An approach to MOFaxanes by threading ultralong polymers through metal-organic framework microcrystals.

Mechanically interlocked architecture has inspired the fabrication of numerous molecular systems, such as rotaxanes, catenanes, molecular knots, and their polymeric analogues. However, to date, the studies in this field have only focused on the molecular-scale integrity and topology of its unique penetrating structure. Thus, the topological material design of such architectures has not been fully explored from the nano- to the macroscopic scale. Here, we propose a supramolecular interlocked system, MOFaxane, comprised of long chain molecules penetrating a microcrystal of metal-organic framework (MOF). In this study, we describe the synthesis of polypseudoMOFaxane that is one of the MOFaxane family. This has a polythreaded structure in which multiple polymer chains thread a single MOF microcrystal, forming a topological network in the bulk state. The topological crosslinking architecture is obtained by simply mixing polymers and MOFs, and displays characteristics distinct from those of conventional polyrotaxane materials, including suppression of unthreading reactions.

Effects of remifentanil on the noxiously stimulated somatosensory evoked potentials recorded at the spinal cord in dogs and cats.

This study assessed the somatosensory evoked potentials (SEPs) in dogs and cats to compare the effect of remifentanil on the action potentials evoked by peripheral noxious stimulation in the spinal cord. Five healthy dogs and five healthy cats underwent general anaesthesia induced with propofol and maintained with isoflurane. Each animals received all dosage of a constant-rate infusion of remifentanil at 0 (control), 0.25, 0.5, 1.0 or 2.0 µg/kg/min. The hair of the dorsal foot of a hind limb was clipped and an intraepidermal stimulation electrode that could selectively stimulate the nociceptive Aδ and C fibres was attached. An electrical stimulus was generated by a portable peripheral nerve testing device. The evoked potentials were recorded by two needle electrodes inserted subcutaneously in the dorsal midline between the lumbar vertebra: L3-L4 and L4-L5. Bimodal waveforms were obtained by electrical stimulation in control dogs and cats. The inhibitory effect of remifentanil was evaluated by comparing the changes in the N1P2 and P2N2 amplitudes. The N1P2 amplitude was depressed by remifentanil in a dose-dependent manner in dogs, but it showed no remifentanil-induced changes in cats. While the P2N2 amplitude was also depressed in a dose-dependent manner in dogs, it showed milder remifentanil-induced effects in cats. The N1P2 and P2N2 amplitudes observed herein are assumed to represent the evoked potentials derived from the Aδ and C fibres, respectively. Thus, the inhibitory effect of remifentanil on nociceptive transmission at the spinal cord was much weaker in cats, especially for transmissions possibly derived from Aδ fibres.

Fentanyl sparing effect of ultrasound-guided proximal radial, ulnar, median, and musculocutaneous nerve (RUMM) block for radial and ulnar fracture repair in dogs: a retrospective case-control study.

This study retrospectively evaluated the fentanyl-sparing effect of ultrasound-guided proximal radial, ulnar, median, and musculocutaneous nerve (RUMM) block for radial and ulnar fracture repair in dogs. Fentanyl was prepared for intraoperative analgesia in dogs, although proximal RUMM block was performed using 0.5% or 0.25% bupivacaine before surgery in the block group. Dogs without a nerve block were assigned to the control group. The fentanyl dose in the block group [0.8 (0-1.9) µg/kg/hr] [median (interquartile range)] was significantly lower than in the control group [8.4 (7.2-10) µg/kg/hr]. Surgery was performed without fentanyl in >50% of the dogs (5/7), using 0.5% bupivacaine. Ultrasound-guided proximal RUMM block can be useful as an intraoperative analgesic for radial and ulnar fracture repair in dogs.

Factors associated with elevated blood lactate levels in patients undergoing maintenance hemodialysis.

Factors associated with chronic elevation of the blood lactate levels in patients undergoing chronic maintenance hemodialysis (hereinafter, hemodialysis patients) have not yet been thoroughly investigated. The purpose of the present study was to clarify factors associated with elevated blood lactate levels in hemodialysis patients. We divided the hemodialysis patients into two groups according the blood lactate levels (the high blood lactate group [> 2 mmol/L] and normal blood lactate group), and conducted a retrospective comparison of the following items between the two groups: (1) the creatinine generation rate (%CGR) and the geriatric nutrition risk index (GNRI) as indices of the nutritional status; (2) the left ventricular ejection fraction (LVEF) and E/A, an indicator of diastolic function; (3) the ankle-brachial index (ABI) and transcutaneous partial pressure of oxygen as indices of the adequacy of circulation in the peripheral blood vessels of the lower extremities; (4) the white blood cell count and serum level of C-reactive protein (CRP) before dialysis as markers of an inflammatory state. The mean age and serum CRP level were significantly higher in the high blood lactate group than in the normal blood lactate group. There were no significant differences in the markers of the nutritional status, cardiac function, or adequacy of circulation in the peripheral blood vessels of the lower extremities between the two groups. Advanced age and a state of chronic inflammation appear to be associated with elevated blood lactate levels in patients undergoing chronic maintenance hemodialysis.

Toughening and stabilizing MOF crystals via polymeric guest inclusion.

Improving the mechanical properties and stability of metal-organic frameworks (MOFs) is of significant interest due to their practical applications. Herein, we tune the mechanical properties of MOFs by filling the MOF pores with polymer chains. The mechanical properties reflect the filling rate, molecular weight, and inherent flexibility of the polymeric guests, imparting MOFs with improved resilience and toughness against mechanical pressures.

Pharmacokinetics and effects on clinical and physiological parameters following a single bolus dose of propofol in common marmosets (Callithrix jacchus).

The objectives of this study were (a) to establish a population pharmacokinetic model and (b) to investigate the clinical and physiological effects of a single bolus dose of propofol in common marmosets. In Study 1, pharmacokinetic analysis was performed in six marmosets under sevoflurane anaesthesia. 8 mg/kg of propofol was administrated at a rate of 4 mg kg-1  min-1 . Blood samples were collected 2, 5, 15, 30, 60, 90, 120 or 180 min after starting propofol administration. Plasma concentration was measured, and population pharmacokinetic modelling was performed. A two-compartment model was selected as the final model. The population pharmacokinetic parameters were as follows: V1  = 1.14 L, V2  = 77.6 L, CL1  = 0.00182 L/min, CL2  = 0.0461 L/min. In Study 2, clinical and physiological parameters were assessed and recorded every 2 min after 12 mg/kg of propofol was administrated at a rate of 4 mg kg-1  min-1 . Immobilization was sustained for 5 min following propofol administration without apparent bradycardia. While combination of propofol and sevoflurane caused apnoea in Study 1, apnoea was not observed following single administration of propofol in Study 2. These data provide bases for further investigation on intravenous anaesthesia using propofol in common marmosets.

STM apparent height measurements of molecular wires with different physical length attached on 2-D phase separated templates for evaluation of single molecular conductance.

Single molecular conductance of molecular wires is effectively evaluated by the combination of STM apparent height measurement and a 2-D phase separation technique. Previously the method was only applied to a set of molecular wires with the same physical length, but herein we applied the method to thienylene-based and phenylene-based molecular wires with different physical lengths. By considering the difference in physical molecular height including thermal contribution of conformational isomers, the conductance ratio was determined to be 1.3 ± 0.7, which is in agreement with the reported value determined by a break-junction method.

Enhanced mechanical properties of a metal-organic framework by polymer insertion.

The mechanical strength of metal-organic frameworks (MOFs) is highly relevant for their practical applications. In this research, we show that encapsulation of polymer chains into MOF nanochannels can effectively restrain the breakage of coordination bonding in MOFs and inhibit the amorphization under high physical pressure. The hardness of single MOF crystals was greatly improved, which depended on the direction of the inserted polymers, as revealed by nanoindentation analysis. Insertion of polymer chains did not influence the crystal structure of MOFs, which indicates that this approach should be highly promising for improving the mechanical properties of MOFs.

Comparison of plasma propofol concentration for apnea, response to mechanical ventilation, and airway device between endotracheal tube and supraglottic airway device in Beagles.

The relationships between propofol plasma concentrations and the pharmacodynamic endpoints may differ according to a type of airway device. To clarify these relationships in different airway devices would be useful to avoid the complication such as apnea and intraoperative awareness. The aim of this study was to investigate the influence of difference of airway device on propofol requirement during maintenance of anesthesia in dogs. We compared the influence of airway devices on the plasma propofol concentrations for apnea, response to mechanical ventilation, and response to airway device between endotracheal tube (ETT) and supraglottic airway device (SGAD) in Beagles. The pharmacodynamic effects were repeatedly assessed at varying propofol concentrations. The plasma concentrations (mean ± SD) of propofol in the ETT and SGAD groups were 10.2 ± 1.8 and 10.9 ± 2.4 µg/ml for apnea (P=0.438), 7.9 ± 1.2 and 7.4 ± 1.5 µg/ml for response to mechanical ventilation (P=0.268), and 5.2 ± 0.7 and 5.4 ± 1.5 µg/ml for response to airway device (P=0.580), respectively. Required propofol concentration during maintenance of anesthesia may be similar between ETT and SGAD. Without moderate to strong stimuli such as airway device insertion or painful stimulation during surgery, the type of airway device may have little impact on required propofol concentration during maintenance of anesthesia in dogs.

Functional MRI-based identification of brain regions activated by mechanical noxious stimulation and modulatory effect of remifentanil in cats.

This study was conducted to identify the brain regions corresponding to mechanical noxious stimulation in cats using functional magnetic resonance imaging (fMRI) and to investigate the modulatory effect of remifentanil on the activation of these regions. Six healthy cats were anesthetized using a constant-rate infusion of alfaxalone. Cats were allocated to one of three treatment groups: remifentanil 0 (saline), 0.25, and 0.5µg/kg/min. A 3.0-T MRI unit was used to collect fMRI data. During the fMRI scanning, mechanical noxious stimulation was applied by tail clamping. The brain regions activated by the stimulation were identified based on blood oxygenation level-dependent (BOLD) responses. The modulatory effects of remifentanil were evaluated using a region of interest (ROI) analysis comparing signal changes in each brain region. Increased activity from noxious stimulation was observed in the somatosensory area (the postcruciatus gyrus, the anterior part of the marginalis gyrus, and the anterior part of the ectomarginalis gyrus), the parietal association area (the middle part of the marginalis gyrus and the middle part of the ectomarginalis gyrus), the cingulate cortex, the hippocampus, and the cerebellum. The results of the ROI analysis indicated that activations in the somatosensory area, the cingulate cortex, the hippocampus, and the cerebellum were significantly modulated (P<0.05) by remifentanil. In cats, activation patterns evoked by mechanical noxious stimulation were observed in several brain regions thought to be involved in various aspects of pain processing, including sensory discrimination and integration, affect, and motor response. These brain responses were modulated by remifentanil.

Association between preoperative characteristics and risk of anaesthesia-related death in dogs in small-animal referral hospitals in Japan.

OBJECTIVE: To explore the major risk factors linking preoperative characteristics and anaesthesia-related death in dogs in referral hospitals in Japan. STUDY DESIGN: Observational cohort study. ANIMALS: From April 1, 2010 to March 31, 2011, 4323 dogs anaesthetized in 18 referral hospitals in Japan. METHODS: Questionnaire forms were collated anonymously. Death occurring within 48 hours after extubation was considered as an anaesthesia-related death. Patient outcome (alive or dead) was set as the outcome variable. Preoperative general physical characteristics, complete blood cell counts, serum biochemical examinations and intraoperative complications were set as explanatory variables. The risk factors for anaesthesia-related death were evaluated using chi-square test or Fisher's exact test, followed by multivariable logistic regression analysis of the data. Significance was set at p < 0.05. RESULTS: Thirteen dogs that died from surgical error or euthanasia were excluded from statistical analysis. The total mortality rate in this study was 0.65% [28/4310 dogs; 95% confidence interval (CI), 0.41-0.89]. Furthermore, 75% (95% CI, 55.1-89.3) of anaesthesia-related deaths occurred in dogs with pre-existing diseases. Most of the deaths occurred postoperatively (23/28; 82.1%; 95% CI, 63.1-93.9). Preoperative serum glucose concentration <77 mg dL-1 (6/46; 13.0%; 95% CI, 4.9-26.3), disturbance of consciousness (6/50; 12.0%; 95% CI, 4.5-24.3), white cell count >15,200 µL-1 (16/499; 3.4%; 95% CI, 1.9-5.5) and American Society of Anesthesiologists grade III-V (19/1092; 1.7%; 95% CI, 1.1-2.7) were identified as risk factors for anaesthesia-related death. Intraoperative hypoxaemia (8/34; 23.5%; 95% CI, 10.7-41.2) and tachycardia (4/148; 2.7%; 95% CI, 0.7-6.8) were also risk factors for anaesthesia-related death. CONCLUSIONS AND CLINICAL RELEVANCE: The results revealed that certain preoperative characteristics were associated with increased odds of anaesthesia-related death, specifically low serum glucose concentration and disturbances of consciousness. Greater attention to correcting preanaesthetic patient abnormalities may reduce the risk of anaesthesia-related death.

Selective boron delivery by intra-arterial injection of BSH-WOW emulsion in hepatic cancer model for neutron capture therapy.

OBJECTIVE: Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a 10BSH-entrapped water-in-oil-in-water (WOW) emulsion, evaluated it as a selective boron carrier for the possible application of BNCT in hepatocellular carcinoma treatment. METHODS: We prepared the 10BSH-entrapped WOW emulsion using double emulsification technique and then evaluated the delivery efficacy by performing biodistribution experiment on VX-2 rabbit hepatic tumour model with comparison to iodized poppy-seed oil mix conventional emulsion. Neutron irradiation was carried out at Kyoto University Research Reactor with an average thermal neutron fluence of 5 × 1012 n cm-2. Morphological and pathological analyses were performed on Day 14 after neutron irradiation. RESULTS: Biodistribution results have revealed that 10B atoms delivery with WOW emulsion was superior compared with those using iodized poppy-seed oil conventional emulsion. There was no dissemination in abdomen or lung metastasis observed after neutron irradiation in the groups treated with 10BSH-entrapped WOW emulsion, whereas many tumour nodules were recognized in the liver, abdominal cavity, peritoneum and bilateral lobes of the lung in the non-injected group. CONCLUSION: Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the 10BSH-entrapped WOW emulsion-injected group, indicating its feasibility to be applied as a novel intra-arterial boron carrier for BNCT. Advances in knowledge: The results of the current study have shown that entrapped 10BSH has the potential to increase the range of therapies available for hepatocellular carcinoma which is considered to be one of the most difficult tumours to cure.

Context-sensitive half-time of fentanyl in dogs.

Context-sensitive half-times (CSHTs) of fentanyl in dogs were determined using pharmacokinetic models reported by Murphy et al. and Sano et al., and compared with a human model. The CSHT was defined as the time required for a 50% decrease in drug concentration in the central compartment after the termination of infusion. Although CSHTs increased gradually as the infusion time increased, the CSHTs in dogs were shorter than those in humans. The CSHTs at steady-state were 31.3 and 69.2 min in dogs, and 306.5 min in humans. The CSHTs of fentanyl in dogs are apparently shorter than those in humans; therefore, a continuous infusion of fentanyl may be a rational regimen in dogs, even if duration of infusion is extended.

Incidence of intraoperative hypotension during isoflurane-fentanyl and propofol-fentanyl anaesthesia in dogs.

Most anaesthetic and analgesic drugs affect the cardiovascular system and can cause intraoperative hypotension (IOH). This study aimed to compare the incidence of IOH in anaesthetised dogs when isoflurane-fentanyl was used, compared to propofol-fentanyl. Intraoperative hypotension was defined as an episode of mean blood pressure below 60 mmHg for more than 5 min during anaesthesia. The incidence of IOH was 65.3% for isoflurane-fentanyl and 27.6% for propofol-fentanyl. The adjusted odds ratio for IOH when propofol-fentanyl was compared to isoflurane-fentanyl was 0.2 (95% CI 0.11-0.38). These results suggest that propofol-fentanyl is associated with a lower risk of IOH than isoflurane-fentanyl anaesthesia.

Histological study of right ventricle-pulmonary artery valved conduit implantation (RPVC) in dogs with pulmonic stenosis.

We examined whether right ventricle-pulmonary artery valved conduit (RPVC) implantation can overcome the disadvantages of current procedures for pulmonic stenosis (PS). We histologically evaluated the feasibility of RPVC using a homograft in PS model dogs. Eight dogs underwent pulmonary artery banding (PAB) and then 12 weeks later were assigned to PAB (n=4) or PAB+RPVC (n=4) groups. Dogs in the PAB group received no treatment throughout the experimental period, whereas the PAB+RPVC group underwent RPVC. At 1 year after PAB, hearts and conduits were explanted from euthanized dogs and histologically evaluated. The ratios (%) of myocardial fibrosis on right ventricle (RV) epicardial, median and endocardial layers were significantly lower in the PAB+RPVC, than in the PAB group. The ratio of myocardial fibrosis on left ventricular (LV) epicardial and endocardial layers were significantly lower in the PAB+RPVC, than in the PAB group. Neo-intimal thickness in the anastomosis areas of the Denacol and PAB+RPVC groups was 42.77 +/- 30.19 and 88.30 +/- 27.24 microm, respectively, with no significant differences between the groups. Calcification and neo- intima hypertrophy were not obvious in the valve area. Immunohistological staining showed that the internal surface of the anastomosis and intermediate areas were positive for endothelial cells. We concluded that RPVC using a bioprosthetic graft can apparently overcome the disadvantages of current procedures for pulmonic stenosis.

Cardiovascular effects of right ventricle-pulmonary artery valved conduit implantation in experimental pulmonic stenosis.

Right ventricle (RV)-pulmonary artery (PA) valved conduit (RPVC) implantation decreases RV systolic pressure in pulmonic stenosis (PS) by forming a bypass route between the RV and the PA. The present study evaluates valved conduits derived from canine aortae in a canine model of PS produced by pulmonary artery banding (PAB). Pulmonary stenosis was elicited using PAB in 10 conditioned beagles aged 8 months. Twelve weeks after PAB, the dogs were assigned to one group that did not undergo surgical intervention and another that underwent RPVC using denacol-treated canine aortic valved grafts (PAB+RPVC). Twelve weeks later, the rate of change in the RV-PA systolic pressure gradient was significantly decreased in the PAB+RPVC, compared with the PAB group (60.5 +/- 16.7% vs. 108.9 +/- 22.9%; p<0.01). In addition, the end-diastolic RV free wall thickness (RVFWd) was significantly reduced in the PAB+RPVC, compared with the PAB group (8.2 +/- 0.2 vs. 9.4 +/- 0.7 mm; p<0.05). Thereafter, regurgitation was not evident beyond the conduit valve and the decrease in RV pressure overload induced by RPVC was confirmed. The present results indicate that RPVC can be performed under a beating heart without cardiopulmonary bypass and adapted to dogs with various types of PS, including "supra valvular" PS or PS accompanied by dysplasia of the pulmonary valve. Therefore, we consider that this method is useful for treating PS in small animals.

Right atriotomy using total venous inflow occlusion for removal of heartworms in a cat.

Heartworm infection with caval syndrome was detected in a thirteen-year-old male cat. However, removal of the heartworms via a jugular venotomy was infeasible because the size of the jugular vein limited our ability to use flexible alligator forceps. Therefore, a right atriotomy using total venous inflow occlusion was performed to remove the heartworms. The procedure was accomplished successfully, and the cat recovered from its symptoms. The present case suggests that right atriotomy using venous inflow occlusion is practical for removal and prevention of rupture of heartworms.