Search

Yoshiko Onodera, Megumi Kanao-Kanda, Hirotsugu Kanda, Tomoki Sasakawa, Hiroshi Iwasaki, Takayuki Kunisawa Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan Purpose: Pregnancy-induced analgesia develops during late pregnancy, but it is unclear whether this analgesia is effective against neuropathic pain. The detailed molecular mechanisms underlying pregnancy-induced analgesia have not been investigated. We examined the antinociceptive effect of pregnancy-induced analgesia in a neuropathic pain model and the expression of tumor necrosis factor (TNF)-α, glial fibrillary acidic protein (GFAP), Iba-1, and c-Fos in the spinal dorsal horn just before parturition. Materials and methods: Female Sprague Dawley rats (200–250 g) were randomly assigned to one of four groups (pregnant + chronic constriction injury [CCI]; pregnant + sham injury; not pregnant + CCI; and not pregnant + sham injury). Separate groups were used for the behavioral and tissue analyses. CCI of the left sciatic nerve was surgically induced 3 days after confirming pregnancy in the pregnancy group or on day 3 in the not pregnant group. The spinal cord was extracted 18 days after CCI. TNF-α, GFAP, Iba-1, and c-Fos expression levels in the spinal dorsal horn were measured by Western blot analysis. Mechanical threshold was tested using von Frey filaments. Results: The lowered mechanical threshold induced by CCI was significantly attenuated within 1 day before parturition and decreased after delivery. TNF-α expression in CCI rats was decreased within 1 day before parturition. Further, GFAP, Iba-1, and c-Fos expression in the spinal dorsal horn was reduced in the pregnant rats. Serum TNF-α in all groups was below measurable limits. Conclusion: Our findings indicate that pregnancy-induced analgesia suppresses neuropathic pain through reducing spinal levels of TNF-α, GFAP, Iba-1, and c-Fos in a rat model of CCI. Keywords: pregnancy-induced analgesia, TNF-α, neuropathic pain, glial cell

Abstract: The microstructures of Fe2Si5 based alloys fabricated by spark plasma sintering and the subsequent heat treatment were investigated by X-ray diffraction (XRD) analysis and scanning electron microscope (SEM). The results showed that a two-phase structure consisting of β-FeSi2 and Si dispersoids was obtained by the eutectoid decomposition of α-Fe2Si5 phase during annealing. The thermoelectric properties of Fe2Si5 based alloys were also investigated as compared with the stoichiometric FeSi2 based alloys. It was found that Fe2Si5 based alloys have the same conduction mechanism with stoichiometric FeSi2 alloys doped with Mn and Co, respectively. An increase in carrier scattering caused by Si particles was observed in both Mn- and Co-doped alloys. The effect of Si dispersoids on Seebeck coefficient and electrical resistivity was discussed. Results show that the excessive Si dispersoids in Fe2Si5 based alloys could improve the transport properties of the material, especially for the Co-doped alloys. [Copyright &y& Elsevier]

Introduction. Rocuronium has organ-dependent metabolism and has a prolonged duration of action in elderly patients. The variability in its duration in elderly patients has been reported to be greater than with cisatracurium 0.1 mg kg-1, whose metabolism is organ-independent. Variability in the duration of action of additional increments of rocuronium is unknown. We investigated the effect of the injection time of initial and additional doses of rocuronium on its variability and compared the results in young and elderly patients. Methods. After IRB approval and after obtaining written informed consent, patients undergoing elective surgery requiring general anaesthesia were enrolled in the study. Patients had normal renal and liver function, and a BMI between 20 and 30 kg m-2. Anaesthesia was induced using propofol 1-2 mg kg-1 and remifentanil 0.2-0.25 µg kg-1 min-1 and maintained with sevoflurane 0.7 MAC and remifentanil. The duration of neuromuscular block was defined as the time from injection to return of the twitch height to 25% of the control. The initial dose of rocuronium was 0.6 mg kg-1, and additional 0.15 mg kg-1 increments were given when the twitch height recovered to 25%. Subjects were divided into two groups by age: a young (<65 yr) and an elderly group (≥65 yr). Variability was determined by subtracting the actual duration of action from the mean duration of action in each group. The Mann-Whitney U-test was used for statistical analysis. P<0.05 was considered statistically significant. Results. The duration of action of initial and additional doses of rocuronium was longer in the elderly than in the young group (Fig. 7, P<0.05). Variability in the duration of action of the initial dose was significantly larger in the elderly than the young group, but this difference disappeared with additional increments of rocuronium. Conclusions. There is a greater variability and a longer duration of action of rocuronium in the elderly than in young patients after an initial dose, but not after additional increments. [ABSTRACT FROM AUTHOR]

Background: Cesarean section often requires an urgent transfusion load due to decreased blood pressure after spinal anesthesia. This prospective randomized study aimed to investigate whether a preoperative oral rehydration solution (ORS) stabilized perioperative circulatory dynamics., Methods: Sixty-three parturients scheduled for cesarean section under combined spinal epidural anesthesia (CSEA) were randomly allocated to one of three groups: Group O received 500 mL ORS before bedtime and 500 mL 2 h before CSEA; Group M received mineral water instead of ORS; and Group C had no fluid intake (controls). After entering the operating room, stomach size was measured using ultrasound. Blood samples were obtained, and CSEA was induced. Vasopressors were administered when systolic blood pressure was < 90 mmHg or decreased by > 20%. As a vasopressor, phenylephrine (0.1 mg) was administered at ≥ 60 beats/min heart rate or ephedrine (5 mg) at < 60 beats/min heart rate. The primary outcome was the total number of vasopressor boluses administered. Secondary outcomes were the cross-sectional area of the stomach antrum, maternal plasma glucose levels, serum sodium levels, total intravenous fluid, bleeding volume, urine volume, operative time, and cord blood gas values after delivery., Results: The total number of vasopressor boluses was lower in Group O than in Group C (P < 0.05). Group O had lower total dose of phenylephrine than Group C (P < 0.05). There were no significant differences between Group M and other groups. No differences were detected regarding secondary outcomes., Conclusions: In women scheduled for cesarean section, preoperative ORS stabilized perioperative circulatory dynamics. Neither ORS nor mineral water consumption increased the stomach content volume., Trial Registration: This trial is registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000019825: Date of registration 17/11/2015)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Surgical revascularisation to accomplish limb salvage remains preferable in some patients with chronic limb threatening ischaemia (CLTI). The aim of this study was to evaluate the effectiveness and safety of ultrasound guided lower extremity nerve blockade (UGNB) in infragenicular bypass surgery (IGBS)., Methods: This was a single centre, retrospective clinical study. Fifty-nine patients with CLTI (67 limbs) who underwent IGBS under UGNB (femoral and sciatic nerve blockade) at Asahikawa Medical University between January 2012 and December 2017 were compared with patients with CLTI (137 limbs) who underwent IGBS under general anaesthesia (GA) over the same period. Propensity score matching based on pre-operative comorbidities was used to minimise background differences of the two groups., Results: Fifty-six pairs of CLTIs were matched and analysed (55% dialysis dependent). Procedure duration was similar between the two groups, but intraoperative catecholamine index and intravenous fluid volume were lower with UGNB compared with GA (2.9 ± 4.6 vs. 5.9 ± 6.5; p < .01 and 1831 ± 990 vs. 2335 ± 931 mL; p < .01, respectively). The mean arterial blood pressure during induction of anaesthesia was significantly decreased with GA. Post-operatively, the time period to resume a clear liquid and solid food diet was significantly shorter with UGNB (P<0.01 for both outcome measures). Intravenous fluid volume was significanlty lower, while cardiac complications and delirium, based on the NEECHAM confusion scale, occurred significantly less often with UGNB than GA. These significant differences show advantages of UGNB compared to GA. No mortality or major amputations were observed in either group. Early graft thrombosis was observed in five limbs (8.9%) with UGNB and in four limbs with GA (7.1%) (p = .73)., Conclusions: UGNB has advantages for intra- and post-operative management and could be a useful method to prevent peri-operative complications for high risk patients with CLTI. To ensure the effectiveness of UGNB for IGBS for future indications, a randomised study is required., (Copyright © 2019 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

The objective of this study was to determine the point after sugammadex administration at which sufficient or insufficient dose could be determined, using first twitch height of train-of-four (T1 height) or train-of-four ratio (TOFR) as indicators. Groups A and B received 1 mg/kg and 0.5 mg/kg of sugammadex, respectively, as a first dose when the second twitch reappeared in train-of-four stimulation, and Groups C and D received 1 mg/kg and 0.5 mg/kg of sugammadex, respectively, as the first dose at posttetanic counts 1-3. Five minutes after the first dose, an additional 1 mg/kg of sugammadex was administered and changes in T1 height and TOFR were observed. Patients were divided into a recovered group and a partly recovered group, based on percentage changes in T1 height after additional dosing. T1 height and TOFR during the 5 min after first dose were then compared. In the recovered group, TOFR exceeded 90% in all patients at 3 min after sugammadex administration. In the partly recovered group, none of the patients had a TOFR above 90% at 3 min after sugammadex administration. An additional dose of sugammadex can be considered unnecessary if the train-of-four ratio is ≥90% at 3 min after sugammadex administration. This trial is registered with UMIN000007245.

Background: Mature acetylcholine receptor (AChR) isoform normally mediates muscle contraction. The hypothesis that α7AChRs up-regulate during immobilization and contribute to neurotransmission was tested pharmacologically using specific blockers to mature (waglerin-1), immature (αA-OIVA), and α7AChRs (methyllycaconitine), and nonspecific muscle AChR antagonist, α-bungarotoxin., Methods: Mice were immobilized; contralateral limbs were controls. Fourteen days later, anesthetized mice were mechanically ventilated. Nerve-stimulated tibialis muscle contractions on both sides were recorded, and blockers enumerated above sequentially administered via jugular vein. Data are mean ± standard error., Results: Immobilization (N = 7) induced tibialis muscle atrophy (40.6 ± 2.8 vs. 52.1 ± 2.0 mg; P < 0.01) and decrease of twitch tension (34.8 ± 1.1 vs. 42.9 ± 1.5 g; P < 0.01). Waglerin-1 (0.3 ± 0.05 μg/g) significantly (P = 0.001; N = 9) depressed twitch tension on contralateral (≥97%) versus immobilized side (approximately 45%). Additional waglerin-1 (total dose 1.06 ± 0.12 μg/g or approximately 15.0 × ED50 in normals) could not depress twitch of 80% or greater on immobilized side. Immature AChR blocker, αA-OIVA (17.0 ± 0.25 μg/g) did not change tension bilaterally. Administration of α-bungarotoxin (N = 4) or methyllycaconitine (N = 3) caused 96% or greater suppression of the remaining twitch tension on immobilized side. Methyllycaconitine, administered first (N = 3), caused equipotent inhibition by waglerin-1 on both sides. Protein expression of α7AChRs was significantly (N = 3; P < 0.01) increased on the immobilized side., Conclusions: Ineffectiveness of waglerin-1 suggests that the twitch tension during immobilization is maintained by receptors other than mature AChRs. Because αA-OIVA caused no neuromuscular changes, it can be concluded that immature AChRs contribute minimally to neurotransmission. During immobilization approximately 20% of twitch tension is maintained by up-regulation of α-bungarotoxin- and methyllycaconitine-sensitive α7AChRs.

Purpose. Hypoglossal nerve palsy after use of the laryngeal mask airway (LMA) is an exceptionally rare complication. We present the first case of unilateral hypoglossal nerve palsy after use of the LMA Supreme. Clinical Features. A healthy 67-year-old female was scheduled for a hallux valgus correction under general anesthesia combined with femoral and sciatic nerve blocks. A size 4 LMA Supreme was inserted successfully at the first attempt and the cuff was inflated with air at an intracuff pressure of 60 cmH2O using cuff pressure gauge. Anesthesia was maintained with oxygen, nitrous oxide (67%), and sevoflurane under spontaneous breathing. The surgery was uneventful and the duration of anesthesia was two hours. The LMA was removed as the patient woke and there were no immediate postoperative complications. The next morning, the patient complained of dysarthria and dysphasia. These symptoms were considered to be caused by the LMA compressing the nerve against the hyoid bone. Conservative treatment was chosen and the paralysis recovered completely after 5 months. Conclusion. Hypoglossal nerve injury may occur despite correct positioning of the LMA under the appropriate intracuff pressure. A follow-up period of at least 6 months should be taken into account for the recovery.

FK506 suppresses activation of T cells; however, it down-regulates E-selectin, ICAM-1 and VCAM-1 expression in inflamed tissues. In this study, we investigated the effect of FK506 on expression of those adhesion molecules on human vascular endothelial cells (HMVEC). Culture supernatant from peripheral blood mononuclear cells (PBMC) stimulated with anti-CD3 plus anti-CD2 antibodies effectively induced the expression of E-selectin, ICAM-1 and VCAM-1 on HMVEC, and treatment with FK506 down-regulated their expression. Culture supernatant contained tumor necrosis factor (TNF) alpha and interleukin (IL)-1beta, which effectively induced adhesion molecules, and FK506 suppressed both cytokine secretions. TNFalpha content in culture supernatant was parallel to the induction of adhesion molecules by the culture supernatant. IL-1beta content was not enough to induce those adhesion molecules. Anti-TNFalpha antibody completely inhibited those expressions. FK506 did not inhibit either TNFalpha- or IL-1beta-induced expression of adhesion molecules, or viability of HMVEC. These results indicate that FK506 suppresses migration of inflammatory cells through the inhibition of TNFalpha secretion from leukocytes.

The aim of this study was to elucidate the in vitro inhibitory potency of FK506 on production of the inflammatory cytokines, tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta, with a view to assessing this immunosuppressive agent as a potential anti-rheumatic drug. We employed an in vitro model which produces TNF-alpha and IL-1beta through T cell activation. Human peripheral blood mononuclear cells (PBMC) were cultured with immobilized anti-CD3/CD28 monoclonal antibody in this model. FK506 inhibited anti-CD3/CD28 induced TNF-alpha and IL-1beta production at concentrations less than 1 ng ml(-1). Flow cytometric analysis of intracellular TNF-alpha and IL-1beta positive cells showed that FK506 potently suppresses inflammatory cytokine production from CD14+ monocytes as well as from T cells. Cyclosporin A (CsA) and dexamethasone (DEX) also inhibited the anti-CD3/CD28 induced cytokine production, but were less potent than FK506. FK506 and CsA, but not DEX, specifically inhibited anti-CD3/CD28 induced inflammatory cytokine production without affecting the lipopolysaccaride (LPS) induced effect. Methotrexate (MTX) was completely inactive for suppressing cytokine production under either condition. Anti-CD3/CD28 stimulated PBMC culture supernatants were found to enhance the expression of adhesion molecules in human vascular endothelial cells. FK506, CsA and DEX led to the suppression of adhesion molecule expression probably by inhibiting cytokine production from PBMC. The inhibitory potency of agents on TNF-alpha and IL-1beta production was compared with cytotoxicity and FK506 was not cytotoxic at concentrations several orders of magnitude greater than those required for cytokine inhibition. These results strongly suggest that FK506 may be most effective to specifically prevent T cell activation mediated inflammatory cytokine production in a clinical setting.

The levels of HMG 2a chromosomal protein and its mRNA change during the post-hatched development of chicks were investigated. The contents of both HMG 2a and 2b proteins of liver, heart, brain, muscle and gizzard were abundant in the newly hatched chicks but their contents decreased significantly in those tissues of the 70-day-old chicks. The HMG 2a mRNA levels of liver, heart and brain in 70-day-old chick decreased to about 40% of those mRNA in the newly hatched chicks while the HMG 2a mRNA levels of muscle and gizzard in the 70-day-old chicks increased 5- and 3-fold, respectively. These results suggest that the decrease in the HMG 2a protein contents of the muscle and gizzard in the 70-day-old chicks may be largely due to the stimulation of HMG 2a protein degradation or the reduction of HMG 2a mRNA translation.