minutes and was 20 (10-35) min for spontaneous recovery (p < 0.0001). The R2 for rocuronium and sugammadex doses and recovery times were 0.19 (p = 0.2) and 0.012 (p = 0.758). CONCLUSIONS AND CLINICAL RELEVANCE: Sugammadex 2.9-5.5 mg kg-1 reversed moderate (TOF count 1-3) or deep (TOF count 0) rocuronium-induced NMB within 3 minutes, substantially faster than spontaneous recovery.

Effect of cinnamon essential oil/γ-cyclodextrin inclusion complex on papaya quality and shelf-life.

BACKGROUND: Papaya, a highly nutritious and economically significant fruit, is susceptible to infections caused by phytopathogenic fungi. Cinnamon essential oil, derived from Cinnamomum cassia (CC), shows promise in preserving papaya due to its antifungal properties. However, CC is volatile, sensitive to environmental factors, and carries a strong aroma. γ-Cyclodextrin (γ-CD) is known for encapsulating hydrophilic molecules, shielding them from environmental influences, reducing odor, and enabling controlled release due to its unique channel structure. This study aimed to tackle these challenges by preparing and characterizing an inclusion complex of CC with γ-CD (CC-γ-CD), and subsequently evaluating its efficacy in preserving papaya fruits. RESULTS: Analyses, including Fourier-infrared, powder X-ray diffraction, thermal gravity analysis, differential scanning calorimeter, and scanning electron microscopy, revealed successful encapsulation of CC components within the γ-CD cavity. Evaluations of the CC-γ-CD complex's impact on papaya fruit shelf life and quality showed notable enhancements. Fruits treated with CC-γ-CD inclusion complex at a dose of 10 g kg-1 exhibited a 55% extension in shelf-life, evidenced by reduced disease severity index compared with untreated fruit in the same storage conditions. Detailed physicochemical and bromatological assessments highlighted significant improvements, particularly in fruit treated with CC-γ-CD inclusion complex at a dose of 10 g kg-1. CONCLUSION: The application of CC-γ-CD inclusion complex at 10 g kg-1 extended the shelf-life of papaya fruit, significantly and markedly improved the overall quality. These findings underscore the potential of the CC-γ-CD inclusion complex as an effective preservative for papaya, offering a promising solution for its postharvest management and marketability. © 2024 Society of Chemical Industry.

Enhanced Stability and Solidification of Volatile Eugenol by Cyclodextrin-Metal Organic Framework for Nasal Powder Delivery.

Eugenol (Eug) holds potential as a treatment for bacterial rhinosinusitis by nasal powder drug delivery. To stabilization and solidification of volatile Eug, herein, nasal inhalable γ-cyclodextrin metal-organic framework (γ-CD-MOF) was investigated as a carrier by gas-solid adsorption method. The results showed that the particle size of Eug loaded by γ-CD-MOF (Eug@γ-CD-MOF) distributed in the range of 10-150 µm well. In comparison to γ-CD and ß-CD-MOF, γ-CD-MOF has higher thermal stability to Eug. And the intermolecular interactions between Eug and the carriers were verified by characterizations and molecular docking. Based on the bionic human nasal cavity model, Eug@γ-CD-MOF had a high deposition distribution (90.07 ± 1.58%). Compared with free Eug, the retention time Eug@γ-CD-MOF in the nasal cavity was prolonged from 5 min to 60 min. In addition, the cell viability showed that Eug@γ-CD-MOF (Eug content range 3.125-200 µg/mL) was non-cytotoxic. And the encapsulation of γ-CD-MOF could not reduce the bacteriostatic effect of Eug. Therefore, the biocompatible γ-CD-MOF could be a potential and valuable carrier for nasal drug delivery to realize solidification and nasal therapeutic effects of volatile oils.

Sugammadex and oral contraceptives.

PURPOSE OF REVIEW: This review article explores the evidence regarding sugammadex (MSD Australia) and its potential interaction with hormonal contraceptives. The impact of recent clinical trials and review articles is examined. RECENT FINDINGS: Recent clinical data suggest that the interaction between sugammadex and estrogen and progesterone concentrations may not be clinically significant and may confer some protection against ovulation. There are no clinical trials reporting interactions between sugammadex and the exogenous hormonal compounds found in oral contraceptive pills. The method of contraception is an important consideration, as sugammadex theoretically affects oral and nonoral, and combined versus single agent methods differently. Two large retrospective database studies have reported two cases of pregnancy postoperatively in patients on hormonal contraceptives whose anesthetic included sugammadex. SUMMARY: Strong clinical evidence to support or refute claims of a significant impact of sugammadex on contraceptive efficacy in women on contraception is lacking. The existing evidence does not suggest a basis for concern regarding the impact of sugammadex on contraception in the perioperative setting.

Removal of fluorouracil from aqueous environment using magnetite graphene oxide modified with γ-cyclodextrin.

Fluorouracil (FU) is a widely utilized antineoplastic medication in the pharmaceutical industry for combating gastrointestinal cancers. However, its presence in wastewater originating from pharmaceutical facilities and hospital effluents has a potential effect on DNA, and cannot be efficiently eliminated through conventional treatment methods. Consequently, the adoption of advanced technologies becomes crucial for effectively treating such wastewater. Accordingly, this study investigated the efficiency of magnetite graphene oxide nanocomposite functionalized with γ-cyclodextrin for removing fluorouracil from aqueous solutions. The magnetite graphene oxide nanocomposite functionalized with γ-cyclodextrin was synthesized via the hydrothermal method. Next, the effect of pH, temperature, adsorbent content, and contact time on the fluorouracil removal efficiency was explored. Ultimately, the experimental data were matched against Langmuir, Freundlich, and Temkin isotherms and Kinetic models. Accordingly, the efficiency of the absorbent used was dependent on the pH, contact time, temperature, and initial concentration of the adsorbent. The results indicated that the maximum removal efficiency for fluorouracil was achieved within the contact time of 45 min and adsorbent content of 0.020 g. In addition, the optimal pH for removing the medicine was 7. The conditions of the adsorption process followed Langmuir isotherm with correlation coefficients of 0.992 and a quasi-second kinetic model with a correlation coefficient of 0.999, with the maximum adsorption capacity of the adsorbent synthesized for the evaluated medicine estimated as 190.9 mg/g. The results showed that the magnetite graphene oxide nanocomposite functionalized with γ-cyclodextrin could be used as an effective and available adsorbent for removing fluorouracil from pharmaceutical wastewater.

Encapsulation Dynamics of Neuromuscular Blocking Drugs by Sugammadex.

BACKGROUND: The clinical actions of sugammadex have been well studied, but the detailed molecular mechanism of the drug encapsulation process has not been systematically documented. The hypothesis was that sugammadex would attract rocuronium and vecuronium via interaction with the sugammadex side-chain "tentacles," as previously suggested. METHODS: Computational molecular dynamics simulations were done to investigate docking of sugammadex with rocuronium and vecuronium. To validate these methods, strength of binding was assessed between sugammadex and a heterogeneous group of nine other drugs, the binding affinities of which have been experimentally determined. These observations hinted that high concentrations of unbound sugammadex could bind to propofol, potentially altering its pharmacokinetic profile. This was tested experimentally in in vitro cortical slices. RESULTS: Sugammadex encapsulation of rocuronium involved a sequential progression down a series of metastable states. After initially binding beside the sugammadex molecule (mean ± SD center-of-mass distance = 1.17 ± 0.13 nm), rocuronium then moved to the opposite side to that hypothesized, where it optimally aligned with the 16 hydroxyl groups (distance, 0.82 ± 0.04 nm) before entering the sugammadex cavity to achieve energetically stable encapsulation by approximately 120 ns (distance, 0.35 ± 0.12 nm). Vecuronium formed fewer hydrogen bonds with sugammadex than did rocuronium; hence, it was less avidly bound. For the other molecules, the computational results showed good agreement with the available experimental data, showing a clear bilogarithmic relation between the relative binding free energy and the association constant (R2 = 0.98). Weaker binding was manifest by periodic unbinding. The brain slice results confirmed the presence of a weak propofol-sugammadex interaction. CONCLUSIONS: Computational simulations demonstrate the dynamics of neuromuscular blocking drug encapsulation by sugammadex occurring from the opposite direction to that hypothesized and also how high concentrations of unbound sugammadex can potentially weakly bind to other drugs given during general anesthesia.

A Dose-finding Study of Sugammadex for Reversal of Rocuronium in Cardiac Surgery Patients and Postoperative Monitoring for Recurrent Paralysis.

BACKGROUND: The dose of sugammadex recommended by the manufacturer for reversal of rocuronium is 2 mg/kg when the train-of-four count is 2 or more and 4 mg/kg when it is less than 2 but there is a posttetanic count of at least 1. The purpose of this dose-finding study was to titrate sugammadex to produce a train-of-four ratio 0.9 or greater at the conclusion of cardiac surgery, and to continue monitoring neuromuscular blockade in the intensive care unit to identify recurrent paralysis. The hypothesis was that many patients would require less than the recommended dose of sugammadex, but that some would require more, and that recurrent paralysis would not occur. METHODS: Neuromuscular blockade was monitored using electromyography during cardiac surgery. Administration of rocuronium was at the discretion of the anesthesia care team. During sternal closure, sugammadex was titrated in 50-mg increments every 5 min until a train-of-four ratio 0.9 or greater was obtained. Neuromuscular blockade was monitored with electromyography in the intensive care unit until sedation was discontinued before extubation or for a maximum of 7 h. RESULTS: Ninety-seven patients were evaluated. The dose of sugammadex required to achieve a train-of-four ratio of 0.9 or greater varied from 0.43 to 5.6 mg/kg. There was a statistically significant relationship between the depth of neuromuscular blockade and the sugammadex dose required for reversal, but there was a large variation in dose required at any depth of neuromuscular blockade. Eighty-four of 97 patients (87%) required less than the recommended dose, and 13 (13%) required more. Two patients required additional sugammadex administration for recurrent paralysis. CONCLUSIONS: When sugammadex was titrated to effect, the dose was usually less than the recommended dose, but it was more in some patients. Therefore, quantitative twitch monitoring is essential for ascertaining that adequate reversal has taken place after sugammadex administration. Recurrent paralysis was observed in two patients.

Safety of sugammadex for reversal of neuromuscular block: A postmarketing study based on the World Health Organization pharmacovigilance database.

AIM: Residual neuromuscular blockade is a common complication after general anaesthesia. Sugammadex can reverse the action of aminosteroid neuromuscular blockers. This study aimed to explore sugammadex safety issues in the real world and determine the spectrum of adverse reactions. METHODS: All sugammadex-related adverse events reported in VigiBase between 2010 and 2019 were classified by group queries according to the Medical Dictionary for Regulatory Activities. A disproportionality analysis of data was performed using the information component (IC); positive IC values were deemed significant. RESULTS: Overall, 16 219 410 adverse events were reported and 2032 were associated with sugammadex. The frequent reactions were recurrence of neuromuscular blockade (n = 54, IC 6.74, IC025 6.33), laryngospasm (n = 53, IC 6.05, IC025 5.64), bronchospasm (n = 119, IC 5.63, IC025 5.36) and bradycardia (n = 169, IC 5.13, IC025 4.90). Fatal cases were more likely among patients with cardiac disorders, especially those over 65 years. In addition, the common adverse drug reactions (ADRs) differed between different age groups (P < .01). ADRs were higher in the 0-17 years age group than in other age groups. The onset time of common ADRs was typically within 1 day and 68.9% occurred within half an hour after sugammadex administration. CONCLUSIONS: Anaesthesiologists should carefully monitor the anaesthesia recovery period to correct the ADRs caused by sugammadex and recommend monitoring neuromuscular function throughout the anaesthesia process. Sugammadex should be used carefully in patients with cardiovascular diseases, and electrocardiography and hemodynamic changes should be monitored after medication.

Economical synthesis of γ-cyclodextrin catalyzed by oriented cyclodextrin glycosyltransferase displayed on bacterial polyhydroxyalkanoate nanogranules.

BACKGROUND: The advantages of γ-cyclodextrin (γ-CD) include its high solubility, ability to form inclusion complexes with various poorly water-soluble molecules, and favorable toxicological profile; thus, γ-CD is an attractive functional excipient widely used in many industrial settings. Unfortunately, the high cost of γ-CD caused by the low activity and stability of γ-cyclodextrin glycosyltransferase (γ-CGTase) has hampered large-scale production and application. RESULTS: This study reports the in vivo one-step production of immobilized γ-CGTase decorated on the surface of polyhydroxyalkanoate (PHA) nanogranules by the N-terminal fusion of γ-CGTase to PHA synthase via a designed linker. The immobilized γ-CGTase-PHA nanogranules showed outstanding cyclization activity of 61.25 ± 3.94 U/mg (γ-CGTase protein) and hydrolysis activity of 36,273.99 ± 1892.49 U/mg, 44.74% and 18.83% higher than that of free γ-CGTase, respectively. The nanogranules also exhibited wider optimal pH (cyclization activity 7.0-9.0, hydrolysis activity 10.0-11.0) and temperature (55-60 °C) ranges and remarkable thermo- and pH-stability, expanding its utility to adapt to wider and more severe reaction conditions than the free enzyme. A high yield of CDs (22.73%) converted from starch and a high ratio (90.86%) of γ-CD in the catalysate were achieved at pH 9.0 and 50 °C for 10 h with 1 mmol/L K+, Ca2+, and Mg2+ added to the reaction system. Moreover, γ-CGTase-PHA beads can be used at least eight times, retaining 82.04% of its initial hydrolysis activity and 75.73% of its initial cyclization activity. CONCLUSIONS: This study provides a promising nanobiocatalyst for the cost-efficient production of γ-CD, which could greatly facilitate process control and economize the production cost.

Evaluation of a Protocol for the Management of Maintenance and Reversal of Rocuronium Block Using Neostigmine or Sugammadex.

BACKGROUND: Postoperative residual neuromuscular blockade (PRNB) is defined as an adductor pollicis train-of-four ratio (TOFR) <0.9. It is a common postoperative complication when nondepolarizing muscle relaxants are either not reversed or reversed with neostigmine. PRNB has been reported in 25% to 58% of patients who receive intermediate-acting nondepolarizing muscle relaxants, and it is associated with increased morbidity and decreased patient satisfaction. We conducted a prospective descriptive cohort study during the implementation of a practice guideline that included the selective use of sugammadex or neostigmine. The primary study aim of this pragmatic study was to estimate the incidence of PRNB at arrival to the postanesthesia care unit (PACU) when the practice guideline is followed. METHODS: We enrolled patients undergoing orthopedic or abdominal surgery requiring neuromuscular blockade. Rocuronium administration was guided by surgical requirements and based on ideal body weight, with dose reductions for women and/or age >55 years. Only qualitative monitoring was available to the anesthesia providers, and selection of sugammadex or neostigmine was guided by tactile assessments of the response to train-of-four (TOF) stimulation by a peripheral nerve stimulator. Neostigmine was administered if no fade was detected in the TOF response at the thumb. Deeper blocks were reversed with sugammadex. The prespecified primary and secondary end points were the incidence of PRNB at arrival to the PACU, defined as a normalized TOFR (nTOFR) < 0.9, and severe PRNB, defined as nTOFR <0.7 on arrival to the PACU. Anesthesia providers were blinded to all quantitative measurements made by research staff. RESULTS: Analysis included 163 patients, and 145 underwent orthopedic and 18 abdominal surgeries. Of the 163 patients, 92 (56%) were reversed with neostigmine and 71 (44%) with sugammadex. The overall incidence of PRNB at PACU arrival was 5 of 163 or 3% (95% confidence interval [CI], 1-7). The incidence of severe PRNB in PACU was 1% (95% CI, 0-4). Three of the 5 subjects with PRNB had TOFR <0.4 at time of reversal but were given neostigmine since anesthesia providers detected no fade by qualitative assessment. CONCLUSIONS: The use of a protocol that specifies rocuronium dosing and selective use of sugammadex versus neostigmine based on qualitative assessment of TOF count and fade allowed us to achieve an incidence of PRNB of 3% (95% CI, 1-7) at PACU arrival. Quantitative monitoring may be needed to further reduce this incidence.

Direct chiral separation of abscisic acid by high-performance liquid chromatography with a phenyl column and a mobile phase containing γ-cyclodextrin.

Abscisic acid (2-cis,4-trans-abscisic acid) is a plant hormone that has an asymmetric carbon atom. We tried to separate the enantiomers of native abscisic acid by HPLC using a phenyl column and a chiral mobile phase containing γ-cyclodextrin. The optimum mobile phase conditions were found to be 0.8% (w/v) γ-cyclodextrin, 4% (v/v) acetonitrile, and 20 mM phosphate buffer (pH 6.0). It was found that (R)-abscisic acid was earlier detected than (S)-abscisic acid. Since γ-cyclodextrin is hardly retained on a phenyl column, it was suggested that (R)-abscisic acid formed a more stable complex with γ-cyclodextrin than the (S)-abscisic acid. Abscisic acid in an acacia honey sample was successfully enantioseparated with the proposed method and only (S)-abscisic acid was detected. A biologically inactive 2-trans,4-trans-abscisic acid, which was prepared by irradiation of abscisic acid with a light-emitting diode lamp at 365 nm, was partially enantioseparated by the proposed method. Since the irradiation of (S)-abscisic acid-induced cis-to-trans isomerization to produce one 2-trans,4-trans-abscisic acid enantiomer, it is reasonable that racemization did not proceed during the cis-to-trans isomerization. (S)-Abscisic acid and probably (S)-2-trans,4-trans-abscisic acid were detected in a honey sample, where the peak area of (S)-abscisic acid was 7 times larger than that of (S)-2-trans,4-trans-abscisic acid.

Increased bioavailability of diosmetin-7-glucoside-γ-cyclodextrin inclusion complex compared with diosmin in Sprague-Dawley rats.

Diosmin (DSN) is found mainly in citrus fruits, and has potent antioxidant effects. This study aimed to evaluate pharmacokinetics of diosmetin-7-glucoside-γ-cyclodextrin (DIOSG-CD) inclusion complex. The area under the curve values from AUC0-24 of DIOSG-CD, prepared by reacting DSN and naringinase with γ-CD, were approximately 800-fold higher than those of DSN following their administration in Sprague-Dawley rats.